Abstract
Background:
The reported complication rates of neck dissection are not specific patients with papillary thyroid cancer` with metastatic lymph nodes. This study aimed to describe the complication profile of neck dissection and the effect of concurrent lateral neck dissection on complication rates.
Methods:
This single-center prospective cohort study analyzed the data of 52 patients who underwent a total thyroidectomy and therapeutic lymph node dissection between March 2021 and March 2023. The clinicopathologic characteristics of patients and surgical complications were analyzed.
Results:
The transient recurrent laryngeal nerve palsy (RLNP) and hypoparathyroidism rates were 55.8% and 51.9%, respectively. The chyle leakage rate was 5.8%. Tracheostomy was performed on 1 patient (1.9%). Patients with transient RLNP had more retrieved lymph nodes than patients without RLNP (5.5 ± 2.7 vs 3.9 ± 1.5, P = .013). The rates of transient RLNP and hypoparathyroidism were higher in the total thyroidectomy with central and lateral neck dissection group than the total thyroidectomy with central neck dissection group (62.2% vs 14.3%, P = .035 and 57.8% vs 14.3%, P = .046). Multivariate analysis showed that the increased number of retrieved lymph nodes in the central compartment and the addition of lateral neck dissection were independent risk factors for transient RLNP, with odds ratio (OR) (95% confidence interval) of 0.72 (0.53-0.98) and 9.42 (1.02-87.34).
Conclusion:
The rates of transient RLNP and hypoparathyroidism after lymph node dissection in patients with papillary thyroid cancer with metastatic lymph nodes were high, and a greater number of retrieved lymph nodes in the central neck and the addition of lateral neck dissection were predictors for transient RLNP. These data may be used to discuss preoperatively with patients and make surgeons more cautious and meticulous during surgery to minimize complications.
Introduction
Papillary thyroid carcinoma (PTC) is the most common thyroid cancer, accounting for more than 80% of all thyroid malignancies. In patients with PTC, nodal metastases have been reported in 30% to 80% of cases.1-4 Despite this high incidence, the overall prognosis is still excellent. In a study conducted on 5897 patients with PTC, of whom only 68 had distant metastases, the results showed that up to 97% of patients survived for 10 years or more. 5 However, an analysis of more than 9900 patients in the Surveillance, Epidemiology, and End Results (SEER) database found a significant difference in survival at 14 years for those with and without lymph node metastases (79% vs 82%, respectively). 6 Therefore, the early detection of metastatic cervical lymph nodes plays an essential role in deciding on the optimal surgical treatment plan for most patients, allowing careful postoperative screening and adjuvant therapies and minimizing the chance of disease recurrence. 7 A therapeutic lymph node dissection of involved compartments is performed for patients with biopsy-proven or clinically apparent cervical lymph node metastases. 8 The central neck (level VI) and lateral neck (levels II, III, and IV) are at the greater risk for metastasis in patients with PTC.9-12 Several articles reported the complication rates of neck dissection. But the groups of patients who underwent cervical lymph node dissection in those studies were mainly based on the macroscopic characteristics of the lymph nodes before or during surgery or if malignancy was suspected based on preoperative imaging examinations, so there were overtreatment cases. The rates of complications described in these studies are not completely representative of the group of patients with actual lymph node metastases. This study aimed to describe the complication profile of neck dissection and the effect of concurrent lateral neck dissection on complication rates.
