A Surgical Procedure for Thyroidectomy: Para-Tracheal Capsular Dissection and its Benefit in the Protection of the Parathyroid Gland

Summary

Para-tracheal capsular dissection in thyroidectomy better preserves parathyroid function than the conventional method, shown by higher postoperative parathyroid hormone (PTH) levels and fewer cases of hypoparathyroidism without affecting calcium levels, suggesting its superiority in safeguarding parathyroid health. Here, we present a step-by-step protocol describing para-tracheal capsular dissection.

Abstract

Para-tracheal capsular dissection, conducted adjacent to the trachea, is postulated to mitigate the risk of parathyroid gland injury. This study compares postoperative parathyroid function following para-tracheal and conventional capsular dissection in thyroidectomy procedures. A retrospective analysis was performed on the medical records of 142 patients who underwent bilateral thyroidectomy with capsular dissection. In this randomized trial, 76 patients received para-tracheal capsular dissection, while 66 underwent the conventional approach. All patients were administered carbon nanoparticles as a lymphatic tracer, and their serum parathyroid hormone (PTH) and calcium (Ca²⁺) levels were evaluated postoperatively. Those presenting with serum PTH and/or Ca²⁺ levels below the normal range on the first postoperative day received management and follow-up. On the first postoperative day, the para-tracheal group exhibited significantly higher serum PTH levels (2.26 pmol/L, interquartile range [IQR] 1.46-3.53 pmol/L) compared to the conventional group (2.00 pmol/L, IQR 0.93-2.95 pmol/L, P = 0.04). Additionally, the para-tracheal group demonstrated a lesser reduction in PTH levels (47% vs. 58% from the pre-surgical level, P = 0.06). The proportion of patients with low PTH levels on the first postoperative day was significantly lower in the para-tracheal group (21/76, 27.6%) than in the conventional group (29/66, 43.9%; P < 0.05). There was no significant difference in serum Ca²⁺ levels between the groups on the first postoperative day, indicating that calcium supplement prophylaxis could prevent hypocalcemia. Follow-up results showed a significant reduction in transient hypoparathyroidism in the para-tracheal group (0/76) compared to the conventional group (4/66, P = 0.04, Fisher's exact test). The incidence of permanent hypoparathyroidism was also lower in the para-tracheal group (0/76) compared to the conventional group (2/66, P = 0.21, Fisher's exact test). Para-tracheal capsular dissection appears to offer superior protection of the parathyroid glands compared to conventional dissection, potentially reducing the risk of both transient and permanent postoperative hypoparathyroidism.

Introduction

Thyroid cancer represents the most prevalent endocrine malignancy, with an incidence that has been steadily increasing, marking it as the malignancy with the highest growth rate in recent years. Statistics from the National Cancer Database in the United States indicate that thyroid cancer now ranks among the top three cancers in terms of incidence among female patients¹. Given the favorable prognosis associated with differentiated thyroid cancer (DTC), contemporary guidelines advocate for total thyroidectomy as the optimal surgical intervention for DTC². However, complications can arise during total thyroidectomy due to the non-identification and preservation of the parathyroid glands, leading to postoperative hypocalcemia and permanent hypoparathyroidism. The occurrence rates of transient hypoparathyroidism can reach up to 30%, while permanent hypoparathyroidism is reported in 0.9% to 6.6% of cases³.

Research has uncovered that patients undergoing both total thyroidectomy and central-compartment neck dissection for malignant nodules exhibit lower intraoperative Parathyroid Hormone levels, signifying an elevated risk for hypoparathyroidism⁴. In light of these challenges, there has been a push towards developing and refining para-tracheal thyroidectomy techniques aimed at enhancing patient outcomes through the minimization of parathyroid gland injury. This surgical approach, initiating dissection at the thyroid isthmus and advancing towards the lateral lobes, offers a strategic advantage in preserving the integrity of the parathyroid glands over the traditional lateral approach to capsular resection. This strategic shift is predicated on the understanding that a closer dissection proximal to the trachea, combined with meticulous anatomical precision, significantly reduces the risk of inadvertent parathyroid gland damage^5,6.

The complex vasculature of the parathyroid glands, primarily supplied by the inferior thyroid artery with potential anastomoses from the superior thyroid artery, serves as a critical factor in parathyroid injury during surgery. This vascular arrangement is also a key intraoperative landmark for parathyroid gland localization, emphasizing the importance of meticulous surgical planning⁷. Employing magnification devices, such as loupes (2.5×), has been shown to significantly decrease the rate of accidental parathyroidectomy (3.8% vs. 7.8%) as well as postoperative biochemical (20.6% vs. 33.9%; p = 0.028) and clinical hypocalcemia (12.7% vs. 33%; p < 0.001). Additionally, gentle capsular dissection that carefully separates perithyroidal fatty tissues from the thyroid surface can preserve parathyroid blood supply, necessitating dissection immediately on the medial or anterior surface of the thyroid gland close to the parathyroids⁸. This surgical protocol, building upon these principles, focuses on preserving the main branches of the superior and inferior thyroid arteries to mitigate parathyroid gland injury and reduce the incidence of hypoparathyroidism.

