Abstract
The role of prophylactic central compartment neck dissection (CCND) in total thyroidectomy (TT) is controversial in patients without clinically evident lymph nodes metastasis (cN0) because of association with transient and permanent hypoparathyroidism (HPT) as well as transient and permanent recurrent laryngeal nerve (RLN) injury. Instead of bilateral central neck dissection (bCCND), ipsilateral central compartment neck dissection (iCCND) has recently been proposed as a safer, alternative treatment for selected patients. The aim of this study is to characterize the morbidity that CCND (ipsilateral and bilateral) adds to TT. We enrolled 453 patients: Group A (316 patients) underwent TT alone, Group B (86 patients) underwent TT + iCCND, Group C (51 patients) underwent TT + bCCND. We compared the rates of RLN injury and HPT in three groups and data analysis showed that iCCND was associated with increased rate of transient HPT but not permanent HPT and bCCND was associated with increased rate of transient and permanent HPT, when compared with TT alone. Further studies are needed to evaluate the clear advantages of CCND (both ipsilateral and bilateral), but this should be considered in the context of an higher risk of surgical complications (especially transient and permanent hypoparathyroidism), in comparison with TT alone.
Keywords: Thyroidectomy, Central compartment neck dissection, Ipsilateral, Bilateral, Hypoparathyroidism, Recurrent laryngeal nerve injury, Complications
Introduction
Differentiated thyroid carcinoma (DTC) (particularly papillary) represents the most frequent thyroid malignancy, accounting for more than 90% of all thyroid cancers [1].
DTC has generally an indolent clinical course, an excellent prognosis and is associated with a low mortality rate. Well differentiated (papillary and follicular) thyroid cancer had an expected 20-year survival of 90% or greater, exclusive of other causes of mortality [2].
Total thyroidectomy (TT) is the gold standard procedure for DTC exceeding 10 mm in diameter [3, 4].
Despite this excellent prognosis, cervical lymph node metastases are frequent, being observed in 20–50% of patients [5].
Micrometastases are even more frequent, occurring in up to 90% of patients, and the central compartment (level VI) is the most frequently involved locoregional site [6].
Neck ultrasonography (US), fine-needle aspiration cytology (FNAC) and fine-needle aspiration thyroglobulin (Tg) measurements are reliable tools for evaluation of lateral compartment of the neck before thyroid surgery. This procedures can discover non palpable lymph node metastases [7], and help to plan surgical lateral dissections with total thyroidectomy. Nevertheless, it doesn’t currently exist a totally reliable tool to preoperatively detect lymph nodes metastases in the central compartment of the neck [8–10].
The risk factors for lymph node metastasis include patient age, larger size of the primary tumor, multifocality, and extrathyroidal extension [11].
Tumor histotype certainly influences the survival and recurrence rate, representing the most significant prognostic factor. According to ESMO (European Society of Medical Oncology), BTA (British Thyroid Association), ATA (American Thyroid Association), NCCN (National Comprehensive Cancer Network), central neck dissection should be performed in case of clinical or ultrasonographic evidence of lymph nodes metastases in central compartment [12–15].
while the role of prophylactic central neck dissection remains controversial in patients without clinically evident lymph nodes metastasis.
Some authors [16–23] recommend routine CCND in order to prevent future recurrences, citing the high risk of positive lymph nodes, the accuracy of staging, reduced postoperative Thyroglobulin (Tg) levels, the possibility to have pathological evidence for the adjuvant radioiodine (RAI) treatment and a lower morbidity rate associated with initial thyroid surgery (compared with reoperation), whereas others [5, 24–28].
affirm that this procedure increases the rate of complications, without any demonstrable benefits in terms of long-term survival rate.
The complications related with CCND are similar to and may be additive to TT and include recurrent laryngeal nerve (RLN) injury and parathyroid glands (PG) devascularization or incidental removal with resultant temporary or permanent hypoparathyroidism (HPT).
The aim of this study is to characterize the morbidity that CCND adds to total thyroidectomy.
Materials and Methods
This retrospective controlled study was performed enrolling patients who underwent surgery between 2007 and 2019 in the Department of Surgery "P. Valdoni", Sapienza University of Rome, Rome, Italy. All patients underwent total thyroidectomy (TT). Some of them underwent concomitant ipsilateral central compartment neck dissection (iCCND) while others underwent bilateral central compartment neck dissection (bCCND); in case of iCCND, frozen section analysis was performed to determine if lymph node metastases are present and if go on with bCCND.