Materials and Methods
Patient and study design
This prospective cohort study was conducted to assess the complications of neck dissection and the effect of concurrent lateral lymph node dissection (LLND) on complication rates. Between March 2021 and March 2023, consecutive PTC patients with preoperative evidence of lymph node metastases (cN1) at the Head and Neck Surgery Department, Can Tho Oncology Hospital were invited to participate in this study. All enrolled patients met strict eligibility criteria. The inclusion criteria were as follows: (1) preoperative cytology or histopathology of the thyroid nodule and cervical lymph nodes confirms papillary thyroid cancer with lymph node metastasis; (2) patients underwent a total thyroidectomy and therapeutic lymph node dissection; and (3) the final pathological results of the thyroid nodule and cervical lymph nodes were PTC. The exclusion criteria were as follows: (1) a thyroid or neck surgery history for other diseases or radiation exposure; (2) distant metastases; and (3) patients with inadequate follow-up data. The following information was recorded: age, sex, tumor size, extrathyroidal extension, number of retrieved lymph nodes, number of positive retrieved lymph nodes, size of positive nodes, extranodal extension, surgery duration, postoperative length of stay, calcium levels, and surgical complications. We classified our patients using the eighth edition of the American Joint Committee on Cancer (AJCC) and the tumor, node, metastasis (TNM) staging system. 13
Surgical procedures
Surgery was performed by 2 experienced surgeons at Can Tho City Oncology Hospital. Because the patients in our study all had lymph node metastasis, all of them underwent total thyroidectomy (TT). The parathyroid glands and recurrent laryngeal nerve were identified and preserved during surgery. Our institution does not perform prophylactic cervical neck dissection, and cases with evidence of lymph node metastasis will be treated with therapeutic lymphadenectomy. Depending on the level of lymph nodes involved, 1 of the following 2 techniques was used: (1) central lymph node dissection (CLND), including prelaryngeal, pretracheal, and paratracheal dissection for patients with evidence of central compartment involvements and (2) CLND plus LLND including levels II, III, and IV with preservation of the sternocleidomastoid muscle, internal jugular vein, and spinal accessory nerve for patients with evidence of lateral lymph node involvement. 14
Surgical complications
Postoperative hematoma was suggested when the patient presented with symptoms such as swelling in the neck, increasing pain, and developing respiratory distress. A wound infection was defined as the presence of pus or an abscess on the surgical site. A tracheostomy was indicated when the patient was suspected of having bilateral vocal cord palsy, and the typical symptoms included severe dyspnea or inspiratory stridor. A chyle leakage was diagnosed when the patient increased the volume of milky-colored fluid through the drains. Transient hypoparathyroidism was defined as a patient presenting with hypocalcemia symptoms or signs such as tingling or numbness in the hands and/or feet, Chvostek’s sign, and/or Trousseau’s sign. Permanent hypoparathyroidism was defined as a patient who still had tingling or numbness in the hands and/or feet and required oral calcium supplements to control these symptoms for more than 6 months after surgery. Transient recurrent laryngeal nerve palsy (RLNP) was defined as postoperative hoarseness evaluated based on the surgeon’s judgment and the patient’s complaints in the postoperative period. Permanent RLNP was defined as the patient’s hoarseness lasting more than 6 months after initial surgery. Complications were evaluated at 1, 3, and 6 months after surgery.
Statistical analysis
Statistical analysis was performed using IBM SPSS (Statistical Package for the Social Sciences) Statistics version 29.0 (IBM Corp). Category variables are expressed as frequencies and percentages and analyzed using the chi-square or Fisher exact tests. Continuous data are expressed as mean ± standard deviation. Multivariate logistic regression analysis was performed to identify risk factors for complications. Statistical significance was defined as P < .05.
Results
There were 59 patients with PTC fulfilling the inclusion criteria; we removed 1 patient with prior lumpectomy of the thyroid in other hospital, 3 patients with distant, and 4 patients with inadequate follow-up data. Finally, the study population included 52 patients with PTC. The clinicopathologic characteristics of the 52 patients are summarized in Table 1. The mean age was 40 years, with more women than men (71.1% vs 28.9%, respectively). In all, 86.5% of patients underwent TT with CLND and LLND, and the mean operating time in this group (129.9 min) was longer by about 60 minutes when compared with the TT with CLND group (71.4 min). The mean number of retrieved central lymph nodes was 4.8, and the mean number of retrieved lateral lymph nodes was 20.7. The mean number of positive retrieved central and lateral lymph nodes was 2.9 and 6.8, respectively. Twenty-eight patients exhibited extrathyroidal extension, and 34 patients exhibited extranodal extension. Metastatic lymph nodes >3 cm were present in 10 patients (19.2%). Thirty-four patients (65.4%) had more than 5 metastatic lymph nodes on the final pathology report. Based on AJCC staging, stages I, II, and III were 86.5%, 7.7%, and 5.8%, respectively.
