Introduction
Transoral microresection for treatment of vocal cord lesions involving the anterior commissure (AC) may result in anterior glottic webs, which can cause symptoms, including dysphonia, exercise intolerance, and airway obstruction [
1]. This disease was traditionally treated through an external approach that comprises anterior thyrotomy and tracheostomy [
2]. Recently, endoscopic lysis and silicone keel placement have become the preferred treatment options [
3]. In 1991, Lichtenberger and Toohill [
4] designed an endo-extralaryngeal needle carrier that can pass sutures from the endolarynx outward through the neck; this instrument was used to place silicone elastomer sheets to treat anterior glottic webs [
5]. Since then, many studies applied this technique because it does not need tracheostomy and does not compromise airways [
2,
6,
7]. Nevertheless, treatment of anterior glottic webs remains challenging for laryngologists.
Glottic webs are often formed after surgical procedures for bilateral vocal cord lesions involving the AC. This anomaly is better to be prevented than treated. Web formation can be prevented through mitomycin C (MMC) treatment, endoscopic keel placement, and two-stage surgery. However, these approaches are not effective for all patients, and the precise etiology of glottic web formation remains unclear. In the present study, we determined the effectiveness of endoscopic silicone keel placement and analyzed the potential risk factors of web formation.
Patients and methods
Patients
This study performed a retrospective review of patients who underwent transoral microresection for bilateral glottic lesions with AC involvement at the Department of Otolaryngology–Head and Neck Surgery, Eye, Ear, Nose, and Throat Hospital of Fudan University between 2011 and 2015. Patients selected MMC, endoscopic keel placement, or two-stage surgery for laryngeal web prevention after being well informed. Patients were excluded if they chose two-stage surgery, had less than 1 year of follow-up after surgery, or had been treated previously. Of the 54 patients identified, 43 patients underwent endoscopic keel placement and 11 patients underwent MMC. Table 1 summarizes the demographic information of the patients. The institutional review board approved the study, and all patients provided informed consents.
Surgical approach
Suspension laryngoscopy (Karl Storz, Germany) and surgical microscopy (S88, Zeiss, Germany) were conducted to expose glottic lesions after oral intubation of the patients under general anesthesia. Laser cordectomy was performed to manage glottic carcinoma, and laser stripping was conducted to manage other conditions. Procedures for prevention of laryngeal web formation were then conducted. In the keel placement group, a silicone keel (0.3 mm thick) was placed through the laryngoscope by using a Lichtenberger’s endo-extralaryngeal needle holder (Wolf 8267.50) (Fig. 1A) [
6]. The lower needle was inserted inferior to the vocal folds and advanced through the cricothyroid membrane, and the upper needle was inserted superior to the AC or the base of the epiglottis and advanced through thyroid cartilage (female) or thyroid notch (male). The raw laryngeal surfaces were completely separated by the keel (Fig. 1B), and the suture was tied over a sterile button to secure externally on the neck. The patients were discharged home the next day with the keel in place. After 4 weeks, the keel was removed through fiberoptic laryngoscopy with biopsy forceps. In the control group, MMC solution (0.4 mg/mL) was applied to the raw surface of the vocal cords and AC for 10 min immediately after the lesions were removed. Patients received laryngoscopic examinations before surgery, at the time of keel removal (only keel placement group), and 3 months after the surgery. The self-assessment of voice handicap was measured using a validated and simplified voice handicap index (VHI-10) questionnaire [
8] before and 3 months after the surgery. Cases with recurrent disease after the initial surgery were treated by repeat microsurgery with keel placement.
Statistical analysis
A laryngeal web was defined as a visible adhesion with length of 1 mm or higher. The gray tough outer layer covering the vocal cord wounds was regarded as pseudomembrane, which was easily distinguished from epithelialized mucosa. Chi-square test was used to compare the glottic web formation rate between the two groups and determine the association between pseudomembrane and web formation in the keel placement group. Pre- and post-surgical VHI-10 scores were expressed as mean±standard deviation and compared using two-tailed t test. Statistical analysis was performed using SPSS 19.0 statistical package, and P<0.05 was accepted as statistically significant.
