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Surgical complications and recurrence after central neck dissection in cN0 papillary thyroid carcinoma
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Surgical complications and recurrence after central neck dissection in cN0 papillary thyroid carcinoma Dongbin Ahn a, Jin Ho Sohn a,*, Ji Young Park b a b
Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
A R T I C L E I N F O
A B S T R A C T
Article history: Received 24 April 2013 Accepted 29 June 2013 Available online xxx
Objectives: To evaluate surgical complications and recurrence patterns after central neck dissection (CND) in papillary thyroid carcinoma (PTC). Methods: A retrospective analysis was performed on 361 patients who underwent total thyroidectomy with or without CND for PTC from 2000 to 2007. Clinicopathological results and recurrence were stratified according to treatment modality. Results: Incidence of occult central metastasis of PTC was 64.3%. With respect to surgical morbidities, the total thyroidectomy (TT) with CND group exhibited a significantly higher incidence of transient vocal fold paralysis (10.0% vs 3.4%, p = 0.029) and permanent hypocalcaemia (11.4% vs 4.5%, p = 0.041), and significantly prolonged mean operating time (195.8 min vs 153.0 min, p < 0.001) than the TT alone group. Analysis of the recurrence patterns revealed that level IV was most commonly involved in both groups. When the location of recurrence was categorised into central and lateral neck, the recurrence rate in the lateral neck was significantly higher than that in the central neck, regardless of initial CND. Conclusions: CND was associated with permanent hypocalcaemia and transient vocal fold paralysis. The lateral neck was mainly involved in recurrence regardless of initial CND, suggesting the clinical benefit of CND may be small. ß 2013 Elsevier Ireland Ltd. All rights reserved.
Keywords: Hypocalcaemia Vocal cord paralysis Lymph node dissection Thyroid cancer
1. Introduction Thyroid cancer, especially papillary thyroid carcinoma, is the most common head and neck malignancy worldwide, and its prevalence is on the rise, accounting for up to 1% of all cancers in the US [1,2]. Although the overall 10-year survival rate is over 90%, papillary thyroid carcinoma is frequently recurrent and metastatic to the regional lymph nodes [1,3]. Ironically, the prolonged natural history of disease plays an important part in the controversies surrounding management philosophies, and one of the major debates in the surgical treatment of thyroid cancer revolves around the role of central compartment clearance [4–6]. With improvements in the accuracy of preoperative diagnostic modalities, there has been a recent tendency towards more conservative surgical management patterns in most malignancies. Shifts from radical neck dissection to super-selective strategies for the management of neck metastases, and from invasive open
surgery to trans-oral laser surgery in larynx or hypopharyngeal cancers are well-known examples [7–9]. In contrast to recent trends towards preservation surgeries, routine prophylactic central neck dissection for papillary thyroid carcinoma is well supported by numerous studies [5,10,11]. However, the impact of central lymph node metastasis on the prognosis and clinical benefits of central neck dissection has not been clearly demonstrated to date. In addition, the recurrence pattern after central neck dissection has not been established and some studies reported that central neck dissection may be associated with a higher rate of complications than total thyroidectomy alone [11– 13]. The aim of our study was to evaluate surgical complications after central neck dissection using data from a well-documented database, and to analyse the regional recurrence pattern in patients with or without central neck dissection. 2. Materials and methods 2.1. Study population
* Corresponding author at: Department of Otorhinolaryngology-Head and Neck Surgery, Kyungpook National University Medical Center, 807 Hogukno, Buk-gu, Daegu 702-210, Republic of Korea. Tel.: +82 53 200 5777; fax: +82 53 423 4524. E-mail address: [email protected] (J.H. Sohn).
A database of patients with thyroid cancer was established upon inception of the thyroid cancer centre of our institution in 1997. Since then, thyroid cancer patient data have been recorded
0385-8146/$ – see front matter ß 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.anl.2013.06.002
Please cite this article in press as: Ahn D, et al. Surgical complications and recurrence after central neck dissection in cN0 papillary thyroid carcinoma. Auris Nasus Larynx (2013), http://dx.doi.org/10.1016/j.anl.2013.06.002
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from operation to last follow-up, and these data were reviewed in the present study. Analysis of patient data revealed that 1275 patients underwent thyroid surgery at our institution in an 8-yearperiod between January 2000 and December 2007. Of these patients, 361 were enrolled in the study and met the following inclusion criteria: (1) underwent total thyroidectomy alone or with concurrent central neck dissection as initial treatment. Compartment of the central neck is bounded superiorly by the hyoid bone, inferiorly by the innominate artery, medially by the trachea, and laterally by the carotid artery; (2) had histologically confirmed papillary thyroid carcinoma; (3) evaluated by preoperative imaging studies including neck ultrasonography, computed tomography (CT), and/or positron emission tomography/computed tomography (PET/CT) scans; (4) staged as clinical N0 based on preoperative evaluations including the above-mentioned imaging studies; (5) received high dose radioactive iodine remnant ablation using 100–200 mCi 131I followed by thyroid surgery; and (6) medical records and pathology slides were available for review. From the initial cohort of 1275 patients, patients with a histopathological diagnosis other than papillary thyroid carcinoma (such as benign thyroid disease, follicular thyroid carcinoma, medullary thyroid carcinoma, and anaplastic thyroid carcinoma); patients who underwent hemi-thyroidectomy or total thyroidectomy with additional concomitant lateral compartment neck dissection as initial treatment; patients who underwent revision surgery; and patients with distant metastasis at the time of initial diagnosis of papillary thyroid carcinoma were excluded from this evaluation. Furthermore, 6 patients did not receive radioactive iodine ablation although they were indicated for radioactive iodine treatment, and 21 patients received low-dose radioactive iodine remnant ablation using 30–40 mCi 131I; these patients were also excluded from this evaluation for uniform design of the present study. Four patients were excluded as their medical records or histologic slides were inadequate for review. The cohort of 361 patients comprised 53 (14.7%) men and 308 (85.3%) women, with a mean age of 47.6 12.8 years at the time of surgery. The mean follow-up period was 58.1 23.0 months. Total thyroidectomy alone was performed in 291 (80.6%) patients, whereas total thyroidectomy with concurrent central neck dissection was performed in 70 (19.4%) patients. 2.2. Preoperative imaging studies Ultrasonography was preoperatively performed by one of the 2 thyroid oncologists who specialise in head and neck ultrasonography. The ultrasonographic examination included both thyroid lobes and all neck levels (I–VI). Additionally, all patients underwent contrast-enhanced CT scan with a reconstructed slice thickness of 3.5 mm for axial and coronal images to detect metastatic lymph nodes and to identify vascular anomalies, such as retro-oesophageal subclavian artery, which could indicate the presence of non-recurrent laryngeal nerve. Although the results of these 2 imaging studies revealed no evidence of lymph node metastases, PET/CT scan was performed in selected patients with a tumour size of >1 cm and definite extra-thyroidal extension in ultrasonography and CT scan according to our protocol for preoperative evaluation of thyroid cancer. 2.3. Treatment policy for papillary thyroid carcinoma All surgeries were performed by 2 experienced head and neck surgeons. Total thyroidectomy alone was performed when at least one of the following criteria was met: the cancer was extrathyroidal, multifocal, or macrocarcinoma (>1 cm), with no cervical lymph node involvement. Patient factors such as age, sex, family history, or history of radiation were not considered. Concurrent
