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.
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