Introduction
Early Transoral Vestibular Approach Endoscopic Thyroid Surgery (TOETVA) was mostly used in benign thyroid diseases1and then more scholars began to explore its application in differentiated thyroid cancer, and achieved initial success2,3.The central lymph nodes (CLN) metastasis rate of differentiated thyroid cancer (DTC) is 30%-80%, and the CLN metastasis rate of pT1 is about 10–40%4. Therefore, except for some patients with microcarcinoma, most DTC patients need to dissect the ipsilateral CLN5.Guo et al. initially proved that CLN dissection in transoral approach endoscopic thyroid surgery (ETS) is feasible6and then Benhidjeb et al. proved its feasibility again from neck anatomy7.There have been many reports on the use of TOETVA in DTC: the systematic review by Jongekkasit et al.3 showed the application of TOETVA in DTC by 5 researchers, and pointed out that in the case of tumor diameter ≤ 2 cm and no evidence of lateral neck lymph node metastasis, its overall safety and resection effect are roughly equivalent to those of OT.However, the number of cases of these 5 researchers is small, mostly less than 20 cases, and there is no control group.In our previous study, TOETVA was used in 59 patients with DTC and 46 patients with benign thyroid disease, but the effect of CLN dissection was not compared8.Some centers still question the application of this technique in DTC, mainly questioning whether the endoscopic CLN dissection is thorough, thus limiting its promotion.
At present, TOETVA is still new, and thyroid cancer is mostly an indolent tumor. To obtain accurate survival rate and disease-free survival rate compared with other malignant tumors, a longer-term follow-up is required. There is no long-term follow-up data with a high level of evidence in the literature at this stage. However, the data on whether the CLN dissection is thorough in TOETVA can be obtained by counting the number of lymph nodes and the positive rate in the near future. If the CLN sweeping effect is about the same, it will provide strong evidence for the view that TOETVA has a good long-term effect in DTC.
Since the 1950s, some biological dyes have been used as lymphatic tracers for intraoperative identification of lymph nodes, thereby facilitating lymphadenectomy, with the earliest use being methylene blue in breast cancer. Nano-carbon (CN) suspension injection is the third generation lymphatic tracer, which has a high degree of tropism to the lymphatic system, and the average particle diameter is 150 nm. Post-injection into the local tumor, CN is phagocytized by macrophages. Given the capillary endothelial cell gap for blood vessels (20–50 nm) vs. lymphatic vessels (120–500 nm), and the underdeveloped basement membrane, CN enters the lymphatic system rather than blood vessels, reducing adverse reactions8.Unlike methylene blue, it doesn’t blacken surrounding tissues or stain parathyroid glands, aiding lymph node dissection and parathyroid protection. In a study comparing the two dyes on 96 papillary thyroid carcinoma (PTC) patients, both worked well for assessing central lymph node status, but CN showed a lower incidence of parathyroid damage9.
The application of CN in open thyroidectomy (OT) has been reported in many studies9,10. Due to the successful use of CN in OT, most scholars continue to encourage its application in TOETVA. At present, there is a notable lack of large-scale studies reporting on the use of CN in TOETVA to assess the efficacy of CLN dissection. Therefore, we designed a single-center prospective non-randomized controlled study aimed at exploring whether the effectiveness of CLN dissection in TOETVA is consistent with that in OT through lymph node tracing using CN.
Materials and methods
Inclusion and exclusion criteria
This study is a single-center prospective non-randomized controlled retrospective study.
Inclusion criteria: (1) The first diagnosis is DTC, and the imaging shows that the largest diameter of the tumor is < 2 cm; (2) If there is no preoperative pathological diagnosis, the surgeon and radiologist need to jointly judge the imaging data as suspicious DTC; (3)Goiter ≤ II degree. DTC was made by fine - needle aspiration biopsy (FNA). Under ultrasound guidance, a thin needle is inserted into a thyroid nodule to collect cell samples for cytological examination. This is a gold - standard diagnostic method for DTC. Microscopic examination of the samples can detect cancer cells, but sometimes the results are inconclusive. In such cases, further examination, including surgical removal followed by paraffin - section pathology, immunohistochemical staining, and gene testing, may be needed. Grade II thyroid enlargement refers to a specific degree of thyroid swelling. The enlarged thyroid is visible, but doesn’t extend beyond the outer edge of the sternocleidomastoid muscle by inspection. During swallowing, the thyroid moves over the sternocleidomastoid muscle, with its edge lying inside or roughly parallel to this muscle by palpation.
Exclusion criteria: (1) Imaging and preoperative pathological diagnosis considered benign thyroid disease.(2) The mass is close to the trachea or breaks through the capsule; (3) Imaging examination shows lymph node metastasis in the lateral neck region or systemic metastasis; (4) Intolerant to general anesthesia surgery; (5) History of neck surgery or radiotherapy; (6)) Oral abscesses, mucosal ulcers.
Enrollment situation
Among the DTC patients who underwent surgery in our hospital from September 2019 to January 2020, a total of 185 patients met the inclusion and exclusion criteria and signed the consent form for surgery. According to the cosmetic needs of patients, the patients were divided into: experimental group: TOETVA group, a total of 119 people. Control group: OT group, a total of 66 people. Note: For patients who meet the indications for TOETVA surgery, the surgical procedure should follow the patient’s wishes rather than random grouping, otherwise it is unethical. Therefore, randomized controlled trials cannot be used in this experiment, and patients cannot be blinded.