Inclusion criteria were:
-
preoperative cytological diagnosis of DTC with absence of suspicious clinical nodal metastasis at US or CT scan (cN0)
Exclusion criteria were:
previous thyroid or parathyroid surgery
previous neck surgery
previous neck irradiation
concomitant surgery for hyperparathyroidism
surgery for locoregional recurrence
completion thyroidectomy
We enrolled a population of 453 patients, who were grouped on the basis of the treatment received.
Group A was composed of 316 patients (69.75%) who underwent TT alone; this control group contained all patients treated for benign thyroid disease and incidental diagnosis of DTC on final histopathology, patients staged as cT1 or cT2, patients with previous cytopathological diagnosis of DTC follicular variant on final histopathology, patients in whom concomitant prophylactic iCCND was not performed because anatomical or surgical conditions put the RLN at a great risk of injury.
Group B was composed of 86 patients (18.98%) who underwent TT + iCCND; this group contained all patients with DTC staged as cT3 or cT4, without evidence of ipsilateral pretracheal and paratracheal lymph node metastasis on intraoperative frozen section specimens.
Group C was composed of 51 patients (11.25%) who underwent TT + bCCND; this group contained all patients with DTC staged as cT3 or cT4 and evidence of lymph node metastasis on ipsilateral intraoperative frozen section specimens and patients with cytopathological or intraoperative diagnosis of DTC staged as cT3 or cT4 in both lobes or in the isthmus of the thyroid gland.
All the patients included in the study had undergone a preoperative physical examination, high-resolution neck US or CT, FNAC of suspicious nodules, and measurement of serum thyroid hormones, TSH, Tg, and anti-Tg antibodies; preoperative fibrolaryngoscopy was also routinely performed.
In each patient, extracapsular TT was performed; RLN were routinely exposed until their insertion into the larynx, and preservation of the PG was always searched.
During bCCND pre-laryngeal, pretracheal, and both the right and the left paratracheal nodal basins were removed, while during iCCND pre-laryngeal, pretracheal and the paratracheal nodal basins on the side of the tumor were removed. Drainage was routinely used.
The parathyroid glands were not routinely exposed during thyroidectomy. However, if a parathyroid gland was encountered during surgery, its blood supply was confirmed by means of the fine-needle.
pricking test. A gland with blood oozing after the test was considered to be vascularized, otherwise considered as devascularized, so removed and autotransplanted into the sternocleidomastoid muscle.
Vocal cord mobility was assessed postoperatively by flexible fiber optic laringoscopy and RLN injury was defined as a postoperative impairment of the motility of one or both vocal cords, compared to the preoperative finding, ranging from mild reduction of motility to a vocal cord fixity.
RLN injury was considered transient in patients who regained normal vocal cord motility within 6 months after surgery; otherwise, it was considered permanent.
Albumin-adjusted total serum calcium levels were measured preoperatively and once daily on postoperative days 1,2 and 3, and then at follow-up visits.
The diagnosis of post-operative hypocalcemia was determined clinically and biochemically. Symptomatic hypocalcemia was considered if any episode of symptoms or signs of hypocalcemia appeared (tingling or numbness in the lips, hands and/or feet, Chvostek’s sign, Trousseau’s sign, muscle cramp or tetany.
Transient HPT was defined as postoperative hypocalcemia with an albumin adjusted total serum calcium level lower than 2.0 mM (8.0 mg/dL; normal range, 8.5–10.2 mg/dL). Permanent HPT was defined as postoperative hypocalcemia persisting 6 months after surgery requiring calcium and vitamin D supplements.
Transient or permanent RLN injury and transient or permanent HPT were taken as primary endpoints for the statistical analysis and were assessed at follow up visits. The follow up end points were established at 1, 6 and 12 months after surgery (except for patients who required more frequent controls).
The study has been approved by the local Institutional Ethical Committees of University of Rome “La Sapienza”.
Data are presented as number (percentage) except where explicitly stated. The whole analysis was performed by Software Statistica 12 (Statsof). We used the Fisher's exact test and applied the Bonferroni correction for multiple tests. A value of p < 0.025 was considered to be statistically significant.
Results
The total number of patients enrolled in the study was of 453 patients, 329 women (72, 62%) an 124 men (27,37%). Patient mean age was 46, 3 years.
Transient RLN injury was found in 7 of 316 patients of Group A (2.22%), in 3 of 86 patients of Group B (3.49%) and in 2 of 51 patients of Group C (3.92%).
