Comparison of transoral robotic surgery with other surgeries for obstructive sleep apnea

This study compared the characteristic surgical parameters and clinical effects of transoral robotic surgery (TORS) and other available methods used to alleviate obstructive sleep apnea. Articles on TORS and other surgeries for obstructive sleep apnea were identified in the PubMed and EMBASE databases. Two investigators independently reviewed the articles and classified the data for meta-analysis. The pooled effect sizes of TORS (standardized mean difference; SMD = − 2.38), coblation tongue base resection (CTBR; SMD = − 2.00) and upper airway stimulation (UAS; SMD = − 0.94) revealed significant improvement in the apnea–hypopnea index (AHI; p < 0.05). The lowest O2 saturation reported was significantly increased following TORS (SMD = 1.43), CTBR (SMD = 0.86) and UAS (SMD = 1.24, p < 0.05). Furthermore, TORS (SMD = − 2.91) and CTBR (SMD = − 1.51, p < 0.05) significantly reduced the Epworth Sleepiness Scale (ESS) score. No significant difference in operation time, success rate, or instances of complication were observed between TORS and the other compared interventions. The use of TORS in obstructive sleep apnea has the same rate of success and failure as other methods of surgical intervention for obstructive sleep apnea with no statistical difference in operation times. The reported clinical effects on the AHI, lowest O2 saturation, and ESS scores of TORS were similar to those of other surgeries.


Results
In January 2020, 76 articles were identified in a preliminary search, and 8 of these articles met the criteria for review 4,[11][12][13][14][15][16][17] . The results of QUADAS-2 assessment of the included articles are illustrated in Table 1. A funnel plot was used to examine bias for meta-analysis ( Fig. 2) and revealed a significant treatment effect in these studies (p < 0.05). Among the included studies, six were retrospective [11][12][13][14][15]17 , one had a pre-post-test design 16 , and one was prospective 4 . In total, 188 patients with obstructive sleep apnea treated with TORS and 230 cases treated with alternative interventions were included in the analysis. Three studies investigated coblation tongue base resection (CTBR, total n = 79) [11][12][13] , and two studies investigated upper airway stimulation (UAS, total n = 105) 14,15 . Three articles reported on radiofrequency (n = 20), CO 2 laser (n = 10), and endoscopic partial midline glossectomy (EPMG, n = 16) 4,16,17 . The success numbers of TORS and alternative interventions are represented in Table 2. However, the post-operation cure rate in the article of Yu et al. was defined as AHI < 5 15 , whereas other studies used the success rate.

AHI, lowest O 2 saturation, and ESS score after TORS and alternative interventions. Preopera-
tion and postoperation AHIs were reported in all the papers ( Table 2) 4,[11][12][13][14][15][16][17] . All patients treated with TORS displayed a significant decrease in AHI (p < 0.05), and the total random effect was − 2.38 (a decline in average AHI from 41.56 to 17.10 events/h), as displayed in These studies did not include pooled effect sizes of AHI for radiofrequency, CO 2 laser or EPMG. Six studies measured the lowest O 2 saturation before and after the operation 11,13-17 . As illustrated in Table 4, a comparison of SMD in TORS revealed a significant increase in lowest O 2 saturation (increase in average lowest O 2 saturation from 79.83 to 86.81%; total random effect = 1.43, p < 0.05). The pooled effect sizes for CTBR (increase in average lowest O 2 saturation from 76.25 to 83.01%; total fixed effect = 0.86) and UAS (an increase in average lowest O 2 saturation from 79.45 to 85.55%; total fixed effect = 1.24) also revealed significant increases in Table 1. The results of QUADAS-2 in included studies. , low risk; , high risk, ?, unclear risk.  16 and one on EPMG 17 reported that of lowest O 2 saturation was improved, and the effect sizes were 2.57 and 0.32, respectively. As displayed in Table 5, five studies measured ESS score before and after the operation [11][12][13]16,17 . Comparison of the effect size after treatment with TORS revealed a significant decrease in ESS scores (decline in average ESS score from 12.82 to 5.33; total random effect = − 2.91, p < 0.05). Comparison of the pre-operative and postoperative ESS scores in three studies revealed that CTBR caused a significant decrease (decline in average ESS score from 10.66 to 6.43; total random effect = − 1.51, p < 0.05). However, the ESS scores of patients treated with CTBR were higher than those of patients treated with TORS. One article on radiofrequency 16 and one article on EPMG 17 revealed a reduction in ESS score at − 4.19 and − 0.83, respectively.

Operation time in TORS and compared interventions.
Three articles reported data on operation time 11,12,16 . A comparison of effect size between TORS and the alternative interventions, CTBR and radiofrequency, revealed no significant differences in operation time for the treatment of obstructive sleep apnea (p > 0.05, Fig. 3).

