Most thyroid cancers, especially PTC, exhibit better biological behaviors than other endocrine malignancies like pancreatic carcinoma and breast carcinoma, are less invasive and malignant, and do not require conventional radiotherapy and chemotherapy after surgery. However, patients with PTC are more likely to develop lymph node metastasis in the neck, which has an impact on their prognosis[a15a]. Long-standing research has shown that improper and incomplete lymph node dissection during the first or early surgery can easily result in postoperative recurrence and metastasis[a16a],[a17a], necessitating additional treatments like reoperation or ablation and adding to the burden placed on the patient.In accordance with the principles of tumor treatment, prophylactic central lymph node dissection (PCCND) is highly advised for cN0 patients in order toprovide accurate pathological staging for clinical purposes[a18a],[a19a],[a20a], lower the risk of post-operative recurrence, prevent secondary trauma, and lessen doctor-patient conflicts. In addition to improving, standardizing, and streamlining surgical procedures, it is possible to use lymph node tracing techniques like chlorophyll, ink, methylene blue, toluidine blue-low molecular dextrose (dextran-40,TB-Dex-40)[a21a], indocyanine green fluorescence[a22a], carbon nanoparticles, etc. to more thoroughly remove the lymph nodes in the central region.
In malignant tumors, such as radical gastrectomy, radical mastectomy, etc[a23a],[a24a], carbon nanoparticles has been widely used as a lymph node developer because it is stable by nature, has good lymph node convergence, and is simple to use. Carbon nanoparticles suspension is a nano-sized carbon particle suspension, the average diameter of its particles is about 150nm, while the gap between capillary endothelial cells is only 20-50nm, much smaller than the diameter of carbon nanoparticles particles, which will not easily penetrate the endothelium of blood vessels unless directly injected into large blood vessels. Since there is a 120–500nm gap between capillary lymphatic endothelial cells, carbon nanoparticlesis primarily metabolized through the lymphatic pathway, entering lymphatic vessels, and then being engulfed by macrophages[a25a],[a26a],[a27a]. The majority of the carbon nanoparticles is then eliminated following the surgical removal of the thyroid gland and irrigation of the central lymph nodes. Effective pharmacokinetic measurements are challenging due to carbon nanoparticles's inability to enter the bloodstream. After being ingested, a small number of carbon nanoparticles particles are absorbed by macrophages, and then eventually shed through the intestinal endothelium and lung epithelium and excreted in secretions and feces after a few months. Because of this, carbon nanoparticles has few side effects and can be used prior to surgery due to the special lymphatic tendency's lack of significant negative effects.
It has also been shown that the combined use of indocyanine green and intraoperative use of near-infrared fluorescence technology can improve lymph node dissection and parathyroid contrast[a28a]; however, it increases the financial cost and lengthens the operative procedures. Numerous studies have demonstrated that the use of carbon nanoparticles as a lymph node developer during thyroid cancer surgery leads to a significant increase in lymph nodes, a more thorough removal of the tumor, improved lymph node positivity, and positive outcomes for patients[a29a],[a30a]. Because of its earlier initial tracing time and longer continuous tracing time compared to methylene blue[a31a], carbon nanoparticles is frequently used as a lymph node developer for radical thyroid cancer surgery in our unit. The average number of lymph nodes dissected in our study was 7, with more than 70% of patients have 5 or more final lymph nodes dissected, and the rate of lymph node metastasis was nearly 50%, which is higher than the results of previous studies in our centre: the rate of positive lymph nodes in the central region was about 35.1%, and the average number of lymph nodes dissected was 6.2±4.5 (3-27)[a32a],[a33a],[a34a],[a35a]; also higher than the results of other centres were the results of the study by Yiming Cao et al[a36a]: lumpectomy for radical thyroid cancer removed a mean of 6.12±3.54 lymph nodes, with a lymph node metastasis rate of 34.7% (33/95).
Preoperative injection of carbon nanoparticles produced better lymph node visualization than intraoperative injection because the gland and surrounding lymphatic drainage structures were not altered by the surgical manipulation and corresponded to the normal physiological state. The potential effects of intraoperative injection included: (1) the staining time of carbon nanoparticles was significantly shorter than that of preoperative injection; (2) during thyroid surgery, dissection of the capsule inevitably results in partial disconnection of lymphatic vessels. (3) pulling and squeezing of the gland during surgery, which impacted lymphatic reflux. These studies demonstrate that carbon nanoparticles preoperative injection results in more lymph nodes being removed and a higher positive rate situation than intraoperative injection, and that it does not affect the outcome of the procedure.
Regarding the method of lumpectomy, our centre has successfully performed thyroid surgery via the oral, submental, anterior chest, chest-breast, total areola, and axillary approaches, but has not yet performed robotic thyroid surgery, and primarily using a traditional lumpectomy system. In the early stages, the centre performed radical thyroid surgery using the thoracic and breast mammary approaches. However, with further understanding, study visits and guidance from colleagues, it was found that the bottom-up lumpectomy approach had obvious defects in lymph node clearance in the central region and that transoral assistance could compensate for this defect, reduce lymph node leakage and reduce the risk of recurrence. The transthoracic and total areola approaches are mainly used for benign thyroid nodules. Initially, our centre performed radical thyroid surgery via the anterior chest, chest-breast and total areola approaches. However, with further understanding, study visits and guidance from colleagues, we found that the bottom-up lumpectomy approach has obvious defects in central lymph node clearance and that transoral assistance can compensate for this defect[a37a],[a38a],[a39a], reduce lymph node leakage and reduce the risk of recurrence. Therefore, at present, the transoral or transsubmental approaches are mainly used for radical thyroidectomy at our centre, while the transthoracic and total areola route is mainly used for benign thyroid nodule surgery.
