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\begin{document}

\title{Endoscopic modified transseptal bi-nostril approach for pituitary
surgery does not impact olfaction: A retrospective study}



\author[1]{Teppei Takeda}%
\author[1]{Kazuhiro Omura}%
\author[1]{Eri Mori}%
\author[1]{Teru Ebihara}%
\author[2]{Satoshi Aoki}%
\author[2]{Kosuke Tochigi}%
\author[1]{Hirokazu Koseki}%
\author[1]{Ryosuke Mori}%
\author[1]{Yudo Ishii}%
\author[1]{Nobuyoshi Otori}%
\affil[1]{Jikei University School of Medicine}%
\affil[2]{Dokkyo Medical University Saitama Medical Center}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\selectlanguage{english}
\begin{abstract}
Objectives: To preserve olfactory function in each nostril following
pituitary surgery is important in the long term. However, no reports
evaluating olfactory outcomes in individual nasal cavities following
endoscopic endonasal transsphenoidal approach (EETSA) for pituitary
surgery have been published. Here, we used an endoscopic modified
transseptal bi-nostril approach for pituitary surgery, with possible
olfaction preservation without turbinate resection, and evaluated
olfactory outcomes in both left and right nostrils. Design: A
single-centre, retrospective study Setting and participants: Overall, 41
patients who underwent endoscopic modified transseptal pituitary surgery
with an olfactory and turbinate preservation approach at our hospital
between April 2018 and December 2019 were included in this study. Main
outcome measures: To completely protect the bilateral turbinates and
olfactory epithelium, this procedure provides access to the sphenoid
sinus by a transseptal approach via the left nasal cavity and by the
olfactory cleft approach via the right nasal cavity without resecting
any turbinate. A jet stream olfactometer (JSO) was used to assess the
mean recognitive threshold of the left, right, and bilateral nasal
passages before and after surgery. Results: The postoperative JSO test
values of the right, left, and bilateral nasal cavities were markedly
improved (p\textless{}0.01 for all) compared with the preoperative
values, but there was no difference in the values between the right and
left nasal cavities (p=0.85). No recurrence or olfactory dysfunction was
observed in any patient during the study period. Conclusion: Our
modified EETSA may be one method to approach preserving every turbinate
and olfaction.%
\end{abstract}%



\sloppy


ORIGINAL ARTICLE

Endoscopic modified transseptal bi-nostril approach for pituitary
surgery does not impact olfaction: A retrospective study

SUMMARY

\emph{\textbf{Objectives}: To preserve olfactory function in each
nostril following pituitary surgery is important in the long term.
However, no reports evaluating olfactory outcomes in individual nasal
cavities following endoscopic endonasal transsphenoidal approach (EETSA)
for pituitary surgery have been published. Here, we used an endoscopic
modified transseptal bi-nostril approach for pituitary surgery, with
possible olfaction preservation without turbinate resection, and
evaluated olfactory outcomes in both left and right nostrils.}

\emph{\textbf{Design:} A single-centre, retrospective study}

\emph{\textbf{Setting and participants}: Overall, 41 patients who
underwent endoscopic modified transseptal pituitary surgery with an
olfactory and turbinate preservation approach at our hospital between
April 2018 and December 2019 were included in this study.}

\emph{\textbf{Main outcome measures:} To completely protect the
bilateral turbinates and olfactory epithelium, this procedure provides
access to the sphenoid sinus by a transseptal approach via the left
nasal cavity and by the olfactory cleft approach via the right nasal
cavity without resecting any turbinate. A jet stream olfactometer (JSO)
was used to assess the mean recognitive threshold of the left, right,
and bilateral nasal passages before and after surgery.}

\emph{\textbf{Results}: The postoperative JSO test values of the right,
left, and bilateral nasal cavities were markedly improved
(p\textless{}0.01 for all) compared with the preoperative values, but
there was no difference in the values between the right and left nasal
cavities (p=0.85). No recurrence or olfactory dysfunction was observed
in any patient during the study period.}

\emph{\textbf{Conclusion}: Our modified EETSA may be one method to
approach preserving every turbinate and olfaction.}

\emph{\textbf{Keywords}: Nasal Surgical Procedure, Olfactory Mucosa,
Pituitary Gland, Smell}

