Single-center, Retrospective Study of Retro-Auricular Single-Site Endoscopic, Transoral Endoscopic Thyroidectomy Vestibular Approach and Transareola Endoscopic Thyroidectomy in Patients With Early Stage Papillary Thyroid Carcinoma
Phase: NA
Conditions: Papillary Thyroid Carcinoma
Sponsor: Sun Yat-sen University

Single-center, Retrospective Study 
of Retro‐Auricular Single‐Site 
Endoscopic, Transoral Endoscopic 
Thyroidectomy Vestibular Approach 
and Transareola Endoscopic 
Thyroidectomy in Patients With 
Early Stage Papillary Thyroid 
Carcinoma 
 
Study Protocol 
 
 
Version date: February 11, 2023  
 
 
 
 
 
 
 
 
                        

Official Title 
Single-center, Retrospective Study of Retro‐Auricular Single‐Site 
Endoscopic, Transoral Endoscopic Thyroidectomy Vestibular Approach 
and Transareola Endoscopic Thyroidectomy in Patients With Early 
Stage Papillary Thyroid Carcinoma 
Brief 
Summary 
The goal of this retrospective study is to compare the safety and 
efficiacy of endoscopic thyroidectomy via retro‐auricular single‐site 
approach, transoral endoscopic thyroidectomy vestibular approach and 
transareola approach. 
Conditions 
Age: 18～70 years.Patients with early stage papillary thyroid 
carcinoma.   
Sample Size  160 
Inclusion 
Criteria 
 
⚫ Age 18-70 years old, no gender restrictions. 
⚫ Fine-needle aspiration cytology(FNA) confirmed papillary thyroid 
carcinoma(PTC). 
⚫ Early stage PTC (stage T1N0M0). 
⚫ Preoperative ultrasonography showed unilateral glandular lobe 
malignant tumor and the largest diameter was not more than 2cm,  
without cervical lymph node metastasis and extensive metastasis. 
⚫ Patients undergoing thyroid lobectomy and central lymph node 
dissection. 
⚫ Patients who have signed an approved Informed Consent. 
Exclusion 
Criteria 
⚫ Patients who do not accept case data collection for various 
reasons. 
⚫ The clinical data unfit this study （at the discretion of the 
investigator）. 
⚫ Patients who have undergone neck surgery or radiotherapy before 
this trail. 
⚫ Patients who have uncontrolled hyperthyroidism. 
Elimination 
Criteria 
⚫ Patients who violated the requirements of the research protocol. 
⚫ The quality of data records is incomplete and inaccurate. 
⚫ Lost cases. 
Study 
Completion  
2023-02-28 
Locations 
1 
Statistical 
Analysis 
Plan 
All analyses were performed using SPSS 26.0, and a P value less than 
0.05 was considered significant. Normally distributed quantitative data 
are represented by mean (SD) [range]. Non-normally distributed 
quantitative data are represented by M（QR）. Comparison between 
groups was performed using the Mann-Whitney U test. 
Categorical data are expressed as frequencies and percentages. 
Comparisons between groups were performed using theχ2 test or 
Fisher's exact test. 
 

Study Protocol 
1.Background 
Thyroid cancer is one of the most common malignant tumors in the head and neck. 
Among it, papillary thyroid carcinoma accounts for about 70% of thyroid cancer. The 
degree of malignancy is low, but there is a tendency for multicentricity, and cervical lymph 
node metastasis occurs early. Due to the development of diagnosis technology, the 
amount of papillary microcarcinoma is getting higher and higher. At the same time, the 
change of aesthetic makes young women pursue a scarless neck1, 2. 
Surgery is the first choice of treatments for early-stage thyroid cancer.3, 4 Traditional open 
surgery tended to leave a long scar on the neck, which affects the cosmetic outcome. At 
present, many reported approaches, such as trans-areola approach5, trans-axillary 
approach6, trans-oral approach 7, 8or some combined approaches9, all have wider flap 
dissection or greater body trauma, and at the same time, these above approaches are 
difficult to achieve complete dissection of central lymph nodes10.  
Therefore, based on the experience of transauricular hairline endoscopic 
thyroidectomy11-13, we established a new operative method-the Retro-auricular single-site 
endoscopic thyroidectomy (RASSET). The incision is only 3cm and located at the 
posterior sulcus of the auricle, which can meet the cosmetic needs. Compared with other 
endoscopic approaches, the dissection area is small and the flap dissection is small, 
which may reduce the surgical trauma. The RASSET is easy to resect the upper pole of 
the thyroid gland, and can achieve complete dissection of the central lymph nodes.  
The article titled " A comparative study between retro‐auricular single‐site endoscopic 
thyroidectomy and transoral endoscopic thyroidectomy vestibular approach: a single‐
center retrospective analysis " has been published in " Chin J Surg "14. Guangdong 
Medical Information Research Institute recognized that there was no report of endoscopic 
thyroid surgery for this approach at home and abroad, and it also passed the new 
technology evaluation in the Sun Yat-sen University Cancer Center, and was recognized 
as an international leader. 
 