Protocol

The study was conducted according to the tenets of the Declaration of Helsinki and received ethics approval from the Shanghai Ruijin Rehabilitation Hospital ethics committee.

1. Conventional capsular dissection thyroidectomy

1. As a preoperative preparation, have the patient fast and abstain from water.
2. Administer general anesthesia to the patient. Induce anesthesia with intravenous administration of sedatives, analgesics, and muscle relaxants. Once the patient enters a state of sedation, analgesia, and muscle relaxation, intubate the trachea using an oral laryngoscope and ventilate the patient, connecting them to the anesthesia machine to complete the induction of anesthesia.
3. Assist the patient in preparing for the position: elevate the neck, slightly recline the head, and fully expose the skin of the neck.
4. Make a surgical incision of two transverse fingers above the supraclavicular fossa, approximately 5-8 cm in length. Dissect subcutaneously to the deep level of the platysma muscle and in front of the anterior jugular veins.
5. Expose the thyroid isthmus by cutting along the white line of the neck and bluntly dissecting it to expose the notch of the thyroid cartilage and manubrium using hemostatic forceps.
6. Separate the anterior cervical muscle group first. Then, elevate the thyroid gland to expose its posterior aspect, identify the parathyroid glands, and the recurrent laryngeal nerve. During this process, due to lateral dissection of the thyroid, there may be vascular disruption and blood supply to the parathyroid glands.
7. Cut the suspensory ligament of the thyroid and the thyroid gland itself.

2. Para-tracheal capsular dissection thyroidectomy

1. As a preoperative preparation, have the patient fast and abstain from water.
2. Administer general anesthesia to the patient. Induce anesthesia with intravenous administration of sedatives, analgesics, and muscle relaxants. Once the patient enters a state of sedation, analgesia, and muscle relaxation, intubate the trachea using an oral laryngoscope and ventilate the patient, connecting them to the anesthesia machine to complete the induction of anesthesia.
3. Assist the patient in preparing for the position: elevate the neck, slightly recline the head, and fully expose the skin of the neck.
4. Make a surgical incision of two transverse fingers above the supraclavicular fossa, approximately 5-8 cm in length. Dissect subcutaneously to the deep level of the platysma muscle and in front of the anterior jugular veins.
5. Expose the thyroid isthmus by cutting along the white line of the neck and bluntly dissecting it to expose the notch of the thyroid cartilage and manubrium using hemostatic forceps.
6. Follow the steps below during the dissection.
   1. Start with a central incision at the thyroid isthmus, revealing a segment of the thyroid gland.
   2. Identify and cleave the isthmus using an ultrasonic scalpel, followed by dissection of the thyroid gland adjacent to the trachea.
   3. Expose the inferior pole of the thyroid gland, extending the dissection to the supraclavicular plane using tracheal and thyroid gland hooks.
   4. Pinpoint the recurrent laryngeal nerve and excise connective tissues and lymph nodes within the plane.
   5. Dissect along the recurrent laryngeal nerve up to its entry into the larynx, severing the suspensory ligament.
   6. Loosen the tracheal side of the thyroid capsule, elevate the thyroid gland, and introduce spacer fluid (sodium hyaluronate) externally to the capsule.
   7. Pull back the anterior segment of the thyroid capsule and carefully dissect the inferior parathyroid, preserving its vascular supply.
   8. Detach the thyroid from the capsule, proceeding towards the superior pole, ensuring its in situ placement to avoid harm to the dorsal parathyroid's vessels.
7. Administer oral calcium at a dosage of 1 g every 12 h, totaling 2 g/day, and a once-daily dose of intravenous calcium gluconate at 1 g/day on the first and second postoperative days.
   1. Increase the dose of oral calcium to 2.5 g every 12 h (5 g/day) and intravenous calcium gluconate to 2 g every 12 h (4 g/day) if parathyroid hormone (PTH) levels are below the standard reference range (1.6-6.9 pmol/L) on the first postoperative day, starting from the second to the third postoperative day.
8. Perform autotransplantation immediately if the parathyroid glands are inadvertently excised or invaded by cancer, transplanting retained glands into the sternocleidomastoid.
   NOTE: Carbon nanoparticle suspension injection (CNSI; Table of Materials) can be added to the materials for injection as a lymphatic tracer. After retracting the strap muscles to expose the ventral side of the thyroid gland, carbon nanoparticle suspension can be injected at multiple points on the upper, middle, and lower poles of the thyroid, with approximately 0.1 mL at each site using a 1 mL insulin syringe.

