Article published online: 2022-08-09

602 Review Article

Optimizing Quality of Life and Minimizing Morbidity

through Nasal Preservation in Endoscopic Skull Base
Surgery: A Contemporary Review
Carlos Pinheiro-Neto1,3 Nicholas R. Rowan2 Maria Peris Celda1,3 Debraj Mukherjee4
Jamie J. Van Gompel1,3 Garret Choby1,3

1 Department of Otolaryngology—Head & Neck Surgery, Mayo Clinic, Address for correspondence Garret Choby, MD, Department of
Rochester, Minnesota, United States Otorhinolaryngology—Head and Neck Surgery, Department of
2 Department of Otolaryngology—Head & Neck Surgery, Johns Neurologic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN
Hopkins University, Baltimore, Maryland, United States 55905, United States (e-mail: choby.garret@mayo.edu).

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
3 Department of Neurologic Surgery, Mayo Clinic, Rochester,
Minnesota, United States
4 Department of Neurologic Surgery, Johns Hopkins University,
Baltimore, Maryland, United States

J Neurol Surg B Skull Base 2022;83:602–610.

Abstract Introduction Endoscopic endonasal approaches (EEAs) are increasingly utilized for
intracranial pathology. As opposed to sinonasal tumors, the nasal cavity is being used as
a corridor to access these intracranial tumors but is not the site of primary surgical intent.
Accordingly, there has been recent interest in preserving intranasal structures not directly
involved by tumor and improving postoperative sinonasal quality of life (QOL).
Objectives The aim of the study is to highlight recent advances in EEA techniques
focused on improving sinonasal QOL including turbinate preservation, reducing the
morbidity of reconstructive techniques, and the development of alternative minimally
invasive EEA corridors.
Methods The method of the study involves contemporary literature review and
summary of implications for clinical practice.
Keywords Results Nasoseptal flap (NSF) harvest is associated with significant morbidity includ-
► endoscopic skull base ing septal perforation, prolonged nasal crusting, and external nasal deformities.
surgery Various grafting and local rotational flaps have demonstrated the ability to significantly
► expanded endonasal limit donor site morbidity. Free mucosal grafts have re-emerged as a reliable
approach reconstructive option for sellar defects with an excellent sinonasal morbidity profile.
► nasal preservation Middle turbinate preservation is achievable in most EEA cases and has not been shown
► turbinates to cause postoperative obstructive sinusitis. Recently developed minimally invasive
► nasoseptal flap EEA techniques such as the superior ethmoidal approach have been described to better
► free mucosal graft preserve intranasal structures while allowing intracranial access to resect skull base
► CSF leak tumors and have shown promising sinonasal QOL results.
► sinonasal malignancy Conclusion This contemporary review discusses balancing effective skull base recon-
► chordoma structive techniques with associated morbidity, the role of turbinate preservation in
► olfaction EEA, and the development of unique EEA techniques that allow for increased nasal
► quality of life structure preservation.

received © 2022. Thieme. All rights reserved. DOI https://doi.org/

September 21, 2021 Georg Thieme Verlag KG, 10.1055/s-0042-1749654.
accepted Rüdigerstraße 14, ISSN 2193-6331.
April 21, 2022 70469 Stuttgart, Germany
published online
August 9, 2022

