Is transoral endoscopic thyroidectomy via vestibular approach safe for total thyroidectomy compared to open thyroidectomy? A propensity-score matched cohort study of 101 matched patient pairs with papillary thyroid carcinoma.

doi:10.21203/rs.3.rs-2116880/v1

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Research Article

Is transoral endoscopic thyroidectomy via vestibular approach safe for total thyroidectomy compared to open thyroidectomy? A propensity-score matched cohort study of 101 matched patient pairs with papillary thyroid carcinoma.

https://doi.org/10.21203/rs.3.rs-2116880/v1

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Background

Transoral endoscopic thyroidectomy via vestibular approach (TOETVA) has become increasingly popular in the treatment of papillary thyroid cancer. This study aimed to describe the safety and feasibility of total thyroidectomy between the TOETVA and open thyroidectomy (OT) approaches for the treatment of patients with papillary thyroid cancer (PTC).

Methods

We retrospectively reviewed 780 consecutive patients suffering from PTC that had undergone total thyroidectomy using TOETVA (n = 107) and OT (n = 673) between April 2016 and October 2021 at our institute. Afterward, A total of 101 matched patients’ surgical outcomes were compared using propensity score matching (PSM) analysis.

Results

Before PSM, the patients in the TOETVA group were younger (p < 0.001), had a lower BMI (p < 0.001) and a greater female population (p < 0.001). After PSM, the TOETVA group was associated with significantly longer operative time (p < 0.001), greater blood loss (p < 0.001), total drainage amount (p < 0.001), higher WBC count (p < 0.001) and CRP (p < 0.001), better cosmetic satisfaction (p < 0.001) and quality of life (p < 0.001) and lower scar self-consciousness (p < 0.001). There was no statistical difference between the groups in the attenuation or disappearance of RLN signal, rate of parathyroid autotransplantation and bilateral lymph node dissection, the positivity of lymph node metastasis, number of dissected lymph nodes and positive lymph nodes, multifocality, postoperative level of blood calcium and PTH, rate of PTH < 15ng/mL, VAS score, duration of hospital stay, complications, mean TSH-stimulated Tg level before RAI, mean Tg level without TSH stimulation, and the proportion of serum Tg level of < 1.

Conclusion

TOETVA is a safe and feasible technique for better cosmetic effects and similar surgical outcomes compared to conventional open surgery for the studied patients that required total thyroidectomy.

Total thyroidectomy

Transoral endoscopic thyroidectomy vestibular approach

Open thyroidectomy

Safety

Feasibility

Cosmetic outcomes

Thyroid cancer has rapidly increased over the past 30 years and ranked 9th among all cancers worldwide in 2020, with 75% of the cases occurring in women ^[1]. Conventional open thyroidectomy (COT) is the standard treatment for thyroid cancer, particularly papillary thyroid cancer (PTC) ^[2]. However, a visible neck scar may induce self-concern and psychological social burden in patients, especially young women, which promotes the development of endoscopic techniques ^{[3, 4]}. With the development of natural orifice transluminal endoscopic surgery (NOTES) ^[5], Anuwong successfully operated upon 60 cases using the transoral endoscopic thyroidectomy vestibular approach (TOETVA) technique and demonstrated favorable safety and feasibility ^[6]. Since then, TOETVA is becoming increasingly popular and has been favored by thyroid surgeons worldwide.

Thereafter, several studies involving at least 1000 patients subjected to TOETVA have reported encouraging results, such as rare complications, satisfactory cosmetic effect, and advantages in the dissection of the central lymph node ^[7–10]. As total thyroidectomy is frequently associated with complications ^[11], it is commonly performed for benign nodules or unilateral papillary thyroid cancer. Ahn ^[12] and Luna-Ortiz ^[13] performed total thyroidectomy with TOETVA in 40 and 44 patients suffering from PTC, respectively, and suggested that it was an acceptable approach. However, A large-sample retrospective study on the comparison of total thyroidectomy between TOETVA and OT has not been reported to date.