Success rate and complication rate in TORS and compared interventions.
Seven studies compared the success rate of TORS with that of alternative interventions (CTBR, UAS, radiofrequency, CO 2 laser and EPMG) 4,[11][12][13][14]16,17 . The odds ratio revealed that no significant differences were observed in the success rates using TORS and other interventions for obstructive sleep apnea (pooled odds ratio = 0.82, p > 0.05, Fig. 4). Five studies reported the complication rates after treatment with TORS or a comparedintervention (CTBR, UAS, or radiofrequency) [11][12][13][14]16 . An assessment of the relative risk revealed that the complication rate of TORS was higher than those of the alternative interventions. However, this difference was also non-significant (pooled relative risk = 1.30, p > 0.05, Fig. 5). Table 2. Overview of studies on TORS and compared studies. NA, not available; M/F, male/female; BMI, body mass index; TORS, transoral robotic surgery; CTBS, coblation tongue base resection; UAS, upper airway stimulation; EPMG, endoscopic partial midline glossectomy; AHI, apnea-hypopnea index; ESS, Epworth Sleepiness Scale. a Average age; b cure no. of patients; *Statistical significance in pre-and post-operation (p < 0.05).

Author (year) Design Intervention (n)
Obstructive sleep apnea patients

Discussion
TORS is a novel and technologically advanced surgery that has been used to treat obstructive sleep apnea. This systematic review was conducted to compare the clinical effects of the surgical interventions, such as TORS, CTBR, UAS, radiofrequency, CO 2 laser, and EPMG. Clinical outcome (AHI, lowest O2 saturation, and ESS score) and surgical effect (operation time, success rate, and complication rate) data for TORS and alternative interventions were compared using meta-analysis. The eight published articles included in our analysis are summarized in Table 2. Our results demonstrated that TORS, and the other interventions, significantly reduced the AHI and ESS score and increased the lowest O 2 saturation in patients with obstructive sleep apnea patients. No significant differences in operation time, success rate, or complication rate were observed between TORS and the compared interventions (p > 0.05).
A meta-analysis of the procedures revealed that the pooled SMD in the AHI, lowest O 2 saturation, and ESS score for TORS were larger than those for CTBR and UAS. All three interventions had significant effects on   www.nature.com/scientificreports/ obstructive sleep apnea (p < 0.05). However, UAS is currently considered to be the optimal method for widening the oropharynx and retroglossal space 18 . The Food and Drug Administration approves of UAS in patients with tongue base anterior-posterior collapse and an AHI of < 50/h 19 . Huntley et al. indicated that the UAS surgical procedure is a multilevel procedure and focuses on tongue base obstruction and airway caliber in patients with obstructive sleep apnea. CTBR has the advantages of minimal training time and lower cost than TORS 14 . However, the excitement of electrodes on the instrument can create ionized particles in saline solution and disrupt intercellular bonds. The outcomes of CTBR show unfavorable effects of necrosis and scar tissue formation in patients who underwent the procedure 20 . However, in our systematic review, we found that patients treated with TORS had reduction in both AHI and lowest O 2 saturation values as well as ESS improvement, and the effect size of TORS was slightly superior to those of CTBR and UAS. We thought that this is because TORS is performed using a real layer resection of lingual tonsils and a partial resection of tongue base muscle. Therefore, the volume reduction is more prominent than the volume reduction following radiofrequency or CTBR. Radiofrequency and CTBR may exhibit a firewall effect, meaning that the volume-reduction effects may be minimized by denatured tissue blocking energy transfer from the core of the surgical devices. Furthermore, UAS electric titration is not sufficiently powerful for most cases of huge tongue collapse or lateral pharyngeal collapse. The rate of increased volume varies depending on the quantity of electric power used, which also explains the unstable improvements in AHI, lowest O 2 saturation, and ESS score. We identified few data comparisons of AHI, lowest O 2 saturation and ESS score following treatment with radiofrequency, CO 2 laser, and EPMG. The radiofrequency method reduces tissue volume using high-frequency current flow to apply a selective temperatures 21 . Patients with obstructive sleep apnea had decreased snoring and improved respiratory effort when treated with radiofrequency applied to the soft palate 22 . The results reported by Aynacı et al. indicated that the radiofrequency method had better outcomes than TORS in terms of operation duration, length of post-operation hospitalization, and oral feeding duration 16 . Furthermore, 15% of complications from all methods were found after treatment with TORS, while no complications occurred after treatment with radiofrequency. CO 2 laser treatment is a cost-effective surgery that causes less thermal damage from tissue cutting and coagulation than alternative methods 23 . Karaman et al. determined that the CO 2 laser method has a lower complication rate, operation duration, length of postoperative hospitalization, and oral feeding time than TORS. After treatment with CO 2 laser, patients with sleep apnea patients had a significantly lower AHI and significantly less postoperative pain (p < 0.05) 4 . Furthermore, tissue resection is easier using CO 2 laser treatment compared with TORS 4,24 . EPMG was reported to be an effective surgical procedure in treating obstructive sleep apnea 25 . Folk et al. compared the changes in AHI, lowest O 2 saturation, and ESS score pre-and post-operation, but no significant differences were observed (p > 0.05) 17 . TORS has been demonstrated to have superior clinical effects to EPMG in patients with sleep apnea. Few studies have compared TORS to methods such as radiofrequency, CO 2 laser, and EPMG. Therefore, discussion regarding the clinical implications of these interventions has been limited.
