Figure.2. Weighted complication rates for three treatment modalities undertaken to treat RRP, with straight lines depicting 95% confidence intervals for individual studies and diamond depicting 95% confidence intervals for the weigh.

This systematic review and meta-analysis is the first to summarize the existing literature on complication rate of different Treatment Modalities of RRP. Heterogeneity precluded a direct comparison between studies within the same surgical techniques.

Benboujja^[38] investigated the depth of RRP using optical coherence tomography and found that the tumor was limited to above the basement membrane. In other words, removing the upper layer of the lesion above the surface is sufficient to remove RRP. Such microsurgery is essential to preserve the layered structure of the vocal cords, avoid fibrosis or scarring, and restore normal vocal function.

The rate of complications reported for each is variable, the reason can be explained by the working mechanism of surgical instrument itself. On the one hand, cold steel instruments (like microdebrider) avoid heat transfer to the surrounding tissue and thereby the possibility of scar retraction. On the other hand, hot methods (laser) allow for better hemostasis and vaporization of the flat superficial lesions while preserving normal tissue.

Due to the blood-rich nature of RRP, KTP laser, which belongs to the angiolytic laser, seems has great advantages in RRP resection^[15]. Unlike the CO2 laser, the angiolytic laser uses the peak in the absorption spectrum of the oxygen hemoglobin rather than water, which helps to selectively ablate the vascularized lesion without excessive thermal damage^[39]. In other words, the KTP laser can better preserve the surrounding tissue and hemostasis control^[40]. Burns^[41] also argues that diseases in the anterior commissure of glottis can be treated with minimal risk of scarring or adhesions, whether using KTP lasers alone or as a complement to other surgical modalities, with minimal preservation of the potential superficial intrinsic layer.

The wavelength of the CO2 laser (10 600 nm) is absorbed by water, allowing the lesion to evaporate with a high percentage of intracellular water. CO2 laser was applied to the treatment of RRP as early as the early 1970s, which replaced the traditional micro-cold device, and gradually become a recognized treatment method for laryngeal diseases due to the better hemostasis effect, lesion clearance and other characteristics^{[37, 42, 43]}. In 2015, Murono published a questionnaire to the department of otolaryngology at all 80 Chuo University hospitals in Japan with regard to the use of surgical instruments. A trend was observed towards lasers (50 hospitals) rather than micro devices (16 hospitals) or cold instruments (20 hospitals). Among the 50 hospitals that regularly undergo laser surgery, the most commonly used carbon dioxide (CO2) laser is followed by titanium-based potassium phosphate laser^[44]. In 2016, a Germany multicenter cohort study reported that CO2 laser remained the most common surgical modality used alone or in combination with other treatment modalities^[9]. At present, CO2 laser fiber is available, and outpatient-based CO2 laser surgery provides great benefits for RRP patients who need multiple surgeries to control the disease, the time and cost of treatment are greatly reduced, and the need for general anesthesia is reduced^[27]. However, CO2 laser operation is time-consuming, expensive, and potentially dangerous. If the intraoperative procedure is improper may lead to serious complications, such as airway combustion, normal tissue burns and medical staff damaged, which limit its development.

Microdebrider is a dynamic rotational dissection device with suction assist, was initially used in plastic surgery and rhinology. In 1999, Myer first reported the use of microdebrider in the larynx for the treatment of recurrent respiratory trait tumors^[45]. Under the endoscopic auxiliary support laryngoscopy, microdebrider can easily reach the throat, trachea and other parts, with its continuous suction cutting effect. Therefore, it can easily push the mass away from the base and suck up, remove the mass accurately, and has gradually become the preferred treatment for handling JO-RRP in recent years^{[18, 32]}. Wenbin^[6] retrospectively analyzed the case series of RRP, microdebrider can quickly remove tumors, with few complications and satisfactory postoperative short-term sound quality. El-Bitar^[25]conducted a retrospective study of seventy-three operations, the microdebrider was proved to be less time-consuming than the carbon dioxide laser when used in patients with juvenile-onset recurrent respiratory papillomatosis, whit soft tissue complications were nonexistent. Pasquale^[46] was the first to compare microdebrider with CO2 laser, there was no significant difference in postoperative pain between the two groups, but this was a short-term study that provided initial data in a relatively small patient population. Similarly, in a retrospective study collaborated by Patel^[5], it was noted that since the C02 laser switched to microdebrider, the operation time was significantly shortened without affecting the accuracy of the operation, saving surgical costs, avoiding the risk of airway burns that may occur during laser surgery and the possibility of vaporization of virus particles. Rees^[34] found no statistically significant difference in postoperative pain scores between the microdebriders or CO2 laser treatment groups. Unlike in the case of lasers, microdebrider has some drawbacks, where hemostasis is an issue with cold techniques, but due to the suction of the connection, the surgical field could remains clear most of the time^[34]. Rare complications of microdebrider include mediastinal emphysema and retroperitoneal air^[47] and subglottic injuries^[48]. Granulomas that occur after vocal cord polyps have also been reported^[49]. Because of these advantages above, microdebrider may replace CO2 lasers, the preferred method of airway clearance in these patients, and become the surgical modality of choice for RRP^[50]. In addition, since microdebriders are more effective at removing bulky diseases than lasers alone, microdebriders may be a more cost-effective tool for removing tumors ^[15].

