Randomized Controlled Trial of Awake Transnasal Laser-assisted Surgery (TNLS) and Microlaryngeal Surgery for Vocal Cord Cyst
Phase: NA
Conditions: Vocal Cord Cyst
Sponsor: Chinese University of Hong Kong

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Randomized controlled trial of awake transnasal 
laser-assisted surgery (TNLS) and microlaryngeal 
surgery for vocal cord cyst 
 
CREC Ref No: 2023.644-T 
 
 
 

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Background 
Office-based awake transnasal laser-assisted surgery (TNLS) has been gaining 
popularity in treating different laryngeal lesions, with the advantages of avoiding general 
anesthetic risks and minimizing healthcare-related costs. (1-4) In addition, the general waiting 
time for surgeries under general anesthesia in public hospitals is getting longer due to the 
increasing population and limited resources. We have recently conducted a novel randomized 
controlled trial in 2021-2022 comparing the functional and cost-effectiveness of traditional 
microlaryngeal surgery (MLS) under general anesthesia and TNLS for benign laryngeal lesions 
(vocal cord polyps, nodules, cysts, granuloma and Reinke’s edema), and found that TNLS was 
superior to MLS in terms of length of stay, intraoperative complications, perioperative throat 
discomfort and hospital costs; while it was equivalent to MLS in terms of functional outcome, 
operative time and recurrence rate. (5) However, since our previous study's main goal was to 
compare TNLS to MLS in a macroscopic perspective in terms of functional outcomes and cost-
effectiveness, it had included a wide variety of benign laryngeal lesions, and different vocal cord 
lesions may respond differently to laser surgery.  
Vocal cord cyst is a fluid-filled sac inside the vocal cord, with 2 subtypes: 1) Epidermoid 
cyst due to epithelial inclusion  2) Mucous retention cyst due to glandular ductal obstruction. 
Vocal cord cysts typically do not resolve with voice therapy, and are traditionally excised with 
microlaryngeal surgery with microflap technique or marsupialization. (6,7) In our previous RCT 
study, subgroup analysis did not show a significant difference of vocal cord cyst recurrence in 
both TNLS and MLS group. However, our cohort had a higher overall vocal cord cyst recurrence 
rate (13.8%) compared to historic cohort rate of 2.2-8.7%(5, 8) , which may be accounted by that 
our vocal cord cysts were ablated and marsupialized instead of removed in the TNLS group. 
Nevertheless, a recent case series by Gao and colleagues showed a good functional outcome 
of awake KTP-laser marsupialization in selected cases. 9 A larger cohort is warranted to 
compare TNLS to MLS for vocal cord cyst. Therefore, our authors would like to conduct a 
randomized controlled trial to compared tradition MLS surgery to TNLS, with hypothesis that 
TNLS would be non-inferior to traditional microlaryngeal surgery in benign laryngeal lesions, 
and with its additional benefits on minimization of anesthetic risks and hospital expenses, 
hopefully to expand its further application. 
 
Methodology 
Study setting 
This is a prospective, single-cluster randomized controlled trial conducted at two 
tertiary referral hospitals (Prince of Wales Hospital and Alice Ho Miu Ling Nethersole Hospital, 
NTEC) in Hong Kong to compare the clinical and functional outcomes of office-based TNLS 
to traditional microlaryngeal surgery under general anesthesia for vocal cord cysts. 
 

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Eligibility criteria 
All consecutive patients with vocal cord cysts interested in operative management will be 
screened for eligibility. 
 
Inclusion criteria 
Patients who are (i) older than 18-year-old; (ii) able to independently provide consent; 
and (iii) able to tolerate flexible laryngoscopy would be recruited. 
 
Exclusion criteria 
 
Patients who are (i) under 18-year-old; (ii) unable to independently give an informed 
consent; (iii) unable to tolerate flexible laryngoscopy; (iv) allergic to local anesthesia; (v) had 
unfavorable anatomy such as prolapsing epiglottis precluding adequate visualization, extensive 
lesions and an expected difficult operation as judged by the surgeons; and (vi) with pathologies 
other than vocal cord cyst would be excluded from the study. 
 
Study intervention 
The active comparator is traditional microlaryngeal surgery under general anesthesia, 
which is the standard surgical care for vocal cord cyst at our institution. The experimental 
intervention would be awake transnasal laser-assisted surgery under local anesthesia, carried 
out in minor operation theater as a day-case basis in ENT ambulatory center. 
 
Microlaryngeal surgery (MLS) 
For traditional MLS under general anesthesia, the patient is admitted on the same day 
morning of the surgery with prior outpatient anesthetist assessment, or one day earlier to 
receive inpatient anesthesia assessment in special cases. The patient will be kept fast 
according to anesthetist assessment before surgery begins. After general anesthesia and 
intubation with microlaryngeal tube, the patient would be positioned on head-ring support for 
better alignment and access to glottis. After insertion of teeth guard, a laryngoscope will be 
inserted transorally under direct vision, and suspended with chest table support. Vocal cord 
cysts are visualized with microscope, and removed with microsurgery instruments with microflap 
technique and sent for routine section. Hemostasis is ascertained, then the laryngoscope is 
removed carefully under direct vision and injuries to pharyngeal walls, tongue base, teeth, lips 
and temporomandibular joints are checked. After the surgery, the patient is kept nil-by-mouth 
until fully awake, and is discharged on same day or the next day depending on the post- 
operative recovery. Patient will be discharged with voice rest for 3 days and prescription of 
Pantoprazole 40mg daily 4 weeks and Paracetamol as needed. 
 

