Morbidity of central compartment clearance: Comparison of lesser versus complete clearance in patients with thyroid cancer

Abstract

Background: Extent of central compartment neck dissection (CCND) in thyroid cancers has been a debate because of associated morbidity. There have been attempts to reduce the extent of surgery in an attempt to decrease morbidity.
Patients and Methods: We analyzed the morbidity of CCND from our prospectively maintained surgical morbidity database. CCND was divided into bilateral complete clearance (BCC) and less than complete clearance (LCC). LCC was performed for clinicoradiologically node negative patients. Rates of hypocalcemia and recurrent laryngeal nerve (RLN) palsy rates were compared for LCC versus BCC. We also classified procedures performed in the central neck according to the extent of dissection.
Results: Of 153 evaluable patients, BCC was performed in 43.8% and LCC in 56.2%. Rate of postoperative hypocalcemia was 40.2% in BCC group versus 17.4% in LCC group. We had an overall RLN palsy rate of 7.4%. There was no significant difference in RLN palsy rates between the groups.
Conclusion: Lesser extent of dissection in central compartment reduces postoperative hypocalcemia but has no influence on RLN palsy rates.

Full text

102 © 2017 Journal of Cancer Research and Therapeutics | Published by Wolters Kluwer - Medknow
Gouri Pantvaidya,
Rakesh Katna,
Anuja Deshmukh,
Deepa Nair,
Anil D’Cruz
DepartmentofHead
andNeckSurgery,Tata
MemorialHospital,
Mumbai,Maharashtra,
India
For correspondence:
Dr.GouriPantvaidya,
Departmentof
HeadandNeck
Oncosurgery,Tata
MemorialHospital,
Parel,Mumbai,
Maharashtra,India.
E-mail:docgouri@
gmail.com
Morbidity of central compartment
clearance: Comparison of lesser versus
complete clearance in patients with thyroid
cancer
ABSTRACT
Background: Extent of central compartment neck dissection (CCND) in thyroid cancers has been a debate because of associated
morbidity. There have been attempts to reduce the extent of surgery in an attempt to decrease morbidity.
Patients and Methods: We analyzed the morbidity of CCND from our prospectively maintained surgical morbidity database. CCND was
divided into bilateral complete clearance (BCC) and less than complete clearance (LCC). LCC was performed for clinicoradiologically
node negative patients. Rates of hypocalcemia and recurrent laryngeal nerve (RLN) palsy rates were compared for LCC versus BCC.
We also classified procedures performed in the central neck according to the extent of dissection.
Results: Of 153 evaluable patients, BCC was performed in 43.8% and LCC in 56.2%. Rate of postoperative hypocalcemia was
40.2% in BCC group versus 17.4% in LCC group. We had an overall RLN palsy rate of 7.4%. There was no significant difference
in RLN palsy rates between the groups.
Conclusion: Lesser extent of dissection in central compartment reduces postoperative hypocalcemia but has no influence on RLN
palsy rates.
KEY WORDS: Central compartment clearance, neck dissection, papillary thyroid cancer, thyroid cancer
Original Article
INTRODUCTION
Differentiated thyroid cancers (DTC) constitute
90% of all thyroid cancers and carry an excellent
long‑term prognosis.[1] The long survival rates
mandate that the quality of life in these patients
is optimal with minimum morbidity of treatment.
The incidence of lymph node metastases is high
in patients with papillary thyroid cancers (PTCs)
ranging from 45% to 60%. Clinical examination
will detect metastases in approximately 10%–15%
of these patients.[2] However, occult central
compartment nodal disease is seen in a much higher
number of patients. Central compartment disease
has been consistently shown to be associated with
increased incidence of locoregional recurrences.[3‑5]
Current standard of care for central compartment
disease is “central compartment clearance (CCC)
from the hyoid superiorly to innominate artery
inferiorly and from carotid to carotid”. However,
the need for such extensive nodal clearance in all
patients with DTC is a matter of debate, because of
the need to balance the associated morbidity and
better disease control.