Results
Patient demographics
The keel placement group comprised two cases with glottic carcinoma, ten cases with laryngeal papilloma, eight cases with hypertrophic laryngitis, and 23 cases with glottic leukoplakia. The control group comprised 11 cases of glottic leukoplakia. Overall, 49 men and 5 women, with a mean age of 54 years (22–80 years), participated in the study. The age and sex distribution of patients were not significantly different between the two groups. All cases were confirmed by pathological examination. Most patients in the keel placement group reported irritable cough and skin itching, swelling, and redness induced by the positioned button, but these symptoms rapidly vanished after keel removal. The suture ruptured 2 weeks after the surgery in one case. Therefore, we reduced the tension of sutures in the other cases, and no further suture ruptured. Six cases showed recurrence of the original disease and accepted keel placement once again when treated by repeat microsurgery. All remaining patients exhibited complete resolution of their original diseases during the 1-year follow-up. No other complications were found, and none of the patients required a tracheotomy. Table 1 summarizes the demographic characteristics of the patients. Postoperative details are described in Supplementary Tables S1 and S2.
Endoscopic keel placement was an effective approach to prevent laryngeal web formation for bilateral vocal cord lesions
In the control group, 11 cases underwent MMC; of these cases, six patients (54.5%) were detected with an obvious anterior glottic web after follow-up of at least 1 year. In the keel placement group, only 18.6% patients (8 of 43) formed webs, and this number was significantly lower than that in the control group (c2 = 4.169, P<0.05, Table 2). Six cases in the keel placement group and none in the control group had recurrent disease after the initial surgery and were treated by repeat microsurgery with keel placement. No dyspnea was observed in any of the patients with a laryngeal web.
Patients treated to prevent web formation showed improved voice quality after surgery
The voice quality of the patients during pre- and post-surgery was assessed using the VHI-10 questionnaire. The VHI-10 score for patients without web formation in the keel placement group was 19.34±4.73 before surgery, and the score decreased to 8.51±3.95 post-surgery; this finding implied that the voice quality of these patients improved significantly (P<0.0001, Fig. 2A). In the control group, patients without web formation reported significantly lower post-surgical VHI-10 score than the pre-surgical score (9.60±2.41 vs. 19.80±2.95, P<0.001; Fig. 2B). However, the VHI-10 score was not significantly different before and after the surgery in patients with web formation in the keel placement group (23.38±4.93 vs. 19.13±7.22, P>0.05) and control group (20.50±6.22 vs. 17.17±3.71, P>0.05; Fig. 2A and 2B). These patients were satisfied with their voices and refused further treatments.
Pseudomembrane discovered at the time of keel removal was associated with web formation
A pseudomembrane covering the vocal cord wound was observed in 16.3% cases (7 of 43) when the keel was removed (Fig. 3, Table 3). After follow-up of at least 1 year, 100% of these cases (7 of 7) formed laryngeal webs (Fig. 3, Table 3). Among the 36 cases without pseudomembrane at the time of keel removal in the keel placement group, only one case (2.8%) had web formation (Fig. 4, Table 3). The association between the presence of pseudomembrane and web formation was significant (c2 = 30.441, P<0.001; Table 3).
Discussion
Patients who undergo CO
2 laser treatment of malignant and premalignant lesions of the AC have a high risk of anterior glottic web formation because bilateral vocal cord surgery results in raw mucosal surfaces in close proximity. Bilateral mucosal stripping procedures both in animal models and humans induce laryngeal stenosis [
9,
10]. Holland
et al. reported that 13 of 31 pediatric patients with papilloma treated by CO
2 laser had formed laryngeal webs [
11]. Although these patients can be treated in two stages, in which the first side is allowed to heal before surgery on the contralateral side [
12], a second surgery may increase the discomfort and economic burden of the patients. Therefore, an effective approach for preventing web formation during the treatment of these diseases must be developed.
MMC can inhibit fibroblast proliferation and is used to prevent scarring and fibrosis after surgery [
13]. A single topical application of MMC can significantly reduce the severity of laryngotracheal stenosis in a canine model [
9,
14,
15]. MMC is also used to prevent the formation of anterior glottic webs after transoral microresection for bilateral glottic lesions involving the AC, but the efficacy of MMC has not been fully established yet. In a previous study, 5 of 16 patients (31%) developed small webs despite MMC application [
16]; this rate is even higher (54.5%) than that reported in the present study. Medical chitosan is another inhibitor of fibroblast growth and can be more effective than MMC in preventing anterior glottic stenosis after CO
2 laser cordectomy in dogs [
17]. However, the utility and safety of MMC as an adjuvant therapy for prevention of laryngeal web formation must be further investigated [
18].