After starting the trial, if the following situations occur, they will be excluded and will no longer be included in the statistical scope: the operation is performed by other doctors who are not in the team. the lymph node specimens are not processed according to the experimental protocol, resulting in incomplete data. TOETVA surgery is converted to open surgery. rapid disease during operation examination or postoperative routine pathological examination showed non-DTC. One patient in the TOETVA group had subclavian vein hemorrhage during operation and was converted to open surgery. For the rest, see Flowchart 1 (Fig. 1) for details. Finally, 75 patients were excluded, and the remaining 110 patients (80 in the TOETVA group and 30 in the OT group) were included in this study.
Fig. 1 [Images not available. See PDF.]
Flowchart 1 for Enrollment situation.
General information
The following general clinical data were collected (Table 1): age, gender, extent of thyroidectomy (unilateral lobe and isthmus resection is referred to as “unilateral resection”, subtotal or total thyroidectomy is referred to as “total resection”), CLN Extent of cleaning (unilateral central lymph node removal is “unilateral” and bilateral central lymph node removal is “bilateral”).
Table 1. Comparison of preoperative clinical data between TOETVA and OT groups.
Clinical information | Experimental group (TOETVA group) (n = 80) | Control group (OT group) (n = 30) | P value |
|---|---|---|---|
Age, mean ± standard deviation, years | 37.0 ± 10.0 | 47.4 ± 7.9 | 0.000a |
Gender Male, number of cases (%) Female, number of cases (%) | 7(8.8%) 73(91.2) | 10(33.3%) 20(66.7%) | 0.004b |
Extent of thyroidectomy, Unilateral incision, number of cases (%) Total cut, number of cases (%) | 63(78.8%) 17(21.2%) | 17(56.7%) 13(43.3%) | 0.021c |
CLN cleaning range, Unilateral, cases (%) Bilateral, case number (%) | 61(76.2%) 19(23.8%) | 13(43.3%) 17(56.7%) | 0.001c |
Intraoperative management
Both groups were operated by the same senior physician and his team.
The operation steps of the TOETVA group were as follows according to our previous study11: Orotracheal intubation was used for general anesthesia, and second-generation cephalosporin was routinely used before operation due to the type II incision. A transoral vestibular approach was used to dissect the mental nerve, establish a subcutaneous tunnel, open the linea alba, separate and suspend the strap muscles, and expose the thyroid isthmus and conical lobe.
At this time, start to inject CN mixed injection (brand: Canalin). Steps: Use a 1 ml syringe to extract a small amount of Canalin, pierce the skin, and look for the injection point under the laparoscopic monitor. Single-point injection is used, and the volume is about 0.05 ml near the tumor around the lower outer surface of the thyroid gland (just below the needle tip), avoiding blood vessels and tumors. After injection, withdraw and withdraw while pumping. If both glandular lobes are suspected to be malignant, each of the two glandular lobes needs to be injected once, and the other lobe should be injected immediately after the injection of one lobe.
The conical lobe was freed until the isthmus, and the ultrasonic knife was used to transect the isthmus on the surface of the trachea, and the upper pole of the thyroid was continued to be freed. About 20 min after the injection, the CN gradually stained the thyroid gland and surrounding lymph node tissue black, which was removed. The parathyroid glands are not stained with CN black (i.e., negative image development), and the identification is clearer, which is conducive to the protection of the parathyroid glands.
The recurrent laryngeal nerve was avoided, and the thyroid gland and tumor were completely removed. The specimen is put into the specimen bag and taken out. Flush the surgical field and carefully stop the bleeding. There is no need to suture the white line of the neck, and a disposable central venous catheter is used as the drainage tube. Due to the small diameter of the tube, the scar after extubation can be greatly reduced. For patients with less intraoperative bleeding, no drainage was placed depending on the situation. The incision was closed with interrupted 5 − 0 absorbable sutures.
The OT group underwent conventional open thyroid surgery. After exposing the gland, inject CN under direct vision, the method is the same as above.
The extent of thyroidectomy and CLN dissection in the two groups were performed in accordance with the 8th edition of the AJCC guidelines5. If the preoperative pathological examination shows DTC, there is no need to send the thyroid tissue for rapid pathological examination during the operation, and it is directly treated as DTC. If there is no preoperative pathological data, a rapid pathological examination should be sent during the operation. If the rapid pathological examination revealed non-DTC, and the clinical judgment did not require CLN dissection, the case was excluded.
Thyroid specimen processing: directly use a sterilized steel ruler to measure the tumor diameter on the gross specimen (in mm, accurate to 1 mm). Processing of CLN specimens: In order to increase the detection rate, the dissected lymph nodes were picked out one by one under the guidance of a senior thyroid surgeon (Fig. 2). The total number of dissected lymph nodes recognized by the operator with naked eyes was recorded as the total number of roughly detected CLN (Row retrieved lymph nodes, RRLN-total).Record the number of lymph nodes with a diameter less than 5 mm (RRLN < 5 mm) and lymph nodes with a diameter greater than or equal to 5 mm (RRLN ≥ 5 mm), and divide them into two specimen bags for inspection.
Fig. 2 [Images not available. See PDF.]
Thyroid lobectomy + central lymph node dissection. After the specimen is taken out, the dissected lymph nodes are actively picked out. The picture on the left shows the patient who used CN, see black staining of lymph nodes. The picture on the right is without using nano carbon.