Currently, surgical reduction of retroglossal airway obstruction is a common method for treating tongue base collapse. Effect parameters (AHI, lowest O 2 saturation, and ESS score) were used in the present study to assess pre-and post-operation conditions. The information provided by each article was not sufficient to perform a meta-analysis of surgical characteristics. Only three articles provided operation time data 11,12,16 . No significant differences were observed in operation times among TORS, CTBR, and radiofrequency (p > 0.05). However, when performed by an experienced surgeon with a low docking times, TORS was less time consuming than the other interventions. We also identified no significant differences in the success and complication rates of TORS and other surgical interventions for obstructive sleep apnea (p > 0.05). The volume of the tongue base is considered to be unrelated to surgical outcomes if Sher's criteria are used (post-operative AHI < 20 and > 50% reduction of preoperative AHI). However, the AHI and lowest O 2 saturation displayed larger improvements after TORS than other interventions. The TORS and CTBR methods of tongue-base reduction exhibited competitive surgical results 26 . Furthermore, no significant differences in ESS score, lowest O 2 saturation, operation time, or complication rate were observed between the two methods. A previous study revealed increased O 2 saturation and a reduction in AHI after treatment with TORS, however, the study also reported that TORS resulted in a higher pain score 27 . Hoff et al. reported that the TORS procedure had a shorter operation times than other interventions 28 . Studies on CTBR reported comorbidities of bleeding, pain, transient dysphagia, and dysgeusia 29,30 . Studies reported a taste disturbance rate of 13.8-17.5% following CTBR, comparable to the reported dysgeusia rates in three www.nature.com/scientificreports/ systematic review studies on TORS 29,31,32 . We determined that TORS led to a higher AHI reduction even with a higher baseline in some studies 6,13,26 . However, the TORS still yielded results were comparable to those of other methods such as CTBR or CO 2 laser surgery. TORS has been demonstrated to lower the AHI and reduce the severity of sleep apnea by reducing tongue base volume. However, the volume of tongue reduction is not proportional to the AHI reduction in each patient. A tailor-made surgical strategies and personalized treatments should be considered for each patient with sleep apnea. For patients with severe obstructive sleep apnea, surgical methods, such as TORS or CTBR, are a viable option for tongue base management. TORS is beneficial in terms of increasing O 2 saturation to 90%, reducing the ESS score, not worsening comorbidities, and reducing comparative operation time. Furthermore, this surgery is preferable for drug-induced sleep endoscopy grade III-IV lingual tonsil hypertrophy. Vicini et al. reported that the resection tissue volume was significantly correlated with surgical success 33 . However, other studies have reported that the resection tissue volume is not related to surgical success but that creating a relatively stable channel for airway flow is crucial to reducing obstruction severity 27,34 . Therefore, although Vicini et al. suggested resection volume as a factor indicating surgical success 33 , smaller resection volumes can also lead to a significant reduction in the AHI and increase in the lowest O 2 saturation. Furthermore, more favorable prolonged and sustained airway patenting results could be achieved using the TORS approach compared with radiofrequency (higher recurrence rate because of tissue recovery response) and CTBR (tissue firewall response hinders the resection tongue base volume). High magnification and precision was also possible using TORS, improving the surgical procedure and hemostatic control 35 . Moreover, we believe that the cost-effectiveness of TORS is more favorable than that of other methods. Because of its once for all characteristic and one time multilevel though out surgery, reducing the need for surgical salvage and postoperative continuous positive airway pressure salvage, which increases the effectiveness and reduces the cost of therapy. Friedman et al. indicated that TORS is more expensive but also more efficacious for obstructive sleep apnea than other surgeries 6 . Furthermore, the use of robotic surgery offers improved surgical views during surgery, involves less working trauma to the patient, and adversely affects the health of surgeons less. For instance, the risk of a cervical and lumbar spine condition or wrist injury is lower compared with other traditional intraoral surgical methods. Therefore, TORS is a valuable alternative method for sleep surgeons and patients with obstructive sleep apnea and tongue base problems. The information obtained from the included articles provided numerous insights. However, the present study had limitations. First, most of the articles included were retrospective case studies that lacked details regarding experimental research design, resulting in a high risk of bias in the studies used in our systematic review. Second, TORS is an innovative example of technology-assisted medical treatment. However, the operation time was the only surgical parameter observed in the meta-analysis. Other surgical characteristic parameters were not sufficiently defined in the selected articles, which further limited comparison between TORS and alternative interventions.

Conclusion
Our systematic review revealed that the use of TORS to treat obstructive sleep apnea had the same success and failure rates as other compared interventions with no statistical difference in operation times. The clinical effects on the AHI, lowest O 2 saturation, and ESS score of treatment with TORS were comparable to the effects of alternative surgeries. In addition to TORS, numerous other methods are available for treating obstructive sleep apnea, such as CTBR and radiofrequency.

Data availability
Data supporting the findings of the current study are available from the corresponding author on reasonable request.