Permanent RLN injury was found in 4 of 316 patients of Group A (1.27%), in 2 of 86 patients of Group B (2.33%) and in 2 of 51 patients of Group C (3.92%).
There were no cases of bilateral RLN injury.
Transient hypoparathyroidism was found in 42 of 316 patients of Group A (13.29%), in 25 of 86 patients of Group B (29.07%) and in 18 of 51 patients of Group C (35.29%).
Permanent hypoparathyroidism was found in 6 of 316 patients of Group A (1.90%), in 2 of 86 patients of Group B (2.33%) and in 8 of 51 patients of Group C (15.68%).
Statystical analysis showed no significant differences in rate of transient and permanent RLN injury between the three study groups (Table 1).
TABLE 1.
Population of patients and complications rates
| Group A | Group B | Group C | A vs B | A vs C | |
|---|---|---|---|---|---|
| Patients number (female) | 316 (247) | 86 (47) | 51 (35) | ||
| Age range (median) | 47.9 years | 44.3 years | 45.1 years | ||
| Transient RLN injury Patients (%) | 7 (2.22%) | 3 (3.49%) | 2 (3.92%) | p = 0.36 | p = 0.36 |
| Permanent RLN injury Patients (%) | 4 (1.27%) | 2 (2.33%) | 2 (3.92%) | p = 0.38 | p = 0.19 |
| Transient hypoparathyroidism Patients (%) | 42 (13.29%) | 25 (29.07%) | 18 (35.29%) | p < 0.01 | p < 0.01 |
| Permanent hypoparathyroidism Patients (%) | 6 (1.90%) | 2 (2.33%) | 8 (15.68%) | p = 0.53 | p < 0.01 |
About transient hypoparathyroidism, data showed a significantly higher rate of this surgical complication among patients in Group B (p < 0.01) and in Group C (p < 0.01), if compared with patients in Group A (Table 1).
About permanent hypoparathyroidism, data showed no differences in rate of this surgical complication between patients in Group A and Group B, while documented a significantly higher rate in patients in Group C (p < 0.01), if compared with patients of Group A and Group B (Table 1).
Discussion
The treatment of DTC have changed drastically in last years because of new evidences and constant guidelines revisions.
Nevertheless, there are still many controversial aspects extensively debated in Literature and prophylactic central neck dissection is one of the major discussed topic. Indeed, while there is a common consensus about recommendation of lateral neck dissection in case of clinically involved lymph nodes, the role of prophylactic central neck dissection for cN0 DTC is still controversial. The 2009 ATA guidelines had a relatively neutral stand on the argument, whereas the consensus among Chinese surgeons suggests that prophylactic central neck dissection was indicated during thyroidectomy [29].
In contrast to the ATA guidelines of 2009 [30], in the 2015 version [31] there was a strong recommendation to not perform pCCND for smaller DTC (T1-T2 cN0) while it should be considered (weak recommendation) in case of a laterocervical lymph node involvement (cN1b) of a T3-T4 tumor or in order to stage the neoplasm and plan a subsequent RAI ablation.
A consensus report by the European Society of Endocrine Surgeons (ESES) stated that larger tumours (T3, T4), patients over 45 years or under 15 years, male patients, patients with bilateral or multifocal tumours and patients with known involved lateral lymph nodes should all be candidates for routine unilateral level 6 dissection [32].
Anyway, the prognostic importance of lymphatic involvement in locoregional recurrence and long-term survival still remains a matter of debate.
This animated debate is caused by the scarcity of high quality comparative prospective trials about recurrence rate and overall prognosis in patients who underwent prophylactic central neck dissection [21, 33] but even to the lack of a complete knowledge about rates of complications in CCND.
Some authors affirmed that it is associated with higher injury rate to parathyroid glands (especially the lower glands), with rates of transient hypoparathyroidism at 14–60%, permanent hypoparathyroism at 0–14%, transient RLN damage at 0–10% and permanent RLN damage at 0–5% [34–36].
However, other authors have reported that rate of RLN damage and permanent hypoparathyroidism in patients treated with TT and CND may be overestimated [6].
The number of central neck lymph nodes that need to be removed during prophylactic central neck dissection to achieve an accurate assessment of lymph node status seems to be dependent on the associated risk of the primary tumor and range from six excised lymph nodes in patients with T1b tumors up to eighteen excised lymph nodes in patients with T3 tumors to rule out occult nodal disease with 90% confidence [37].