Postoperative treatment
In the TOETVA group, a saline pad was placed under the chin, fixed under pressure, and an ice pack was applied to the chin to reduce postoperative edema and pain. After 6 h, eat fluids, and rinse your mouth with salt water after each meal. Antibiotics were used continuously for 2 days. The wounds in the OT group can be covered with dry and clean dressings, without pressurization, and appropriate ice compresses can be applied. There are no special restrictions on postoperative diet. Because of the type I incision, no antibiotics are required. If a drainage tube is placed, it will be removed about 2 days after the operation. All patients were instructed to carry out head-raising exercise training after discharge to prevent neck stretching. For patients with total thyroidectomy, calcium carbonate granules 3 g three times a day (Tid) are routinely taken orally after surgery, and the drug is discontinued until the blood calcium is normal again on the day of discharge after surgery.
The incidence of postoperative complications was recorded during hospitalization: subcutaneous effusion, hematoma, local infection, temporary hoarseness, and temporary hypocalcemia. Tube blockage: The blockage of the drainage tube causes poor drainage, which may be caused by blood clot blockage or bending of the catheter. Leakage: refers to the loss of negative pressure in the high negative pressure drainage bottle within a short period of time. Subcutaneous effusion and hematoma: manifested as subcutaneous swelling, effusion usually occurs after 24 h after operation, and hematoma usually occurs within 24 h, which can be confirmed by puncture or reoperation. Local infection: subcutaneous redness, swelling, heat pain, pus when punctured, which can be confirmed by bacterial culture. Temporary hoarseness: manifested as hoarseness, which can be confirmed by laryngoscopy. Temporary hypocalcemia: blood calcium is lower than 2.0mmol/L.
On the first day after surgery, the visual analogue scale (VAS) was used to record the pain score. The score ranged from 0 to 10. The higher the score, the more painful. 0 means no pain at all, and 10 means pain Unbearable. After removing the drainage tube, read the scale ml of the high negative pressure drainage bottle, which is accurate to single digits. If no drainage tube is placed, the drainage volume is recorded as 0 ml.
About 1 week after the operation, the general pathological examination results can be found. The following data was recorded: Retrieved lymph nodes (RLN) in the central region, record the total number of detected lymph nodes (RLN-total), lymph node diameter less than 5 mm (RLN < 5 mm, referred to as small lymph nodes) and larger than equal to the detected number of 5 mm (RLN ≥ 5 mm, referred to as large lymph nodes). Positive central lymph nodes (Positive lymph nodes, PLN), record the total positive number (PLN-total), lymph node diameter less than 5 mm (PLN < 5 mm) and positive lymph nodes greater than or equal to 5 mm (PLN ≥ 5 mm) for each patient number.
Among them, RLN and PLN are the main evaluation indicators. RRLN is the secondary evaluation index.
Statistical analysis
Statistical results were analyzed by using SPSS 20.0, the mean and standard deviation of quantitative data were calculated, and t test or t’ test was used for comparison of quantitative data. Qualitative data need to be counted and the composition ratio calculated, using X² test or chi-square test with continuous correction or Fisher’s exact probability method. p < 0.05 was considered statistically significant.
The preoperative general clinical data are summarized in Table 1, the postoperative general results are summarized in Table 2, and the results of CLN are summarized in Table 3. Paired t-tests were performed on the indicators of the size of lymph nodes in each group to explore whether the size of lymph nodes affects the number of detection and the positive rate. The results are listed in Tables 3, 4 and 5.RRLN was compared with RLN to test the accuracy of picking out lymph nodes. The results are listed in Table 3.
Table 2. Comparison of postoperative general results between TOETVA group and OT group.
Result | Experimental group (TOETVA group) (n = 80) | Control group (OT group) (n = 30) | P value |
|---|---|---|---|
Intraoperative blood loss, mean ± standard deviation, ml | 22.3 ± 9.4 | 21.0 ± 6.2 | 0.422a |
Postoperative short-term complications, total number, % | 8(10.0%) | 3(10.0%) | 1.000b |
Subcutaneous effusion, total, % | 2(2.5%) | 0% | 1.000c |
Hematoma, total, % | 1(1.2%) | 0% | 1.000c |
Infection, total, % | 2(2.5%) | 0% | 1.000c |
Temporary hoarseness, total, % | 3(3.8%) | 2(6.7%) | 1.000c |
Temporary low calcium, total, % | 3(3.8%) | 1(3.3%) | 0.612c |
VAS score, mean ± standard deviation | 2.4 ± 1.0 | 2.1 ± 0.8 | 0.172a |
Total postoperative drainage volume, mean ± standard deviation, ml | 69.3 ± 26.1 | 65.3 ± 23.5 | 0.469c |
at’ test when variances are not homogeneous. bContinuously corrected chi-square test. cFisher’s exact test.
Table 3. Comparison of lymph node dissection results between TOETVA group and OT group.
