Abstract
Central compartment nodes of neck are the first echelon nodes in papillary thyroid cancers (PTC). This study analyses the adverse parameters associated with central compartment nodal metastasis in cN0 PTC and also the usefulness of performing central compartment neck dissection routinely. A total of 236 patients with cNo PTC who underwent prophylactic central compartment neck dissection, from January 2008 to June 2017 in the Department of Oncology, Madurai Medical College, were included in study. Analysis of various adverse factors associated with central compartment nodal metastasis was made. Patients (46.18%) had metastatic nodes in the central compartment. Incidence of nodal metastasis increased with tumour size, capsular invasion, extrathyroidal extension, tracheal invasion and pulmonary metastasis. More than 50% patients did not have any of the statistically significant known adverse risk factors except for age and sex. Routine central compartment neck dissection has therapeutic value in PTC even in absence of known adverse factors and can be recommended in cases of clinically negative nodes. A meticulous dissection in experienced hands carries less complication rates as with thyroidectomy alone. In a resource limited country like ours, where the cost of re-surgery and radioiodine scans are high, a meticulous initial surgery incorporating central compartment neck dissection would really mean a difference.
Keywords: Prophylactic central compartment neck dissection, Papillary thyroid cancer, cN0 PTC, Nodal metastasis
Introduction
Papillary thyroid carcinoma (PTC) is the most common histology of thyroid cancer and constitutes more than 80% of thyroid cancers. PTCs have excellent prognosis overall with 10-year survival rates exceeding 90%. Cervical nodal metastasis is a frequent accomplice in PTC with involvement of central compartment nodes in 20–50% of patients and lateral compartment nodes in 10–30% of patients. The standard of care for PTC (> 1 cm) with nodal metastasis on diagnosis is total thyroidectomy with therapeutic central and lateral compartment neck dissection [1]. Although the American Thyroid Association guidelines recommend prophylactic central compartment neck dissection (PCND) for all patients with PTC, it is not uniformly practiced and is still a matter of debate. Adverse factors associated with metastasis to the central compartment nodes include large tumour size, extrathyroidal extension, aggressive variants, younger age, and distant metastasis which are described in literature already [2–5]. The objective of this study is to analyse the various adverse parameters associated with central compartment nodal metastasis in clinically node negative PTC and also its usefulness as being performed routinely irrespective of the presence of adverse factors.
Methods
Between January 2008 and June 2017, 510 patients underwent surgery for papillary thyroid carcinoma in the Department of Oncology, Madurai Medical College, Madurai, India. Of these, 236 patients had cNo PTC and were included in this study. Exclusion criteria included histology other than papillary thyroid cancer; lymphnodal involvement detected preoperatively by clinical examination or ultrasound. Patients without nodal involvement by clinical examination or ultrasound were designated cN0. Informed written consent was obtained from the participants. The patients were evaluated preoperatively with ultrasound of the neck, serum-free thyroid hormones (FT3, FT4), and thyroid stimulating hormone (TSH) levels, FNAC of thyroid lesion. Fibreoptic laryngoscopy was performed to document the vocal cord status of the patients.. PCND was performed for all those 236 patients. The template for nodal dissection included bilateral central compartments extending superiorly up to hyoid bone inferiorly up to brachiocephalic vessel, and laterally up to carotid arteries. The details collected for each patient included age, gender, tumour size, histopathologic features, nodal status, and postoperative complications. Postoperatively, the patients were planned to undergo radioactive iodine ablation (RIA) when indicated and kept under follow-up. Clinical examination and neck ultrasound was performed on each visit. Serum thyroglobulin was performed at 6th month and annually thereafter and when clinically indicated. A detailed analysis of various adverse factors associated with central compartment nodal metastasis was made. Figure 1 shows the method of study.
Fig.1.
Flowchart showing method of study
Statistical Analysis
Descriptive statistics were reported as mean (SD) for continuous variables, frequencies (percentage) for categorical variables. Univariate logistic regression model was used to find the significant determinants. A two-sided α of less than 0.05 was considered statistically significant. Data were statistically evaluated with IBM SPSS Statistics for Windows, Version 20.0., IBM Corp., Chicago, IL.