The definition of a bilateral central compartment neck dissection (bCCND) is the removal of the lymph nodes in level 6 from the hyoid bone cranially to the innominate artery on the right and the associated level on the left caudally, laterally to the medial border of the common carotid artery, and from the strap muscles anteriorly to the prevertebral fascia posteriorly to also include the lymph nodes posterior to the recurrent laryngeal nerves [30, 32]
Because of the risk of complications following bCCND, an ipsilateral central compartment neck dissection (iCCND) has recently been proposed as a safer, alternative treatment for patients with unilateral DTC; it includes the lymph nodes in level 6 on the side of the primary tumor and extends to the midline pretracheal and prelaryngeal lymph nodes [20, 38–42]
In this study, we evaluated the morbidity of CCND comparing the rates of the two major complications (RLN injury and HPT) in three groups of patients affected by DTC with clinically negative neck lymph nodes and treated with TT, TT + iCCND and TT + bCCND.
Data analysis showed that iCCND and bCCND are not associated with an increased rate of transient or permanent RLN injury, when these procedures are associated with TT.
Conversely, iCCND seems associated with an increased rate of transient HPT but not permanent HPT, and bCCND seems associated with an increased rate of transient and permanent HPT, when performed together with TT.
Parathyroid glands are often embedded with lymph nodes and can be more difficult to identify them in patients with enlarged lymph nodes in the central compartment of the neck from cancer or Hashimoto’s thyroiditis [43] and this relationship with transient and permanent HPT could be explained by the fact that iCCND and mainly bCCND may increase the risk of traumatic or ischemic damage to parathyroid glands caused by surgical manipulation [44, 45]
In fact, HPT is usually caused by intraoperative damage, devascularization or accidental removal of the parathyroid glands. A meta-analysis from 2014 reported a prevalence of transient and permanent HPT of 19–38% and 0–3%, respectively, although both are probably underestimated [46]
Unintentional parathyroidectomy during total thyroidectomy has been recognized only recently.
as a major cause of postoperative hypoparathyroidism, because the number of parathyroid glands left in situ is however a powerful, independent, predictive variable of rate of permanent hypoparathyroidism [47, 48].
But parathyroid glands may have multiple and unexpected relationships with thyroid gland [49] and sometimes their removal cannot be prevented.
Another important factor during TT is the blood supply of parathyroid glands: the inferior parathyroid gland takes blood supply from the inferior thyroid artery, while the superior parathyroid gland is supplied by the inferior thyroid artery or by an anastomotic branch between inferior thyroid and superior thyroid artery.
If arterial blood supply is interrupted, PTG suffer from ischemia, while disruption of venous drainage causes stasis, resulting in PTGs infarction. Therefore, both arterial and venous vascularization, are fundamental for a correct parathyroid function and for prevention of HPT.
During TT with CCND, the inferior parathyroid gland (IPTG) typically undergoes dissection twice. At first it is exposed and preserved by meticulous capsular dissection during thyroid lobectomy. Later, the IPTG is identified and preserved while the central neck fibro-fatty tissue is removed with lymph nodes. The first dissection is the premise and basis of the second dissection, because preservation of the IPTG in CCND becomes impossible if the IPTG has been devascularized or removed during thyroid lobectomy. Failure to identify the IPTG during the thyroid lobectomy makes the following preservation of the IPTG in CCND very difficult because of the variable positions of IPTGs in the adult neck and their locationing in the area of central neck lymph node dissection.
So, every effort must be made to preserve vascular supply to the superior parathyroid gland. Anyway, in cases of ischemia of a parathyroid gland during CCND, it has to be removed, sliced into a few 1–2-mm pieces, confirmed on intraoperative frozen-section pathology to avoid autograft of a lymph node metastasis, and autotransplanted into an individual pocket created within the sternal belly of the sternocleidomastoid muscle [50].
Other studies that compared the surgical complication rate of TT + CCND to TT alone come to the conclusion that the rate of RLN injury is similar, while the rate of temporary and possibly permanent hypoparathyroidism is higher when is associated CCND [51–53].
One interesting study that compared rate of complications in TT, TT + iCCND and TT + bCCND [54] reached our same conclusions, affirming that there is an increased risk of transient HPT if is performed iCCND and an increased risk of transient and permanent HPT if is performed bCCND, correlating closely the extent of surgery with incidental damage of PG.