Various indicators of central lymph node dissection | Experimental group (TOETVA group) (n = 80) | Control group (OT group) (n = 30) | P value |
|---|---|---|---|
RRLN-total, mean ± standard deviation, individual | 12.2 ± 6.0 | 12.1 ± 6.0 | 0.979a |
RRLN < 5 mm, each | 7.0 ± 4.0 | 7.0 ± 4.0 | 7.1 ± 4.4 |
RRLN%<5 mm, % | 57.4% | 58.0% | - |
RRLN ≥ 5 mm, each | 5.2 ± 3.4 | 5.2 ± 3.1 | 0.963a |
RRLN%≥5 mm | 42.6% | 42.0% | - |
P value (RRLN size lymph nodes) | 0.001b | 0.026b | - |
RLN-total, mean ± standard deviation, individual | 11.3 ± 6.3 | 11.4 ± 5.3 | 0.931a |
RLN < 5 mm, each | 6.3 ± 4.3 | 6.6 ± 3.8 | 0.748a |
RLN%<5 mm, % | 55.9% | 57.9% | - |
RLN ≥ 5 mm, each | 5.0 ± 3.7 | 4.9 ± 2.8 | 0.908a |
RLN%≥5 mm, % | 44.1% | 42.1 | - |
P value (RLN size lymph nodes) | 0.021b | 0.025b | - |
P value (RRLN-total and RLN-total) | 0.002b | 0.034b | - |
P value (< 5 mm RRLN vs. RLN) | 0.004b | 0.096b | - |
P value (≥ 5 mm RRLN vs. RLN) | 0.148b | 0.043b | - |
PLN-total, mean ± standard deviation, individual | 1.7 ± 2.6 | 1.8 ± 2.5 | 0.808a |
PLN < 5 mm, each | 0.8 ± 1.6 | 0.9 ± 1.2 | 0.748a |
PLN%<5 mm, % | 44.9% | 47.2% | - |
PLN ≥ 5 mm, each | 1.0 ± 1.5 | 1.0 ± 1.6 | 1.000a |
PLN%≥5 mm, % | 55.1% | 52.8% | - |
P value (PLN size lymph nodes) | 0.221b | 0.546b | - |
PR-total, pcs (%) | 137(15.2%) | 56(16.2%) | 0.638c |
PR < 5 mm, each (%) | 61(12.0%) | 26(13.1%) | 0.703c |
PR ≥ 5 mm, each (%) | 76(19.0%) | 30(20.4%) | 0.721c |
P value (PR size lymph nodes) | 0.003c | 0.070c | - |
Those with positive lymph nodes, cases (%) | 41(51.3%) | 17(56.7%) | 0.612c |
Bold fonts represent statistically significant P values.
Since the extent of lymph node dissection significantly affects the number of lymph nodes, and the baselines of the extent of lymph node dissection in the experimental group and the control group are inconsistent, it is necessary to divide them into two subgroups: “unilateral CLN dissection” and “bilateral CLN dissection”. Discussion, the obtained data are summarized in Tables 4 and 5 respectively.
Table 4. Comparison of lymph node dissection results between TOETVA group and OT group in unilateral central area dissection bold represents statistically significant P values.
Various indicators of central lymph node dissection | Experimental group (TOETVA group) (n = 61) | Control group (OT group) (n = 13) | P value |
|---|---|---|---|
RRLN-total, mean ± standard deviation, individual | 10.9 ± 5.1 | 8.0 ± 3.7 | 0.055a |
RRLN < 5 mm, | 6.3 ± 3.8 | 4.2 ± 2.7 | 0.072a |
RRLN%<5 mm | 57.4% | 52.9% | - |
RRLN ≥ 5 mm, each | 4.7 ± 2.9 | 3.7 ± 2.8 | 0.330a |
RRLN%≥5 mm | 42.6% | 47.1% | - |
P value (RRLN size lymph nodes) | 0.007b | 0.690b | - |
RLN-total, mean ± standard deviation, individual | 10.2 ± 5.6 | 7.7 ± 3.4 | 0.124a |
RLN < 5 mm, each | 5.8 ± 4.2 | 4.1 ± 2.4 | 0.161a |
RLN%<5 mm | 57.0% | 53.0% | - |
RLN ≥ 5 mm, each | 4.4 ± 3.3 | 3.6 ± 2.5 | 0.431a |
RLN%≥5 mm | 43.0% | 47.0% | - |
P value (RLN size lymph nodes) | 0.038b | 0.652b | - |
PLN-total, mean ± standard deviation, individual | 1.5 ± 2.3 | 1.2 ± 1.7 | 0.580a |
PLN < 5 mm, each | 0.6 ± 1.2 | 0.5 ± 1.0 | 0.822a |
PLN%<5 mm | 40.4% | 46.7% | - |
PLN ≥ 5 mm, each | 1.0 ± 1.6 | 0.6 ± 1.0 | 0.397a |
PLN%≥5 mm | 64.9% | 53.3% | - |
P value (PLN size lymph nodes) | 0.062b | 0.753b | - |
PR, one (%) | 95(15.2%) | 15(15.0%) | 0.949c |
PR < 5 mm, each (%) | 38(10.7%) | 7(13.2%) | 0.587c |
PR ≥ 5 mm, each (%) | 57(21.3%) | 8(17.0%) | 0.507c |
Those with positive lymph nodes, cases, % | 30(49.2%) | 7(53.8%) | 0.760c |
(a) Independent sample t test (homogeneity of variance), (b) paired sample t test, (c) Pearson Chi-square test.
Table 5. Comparison of lymph node dissection results between TOETVA group and OT group after bilateral CLN dissection. Bold fonts represent statistically significant P values.