The main morbidity associated with CCC is
hypocalcemia (postoperative and permanent)
and recurrent laryngeal nerve (RLN) paralysis.
Attempts have been made to decrease the extent
of surgical procedures in the central compartment.
These have been mainly in the form of avoiding
prophylactic CCC in low risk, node negative patients
or performing unilateral procedures for lateralized
lesions.[6,7] However, there is a dearth of prospective
data evaluating morbidity after lesser surgical
procedures. Does performing lesser procedures
in the central compartment actually translate
into lesser morbidity, is not known. We therefore
decided to evaluate the morbidity of CCC when a Access this article online
Website: www.cancerjournal.net
DOI: 10.4103/0973-1482.199378
PMID: ***
Quick Response Code:
This is an open access article distributed under the terms of the Creative Commons
Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix,
tweak, and build upon the work non‑commercially, as long as the author is credited
and the new creations are licensed under the identical terms.
For reprints contact: reprints@medknow.com
Cite this article as: Pantvaidya G, Katna R, Deshmukh A, Nair D, D’Cruz A. Morbidity of central compartment clearance:
Comparison of lesser versus complete clearance in patients with thyroid cancer. J Can Res Ther 2017;13:102-6.
[Downloaded free from http://www.cancerjournal.net on Tuesday, May 23, 2017, IP: 2.88.216.121]

Pantvaidya, et al.: Morbidity of central compartment clearance in thyroid cancer
103
Journal of Cancer Research and Therapeutics - Volume 13 - Issue 1 - January-March 2017
“less than complete clearance” (LCC) was done as compared
to a “bilateral complete clearance” (BCC) in patients with DTC.
PATIENTS AND METHODS
A 30 days morbidity database of all patients undergoing thyroid
surgery was prospectively maintained from January 2012 to
December 2012. We retrospectively analyzed the morbidity
associated with thyroid surgery and central compartment
dissection from this prospective database.
During surgery, all central compartments were divided into
ipsilateral and contralateral compartments depending upon
the laterality of the cancer in the two lobes of the thyroid and
using the trachea as a midline to divide these compartments.
The pretracheal and prelaryngeal nodes were included in the
ipsilateral central compartment. We classified the different
surgical procedures in each central compartment as follows:
• Clearance was defined as “Complete nodal and soft tissue
clearance from carotid artery laterally till trachea in
midline with pretracheal and prelaryngeal clearance and
superiorly from hyoid to innominate artery inferiorly”
• Sampling was defined as “Nodal tissue clearance along
RLNs (paratracheal tissue)”
• Inspection was defined as “Visual inspection and palpation
of central compartment for any enlarged nodes.”
“Berry picking” is not practiced at our institute for central
compartment disease. The indications for the various surgical
procedures in the central compartment are detailed in Table 1.
Patients with histology other than DTC, those who underwent
hemithyroidectomy and patients in whom the central
compartment was not addressed, were excluded from
the analysis. Patients who underwent unilateral central
compartment dissection were also excluded from final
analysis as morbidity in these patients would be minimal
and not comparable to patients having bilateral procedures.
Hypocalcemia and RLN paralysis within 30 days postsurgery
was documented. For hypocalcemia, symptomatology in
the form of tingling numbness and a positive Chovstek’s
sign was considered as clinical hypocalcemia.[8] The serum
calcium levels were done 48–72 h postsurgery. Patients
with serum calcium levels <8.5 mg/dl were considered as
having biochemical hypocalcemia. Patients were classified
as having clinical (C), biochemical (B), or a combination of
clinical and biochemical (C + B) hypocalcemia. For assessing
recurrent laryngeal dysfunction, patients underwent
indirect laryngoscopy to assess cord mobility in the 30 days
postoperative period.
Clinicopathological parameters documented were as follows;
age, sex, previous surgery for thyroid, type of surgery, tumor
histology, pathological central compartment node positivity,
and nodal yield in central compartment.