Key points

\begin{itemize}
\tightlist
\item
  A single-centre retrospective study with 41 participants was
  conducted.
\item
  An endoscopic modified transseptal bi-nostril approach was used for
  pituitary surgery.
\item
  The procedure protects the bilateral turbinates and olfactory
  epithelium by providing access to the sphenoid sinus by a transseptal
  approach via the left nasal cavity and by the olfactory cleft approach
  via the right nasal cavity without resecting any turbinate.
\item
  The postoperative jet stream olfactometer test values of the right,
  left, and bilateral nasal cavities were markedly improved after
  surgery.
\item
  No recurrence or olfactory dysfunction was observed.
\end{itemize}

INTRODUCTION

Currently, the olfactory dysfunction rate associated with pituitary
surgery has been decreasing with improved approaches to access the
pituitary region. The rate after a sub-microscopic transsphenoidal
approach is approximately 39.7\%,\textsuperscript{2--9} whereas those
associated with the use of a nasoseptal flap (NSF) under endoscopy and
bilateral rescue flaps are approximately 14.4\%\textsuperscript{1,
10-13} and 0-12\%,\textsuperscript{4, 6, 7, 14, 15} respectively.
However, even with the use of bilateral rescue flaps, olfactory
dysfunction after the endoscopic endonasal transsphenoidal approach
(EETSA) remains a risk, attributed to the mechanical irritation to the
nasal septal mucosa and superior turbinate that occurs when securing the
corridor creation and visual field.\textsuperscript{6} Therefore, a less
stressful approach to the nasal septal mucosa and turbinates is needed.

There are also concerns about the olfactory testing methods used after
EETSA. Since most olfactory testing in the literature relies on
bilateral nasal olfactory tests, the test results may depend on the
results of the good side. Therefore, after EETSA surgery, it is unclear
whether the olfactory sense is preserved on one or both side(s).
Therefore, the assessment of olfactory function needs to be performed on
a unilateral basis because unilateral olfactory impairment influences
the ability to identify and discriminate
olfaction\textsuperscript{16}and is more likely to result in overall
olfactory impairment associated with increasing age.\textsuperscript{17}

In our institution, we use the endoscopic modified transseptal
bi-nostril approach to minimize turbinate and olfactory mucosal invasion
and ensure every turbinate's and bilateral olfaction's preservation.
Herein, we investigated the results of olfactory function and changes in
the right and left nostrils before and after surgery for cases using
this approach, and reported them with statistical analysis.

MATERIALS AND METHODS

\emph{Study population}

This single-centre retrospective study enrolled 41 patients who
underwent endoscopic modified transseptal pituitary surgery between
April 2018 and December 2019 at our hospital. The main inclusion
criterion was primary/recurrent pituitary adenoma, with olfactory
testing performed both preoperatively and 3 months postoperatively. The
exclusion criteria were endoscopic surgery combined with craniotomy,
endoscopic sinus surgery (ESS) performed intraoperatively/previously
performed, chronic rhinosinusitis (CRS) with/without nasal polyp, and
allergic rhinitis. All surgeries were performed by the same
otolaryngologist (O.K.) and neurosurgeons (I.Y., M.R.). The research
protocol was approved by the institutional ethics committee (Protocol
No. 32-081). Written informed consent was obtained from all patients.

\emph{Surgical approach} (video 1)