2. Study purpose 
2.1 Primary purpose: 
Compare the traumatic differences between the three groups by comparing the 
preoperative and postoperative CRP levels of the three groups. 
2.2 Secondary purpose: 
Compare the degree of surgical trauma between the three groups by comparing the level 
of SAA, blood loss, VAS pain score, and postoperative drainage. 
Compare the clinicopathologic characteristics between the three groups by comparing the 
number of resected lymph nodes, and the positive rate of lymph nodes. 
Compare the safety between the three groups by comparing the types and rate of 
complications. 
2.3 Primary Outcome Measure: 
CRP level 
2.4 Secondary Outcome Measures: 
⚫ 
Cosmetic outcome: postoperative cosmetic outcomes 
⚫ 
Surgical outcomes: SAA level, blood loss, VAS pain score, postoperative drainage 
volume, Operative time. 
⚫ 
Clinicopathologic characteristics: tumor size, number of lymph nodes, the positive 
rate of lymph nodes. 
⚫ 
Complication: complication rates and types. 
3. Study Eligibility 
3.1 Inclusion Criteria: 
⚫ Age 18-70 years old, no gender restrictions; 
⚫ Patient must be suitable candidates for surgery; 
⚫ Be able to understand the purpose of the test; 
⚫ Preoperative ultrasound showed unilateral glandular lobe malignant tumor and the 
largest diameter was not more than 2cm, and preoperative imaging examination 
showed that the largest diameter of central lymph node was not more than 2cm 
without lateral cervical lymph node metastasis and extensive metastasis; 
⚫ Patients who have cosmetic requirements; 
⚫ Patients who have signed an approved Informed Consent 
3.2 Exclusion Criteria: 
⚫ Patients who do not accept case data collection for various reasons. 
⚫ The clinical data unfit this study （at the discretion of the investigator）. 
⚫ Patients who have undergone neck surgery or radiotherapy before this trail. 
⚫ Patients who have uncontrolled hyperthyroidism. 
3.3 Withdrawal criteria: 
(A withdrawal case refers to a patient who withdraws from treatment for various reasons 
in study. Patients with the following conditions will be withdrawn from investigational 
treatment.) 
⚫ The patient himself or his legal representative requests to withdraw; 
⚫ In the opinion of the investigator, the patient's continued participation in the study will 

be detrimental to his health. 
3.4 Elimination Criteria: 
⚫ Patients who violated the requirements of the research protocol; 
⚫ The quality of data records is incomplete and inaccurate. 
⚫ Lost cases. 
4. Case Screening 
4.1 examination items 
All cases must complete the following examination items before being considered for 
entry into this study. It is generally required to be completed within 7 days before 
treatment. 
⚫ Complete medical history and comprehensive physical examination, including 
symptoms, signs and specialist examination. 
⚫ Check items that must be done before routine treatment, including: 
Blood routine: neutrophil/lymphocyte ratio, 
Coagulation function: d-dimer, 
Serological tests: CRP, SAA, procalcitonin, calcium level, 
Thyroid function: TSH level, parathyroid hormone level, 
Thyroid ultrasonography and FNA, thyroid Computed tomography scan if necessary, 
Chest X-ray, abdominal ultrasonography, electrocardiogram. 
The above examinations are all routine preoperative examinations, which do not 
cause additional financial burden on patients. 
4.2 Case screening 
According to various examinations, those who meet the inclusion criterias are screened 
out. 
The patients entered the study after completing the required examinations and being 
evaluated according to the inclusion criterias. Then sign the informed consent form and 
get treatment. 
5. Study Process 
 