central neck dissection was performed on the basis of the surgeons’ judgement of the surgical field despite negative preoperative evaluations, mainly in patients who had macroscopic extrathyroidal extension with macrocarcinoma or suspicious or enlarged central lymph nodes in the surgical field [6]. Novel haemostatic devices, such as Harmonic Scalpels or LigaSure, which have replaced the classical clamp-and-tie technique in our institution after 2009, were not used. Radioactive iodine remnant ablation was performed using 100–200 mCi 131I for the same indications as those for total thyroidectomy. All patients received adequate doses of thyroxine immediately after surgery to suppress thyrotropin levels according to risk stratification. 2.4. Postoperative complications All patients underwent pre- and post-operative laryngoscopic examinations, and serum total calcium levels and intact parathyroid hormone concentrations were monitored. Transient recurrent laryngeal nerve injury was defined as vocal fold paralysis showing recovery within 6 months after surgery. Permanent recurrent laryngeal nerve injury was defined as vocal fold paralysis, confirmed with laryngoscopic and stroboscopic examinations, persisting for more than 6 months. Transient hypocalcaemia was defined as a serum calcium level lower than 8.0 mg/dL with the associated clinical signs or symptoms, showing recovery within 6 months after surgery. Permanent hypocalcaemia was defined as a serum calcium level lower than 8.0 mg/dL, associated with low parathyroid hormone level and requiring oral calcium supplementation for more than 6 months after surgery. 2.5. Follow-up strategy During the follow-up period, all patients received regular physical examinations every 3–6 months, and plain chest radiographs were obtained once a year. For all patients, first diagnostic whole body scan with 150 mCi 131I and measurement of thyroglobulin levels during thyroid hormone withdrawal were carried out 6–12 months after remnant ablation. Following these examinations, diagnostic 131I whole body scans were routinely scheduled at 1-year intervals. Serum thyroglobulin measurements, antithyroglobulin antibody assays, and thyrotropin measurements were also concurrently performed with the whole body scans. When the serum thyroglobulin level was >5 mg/L or in cases wherein recurrence was clinically suspected, one or more nonradioiodine imaging methods, mainly neck ultrasonography and PET/CT, was performed to diagnose and localise the recurrence. When suspicious recurrent lesions were identified within imaging studies, we performed fine needle aspiration cytology if possible and then we planned surgery to remove and confirm the disease. 2.6. Statistical analysis SPSS for Windows (version 12.0; SPSS, Chicago, IL, USA) was used to analyse data. Continuous data are represented as mean standard deviation. To compare continuous variables, such as age, tumour size, operating times, and duration of hospital stay, an independent t-test was performed. The associations between central neck dissection and prognostic or morbidity variables such as gender, extra-thyroidal extension (present or absent), multifocality (unifocal or multifocal), lymph node metastases (positive or negative), pathologic staging system, incidence of complications, and the recurrence rate in the 2 compartment of the neck (central and lateral) were assessed using a Chi-square test or Fisher’s exact test. Statistical significance was defined as a p value of <0.05 and p-values were 2-sided throughout.
Please cite this article in press as: Ahn D, et al. Surgical complications and recurrence after central neck dissection in cN0 papillary thyroid carcinoma. Auris Nasus Larynx (2013), http://dx.doi.org/10.1016/j.anl.2013.06.002
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3. Results
3.2. Surgical complications
3.1. Histopathological examinations
Surgical complications as a function of central neck dissection are listed in Table 2. The mean operating time, defined as the timeperiod from beginning to end of general anaesthesia, was significantly longer for the total thyroidectomy with central neck dissection group than the total thyroidectomy group. Of the several surgical complications, incidence of transient vocal fold paralysis and permanent hypocalcaemia were significantly higher in the total thyroidectomy with central neck dissection group. Inadvertently excised parathyroid gland was identified in the histopathological analyses of 4.5% patients in the total thyroidectomy alone group and 11.4% patients in the total thyroidectomy with central neck dissection group. This difference was statistically significant.
Histopathological analysis of the of the 361 patients with papillary thyroid carcinoma revealed no significant difference between the total thyroidectomy group and the total thyroidectomy with central neck dissection group with respect to the proportion of patients with conventional papillary thyroid carcinoma, stages I–IV, and overall extra-thyroidal extension. However, compared to the total thyroidectomy alone group, the total thyroidectomy with central neck dissection group showed larger mean tumour size and greater incidence of macroscopic extra-thyroidal extension, multifocal disease, and concurrent Hashimoto’s thyroiditis (Table 1). The central lymph node metastasis was found to be in 45 patients (64.3%) of the central neck dissection group. The mean nodal yield for central neck dissection in the total thyroidectomy with central neck dissection group was 6.6 2.8 nodes as documented by a pathologic review, and the mean number of positive central lymph nodes was 3.2 2.0.
3.3. Recurrence and pattern of regional recurrence During the mean 58.1-month follow-up period (58.1 months in the total thyroidectomy alone group and 58.5 months in the
Table 1 Clinicopathological characteristics.
Subtype of PTC Conventional Follicular variant Tall cell variant Tumour size (cm) Microcarcinoma (1 cm) Extra-thyroidal extension Macroscopic Multifocality Concurrent Hashimoto’s thyroiditis Lymph node metastasis Yielded central lymph node Number of positive central lymph node Stage I II III IV
Total thyroidectomy alone (n = 291)
Total thyroidectomy with central neck dissection (n = 70)
p-Value
275 (94.5) 13 (4.5) 3 (1.0) 1.6 1.1 (range, 0.1–3.3) 89 (30.6) 171 (58.8) 32 (11.0) 87 (29.1) 67 (23.0) – – –
68 (97.1) 2 (2.9) 0 (0.0) 2.2 1.4 (range, 0.3–6.0) 6 (8.6) 48 (68.6) 22 (31.4) 28 (40.0) 27 (38.6) 45 (64.3) 6.6 2.8 (range, 3–16) 3.2 2.0 (range, 1–10)
0.543 0.745 1.000 0.001* <0.001* 0.131 <0.001* <0.001* 0.008* – – –
133 (45.7) 22 (7.6) 125 (43.0) 11 (3.8)
28 (40.0) 4 (5.7) 34 (48.6) 4 (5.7)
0.389 0.592 0.395 0.503
Percentages are given in parentheses. * Statistically significant.