3. Outcomes measurement

1. Measure serum PTH levels using a PTH immunoassay kit and serum calcium (Ca²⁺) level using the methyl xylenol blue method.
2. Define hypoparathyroidism as serum PTH < 1.6 pmol/L and hypocalcemia as serum Ca²⁺ < 2.00 mmol/L. Calculate the reduction in PTH or Ca²⁺ level relative to preoperative levels, defining it as 0% if the postoperative value exceeds the preoperative one.

4. Follow-up care

1. Monitor patients with serum PTH and/or Ca²⁺ levels below the standard threshold on the first postoperative day during the initial phase from 2 weeks to 6 months post-operation.
2. Continue observation from 6 months to 24 months post-operation for patients with substandard serum PTH and/or Ca²⁺ levels during the first phase, allowing patients to schedule follow-up visits as needed.
3. Aim for the normalization of PTH and/or Ca²⁺ levels, scheduling a single follow-up session if achieved. If levels remain aberrant, continue monitoring until normalization.

5. Statistical analysis

1. Represent data with a normal distribution as mean ± standard deviation and evaluate inter-group variations using the Student's t-test.
2. Use the median and interquartile range (IQR) for data with a non-normal distribution and assess differences with the Mann-Whitney U test.
3. Denote categorical data in percentages and assess with Fisher's exact test. Consider a P-value of <0.05 as statistically significant.
4. Conduct all statistical computations using appropriate data analysis software.

Results

Patient characteristics
The study was conducted in accordance with the Declaration of Helsinki and received ethics approval from the Shanghai Ruijin Rehabilitation Hospital ethics committee. We included patients undergoing total bilateral thyroidectomy from July 1, 2016, to December 31, 2019, in a randomized trial, excluding those who underwent extended radical resection or had abnormal pre-surgery serum PTH or Ca²⁺ levels. All patients were diagnosed with papillary thyroid carcinoma.

Among 238 patients screened, 66 who underwent conventional capsular dissection and 76 who underwent para-tracheal capsular dissection were included in the final analysis (Figure 1). Both groups were comparable in age, sex distribution, and preoperative serum PTH and Ca²⁺ levels (Table 1). The median operation time was slightly shorter for the para-tracheal group (36 min, IQR 29-47 min) compared to the conventional group (43 min, IQR 36-56 min), though not statistically significant. No patients required blood transfusions in either group.

Outcomes among all patients
On postoperative day 1, the serum PTH level was significantly lower in the conventional group (2.00 pmol/L, IQR 0.93-2.95 pmol/L) than in the para-tracheal group (2.26 pmol/L, IQR 1.46-3.53 pmol/L; P = 0.04). The relative reduction in serum PTH from baseline to day 1 post-surgery was significantly smaller in the para-tracheal group (47% vs. 58%, P = 0.02), corresponding to a lower incidence of parahypothyroidism (27.6% vs. 43.9%; P = 0.04; Table 2). The serum Ca²⁺ level on postoperative day 1 was similar between groups (2.28 ± 0.17 mmol/L vs. 2.32 ± 0.15 mmol/L, P = 0.24), as were the relative reduction in serum Ca²⁺ from baseline (10% vs. 8%, P = 0.06) and the rate of hypocalcemia (3.0% vs. 1.3%; P = 0.48; Table 2).

Outcomes of patients who underwent parathyroid autologous transplantation
The number of patients who underwent autologous parathyroid transplantation was similar in both groups: four in the conventional group and seven in the para-tracheal group (P = 0.54, Fisher's exact test). Patients who underwent transplantation had significantly lower serum PTH levels on postoperative day 1 (median 1.14 pmol/L, IQR 0.68-1.61 pmol/L) compared to those who did not (2.30 pmol/L, IQR 1.23-3.29 pmol/L; P = 0.01). However, serum Ca²⁺ levels were comparable between patients who underwent transplantation (2.28 ± 0.19 mmol/L) and those who did not (2.31 mmol/L, IQR 2.21-2.43 mmol/L; P = 0.51; Table 3).