Clinicopathologic characteristics of patients who underwent thyroidectomy and cervical lymph node dissection.
Abbreviations: AJCC, American Joint Committee on Cancer; CLND, central lymph node dissection; LLND, lateral lymph node dissection; TNM, tumor, node, metastasis; TT, total thyroidectomy.
Values are presented as mean ± standard deviation, or number (%).
The overall postoperative length of stay was less than 6 days in 33 patients (63.5%), 6 to 10 days in 14 patients (26.9%), and more than 10 days in 5 patients (9.6%). The medium duration until discharge was 5 days (2-32 days). The patients with over a month of hospitalization in our study had severe and prolonged chyle leakage.
Out of 52 patients underwent TT with neck dissection, 29 (55.8%) experienced transient RLNP (hoarseness), 26 of those resolved within 6 months, and only 3 patients (5.8%) with hoarseness lasting more than 6 months. In our study, 27 patients (51.9%) with symptoms of hypocalcemia postoperatively got serum calcium levels measured. The mean serum calcium levels were 1.8 ± 0.2, which was below the normal range of our laboratory (2.1-2.6 mmol/L). These patients were treated with calcium and vitamin D supplements. Twenty-three of 27 patients resolved within 6 months after surgery, and only 4 patients (7.7%) with clinical symptoms of hypocalcemia lasting more than 6 months required medications. Three cases of chyle leakage were recorded, all of which occurred in patients who underwent LLND on the left side of the neck. These failed to respond to conservative management, and surgical explorations to ligate the lymphatic duct were performed. Only 1 patient with dyspnea required an emergency tracheostomy (due to bilateral vocal cord palsy). No cases of hematomas or wound infections were observed (Table 2).
Postoperative complication rates of patients.
RLNP, recurrent laryngeal nerve palsy.
Values are presented as numbers (%).
When examining the central compartment, patients with transient RLNP had more retrieved lymph nodes than patients without RLNP (5.5 ± 2.7 vs 3.9 ± 1.5, P = .013). The sizes of metastatic lymph nodes in the central neck and tumors were larger among patients with transient hypoparathyroidism than those without this complication (1.7 ± 1.1 vs 1.2 ± 0.7, P = .033 and 2.7 ± 1.4 vs 2.0 ± 1.1, P = .047, respectively). In addition, the number of metastatic lymph nodes in the central compartment and extrathyroidal extension status were similar among patients with or without transient RNLP or hypoparathyroidism (P > .05). Furthermore, patients who underwent TT + CLND + LLND were more likely to experience transient RLNP and hypoparathyroidism compared with the TT + CLND group (62.2% vs 14.3%, P = .035 and 57.8% vs 14.3%, P = .046, respectively; Table 3).
Clinicopathologic characteristics for risk of transient recurrent laryngeal nerve palsy and hypoparathyroidism by univariate analysis.
Abbreviations: CLND, central lymph node dissection; LLND, lateral lymph node dissection; TT, total thyroidectomy; RLNP, recurrent laryngeal nerve palsy.
Values are presented as mean ± standard deviation, or number (%).
A 2-tailed P < .05 was indicated in bold values. And it was highlighted that the difference was statistically significant.
Variables with statistical differences were included in a multivariate model to identify risk factors for transient RLNP and hypoparathyroidism. We found that an increased number of retrieved lymph nodes in the central neck and the addition of LLND were independently associated with a risk of transient RLNP, with an odds ratio (OR) (95% confidence interval) of 0.72 (0.53-0.98) and 9.42 (1.02-87.34). No clear predictors for transient hypoparathyroidism were found (Table 4).
Multivariate analysis of the risk factors for transient recurrent laryngeal nerve palsy and hypoparathyroidism.
Abbreviations: CI, confidence interval; CLND, central lymph node dissection; LLND, lateral lymph node dissection; OR, odds ratio; TT, total thyroidectomy.
A 2-tailed P < .05 was indicated in bold values. And it was highlighted that the difference was statistically significant.