Table 2 Surgical complications related with central neck dissection.
Operating time (minutes) Duration of hospital stay (days) Vocal fold paralysis Transient Right Left Permanent Right Left Hypocalcaemia Transient Permanent Inadvertently excised parathyroid gland Post-operative bleeding Seroma collection
Total thyroidectomy alone (n = 291)
Total thyroidectomy with central neck dissection (n = 70)
p-Value
153.0 33.9 (range, 105–227) 4.8 2.4 (range, 1–10)
195.8 48.9 (range, 94–290) 5.0 2.3 (range, 2–10)
<0.001* 0.435
10 (3.4) 6 4 8 (2.7) 4 4
7 (10.0) 5 2 1 (1.4) 1 0
0.029* 1.000
22 (7.6) 13 (4.5) 13 (4.5) 1 (0.3) 9 (3.1)
5 8 8 1 5
0.905 0.041* 0.041* 0.351 0.159
(7.1) (11.4) (11.4) (1.4) (7.1)
1.000 1.000
Percentages are given in parentheses. All vocal fold paralysis including transient and permanent types was unilateral. * Statistically significant.
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total thyroidectomy with central neck dissection group), 40 out of 361 patients experienced recurrence, representing an overall recurrence rate of 11.1%. Among them, 25 (8.6%) patients were in the total thyroidectomy alone group, and 15 (21.4%) in the total thyroidectomy with central neck dissection group. This difference in recurrence was statistically significant (p = 0.002). In both groups, the most frequent site of recurrence was the regional lymph nodes. There was no recurrence at the primary site (thyroid bed) in either group, and only 3 (0.8%) patients had recurrence with distant metastases to the lung. Mortality occurred in 4 (1.1%) patients, including 3 (1.0%) patients in the total thyroidectomy alone group and 1 (1.4%) in the central neck dissection group. Among them, however, only 1 (0.3%) patient died of PTC during the study period owing to transformation of the papillary thyroid carcinoma to anaplastic thyroid cancer over multiple rounds of recurrence. Of the 37 patients with regional recurrence, 33 (89.2%) exhibited ipsilateral metastases, and 2 patients (5.4%) exhibited bilateral metastases and contralateral neck metastases without ipsilateral metastasis, respectively. Pattern of regional recurrence in the both groups are presented in Fig. 1. The recurrence rate was highest at level IV (13/291, 4.5%), followed by level III (8/291, 2.7%) and level VI (7/291, 2.4%) in the total thyroidectomy alone group. In the total thyroidectomy with central neck dissection group, level IV (10/70, 14.3%) was again most commonly involved in recurrence, followed by level VI (4/70, 5.8%) and level III (3/70, 4.3%). When the locations of the recurrence were categorised into central and lateral neck, the recurrence rate in the lateral neck was significantly higher than that in the central neck in both groups (7.9% vs 2.4%, p = 0.003 in the total thyroidectomy alone group;
Fig. 2. Comparison of the recurrence rates in the central and lateral compartments of the neck between the total thyroidectomy alone group (a) and the total thyroidectomy with central neck dissection group (b). The recurrence rate in the lateral neck is significantly higher than that in the central neck regardless of previous central neck dissection.
22.9% vs 5.8%, p = 0.001 in the total thyroidectomy with central neck dissection group) (Fig. 2). 4. Discussion
Fig. 1. Recurrence rates in the different compartments of the neck (level II–VI) in the total thyroidectomy alone group (a) and the total thyroidectomy with central neck dissection group (b). Level IV is most commonly involved in both groups.
According to recommendations of the American Thyroid Association guidelines revised in 2009, the diagnosis of metastatic lymph node is possibly based on the imaging results of preoperative ultrasonography alone [11]. However, preoperative ultrasonography alone may not be sufficient for the identification of lymph node metastasis and this can be related to the overestimated incidence and clinical impact of occult central metastasis. Actually, in a study of 165 patients with surgically proven papillary thyroid carcinoma, a combination of ultrasonography and CT imaging was shown to be superior to ultrasonography alone for the detection of metastatic lymph nodes [14]. Therefore, we defined preoperative N0 stage based on the comprehensive imaging studies including CT and/or PET/CT scans as well as ultrasonography. However, despite negative results in these preoperative evaluations, 45 patients (64.3%) exhibited with central lymph node metastases after surgery on the basis of the surgeons’ judgement. These results suggest that occult central lymph node metastasis is very common in patients with macrocarcinoma with gross extra-thyroidal extension which were our criteria for central neck dissection. In addition, these results suggest that comprehensive imaging studies have limitations for detecting all metastases of the central compartment. The current results show that although the incidence of transient vocal fold paralysis was significantly higher in the total thyroidectomy with central neck dissection group than in the total
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thyroidectomy alone group, the incidence of permanent vocal fold paralysis was similar in the 2 groups. This result indicates that even in central neck dissection procedures requiring increased handling of recurrent laryngeal nerve, permanent loss of its function is not likely unless the surgeon transects the nerve itself [6,15]. In terms of hypocalcaemia, however, the results are different from those of nerve injury. Although surgeons may preserve the parathyroid gland itself, loss of function is possible [15]. Enlarged lymph nodes may have an appearance similar to that of normal parathyroid tissue and share the same route of blood supply; central neck dissection is, therefore, associated with an increased rate of postoperative hypoparathyroidism [4,16]. Furthermore, central neck dissection requires a longer operating time, which also has a negative effect on the preservation of normal parathyroid function because of hypothermal injury to the parathyroid gland during surgery [4]. Whether central neck dissection increases the risk of permanent hypocalcaemia and permanent recurrent laryngeal nerve injury is a subject of substantial controversy. However, considering that complication rates are significantly underreported by occasional thyroid surgeons, who represent at least 50% of all surgeons performing these procedures, several recent studies concluded that there may be a higher rate of permanent hypoparathyroidism and unintentional permanent nerve injury when central neck dissection is performed with total thyroidectomy than in total thyroidectomy alone [6,15,17]. In