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Awake transnasal laser-assisted surgery (TNLS) 
For TNLS, patients are admitted to the day ward center on the same morning or 
afternoon of the surgery with fasting prior 6 hours. Physical examination would be repeated to 
ensure that the patient is fit and able to tolerate transnasal laser surgery under local anesthesia. 
The surgery would be done by or under supervision of ENT specialists with laryngeal laser 
experience. Following administration 2-4 puffs of 5% lidocaine/0.5% phenylephrine (Co-
phenylcaine) nasal spray and 2 puffs of 10% oral Xylocaine spray, a transnasal channel flexible 
laryngoscope is introduced. The epiglottis, laryngeal inlet and subglottis are further anesthetized 
with 3ml 2% xylocaine during phonation via working channel. Adequacy of anesthesia is 
confirmed with absence of gag reflex or discomfort when gently palpating the epiglottis and 
arytenoids with endoscope tip. Should the patient still have insufficient anesthesia, another 1-
2ml 2% xylocaine will be injected with 20G needle for superior laryngeal nerve block. The total 
dose of local anesthesia shall not exceed maximum dose per kg body weight. A 445nm blue 
laser is introduced via a working channel of bronchoscope and laser ablation of vocal cord cyst 
is performed. During the operation, patient will receive continuous SpO2 monitoring with regular 
blood pressure monitoring. Standardized emergency trolley will be available in case of airway 
emergency. After the procedure, patients are kept nil-by-mouth for 2 hours until anesthesia 
wears off, meanwhile with close observation in day ward with continuous SpO2 monitor for 1 
hour. Patients will be discharged on the same day of the procedure, with voice rest for 3 days 
and prescription of Pantoprazole 40mg daily 4 weeks and Paracetamol as needed. 
 
Laser safety 
Laser surgery is regarded as a high-risk aerosol generating procedure during the COVID 
pandemic. Full personal protective equipment with N95 mask, laser eye-shield would be worn 
by all team members throughout the laser surgery. Doctors and nurses participating in the 
surgery would receive prior laser surgery safety training. For patients who are on anticoagulant 
or antithrombotics, the medications will be withheld according to our local hospital guideline 
balancing on the bleeding and thrombotic risks. 
 
Recruitment and Pre-operative assessment, Consent and Withdrawal of 
consent 
All eligible patients will be assessed in our out-patient clinic in a standardized manner 
as follow: 
1. History taking 
2. Complete head and neck physical examination 
3. Flexible laryngoscopy for confirmation of diagnosis, with photo documentation of 
site and size (in relative to length of vocal cord in full abduction) 
Diagnosis would be explained to patients, and management options of conservative, 
microlaryngeal surgery under general anesthesia, and TNLS with their pros and cons would 
be discussed. Patient information sheet and informed consent are provided to facilitate the 

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process. Should the patient decide to participate in the study, consent of the study would be 
signed in the same clinic session. Patient would be informed of his randomized treatment 
group, and consent of the surgery would be also signed in the same section. Participation is 
voluntary and any study subject can decide to withdraw at any time of the study period. 
Upon study withdrawal, the patient will continue to receive standard treatment according to 
disease status. 
In addition to above mentioned assessments, patient would also be assessed in a 
multidisciplinary voice clinic undergoing a detailed voice assessment co-organized with speech 
language pathologist, including Voice-Handicap Index (VHI-30), perceptual evaluation of voice, 
acoustic voice analysis, aerodynamic measures and laryngeal imaging. 
 
Failure of study intervention 
When patients cannot tolerate the allocated intervention, for example patients 
randomized to MLS group but contraindicated to general anesthesia, or patients randomized to 
TNLS but cannot tolerate transnasal laser surgery due to discomfort or anxiety, can crossover to 
other study arm. Outcomes would be analyzed by intention-to-treat principle. 
 
Follow-up schedule 
All patients would have follow-up in a multi-disciplinary voice clinic on post-op 2 weeks, 6 
weeks, 3 months, 6 months and 1 year. During the postoperative follow-ups, patients are 
required to fill in a questionnaire and undergo voice assessments as mentioned above. 
 
Primary outcome 
 
The primary outcome was to compare the pre- and post-operative Voice-Handicap Index 
(VHI-30) of TNLS and MLS groups. The VHI-30 is a 30-item self-administered questionnaire, 
which has been shown to be a reliable measure for voice treatment outcome. (10,11) It consists of 
three subscales, namely physical, functional and emotional. It provides an overall measurement 
of a person’s vocal function and how it influences a person’s everyday functioning and 
experience. 
 