Intraoperative dissection of the upper mediastinal lymph nodes via the anterior chest, chest-breast, total areola, or axillary approaches can be achieved by lifting and pulling the soft and lymphatic tissues of the central region, summarised as: lifting, pulling, dragging and tugging, but the commonly used lumpectomy system with a mirror angle of 30° cannot adjust the field of view, and the conventional lumpectomy instrument does not provide multidimensional angle change, so there is inevitably a blind field of view, which can easily lead to omissions and residuals, while the cervical miccoli or transoral approach can eliminate the visual blindness and supplement the clearance[a40a][a41a]. Therefore, we exclude the anterior chest, chest-breast, total areola, or axillary approaches and only include the oral and submental approaches.
There is a lack of clear reporting of the specifics of carbon nanoparticles injections in other literature, as well as a lack of specific steps and images that are pertinent. At the earliest, we refer to the guidelines, which recommend preoperative ultrasound guidance, local disinfection, change of injection needle to avoid blackening of the skin, and continuous pumping back of the empty needle after injection if the needle recedes under the skin, causing negative pressure to pull the needle out, resulting in blackening of the skin[a42a]. (Figure 2, Diagram of syringe)
As we progressed through the clinical work, we made adjustments based on the issues we encountered. To date, a total of three patients with dark skin staining have been informed of their condition and are being followed regularly, without particular complaints at present.
Our problems: (Figure 3)
1. If the needle pin is not tightly connected to the nipple, this can also result in carbon nanoparticles residue on the needle tip and dark skin staining.
2. Carbon nanoparticles contact with the plunger, non-continuation, intermixing of air, suspension breakage, all can leave some carbon nanoparticles in the syringe needle after injection and also cause dark skin staining.
3. When extracting carbon nanoparticles, direct extraction of the suspension immediately creates a negative pressure in the bottle, and the pressure fluctuates after the needle is removed, so air can easily and quickly enter the syringe, causing the suspension to not continue and break in the middle.
4. The volume of carbon nanoparticles is only 0.5ml or 1ml, and the bottle itself is mixed with gas. The depth of needle insertion or the orientation of the bottle during extraction will have an effect and the solution may not be extracted or the solution may be broken and mixed with air after extraction.
5. The negative pressure needle extraction procedure is not convenient, must be consciously withdrawn to maintain negative pressure. In addition, there are no established pressure standards, making it impossible to regulate the precise level of negative pressure.
6. The plunger is in direct contact with the suspension without air reserved, the needle must have residual carbon nanoparticles after injection while the skin is easily blackened and stained.
Our improved solution: (Figure 4)
1. Before extracting the carbon nanoparticles, extract 0.4ml of air from a 1ml syringe, insert the needle tip down into the bottle—1-2 mm should be sufficient—keep the needle tip down, inject 0.2ml of air into the bottle, then invert the syringe—carbon nanoparticles bottle, keep the carbon nanoparticles bottle slightly above the level of the syringe, and slowly extract the carbon nanoparticles.
2. Make sure the suspension in the syringe is continuous and intact, avoid mixing air with the medication, avoid contact with the plunger, and reserve air before and after.
3. Replace the 1ml syringe needle with a 10ml syringe needle for injection after extracting the suspension, and be careful to clean the nipple of any potential carbon nanoparticles residue. Then, extract 0.1ml of air before replacing the needle to prevent any residual carbon nanoparticles at the needle plug and nipple.
4. Avoiding blood vessels at the injection site and paying close attention to the anterior jugular vein for the median jugular route and the external jugular vein for the lateral sternocleidomastoid route are both recommended.
5. When withdrawing before injection, air is reserved to make it easier to determine whether the tip enter the large vessels within the gland; if the tip does enter the vessels, withdrawing with blood is more obvious and easier to observe; if no air is reserved and the tip does enter the vessels, blood mixed with carbon nanoparticles after withdrawing affects identification. Injecting air confirms that it is inside the gland and not the large vessels within the gland by making clear high echoes visible under ultrasound; if air enters the large vessels; high echoes under ultrasound quickly disappear and disperse.
6. After suspension, air is left in place to help evacuate the remaining carbon nanoparticles from the nipple, pin and tip. After all the carbon nanoparticles has been slowly injected, 0.1 ml of air is injected again and the syringe is slowly withdrawn at atmospheric pressure, with the needle tip between the glandular surface and the strap muscles, the remaining air is injected, again avoiding residual carbon nanoparticles at the needle tip, and the needle is slowly withdrawn directly, without vacuum, to facilitate the operation.
In conclusion, ultrasound-guided preoperative injection of carbon nanoparticles has some clinical application value in the preoperative preparation of endoscopic radical thyroidectomy. It is easy, convenient, increases the number of cleared lymph nodes, increases the rate of positive lymph nodes, and does not require additional intraoperative steps, making the procedure more fluid and improving surgical efficiency. A prospective study could be conducted to increase the sample size and combine with additional studies in multiple centres as this study is a single-centre, retrospective study with a small sample size.