6. Surgical Technique 
6.1 Retro-auricular single-site endoscopic thyroidectomy (RASSET ) 

For the RASSET technique, in the beginnig, patient was placed in a supine position with 
slight neck bending. When the lower pole of the thyroid gland was going to be dissected, 
the patient was placed in a supine position with slight neck extension. Mark the operation 
path on the surface. Slit the skin, subcutaneous tissue and superficial cervical fascia in 
turn. Expose the middle branch of the great auricular nerve and the sternocleidomastoid 
muscle under direct vision. The working space was created in the superficial layer of deep 
cervical fascia between the sternocleidomastoid muscle and the platysma muscle, which 
meets the principle of membrane anatomy. The area of flap dissection just includes the 
anterior cervical muscle and the anterior edge of the sternocleidomastoid muscle, which is 
so narrow to minimize the traumatic dissection. Pulling apart the anterior cervical muscle 
and the sternocleidomastoid muscle along the deep cervical fascia can fully expose the 
thyroid gland, the recurrent laryngeal nerve (RLN) and common carotid artery that are 
surrounded by the middle layer of deep cervical fascia and ensure that tumor and central 
lymph nodes en‐bloc resection can be operated in the middle layer of deep cervical fascia 
to conform the natural anatomical region. For details, please refer to "Retroauricular Single-
Site Endoscopic Thyroidectomy—A Balanced Endoscopic Approach for Thyroid Excision". 
6.2 Transoral Endoscopic Thyroidectomy Vestibular Approach(TOETVA) 
For the TOETVA technique, the patient was placed in a supine position with slight neck 
extension under nasotracheal intubation. Amoxicillin–clavulanic acid, 1.2 g, was 
administered 30 minutes before incision.Three laparoscopic ports (a 10-mm port at 
midline and two 5-mm ports at the lateral junction between the canine and first premolar 
teeth) were inserted under the lower lip at the oral vestibular area. A standard 10-mm 30° 
laparoscope was used, allowing top-down visualization. The working space was created 
down to the sternal notch with the lateral border at the sternocleidomastoid muscles. The 
strap muscles were separated in the midline and retracted laterally by a transcutaneous 
2/0 silk suture to expose the thyroid and trachea. The thyroid isthmus was divided first. 
Next, the superior pole was dissected, and the branches of the upper pole vessels were 
divided using ultrasonic shears (Harmonic Scalpel) on the surface of the thyroid gland. 
Upper parathyroid and lower parathyroid glands were identified and preserved. The 
recurrent laryngeal nerve (RLN) was identified at the insertion to the larynx, then followed 
downandparallel tothe trachea inferiorly. A thyroid lobe specimen was placed in a 
specimen pouch and retrieved through the 10- to 15-mm central incision. 
6.3 Transareola Endoscopic Thyroidectomy 
After endotracheal intubation and general anesthesia, the patient was placed in supine 
position. Incision was made inside the right areola and a 10-mm port was placed, 
subcutaneous tunnel separation rod was used to separate the space, and a 30° 
laparoscope was introduced, a 5-mm port was placed in the 5mm incision in the left areola, 
free flap with ultrasonic shears, and subcutaneous separation space in the upper sternal 
segment. A 5-mm port was placed on the lateral side of the right areola, and the anterior 
cervical flap was further dissociated to establish space. Above the flap was the thyroid 
cartilage and behind the sternocleidomastoid muscle on both sides, the median cervical 
line was cut, the isthmus of the thyroid was cut off, and the tracheal fascia ligament of the 
thyroid was separated on both sides, and the lower pole blood vessel and the lateral middle 
vein were treated close to the gland, and the inferior parathyroid gland was exposed. The 

recurrent laryngeal nerve was exposed in the parathyroid groove at the lower pole of the 
gland, the space along the nerve was separated to protect the nerve and protect the 
superior parathyroid gland, the suspensory ligament was cut off, the upper pole blood 
vessels were treated close to the upper pole glands, and the affected lobe glands were 
excised.  
7. Outcome Measures   
7.1 Baseline Characteristics of Patients 
Gender, Age, BMI, Tumor size, Pathological type, Tumor location, ASA grade. 
7.2 Postoperative Outcomes 
⚫ 
Surgical outcomes: CRP level, SAA level, Drainage volume, intraoperative blood loss, 
VAS pain score, Operative time. 
⚫ 
Clinicopathologic characteristics: tumor size, number of lymph nodes, the positive rate 
of lymph nodes. 
⚫ 
Complications: complication rates and types. 
7.3 Primary Outcome Measure: CRP level 
8. Code of Ethics 
8.1 Informed consent 
Before each patient was enrolled in this study, the research investigators are responsible 
for a complete and comprehensive introduction to the surgical method of this study, its 
possible side effects and possible risks, and let patients know their rights, risks and benefits 
to be assumed. Patients should have signed informed consent before enrollment. 
8.2 Ethical norms and policies and regulations 
This clinical trial must comply with the Declaration of Helsinki (2000 Edition), the Good 
Clinical Practice (GCP) promulgated by the SFDA, and related regulations. Before the start 
of the trial, the study could be started only after the protocol was approved by the ethics 
committee of the lead unit. Any modification of the trial protocol during clinical research 
should be reported to the ethics committee and filed. 
8.3 Obtaining ethics approval 
Ethical approval has been obtained. 
9. Quality Assurance 
In order to ensure that this trial can be carried out in strict accordance with the clinical 
research protocol, during the entire process of the clinical trial, clinical investigators and 
clinical sponsors should behave in strict accordance with the requirements of the Good 
Clinical Practice for Drugs (GCP), and be sure to follow the trial procedures. Standardized, 
accurate test data, and reliable research conclusions. Specific requirements are as follows: 
1. Requirements for collaborators: 
⚫ 
Lectures on clinical programs, CRF filling, etc. are given to the researchers before the 
clinical start. 
⚫ 
Send clinical monitors to conduct on-site inspections. 
⚫ 
Ensure that the researchers can keep in touch with the researchers at any time by 
telephone or email. 