Introduction
As expanded endoscopic endonasal approaches (EEAs) for
the management of skull base lesions have advanced, larger
and more complex tumors have increasingly been removed
via EEA. Skull base reconstruction was once the “Achilles
Heel” of endoscopic tumor resection with initial postopera-
tive cerebrospinal fluid (CSF) leak rates as high as 40 to
50%.1,2 With the advent of local and regional pedicled
vascularized reconstructive flaps, the rate of postoperative
CSF leak has considerably reduced. In cases of EEA for
pituitary tumors, the rates of postoperative CSF leak have
been reported to be 1 to 3%.3–5 Moreover, in cases of high
flow intraoperative CSF leaks defined by large dural defects
>2cm or direct communication with a cistern or opening of
the ventricular system, utilization of vascularized recon-
structive options has reduced postoperative CSF leak rates
to 6% or less.6
For many cases, utilization of EEA for tumor resection
offers a minimally invasive endoscopic approach that also
affords maximal exposure and visualization. For instance,
EEA may offer the advantage of direct access and improved
visualization of clival chordomas and clear delineation of
tumor attachment points for sinonasal malignancies.7–9
With sinonasal malignancies, a negative margin resection
is of utmost importance and thus is the primary goal of
surgery. Surgeons need to use all approaches in their arma-
mentarium to achieve this goal, including open approaches
when needed.8,10 Regardless of functional capacity, all sino-
nasal tissue with tumor involvement must be fully resected.
This may result in some degree of sinonasal morbidity and
impaired quality of life (QOL) which is generally considered
acceptable to achieve tumor resection.
Moreover, EEA is also utilized with increased frequency
for benign cranial base or intracranial tumors such as pitui-
tary adenomas, craniopharyngiomas, and meningiomas
(►Fig. 1). In these cases, as opposed to sinonasal malignan-
cies, the nasal cavity is being utilized as a corridor to access
Fig. 1 Primarily intracranial tumor approached through expanded endonasal approaches; (A) Coronal T1 post-gadolinium MRI of olfactory
groove meningioma; (B) Sagittal T1 post-gadolinium MRI of adamantinomatous craniopharyngioma.
Journal of Neurological Surgery—Part B
Nasal Preservation and QOL in EEA Pinheiro-Neto et al. 603
these benign cranial base tumors. In other words, the nasal
cavity is the gateway to tumor access, but is not the site of the
primary surgical intent. As experience of EEA with these
benign tumors has increased and surgeons have advanced on
the learning curve, some groups have begun to advocate for
an increased focus on minimizing sinonasal morbidity and
improving long-term patient QOL.11–15 In this very recent
and rapidly evolving area of EEA investigation, a variety of
initiatives have been described including preservation of
turbinates, minimizing the morbidity of reconstructive tech-
niques, development of alternative minimally invasive EEA
corridors, and more accurately measuring QOL following
EEA. Thus, the purpose of this contemporary review is to
highlight recent efforts focused on minimizing sinonasal
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morbidity following EEA and to describe a variety of techni-
ques that can be considered in this effort.
Materials and Methods
Literature Review: Data Sources and Search Strategies
A contemporary review of several databases from Jan 1, 2005
through June 1, 2021, any language, was conducted of all
studies examining QOL outcomes and techniques in EEA. The
databases included Ovid MEDLINE(R) and Epub Ahead of
Print, Ovid EMBASE and Scopus. The search strategy was
designed and conducted by the study’s principal investigator
with input from an experienced research librarian. Con-
trolled vocabulary supplemented with keywords was used
to search for endoscopic skull base surgery and QOL, skull
base reconstruction, turbinate preservation, and morbidity.
Prospective, retrospective, and in vitro studies were includ-
ed. Articles were excluded if they were conference abstracts,
lacked relevant clinical information or did not have relevance
to the literature review. Articles were selected based upon
their quality and relevance to the below sections including
skull base reconstruction, turbinate preservation, and
unique techniques to preserve sinonasal structures in EEA.
For each specified section, the aggregate level of evidence
Vol. 83 No. B6/2022 © 2022. Thieme. All rights reserved.
604 Nasal Preservation and QOL in EEA Pinheiro-Neto et al.
Fig. 2 Morbidity of the nasoseptal flap. (A) Prolonged nasal crusting of NSF donor site of right side of nasal septum 8 weeks following
