Sphenoid Sinus Mucosal Flap after Transsphenoidal Surgery—A Systematic Review

Background and Objectives: Skull base reconstruction is a crucial step during transsphenoidal surgery. Sphenoid mucosa is a mucosal membrane located in the sphenoid sinus. Preservation and lateral shifting of sphenoid mucosa as sphenoid mucosal flap (SMF) during the transsphenoidal exposure of the sella may be important for later closure. This is the first systematic review to evaluate the utility of sphenoid mucosal flap for sellar reconstruction after transsphenoidal surgery. Materials and Methods: A systematic literature search was performed in January 2023: Cochrane, EMBASE, PubMed, Scopus, and Web of Science. The following keywords and their combinations were used: “sphenoid mucosa”, “sphenoid sinus mucosa”, “sphenoid mucosal flap”, “sphenoid sinus mucosal flap”. From a total number of 749 records, 10 articles involving 1671 patients were included in our systematic review. Results: Sphenoid sinus mucosa used to be applied for sellar reconstruction as either a vascularized pedicled flap or as a free flap. Three different types of mucosal flaps, an intersinus septal flap, a superiorly based flap and an inferiorly based flap, were described in the literature. Total SMF covering compared to partial or no SMF covering in sellar floor reconstruction resulted in fewer postoperative CSF leaks (p = 0.008) and a shorter duration of the postoperative lumbar drain (p = 0.003), if applied. Total or partial SMF resulted in fewer local complications (p = 0.012), such as fat graft necrosis, bone graft necrosis, sinusitis or fungal infection, in contrast to no SMF implementation. Conclusions: SMF seems to be an effective technique for skull base reconstruction after transsphenoidal surgery, as it can reduce the usage of avascular grafts such as fat along with the incidence of local complications, such as fat graft necrosis, bone graft necrosis, sinusitis and fungal infection, or it may improve the sinonasal quality of life by maintaining favorable wound healing through vascular flap and promote the normalization of the sphenoid sinus posterior wall. Further clinical studies evaluating sphenoid mucosal flap preservation and application in combination with other techniques, particularly for higher-grade CSF leaks, are required.

The sphenoid sinus is air-filled space within sphenoid bone and lined with mucosal membrane commonly known as sphenoid mucosa.Preservation and lateral shifting of the sphenoid mucosal flap during the transsphenoidal exposure of the sella may be important, as several studies reported the advantage of sphenoid mucosal flap (SMF) application for skull base reconstruction after transsphenoidal surgery [17,18,[21][22][23][24][25][26][27][28].This is the first systematic review to evaluate the utility of SMF for skull base reconstruction after transsphenoidal surgery.
The sphenoid sinus is air-filled space within sphenoid bone and lined with mucosal membrane commonly known as sphenoid mucosa.Preservation and lateral shifting of the sphenoid mucosal flap during the transsphenoidal exposure of the sella may be important, as several studies reported the advantage of sphenoid mucosal flap (SMF) application for skull base reconstruction after transsphenoidal surgery [17,18,[21][22][23][24][25][26][27][28].This is the first systematic review to evaluate the utility of SMF for skull base reconstruction after transsphenoidal surgery.

Search Strategy
A systematic literature review based on Cochrane, EMBASE, PubMed, Scopus, and Web of Science databases was performed in May 2023 according to ENTREQ guidelines (see Reporting guideline checklist and Figure 1) by two independent reviewers (P.S. and M.P.) [29].The following keywords and their combinations were used: "sphenoid mucosa", "sphenoid sinus mucosa", "sphenoid mucosal flap", "sphenoid sinus mucosal flap".Duplicate articles were excluded.The study was not registered in any systematic review database.The following keywords and their combinations were used: "sphenoid mucosa", "sphenoid sinus mucosa", "sphenoid mucosal flap", "sphenoid sinus mucosal flap".Duplicate articles were excluded.The study was not registered in any systematic review database.

Quality Appraisal
Quality appraisal using Critical Appraisal Skills Program (CASP) guidelines was conducted for all potentially relevant studies by two reviewers (P.S. and M.P.) [30].Each selected study was appraised for quality and internal validity according to the CASP checklist (see CASP Checklist) for qualitative research.The CASP checklist contains 10 questions to assess the quality of qualitative research.

Data Extraction
Extracted data with an overview of included studies are presented in Tables 1 and 2. For the organization of extracted data, a unified matrix was utilized to record specific characteristics of included studies.Extracted data comprised: reference details (author, year, title, journal/publisher), objectives or aims of the study, study design, ethics (how ethical issues were addressed), sampling methodology, sample size, indication for sellar reconstruction, anatomical aspects, description of operative technique, complications and outcome after surgery.All calculations were performed on Microsoft Excel (version 2019; Microsoft).