Results
Of the 236 patients with cNo PTC, 109 patients had metastatic nodes in central compartment (46.18%). Metastatic central compartment nodes were found in 40 of 134 females (29.85%) and 69 of 102 males (67.64%). Average nodal yield was 4.2 (3 to 8). Among 109 node positive patients, 61 patients had single node positive, and 48 patients had multiple positive nodes. Incidence of nodal metastasis was 13.6% in pT1a, 22.8% in pT1b, 49.13% in pT2, 92.45% in pT3, 100% in pT4, 100% in capsular invasion (12 patients), 100% in extrathyroidal extension (9 patients), 100% in tracheal invasion (one patient), and 100% in pulmonary metastasis (1 patient) as shown in Table 1. In our study, 109 of the 236 (46.2%) patients had involvement of central compartment nodes. More than 50% of patients did not have any of these known adverse risk factors, except that in these categories 69 (63.3%) were males, 76 (69.7%) were less than 45 years of age without other proposed risk factors. The other proposed risk factors listed in our study were tumour size pT1b and above in 37(66.1%), extrathyroidal extension in 9 (8.3%), capsular invasion in 12 (11.1%), tracheal invasion in 1 (0.9%), and pulmonary metastasis in 1 (0.9%) patients. Out of these other proposed risk factors, only extrathyroidal extension and capsular invasion even have a significant odds ratio. But they have got broader confidence interval; therefore, uncertainty is greater. Moreover, these statistically significant risk factors involve only less than 50% of patients with central compartment nodes. Postoperative complications seen were transient hypocalcemia in 19 patients (5.65%), prolonged hypocalcemia in 2 patients (< 1%), and recurrent laryngeal nerve (RLN) injury in 3 patients (1.2%) which recovered in 2–3 months. One patient had permanent hypoparathyroidism. Mortality was nil in this group. RIA was indicated in 112 patients as shown in Fig. 2. Nodal metastasis was the only indication in 84 out of 112 patients. RIA was defaulted by 91 patients, and cost factor was the reason with majority of patients for defaulting RIA. No patients developed recurrence after a median follow-up of 5 years, and 3 patients died of causes unrelated to thyroid malignancy on follow-up.
Table 1.
Univariate analysis of risk factors associated with positive central compartment nodes
| S. No | Risk factor | Involvement of central compartment nodes | Odds Ratio(OR) | 95% CI | P value | |
|---|---|---|---|---|---|---|
| Yes (n = 109) | No (n = 127) | |||||
| 1 | Gender | < 0.001 Sig | ||||
| Male | 69 (63.3) | 33 (25.9) | 4.91 | 2.82 to 8.57 | ||
| Female | 40 (36.7) | 94 (74.1) | 1 | |||
| 2 | Age | |||||
| < 45 years | 76 (69.7) | 48 (37.8) | 3.79 | 2.20 to 6.53 | < 0.001 Sig | |
| > 45 years | 33 (30.3) | 79 (62.2) | 1 | |||
| 3 | Tumour size | |||||
| < 1 cm | 37 (33.9) | 58 (45.7) | 1 | 0.96 to 2.77 | 0.06 NS | |
| PT1b and above | 72 (66.1) | 69 (54.3) | 1.63 | |||
| 4 | Extrathyroidal extension | |||||
| Present | 9 (8.3) | 1 (0.9) | 11.34 | 1.41 to 91.00 | 0.02 Sig | |
| Absent | 100 (91.7) | 126 (99.1) | 1 | |||
| 5 | Capsular invasion | |||||
| Present | 12 (11.1) | 2 (1.6) | 7.73 | 1.69 to 35.36 | 0.008 Sig | |
| Absent | 97 (88.9) | 125 (98.4) | 1 | |||
| 6 | Tracheal invasion | |||||
| Present | 1 (0.9) | 0 (0) | 3.52 | 0.14 to 87.43 | 0.44 NS | |
| Absent | 108 (99.1) | 127 (100) | 1 | |||
| 7 | Pulmonary metastasis | |||||
| Present | 1 (0.9) | 0 (0) | 3.52 | 0.14 to 87.43 | 0.44 NS | |
| Absent | 108 (99.1) | 127 (100) | 1 |
Sig statistically significant, NS statistically non-significant
Fig. 2.