Our team has extensive experience in TOETVA since its was first carried out in November 2014 and has completed over 100 cases of total thyroidectomy. This article aims to compare the safety, feasibility, and cosmetic outcomes of total thyroidectomy using TOETVA and COT on patients with PTC.

Patients

We retrospectively reviewed 780 consecutive patients with PTC who had undergone total thyroidectomy with unilateral or bilateral central lymph node dissection between April 2016 and December 2021 at the Department of Jiefang Road Thyroid Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine. Among these, 107 patients had undergone transoral endoscopic thyroidectomy vestibular approach (TOETVA group), and 673 patients had undergone open thyroidectomy (OT group).

The inclusion criteria were: (1) age from 18 to 55; (2) multiple bilateral nodules, of which, at least one was confirmed as PTC; (3) total thyroidectomy with unilateral or bilateral dissection of the central lymph node; (4) diameter of PTC ≤ 2 cm and benign nodules ≤ 4 cm (if they existed). The exclusion criteria were: (1) cervical lateral lymph nodes or distant metastasis; (2) follicular or medullary or anaplastic thyroid carcinoma; (3) extrathyroidal or capsular invasion; (4) previous neck surgery or radiation. All patients were apprised of the procedures of TOETVA and COT and had signed written informed consent. This study was approved by The Ethical Committee of the Second Affiliated Hospital of Zhejiang University’s School of Medicine.

Surgical procedures and perioperative management

The detailed surgical procedures of TOETVA ^[14] has been described in previous articles. In brief, three incisions were located in the middle of the vestibule (10 mm) and each side at the upper lateral of mandibular first premolars (5 mm). Trocars were inserted and subplatysmal working place was created and maintained by 6 mmHg CO₂ pressure with or without suspension device. After the division of the isthmus, unilateral thyroid gland was removed while protecting the RLN and parathyroid gland, followed by the contralateral. For the OT ^[15] procedure, about 5 cm skin crease collar incision was made 2 cm above the sternal notch, the tissue was separated and bilateral thyroid was resected. All surgeries used intraoperative nerve monitoring (IONM) ^[16] to recognize and protect the RLN. For the TOETVA group only, tinidazole mouthwash was routinely used before surgery, and intravenous antibiotics were used for 48 h postoperatively to prevent infection. In addition, the mandible was pressurized for 12 hours. The pain of each patient without the use of analgesics was assessed on the day-1 post-operation, according to the visual analog scale (VAS) ^[17].

Clinical data

The clinical data that were collected and summarized included population characteristics such as sex, age, body mass index (BMI), the maximum diameter of tumor, Hashimoto’s thyroiditis, multifocality as well as intraoperative and postoperative outcomes such as operation time, blood loss, number of dissected lymph nodes and proportion of decline or disappearance of the recurrent laryngeal nerve (RLN) signal, hospitalization time, total drainage volume, postoperative parathyroid hormone (PTH) and its proportion of < 15 ng/ml, C-reaction protein (CRP), WBC count, and complications.

Multifocality was defined as the number of PTC ≥ 2 according to the pathological results. Transient hypoparathyroidism was defined as clinical symptom of limbs numbness with a serum parathyroid hormone < 15 pg/mL, recovered within 6 months. Transient RLN injury was recognized by postoperative hoarseness resulted from vocal cord palsy and lasted less than 6 months. Other complications such as chocking cough, chyle fistula, corners of mouth ulcer, infection and hematoma, as defined in a previous article ^[18]. Follow-up duration was defined as the time length between the day-1 post-operation and March, 2022.

Follow-up

All patients were treated with a low dose (50 µg) of levothyroxine and assessed the oncologic completeness 3 weeks after discharge, as demonstrated by the serum stimulated Tg (sTg) level and the percent of which below 1.0 µg/L. Whereafter, radioactive iodine (RAI) therapy or suppression therapy was provided according to the 2015 ATA Management Guidelines ^[19] for patients, and they underwent serum thyroid function testing and neck ultrasonography at intervals, usually 3 or 6 months, to assess the situation of recurrence. At 3 months after discharge, cosmetic satisfaction, scar self-consciousness, and quality of life were evaluated with questionnaires, as mentioned in our previous article ^[18]. The cosmetic satisfaction was scaled with scores ranging from 0 (dissatisfied) to 3 (very satisfied). The scar self-consciousness was scaled with scores ranging from 0 (not at all conscious) to 3 (very conscious). The quality of life was assessed with a score from 0 to 10, with a higher score pointing a better results.