Discussion
This study is a continuation of our previous work, which described the clinical and imaging characteristics of patients with PTC with metastatic lymph nodes. 7 The current research reports the surgical outcomes of those patients, and we found that the rates of transient RLNP and hypoparathyroidism were higher than in other studies, and the rate of these complications was also higher in patients with CLND and LLND than in patients with only CLND.
Rates of RLNP in the literature vary widely, with transient rates ranging from 2.6% to 12.9% and permanent rates ranging from 0% to 4.0%.15-19 We find a higher rate in this study, with 55.8% for transient RLNP. Prior studies show transient hypoparathyroidism rates, which vary widely from 15.4% to 30.5%, and permanent rates ranging from 2.6% to 8.8%.15-19 We show that transient hypoparathyroidism is observed in 51.9% of patients, which is also higher than prior studies. Chyle leakage is also a common complication of neck dissection, and this complication rate ranges from 1.2% to 2.6% in the literature.17,20 Because the main thoracic duct terminates on the left side of the neck in 94.6% of cases, this complication is usually recorded in patients who underwent neck dissection on the left side. 21 In this study, there were 3 patients with chyle leakage after surgery, accounting for 5.8%, and all occurred on the left side of the neck. This result is similar to those previously published. Rates of tracheostomy reported in the literature are low, ranging from 0.01% to 1.2%.17,22 This study has a similar rate, with 1.9% for tracheostomy.
Postoperative hypoparathyroidism or hypocalcemia is caused mainly by a reduction in the functional parathyroid parenchyma owing to a combination of factors, including fragmentation, thermal injury, inadvertent parathyroidectomy, parathyroid gland autotransplantation, and gland devascularization. 23 The injury to the recurrent laryngeal nerve (RLN) in surgery is probably because surgeons failed to expose the RLN, but this is not always easy, especially in some cases such as the RLN being infiltrated by a thyroid tumor, intraoperative hemorrhage, the occurrence of a nonrecurrent laryngeal nerve, and other anatomical and pathological variations. Even though the RLNs were identified and clearly observed during surgery, some patients still had hoarseness in the postoperative period. This can be explained by the fact that the RLN is very sensitive and vulnerable to various factors during surgery, such as excessive traction/stretching, contusion, clamping, ligation, suturing, burning, and cutting. 24
To our knowledge, this is the first prospective study focusing on the complications of neck dissection in patients with PTC with metastatic lymph nodes. The few series of neck dissections that exist were retrospective ones, and the reporting of surgical complications is secondary to the reporting of oncologic outcomes. Moreover, in those studies, the indications for LLND varied; there were studies where the indications were based on preoperative imaging characteristics suggesting metastatic lateral cervical lymph nodes. Others are based on the macroscopic characteristics of the lymph nodes before or during surgery. Therefore, there were cases where the final postoperative pathology results of the lateral cervical compartment showed no positive lymph nodes. Chung et al studied 245 patients with PTC, including 39 who underwent LLND, and its indication was based on preoperative imaging studies that were suspicious for malignancy. The lateral lymph node metastasis incidence was 12 (30.8%) of 39. 16 Another study also performed LLND for patients with preoperatively detected lateral lymph node metastasis by ultrasound, and the rate of positive lateral lymph nodes on the final pathology report was 84.4% (103/122 patients). 19 Bardet et al studied 545 patients with PTC ⩾1.0 cm who underwent TT, and the proportion of patients with lymph node metastasis among patients with bilateral lymph node dissection of the central and lateral compartments was 56% (102/181 patients). In this study, lymph node dissection was always performed in the context of macroscopic lymph node metastases (visible or palpable before or during surgery or suspected on preoperative ultrasound). In addition, for patients with no evidence of lymph node involvement before or during surgery, LND was also performed. 15 Roh et al studied 155 patients with PTC, of whom 26 patients with palpable lateral nodes underwent TT + CLND + LLND. The number of patients with lymph node metastasis in this group was 21 (80.8%). 18 The cervical lymph nodes in the negative cases in the above studies can be either inflamed or tuberculous lymph nodes, which may make the surgery easier because these nodes tend to have less aggressive characteristics such as small lymph node size and volume, no extranodal extension and do not invade adjacent structures compared with the metastatic nodes. In contrast, in our study, all patients had preoperative fine-needle aspiration of the cervical lymph node confirmed as malignant or suspicious for malignant and confirmed again on the final pathology results. Therefore, 100% of patients had lymph node involvement. The rate of positive lymph nodes >3 cm in size was 19.2%, and the rates of >5 lymph nodes involved and extranodal extension were identical at 65.4%. These features made LLND procedures more difficult because the surgeons have to deal with the larger size and volume of the metastatic lymph nodes and invasion of surrounding structures (this study recorded 4 cases of internal jugular vein invasion and 1 case of the common carotid artery, internal jugular vein, and vagus nerve). As a result, the operating time was longer, which also meant the RLN, and parathyroid glands had a longer exposure to the mentioned risk factors. This explains why our study’s rate of transient RLNP and hypoparathyroidism was higher than in prior studies.