Therefore, iCCND could be an interesting surgical option considering the lower rate of permanent HPT compared to bCCND, but the incidence of transient HPT appear still higher than TT alone, so its role must be validated by further studies.
The role of prophylactic central neck dissection (CCND) associated with total thyroidectomy (TT) in patients with differentiated thyroid carcinoma (DTC) without evidence of cervical lymph node metastasis on preoperative evaluation /cN0) is still controversial, and an aggressive approach with extensive prophylactic lymph node dissection, must be carefully evaluated.
Further randomized controlled studies are needed in order to evaluate the clear advantages of CCND (both ipsilateral and bilateral), but this should be considered in the context of an higher risk of transient and permanent hypoparathyroidism, if compared with TT alone.
Even if are indispensable large metanalysis and high quality prospective randomized trials to understand if CCND decrease locoregional recurrence, improve disease-free survival, allows a more tailored use of radioiodine therapy (RAI) due to improved lymph node staging and lead to lower postoperative thyroglobulin levels, with this study we can affirm that TT + iCCND presents a significantly increased risk of transient hypoparathyroidism and TT + bCCND presents a significantly increased risk of transient and permanent hypoparathyroidism, when compared with TT alone.
Funding
We have no fundings for this paper.
Declarations
Conflict of interest
The authors declare that they don’t have potential conflict of interest.
Informed Consent
All the participants to the research underwent an informed consent to take part to the study.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Aydin OU, Soylu L, Ozbas S, et al. The risk of hypoparathyroidism after central compartment lymph node dissection in the surgical treatment of pT1, N0 thyroid papillary carcinoma. Eur Rev Med Pharmacol Sci. 2016;20(9):1781–1787. [PubMed] [Google Scholar]
- 2.Chereau N, Trésallet C, Noullet S, et al. Prognosis of papillary thyroid carcinoma in elderly patients after thyroid resection: a retrospective cohort analysis. Medicine (Baltimore) 2016;95(47):e5450. doi: 10.1097/MD.0000000000005450. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Calò PG, Pisano G, Medas F, et al. Total thyroidectomy without prophylactic central neck dissection in clinically node negative papillary thyroid cancer: Is it an adequate treatment? World J Surg Oncol. 2014;12:152. doi: 10.1186/1477-7819-12-152. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Minni A, Rosati D, Cavaliere C, et al. (2019). Total versus completion thyroidectomy: a multidimensional evaluation of long-term vocal alterations. Ear Nose Throat J, 145561319886156. [DOI] [PubMed]
- 5.Roh JL, Kim JM, Park CI. Central cervical nodal metastasis from papillary thyroid microcarcinoma: pattern and factors predictive of nodal metastasis. Ann Surg Oncol. 2008;15:2482–2486. doi: 10.1245/s10434-008-0044-6. [DOI] [PubMed] [Google Scholar]
- 6.Chisholm EJ, Kulinskaya E, Tolley NS. Systematic review and meta-analysis of the adverse effects of thyroidectomy combined with central neck dissection as compared with thyroidectomy alone. Laryngoscope. 2009;119:1135–1139. doi: 10.1002/lary.20236. [DOI] [PubMed] [Google Scholar]
- 7.Salmaslıog˘ lu A, Erbil Y, Cıtlak G, et al. Diagnostic value of thyroglobulin measurement in fine-needle aspiration biopsy for detecting metastatic lymph nodes in patients with papillary thyroid carcinoma. Langenbecks Arch Surg. 2011;396:77–81. doi: 10.1007/s00423-010-0723-1. [DOI] [PubMed] [Google Scholar]
- 8.Ito Y, Tomoda C, Uruno T, et al. Clinical significance of metastasis to the central compartment from papillary microcarcinoma of the thyroid. World J Surg. 2006;30:91–99. doi: 10.1007/s00268-005-0113-y. [DOI] [PubMed] [Google Scholar]
- 9.Kouvaraki MA, Shapiro SE, Fornage BD, et al. Role of preoperative ultrasonography in the surgical management of patients with thyroid cancer. Surgery. 2003;134:946–954. doi: 10.1016/s0039-6060(03)00424-0. [DOI] [PubMed] [Google Scholar]
- 10.Wada N, Duh QY, Sugino K, et al. Lymph node metastasis from 259 papillary thyroid microcarcinomas: frequency, pattern of occurrence and recurrence, and optimal strategy for neck dissection. Ann Surg. 2003;237(3):399–407. doi: 10.1097/01.SLA.0000055273.58908.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Roh JL, Kim JM, Park CI. Central lymph node metastasis of unilateral papillary thyroid carcinoma: patterns and factors predictive of nodal metastasis, morbidity, and recurrence. Ann Surg Oncol. 2011;18(8):2245–2250. doi: 10.1245/s10434-011-1600-z. [DOI] [PubMed] [Google Scholar]
- 12.Pacini F, Castagna MG, Brilli L, Pentheroudakis G (2012), ESMO Guidelines Working Group. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. AnnOncol. 23 (Suppl7): vii110–9. 9.