the initial diagnosis of papillary thyroid carcinoma, lymph node metastasis is most frequently identified in the central compartment [5]. However, in the present study for the patients who underwent total thyroidectomy with or without central neck dissection, analysis of the recurrence patterns revealed that clinical recurrence most commonly occurred at level IV in both groups, regardless of central neck dissection. Interestingly, even among the 291 patients without central neck dissection, recurrence at level VI occurred in only 7 patients (2.4%), whereas recurrence in the lateral compartment was detected in 23 patients (7.9%). These results suggest that the absolute benefit of central neck dissection may be small, particularly in patients who only have microscopic extrathyroidal extension with small tumours. In a study comprising a cohort of 342 patients who underwent total thyroidectomy with or without neck dissection for papillary thyroid carcinoma, the overall recurrence rate was 8.2% (28/342). The majority of recurrences located in the neck were found in the lateral region (n = 19), predominantly in level IV and III, rather than in the central neck (n = 8), even when no central compartment dissection was performed [18]. Our results are in agreement with these findings. Therefore, central neck dissection in a reoperative setting, when clinical recurrence is identified during the follow-up period, appears to be a more reasonable approach [4]. The recurrence rate of papillary thyroid carcinoma after total thyroidectomy followed by radioactive iodine ablation and thyrotropin suppression treatment was reported to be 10–20%, which is comparable to the rate noted in the present study (i.e. 11.1% [40/361] during 5 years) [7,19,20]. Considering this recurrence rate, initial elective central neck dissection was unnecessary in more than 80% of papillary thyroid carcinoma patients without clinical lymph node metastasis. Furthermore, in a retrospective study of 295 patients consisting of 189 cases of initial central neck dissection and 106 cases of reoperative central neck dissection, the latter group exhibited a lower rate of temporary hypocalcaemia, and the similar rates of other complications and recurrence compared to initial central neck dissection [4]. In a reoperative setting, patients may have sufficient time to recover their blood supply to the nerve and parathyroid gland by collateral regeneration of the vessels from relatively undamaged surrounding tissues and scar tissue of the
5
previous surgery. Therefore, even though fibrotic scar tissue makes sharp dissection difficult, the nerve and parathyroid gland may be more resistant to ischaemic injury when central neck dissection is performed in a reoperative setting rather than in a prophylactic setting of central neck dissection, which is performed concurrently with total thyroidectomy. The present study has some limitations. Central neck dissection was performed mainly in patients with suspicious or enlarged central lymph nodes on the basis of the surgeons’ judgement, which could introduce selection bias and may not be representative of a ‘pure’ elective central neck dissection. Therefore, demographic differences were related to the difference of overall recurrence rates between 2 groups. Furthermore, the 58 months of follow-up (mean value) in the current study is not sufficient to evaluate survival. Despite these limitations, we found a clear increase in the complications associated with central neck dissection, such as permanent hypocalcaemia and transient vocal fold paralysis. In addition, we deem that 58 months of follow-up is not a short-term period to evaluate recurrence, although it is not sufficient to evaluate survival. Conflict of interest None to declare. References [1] Tang KT, Lee CH. BRAF mutation in papillary thyroid carcinoma: pathogenic role and clinical implications. J Chin Med Assoc 2010;73:113–28. [2] Ahn D, Heo SJ, Park JH, Kim JH, Sohn JH, Park JY, et al. Clinical relationship between Hashimoto’s thyroiditis and papillary thyroid cancer. Acta Oncol 2011;50:1228–34. [3] Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 1994;97:418–28. [4] Shen WT, Ogawa L, Ruan D, Suh I, Kebebew E, Duh QY, 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;145:272–5. [5] 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;18:2245–50. [6] Iyer NG, Shaha AR. Central compartment dissection for well differentiated thyroid cancer . . . and the band plays on. Curr Opin Otolaryngol Head Neck Surg 2011;19:106–12. [7] Ahn D, Lee SJ, Park SK, Sohn JH, Park JS. Is comprehensive neck dissection a sole choice for the treatment of recurrent papillary thyroid carcinoma in the lateral neck? Korean J Otorhinolaryngol-Head Neck Surg 2011;54:62–8. [8] Caron NR, Tan YY, Ogilvie JB, Triponez F, Reiff ES, Kebebew E, et al. Selective modified radical neck dissection for papillary thyroid cancer – is level I, II and V dissection always necessary? World J Surg 2006;30:833–40. [9] Turanli S. Is the type of dissection in lateral neck metastasis for differentiated thyroid carcinoma important? Otolaryngol Head Neck Surg 2007;136:957–60. [10] Tisell LE, Nilsson B, Molne J, Hansson G, Fjalling M, Jansson S, et al. Improved survival of patients with papillary thyroid cancer after surgical microdissection. World J Surg 1996;20:854–9. [11] Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167–214. [12] Shen WT, Ogawa L, Ruan D, Suh I, Duh QY, Clark OH. Central neck lymph node dissection for papillary thyroid cancer: the reliability of surgeon judgment in predicting which patients will benefit. Surgery 2010;148:398–403. [13] Pereira JA, Jimeno J, Miquel J, Iglesias M, Munne A, Sancho JJ, et al. Nodal yield, morbidity, and recurrence after central neck dissection for papillary thyroid carcinoma. Surgery 2005;138:1095–100. discussion 1100-1. [14] Kim E, Park JS, Son KR, Kim JH, Jeon SJ, Na DG. Preoperative diagnosis of cervical metastatic lymph nodes in papillary thyroid carcinoma: comparison of ultrasound, computed tomography, and combined ultrasound with computed tomography. Thyroid 2008;18:411–8. [15] Mazzaferri EL, Doherty GM, Steward DL. The pros and cons of prophylactic central compartment lymph node dissection for papillary thyroid carcinoma. Thyroid 2009;19:683–9. [16] Cavicchi O, Piccin O, Caliceti U, De Cataldis A, Pasquali R, Ceroni AR. Transient hypoparathyroidism following thyroidectomy: a prospective study and multivariate analysis of 604 consecutive patients. Otolaryngol Head Neck Surg 2007;137:654–8. [17] White ML, Gauger PG, Doherty GM. Central lymph node dissection in differentiated thyroid cancer. World J Surg 2007;31:895–904.