Parathyroid glands were saved whenever possible and auto
transplanted as and when required.
Analysis
We broadly classified central compartment neck
dissection (CCND) into two groups for analysis according to
the extent of surgical dissection in each central compartment.
The two groups which were formed were “Bilateral
Complete Clearance (BCC)” and “Less than Complete
Clearance (LCC)” [Figure 1]. The BCC group had clearance done
on both sides of the trachea i.e., from hyoid to innominate
and from carotid to carotid. The LCC group had both central
compartments addressed in one of the ways described in
Figure 1. The two groups were compared for nodal yield and
pathological node positivity on final histology. The morbidity
with regard to hypocalcemia and RLN injury was compared
between the two groups.
Statistical analysis was performed using SPSS 19.0
software (SPSS, Inc., Chicago, IL, USA). Categorical data was
compared using Chi‑square analysis. Univariate analysis was
performed and any value of P < 0.05 was considered to be
statistically significant.
Figure 1: Classicationofcentralcompartmentneckdissectionfor
analysis
Table1:TataMemorialHospitalclassicationofproceduresinthecentralcompartmentwiththeirrespectiveindications
Procedure in central
compartment
Description Indications
Inspection “Visual inspection and palpation of central compartment for
enlarged nodes”
cN0 patients
Early thyroid tumors
Sampling “Nodal tissue clearance along recurrent laryngeal
nerves (paratracheal tissue)”
Node negative on USG
Enlarged nodes intraoperatively
T4 tumors with extrathyroidal extension
Clearance (unilateral) “Complete nodal and soft tissue clearance from carotid
artery laterally till trachea in midline with pretracheal and
prelaryngeal clearance upto the innominate artery inferiorly”
Node positive on preoperative USG or intraoperatively
cN0=Clinically node negative, USG=Ultrasonography
[Downloaded free from http://www.cancerjournal.net on Tuesday, May 23, 2017, IP: 2.88.216.121]

Pantvaidya, et al.: Morbidity of central compartment clearance in thyroid cancer
104 Journal of Cancer Research and Therapeutics - Volume 13 - Issue 1 - January-March 2017
RESULTS
Demographic details
Two hundred sixty‑two patients underwent thyroid surgery at
our institute in year 2012. Of these, 57 patients were excluded
because they underwent a hemithyroidectomy or had benign/
other histology. Fifty‑two patients who had either bilateral
central compartment inspection alone or unilateral central
compartment dissection performed were excluded and finally
153 patients were analyzed. The selection of patients according
to the inclusion and exclusion criteria is shown in Figure 2.
As mentioned previously, each patient had a unilateral and
contralateral central compartment which was addressed.
Therefore, 306 central compartments were addressed in
153 patients in the study. Of these, 66 central compartments
were inspected, 37 were sampled and 203 were cleared. The
demographic and treatment details for the patients are shown
in Table 2.
Central compartment neck dissection: Bilateral complete
clearance versus less than complete clearance
BCC was performed in 43.8% patients and LCC in 56.2%
patients. Mean number of nodes retrieved in BCC group was
6.2 (range 1–29), whereas in LCC group, it was 3.4 (range 1–14).
Central compartment nodes were positive in 56.2% patients
on final histology. Nodes positive on histology (pN+) in BCC
group were seen in 46/67 (68.6%) patients and in 40/86 (46.5%)
patients in the LCC group. Seventeen patients did not have a
clearance in bilateral compartments i.e., only inspection or
sampling was done in bilateral central compartments. Only
one of 17 such patients had a positive node, indicating that
inspection and sampling was done for node negative patients
only. However, among the patients who underwent bilateral
clearance, 31% were node negative on histology and may not
have required such extensive clearance.
Morbidity of central compartment neck dissection
Overall 27.4% patients had postoperative hypocalcemia.