Data Synthesis
Thematic synthesis is a well-established analytical technique for qualitative research and commonly published according to ENTREQ reporting guidelines [29].
During readings of the studies, similar findings were coded into descriptive themes (see Literature quotations) within and across studies.The process of acquiring the descriptive themes from initial codes was inductive to assessing previously researched phenomena.Two reviewers were involved in the coding and analysis (P.S. and M.P.).

Classification of Sellar Defect
The CSF leak and extension of skull base defect were classified according to the Esposito-Kelly grading system [31].

Results
We identified 749 studies after removing duplicates and excluded 741 studies for the following reasons: (1) the title and/or abstract did not match selection criteria; (2) studies were irrelevant when applied to inclusion criteria.In addition, we included two studies after a related article search.As a result, we included 10 studies in the qualitative synthesis.

Operative Technique
Sphenoid sinus mucosa used to be applied for sellar reconstruction as either a wellvascularized pedicled flap or as a free flap, which can be subsequently sutured or stuck with fibrin glue covering the laceration or larger defect [21].Three different types of sphenoid mucosal flaps, the intersinus septal mucosal flap, a superiorly based mucosal flap and an inferiorly based mucosal flap, were already described by Yoon and colleagues (see Figure 2) [28].The intersinus septal mucosal flap was the most common and predominantly performed one after primary procedures.The superiorly based mucosal flap along with the inferiorly based mucosal flap were harvested mainly after multiple surgeries without an intersinus septum or in cases with multiple septums [28].Furthermore, isolation of more than one flap and closure in a multi-layered fashion is possible [23].SMF could be successfully implemented either by absence or small CSF leak as a stand-alone or in a combined technique for larger ones [17,18,[21][22][23][24][25][26][27][28].

Advantages
When compared to partial or no SMF covering, total SMF covering in sellar floor reconstruction resulted in fewer postoperative CSF leaks (p = 0.008) and a shorter duration of the postoperative lumbar drain (p = 0.003) [28].Total or partial SMF resulted in fewer local complications (p = 0.012), such as fat graft necrosis, bone graft necrosis, sinusitis or fungal infection, in contrast to no SMF implementation [28].Application of SMF may also reduce the usage of fat grafts and the risk of associated necrosis [21,28].SMF also promotes the normalization of the sphenoid sinus posterior wall [26].Sellar reconstruction with SMF results in a better sinonasal QoL compared to NSF, as measured by the SNOT-22 Score for the first 6 weeks postoperatively (p < 0.05) [22].The advantages of SMF are presented in Figure 3.

Advantages
When compared to partial or no SMF covering, total SMF covering in sellar floor reconstruction resulted in fewer postoperative CSF leaks (p = 0.008) and a shorter duration of the postoperative lumbar drain (p = 0.003) [28].Total or partial SMF resulted in fewer local complications (p = 0.012), such as fat graft necrosis, bone graft necrosis, sinusitis or fungal infection, in contrast to no SMF implementation [28].Application of SMF may also reduce the usage of fat grafts and the risk of associated necrosis [21,28].SMF also promotes the normalization of the sphenoid sinus posterior wall [26].Sellar reconstruction with SMF results in a better sinonasal QoL compared to NSF, as measured by the SNOT-22 Score for the first 6 weeks postoperatively (p < 0.05) [22].The advantages of SMF are presented in Figure 3.
plications (p = 0.012), such as fat graft necrosis, bone graft necrosis, sinusitis or fungal infection, in contrast to no SMF implementation [28].Application of SMF may also reduce the usage of fat grafts and the risk of associated necrosis [21,28].SMF also promotes the normalization of the sphenoid sinus posterior wall [26].Sellar reconstruction with SMF results in a better sinonasal QoL compared to NSF, as measured by the SNOT-22 Score for the first 6 weeks postoperatively (p < 0.05) [22].The advantages of SMF are presented in Figure 3.

Limitations
The anatomy of sphenoid sinus and sphenoid mucosa is variable and may limit the application of SMF.Mucosal thickness may vary from being very dense and elastic, suitable for dura and bone defect reconstruction, to being skinny and fragile, susceptible to tearing by bony ridges of the sphenoid sinus or any surgical manipulation [21,23].Anatomical variants such as Onodi cells or multiple intersphenoidal septa were described as limiting the usage of SMF [22].Mucosal quality and its utility for sella repair can be limited by infections or infrasellar tumor invasion, where not only the sella turcica is being destructed but also sphenoid mucosa [21,22].A worse mucosal quality with partial SMF covering is associated with a higher risk of CSF leak [28].Postoperative irradiation may also interrupt the healing process, resulting in a delayed CSF leak [21].Another issue is invagination of SMF after sellar reconstruction, which may be a result of increased intracranial pressure by sneezing, blowing the nose during the early healing process and/or an incompletely unfolded sphenoid mucosa during sellar floor reconstruction [27].Clinically, it may be associated with a reduced improvement of postoperative headaches during early followup [27].Limitations of SMF are summarized in Figure 4.