Statistical analysis

The propensity score matching (PSM) analysis ^[20] was used to reduce the interference of population characteristics such as age, sex, BMI, the maximum diameter of tumor, Hashimoto's thyroiditis and multifocality.

The statistical program SPSS version 26 (SPSS® Inc, Illinois, USA) was used for the data analysis. Continuous variables were analyzed by independent-samples t-test or Mann-Whitney U test and presented as medians ± standard deviations. Categorical variables were analyzed by the Chi-squared test or Fisher’s exact test and expressed as numbers and percentages. A P-value of < 0.05 indicated statistical significance.

Population characteristics

The population characteristics of the TOETVA and OT groups are presented in Table 1. Before matching, Compared to the OT group, patients in the TOETVA group were younger (31.74 ± 7.03y vs. 42.84 ± 9.16y, p < 0.001), had a lower BMI (21.70 ± 2.92 kg/m² vs. 24.00 ± 3.49 kg/m², p < 0.001) and a greater female population (96.4% vs. 71.3%, p < 0.001). There were no differences in terms of maximum tumor diameter (1.11 ± 0.65cm vs. 0.96 ± 0.45cm, p = 0.125), the prevalence of Hashimoto’s thyroiditis (51.4% vs. 45.5%, p = 0.258) and multifocality (68.2% vs. 70.3%, p = 0.666).

Table 1

Population characteristics before and after PSM analysis
Variables	Before PSM			After PSM
	TOETVA(n = 107)	OT before PSM(n = 673)	P	TOETVA(n = 101)	OT after PSM(n = 101)	P
Age(y)	31.74 ± 7.03	42.84 ± 9.16	< .001	32.24 ± 6.97	34.95 ± 8.25	0.227
Sex(n, %)			< .001			1.000
Male	6(5.6)	193(28.7)		6(5.9)	6(5.9)
Female	101(96.4)	480(71.3)		95(94.1)	95(94.1)
BMI(kg/m²)	21.70 ± 2.92	24.00 ± 3.49	< .001	21.73 ± 2.98	22.06 ± 3.09	0.265
Tumor diameter(cm)
Left	0.77 ± 0.47	0.74 ± 0.41	0.817	0.76 ± 0.44	0.78 ± 0.52	0.641
Right	0.92 ± 0.66	0.78 ± 0.44	0.160	0.89 ± 0.65	0.82 ± 0.48	0.698
Maximum	1.11 ± 0.65	0.96 ± 0.45	0.125	1.07 ± 0.64	1.02 ± 0.55	0.819
Hashimoto’s thyroiditis(n, %)	55(51.4)	306(45.5)	0.258	51(50.5)	54(53.5)	0.673
Multifocality^* (n, %)	73(68.2)	473(70.3)	0.666	69(68.3)	77(76.2)	0.209
NOTE: BMI, body mass index;TOETVA, transoral endoscopic thyroidectomy vestibular approach; OT, open thyroidectomy; PSM, propensity score matching

These population characteristics were matched between the two groups by PSM analysis and yielded data of 101 paired patients without statistical differences in age, sex, BMI, tumor diameter, rate of Hashimoto’s thyroiditis and multifocality (Table 1).

Intraoperative outcomes

The intraoperative outcomes are presented in Tables 2. All the patients completed the operation successfully without secondary surgery. For the TOETVA group, 1 patient converted to open due to the invasion of tumor to tracheal cartilage.