transtuburculum and transellar craniopharyngioma resection (triangle on right inferior turbinate and arrows on right side of nasal septum); (B)
Nasal septum perforation following NSF reconstruction for suprasellar defect.
according to the 2011 Oxford Centre for Evidence-Based
Medicine is also included.16–18
Skull Base Reconstruction
Morbidity of the Nasoseptal Flap and Techniques to
Mitigate Donor Site Complications
The nasoseptal flap (NSF) has developed into the workhorse
of skull base reconstruction. The development of the NSF in
200619 helped to revolutionize endoscopic skull base surgery
and has significantly reduced postoperative CSF leak rates.6
This has been especially true for cases with high flow CSF
leaks with large dural defects, direct communication with a
cistern or ventricle, or transdural defects in the posterior
cranial fossa. Numerous techniques have been described to
lengthen the flap, expand its reach, and allow for broader
defect coverage.20–22
Although the NSF is a vitally important tool for all
endoscopic skull base surgeons, its morbidity has also
been well documented including flap necrosis, mucocele
formation, prolonged crusting, and olfactory changes.23 In
a series of 121 cases utilizing NSFs, complications occurred in
27% of the patients. The majority of complications were
related to the septal donor site, including septal perforation,
prolonged nasal crusting, and cartilage necrosis; additional
complications were also documented at the reconstruction
site including flap necrosis and mucocele formation.24 Septal
perforation and prolonged nasal crusting >6 months were
the most common complications, occurring in a combined
17.1% of patients (►Fig. 2).24
In addition to morbidity at the donor and recipient sites,
external nasal deformities following EEA have been docu-
mented. In a series of 328 patients undergoing EEA, 19
patients were documented to have nasal dorsum collapse.
Associated factors included utilization of a NSF and tumor
involvement of more than one subsite.25 In a follow-up
prospective study of 34 patients utilizing blinded review of
postoperative photographs, 15% of patients were noted to
have nasal deformities. The only significant association
factor was reconstruction with a NSF.26 The authors point
Journal of Neurological Surgery—Part B Vol. 83 No. B6/2022
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to reduced vascularity of the residual septal cartilage as a
likely culprit for the changes in external appearance.
Numerous techniques have been described to reduce
donor site morbidity for NSFs. In cases where the middle
turbinate (MT) is resected, a free mucosal graft (FMG) can
be harvested and placed on the NSF donor site. In a study of
61 patients undergoing EEA, utilization of a MT free graft on
the NSF donor site reduced nasal crusting at the 6-week
follow-up visit from 85 to 5%.27 In an analogous technique,
Nayak, et al performed a randomized controlled trial (RCT)
of placement of a porcine small intestine graft to the NSF
donor site following EEA. In this RCT, blinded reviewers
graded re-mucosalization, crusting and edema at 2-, 6-, and
12-weeks after surgery. Subjects undergoing graft place-
ment had excellent re-mucosalization rates at the 12-week
mark and subsequent biopsies with immunohistochemical
analysis demonstrated that the graft helped to recruit basal
cell progenitors.28 Lastly, anatomically shaped nasal access
guides have also been developed to help to reduce septal
mucosa trauma which may theoretically reduce trauma to
the mucosa of the contralateral side of the septal mucosa
after NSF elevation, thus reducing risk of septal
perforation.29
In addition, local rotational mucosal flaps have also been
described to improve NSF donor site morbidity. The inferior
meatus mucosal flap has been described based on the
incisive foramen, containing distal branches of the spheno-
palatine artery. This can be harvested from the nasal floor
and inferior meatus and rotated to cover the exposed
quadrangular cartilage following NSF elevation to re-mucos-
alize the area.30 Similarly, the contralateral reverse rotation
flap for reconstruction of the NSF donor site has been
described. In this technique, the mucosa of the posterior
nasal septum contralateral to the side of the NSF is trans-
ected posteriorly and wrapped around the posterior aspect
of the septectomy defect and pulled anteriorly to cover the
exposed cartilage of the NSF donor site. In a retrospective
study of 49 patients undergoing this technique, the authors
noted 98% re-epithelialization of the donor site during the
11-week follow-up time period31,32 However, it should be
© 2022. Thieme. All rights reserved.

