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<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<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 approach6during 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,22 and
different olfactory outcomes in each unilateral region have been
demonstrated, also suggesting its usefulness.23
There
are limitations to the current study. Although the JSO correlates with
the T&T olfactometer, which is widely used in
Japan,20 no reports compare it to the UPSIT, CCCRC
test, or Sniffin’ Sticks, which are widely used internationally.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
- Harvey RJ, Winder M, Davidson A, et al. The olfactory strip and its
preservation in endoscopic pituitary surgery maintains smell and
sinonasal function. J Neurol Surg B Skull Base 2015;76:464-70.
- Eördögh M, Briner HR, Simmen D, et al. Endoscopic unilateral
transethmoid-paraseptal approach to the central skull base.
Laryngoscope Investig Otolaryngol 2017;2:281-7.
- Griffiths CF, Cutler AR, Duong HT, et al. Avoidance of postoperative
epistaxis and anosmia in endonasal endoscopic skull base surgery: a
technical note. Acta Neurochir (Wien) 2014;156:1393-401.
- Upadhyay S, Buohliqah L, Dolci RLL, et al. Periodic olfactory
assessment in patients undergoing skull base surgery with preservation
of the olfactory strip. Laryngoscope 2017;127:1970-5.
- Rivera-Serrano CM, Snyderman CH, Gardner P, et al. Nasoseptal
“Rescue” flap: A novel modification of the nasoseptal flap technique
for pituitary surgery. Laryngoscope 2011;121;990-3.
- Kuwata F, Kikuchi M, Ishikawa M, et al. Long-term olfactory function
outcomes after pituitary surgery by endoscopic endonasal
transsphenoidal approach. Auris Nasus Larynx 2020;47:227-32.
- Griffiths CF, Barkhoudarian G, Cutler A, et al. Analysis of olfaction
after bilateral nasoseptal rescue flap transsphenoidal approach with
olfactory mucosal preservation. Otolaryngol Neck Surg 2019;161:881-9.
- Kahilogullari G, Beton S, Al-Beyati ESM, et al. Olfactory functions
after transsphenoidal pituitary surgery: Endoscopic versus microscopic
approach. Laryngoscope 2013;123:2112-9.
- Hong SD, Nam D-H, Seol HJ, et al. Endoscopic binostril versus
transnasal transseptal microscopic pituitary surgery: Sinonasal
quality of life and olfactory function. Am J Rhinol Allergy
2015;29:221-5.
- Rotenberg BW, Saunders S, Duggal N. Olfactory outcomes after
endoscopic transsphenoidal pituitary surgery. Laryngoscope
2011;121:1611-3.
- Tam S, Duggal N, Rotenberg BW. Olfactory outcomes following endoscopic
pituitary surgery with or without septal flap reconstruction: a
randomized controlled trial. Int Forum Allergy Rhinol 2013;362-65.
- Chaaban MR, Chaudhry AL, Riley KO, Woodworth BA. Objective assessment
of olfaction after transsphenoidal pituitary surgery. Am J Rhinol
Allergy 2015;29:365-8.
- Soyka MB, Serra C, Regli L, et al. Long-term olfactory outcome after
nasoseptal flap reconstructions in midline skull base surgery. Am J
Rhinol Allergy 2017;31:334-7.
- Hong SD, Nam D-H, Park J, et al. Olfactory outcomes after endoscopic
pituitary surgery with nasoseptal “rescue” flaps: Electrocautery
versus cold knife. Am J Rhinol Allergy 2014;28:517-9.
- Hong SD, Nam DH, Kong DS, et al. Endoscopic modified transseptal
transsphenoidal approach for maximal preservation of sinonasal quality
of life and olfaction. World Neurosurg 2016;87:162-9.
- Frasnelli J, Livermore A, Soiffer A, Hummel T. Comparison of
lateralized and binasal olfactory thresholds. Rhinology
2002;40:129-34.
- Gudziol V, Paech I, Hummel T. Unilateral reduced sense of smell is an
early indicator for global olfactory loss. J Neurol 2010;257:959-63.
- Micko ASG, 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;122:803-11.
- Miwa T, Ikeda K, Kogawa T. Kyuukaku syougai sinryou
gaidorain嗅覚障害診療ガイドライン. Nihon Bika Gakkai Kaishi (Japanese
J Rhinol) 2017;56:487-556 (in Japanese).
- Miwa T, Furukawa M, Matsune S, et al. Clinical usefulness of five
odorant jet stream olfactometry. Nihon Bika Gakkai Kaishi (Japanese J
Rhinol 2004;43:182-7 (abstract in English, text in Japanese).
- Yonezawa N, Mori E, Kojima H, et al. Importance of olfactory function
assessment for olfactory dysfunction. Japanese J Med Technol
2019;68:302-7 (abstract in English, text in Japanese).
- Ikeda K, Tabata K, Oshima T, et al. Unilateral examination of
olfactory threshold using the Jet Stream Olfactometer. Auris Nasus
Larynx 1999;26:435-9.
- Kondo H, Matsuda T, Hashiba M, Baba S. A study of the relationship
between the T&T olfactometer and the University of Pennsylvania Smell
Identification Test in a Japanese population. Am J Rhinol
1998;12:353-8.
- Hong SM, Park IH, Kim KM, et al. Relationship between the Korean
version of the sniffin’ stick test and the T&T olfactometer in the
Korean population. Clin Exp Otorhinolaryngol 2011;4:184-7.