Table 2

Intraoperative outcomes
Variables	TOETVA(n = 101)	OT(n = 101)	P
Operative time(min)	223.24 ± 51.35	95.91 ± 26.83	< .001
Blood loss(ml)	18.73 ± 10.28	14.16 ± 3.87	< .001
RLN signal(n, %)			0.633
attenuation	6(5.9)	9(8.9)
disappearance	2(2.0)	1(1.0)
Parathyroid autotransplantation rate(n, %)	47(46.5)	42(41.6)	0.479
Bilateral lymph node dissection rate(n, %)	90(89.1)	88(87.1)	0.664
Number of dissected lymph nodes(piece)	10.81 ± 6.35	11.36 ± 6.53	0.630
Positive rate(n, %)	52(51.5)	50(49.5)	0.778
Number of positive lymph nodes(piece)	3.63 ± 3.34	3.28 ± 2.63	0.744
Conversion to open	1(1.0)	0	1.000
NOTE: RLN, recurrent laryngeal nerve;TOETVA, transoral endoscopic thyroidectomy vestibular approach; OT, open thyroidectomy

Compared to the OT group, the TOETVA group was associated with significantly longer operative time (223.24 ± 51.35 min vs. 95.91 ± 26.83 min, p < 0.001) and greater blood loss (18.73 ± 10.28 mL vs. 14.16 ± 3.87 mL, p < 0.001). There was no statistical significancer in the attenuation or disappearance of RLN signal (5.9% vs. 8.9% and 2.0% vs. 1.0%, p = 0.633), rate of parathyroid autotransplantation (46.5% vs. 41.6%, p = 0.479) and bilateral lymph node dissection (89.1% vs. 87.1%, p = 0.664), the positivity of lymph node metastasis (51.5% vs. 49.5%, p = 0.778), number of dissected lymph nodes (10.81 ± 6.35 vs. 11.36 ± 6.53, p = 0.630) and positive lymph nodes (3.63 ± 3.34 vs. 3.28 ± 2.63, p = 0.744).

Postoperative outcomes

The postoperative outcomes are presented in Tables 3. The total drainage amount was greater (186.68 ± 60.43 mL vs. 142.13 ± 97.43 mL, p < 0.001) and the WBC count (11.27 ± 8.33 × 10⁹/L vs. 9.04 ± 2.59 × 10⁹/L, p < 0.001) and CRP (15.95 ± 10.63 vs. 7.66 ± 6.02, p < 0.001) were higher in the TOETVA group than in the OT group.There was no statistical difference between the groups in the postoperative level of blood calcium (2.01 ± 0.15 mmol/L vs. 2.03 ± 0.14 mmol/L, p = 0.477) and PTH (18.83 ± 12.48 ng/mL vs. 21.17 ± 14.11 ng/mL, p = 0.276), rate of PTH < 15ng/mL (45.5% vs. 38.6%, p = 0.318), VAS score (1.87 ± 0.46 vs. 1.88 ± 0.36, p = 0.928), and duration of hospital stay (3.96 ± 1.13 d vs. 4.08 ± 1.23 d, p = 0.525).

Table 3

postoperative outcomes
Variables	TOTEVA(n = 101)	OT(n = 101)	P
Blood calcium(mmoL/L)	2.01 ± 0.15	2.03 ± 0.14	0.477
PTH(ng/ml)	18.83 ± 12.48	21.17 ± 14.11	0.276
PTH < 15 ng/ml rate(n, %)	46(45.5)	39(38.6)	0.318
WBC amount(10⁹/L)	11.27 ± 8.33	9.04 ± 2.59	< .001
C-reactive protein(mg/L)	15.95 ± 10.63	7.66 ± 6.02	< .001
VAS(score)	1.87 ± 0.46	1.88 ± 0.36	0.928
Postopeartive hospital stay(day)	3.96 ± 1.13	4.08 ± 1.23	0.525
Total drainage amount(ml)	186.68 ± 60.43	142.13 ± 97.43	< .001
Complication(n, %)
Transient RLN palsy	2(2.0)	4(4.0)	0.683
Permanent RLN palsy	0	0	NA
Transient hypoparathyriodism	23(22.8)	25(24.7)	0.741
Permanent hypoparathyriodism	0	0	NA
Chyle fistula	0	2(2.0)	0.498
Choking cough	1(1.0)	0	1.000
Injury of corners of mouth	3(3.0)	0	0.246
Infection	0	0	NA
Hematoma	0	0	NA
NOTE: PTH, parathyroid hormone;WBC, white blood cells; VAS, visual analog scale; RLN, recurrent laryngeal nerve; TOETVA, transoral endoscopic thyroidectomy vestibular approach; OT, open thyroidectomy; NA, not available