Clinical hypocalcemia was documented in 7 patients,
biochemical hypocalcemia in 9 patients, and combined clinical
and biochemical hypocalcemia in 26 patients. In the BCC group,
rate of postoperative hypocalcemia was 40.2% compared to
17.4% in the LCC group, which was significant on univariate
analysis (P = 0.002).
Five RLNs were sacrificed intraoperatively because of gross
involvement by disease. These five patients have not been
included in the analysis of postoperative RLN paralysis.
Eleven patients had postoperative RLN palsy (7.4%). The
RLN palsy rate was 3.4% if RLNs at risk were considered for
the analysis.
Among these 11 patients with RLN paralysis, 10 patients had
multiple nodes positive in the central compartment. In two
of these patients, the nodal disease was shaved off the nerve,
and in another three patients, there was documented excess
handling of the RLN to remove the nodal disease.
On comparing the two groups; The BCC group had RLN palsy
rate of 4.4% compared to 9.3% in LCC group (P = 0.21). The LCC
group had higher number of recurrent surgical explorations
as compared with the BCC group, i.e., 36 (42%) versus
17 (25%); (P = 0.01). To explain the higher incidence of RLN
palsy in the LCC group, we evaluated only per primum cases.
However, even with the exclusion of cases undergoing redo
surgeries, the RLN palsy rate was higher in the LCC group as
compared to the BCC group (14.5% vs. 2%).
DISCUSSION
CCND in DTC has been a matter of controversy because
of associated morbidity, especially in the clinically node
negative (cN0) patient. American Thyroid Association (ATA)
recommendations for CCND are not based on level I evidence
but on large retrospective studies or nonrandomized
Figure 2: Flow chart depicting selection of patients
Table 2: Demographic details of the patient population
Variable n (%)
Mean age 41 years (13-84)
Sex (male:female) 1:1.6
T staging
Tx 32
T1 28
T2 51
T3 25
T4 17
Nodal staging
N0 59
N1a 10
N1b 84
Procedure performed (%)
Total thyroidectomy 100 (65.3)
Completion thyroidectomy 30 (19.6)
Thyroid bed exploration 13 (8.4)
Central compartment dissection 10 (6.5)
Previous surgical intervention 53 (34.6)
Histology (%)
PTC 118 (77.2)
FVPTC 34 (22.2)
Follicular carcinoma 1 (0.6)
PTC=Papillary thyroid carcinoma, FVPTC=Follicular variant of papillary thyroid
carcinoma
[Downloaded free from http://www.cancerjournal.net on Tuesday, May 23, 2017, IP: 2.88.216.121]

Pantvaidya, et al.: Morbidity of central compartment clearance in thyroid cancer
105
Journal of Cancer Research and Therapeutics - Volume 13 - Issue 1 - January-March 2017
prospective data.[9] The extent of surgical clearance within the
central compartment is not yet standardized and often based
on the surgeon’s discretion.
The controversy on the extent of neck dissection stems
from many issues such as division of a anatomically single
central compartment into an ipsilateral and contralateral
compartment, need for complete dissection from carotid to
carotid and hyoid to innominate in all cases. The ATA guidelines
define CCND as clearance of at least one paratracheal region
with the prelaryngeal, pretracheal nodes.[9] Most surgeons
use a combination of procedures depending on preoperative
node positivity, intraoperative findings after inspection of
the central compartment and poor prognostic features of the
thyroid malignancy.
At our institute, we have tried to define the various extents
of surgical procedures in the central compartment along
with their indications. We defined sampling as removal of
the nodes and fibrofatty tissue medial to the RLN. This would
potentially prevent the injury and vascular compromise to
the parathyroid glands as the inferior thyroid artery would
provide blood supply to the lower parathyroid gland from the
lateral aspect of the gland.