The effect of lateral neck dissection on complication rates has also been described, with widely varying results. Complication rates were higher in 2 of 3 studies when compared with TT with CLND. Roh et al found that LLND increased the rate of transient hypocalcemia compared with central cervical lymph node dissection alone (46.2%, 12/26 vs 23.2%, 13/56, P = .036). There was no difference in the rate of transient RLNP between different groups (P = .394). 18 In the study of Bardet et al, 15 the rate of transient postoperative hypocalcemia after surgery was higher in the TT + CLND + LLND group than in other groups (29/181, 16%, P < .001). However, there was no difference in the rate of transient RLNP between different groups (P = .17). The remaining study by Chung et al showed no difference in the rate of transient hypocalcemia in the CLND + LLND group compared with the CLND group (15.4%, 6/39 vs 14.6%, 30/206, P = .989). There was no significant difference in the incidence of transient RLNP between CLND and CLND + LLND groups (1.9%, 4/206 vs 2.6%, 1/39, P = .801). 16 This study found that patients with transient RLNP had more retrieved lymph nodes in the central compartment than patients without RLNP (5.5 ± 2.7 vs 3.9 ± 1.5, P = .013). In addition, patients with transient hypoparathyroidism had larger metastatic lymph nodes in the central neck and tumors than those without this complication (1.7 ± 1.1 vs 1.2 ± 0.7, P = .033 and 2.7 ± 1.4 vs 2.0 ± 1.1, P = .047, respectively). We further found that patients who underwent TT + CLND + LLND were more likely to experience transient RLNP and hypoparathyroidism (P = .035 and P = .046, respectively). The mechanism of the higher rate of transient hypoparathyroidism and RLNP with the addition of LLND could be disruption of the inferior thyroid arteries at their thyrocervical trunk origin and prolonged exposure to thermal energy of surgical instruments, traction, and compression (RLN is very sensitive and vulnerable to these factors). Multivariate analysis showed that the increased number of retrieved lymph nodes in the central compartment and the addition of LLND were risk factors for transient RLNP. However, no statistically significant predictors were found for transient hypoparathyroidism. This suggests that larger metastatic lymph nodes or tumors, a greater number of retrieved lymph nodes, and extending nodal dissection to cover the central neck to the lateral cervical compartment required more time to perform which could enhance vascular compromise of the parathyroid glands and injured the recurrent laryngeal nerve.