Previous study reported the application of butterfly graft acquired from the own tissue of a patient to replace the silicone keel, and the graft needs not be removed [
19]. However, this technique requires tracheotomy, and the diameter of the graft is restricted. Xiao
et al. developed vocal cord mucosal flap to cover the glottic wound [
20], and this technique successfully cured 87.5% patients with laryngeal webs [
21]. This single-stage procedure acquires satisfactory effects but is unsuitable for prevention of web formation because the mucosal flap cannot be easily obtained. Bhongmakapat
et al. [
22] introduced a small absorbable stent to treat anterior glottic web, but the therapeutic effect of this method remains unclear.
Currently, endoscopic lysis of web with silicone keel placement is used to treat and prevent anterior glottic webs. This surgical approach has been modified by many surgeons in the clinical practice to improve its effectiveness [
7,
23–
25]. The stenting duration for web treatments ranges from 5 days to 8 weeks [
3]. The raw surface of vocal folds after microsurgery is predicted to epithelialize completely within 2 weeks after laser stripping, and new granulations, necrosis, or scarring will develop if the keel is kept for too long [
3,
26]. In the present study, we placed the keel for 4 weeks. Edwards
et al. reported a recurrence rate of 10% in patients with laryngeal web who underwent endoscopic lysis and keel placement [
7]. Benmansours
et al. treated 18 patients by the combination of keel placement and MMC application, and none of them showed recurrence during the follow-up [
2]. Paniello successfully treated 88.9% of patients with keel placement after web lysis [
6]. No dyspnea was observed, and no tracheostomy was required. Thus, lysis and keel placement can be a simple and suitable approach to prevent web formation.
Few studies reported about AC web prophylaxis. Paniello placed silastic sheets prophylactically into the larynx to prevent anterior glottic webs in four patients with bilateral large anterior vocal fold polyps, recurrent papilloma, and laryngeal cancer [
6]. In the present trial, 81.4% of patients (35 of 43) were protected from web formation. Hence, patients may benefit more from the combined application of MMC and keel placement than from their individual application.
In this study, eight cases formed obvious webs despite keel placement for 4 weeks; seven of these cases had pseudomembrane at the time of keel removal. Web formation was found to be closely related to the presence of pseudomembrane at the time of keel removal (Table 3). Considering that the vocal cord wounds in most cases without web formation were covered and protected by epithelia (Fig. 3), we hypothesize that pseudomembrane may imply a delayed or lack of epithelialization of the vocal cord and the AC. A laryngeal web could form if the keel was removed in this situation, and its relation to technical factors (e.g., subtle differences in placement) or patient factors (e.g., forceful coughing) remains unclear. The type of vocal fold lesion may affect web formation. In our trial, both glottic carcinoma cases undergoing laser cordectomy had pseudomembrane at the time of keel removal (Supplementary Table S1, Fig. 3), and both developed laryngeal webs, despite keel placement. Malignant lesions required cordectomy to remove the deeper layers of the vocal fold, whereas benign or premalignant lesions were resected more conservatively. Injury to the deep structures will prolong the time of epithelialization of the vocal cord wounds; thus, keel placement should be prolonged in this condition. However, a method for evaluating the extent of vocal cord wounds and determining the duration of stent placement must be further explored.
This study presents several limitations. The voice quality of the patients was assessed using the VHI-10 questionnaire, resulting in failure to acquire objective voice outcomes. The duration of keel placement in malignant cases may be unsuitable and must be further explored. The procedural differences among different patients were unavoidable, and the case number was limited by the infrequency of this disease.
Conclusions
Anterior glottic webs are a significant complication of bilateral resection of anterior vocal fold lesions. In this study, endoscopic keel placement can be an effective approach to prevent anterior glottic web formation and voice loss after transoral microresection for bilateral glottic lesions involving the AC. Pseudomembrane observed at the time of keel removal may be due to deep vocal cord wounds and may imply a high risk of web formation. In this condition, keel placement must be prolonged.
Higher Education Press and Springer-Verlag Berlin Heidelberg