- 13.Perros P, Boelaert K, Colley S, et al. (2014). British thyroid association. Guidelines for the management of thyroid cancer. Clin Endocrinol (Oxf). 81(Suppl 1): 1–122. 10. [DOI] [PubMed]
- 14.Ferris RL, Baloch Z, Bernet V, et al. (2015). American thyroid association surgical affairs committee. American thyroid association statement on surgical application of molecular profiling for thyroid nodules: current impact on perioperative decision making. Thyroid. 25(7): 760–8. 11. [DOI] [PMC free article] [PubMed]
- 15.Tuttle RM, Haddad RI, Ball DW, et al. (2014). Thyroid carcinoma, version 2. 2014. J Nat l Compr Cancer Netw. 12(12): 1671–80. [DOI] [PubMed]
- 16.Pereira JA, Jimeno J, Miquel J, et al. Nodal yield, morbidity, and recurrence after central neck dissection for papillary thyroid carcinoma. Surgery. 2005;138:1095–1101. doi: 10.1016/j.surg.2005.09.013. [DOI] [PubMed] [Google Scholar]
- 17.Shen WT, Ogawa L, Ruan D, et al. Central neck lymph node dissection for papillary thyroid cancer. Comparison of complication and recurrence rates in 295 initial dissections and reoperations. Arch Surg. 2010;145:272–275. doi: 10.1001/archsurg.2010.9. [DOI] [PubMed] [Google Scholar]
- 18.Sadowski BM, Snyder SK, Lairmore TC. Routine bilateral central lymph node clearance for papillary thyroid cancer. Surgery. 2009;146:696–705. doi: 10.1016/j.surg.2009.06.046. [DOI] [PubMed] [Google Scholar]
- 19.Conzo G, Docimo G, Mauriello C, et al. The current status of lymph node dissection in the treatment of papillary thyroid cancer a liter¬ature review. Clin Ter. 2013;164:e343–e346. doi: 10.7417/CT.2013.1599. [DOI] [PubMed] [Google Scholar]
- 20.Raffaelli M, De Crea C, Sessa L, et al. Prospective evaluation of total thyroidectomy versus ipsilateral versus bilateral central neck dissection in patients with clinically node-negative papillary thyroid carcinoma. Surgery. 2012;152:957–964. doi: 10.1016/j.surg.2012.08.053. [DOI] [PubMed] [Google Scholar]
- 21.Lang BH, Ng SH, Lau LL, Cowling BJ, Wong KP, Wan KY. A systematic review and meta-analysis of prophylactic central neck dissection on short-term locoregional recurrence in papillary thyroid carcinoma after total thyroidectomy. Thyroid. 2013;23(9):1087–1098. doi: 10.1089/thy.2012.0608. [DOI] [PubMed] [Google Scholar]
- 22.Barczynnski M, Konturek A, Stopa M, Nowak W. Pro¬phylactic central neck dissection for papillary thy-roid cancer. Br J Surg. 2013;100:410–418. doi: 10.1002/bjs.8985. [DOI] [PubMed] [Google Scholar]
- 23.Palestini N, Boras A, Cestino L, Freddi M, Odasso C, Robecchi A. Is central neck dissection a safe procedure in the treatment of papillary thyroid cancer? Our experience. Langenbecks Arch Surg. 2008;393:693–698. doi: 10.1007/s00423-008-0360-0. [DOI] [PubMed] [Google Scholar]
- 24.Zetoune T, Keutgen X, Buitrago D, et al. Prophylactic central neck dissection and local recurrence in papillary thyroid cancer: a meta-analysis. Ann Surg Oncol. 2010;17(12):3287–3293. doi: 10.1245/s10434-010-1137-6. [DOI] [PubMed] [Google Scholar]
- 25.Nixon IJ, Ganly I, Patel SG, et al. Observation of clinically negative central compartment lymph nodes in papillary thyroid carcinoma. Surgery. 2013;154(6):1166–1173. doi: 10.1016/j.surg.2013.04.035. [DOI] [PubMed] [Google Scholar]
- 26.Conzo G, Pasquali D, Bellastella G, et al. Total thyroidectomy, without prophylactic central lymph node dissection, in the treatment of differentiated thyroid cancer Clinical retrospective study on 221 cases. Endocrin. 2013;44:419–425. doi: 10.1007/s12020-013-9877-2. [DOI] [PubMed] [Google Scholar]