noted that utilization of this flap precludes the use of the
contralateral NSF in the future.
NSF elevation also conveys a theoretical risk of postoper-
ative olfactory dysfunction due to the upper limb incision
proximity to the olfactory fila. However, published data has
been mixed on NSF and risk of long-term olfactory loss. In a
study of 20 patients, those who underwent NSF elevation
during EEA had worsened olfaction at 6 months postopera-
tively on University of Pennsylvania Smell Identification
Testing (UPSIT) compared with those who did not have
NSF elevation. However, it should also be noted that both
NSF and non-NSF patients in the study had persistent
olfactory dysfunction at 6 months postoperatively. In con-
trast, a RCT demonstrated no diminishment in UPSIT scores
in patients undergoing NSF elevation during EEA regardless
of electrocautery or cold steel techniques at 3-months or 12-
months postoperatively compared with baseline scores.14
Moreover, a 2016 study showed that patients undergoing
EEA with NSF elevation had worsened subjective olfaction at
1 month postoperatively compared with those who under-
went alternative reconstructive techniques, but this change
returned to preoperative baseline in both groups by
3 months.33 Lastly, pooled meta-analysis data of patients
undergoing EEA for sellar and parasellar lesions regardless of
reconstructive technique demonstrated no significant differ-
ence in preoperative and postoperative UPSIT results.34
Implications for clinical practice: The NSF is a robust and
reliable reconstructive option for large and high flow skull
base defects. Patients should be counseled regarding post-
operative morbidity associated with this flap, including the
potential for prolonged nasal crusting, septal perforation and
external nasal deformities. When the NSF is utilized, sur-
geons should consider grafting or rotational mucosal flaps to
cover the donor site and reduce prolonged crusting and other
donor site morbidity. When used for donor site re-mucosal-
ization, utilization of the contralateral reverse rotation flap
precludes the use of the contralateral NSF in future cases.
Aggregate level of evidence: 3
Utilization of Free Mucosal Grafts
FMGs have historically been utilized for small skull base
defects and were key components of cranial base reconstruc-
tion prior to the advent of the NSF and secondary vascular-
ized reconstructive options.35,36 FMGs do not have a direct
axial blood supply and can be harvested from several areas
including the nasal septum, MT, and nasal floor.37 As the
morbidity of the NSF donor site has become increasingly
recognized, there has been a renewed interest in FMG for
reconstructing routine small cranial base defects <1.5cm
and low flow CSF leaks without direct entrance to a cistern or
ventricle. Nasal floor FMGs are large, pliable and easily
harvested. Likely due to the relatively reduced air flow
through the inferior meatus and nasal floor compared with
the anterior nasal septum, the donor site in this region heals
remarkably well with little crusting and no risk of septal
perforation (►Fig. 3).38
Amongst the recent published reports of experience with
FMG utilization for sellar reconstruction, results have been
Journal of Neurological Surgery—Part B
Nasal Preservation and QOL in EEA Pinheiro-Neto et al. 605
promising. In an early experience with 50 consecutive FMGs
for sellar reconstruction, there were no postoperative CSF
leaks during the follow-up period. In addition, there was no
reduction in patient SNOT-22 scores at 1-month follow-up
compared with baseline, indicating no worsened nasal QOL
utilizing this technique. Lastly, nasal endoscopy at 1 month
demonstrated a completely re-mucosalized donor site in all
50 cases.39 In a follow-up study of 158 consecutive patients
undergoing sellar surgery, similar findings were reported.
The postoperative CSF leak rate for FMG graft patients was
0.82% and there was no difference in 1-month postoperative
SNOT-22 scores compared with baseline.40 It should be noted
that the technique in these studies included harvest of a
robust FMG including the nasal floor and a large portion of
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the inferior meatus mucosa, which allows for the large graft
to cover the entirety of the sella and clival recess.
Caution should be exercised, however, when reconstruct-
ing large or high flow cranial base defects. In a systematic
review of large skull base defects undergoing reconstruction,
pedicled vascularized flaps demonstrated a lower postoper-
ative CSF leak rate (6.7%) compared with FMGs (15.6%;
p ¼ 0.001).41 As with the selection of reconstruction for
any skull base defect, consideration must be given to the
balance between the need for a robust reconstructive option,
need to prevent postoperative CSF leak, and the associated
morbidity of the reconstructive options.
Implications for clinical practice: FMG reconstruction of
standard sellar defects appears to have favorable success
with prevention of postoperative CSF leaks and has a more
favorable donor site morbidity profile compared with NSF
reconstruction. Additionally, the role of pedicled vascular-
ized reconstructive options remains vitally important for
large or high flow cranial base defects.
Aggregate level of evidence: 4.
Turbinate Preservation
Most early descriptions of EEA techniques included resection
of the right or bilateral MT to facilitate surgical access and
tumor exposure. In addition, some authors have advocated
routine MT resection to prevent the risk of postoperative
iatrogenic frontal sinus outflow obstruction. However, the
necessity of MT resection for routine EEA cases has increas-
ingly been questioned. Advocates of MT preservation point to
its role in olfaction, nasal moisturization and nasal airflow
direction, as well as the theoretical increased risk of epistaxis
postoperatively with MT resection.42–45
In the initial description of routine MT preservation for
sellar surgery, Nyquist et al describe MT preservation in 163
consecutive EEA cases, of which 99 were pituitary adenoma
resections. In this series, they were able to preserve bilateral
MTs in 160/163 cases. They found that there were no cases of
postoperative frontal sinus obstruction on routinely
obtained 2-month postoperative MRI scans.44
Building on this concept, Willson et al describe a retro-
spective review of 122 sellar and suprasellar EEA cases. In
this series they compared postoperative MRI scan Lund-
MacKay scores (LM) at 0 to 3 months, 3 to 6 months, and
>6 months following EEA between MT resection and MT
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606 Nasal Preservation and QOL in EEA Pinheiro-Neto et al.