Regarding complications in the TOETVA group, transient RLN palsy or hypoparathyroidism occurred in 2 (2.0%) or 23 (22.8%) patients, respectively, all of whom recovered within 6 months. 1 patient (1.0%) suffered from a choking cough that lasted only a few days. Injury of corners of mouth were observed in 3 patients, which were cured rapidly due to the use of the Recombinant Bovine Basic Fibroblast Growth Factor Gel. There was no postoperative infection, hematoma, mental injury, chylous fistula, skin burns, carbon dioxide embolism, permanent RLN palsy or hypoparathyroidism. All the mentioned complications did not vary significantly between the TOETVA and OT groups.

Follow-up outcomes

We followed 84 in the TOETVA group and 87 patients in the OT group, respectively, for at least 3 months and the results were presented in Table 4. Compare to the OT group, the cosmetic satisfaction (2.55 ± 0.51 vs. 1.59 ± 0.68, p < 0.001) and quality of life (8.80 ± 0.70 vs. 7.86 ± 0.74, p < 0.001) were signifificantly better in the TOETVA group, and the scar self-consciousness (0.35 ± 0.59 vs. 1.31 ± 0.60, p < 0.001) was lower in the TOETVA group. Three months after operation, the mean Tg level without TSH stimulation and TgAb level in the TOETVA group was 0.19 ± 0.39 µg/L and 44.18 ± 80.19 IU/mL, respectively, showing no difference with the OT group (0.28 ± 0.76 µg/L, p = 0.476 and 32.54 ± 107.64 IU/mL, p = 0.226, respectively). The proportion of patients between the two groups with the serum Tg level of < 1 was 95.2% and 93.1%, respectively. 14 and 13 patients received RAI therapy in the TOETVA and OT group, respectively. There was no significant difference in the mean TSH-stimulated Tg (sTg) level before RAI (1.24 ± 2.23 µg/L vs. 1.67 ± 1.98 µg/L, p = 0.157) and the proportion of sTg level of < 1 (57.1% vs. 61.5%, p = 0.816). During the follow-up period, no patients suffered recurrence in the TOTEVA group but 1 patient in the OT group was found left III area lymph node metastasis at 51 months after surgery and received the secondary operation.

Table 4

surgical completeness
Variables	TOETVA(n = 84)	OT(n = 87)	P
Cosmetic satisfaction(score)	2.55 ± 0.51	1.59 ± 0.68	< .001
Scar self-consciousness(score)	0.35 ± 0.59	1.31 ± 0.60	< .001
Quality of life(score)	8.80 ± 0.70	7.86 ± 0.74	< .001
Postoperative 3 months Tg level	0.19 ± 0.39	0.28 ± 0.76	0.476
<1(n, %)	80(95.2)	81(93.1)	0.747
≥1(n, %)	4(4.8)	6(6.9)
Postoperative 3 months TgAb level	44.18 ± 80.59	32.54 ± 107.64	0.226
Rate of receiving RAI(n, %)	14(16.7)	13(14.9)	0.836
TSH level before RAI(mIU/L)	29.04 ± 18.68	46.82 ± 31.43	0.128
Stimulated Tg level before RAI(µg/L)	1.24 ± 2.23	1.67 ± 1.98	0.157
<1(n, %)	8(57.1)	8(61.5)	0.816
≥1(n, %)	6(42.9)	5(38.5)
Follow-up duration(months)	47.33 ± 11.11	42.95 ± 17.57	0.159
Recurrence(n, %)	0	1	1
NOTE: Tg, thyroglobulin; TgAb, thyroglobulin antibody; TSH, thyroid stimulating hormone; RAI, radioactive iodine therapy; TOETVA, transoral endoscopic thyroidectomy vestibular approach; OT, open thyroidectomy