- 27.Hughes DT, Rosen JE, Evans DB, Grubbs E, Wang TS, Solórzano CC. Prophylactic central compartment neck dissection in papillary thyroid cancer and effect on locoregional recurrence. Ann Surg Oncol. 2018;25(9):2526–2534. doi: 10.1245/s10434-018-6528-0. [DOI] [PubMed] [Google Scholar]
- 28.Mc Henry CR, Stulberg JJ. Prophylactic central compartment neck dissection for papillary thyroid cancer. Surg Clin N Am. 2014;94:529–540. doi: 10.1016/j.suc.2014.02.003. [DOI] [PubMed] [Google Scholar]
- 29.Chinese Society of Endocrinology; Chinese Society of Surgery, the Society of Head and Neck Surgery of Chinese Anti-Cancer Association; Chinese Society of Nuclear Medicine. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer 2012 Chinese edition) Chin J Clin Oncol 2012: 39: 1249–1272
- 30.American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009; 19: 1167–1214. [DOI] [PubMed]
- 31.Haugen BR, Alexander EK, Bible KC, et al. American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26:1–133. doi: 10.1089/thy.2015.0020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Sancho JJ, Lennard TW, Paunovic I, Triponez F, Sitges-Serra A. Prophylactic central neck dissection in papillary thyroid cancer: a consensus report of the European society of endocrine surgeons (ESES) Langenbecks Arch Surg. 2014;399:155–163. doi: 10.1007/s00423-013-1152-8. [DOI] [PubMed] [Google Scholar]
- 33.Randolph GW, Duh QY, Heller KS, et al. The prognostic significance of nodal metastases from papillary thyroid carcinoma can be stratified based on the size and number of metastatic lymph nodes, as well as the presence of extranodal extension. Thyroid. 2012;22:1144–1152. doi: 10.1089/thy.2012.0043. [DOI] [PubMed] [Google Scholar]
- 34.Boute P, Merlin J, Biet A, Cuvelier P, Strunski V, Page C. Morbidity of central compartment dissection for differentiated thyroid carcinoma of the follicular epithelium. Eur Ann Otorhinolaryngol Head Neck Dis. 2013;130:245–249. doi: 10.1016/j.anorl.2012.10.004. [DOI] [PubMed] [Google Scholar]
- 35.Rosenbaum MA, McHenry CR. Central neck dissection for papillary thyroid cancer. Arch Otolaryngol Head Neck Surg. 2009;135:1092–1097. doi: 10.1001/archoto.2009.158. [DOI] [PubMed] [Google Scholar]
- 36.Roh JL, Kim JM, Park CI. Central compartment reoperation for recurrent/persistent differentiated thyroid cancer: patterns of recurrence, morbidity, and prediction of postoperative hypocalcemia. Ann Surg Oncol. 2011;18:1312–1318. doi: 10.1245/s10434-010-1470-9. [DOI] [PubMed] [Google Scholar]
- 37.Robinson TJ, Thomas S, Dinan MA, Roman S, Sosa JA, Hyslop T. How many lymph nodes are enough? Assessing the adequacy of lymph node yield for papillary thyroid cancer. J Clin Oncol. 2016;34(28):3434–3439. doi: 10.1200/JCO.2016.67.6437. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Sitges-Serra A, Lorente L, Mateu G, Sancho JJ. Central neck dissection: a step forward in the treatment of papillary thyroid cancer. Eur J Endocrinol. 2015;173:R199–206. doi: 10.1530/EJE-15-0481. [DOI] [PubMed] [Google Scholar]
- 39.Raffaelli M, De Crea C, Sessa L, Giustacchini P, Belantone R, Lombardi CP. Can intraoperative frozen section influence the extension of central neck dissection in cN0 papillary thyroid carcinoma? Langenbecks Arch Surg. 2013;398:383–388. doi: 10.1007/s00423-012-1036-3. [DOI] [PubMed] [Google Scholar]