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Fig. 3 Right-sided nasal floor free mucosal graft harvest for reconstruction of sellar defect. (A) Donor site exam at 1 week, (B) 6 weeks, and (C)
3 months postoperatively. (D) View of the reconstructed sellar defect at 3 months postoperatively.

preservation cohorts. In this comparative study, there were
no differences in LM scores at any time point between the MT
resection and MT preservation cohorts, suggesting that MT
preservation does not cause significant iatrogenic obstruc-
tive sinusitis compared with MT resection.46
However, there may be cases when MT resection is
necessary to achieve adequate visualization of tumor, espe-
cially for extensive sellar tumors with Knosp-Steiner grade 4
involvement, suprasellar extension, or extensive carotid
artery involvement. In these cases, it appears that the
morbidity of MT resection may not be as severe as initially
thought. Dolci et al prospectively studied olfaction in 50
patients undergoing EEA who were divided into those who
had a partial unilateral MT resection (with preservation of
the superior one-third of the MT) and those who underwent
complete bilateral MT resection. In both groups, there was
diminished olfaction on Connecticut Chemosensory Clinical
Research Center tests at 1 and 3 months after surgery, but
olfaction returned to baseline by 6 months postoperatively.
However, there was no difference between the partial uni-
lateral MT resection group and complete bilateral MT resec-
tion group.47 Similar data has also been demonstrated with
bilateral superior turbinate resection during EEA, with re-
turn to baseline olfaction 2 months postoperatively, follow-
ing a transient decrease in olfaction over the first 2 to 6 weeks
postoperatively.48
Although there is a theoretical risk of inducing empty nose
syndrome (ENS) with MT resection, largely due to a 2006 case
report,49 the actual risk of ENS appears to be more correlated
with inferior turbinate resection than MT resection.50–52 Law
et al studied a prospective series of 95 consecutive patients
undergoing bilateral partial or complete MT resection for a
variety of sinonasal procedures. They formally evaluated
these patients with Empty Nose Syndrome 6-Item Question-
naire (ENS6Q) during the postoperative time period with a
mean follow-up of 19.4 months. In this cohort, 97.9% of
patients had ENS6Q scores that were within normal limits at
the date of their last follow-up and 93.7% had no visible
crusting at the date of their last follow-up.53
Implications for clinical practice: In the majority of EEA
cases, MTs can be preserved. MT preservation does not
appear to be associated with iatrogenic obstructive sinusitis.
However, in cases when tumor access necessitates MT resec-
tion, it does not appear to be associated with long-term
olfactory dysfunction or risk of ENS.
Aggregate level of evidence: 4

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 Nasal Preservation and QOL in EEA Pinheiro-Neto et al. 607

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Fig. 4 The superior ethmoidal approach for an olfactory groove meningioma; preoperative T1 post-gadolinium MRI (A) coronal view and (B)
sagittal view. Postoperative MRI T1 with contrast showing the superior ethmoidal space used for access and the middle turbinates preserved. (C)
coronal view and (D) sagittal view.