Secondary outcomes 
The secondary outcomes included other voice-related outcomes (i.e. perceptual  
analysis, acoustic voice analysis, aerodynamic measure, visual analog scale (VAS) on voice 
quality), procedure-oriented outcomes, patient-oriented outcomes and hospital costs. 
Perceptual evaluation of voice using the GBRAS scale, in which patients would be required to 
produce sustained vowel and connected speech voice samples. Two experienced speech-
language pathologists blinded to the patient’s information would rate the audio recordings. For 
acoustic voice analysis, it would be conducted using PRATT program with parameters including 

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jitter, shimmer, noise-to-harmonic ratio measures and cepstral peak performance. For 
aerodynamic measure, maximal phonation time (MPT) would be measured by instructing 
patients to phonate /a:/ sound for as long as possible after maximal inspiration, at a 
spontaneous, comfortable pitch and loudness level, for three consequent trials. In VAS, patients 
would be asked to self-rate their voice quality on a visual analog scale of 0 (best) to 10 (worst). 
Videostroboscopy would be conducted on all patients to identify any anatomical and 
physiological changes, which included presence of laryngeal pathology, vocal fold closure 
pattern, and mucosal wave pattern. 
 
Procedure-oriented outcomes include operation time, completeness of lesion removal, 
complications in Clavien-Dindo classification, length of hospital stay, disease recurrence rate, 
and reoperation.  
Patient-oriented outcomes included peri-operative throat, nose, and overall discomfort in 
visual analogue scale, a 10-point scale with 0 (least uncomfortable) to 10 (most uncomfortable). 
 
Medical costs of both interventions would be also calculated respectively, including costs 
for inpatient hospital stay, medical staff, operating theater and consumables. 
 
Sample size calculation 
Power calculation demonstrated that with a sample size of 21 per group, a two-arm 
study has a power of 80% to demonstrate a non-inferiority margin 7 absolute score, with one-
sided significance of 0.05 regarding the primary outcome parameter, i.e. VHI-30. The calculation 
was based on published data from Misono et al. 12 in which a VHI-30 score over 16 was 
determined as a minimal important difference. Assuming a 20% drop-out rate, at least 54 
patients were required, with 27 patients in each arm. 
 
 
 
 

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Participant timeline 
 
 

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Randomization 
Patients are randomized to receive either MLS under general anesthesia or TNLS 
under local anesthesia. Block randomization is used to ensure equal distribution between 
two treatment arms. To avoid selection bias, the blocking mechanism is designed by a third 
party not involved in the study, and is not disclosed to investigators. Randomization is only 
performed on the day of recruitment, which the recruiter shall contact the third party for the 
result randomized treatment group. Both the patients and the laryngologists cannot be 
blinded due to the nature of operation. 
 
Statistical method 
 
All outcome measurements will be analyzed with an intention-to-treat principle. 
Independent samples t-test will be used for parametric continuous variables; Mann-Whitney U 
test will be used for non-parametric continuous variables; chi-square test will be used for 
categorical variables. A p-value less than 0.05 will be considered to be statistically significant. 
All statistical analysis will be performed using SPSS version 26.0. 
 
Data monitoring and confidentiality 
Patient demographics and clinical data are obtained from a territory-wide electronic 
medical record system named as Clinical Management System (CMS). Individual patient 
medical information obtained as a result of this study is considered strictly confidential and 
disclosure to third parties is prohibited. Only the principal investigator, co-investigators, study 
personnel and research assistants assigned for data collection with the approval of the principal 
investigator are allowed to have access of the data. Full access to the final data set will be 
reserved for the principal investigator and the statistician involved in this study. All information 
will be stored in a password protected hospital authority computer and a locked file cabinet with 
the key kept by the principal investigator. An Prince of Wales Hospital ENT specialist not 
involved in the study and with surplus experience on laryngeal surgery will be responsible for 
safety monitoring. Names of participants will not be used. Information will be retained for a 
minimum of 10 years after study completion, after which all data will be completely destroyed 
without any identifiable personal information. All serious adverse events will be reported to the 
committee within 24 hours. 
 
Research ethics approval and protocol amendments 
 
Approval will be obtained from the Joint Chinese University of Hong Kong – New 
Territories East Cluster Clinical Research Ethics Committee, which is the institutional review 
board of our university. The study will be conducted in accordance with the Declaration of 
Helsinki and the International Conference on Harmonisation, Good Clinical Practice Guidelines 
(ICH-GCP). Prior approval from the committee and the designated trial registry will be obtained 
prior to implementation of important protocol modifications. 

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Access to data 
The Chinese University of Hong Kong will control the final trial dataset. Any requests 
for data access can be made to the lead principal investigator. A detailed plan with specific 
objectives and types of data request has to be formulated and submitted. Upon approval, the 
requested information will be available, on request to the corresponding author. 
 
Dissemination policy 
The results of the study will be presented at relevant international conferences and 
published in peer-review journals. 
 
 
 
 
 

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