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[18] Forest VI, Clark JR, Ebrahimi A, Cho EA, Sneddon L, Gao K, et al. Central compartment dissection in thyroid papillary carcinoma. Ann Surg 2011;253:123–30. [19] Sato N, Oyamatsu M, Koyama Y, Emura I, Tamiya Y, Hatakeyama K. Do the level of nodal disease according to the TNM classification and the number of
involved cervical nodes reflect prognosis in patients with differentiated carcinoma of the thyroid gland? J Surg Oncol 1998;69:151–5. [20] Ahn D, Park JS, Sohn JH, Kim JH, Park SK, Seo AN, et al. BRAFV600E mutation does not serve as a prognostic factor in Korean patients with papillary thyroid carcinoma. Auris Nasus Larynx 2012;39:198–203.
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Surgical complications and recurrence after central neck dissection in cN0 papillary thyroid carcinoma Dongbin Ahn a, Jin Ho Sohn a,*, Ji Young Park b a b
Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
A R T I C L E I N F O
A B S T R A C T
Article history: Received 24 April 2013 Accepted 29 June 2013 Available online xxx
Objectives: To evaluate surgical complications and recurrence patterns after central neck dissection (CND) in papillary thyroid carcinoma (PTC). Methods: A retrospective analysis was performed on 361 patients who underwent total thyroidectomy with or without CND for PTC from 2000 to 2007. Clinicopathological results and recurrence were stratified according to treatment modality. Results: Incidence of occult central metastasis of PTC was 64.3%. With respect to surgical morbidities, the total thyroidectomy (TT) with CND group exhibited a significantly higher incidence of transient vocal fold paralysis (10.0% vs 3.4%, p = 0.029) and permanent hypocalcaemia (11.4% vs 4.5%, p = 0.041), and significantly prolonged mean operating time (195.8 min vs 153.0 min, p < 0.001) than the TT alone group. Analysis of the recurrence patterns revealed that level IV was most commonly involved in both groups. When the location of recurrence was categorised into central and lateral neck, the recurrence rate in the lateral neck was significantly higher than that in the central neck, regardless of initial CND. Conclusions: CND was associated with permanent hypocalcaemia and transient vocal fold paralysis. The lateral neck was mainly involved in recurrence regardless of initial CND, suggesting the clinical benefit of CND may be small. ß 2013 Elsevier Ireland Ltd. All rights reserved.
Keywords: Hypocalcaemia Vocal cord paralysis Lymph node dissection Thyroid cancer
1. Introduction Thyroid cancer, especially papillary thyroid carcinoma, is the most common head and neck malignancy worldwide, and its prevalence is on the rise, accounting for up to 1% of all cancers in the US [1,2]. Although the overall 10-year survival rate is over 90%, papillary thyroid carcinoma is frequently recurrent and metastatic to the regional lymph nodes [1,3]. Ironically, the prolonged natural history of disease plays an important part in the controversies surrounding management philosophies, and one of the major debates in the surgical treatment of thyroid cancer revolves around the role of central compartment clearance [4–6]. With improvements in the accuracy of preoperative diagnostic modalities, there has been a recent tendency towards more conservative surgical management patterns in most malignancies. Shifts from radical neck dissection to super-selective strategies for the management of neck metastases, and from invasive open
surgery to trans-oral laser surgery in larynx or hypopharyngeal cancers are well-known examples [7–9]. In contrast to recent trends towards preservation surgeries, routine prophylactic central neck dissection for papillary thyroid carcinoma is well supported by numerous studies [5,10,11]. However, the impact of central lymph node metastasis on the prognosis and clinical benefits of central neck dissection has not been clearly demonstrated to date. In addition, the recurrence pattern after central neck dissection has not been established and some studies reported that central neck dissection may be associated with a higher rate of complications than total thyroidectomy alone [11– 13]. The aim of our study was to evaluate surgical complications after central neck dissection using data from a well-documented database, and to analyse the regional recurrence pattern in patients with or without central neck dissection. 2. Materials and methods 2.1. Study population
* Corresponding author at: Department of Otorhinolaryngology-Head and Neck Surgery, Kyungpook National University Medical Center, 807 Hogukno, Buk-gu, Daegu 702-210, Republic of Korea. Tel.: +82 53 200 5777; fax: +82 53 423 4524. E-mail address: [email protected] (J.H. Sohn).
A database of patients with thyroid cancer was established upon inception of the thyroid cancer centre of our institution in 1997. Since then, thyroid cancer patient data have been recorded
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Please cite this article in press as: Ahn D, et al. Surgical complications and recurrence after central neck dissection in cN0 papillary thyroid carcinoma. Auris Nasus Larynx (2013), http://dx.doi.org/10.1016/j.anl.2013.06.002
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from operation to last follow-up, and these data were reviewed in the present study. Analysis of patient data revealed that 1275 patients underwent thyroid surgery at our institution in an 8-yearperiod between January 2000 and December 2007. Of these patients, 361 were enrolled in the study and met the following inclusion criteria: (1) underwent total thyroidectomy alone or with concurrent central neck dissection as initial treatment. Compartment of the central neck is bounded superiorly by the hyoid bone, inferiorly by the innominate artery, medially by the trachea, and laterally by the carotid artery; (2) had histologically confirmed papillary thyroid carcinoma; (3) evaluated by preoperative imaging studies including neck ultrasonography, computed tomography (CT), and/or positron emission tomography/computed tomography (PET/CT) scans; (4) staged as clinical N0 based on preoperative evaluations including the above-mentioned imaging studies; (5) received high dose radioactive iodine remnant ablation using 100–200 mCi 131I followed by thyroid surgery; and (6) medical records and pathology slides were available for review. From the initial cohort of 1275 patients, patients with a histopathological diagnosis other than papillary thyroid carcinoma (such as benign thyroid disease, follicular thyroid carcinoma, medullary thyroid carcinoma, and anaplastic thyroid carcinoma); patients who underwent hemi-thyroidectomy or total thyroidectomy with additional concomitant lateral compartment neck dissection as initial treatment; patients who underwent revision surgery; and patients with distant metastasis at the time of initial diagnosis of papillary thyroid carcinoma were excluded from this evaluation. Furthermore, 6 patients did not receive radioactive iodine ablation although they were indicated for radioactive iodine treatment, and 21 patients received low-dose radioactive iodine remnant ablation using 30–40 mCi 131I; these patients were also excluded from this evaluation for uniform design of the present study. Four patients were excluded as their medical records or histologic slides were inadequate for review. The cohort of 361 patients comprised 53 (14.7%) men and 308 (85.3%) women, with a mean age of 47.6 12.8 years at the time of surgery. The mean follow-up period was 58.1 23.0 months. Total thyroidectomy alone was performed in 291 (80.6%) patients, whereas total thyroidectomy with concurrent central neck dissection was performed in 70 (19.4%) patients. 