Indications for RIA
Discussion
PTCs account for more than 80% of thyroid cancers. Nodal metastasis is very common in PTC. Unlike many other malignancies, nodal metastasis in PTC does not always reflect in survival rates. Nodal metastasis in young patients (< 45 years) is not associated with decreased survival, whereas older patients have decreased survival rates [6]. However, nodal metastasis at diagnosis is uniformly associated with increased recurrence rate in all age group which substantially increases disease-related morbidity [7].
Central compartment nodes of neck include pretracheal, paratracheal, and prelaryngeal nodes. These are the first echelon nodes in PTC. Papillary thyroid cancer spreads in an orderly fashion from central neck to lateral neck nodes. Skip metastasis can occur in 5–25% [8]. A disease in lateral neck nodes mandates meticulous central node dissection due to this orderly spread and is usually done as a part of therapeutic neck dissection. However, performing central neck dissection as a routine in all cN0 cases is still under debate.
The sensitivity of preoperative sonography and peroperative evaluation to accurately detect lymph node involvement is low [9, 10]. Adverse factors associated with central compartment nodal metastasis from our study were pT1b and above tumours, male sex, age less than 45, capsular invasion,tracheal invasion, gross extrathyroid disease, and distant metastasis. This has been described in literature [2–5]. However, in our study, we see that nearly 50% of these patients who had metastatic central compartment nodes did not have any of these adverse factors except male sex. Male sex was a risk factor in our study, although the disease is more common in females.
The surgical society stands split into proponents and opponents for PCND. The proponents have put forth numerous factors which favour PCND. One of those is improved TNM staging and stratification of RIA therapy which can reduce recurrence and hence impact long-term survival. In our study, 61.6% of patients overall and 29% of patients above 45 years of age are upstaged from cN0 to pN1. This leads to change in management as those with nodal metastasis benefit from RIA therapy. This is in accordance with two retrospective studies [11, 12]. Nodal metastasis was the only indication for RIA in majority of patients in our study. However, a huge number of patients defaulted RIA due to lack of awareness about its importance and cost factor.
Central compartment dissection involves meticulous identification of RLN and dissecting fibrofatty tissue anterior medial and posterior to nerve, identification and preservation of parathyroids, and their blood supply. In experienced hands, complication rates are comparable with thyroidectomy alone. Barczynski et al. [13] in their study showed that PCND followed by personalized RIA therapy improved a 10-year disease-specific survival without increase in permanent morbidity. This view is supported by several other studies [14, 15]. Our study too has shown less complication rates comparable to above mentioned series.
However, when reoperation is performed in cases of nodal recurrence, there is considerable increase in complication rates [16]. Missed metastatic lymph nodes are typically found along the RLN in the trachea-oesophageal groove and can increase the chance of RLN injury in re-surgeries. RIA is unreliable in eradicating residual macroscopic disease. PCND would logically lead to reduction in relapse and consequently reoperation.
Although ATA guidelines recommend prophylactic central compartment neck dissection in all cN0 PTCs, it is not practiced in many centres. This is one of the large volume studies favouring routine CCND in cN0 PTCs. The limitation of this study is that it is a single centre study.
Conclusion
A routine central compartment neck dissection has therapeutic value in papillary thyroid cancers even in absence of known adverse factors and can be recommended even in cases of clinically negative nodes. A meticulous dissection in experienced hands carries less complication rates as with thyroidectomy alone. In a resource limited country like ours, where the cost of re-surgery and radioiodine scans are high, a meticulous initial surgery incorporating central compartment neck dissection would really mean a difference.
Declarations
Ethics Approval
This is an observational study and hence exempted from ethical approval by institutional ethical committee.
Informed Consent
Informed consent was obtained from all individuals included in this study for participation in study and publication.
Consent for Publication
Informed consent was obtained from participants for publication of data in the journal.
Conflict of Interest
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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