This is the first study to evaluate the pharyngeal observation ability in patients undergoing transoral UGE under sedation with, versus without, administration of topical pharyngeal anesthesia. Our study revealed that non-inferiority of non-pharyngeal anesthesia was not demonstrated in terms of the pharyngeal observation success rate; and the percentage of suitable quality images at the posterior wall of the oropharynx, vocal fold, and pyriform sinus was significantly inferior. However, in the subgroup analysis of a higher level of sedation, almost no differences in the pharyngeal observation success rate between with and without pharyngeal anesthesia were observed.
However, in ad hoc analysis, the PA + group had a significantly higher pharyngeal observation success rate than the PA- group (p = 0.0012). Naturally, it is not a preset test; however, the PA + group may have better pharyngeal observation ability than PA- group for patients who were administered intravenous anesthesia with midazolam.
The PA + group was significantly superior to the PA- group in terms of the number of observable pharyngeal parts (0.53 parts), observation time (9.0 s), pain measured using VAS (0.53 points), and the number of gag reflexes (1.72 times) owing to the advantages of pharyngeal anesthesia using lidocaine. These differences were presumably small absolute numerical numbers between groups. However, these were clinically important facts for endoscopists focusing on reducing patients' pain as much as possible. Pharyngeal anesthesia may be tolerated after weighing these differences against the side effects.
In the subgroup analysis of each pharyngeal site, the PA- group was statistically inferior to the PA + group in terms of observation of the posterior wall of the oropharynx, epiglottis, vocal fold, and right and left pyriform sinus. This difference could be attributed to multiple comparisons. It is suspected that the effect of anesthesia in the hypopharynx may be stronger in the PA + group; however, more cases need to be evaluated to prove the theory. Further studies on the relationship between the extent of hypopharyngeal anesthesia and pharyngeal observation ability are desirable because the pyriform sinus is the predilection site of pharyngeal cancer.
In the subgroup analysis for each variable, obese patients (BMI ≥ 25) and patients with low sedation levels (Ramsay score < 5) may have low pharyngeal observation success rates in the PA- group. To clarify these differences, it is necessary to evaluate additional cases.
Detailed subgroup analysis of each sedation level revealed that the pharyngeal observation success rate and the number of observable sites were low in the PA- group at the low sedation level (Ramsay score < 5). However, these differences were not observed at the high sedation level (Ramsay score ≥ 5). Based on our study findings, it is reasonable to presume that deep sedation reduces the disadvantage of not using pharyngeal anesthesia. This would be beneficial for patients who cannot use pharyngeal anesthesia because of allergies. Although the possibility of chance by multiple analyses cannot be ruled out, as deep sedation with propofol has shown that pharyngeal anesthesia is unnecessary, the deeper the sedation level, the lesser the pharyngeal anesthesia that might be required.
In the deep sedation group, pharyngeal anesthesia may further reduce pain and pharyngeal observation time. Although difficult to explain theoretically, this may be because pharyngeal anesthesia reduces the patients' pain and the difficulty in observation. Alternatively, considering that there is a similar tendency without significant difference in the low sedation group, it may not be relevant to sedation. A larger study is necessary to investigate this further.
Diagnostic transnasal endoscopy is proven to be more tolerable than the transoral approach (23,24). Furthermore, during the COVID-19 pandemic, transnasal endoscopy has proven to be beneficial in terms of less aerosol spreading (25). However, transoral endoscopy models have magnification and better image quality. Therefore, many endoscopists prefer it.
This study had some limitations. First, it was carried out at a single institution. Second, it was single-blind because the patients knew whether they were administered pharyngeal anesthesia or not. The PA- group did not receive a placebo intervention because of the difficulty of creating a placebo with a flavor similar to lidocaine. Thus, awareness of whether pharyngeal anesthesia was administered or not, might have altered their mental state and affected the outcome. Third, our study did not evaluate the postcricoid area. The nasal Valsalva or sniffing position was reported to improve examination in transoral endoscopy (26,27); however, we did not adopt such methods. Future studies are needed to explore these methods. Fourth, no synthetic opioid analgesics such as pethidine were used as a premedication. However, our findings will be important for facilities still unable to use them. Fifth, high-risk patients with pharyngeal cancer often have a history of alcohol drinking and may be tolerant to sedation. Such patients are considered to be more suitable for participation. Sixth, the definition of successful pharyngeal observation formulated by us may seem controversial among experts. Thus far, no consensus exists among experts in this regard. Hence, it is desirable to establish clear criteria for future clinical research