We prospectively documented the morbidity with regard
to RLN paralysis and hypocalcemia when these procedures
were performed. The main hypothesis behind performing less
than a complete bilateral clearance is to decrease morbidity
associated with extensive bilateral dissections. To the best of
our knowledge, there are no studies in literature, which have
prospectively tested this hypothesis. Whether performing
less surgery in the central compartment really reduces
complications of RLN paralysis and hypocalcemia is unknown.
In our study, inspection and sampling were only performed on
patients who were clinicoradiologically node negative. Only
one of the17 patients who underwent these procedures had a
positive node on histopathology. Needless to say, this cannot
be applied to patients who underwent inspection alone as
no tissue was submitted for histopathology and a true node
negative status in these central compartments can only be
confirmed on long‑term follow‑up.
Central compartment nodes were positive in 56.2% patients
on final histopathology which is similar to the reports in
literature.[10] The nodal positivity rates varied in the two
groups (BCC ‑ 68.6% vs. LCC ‑ 46.5%) expectedly so, as more
patients with positive lymph nodes underwent a BCC. Nodal
yield may act as an indirect marker of adequacy of CCC
though this has not been very well validated. There are few
studies which have reported nodal yield in CCND to around
5–6 nodes.[11,12] Similarly, in a large retrospective series of
PTC, CCND was defined as adequate if there were a minimum
number of 5 nodes on histology.[13] When we looked at the
nodal yield in our two defined groups, we found that mean
number of nodes retrieved in BCC group was 6.2 compared
to 3.4 in LCC group.
Incidence of postoperative hypocalcemia in our cohort was
27.4%, which is in range reported in literature across various
studies.[14‑16] The incidence of postoperative hypocalcemia
was significantly lower in LCC group (P = 0.002). However
the impact of this on the permanent hypocalcemia rate is not
known from this study as we have not included long term follow
up of these patients. It may therefore not be justified to use
lower rates of temporary hypocalcemia as a reason to perform
lesser CCCs. Similar findings of lower hypocalcemia have also
been documented by Moo et al. in a study looking at results of
ipsilateral versus bilateral CCC.[17] In another study by Giordano
et al., both temporary and permanent hypoparathyroidism
was significantly higher in the bilateral clearance group as
compared to the ipsilateral clearance group.[18]
Incidence of permanent RLN paralysis in total thyroidectomy
with CCND has been documented to be 1%–12% by various
authors.[11,18‑20] Most of these studies are retrospective in nature
and may underreport RLN paralysis if routine postoperative
evaluation in all patients, irrespective of symptomatology, is
not done. We report a RLN paralysis rate of 7.4% in our series.
When we compared performing lesser central clearances to
a complete bilateral clearance, we found that there was no
difference in the RLN palsy. In a metanalysis by Zhu et al., there
were no significant differences in temporary or permanent
vocal cord paralysis rates when comparing no central
compartment dissection versus prophylactic node dissection
in node negative patients.[21] A similar finding was noted in a
study by Giordano et al., where they retrospectively evaluated
RLN palsy rates comparing ipsilateral clearance versus
bilateral clearance. They too found no difference in their
palsy rates.[18] Contrary to the hypothesis that lesser surgery
would result in lesser morbidity, we found no difference in
RLN palsy rates.
CONCLUSION
Lesser surgery or avoidance of prophylactic surgery in the
central compartment is being advocated in an attempt to
decrease the morbidity in a cancer where survival outcomes
are extremely favorable. However, this hypothesis has not
been adequately studied. There appears to be a definite
decrease in the rates of temporary hypoparathyroidism when
lesser procedures are performed in the central compartment.
However, its effect on permanent hypoparathyroidism is
not known. RLN palsy rates do not seem to be any different
when lesser procedures are performed. Good technique of
dissection of the RLN is probably of utmost importance,
irrespective of whether unilateral or bilateral procedures are
being performed. To help standardize reporting of central
compartment procedures, we recommend reporting unilateral
versus bilateral procedures and classifying each of these
procedures as per our classification system.