2. Requirements for researchers: 
⚫ 
Responsible for obtaining the "Informed Consent" signed by each subject or his agent. 
⚫ 
Complete the case report form (CRF) carefully as required. 
⚫ 
Regular visits. 
⚫ 
Completely maintain records of clinical records, and original medical records of 
subjects. 
10. Data Processing and Preservation 
10.1 Case report form (CRF) 
The case report form should be filled out by investigators, and the CRF form should be 
filled out in time to ensure accurate content and timely summary. Generally, the CRF form 
should not be altered. If there is an error that needs to be revised, it should be signed at 
the revised place. The CRF form is in triplicate, and after the trial is over, it will be handed 
over to the clinical team leader hospital, the sponsor and the trial hospital for preservation. 
Data entry was performed after the completed case report was reviewed by the clinical 
monitor. The contents of the case report form are no longer modified. 
10.2 Create a database 
After receiving the CRF form, the statistician will verify the question by the researcher, and 
the researcher should answer and return as soon as possible. Statisticians will establish a 
database at the same time. After the database is reviewed, the data will be locked by the 
principal investigators, sponsors, statistician and clinical monitors. To ensure data security, 
irrelevant personnel cannot access and modify the data, and the data must be backed up. 
10.3 Storage of data 
The researcher should keep the data intact. According to the principle of GCP in China, for 
the investigators or hostipals, the data storage should be more than 5 years. 
11. Statistical analysis 
Professional statisticians undertake statistical analysis tasks and participate in the whole 
process from experimental design, implementation to analysis and summary. After the 
study protocol and case report form are completed, a statistical analysis plan shall be 
formulated. After some necessary modifications shall be made during the study process as 
required, and a statistical analysis report shall be provided after the data analysis is 
completed.  
All analyses were performed using SPSS 26.0, and a P value less than 0.05 was 
considered significant. Normally distributed quantitative data are represented by mean (SD) 
[range]. Non-normally distributed quantitative data are represented by M （QR ）. 
Comparison between groups was performed using the Mann-Whitney U test. Categorical 
data are expressed as frequencies and percentages. Comparisons between groups were 
performed using theχ2 test or Fisher's exact test. 
References: 
1. 
Ikeda Y, Takami H, Niimi M, Kan S, Sasaki Y, Takayama J. Endoscopic thyroidectomy and 
parathyroidectomy by the axillary approach. A preliminary report. Surg Endosc. 2002;16(1):92-95. 
2. 
Choi JY, Lee KE, Chung KW, et al. Endoscopic thyroidectomy via bilateral axillo-breast 

approach (BABA): review of 512 cases in a single institute. Surg Endosc. 2012;26(4):948-
955. 
3. 
Anuwong A, Ketwong K, Jitpratoom P, Sasanakietkul T, Duh QY. Safety and Outcomes of 
the 
Transoral 
Endoscopic 
Thyroidectomy 
Vestibular 
Approach. 
Jama 
Surg. 
2018;153(1):21-27. 
4. 
Russell JO, Razavi CR, Al Khadem MG, et al. Anterior cervical incision-sparing 
thyroidectomy: Comparing retroauricular and transoral approaches. Laryngoscope 
Investig Otolaryngol. 2018;3(5):409-414. 
5. 
Sephton BM. Extracervical Approaches to Thyroid Surgery: Evolution and Review. Minim 
Invasive Surg. 2019;2019:5961690. 
6. 
Lee DW, Ko SH, Song CM, Ji YB, Kim JK, Tae K. Comparison of postoperative cosmesis in 
transaxillary, postauricular facelift, and conventional transcervical thyroidectomy. Surg 
Endosc. 2020;34(8):3388-3397. 
7. 
Sun H, Zheng H, Wang X, Zeng Q, Wang P, Wang Y. Comparison of transoral endoscopic 
thyroidectomy vestibular approach, total endoscopic thyroidectomy via areola approach, 
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Endosc. 2020;34(1):268-274. 
8. 
Dong F, Ao Y, Li MT, et al. [A comparative study between retro-auricular single-site 
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9. 
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Balanced Endoscopic Approach for Thyroid Excision. Jama Surg. 2023. 
 
Appendix 
Appendix AJCC 8th Edition/TNM Classification System for 
Differentiated Thyroid Carcinoma