We chose a bi-nostril approach, with the left nostril approaching the
sphenoid sinus via the nasal septum and the right nostril approaching
the sphenoid sinus via the nasal cavity and olfactory cleft. A surgical
field of passage and approach to the sphenoid sinus was devised at our
centre by an otolaryngologist. First, an incision was made in the left
nasal septum mucosa from the anterior superior to the nasal floor. The
mucosa of the left nasal septum and nasal floor was raised from the
nasal septal cartilage and maxillary bone and pulled into the left limen
nasi, allowing a visual field to approach the sphenoid sinus via the
nasal septum. At this time, the greater palatine artery passing through
the canalis incisivus was not dissected (Fig. 1A). Second, septoplasty
was performed with the vomer and perpendicular plate of the ethmoid
removed. At the posterior edge of the nasal septum, an incision was made
from the nasal floor along the upper walls of the right and left choana
to increase the lateral range of motion of the left and right nasal
septal mucosa. The left and right nasal septal mucosa were laterally
deviated, and sphenoidotomy was performed until the bilateral sides of
the optic canal and carotid artery ridges were in the same endoscopic
field of view. (Fig. 1B). Third, the right nasal septal mucosa was
incised horizontally (posteriorly to anteriorly) with the nasal floor
from the upper margin of the sphenoid sinus ostium to the anterior end
of the middle turbinate (Fig. 1C). No turbinate was resected in any of
the cases. The posterior ethmoidal sinus may be opened by endoscopic
ethmoidectomy in cases of pituitary tumours that extend laterally beyond
the cavernous sinus at grade [?]3 according to Knosp
classification.\textsuperscript{18} A 1 mm-thick silicone plate (KOKEN,
Tokyo, Japan) was placed on the outside of the left and right nostrils
to protect the left nasal septal mucosa and right inferior/middle
turbinate and sewn into the nostrils on both sides. This allows for a
two-nostril, one-cavity approach (Fig. 1D). The sphenoid sinus mucosa,
which we call a local flap, was temporarily peeled off and preserved to
cover the wound finally, and the patient then underwent tumour removal
by the neurosurgical team. After pituitary tumour removal and
confirmation that there was no cerebrospinal fluid (CSF) leak,
osteophyte and mucosal reconstructions with a local flap were performed.
In cases of intraoperative CSF leakage, the horizontal incision in the
right nasal septal mucosa was extended and an NSF was prepared. If an
NSF was not used, the right-sided horizontal incision was sutured with
two stitches using 5-0 TF vicryl. The left-sided septal mucosal incision
line was sutured with three stitches, and the left and right nasal septa
were sutured together with three stitches using 4-0 RB-1 vicryl.
Finally, the left and right nasal septal mucosa were sutured with 5-0
nylon thread to sandwich the silicone plate. Nasal rinsing was initiated
1 week postoperatively, and the silicone plate was removed 1 month
postoperatively.

\emph{Olfactory function testing}

The jet stream olfactometer (JSO; Nagashima Medical Instruments, Tokyo,
Japan; Fig. 2) was used for olfactory testing performed according to the
guidelines,\textsuperscript{19-21} using five different olfactory
measurement reference odours. The concentration of each odour was set in
8 steps from -2 to 5, with 5 being the strongest, which was sequentially
diluted 10 times. However, when the concentration of 5 was not
adjustable because of problems with solubility in one type of odour,
there were 7 levels up to a concentration value of 4. The test was
conducted by pressing the stimulation button twice with a nozzle
inserted in the opposite side of the obstructed nasal cavity, and the
concentration of each of the five smells was gradually increased from
-2; the concentration at which a correct answer was provided was defined
as the recognition threshold. Because the olfactory threshold on the
good side is defined as the bilateral olfactory
threshold,\textsuperscript{16} for each of the five olfactory reference
odours, we selected the lowest recognition threshold between the left
and right nostrils as the recognition threshold for the bilateral nasal
cavities. This examination was performed twice, once before the surgery
and once 3 months after. The change in olfactory function was expressed
as the difference between preoperative and postoperative olfactory mean
recognition thresholds and defined as `improvement' when the difference
was positive and `deterioration' when the value was negative. The degree
of improvement was defined as improvement or deterioration when the
change in olfactory function had a value of 1 or higher; no change was
defined as stable olfactory function.

\emph{Evaluation items}

The primary endpoint was the change in olfactory recognitive function
before and after surgery using JSO. The reconstructive procedure,
treatment of superior/middle turbinate, intraoperative/postoperative CSF
leakage, postoperative nasal bleeding, and nasal septal perforation,
adhesions or narrowing of the olfactory cleft, or recurrence were
secondary endpoints.

\emph{Statistical analysis}

The mean recognition threshold in the left, right, and bilateral nasal
passages and the fluctuation of olfactory function in the left and right
nasal passages were analysed using the Wilcoxon signed-rank test.
Subgroup analysis was performed using the Mann--Whitney U test according
to the reconstruction procedure (local flap or NSF) and nasal septal
perforation (none or existence). The level of statistical significance
was set at p\textless{}0.05. GraphPad Prism 8 (GraphPad Software, San
Diego, CA) was used for statistical analyses.

RESULTS

The study included 27 patients who fulfilled the inclusion criteria and
excluded 14---10 did not have either preoperative or postoperative JSO,
2 patients were post-ESS due to CRS, 1 patient had undergone endoscopic
surgery combined with craniotomy, and 1 had strong nasal obstruction
caused by preoperative allergic rhinitis.