[Downloaded free from http://www.cancerjournal.net on Tuesday, May 23, 2017, IP: 2.88.216.121]

Pantvaidya, et al.: Morbidity of central compartment clearance in thyroid cancer
106 Journal of Cancer Research and Therapeutics - Volume 13 - Issue 1 - January-March 2017
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
1. Shaha AR. Implications of prognostic factors and risk groups in
the management of differentiated thyroid cancer. Laryngoscope
2004;114:393‑402.
2. Shaha AR, Shah JP, Loree TR. Patterns of nodal and distant metastasis
based on histologic varieties in differentiated carcinoma of the
thyroid. Am J Surg 1996;172:692‑4.
3. Mazzaferri EL. Papillary thyroid carcinoma: Factors influencing
prognosis and current therapy. Semin Oncol 1987;14:315‑32.
4. Hughes CJ, Shaha AR, Shah JP, Loree TR. Impact of lymph node
metastasis in differentiated carcinoma of the thyroid: A matched‑pair
analysis. Head Neck 1996;18:127‑32.
5. 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.
6. Raffaelli M, De Crea C, Sessa L, Giustacchini P, Revelli L, Bellantone C,
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;152:957‑64.
7. Randolph GW. Papillary cancer nodal surgery and the advisability of
prophylactic central neck dissection: Primum, non nocere. Surgery
2010;148:1108‑12.
8. Hoffman E. The Chvostek sign; a clinical study. Am J Surg
1958;96:33‑7.
9. 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;19:1167‑214.
10. Mirallié E, Visset J, Sagan C, Hamy A, Le Bodic MF, Paineau J.
Localization of cervical node metastasis of papillary thyroid
carcinoma. World J Surg 1999;23:970‑3.
11. Sywak M, Cornford L, Roach P, Stalberg P, Sidhu S, Delbridge L.
Routine ipsilateral level VI lymphadenectomy reduces postoperative
thyroglobulin levels in papillary thyroid cancer. Surgery
2006;140:1000‑5.
12. Hughes DT, White ML, Miller BS, Gauger PG, Burney RE, Doherty GM.
Influence of prophylactic central lymph node dissection on
postoperative thyroglobulin levels and radioiodine treatment in
papillary thyroid cancer. Surgery 2010;148:1100‑6.
13. Grant CS, Stulak JM, Thompson GB, Richards ML, Reading CC, Hay ID.
Risks and adequacy of an optimized surgical approach to the primary
surgical management of papillary thyroid carcinoma treated during
1999‑2006. World J Surg 2010;34:1239‑46.
14. Palestini N, Borasi 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;393:693‑8.
15. Witt RL, McNamara AM. Prognostic factors in mortality and morbidity
in patients with differentiated thyroid cancer. Ear Nose Throat J
2002;81:856‑63.
16. Cheah WK, Arici C, Ituarte PH, Siperstein AE, Duh QY, Clark OH.
Complications of neck dissection for thyroid cancer. World J Surg
2002;26:1013‑6.
17. Moo TA, Umunna B, Kato M, Butriago D, Kundel A, Lee JA, et al.
Ipsilateral versus bilateral central neck lymph node dissection in
papillary thyroid carcinoma. Ann Surg 2009;250:403‑8.
18. Giordano D, Valcavi R, Thompson GB, Pedroni C, Renna L, Gradoni P,
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;22:911‑7.
19. 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;245:604‑10.
20. Henry JF, Gramatica L, Denizot A, Kvachenyuk A, Puccini M,
Defechereux T. Morbidity of prophylactic lymph node dissection in
the central neck area in patients with papillary thyroid carcinoma.
Langenbecks Arch Surg 1998;383:167‑9.
21. Zhu W, Zhong M, Ai Z. Systematic evaluation of prophylactic neck
dissection for the treatment of papillary thyroid carcinoma. Jpn J
Clin Oncol 2013;43:883‑8.
[Downloaded free from http://www.cancerjournal.net on Tuesday, May 23, 2017, IP: 2.88.216.121]