2.2. Preoperative imaging studies Ultrasonography was preoperatively performed by one of the 2 thyroid oncologists who specialise in head and neck ultrasonography. The ultrasonographic examination included both thyroid lobes and all neck levels (I–VI). Additionally, all patients underwent contrast-enhanced CT scan with a reconstructed slice thickness of 3.5 mm for axial and coronal images to detect metastatic lymph nodes and to identify vascular anomalies, such as retro-oesophageal subclavian artery, which could indicate the presence of non-recurrent laryngeal nerve. Although the results of these 2 imaging studies revealed no evidence of lymph node metastases, PET/CT scan was performed in selected patients with a tumour size of >1 cm and definite extra-thyroidal extension in ultrasonography and CT scan according to our protocol for preoperative evaluation of thyroid cancer. 2.3. Treatment policy for papillary thyroid carcinoma All surgeries were performed by 2 experienced head and neck surgeons. Total thyroidectomy alone was performed when at least one of the following criteria was met: the cancer was extrathyroidal, multifocal, or macrocarcinoma (>1 cm), with no cervical lymph node involvement. Patient factors such as age, sex, family history, or history of radiation were not considered. Concurrent
central neck dissection was performed on the basis of the surgeons’ judgement of the surgical field despite negative preoperative evaluations, mainly in patients who had macroscopic extrathyroidal extension with macrocarcinoma or suspicious or enlarged central lymph nodes in the surgical field [6]. Novel haemostatic devices, such as Harmonic Scalpels or LigaSure, which have replaced the classical clamp-and-tie technique in our institution after 2009, were not used. Radioactive iodine remnant ablation was performed using 100–200 mCi 131I for the same indications as those for total thyroidectomy. All patients received adequate doses of thyroxine immediately after surgery to suppress thyrotropin levels according to risk stratification. 2.4. Postoperative complications All patients underwent pre- and post-operative laryngoscopic examinations, and serum total calcium levels and intact parathyroid hormone concentrations were monitored. Transient recurrent laryngeal nerve injury was defined as vocal fold paralysis showing recovery within 6 months after surgery. Permanent recurrent laryngeal nerve injury was defined as vocal fold paralysis, confirmed with laryngoscopic and stroboscopic examinations, persisting for more than 6 months. Transient hypocalcaemia was defined as a serum calcium level lower than 8.0 mg/dL with the associated clinical signs or symptoms, showing recovery within 6 months after surgery. Permanent hypocalcaemia was defined as a serum calcium level lower than 8.0 mg/dL, associated with low parathyroid hormone level and requiring oral calcium supplementation for more than 6 months after surgery. 2.5. Follow-up strategy During the follow-up period, all patients received regular physical examinations every 3–6 months, and plain chest radiographs were obtained once a year. For all patients, first diagnostic whole body scan with 150 mCi 131I and measurement of thyroglobulin levels during thyroid hormone withdrawal were carried out 6–12 months after remnant ablation. Following these examinations, diagnostic 131I whole body scans were routinely scheduled at 1-year intervals. Serum thyroglobulin measurements, antithyroglobulin antibody assays, and thyrotropin measurements were also concurrently performed with the whole body scans. When the serum thyroglobulin level was >5 mg/L or in cases wherein recurrence was clinically suspected, one or more nonradioiodine imaging methods, mainly neck ultrasonography and PET/CT, was performed to diagnose and localise the recurrence. When suspicious recurrent lesions were identified within imaging studies, we performed fine needle aspiration cytology if possible and then we planned surgery to remove and confirm the disease. 2.6. Statistical analysis SPSS for Windows (version 12.0; SPSS, Chicago, IL, USA) was used to analyse data. Continuous data are represented as mean standard deviation. To compare continuous variables, such as age, tumour size, operating times, and duration of hospital stay, an independent t-test was performed. The associations between central neck dissection and prognostic or morbidity variables such as gender, extra-thyroidal extension (present or absent), multifocality (unifocal or multifocal), lymph node metastases (positive or negative), pathologic staging system, incidence of complications, and the recurrence rate in the 2 compartment of the neck (central and lateral) were assessed using a Chi-square test or Fisher’s exact test. Statistical significance was defined as a p value of <0.05 and p-values were 2-sided throughout.
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3. Results
3.2. Surgical complications
3.1. Histopathological examinations
Surgical complications as a function of central neck dissection are listed in Table 2. The mean operating time, defined as the timeperiod from beginning to end of general anaesthesia, was significantly longer for the total thyroidectomy with central neck dissection group than the total thyroidectomy group. Of the several surgical complications, incidence of transient vocal fold paralysis and permanent hypocalcaemia were significantly higher in the total thyroidectomy with central neck dissection group. Inadvertently excised parathyroid gland was identified in the histopathological analyses of 4.5% patients in the total thyroidectomy alone group and 11.4% patients in the total thyroidectomy with central neck dissection group. This difference was statistically significant.
Histopathological analysis of the of the 361 patients with papillary thyroid carcinoma revealed no significant difference between the total thyroidectomy group and the total thyroidectomy with central neck dissection group with respect to the proportion of patients with conventional papillary thyroid carcinoma, stages I–IV, and overall extra-thyroidal extension. However, compared to the total thyroidectomy alone group, the total thyroidectomy with central neck dissection group showed larger mean tumour size and greater incidence of macroscopic extra-thyroidal extension, multifocal disease, and concurrent Hashimoto’s thyroiditis (Table 1). The central lymph node metastasis was found to be in 45 patients (64.3%) of the central neck dissection group. The mean nodal yield for central neck dissection in the total thyroidectomy with central neck dissection group was 6.6 2.8 nodes as documented by a pathologic review, and the mean number of positive central lymph nodes was 3.2 2.0.
3.3. Recurrence and pattern of regional recurrence During the mean 58.1-month follow-up period (58.1 months in the total thyroidectomy alone group and 58.5 months in the
Table 1 Clinicopathological characteristics.