Since Hüscher et al. ^[21] described the first endoscopic thyroidectomy in 1997, endoscopic techniques were increasingly applied to thyroid surgeries, such as axillary ^[22], breast ^[23], retroauricular ^[24], and robotic bilateral axillo-breast approach (BABA) ^[25], which transferred the neck incision to inconspicuous areas but were hardly “minimally invasive” because of the dissection of more tissue ^[10]. Therefore, as a minimally invasive and scar-free approach, TOTEVA catered for higher cosmetic requirement of patients and gained rapid popularity ^[26]. In spite of many advantages, TOETVA had still some limitations such as a notable learning curve caused by the opposite perspective (craniocaudal view), surgical instruments interference, and unique complications including mental injuries and dangerous carbon dioxide embolism, among others ^[27]. In this study, we will explore the safety and feasibility of total thyroidectomy performing TOETVA.

In our study, TOETVA was commonly used by younger and females, who were more concerned about neck scars. A study reported that young patients were willing to pay over USD 2000 and travel up to 700 miles to avoid a neck incision ^[28]. Because of the rare threat to survival by papillary thyroid carcinoma, an increasing number of patients, including elderly people, attach more importance to cosmetic outcomes and postoperative quality of life. Nonetheless, a visible scar negatively impacts the satisfaction and quality of life of patients, especially in the Asian population ^[29], which is a disadvantage of open surgeries. In our research, TOETVA possesses the advantages of enhancing cosmetic satisfaction and lowering self-consciousness due to scars, further improving the long-term quality of life.

After PSM, the population characteristics were matched between the 2 groups and the surgical and follow-up outcomes were analysed. Compared to the matched OT group, patients in the TOETVA group had a longer operative time, greater blood loss, and more postoperative total drainage amount, which was in line with the report of Luna-Ortiz et al. ^[13]. The establishment of surgical space and reduplicative replacement of endoscopic equipment required more time, which led to the separation of the larger flap. For total thyroidectomy, endoscopic equipment was replaced frequently to avoid bilateral RLN injuries. Moreover, Hashimoto’s thyroiditis was connected with the firmness and adhesion to the adjacent structure of the thyroid gland; thus, improving the difficulty of operation ^[30]. This was perhaps more serious for endoscopic surgeries, thus leading to higher operative time and blood loss. Nevertheless, the 10 mL increase in blood loss is acceptable, and luckily, the increase in operative time and flap separation did not increase postoperative pain.

In line with the report of our previous study ^[31], postoperative WBC and CRP were higher in the TOETVA group, which may be attributed to the increase in the operative time and the non-sterile environment of the mouth. Fortunately, none of the patients in the TOETVA group were infected, possibly due to the use of antibiotics and routine postoperative drainage. However, it was not clear whether bilateral thyroidectomy led to further elevation of WBC, CRP, or other inflammatory markers compared to unilateral thyroidectomy, and it needs further investigation.

According to the 2016 Chinese Guidelines for the Treatment of PTC ^[32], ipsilateral central lymph nodes of patients with PTC should be prophylactically dissected. Therefore, bilateral or unilateral lymph node dissection was performed for all patients, and the two groups showed similar results for the number of total or positive lymph nodes, suggesting that TOETVA permitted the same feasibility compared to OT. We believe that the unique symmetrical perspective (craniocaudal view) provided superb visibility for the bilateral VI and VII lymph node area. Permanent RLN palsy and hypoparathyroidism are severe complications and receive more attention compared to unilateral thyroidectomy. In our study, eight patients had RLN signal attenuation or disappearance, however, only two developed hoarseness because the momentary reduction of signal forced the surgeons to explore and protect the RLN more carefully. Although it is unclear if the IONM technique plays a decisive role in the lower rates of transient and permanent RLN palsy ^[33], real-time detection and feedback reduce the difficulty of operation, especially for total thyroidectomy, to prevent irreversible outcomes ^[34].