Limitations
The anatomy of sphenoid sinus and sphenoid mucosa is variable and may limit the application of SMF.Mucosal thickness may vary from being very dense and elastic, suitable for dura and bone defect reconstruction, to being skinny and fragile, susceptible to tearing by bony ridges of the sphenoid sinus or any surgical manipulation [21,23].Anatomical variants such as Onodi cells or multiple intersphenoidal septa were described as limiting the usage of SMF [22].Mucosal quality and its utility for sella repair can be limited by infections or infrasellar tumor invasion, where not only the sella turcica is being destructed but also sphenoid mucosa [21,22].A worse mucosal quality with partial SMF covering is associated with a higher risk of CSF leak [28].Postoperative irradiation may also interrupt the healing process, resulting in a delayed CSF leak [21].Another issue is invagination of SMF after sellar reconstruction, which may be a result of increased intracranial pressure by sneezing, blowing the nose during the early healing process and/or an incompletely unfolded sphenoid mucosa during sellar floor reconstruction [27].Clinically, it may be associated with a reduced improvement of postoperative headaches during early follow-up [27].Limitations of SMF are summarized in Figure 4.

Clinical Significance
Our systematic review presents the utility of SMF for sellar reconstruction after transsphenoidal surgery.SMF is a vascularized flap similar to the nasoseptal mucosal flap, middle turbinate flap or anterior lateral nasal wall flap.All these flaps present with a lower risk of necrosis, lower risk of CSF leak and support a better healing process compared to avascular grafts [32,33].However the usage of NSF and MTF alters the physiological nasal or sphenoidal passage and may be associated with additional adverse effects, such as nasal fossa synechia, internal nasal valve failure, nasal dorsum collapse or septal perforation, while also lowering the sinonasal quality of life compared to SMF [21,22,34,35].For small CSF leaks, both SMF and NSF have a comparable risk of CSF leak, and SMF may be applied as a stand-alone [22].In the case of higher grades of CSF leak, SMF application alone may be insufficient, and the implementation of NSF along with other techniques such as multilayered closure may be necessary [21,22,25,36].Avascular grafts, such as fat, muscle or fascia lata grafts, are usually implanted in the case of a lower risk or CSF rhinorrhoea and reveal a higher risk of local complications than SMF, such as necrosis or infections [28,36].SMF application can reduce the usage rate of fat graft and the duration of lumbar drain for CSF leak [21,28].Studies with sellar reconstruction using biomaterials (dural substitutes and hemostatic agents) disclosed a similar efficacy regarding CSF leaks and a more favorable side-effect profile compared to avascular grafts (fat or fascia lata graft) [14][15][16]19,20,37].
Preserved SMFs maintain the physiological restoration of the posterior sphenoid sinus wall and facilitate exploration through a potential reoperation [26,27].Preoperative planning is not only essential for a surgical approach but also for preparing the strategy for sellar reconstruction.The presence of thin and fragile mucosa susceptible to tearing, Onodi cells, multiple intersphenoidal septa or pathological states, such as mucosal tumor invasion or previous infection, may restrict the application of SMF [21,22,28].Invagination of SMF after sellar reconstruction remains a clinical issue [27].To prevent this condition, the implementation of rigid materials resistant to physical pressure is recommended [27,37].

Limitations
Our review was limited by several aspects.Most of the included studies were noncomparative and investigated the application of SMF in combination with other techniques.As a consequence, the direct impact and significance of SMF for sellar floor reconstruction could not be quantified.Comparative studies were restricted by the small number of sample sizes and their retrospective nature.Therefore, correlations requiring prospective data, larger cohorts and more detailed information could not be conducted.

Perspectives
Future investigations should focus on a more comprehensive clinical and morphological analysis of sphenoid mucosa including different inter-patient anatomical variations to reveal the significance of its restoration and the potential limitation of SMF.To accomplish the highest grade of evidence, multicentric randomized controlled trials shall be designed.

Conclusions
The sphenoid mucosal flap (SMF) seems to be an effective technique for skull base reconstruction after transspenoidal surgery, as it can reduce the usage of avascular grafts, such as fat, along with the incidence of local complications, such as fat graft necrosis, bone graft necrosis, sinusitis or fungal infection, and may improve the sinonasal quality of life by maintaining favorable wound healing through the vascular flap and promote the normalization of the sphenoid sinus posterior wall.Further clinical studies evaluating sphenoid mucosal flap preservation and application in combination with other techniques, especially for higher-grade CSF leaks, are required.
Our systematic review presents the utility of SMF for sellar reconstruction after transsphenoidal surgery.SMF is a vascularized flap similar to the nasoseptal mucosal flap, middle turbinate flap or anterior lateral nasal wall flap.All these flaps present with a lower

Table 1 .
Summary of all SMF studies' characteristics.