- 40.Calò PG, Conzo G, Raffaelli M, et al. Total thyroidectomy alone versus ipsilateral versus bilateral prophylactic central neck dissection in clinically node-negative differentiated thyroid carcinoma A retrospective multicenter study. Eur J Surg Oncol. 2017;43(1):126–132. doi: 10.1016/j.ejso.2016.09.017. [DOI] [PubMed] [Google Scholar]
- 41.Garcia A, Palmer BJA, Parks NA, Liu TH. Routine prophylactic central neck dissection for low-risk papillary thyroid cancer is not cost-effective. Clin Endocrinol. 2014;81:754–761. doi: 10.1111/cen.12506. [DOI] [PubMed] [Google Scholar]
- 42.Moo TA, Umunna B, Kato M, et al. Ipsilateral versus bilateral central neck lymph node dissection in papillary thyroid carcinoma. Ann Surg. 2009;250:403–408. doi: 10.1097/SLA.0b013e3181b3adab. [DOI] [PubMed] [Google Scholar]
- 43.Dzodic R, Santrac N. In situ preservation of parathyroid glands: advanced surgical tips for prevention of permanent hypoparathyroidism in thyroid surgery. J BUON. 2017;22(4):853–855. [PubMed] [Google Scholar]
- 44.Promberger R, Ott J, Kober F, Karik M, Freissmuth M, Hermann M. Normal parathyroid hormone levels do not exclude permanent hypoparathyroidism after thyroidectomy. Thyroid. 2011;21:145–150. doi: 10.1089/thy.2010.0067. [DOI] [PubMed] [Google Scholar]
- 45.Minni A, Rosati D, Cavaliere C, et al. Study on the use of focus harmonic scalpel in thyroidectomies: is it useful also in preserving voice function? Eur Rev Med Pharmacol Sci. 2016;20(17):3544–3551. [PubMed] [Google Scholar]
- 46.Edafe O, Antakia R, Laskar N, Uttley L, Balasubra¬manian SP. Systematic review and meta-analysis of predictors of post-thyroidectomy hypocalcaemia. Br J Surg. 2014;101:307–320. doi: 10.1002/bjs.9384. [DOI] [PubMed] [Google Scholar]
- 47.Lorente-Poch L, Sancho JJ, Ruiz S, Sitges-Serra A. Importance of in situ preservation of parathyroid glands during total thyroidectomy. Br J Surg. 2015;102:359–367. doi: 10.1002/bjs.9676. [DOI] [PubMed] [Google Scholar]
- 48.Lang BH, Chan DT, Chow FC. Visualizing fewer parathyroid glands may be associated with lower hypoparathyroidism following total thyroidectomy. Langenbecks Arch Surg. 2016;401:231–238. doi: 10.1007/s00423-016-1386-3. [DOI] [PubMed] [Google Scholar]
- 49.Zhu JQ, Tian W, Xu ZG, et al. The expert consensus of parathyroid glands protection during thyroidectomy. Chin J Pract Surg. 2015;35:731–736. [Google Scholar]
- 50.Moffett JM, Suliburk J. Parathyroid autotransplantation. Endocr Pract. 2011;17(suppl 1):83–89. doi: 10.4158/EP10377.RA. [DOI] [PubMed] [Google Scholar]
- 51.Roh JL, Park JY, Park CI. Total thyroidectomy plus neck dissection in differentiated papillary thyroid carcinoma patients: pattern of nodal metastasis, morbidity, recurrence, and postoperative levels of serum parathyroid hormone. Ann Surg. 2007;245(4):604–610. doi: 10.1097/01.sla.0000250451.59685.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52.Shan CX, Zhang W, Jiang DZ, Zheng XM, Liu S, Qiu M. Routine central neck dissection in differentiated thyroid carcinoma: a systematic review and meta-analysis. Laryngoscope. 2012;122(4):797–804. doi: 10.1002/lary.22162. [DOI] [PubMed] [Google Scholar]
- 53.Gambardella C, Patrone R, Di Capua F, et al. The role of prophylactic central compartment lymph node dissection in elderly patients with differentiated thyroid cancer: a multicentric study. BMC Surg. 2019; 18 (Suppl 1): 110. Published 2019 Apr 24. [DOI] [PMC free article] [PubMed]
- 54.Giordano D, Valcavi R, Thompson GB, 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;22:911–917. doi: 10.1089/thy.2012.0011. [DOI] [PubMed] [Google Scholar]