Subtype of PTC Conventional Follicular variant Tall cell variant Tumour size (cm) Microcarcinoma (1 cm) Extra-thyroidal extension Macroscopic Multifocality Concurrent Hashimoto’s thyroiditis Lymph node metastasis Yielded central lymph node Number of positive central lymph node Stage I II III IV
Total thyroidectomy alone (n = 291)
Total thyroidectomy with central neck dissection (n = 70)
p-Value
275 (94.5) 13 (4.5) 3 (1.0) 1.6 1.1 (range, 0.1–3.3) 89 (30.6) 171 (58.8) 32 (11.0) 87 (29.1) 67 (23.0) – – –
68 (97.1) 2 (2.9) 0 (0.0) 2.2 1.4 (range, 0.3–6.0) 6 (8.6) 48 (68.6) 22 (31.4) 28 (40.0) 27 (38.6) 45 (64.3) 6.6 2.8 (range, 3–16) 3.2 2.0 (range, 1–10)
0.543 0.745 1.000 0.001* <0.001* 0.131 <0.001* <0.001* 0.008* – – –
133 (45.7) 22 (7.6) 125 (43.0) 11 (3.8)
28 (40.0) 4 (5.7) 34 (48.6) 4 (5.7)
0.389 0.592 0.395 0.503
Percentages are given in parentheses. * Statistically significant.
Table 2 Surgical complications related with central neck dissection.
Operating time (minutes) Duration of hospital stay (days) Vocal fold paralysis Transient Right Left Permanent Right Left Hypocalcaemia Transient Permanent Inadvertently excised parathyroid gland Post-operative bleeding Seroma collection
Total thyroidectomy alone (n = 291)
Total thyroidectomy with central neck dissection (n = 70)
p-Value
153.0 33.9 (range, 105–227) 4.8 2.4 (range, 1–10)
195.8 48.9 (range, 94–290) 5.0 2.3 (range, 2–10)
<0.001* 0.435
10 (3.4) 6 4 8 (2.7) 4 4
7 (10.0) 5 2 1 (1.4) 1 0
0.029* 1.000
22 (7.6) 13 (4.5) 13 (4.5) 1 (0.3) 9 (3.1)
5 8 8 1 5
0.905 0.041* 0.041* 0.351 0.159
(7.1) (11.4) (11.4) (1.4) (7.1)
1.000 1.000
Percentages are given in parentheses. All vocal fold paralysis including transient and permanent types was unilateral. * Statistically significant.
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total thyroidectomy with central neck dissection group), 40 out of 361 patients experienced recurrence, representing an overall recurrence rate of 11.1%. Among them, 25 (8.6%) patients were in the total thyroidectomy alone group, and 15 (21.4%) in the total thyroidectomy with central neck dissection group. This difference in recurrence was statistically significant (p = 0.002). In both groups, the most frequent site of recurrence was the regional lymph nodes. There was no recurrence at the primary site (thyroid bed) in either group, and only 3 (0.8%) patients had recurrence with distant metastases to the lung. Mortality occurred in 4 (1.1%) patients, including 3 (1.0%) patients in the total thyroidectomy alone group and 1 (1.4%) in the central neck dissection group. Among them, however, only 1 (0.3%) patient died of PTC during the study period owing to transformation of the papillary thyroid carcinoma to anaplastic thyroid cancer over multiple rounds of recurrence. Of the 37 patients with regional recurrence, 33 (89.2%) exhibited ipsilateral metastases, and 2 patients (5.4%) exhibited bilateral metastases and contralateral neck metastases without ipsilateral metastasis, respectively. Pattern of regional recurrence in the both groups are presented in Fig. 1. The recurrence rate was highest at level IV (13/291, 4.5%), followed by level III (8/291, 2.7%) and level VI (7/291, 2.4%) in the total thyroidectomy alone group. In the total thyroidectomy with central neck dissection group, level IV (10/70, 14.3%) was again most commonly involved in recurrence, followed by level VI (4/70, 5.8%) and level III (3/70, 4.3%). When the locations of the recurrence were categorised into central and lateral neck, the recurrence rate in the lateral neck was significantly higher than that in the central neck in both groups (7.9% vs 2.4%, p = 0.003 in the total thyroidectomy alone group;
Fig. 2. Comparison of the recurrence rates in the central and lateral compartments of the neck between the total thyroidectomy alone group (a) and the total thyroidectomy with central neck dissection group (b). The recurrence rate in the lateral neck is significantly higher than that in the central neck regardless of previous central neck dissection.
22.9% vs 5.8%, p = 0.001 in the total thyroidectomy with central neck dissection group) (Fig. 2). 4. Discussion
Fig. 1. Recurrence rates in the different compartments of the neck (level II–VI) in the total thyroidectomy alone group (a) and the total thyroidectomy with central neck dissection group (b). Level IV is most commonly involved in both groups.
According to recommendations of the American Thyroid Association guidelines revised in 2009, the diagnosis of metastatic lymph node is possibly based on the imaging results of preoperative ultrasonography alone [11]. However, preoperative ultrasonography alone may not be sufficient for the identification of lymph node metastasis and this can be related to the overestimated incidence and clinical impact of occult central metastasis. Actually, in a study of 165 patients with surgically proven papillary thyroid carcinoma, a combination of ultrasonography and CT imaging was shown to be superior to ultrasonography alone for the detection of metastatic lymph nodes [14]. Therefore, we defined preoperative N0 stage based on the comprehensive imaging studies including CT and/or PET/CT scans as well as ultrasonography. However, despite negative results in these preoperative evaluations, 45 patients (64.3%) exhibited with central lymph node metastases after surgery on the basis of the surgeons’ judgement. These results suggest that occult central lymph node metastasis is very common in patients with macrocarcinoma with gross extra-thyroidal extension which were our criteria for central neck dissection. In addition, these results suggest that comprehensive imaging studies have limitations for detecting all metastases of the central compartment. The current results show that although the incidence of transient vocal fold paralysis was significantly higher in the total thyroidectomy with central neck dissection group than in the total
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thyroidectomy alone group, the incidence of permanent vocal fold paralysis was similar in the 2 groups. This result indicates that even in central neck dissection procedures requiring increased handling of recurrent laryngeal nerve, permanent loss of its function is not likely unless the surgeon transects the nerve itself [6,15]. In terms of hypocalcaemia, however, the results are different from those of nerve injury. Although surgeons may preserve the parathyroid gland itself, loss of function is possible [15]. Enlarged lymph nodes may have an appearance similar to that of normal parathyroid tissue and share the same route of blood supply; central neck dissection is, therefore, associated with an increased rate of postoperative hypoparathyroidism [4,16]. Furthermore, central neck dissection requires a longer operating time, which also has a negative effect on the preservation of normal parathyroid function because of hypothermal injury to the parathyroid gland during surgery [4]. Whether central neck dissection increases the risk of permanent hypocalcaemia and permanent recurrent laryngeal nerve injury is a subject of substantial controversy. However, considering that complication rates are significantly underreported by occasional thyroid surgeons, who represent at least 50% of all