Various indicators of central lymph node dissection | Experimental group (TOETVA group) (n = 19) | Control group (OT group) (n = 17) | P value |
|---|---|---|---|
RRLN-total, mean ± standard deviation, individual | 16.4 ± 6.8 | 15.4 ± 5.4 | 0.667a |
RRLN < 5 mm, each | 9.4 ± 3.9 | 9.3 ± 4.1 | 0.956a |
RRLN%<5 mm | 57.2% | 60.1% | - |
RRLN ≥ 5 mm, each | 7.0 ± 4.2 | 6.2 ± 2.9 | 0.540a |
RRLN%≥5 mm | 42.8% | 39.9% | - |
P value (RRLN size lymph nodes) | 0.034b | 0.015b | - |
RLN-total, mean ± standard deviation, individual | 14.7 ± 7.2 | 14.2 ± 4.7 | 0.804c |
RLN < 5 mm, each | 7.9 ± 4.1 | 8.5 ± 3.5 | 0.621a |
RLN%<5 mm | 53.6% | 59.9% | - |
RLN ≥ 5 mm, each | 6.9 ± 4.4 | 5.8 ± 2.7 | 0.415a |
RLN%≥5 mm | 46.4% | 40.1% | - |
P value (RLN size lymph nodes) | 0.340b | 0.016b | - |
PLN-total, mean ± standard deviation, individual | 2.2 ± 3.2 | 2.4 ± 2.9 | 0.889b |
PLN < 5 mm, each | 1.2 ± 2.3 | 1.1 ± 1.4 | 0.888a |
PLN%<5 mm | 54.8% | 47.5% | - |
PLN ≥ 5 mm, each | 1.0 ± 1.3 | 1.3 ± 1.9 | 0.591a |
PLN%≥5 mm | 45.2% | 52.5% | - |
P value (PLN size lymph nodes) | 0.678b | 0.616b | - |
PR, one (%) | 42(14.9%) | 41(16.7%) | 0.575d |
PR < 5 mm, each (%) | 23(15.3%) | 19(13.1%) | 0.584d |
PR ≥ 5 mm, each (%) | 19(14.5%) | 22(22.0%) | 0.140d |
Those with positive lymph nodes, case (%) | 11(57.9%) | 10(58.8%) | 0.955d |
(a) Independent sample t-test (homogeneous variance), (b) Paired sample t-test, (c) t’ test (homogeneous variance), (d) Pearson Chi-square test.
Tables 4 and 5 illustrate: (1) In the subgroup of unilateral CLN dissection, the average values of RRLN, RLN, and PLN in the experimental group were higher than those in the control group, especially for small lymph nodes. The P value is not less than 0.05, so it is not yet statistically significant. (2) In the bilateral CLN dissection subgroup, there was no significant difference in RRLN, RLN, and PLN between the experimental group and the control group. (3) Comparison of large and small lymph nodes in the same group: the number of small lymph nodes is generally more than that of large lymph nodes, especially in the TOTEVA group with unilateral CLN dissection and the OT group with bilateral CLN dissection.
It should be noted that the calculation method of “RRLN%<5 mm” in Table 3 is: add up the number of dissected lymph nodes less than 5 mm in all patients, and calculate the percentage of the total number of dissected lymph nodes. At the same time, the positive rate (PR) of small lymph nodes, large lymph nodes and overall lymph nodes was calculated, expressed as PR < 5 mm, PR ≥ 5 mm, and PR-total, respectively. The specific calculation formula is as follows:
RRLN%<5 mm = Σ(RRLN<5 mm)/Σ(RRLN-total).
RRLN%≥5 mm = 1- (RRLN%<5 mm).
RLN%<5 mm = Σ(RLN<5 mm)/Σ(RLN-total).
RLN%≥5 mm = 1- (RLN%<5 mm).
PLN%<5 mm = Σ(PLN<5 mm)/Σ(PLN-total).
PLN%≥5 mm = 1- (PLN%<5 mm).
PR-total = (ΣPLN-total)/(ΣRLN-total)×100%.
PR<5 mm = (ΣPLN<5 mm)/(ΣRLN-total)×100%.
PR ≥ 5 mm = (ΣPLN ≥ 5 mm)/(ΣRLN-total)×100%.
All methods were performed in accordance with the relevant guidelines and regulations.
Results
The general results after operation are recorded in Table 2. It can be seen that intraoperative bleeding, postoperative short-term complications, and postoperative. There was no statistically significant difference in the VAS score on the first day and the total drainage volume after operation. The results of CLN dissection are summarized in Table 3.
Comparing the difference between the experimental group and the control group: There was no significant statistical difference in RRLN, RLN, and PLN in terms of the total number, small, and large lymph nodes between the two groups.
Comparing the differences in the size of lymph nodes in the same group: For RRLN and RLN, the number of small lymph nodes in the two groups is more than that of large lymph nodes, and the difference is statistically significant. But for PLN, there was no statistically significant difference in the number of large and small lymph nodes between the two groups.
Comparing the difference between RRLN and RLN: in the experimental group, RRLN is larger than RLN, the difference is statistically significant. For large lymph nodes, the difference was not statistically significant. There is a slight difference between the control group and the experimental group, but the trend is the same as that of the experimental group, RRLN is generally higher than RLN.
Discussion
The effectiveness of CN use in thyroid surgery
This study assessed the clinical significance of CN suspension in CLN dissection during TOETVA. Our research findings indicate that, compared to traditional OT surgery, CN suspension demonstrates the same tracing effect and effectiveness in CLN dissection during TOETVA, while also increasing the detection rate of small lymph nodes, thereby aiding pathologists in identifying lymph nodes. These findings align with previous studies, reporting similar benefits of CN in other surgical settings10,12,13. For example, in 2018, Xue S et al.14 in 406 cases of OT, CN group and non-CN group in RLN (8 vs. 5, p = 0.031) and PLN(3 vs. 1, p = 0.038) were significantly different. Although there are no comparative studies on the use of CN in TOETVA, or only mention of its use, Jongekkasit et al.3 encouraged the application of CN in TOETVA due to its good application in OT. Prior to this, CN has been applied in transthoracic breast ETS, and achieved similar good results to open surgery15. TOETVA is one of ETS, and its application method can be deduced by analogy. The timing and method of injecting CN in ETS are similar to those in OT.ETS needs to be injected percutaneously under the endoscopic monitor. Compared with OT injection under direct vision, it requires slightly higher requirements for the operator15.And according to our experience, there should be as little CN residue as possible on the needle before and after injection, otherwise, when the needle is pulled out during percutaneous injection, CN will leave a black spot on the skin at the injection point, resulting in “iatrogenic mole”. Compared with our research data, in total thyroidectomy combined with bilateral central neck lymph node dissection, the number of lymph nodes removed in the TOETVA and OT groups was 14.7 ± 7.2 and 14.2 ± 4.7 respectively, which is higher than the results reported in Yu, W.‘s study. This also indirectly indicates that our nanocarbon injection method is effective and worth promoting.