Long-term follow-up
On postoperative day 1, 31 of 66 patients in the conventional group and 22 of 76 patients in the para-tracheal group were assigned to the first phase of follow-up due to a drop in serum PTH and/or Ca²⁺ levels below the lower limit of the normal range. By the end of the first follow-up phase, four patients in the conventional group continued to have low PTH levels, while none of the 12 patients in the para-tracheal group did. Two patients in the conventional group with low Ca²⁺ levels returned to the normal range, while one patient in the para-tracheal group did not follow-up. At 6 months' follow-up, transient hypoparathyroidism was significantly lower in the para-tracheal group compared to the conventional group (0/76 vs. 4/66, P = 0.04, Fisher's exact test). In the second follow-up phase, the four patients in the conventional group with low PTH levels at the end of phase 1 continued to be followed. None were lost to follow-up, and two continued to have low PTH levels at 24 months' follow-up. Therefore, permanent hypoparathyroidism was also lower in the para-tracheal group compared to the conventional group (0/76 vs. 2/66, P = 0.21, Fisher's exact test).

Figure 1: Study design. A total of 238 patients were screened, and the final analysis included 66 patients who underwent conventional capsular dissection and 76 patients who underwent para-tracheal capsular dissection. Please click here to view a larger version of this figure.

Characteristic	Transtracheal group (n =76)	Conventional group (n = 66)	P
Age, years	47.50 (38.00–56.00)	46.50 (36.00–56.75)	0.54
Male	18 (24)	10 (15)	0.21
Parathyroid Hormone, pmol/L	4.72 ± 1.19	4.93 ± 1.01	0.29
Ca2+, mmol/L	2.52 ± 0.10	2.54 ± 0.10	0.32
Effectiveness
Tumors with a negative surgical margin	76 (100)	66 (100)	1
Lymph node dissection thoroughly	76 (100)	66 (100)	1
The positive rate of lymph node	28 (36.8)	27 (40.9)	0.62
Security
Fatal hemorrhage	0	0	1
Recurrent laryngeal nerve injury	1 (1.3)	0 (0.0)	1
Permanent hypoparathyroidism	0 (0.0)	2 (3.0)	0.214

Table 1: Clinicodemographic characteristics of patients at baseline. Unless otherwise noted, values are n (%), mean ± SD, or median (interquartile range).

Parameter	Transtracheal group (n = 76)	Conventional group (n = 66)	P
PTH, pmol/L	2.26 (1.46–3.53)	2.00 (0.93–2.95)	0.04
Decrease in PTH below baseline	47% (23%–71%)	58% (40%–82%)	0.02
Patients with serum PTH below normal range	21 (27.6)	29 (43.9)	0.04
Ca2+, mmol/L	2.32 ± 0.15	2.28 ± 0.17	0.24
Decrease in Ca2+ below baseline	8% ± 5%	10% ± 6%	0.06
Patients with serum Ca2+ below normal range	1 (1.3)	2 (3.0)	0.48

Table 2: Comparison of serum parathyroid hormone (PTH) and Ca²⁺ between groups at postoperative day 1. Unless otherwise noted, values are n (%), mean ± SD, or median (interquartile range).

Characteristic	Transplantation (n = 11)	No transplantation (n = 131)	P
Preoperative PTH, pmol/L	4.20 ± 1.34	4.87 ± 1.08	0.06
Postoperative PTH, pmol/L	1.14 (0.68–1.61)	2.30 (1.23–3.29)	0.01
Decrease in PTH from baseline (%)	69 (59–84)	52 (35–71)	0.02
Preoperative Ca2+, mmol/L	2.53 ± 0.14	2.53 ± 0.10	0.97
Postoperative Ca2+, mmol/L	2.28 ± 0.19	2.31 (2.21–2.43)	0.51
Decrease in Ca2+ from baseline	10 ± 7%	8% (5–13%)	0.64

Table 3: Comparison of pre- and postoperative serum parathyroid hormone (PTH) and Ca²⁺ between patients who underwent parathyroid autologous transplantation or not. Unless otherwise noted, values are n (%), mean ± SD or median (interquartile range).

Discussion

Thyroid cancer is a prevalent malignancy of the head and neck⁹, predominantly comprising differentiated cancers such as papillary and follicular thyroid carcinoma¹⁰. Surgery, specifically total thyroidectomy, is the primary treatment for differentiated thyroid cancer and may offer better recurrence-free survival compared to lobectomy¹¹. However, total thyroidectomy poses a significant risk of transient or permanent hypoparathyroidism. Therefore, there is an urgent need to refine the thyroidectomy procedure to minimize parathyroid injury, especially with the rising incidence of thyroid cancer. The findings of this study indicate that para-tracheal capsular dissection may provide superior protection to the parathyroid gland compared to conventional dissection, potentially reducing the risk of postoperative hypoparathyroidism.