surgeons performing these procedures, several recent studies concluded that there may be a higher rate of permanent hypoparathyroidism and unintentional permanent nerve injury when central neck dissection is performed with total thyroidectomy than in total thyroidectomy alone [6,15,17]. In the initial diagnosis of papillary thyroid carcinoma, lymph node metastasis is most frequently identified in the central compartment [5]. However, in the present study for the patients who underwent total thyroidectomy with or without central neck dissection, analysis of the recurrence patterns revealed that clinical recurrence most commonly occurred at level IV in both groups, regardless of central neck dissection. Interestingly, even among the 291 patients without central neck dissection, recurrence at level VI occurred in only 7 patients (2.4%), whereas recurrence in the lateral compartment was detected in 23 patients (7.9%). These results suggest that the absolute benefit of central neck dissection may be small, particularly in patients who only have microscopic extrathyroidal extension with small tumours. In a study comprising a cohort of 342 patients who underwent total thyroidectomy with or without neck dissection for papillary thyroid carcinoma, the overall recurrence rate was 8.2% (28/342). The majority of recurrences located in the neck were found in the lateral region (n = 19), predominantly in level IV and III, rather than in the central neck (n = 8), even when no central compartment dissection was performed [18]. Our results are in agreement with these findings. Therefore, central neck dissection in a reoperative setting, when clinical recurrence is identified during the follow-up period, appears to be a more reasonable approach [4]. The recurrence rate of papillary thyroid carcinoma after total thyroidectomy followed by radioactive iodine ablation and thyrotropin suppression treatment was reported to be 10–20%, which is comparable to the rate noted in the present study (i.e. 11.1% [40/361] during 5 years) [7,19,20]. Considering this recurrence rate, initial elective central neck dissection was unnecessary in more than 80% of papillary thyroid carcinoma patients without clinical lymph node metastasis. Furthermore, in a retrospective study of 295 patients consisting of 189 cases of initial central neck dissection and 106 cases of reoperative central neck dissection, the latter group exhibited a lower rate of temporary hypocalcaemia, and the similar rates of other complications and recurrence compared to initial central neck dissection [4]. In a reoperative setting, patients may have sufficient time to recover their blood supply to the nerve and parathyroid gland by collateral regeneration of the vessels from relatively undamaged surrounding tissues and scar tissue of the
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previous surgery. Therefore, even though fibrotic scar tissue makes sharp dissection difficult, the nerve and parathyroid gland may be more resistant to ischaemic injury when central neck dissection is performed in a reoperative setting rather than in a prophylactic setting of central neck dissection, which is performed concurrently with total thyroidectomy. The present study has some limitations. Central neck dissection was performed mainly in patients with suspicious or enlarged central lymph nodes on the basis of the surgeons’ judgement, which could introduce selection bias and may not be representative of a ‘pure’ elective central neck dissection. Therefore, demographic differences were related to the difference of overall recurrence rates between 2 groups. Furthermore, the 58 months of follow-up (mean value) in the current study is not sufficient to evaluate survival. Despite these limitations, we found a clear increase in the complications associated with central neck dissection, such as permanent hypocalcaemia and transient vocal fold paralysis. In addition, we deem that 58 months of follow-up is not a short-term period to evaluate recurrence, although it is not sufficient to evaluate survival. Conflict of interest None to declare. References [1] Tang KT, Lee CH. BRAF mutation in papillary thyroid carcinoma: pathogenic role and clinical implications. J Chin Med Assoc 2010;73:113–28. [2] Ahn D, Heo SJ, Park JH, Kim JH, Sohn JH, Park JY, et al. Clinical relationship between Hashimoto’s thyroiditis and papillary thyroid cancer. Acta Oncol 2011;50:1228–34. [3] Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 1994;97:418–28. [4] Shen WT, Ogawa L, Ruan D, Suh I, Kebebew E, Duh QY, 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;145:272–5. [5] 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;18:2245–50. [6] Iyer NG, Shaha AR. Central compartment dissection for well differentiated thyroid cancer . . . and the band plays on. Curr Opin Otolaryngol Head Neck Surg 2011;19:106–12. [7] Ahn D, Lee SJ, Park SK, Sohn JH, Park JS. Is comprehensive neck dissection a sole choice for the treatment of recurrent papillary thyroid carcinoma in the lateral neck? Korean J Otorhinolaryngol-Head Neck Surg 2011;54:62–8. [8] Caron NR, Tan YY, Ogilvie JB, Triponez F, Reiff ES, Kebebew E, et al. Selective modified radical neck dissection for papillary thyroid cancer – is level I, II and V dissection always necessary? World J Surg 2006;30:833–40. [9] Turanli S. Is the type of dissection in lateral neck metastasis for differentiated thyroid carcinoma important? Otolaryngol Head Neck Surg 2007;136:957–60. [10] Tisell LE, Nilsson B, Molne J, Hansson G, Fjalling M, Jansson S, et al. Improved survival of patients with papillary thyroid cancer after surgical microdissection. World J Surg 1996;20:854–9. [11] Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167–214. [12] Shen WT, Ogawa L, Ruan D, Suh I, Duh QY, Clark OH. Central neck lymph node dissection for papillary thyroid cancer: the reliability of surgeon judgment in predicting which patients will benefit. Surgery 2010;148:398–403. [13] Pereira JA, Jimeno J, Miquel J, Iglesias M, Munne A, Sancho JJ, et al. Nodal yield, morbidity, and recurrence after central neck dissection for papillary thyroid carcinoma. Surgery 2005;138:1095–100. discussion 1100-1. [14] Kim E, Park JS, Son KR, Kim JH, Jeon SJ, Na DG. Preoperative diagnosis of cervical metastatic lymph nodes in papillary thyroid carcinoma: comparison of ultrasound, computed tomography, and combined ultrasound with computed tomography. Thyroid 2008;18:411–8. [15] Mazzaferri EL, Doherty GM, Steward DL. The pros and cons of prophylactic central compartment lymph node dissection for papillary thyroid carcinoma. Thyroid 2009;19:683–9. [16] Cavicchi O, Piccin O, Caliceti U, De Cataldis A, Pasquali R, Ceroni AR. Transient hypoparathyroidism following thyroidectomy: a prospective study and multivariate analysis of 604 consecutive patients. Otolaryngol Head Neck Surg 2007;137:654–8. [17] White ML, Gauger PG, Doherty GM. Central lymph node dissection in differentiated thyroid cancer. World J Surg 2007;31:895–904.
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Please cite this article in press as: Ahn D, et al. Surgical complications and recurrence after central neck dissection in cN0 papillary thyroid carcinoma. Auris Nasus Larynx (2013), http://dx.doi.org/10.1016/j.anl.2013.06.002