Comparison of CLN cleaning effect in TOETVA and OT
Regarding the effect of CLN dissection, some literature compares the difference between the two surgical methods by counting RLN and PLN16divided the DTC patients into two groups: 150 in the TOETVA group and 125 in the OT group. The results are as follows: For patients with unilateral lobectomy: RLNs in the two groups were 3.19 ± 2.89 and 3.49 ± 2.41 (p = 0.319); PLNs were: 0.39 ± 0.91 and 0.23 ± 0.60 (p = 0.379).For patients with total thyroidectomy: RLN in the two groups were 4.98 ± 3.12 and 5.70 ± 4.35 (p = 0.714), PLN were 1.08 ± 1.46 and 1.70 ± 2.35 (p = 0.334). Initially proved that there was no statistically significant difference between TOETVA and OT in CLN dissection. You et al.17 divided the DTC patients into two groups: 100 cases in the da Vinci robot TOETVA group and 105 cases in the OT group. The results: RLN in the two groups were 4.7 ± 3.75 and 9.4 ± 6.58 (p < 0.05), PLN were 1.0 ± 2.02 1.9 ± 3.28 (p < 0.227).You et al. showed that there were more RLN in OT than in TOETVA, but there was no significant difference in PLN. However, because TOETVA in this study is da Vinci robotic surgery, its equipment and costs are expensive, and it is not realistic to promote it in my country. TOETVA in our study refers to non-robotic surgery, so the reference value of You et al. is limited. In this study, there was no statistically significant difference in RLN and PLN between TOTEVA and OT groups, which is consistent with the above study. And compared with the above studies, we additionally counted the RLN and PLN of the large and small lymph nodes, and the difference was not statistically significant. However, some scholars have suggested that endoscopy has a magnifying effect and is more conducive to identifying fine structures such as small lymph nodes, so it is more conducive to cleaning than OT. This study failed to confirm this point of view, but this trend was found in the subgroup analysis, but p > 0.05 is not yet statistically significant. The possible reasons are that the sample size is not enough, and the clarity of endoscopic equipment is related.
Pros and cons of CLN
In multiple guidelines more demolitive surgery is associated with more severe complications18, 19, 20, 21–22. Interestingly, there is also study indicating that when CLN dissection is performed by experienced surgeons, the complication rate is significantly reduced. For example, some studies have pointed out that in high-volume thyroid surgery centers, the incidence of temporary hypocalcemia can be reduced to 5% − 10%, permanent hypocalcemia to below 1%, and the incidence of temporary and permanent recurrent laryngeal nerve injuries can also be kept at a low level23. Our center has been carrying out TOETVA surgery since 2016 and has maturely mastered the surgical technique24. As thyroid surgery techniques have advanced - for instance, with the use of intra - operative nerve monitoring and intra - operative parathyroid testing - surgeons can operate more precisely. This allows for better protection of the parathyroid glands and recurrent laryngeal nerve, thus reducing complication risks25.In thyroid cancer patients with CLN metastasis, routine CLN dissection can effectively eliminate potential metastases and lower local - regional recurrence. Some long - term follow - up studies indicate that patients undergoing this dissection have relatively higher 10 - year disease - free and overall survival rates23,25. CLN dissection offers accurate staging for thyroid cancer patients, empowering physicians to devise better - suited individualized treatment plans. This includes decisions on post - op 131I and TSH suppression therapies, ultimately enhancing long - term patient prognosis25. Even if pre - op imaging like ultrasonography shows no CLN enlargement, metastasis can’t be ruled out. Literature indicates that in 20% − 30% of thyroid cancer patients, pre - op ultrasonography misses CLN metastasis detected later in post - op pathology23. Selective CLN dissection only for patients with node enlargement may cause some with occult metastasis to miss timely treatment25.For thyroid cancer patients with central lymph node metastasis not detected pre - op, not performing routine CLN dissection may lead to post - op recurrence and re - operation. This would not only increase the patient’s pain and financial burden, but also raise the risk of complications due to the greater difficulty of the second surgery25. Close post - op monitoring can detect complications early and prompt management can be initiated. For temporary hypocalcemia, timely calcium and vitamin D supplementation is given; for hoarseness due to recurrent laryngeal nerve injury, voice training or surgery can be done. These steps can reduce the impact of complications on the patient’s quality of life and prognosis. A multidisciplinary team involving endocrinology, nuclear medicine, medical oncology, etc., offers a more all - encompassing treatment and management plan, such as the center where the author is affiliated26. This approach better addresses potential post - op issues, enhancing overall treatment efficacy and the patient’s quality of life23,25.