Various strategies have been employed to safeguard the parathyroid gland during thyroidectomy, including the injection of carbon nanoparticles as lymphatic tracers^12,13, indocyanine green^13,14, in situ preservation of the parathyroid¹⁵, and autotransplantation¹⁶. Para-tracheal capsular dissection^17,18is an emerging technique that involves dissection along the trachea to preferentially expose the recurrent laryngeal nerve throughout the procedure. This approach avoids the conventional lateral-to-medial dissection of thyroid tissue, thereby preserving the blood supply to the dorsal parathyroid gland.

This study revealed that para-tracheal capsular dissection was associated with a significantly smaller reduction in serum PTH and Ca²⁺ levels 1 day after surgery. These results are consistent with two other studies involving Chinese patients who underwent either capsular or conventional dissection¹⁸. However, this study observed smaller reductions in serum PTH and Ca²⁺ levels compared to a previous study, which may be attributed to the use of lymphatic tracers in both groups, unlike the other study. Serum Ca²⁺ levels 1 day after surgery did not differ significantly between the two groups, possibly because all patients received calcium supplements to prevent hypocalcemia, as per standard practice at our hospital.

None of the patients experienced complications during hospitalization and none of those who followed up reported complications for 24 months. Thus, the results suggest that capsular dissection during thyroidectomy can protect the parathyroid gland and reduce the rate of postoperative complications, such as hypoparathyroidism.

The surgical approach described here can effectively protect the thyroid blood vessels. In patients with thyroid cancer, a central lymph node dissection is required on the affected side. We first perform a central lymph node dissection, followed by a thyroidectomy. We start by exposing the lower segment of the recurrent laryngeal nerve, and during the upward dissection process, we avoid any traction on the recurrent laryngeal nerve, operating closely along the true capsule of the thyroid. This approach allows for better protection of the tertiary vessels and maximizes the chances of preserving the inferior parathyroid gland. After severing the suspensory ligament, the superior parathyroid gland is exposed under direct vision, allowing us to better protect the blood supply to the parathyroid glands while ensuring the superior parathyroid gland remains in situ. We believe that dissection from the lateral approach may elevate the superior parathyroid gland, potentially damaging its blood supply and creating blind spots in the surgical field, increasing the risk of inadvertent injury to the superior parathyroid gland.

Another strength of the study described here is that we did not exclude patients with a history of neck surgery or those who received parathyroid autologous transplantation. In fact, we found that 4 of 66 patients in the conventional group and 7 of 76 patients in the para-tracheal group underwent autologous parathyroid transplantation (P = 0.54, Fisher's exact test). Unfortunately, due to the small sample size, we could not analyze the subgroup of patients with a history of neck surgery, which may limit the generalizability of the results. Capsular dissection may be particularly beneficial for these patients as their parathyroid gland requires more protection than surgery-naive patients.

However, the conclusions of this study should be interpreted with caution due to several limitations. Firstly, we were unable to analyze the subgroup of patients with a history of neck surgery. Secondly, we did not compare the dissection techniques in terms of the function of the recurrent laryngeal nerve or postoperative symptoms. Lastly, we lost a substantial proportion of patients to follow-up because they resided far from the hospital and sought postoperative care from local doctors. Future research is needed to support our findings by assessing the long-term outcomes of para-tracheal capsular dissection.

Despite these limitations, this study suggests that para-tracheal capsular dissection combined with the injection of CNSI in thyroid surgery can lead to higher postoperative serum PTH levels compared with conventional dissection. This may, therefore, be associated with a lower risk of transient or permanent postoperative hypoparathyroidism.

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Calcium E-HA	Wako Pure Chemical Industries	https://labchem-wako.fujifilm.com/asia/product/detail/W01W0103-1277.html
Carbon nanoparticle suspension injection (CNSI)	Chongqing Lesmei Pharmaceutical Co., Ltd.	https://cqlummy.com/about/gsjj/
COBAS Elecsys PTH immunoassay	Roche Diagnostics	https://diagnostics.roche.com/global/en/products/lab/elecsys-pth-cps-000506.html
Intravenous calcium gluconate	Ilsung Pharmaceutical	https://www.ilsungis.com/main/
NIM 3.0 Nerve Monitors	Medtronic USA	https://global.medtronic.com/xg-en/healthcare-professionals/products/ear-nose-throat/nerve-monitoring/nim-nerve-monitoring-systems.html	Nerve tracheal tube with recurrent laryngeal nerve monitoring function
Oral calcium	Pfizer	https://www.pfizer.com/
SPSS	IBM	Version 20.0
Standard thyroid surgery kit	Shanghai Punan Hospital	N/A