The characteristics of the included patients are shown in Table 1. Their
median age was 49 (interquartile range {[}IQR{]}, 41--59) years---16 men
and 11 women. There were 22 cases of first-time surgery and 5 revision
surgeries (4 microscopic and 1 endoscopic pituitary surgeries). There
were 15 cases with non-functional and 12 with functional pituitary
adenomas (5 growth hormone-secreting adenomas, 3 adrenocorticotropic
hormone-secreting adenomas, 3 gonadotrophic-secreting adenomas, and 1
thyroid stimulating hormone-secreting adenoma). The median follow-up
duration was 13 (IQR, 10--20).

The median preoperative JSO were 3.0 (IQR, 2.0--4.2) on the right, 3.0
(2.2--4.2) on the left, and 2.0 (1.6--3.2) in bilateral nasal cavities.
Postoperatively, the median JSO test results were 1.6 (1.0--2.6) on the
right, 1.4 (1.2--2.4) on the left, and 1.0 (0.8--2.2) in bilateral nasal
cavities. Olfactory function had improved in the right, left, and
bilateral nasal cavities according to the JSO test results
(p\textless{}0.01 for all; Fig 3). The change in olfactory function was
1.6 (0.4--2.2) on the right, 1.0 (0.4--2.8) on the left, and 1.0
(0.2--1.8) in bilateral nasal cavities, with significant differences
between the right and bilateral nasal cavities (P=0.04) and between the
left and bilateral nasal cavities (P=0.03); however, there was no
significant difference between the left and right nasal cavities
(P=0.82; Fig. 3). Concerning the degrees of improvement, in the right
nasal cavity, 17 (63\%) improved and 10 (37\%) remained stable; in the
left nasal cavity, 13 (48\%) improved and 14 (52\%) remained stable; and
bilaterally, 15 (56\%) improved and 12 (44\%) remained stable, with no
deterioration in the respective evaluations (Table 2).

All patients underwent surgery for pituitary adenomas following this
surgical approach, with eight cases of intraoperative CSF leaks using
right-sided NSF for reconstruction and other 19 patients requiring only
local flap. There were no cases where the superior/middle turbinate was
sacrificed during the procedure and no cases of postoperative nasal
bleeding or CSF leakage, adhesions or narrowing of the olfactory cleft.
Postoperative nasal septal perforation was observed in two patients who
underwent right-sided NSF and in one patient who underwent local flap
reconstruction; these three patients had a small perforation in the
posterior part of the nasal septum. There were no cases of recurrence
during the follow-up period. There was no significant difference in the
change in olfactory function or the presence of nasal septal perforation
between different reconstruction methods (Table 3).

DISCUSSION

This approach aims at preserving every turbinate and minimally
invasively manipulating the olfactory mucosa to preserve bilateral
olfaction. The JSO test showed that no patients, regardless of the
reconstructive technique, experienced deterioration in olfaction after
EETSA in the right, left, or bilateral nasal assessments. There was no
change in olfactory function between the right and left nasal cavities.

The modification point of EETSA is the addition of an incision centred
on the choana and posterior edge of the nasal septum and a posterior
horizontal incision of the right septal mucosa to the transseptal
approach. This approach seems more invasive than the conventional
transseptal approach because of the mucosal incision. However, the
conventional transseptal approach is a single nostril approach, and the
working space for forceps is narrow. Contrarily, in this modified
transseptal approach, a unilateral horizontal incision added posterior
to the nasal septum allows for a bi-nostril approach, an incision added
at the posterior edge of the nasal septum eliminates its narrowing, and
the blood that accumulates in the nasal septum flows to the choana,
greatly increasing the space for the endoscope and forceps. Compared to
the bilateral rescue flap approach, the invasiveness associated with
mucosal incision seems to have increased. However, in this approach, the
incision into the olfactory mucosa requires only a unilateral posterior
horizontal incision of the nasal septum and hence, is less invasive into
the olfactory mucosa than the bilateral rescue flap approach with
bilateral posterior horizontal incisions of the nasal septum.
Furthermore, this approach allows us to resect the anterior wall of the
sphenoid sinus through the nasal septum, providing us with a good field
of view while avoiding damage to the right and left nasal septal mucosa,
and to perform surgery with the nasal turbinates and olfactory mucosa on
one side (left side) completely intact. Therefore, the mechanical
irritation to the bilateral nasal septal mucosa and superior turbinate
that occurs with the bilateral rescue flap
approach\textsuperscript{6}during visual field acquisition and tumour
removal operation is completely eliminated, at least on one side, using
this approach. In the right nasal cavity, manipulating the nasal septal
mucosa by creating a horizontal incision and NSFs and inserting and
removing endoscopes and forceps physically impaired the turbinate, but
using a silicone plate in the right nasal cavity protected the right
inferior and middle turbinate and reduced mechanical irritation. This
reduced the risk of nasal septal perforation because of damage to the
mucosa of the nasal septum, and the risk of postoperative olfactory
cleft adhesions and olfactory dysfunction because of damage to the
tissue mucosa, such as turbinates, and bleeding.