About the probability of RRLN, RLN, PLN, PR, lymph node positive
In our study, comparing the difference between RRLN and RLN: Generally speaking, in the experimental group, RRLN is larger than RLN, that is, surgeons have errors in selecting lymph nodes and will “choose more”, especially for small lymph nodes, the difference is statistically significant. For large lymph nodes, perhaps because large lymph nodes are better identified, surgeons made less error in selecting large lymph nodes, and the difference was not statistically significant. Sometimes some charred tissues are mistaken for small black-stained lymph nodes. There is a slight difference between the control group and the experimental group, which may be caused by a small sample size error, but the trend is the same as that of the experimental group, that is, RRLN is generally higher than RLN. Overall, the RLNs in our study (11.3 ± 6.3 in the experimental group and 11.4 ± 5.3 in the control group) were higher than the other Research10,14,16,17.This is because of the application of CN, and the second is because the operator directly dissects the specimen during the operation, picks out all CLNs from the adipose tissue, and then submits them for inspection to improve the detection rate. This is rarely done by other researchers. Although the inconsistency between RRLN and RLN will lead to errors to a certain extent, it can initially improve the detection rate of lymph nodes, which can be further verified in later studies. The PLNs in this study were: 1.7 ± 2.6 in the experimental group and 1.8 ± 2.5 in the control group. It is basically consistent with the results of the one at16. and the one at17.However, it cannot be explained that increasing RLN can increase PLN, so the role of CN and picking out lymph nodes during operation should not be overstated. In this experiment, the PR was about 16%, but the proportion of positive lymph nodes was 47.8%~58.8%.This is mainly because: the increase in the number of dissected lymph nodes resulted in a larger denominator when calculating PR, resulting in a decrease in this value. However, it is obvious that each additional lymph node during dissection will increase the positive detection rate, so the metastasis rate of positive lymph nodes in this study is higher than that of pT1 stage CLN in other studies (10–40%)4.At the same time, we found that, although there was no statistical difference in the number of PLN among large and small lymph nodes, overall, the metastasis rate of large lymph nodes was slightly higher than that of small lymph nodes. However, this does not mean that the dissection of small lymph nodes can be ignored. In this group of experiments, there were several cases of PLN with more small lymph nodes than large lymph nodes. This non-randomized experiment lacks a control group not using CN or actively identifying lymph nodes intraoperatively, so the benefits of these two factors for CLN dissection in TOETVA surgery can’t be directly shown and can only be compared with prior literature.
Limitations of the study
This study has several limitations that should be acknowledged. First, this non-randomized experiment lacks a control group not using CN or actively identifying lymph nodes intraoperatively, so the benefits of these two factors for CLN dissection in TOETVA surgery can’t be directly shown and can only be compared with prior literature. Postoperative thyroglobulin (Tg) levels can be influenced by multiple factors, including the presence of anti-thyroglobulin antibodies, the extent of thyroidectomy, and the timing of measurement relative to thyroid hormone withdrawal or recombinant TSH stimulation. Due to the retrospective design and lack of a control group, we were unable to fully account for these confounding variables. Additionally, the absence of randomized controlled trial (RCT) data limits our ability to draw definitive causal conclusions. These factors may affect the generalizability of our findings and should be considered when interpreting the results.
Conclusion
The application of CN in TOETVA is feasible, and the lymph node clearance effect of TOETVA is essentially the same as that of OT. This demonstrates that TOETVA is a safe and effective new minimally invasive technique for the treatment of thyroid cancer. TOETVA tends to dissect more small lymph nodes. It is recommended to use CN during the surgical procedure to avoid omitting small lymph nodes and to actively identify lymph nodes in the CLN.
Acknowledgements
The authors extend their appreciation to the Research Project of Science Popularization Special Project of Hunan Provincial Department of Science and Technology (2024ZK4141), Hunan Provincial Natural Science Foundation of China (2024JJ9251), and Hunan Cancer Hospital Research Climbing Plan (Fostering Program of the NSFC, 2020NSFC-B007) for funding this research work.
Author contributions
Wu Li contributed to the conception and design of the experiment. Hui Li analysis of the data and writing the manuscript with assistance Zeyang Liu.
Funding
The study received funding from Research Project of Science Popularization Special Project of Hunan Provincial Department of Science and Technology (2024ZK4141), Hunan Provincial Natural Science Foundation of China (2024JJ9251), and Hunan Cancer Hospital Research Climbing Plan (Fostering Program of the NSFC, 2020NSFC-B007).
Data availability
Data will be made available upon reasonable request from the corresponding author.
Declarations
Competing interests
The authors declare no competing interests.
Ethics approval and consent to participate
For human samples, approval was obtained from the Institutional Review Board of Hunan Cancer Hospital (2023 Scientific Research Rapid Review No. 61). A waiver of informed consent was granted by the Institutional Review Board of Hunan Cancer Hospital.