utilizing a unilateral endonasal transcribriform approach

Other Minimally Invasive Approaches
Septal Transposition for Olfactory Groove Meningiomas
As interest in nasal preservation has evolved, new techniques
have been described that allow for preservation of more
nasal structures during EEAs. Initially described by Rosen
et al in 2014, EEA for olfactory groove meningiomas can be
completed with a septal transposition technique, thus pre-
serving sinonasal anatomy and avoiding a resultant large
septal perforation. In this technique, the cartilaginous and
bony septum are mobilized and transposed to the side,
allowing full access to the anterior cranial base; the septum
is then placed back in the midline at the conclusion of the
case.54 Youssef et al described a similar technique in 2016,
with septal transposition in a cadaveric model and its
subsequent application in surgery for an olfactory groove
meningioma. Utilizing this technique, they were able to
achieve a gross total resection of the meningioma, while
preserving the contralateral olfactory apparatus and avoid-
ing disruption of the contralateral nasal cavity. At 1-year
follow-up, the patient retained olfaction with evidence of
microsomia on objective olfactory testing.55
Superior Ethmoidal Approach to the Anterior Cranial Base
Peris Celda, et al have described the development of an
endoscopic superior ethmoidal approach (SEA) for anterior
cranial base resection.56 This technique was developed in a

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608 Nasal Preservation and QOL in EEA Pinheiro-Neto et al.

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Fig. 5 Postoperative pictures obtained with a 30-degree endoscope of a patient who underwent endoscopic superior ethmoidal approach for
resection of an olfactory groove meningioma. Observe the middle turbinates preserved on the (A) right side and (B) left side. (C and D) View of
the left-sided nasoseptal flap well healed. Observe the pedicle along the left orbital wall and the sphenoid sinuses open.

cadaveric model and includes an inside-out Draf III frontal
sinusotomy with a limited anterosuperior septectomy with
exposure of the anterior cribriform fossa. Bilateral MTs are
then lateralized and a limited superior septectomy is per-
formed further posteriorly followed by resection of the
superior aspect of the MT basal lamella and superior turbi-
nates with a limited dissection of the superior ethmoid cells
and sphenoidotomy. Thus, anterior nasal structures which
encounter the majority of nasal airflow are preserved, in-
cluding the anterior portion of the MT and middle meatus
ostiomeatal complex. This technique was then utilized in
two cases of olfactory groove meningiomas achieving a gross
total resection (►Figs. 4 and 5).
A follow-up study was published in 2020 comparing the
nasal physiology of the SEA technique with traditional
endoscopic cranial base resections utilizing computational
flow dynamics (CFD).57 CFD results in SEA patients mirrored
that of non-operated control patients, with the majority of
airflow directed along the nasal floor and inferior turbinates
and equivalent air temperature to control patients (33.7–
32.72°C, p ¼ 0.468). On the other hand, patients who under-
went traditional endoscopic cranial base resections had
increased airflow directed at the maxillary sinus, sphenoid
sinus, and nasal cavity roof. In addition, the average nasal
temperature was lower than control or SEA patients (33.77–
30.3°C, p ¼ 0.015).
Implications for clinical practice: New EEA techniques that
allow for increased preservation of nasal structures for
purely intracranial tumors such as meningiomas are begin-
ning to be developed. The SEA may allow for more normal-
ized postoperative nasal physiology compared with
traditional endoscopic cranial base resection approaches.
As feasibility studies are performed and effects on nasal
QOL are investigated, these new techniques may be incorpo-
rated in one’s surgical armamentarium for appropriate cases.
Aggregate level of evidence: 4.

Journal of Neurological Surgery—Part B Vol. 83 No. B6/2022 © 2022. Thieme. All rights reserved.

Conclusion
As EEA techniques are increasingly utilized for intracranial
tumors, there has been recent interest in improved preser-
vation of nasal structures and minimizing nasal morbidity.
This contemporary review discusses balancing effective skull
base reconstructive techniques with associated morbidity,
the role of turbinate preservation in EEA, and the develop-
ment of unique EEA techniques that allow for increased nasal
structure preservation.
Conflict of Interest
None declared.
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