Herein, we investigated the olfactory fluctuation associated with this
approach using JSO. JSO was developed to quantify olfactory stimuli
exploiting the features of the T\&T olfactometer (Daiichi Yakuhin
Sangyo, Tokyo, Japan). Bilateral nasal olfactory tests, such as the
University of Pennsylvania smell identification test (UPSIT),
Connecticut Chemosensory Clinical Research Center test (CCCRC test), and
Sniffin' Sticks, are less likely to elucidate the effects of olfaction
on either nasal cavity. In contrast, the JSO, which allows for the study
of olfaction in each individual nasal cavity, may be more useful because
it can provide specific olfactory outcomes. There were no cases of
deterioration of olfaction in both the right and left nasal passages
after this approach was applied. Rather, the JSO test showed an improved
sense of smell in the nasal cavities bilaterally. Since we did not
perform rhinomanometry or computational fluid dynamics analysis of the
nasal cavity, or pre- and post-operative measurement of olfactory cleft
width, we could not confirm the reason for the improvement. However,
since this approach was performed via the nasal septum and there was
less invasion of the olfactory cleft, there were no cases of adhesions
or narrowing of the cleft, which we believe contributed to the
preservation of olfaction. Although there have been no reports of
unilateral olfactory investigations using JSO for EETSA, there have been
reports of different olfactory thresholds in the left and right nasal
passages using JSO in patients with sinusitis,\textsuperscript{22} and
different olfactory outcomes in each unilateral region have been
demonstrated, also suggesting its usefulness.\textsuperscript{23}

There are limitations to the current study. Although the JSO correlates
with the T\&T olfactometer, which is widely used in
Japan,\textsuperscript{20} no reports compare it to the UPSIT, CCCRC
test, or Sniffin' Sticks, which are widely used
internationally.\textsuperscript{23,24} Therefore, the other tests
should also be used in the future to confirm that this approach does
improve olfaction. In addition, as the sample size was small, a Type 2
error is possible. This was a retrospective study and the results of
this study need to be interpreted with caution.

CONFLICT OF INTEREST

The authors have no conflict of interest to declare.

DATA SHARING AND DATA AVAILABILITY

Data supporting the findings of this study are available upon request to
the corresponding author. The data are not publicly available due to
privacy and ethical restrictions.

REFERENCES

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\textbf{Table 1}

Patient characteristics (n =27)\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
Characteristic & & & &\tabularnewline
\midrule
\endhead
Age (year)\textsuperscript{a} & & & 49 & (41--59)\tabularnewline
Follow-up period (months)\textsuperscript{a} & & & 13 &
(10--20)\tabularnewline
Sex \textsuperscript{b} & Male & & 16 & (59)\tabularnewline
& Female & & 11 & (41)\tabularnewline
Past history of pituitary surgery \textsuperscript{b} & None & & 22 &
(81)\tabularnewline
& Revision & Microscopic & 4 & (15)\tabularnewline
& & Endoscopic & 1 & (4)\tabularnewline
Histopathology \textsuperscript{b} & NFA & & 15 & (56)\tabularnewline
& FA & GHoma & 5 & (19)\tabularnewline
& & ACTHoma & 3 & (11)\tabularnewline
& & LH/FSHoma & 3 & (11)\tabularnewline
& & TSHoma & 1 & (4)\tabularnewline
\bottomrule
\end{longtable}

Microscopic: A case of a previous microscopic pituitary surgery.
Endoscopic: A case of a previous endoscopic pituitary surgery.

Abbreviations: ACTHoma: adrenocorticotropic hormone-secreting pituitary
adenoma; FA: functioning pituitary adenoma; GHoma: growth
hormone-secreting pituitary adenoma; NFA: non-functioning pituitary
adenoma; LH/FSHoma: gonadotropin-secreting pituitary adenoma; TSHoma:
thyroid stimulating hormone-secreting pituitary adenoma.

a: ~data are presented as medians (IQRs; interquartile ranges).

b: ~data are presented as numbers (percentages).