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
1. Jitpratoom, P et al. Transoral endoscopic thyroidectomy vestibular approach (TOETVA) for graves’ disease: a comparison of surgical results with open thyroidectomy. Gland Surg.; 2016; 5,
2. Anuwong, A et al. Safety and outcomes of the transoral endoscopic thyroidectomy vestibular approach. JAMA Surg.; 2018; 153,
3. Jongekkasit, I et al. Transoral endoscopic thyroidectomy for thyroid cancer. Endocrinol. Metab. Clin. North. Am.; 2019; 48,
4. Sun, W et al. Risk factors for central lymph node metastasis in CN0 papillary thyroid carcinoma: A systematic review and Meta-Analysis. PLoS One; 2015; 10,
5. Doescher, J; Veit, JA; Hoffmann, TK. The 8th edition of the AJCC cancer staging manual: updates in otorhinolaryngology, head and neck surgery. HNO; 2017; 65,
6. Guo, P et al. Transoral endoscopic thyroidectomy with central neck dissection: experimental studies on human cadavers. Chin. Med. J. (Engl); 2014; 127,
7. Benhidjeb, T. Transoral endoscopic thyroidectomy with central neck dissection. Chin. Med. J. (Engl); 2015; 128,
8. Yang, F et al. Magnetic functionalised carbon nanotubes as drug vehicles for cancer lymph node metastasis treatment. Eur. J. Cancer; 2011; 47,
9. Liu, F et al. Recognition of Sentinel lymph nodes in patients with papillary thyroid cancer by nano-carbon and methylene blue. Pak J. Med. Sci.; 2017; 33,
10. Yu, W et al. Potential role for carbon nanoparticles to guide central neck dissection in patients with papillary thyroid cancer. Surgery; 2016; 160,
11. Peng, X et al. The clinical application of mental nerve dissection in transoral endoscopic thyroidectomy via an oral vestibular approach. Surg. Endosc; 2020; 34,
12. Zhao, J et al. Safety and effectiveness of carbon nanoparticles suspension-guided lymph node dissection during thyroidectomy in patients with thyroid papillary cancer: a prospective, multicenter, randomized, blank-controlled trial. Front. Endocrinol. (Lausanne); 2023; 14, 1251820.
13. Lin, D et al. Enhancing parathyroid preservation in papillary thyroid carcinoma surgery using nano-carbon suspension. Sci. Rep.; 2024; 14,
14. Xue, S et al. Short and Long-Term potential role of carbon nanoparticles in total thyroidectomy with central lymph node dissection. Sci. Rep.; 2018; 8,
15. Wang, B et al. The role of carbon nanoparticles in identifying lymph nodes and preserving parathyroid in total endoscopic surgery of thyroid carcinoma. Surg. Endosc; 2015; 29,
16. Ahn, J; Yi, JW. Transoral endoscopic thyroidectomy for thyroid carcinoma: outcomes and surgical completeness in 150 single-surgeon cases. Surg. Endosc; 2020; 34,
17. You, JY et al. Transoral robotic thyroidectomy versus conventional open thyroidectomy: comparative analysis of surgical outcomes in thyroid malignancies. J. Laparoendosc Adv. Surg. Tech. A; 2019; 29,
18. Conzo, G et al. Surgical treatment of papillary thyroid carcinoma without lymph nodal involvement. G Chir.; 2012; 33,
19. Giordano, D et al. Complications of central neck dissection in patients with papillary thyroid carcinoma: results of a study on 1087 patients and review of the literature. Thyroid; 2012; 22,
20. Haugen, B. R. et al. The American Thyroid Association Guidelines Task Force on thyroid nodules and differentiated thyroid cancer. Thyroid26(1), 1–133 (2015).
21. Haddad, RI et al. Version 2.2022, NCCN clinical practice guidelines in oncology. J. Natl. Compr. Canc Netw.; 2022; 20,
22. Filetti, S et al. Thyroid cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-updagger. Ann. Oncol.; 2019; 30,
23. Sun, H; Tian, W. Chinese guidelines on intraoperative neuromonitoring in thyroid and parathyroid surgery (2023 edition). Gland Surg.; 2023; 12,
24. Peng, X et al. Modified transoral endoscopic thyroid surgery for treatment of thyroid cancer: operative steps and video. Gland Surg.; 2017; 6,
25. Baud, G. et al. Impact of lymph node dissection on postoperative complications of total thyroidectomy in patients with thyroid carcinoma. Cancers (Basel)14 (21), 2072–6694 (2022).
26. Zhou, S et al. Challenging routine: technical difficulties and solutions of endoscopic thyroidectomy via a combined transoral and breast approach - a case-series and learning curve. Int. J. Surg.; 2023; 109,
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Abstract
This research seeks to explore the application value of carbon nanoparticle (CN) in transoral endoscopic thyroidectomy vestibular approach (TOETVA) with the goal of providing more reliable clinical evidence for minimally invasive treatment of thyroid cancer.A total of 110 patients with differentiated thyroid cancer (DTC) met the inclusion and exclusion criteria from September 2019 to January 2020. They were divided into an experimental group (TOETVA group) of 80 patients and a control group (OT group) of 30 patients based on their cosmetic preferences. All patients were treated with CN during surgery, and the surgeon actively selected lymph nodes and sent them separately for examination according to < 5 mm (small) and ≥ 5 mm (large), recording the number of row retrieved lymph nodes (RRLN). Routine medical examination was conducted to report the number of retrieved lymph nodes (RLN) and positive central lymph nodes (PLNs) detected one week after surgery. The positive rate (PR) of lymph nodes and the proportion of lymph node positive individuals were calculated. Compared with the control group, there was no significant difference between the experimental group and the control group in the proportion of RRLN, RLN, PLN, PR, and lymph node positivity. The differences in the number of lymph nodes of the same group: small lymph nodes have more RRLN and RLN than large lymph nodes, and the difference is statistically significant. In the experimental group, RRLN is larger than RLN, the difference is statistically significant. There is a slight difference between the control group and the experimental group, RRLN is generally higher than RLN. The lymph node clearance effect of TOETVA and OT is basically consistent. The use of CN can improve the detection rate of small lymph nodes in TOETVA, and it is recommended to use CN during the procedure.
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Details
1 Department of Thyroid Surgery, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410006, Changsha, Hunan, China (ROR: https://ror.org/00f1zfq44) (GRID: grid.216417.7) (ISNI: 0000 0001 0379 7164)