For bulky exogenous trait tumors, several surgical methods are often combined to learn from each other’s strengths and improve surgical efficiency. But there is currently insufficient data to prove whether combined surgery can reduce the occurrence of surgical complications. Huang^[24]notes that the surgeons prefer to use microdebrider for bulky tumors and use KTP laser peeling technique for near-normal structure. This mixing mode can help surgeons shorten surgery time and make it easier to control bleeding, and it may avoid injury to the stratified structure of the vocal cords.

Improvements in surgical modalities may reduce the complications associated with surgical treatment of RRP. The recent introduction of blue laser to office-based laryngology presents potential advantages, which includes a desirable combination of cutting and photoangiolytic qualities and a lightweight, shock-resistant design. Miller^[51] present a case series(thirty-six cases) and overview of office 445 nm blue laser transnasal flexible laser surgery, which support conclusion that blue laser is safe and effective in the treatment of RRP and a range of benign laryngeal lesions. Future research should compare the efficacy and safety of blue laser with potassium titanyl phosphate laser in office-based treatment of these conditions. In addition to improving surgical instruments, the development of imaging technology may also help. The use of OCT imaging for simultaneous monitoring alongside laser treatment may provide the best, patient-specific treatment to improve postoperative prognosis for patients with RRP in the future^[38].

There are several limitations to this systematic review. First, due to the lack of adequate literature, this study did not conduct a meta-analysis of other influencing factors of complications. For example, the location of the lesion, surgeon surgical techniques and the number of surgeries the patient undergoes may also be the influencing factors of complications. Huang^[24] reported three patients with RRP developed anterior glottis after continuous KTP laser surgery in his retrospective case analysis, but all three patients received RRP treatment near the front at the same time. They then performed a staging procedure for papillomas of the bilateral vocal cords, reducing the incidence of anterior commissure web. As mentioned earlier, the discovery of Benboujja^[38] proves that the upper layer of the lesion above the surface is sufficient to remove RRP, except whyich requires surgeons to have superb surgical skills in order to precisely control the depth of resection. Finally, a higher number of surgeries may be associated with a higher rate of surgical complications. PAPAIOANNOU ^[14] believes that patients who undergo more surgeries are more likely to develop complications than patients with fewer surgeries. Scatolini^[21] conducted a retrospective analysis of 74 patients with adolescent RRP and found that patients who had undergone more than 10 surgeries or who had previously had a history of surgery in an external institution had a higher frequency of throat scarring. However, El-Bitar^[25] argued that the incidence of postoperative complications of RRP was related to the surgical technique used, not to the number of surgeries or the interval between surgeries. Due to the fact that most of the existing studies are retrospective studies, made it difficult to control these variables.

Studies in the future would require detailed reporting of disease burden, so that patients could be risk stratified by group. Pre- and post-op Derkay scores or other consisten quantitative metrics are necessary, to accurately stage the bulk and severity of disease to allow for more standardized reporting of disease. Complications in these groups could then be compared to help determine the security of instruments used in the surgical procedures, so that we can provide data support for patients to make the best choice.

This systematic review summarizes the complications and complication rate of RRP patients treated by surgery using three kinds of surgical modalities as an independent way. Only one study compared outcomes of those three kinds of surgical modalities simultaneously, two studies compared microdebrider and CO2 laser, and the remaining studies focused on only one of three treatments. While definitive conclusions cannot be drawn from the available literature, it is possible that CO2 lasers in the surgical treatment of RRP may lead to more surgical complications, and microdebrider and KTP lasers may be safer. However, the heterogeneous data limits any strong comparison of outcomes of different treatment of laryngeal papillomas is needed. Future Randomised controlled trials that directly compare the safety of different surgical modalities are needed.

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