Indications for prophylactic CLND (pCLND) are divided into 2 groups. Patients with clinical evidence or biopsy-proven central compartment lymph node metastases are treated with therapeutic central neck dissection. However, in clinically negative lymph node (cN0) patients with PTC, the pCLND is still debated. The 2015 American Thyroid Association (ATA) and the European Society of Endocrine Surgeons recommended that pCLND be considered in patients with advanced primary tumors (T3 or T4) and known involved lateral lymph nodes.25,26 Prophylactic dissection has been suggested to reduce local-regional recurrence compared with no pCLND but is accompanied by numerous adverse effects such as temporary and permanent hypoparathyroidism and temporary RLNP, as shown by 2 recent meta-analyses.27,28 Shahriarirad et al 29 reported the rate of central lymph node involvement is high, and prophylactic bilateral CLND should be performed to prevent patients with PTC from undergoing reoperation or developing metastases. However, some randomized trials showed that prophylactic dissection has not improved patient outcomes. Sippel et al studied 60 patients with cN0 PTC who were randomly assigned to a TT or a TT + pCLND. The study focused on the short-term predictors of disease recurrence, including unstimulated thyroglobulin (Tg) and stimulated Tg (sTg) levels, and at 1 year, the rates of Tg < 0.2 (88.9% vs 90.0%, P = 1.00) and sTg < 1 (93.8% vs 92.3%, P = 1.00) remained similar between groups. 30 In a randomized trial of 181 patients with PTC, Viola et al 31 found that the percentage of persistent disease, either biochemical or structural, was similar between the TT group and the TT + pCLND group (8.0% vs 7.5%, respectively, P = .9) after 5 years of follow-up. Recently, Ahn et al 32 found no significant difference in the number of patients with loco-regional recurrence between TT (TTx) group and TTx + pCLND group (P = .945). Moreover, Yuan et al 33 showed that the rates of lymph node recurrence in the TT alone and TT with pCLND groups were similar (7.3% vs 4.6%, P = .247), but there were significantly higher rates of overall morbidity (6.6% vs 19.1%, P < .001) when pCLND was performed.
Usually, the stepwise lymphatic spread in PTC occurs first in the central compartment, followed by the lateral compartment, and the reported rate of skip metastases in cN1b patients with no pathological central nodal disease is low, ranging between 8.7% and 14.9% in the literature. 34 A pCLND is recommended in patients with clinically involved lateral nodal disease. However, multiple studies showed no advantage in preventing loco-regional recurrence for cN1b patients with PTC treated with a pCLND, and pCLND may increase complications.35,36 The findings of these studies and the high rates of complications when performing therapeutic CLND in our study, taken together, undermine the paradigm of pCLND in cN0 and cN1b patients without clinical evidence of central neck metastases.
This study has several limitations. First, the number of patients in the TT + CLND group was small. Second, the criteria for evaluating permanent RLNP and hypoparathyroidism were based on clinical symptoms only. A randomized control trial that uses another surgical approach in patients with PTC with metastatic lymph nodes is needed to analyze whether that approach has lower complication rates than open surgery.
However, our study has several strengths. All patients were treated at a single center, the only oncology center in the Mekong Delta region, where about 18% of the Vietnamese population resides, with strict inclusion and exclusion criteria to ensure that all of them had metastatic lymph nodes. Therefore, the data analyzed were clear, accurate, and specific to this population. It also showed that postoperative complications such as transient RLNP hypoparathyroidism were higher in patients with LLND.
Conclusions
In conclusion, the rates of transient RLNP and hypoparathyroidism after lymph node dissection in patients with PTC with metastatic lymph nodes were high, and a greater number of retrieved lymph nodes in the central neck and the addition of lateral neck dissection were predictors for transient RLNP. These data may be used to discuss preoperatively with patients and make surgeons more cautious and meticulous during surgery to minimize complications.
Footnotes
Acknowledgements
The authors would like to express our sincere gratitude to the Rectorate Board of Can Tho University of Medicine and Pharmacy for facilitating the conduct of this study.
Author Contributions
M-CP, H-PN, and TN designed the study. M-CP collected the data, calculated the statistics, and wrote the article. H-PN and TN supplied critical commentary. All authors reviewed and approved the final version of the article.
Declaration of conflicting interests:
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding:
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Availability of Data and Materials
The data supporting the findings of this study are accessible from the corresponding authors on reasonable request.
Consent for Publication
None.
Ethics Approval and Consent to Participate
The study was approved by the Institutional Review Board (IRB) of the Ethics Committee of Biomedical Research of Can Tho University of Medicine and Pharmacy, Can Tho, Viet Nam (grant no. 64/PCT-HĐĐĐ). Written informed consent was obtained from the patient for anonymized patient information to be published in this article.