\textbf{Table 2}

Results of postoperative olfactory function with jet stream olfactometer
testing of the right, left, and bilateral nasal cavities.\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Postoperative olfactory function\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Postoperative olfactory function\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Postoperative olfactory function\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Evaluation by jet stream olfactometer\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Improved\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Stable\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Deteriorated\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
n, (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
n, (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
n, (\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Right side\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
17 (63)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
10 (37)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Left side\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
13 (48)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
14 (52)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Bilateral\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
15 (56)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
12 (44)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Right side: examination of olfaction in the right nasal cavity.

Left side: examination of olfaction in the left nasal cavity.

Bilateral: examination of olfaction in the bilateral nasal cavity.

\textbf{Table 3}

Results of subgroup analysis of the degree of olfactory improvement in
the left, right, and bilateral nasal passages\selectlanguage{english}
\begin{longtable}[]{@{}lllllllll@{}}
\toprule
Characteristic & & & Change in olfactory function in
JSO\textsuperscript{a} & Change in olfactory function in
JSO\textsuperscript{a} & Change in olfactory function in
JSO\textsuperscript{a} & Change in olfactory function in
JSO\textsuperscript{a} & Change in olfactory function in
JSO\textsuperscript{a} & Change in olfactory function in
JSO\textsuperscript{a}\tabularnewline
\midrule
\endhead
& & & Right side & P-value & Left side & P-value & Bilateral &
P-value\tabularnewline
Reconstruction procedure & Rescue flap & n= 19 & 1.6 (0.4--2.6) & 0.35 &
1.4 (0.6--3.0) & 0.23 & 1.0 (0.4--1.8) & 0.26\tabularnewline
& Nasoseptal flap & n= 8 & 1.5 (0.1--2.0) & & 0.6 (0.3--1.6) & & 0.4
(-0.3 to 1.7) &\tabularnewline
Nasal septum perforation & None & n= 24 & 1.4 (0.3--2.2) & 0.47 & 0.9
(0.3--2.6) & 0.59 & 0.9 (0.1--1.8) & 0.12\tabularnewline
& Existence & n= 3 & 1.8 (1.2--3.2) & & 1.8 (0.4--3.4) & & 1.8
(1.2--2.8) &\tabularnewline
\bottomrule
\end{longtable}

JSO: The jet stream olfactometer.

\textsuperscript{a}~data are presented as medians (interquartile ranges
{[}IQRs{]}).

Statistical comparison using the Mann--Whitney U test.

\textbf{Figure legends}

\textbf{Figure 1} Surgical approach (Supplement with Video)

A: A mucosal incision was made from the upper nasal septum to the nasal
floor along the red line. The left nasal septal mucosa was shifted to
the left limen nasi. At this time, the greater palatine artery passing
through the canalis incisivus was not dissected (white allow).
Septoplasty was performed with the vomer and perpendicular plate of the
ethmoid removed, it provided an approach route from the left nasal
cavity through the nasal septum to the sphenoid sinus.

B: A Y-shaped nasal septal mucosal incision (white dotted line) was made
from the nasal floor along the posterior edge of the nasal septum and
upper walls of the right and left choana. The left and right nasal
septal mucous membranes were laterally deviated, and the anterior walls
of the sphenoid sinus were excised until the optic nerve canal and
carotid artery prominences on both sides were in the same field of view.

C: The horizontal incision was made in the right nasal septal mucosa up
to the anterior end of the middle turbinate.

D: The silicone plate was sewn into the bilateral nostrils and it acted
as a spacer to ensure a good working space.

\textbf{Figure 2} The jet stream olfactometer (JSO; Nagashima Medical
Instruments, Tokyo, Japan)

\textbf{Figure 3} Results of the jet stream olfactometer test for the
study subjects (n= 27).

The X-axis represents the evaluation of the jet stream olfactometer
(JSO) in the left and right and bilateral nasal passages. The Y-axis
represents the average recognitive threshold of the JSO.

\emph{Pre-op:} Preoperative olfactory function testing.

\emph{Post-op:} Postoperative olfactory function testing.

a: data are presented as medians (IQRs; interquartile ranges).

*: Statistically significant difference (Wilcoxon signed-rank test).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/EETSA-Fig-1/EETSA-Fig-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/EETSA-Figure2/EETSA-Figure2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/EETSA-Fig-3/EETSA-Fig-3}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