For the TOETVA group in our study, 45.5% patients’ postoperative PTH were below the normal range while half of them suffered limbs numbness, which related to our high proportion of parathyroid auto-transplantation.For ischemic parathyroid glands and inferior parathyroid glands mixed with enlarged lymph nodes, we chose the treatment of auto-transplantation rather than preservation in situ, which will increase the number of patients with short-term calcium deficiency ^[35] but lower the incidence of permanent hypoparathyroidism and recurrence of central lymph node ^[36], which is important for patients with total thyroidectomy. In this study, despite the lack of significant differences, the rate of auto-transplantation was higher in the TOETVA group (46.5%). Compared with OT, we indicate it is more difficult to retain parathyroid in situ through TOETVA, especially the classified A1 parathyroid glands ^[37]. The occurrences of other common complications were not significantly different between the two groups and rarely occurred. We believe it is safe to perform the total removal of the thyroid using TOETVA. However, few patients complained that the pulling sensation lasted 3 to 6 months or even longer after TOETVA, which probably resulted from subplatysmal fibrosis or scarring ^[38].

The duration of hospital stay in the two groups was similar, and two days in the hospital following operation was enough, which highlighted the safety and minimally invasive nature of TOETVA. It was general agreed, for total thyroidectomy, that the number of dissected central lymph nodes and postoperative serum Tg level represent the oncological safety of thyroid cancer ^[39]. The results in our study suggested the feasibility in harvesting central lymph nodes by TOETVA. Moreover, the postoperative serum Tg level without TSH stimulation confirmed that complete removal of the bilateral thyroid tissue could be achieved by TOETVA, despite its limited access to the upper pole or pyramidal lobe of the thyroid ^[40]. The proportion of patients receiving RAI, the mean serum stimulated Tg (sTg) level before RAI and the proportion of sTg of < 1.0 µg/L had no difference between TOETVA and OT, showing the surgical completeness of TOETVA. During the following period, 1 patient in the OT group found enlarge lymph node in the left cervical III area at 51 months after operation without increasing Tg level, which was confirmed as metastatic PTC by fine needle aspiration. A secondary surgery was performed and no evidence of recurrence or persistent in the subsequence follow-up period.

In February 2017, because of the invasion of tracheal cartilage, one patient in the TOETVA group with a tumor of 2 cm was transited to open ensuring the complete removal. We followed this patient every 3 or 6 months, whose Tg level maintained of < 0.04 µg/L and no evidence of recurrence by ultrasound. Previous study indicated that the initial learning curve of TOETVA was 15–20 cases ^{[41, 42]}, and the operative time gradually decreased with improvement in proficiency. However, for less experienced surgeons, it is inappropriate to perform total thyroidectomy via TOETVA unless they accumulated more than 50 cases in benign nodules and unilateral thyroidectomy ^[42].

This article is a single-center retrospective study reporting the compared results of patients undergoing total thyroidectomy between TOTEVA and OT. The limitations are the small sample size, short follow-up time, and selection bias of surgical methods. Besides, some new problems also need consideration. For example, in the case of total thyroidectomy by TOETVA, it is not yet clear which indication is safe enough for avoiding conversion to open to protect contralateral RLN when unilateral RLN is damaged.

In conclusion, for the selected patients requiring total thyroidectomy, TOETVA is a safe and feasible technique that provides better cosmetic effects and similar surgical outcomes compared to conventional open surgery. More large-sample, long-term follow-up or prospective studies are needed to confirm its surgical outcomes and oncological results.

Acknowledgments

This study was supported by Basic Public Welfare Research Project of Zhejiang Province (LGF22H070002).

Compliance with ethical standards

Disclosures

Yujun Li, Zhaodi Liu, Yong Wang, Xing Yu, Tiantian Wang, Cheng Xiang, Ping Wang declare that they have no conflicts of interest or financial ties to disclose

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Is transoral endoscopic thyroidectomy via vestibular approach safe for total thyroidectomy compared to open thyroidectomy? A propensity-score matched cohort study of 101 matched patient pairs with papillary thyroid carcinoma.

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