1. Joint Hospital Surgical Grand Round United Christian Hospital
Review of Central Compartment Dissection in Papillary Carcinoma of Thyroid
Joint Hospital Surgical Grand Round
2nd February 2013
Dr. WY Kwan
United Christian Hospital

2. Outline
Introduction
Lymph node metastasis in papillary carcinoma of thyroid (PTC)
Pattern and significance
Central compartment dissection (CCD)
Principles and definition
Benefits and complications of prophylactic CCD
Current guidelines on prophylactic CCD
Extent of dissection
Conclusion

3. Thyroid Cancer The most common endocrine malignancy
~ 650 new cases in 2010 in HK
Papillary thyroid carcinoma (PTC):
the most common histological subtype ~ 80%
Hong Kong Cancer Registry.

4. Lymph Node Metastasis in PTC
Cervical lymph nodes are the principle sites of metastasis
20% - 80% of patients with PTC
Central compartment > Lateral compartment
White ML et al. Central lymph node dissection in differentiated thyroid cancer. World J Surg 2007;5:

5. Central compartment = Level VI Lateral compartment = Levels II - V IIB
IIA VA VB
III IB IA IV VI
VII
Central compartment
= Level VI
Lateral compartment
= Levels II - V
American Thyroid Association Surgery Working Group et al. Consensus statement on the terminology and classification of central neck dissection for thyroid cancer. Thyroid 2009;11:

6. Patterns of LN Metastasis
Thyroid Gland
Ipsilateral
central compartment
Contralateral
central compartment
Thyroid tumour cells spread through the lymphatic system in a sequential fashion
Central compartment is most commonly involved
Skip metastasis (5% to 20%)
Contralateral
lateral compartment
Ipsilateral
lateral compartment
Mediastinal
compartment

7. Significance of LN Metastasis In The Central Compartment?

8. LN Status NOT Included In Most Prognostic Scoring Systems for PTC
AMES- Age, Metastasis, Extrathyroidal extension, Size
AGES- Age, Grade, Extrathyroidal extension, Size
MACIS- Metastasis, Age, Completeness of resection, Invasion (extrathyroidal), Size (modification of the AGES system)
TNM staging- Tumor, Node, Metastasis
AMES from Lahey clinic – age < 40 in man or < 50 in women, size < 5cm = low risks, high risks if any risk factor
AGES from Mayo clinic – age < 45, size < 4cm
FactorsScoredistant Metastasis: Did the tumor spread to other parts of the body outside of the region of the neck?yes = 3 no = 0Age at the time the tumor was foundLess than 39 years = 3.1 over 40 = 0.08 x ageInvasion: Did the surgeon see that the tumor had extended beyond the thyroid into other regions of the neck?yes = 1 no = 0Completeness of resection: Were there parts of the tumor that the surgeon was unable to remove (for example a part that was attached to the windpipe)?yes = 1 no = 0Size of tumor (measured by the pathologist)0.3 x size in cm
20-year survival rate according to MAICS scoreMAICS Score< > yr Survival99%89%56%24%

9. Significance of LN Metastasis
LN metastasis in PTC probably associated with a higher rate of loco-regional recurrence
↑no. of LN metastasis in central compartment
 ↑ risks of lateral compartment metastasis as well ↑↓
Hay ID et al. Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery. 1992;112;6: discussion
Spires JR et al. Metastatic papillary carcinoma of the thyroid: the significance of extranodal extension. Head Neck 1989;11:

10. Significance of LN Metastasis
Conflicting data on the impact of LN metastasis on survival
No prospective RCT available
Swedish study patients
Lymph node metastasis was associated with diminished survival, even when adjusted for TNM staging
Harwood J et al. Significance of lymph node metastasis in differentiated thyroid cancer. Am J Surg. 1978;136:
Lundgren CI et al. Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study. Cancer. 2006;106;3:
Hay ID et al. Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery. 1992;112;6: discussion
Spires JR et al. Metastatic papillary carcinoma of the thyroid: the significance of extranodal extension. Head Neck 1989;11:

11. LN Dissection - Principles
Compartment-oriented LN clearance
Berry picking not recommended

12. Central Compartment Dissection (CCD)
Pre-cricoid laryngeal (Delphian) nodes
Paratracheal nodes
Pre-tracheal nodes
Central Compartment Dissection (CCD)
Bilateral CCD  Bilateral paratracheal LN
Ipsilateral CCD  Ipsilateral paratracheal LN

13. LN Dissection - Definitions
Therapeutic-
Clearance of lymphatic tissues when there are involved LNs preoperatively or intraoperatively
Prophylactic-
No suspicious LN preoperatively or intraoperatively
clinical palpation,
USG,
FNAC,
intraoperative inspection
frozen section

14. Routine Prophylactic Central Compartment Dissection For Patients with PTC?

15. Use Of USG In Detecting LN Metastasis
Sensitivity in detecting cervical LN metastasis: 40 – 83%
Argument:
“In papillary thyroid cancer, preoperative central neck ultrasound detects only macroscopic surgical disease, but negative findings predict excellent long term regional control and survival”
“USG of the central compartment is an age-independent predictor for survival and central compartment recurrence-free survival.
Stulak JM et al. Value of preoperative ultrasonography in the surgical management of initial and reoperative papillary thyroid cancer. Arch Surg 2006;141;5: discussion:

16. Prophylactic CCD And Serum Thyroglobulin (Tg)
Popadich et al, retrospective multicenter study (Australia, USA, UK)
606 patients with PTC, clinically node –ve
Group A: Total thyroidectomy
Group B: Total thyroidectomy with routine CCD
78% ipsilaterasl CCD
Popadich A et al. A multicenter cohort study of total thyroidectomy and routine central lymph node dissection for cN0 papillary thyroid cancer. Surgery. 2011;150;6:

17. Prophylactic CCD And Serum Thyroglobulin (Tg)
Stimulated Thyroglobulin values ng/mL
p = 0.025 NS
Popadich A et al. A multicenter cohort study of total thyroidectomy and routine central lymph node dissection for cN0 papillary thyroid cancer. Surgery. 2011;150;6:
NS = Not statistically significant

18. Prophylactic CCD And Recurrence
Meta-analysis, 5 retrospective studies
1264 patients, FU 6 months to 27 years
Group A: Total thyroidectomy + prophylactic CCD
Group B: Total thyroidectomy alone
Local recurrence rates:
Group A: 2.02% Odds ratio= 1.05 (CI )
Group B: 3.92% Not Significant
“ the available studies have substantial limitations…”
Zetoune T et al Prophylactic central neck dissection and local recurrence in papillary thyroid cancer; a meta-analysis Ann Surg Oncol. 2010; 17:

19. Prophylactic CCD and Survival
Comparative study from Sweden
562 patients, 13-year FU
Disease-specific mortality rate in
CCD (1.6%) VS no CCD (1.9%)
Tisell LE et al. Improved survival of patients with papillary thyroid cancer after surgical microdissection. World J Surg :854–859.

20. Complication Rates Of Total Thyroidectomy +/- CCD
Transient RLN injury: 1% to 13%
Permanent RLN injury: 0% to 3.6%
Transient hypoparathyroidism: 14% to 60%
Permanent hypoparathyroidism: 0% to 11%
Lee YS et al. Extent of routine central lymph node dissection with small papillary thyroid carcinoma. World J Surg 2007;10:
Henry JF et al. Morbidity of prophylactic lymph node dissection in the central neck area in patients with papillary thyroid carcinoma. Langenbecks Arch Surg 1998;2:167-9.
Pereira JA et al. Nodal yield, morbidity, and recurrence after central neck dissection for papillary thyroid carcinoma. Surgery 2005;6:
Sywak M et al. Routine level six lymphadenectomy reduces postoperative thyroglobulin levels in papillary thyroid cancer. Surgery 2006;140:1000–1005
Roh JL et al. Total thyroidectomy plus neck dissection in differentiated papillary thyroid carcinoma patients: Pattern of nodal metastasis, morbidity, recurrence, postoperative levels of serum parathyroid hormone. Ann Surg 2007; 245:604–610.
Palestini N et al. Is central neck dissection a safe procedure in the treatment of papillary thyroid cancer? Our experience. Langenbecks Arch Surg 2008;393:693–698.

21. Complications Of CCD Meta-analysis from UK, 5 studies, 1132 patients
For every 7.7 CCD performed with thyroidectomy, there was one extra case of temporary hypocalcaemia when compared to thyroidectomy alone
“…..There is no increased permanent morbidity by performing the procedure at the same time as thyroidectomy.”
Chrisholm et al. Systematic review and meta-analysis of the adverse effects of thyroidectomy combined with central neck dissection as compared with thyroidectomy alone. Laryngoscope 2009 Jun;119(6):1135-9

22. Prophylactic CCD: Continuous Debates
Pros
LN metastasis have a negative effect on patient outcome
LN metastasis in the central neck cannot be reliably identified preoperatively or at operation
Accurate staging and guides RAI treatment
No increased risks of permanent complications
Reduce morbidity of reoperation for central neck recurrence
Cons
Increased risks of temporary hypoparathyroidism
Survival benefit not certain

23. A Lack Of High Level Evidence
Given the low rates of recurrence
5840 patients would have to be recruited in an RCT to achieve adequate statistical power
Carling T et al. American Thyroid Association design and feasibility of a prospective randomized controlled trial of prophylactic central lymph node dissection for papillary thyroid carcinoma. Thyroid 2012;3:

24. Current Guidelines On Prophylactic Central Compartment Dissection?

25. Comparison Of Guidelines On Prophylactic CCD
National
Comprehensive Cancer Network (1/2013)
“Can be considered”: age <15 or > 45 years; radiation Hx; M1; extrathyroidal extension; tumour > 4cm; aggressive histological variant
American Thyroid Association 2009
“Ipsilateral/ bilateral CCD may be performed”, esp. T3 / T4 tumours. TT without CCD may be appropriate for T1/T2 and noninvasive PTC
British Thyroid Association
2007
Should be performed if: male / age>45 / tumour>4cm /extracapsular or extrathyroidal extension/ suspicious nodes intraoperatively
European Thyroid Association 2006
Controversial benefits; No evidence to improve recurrence or mortality; may perform to guide treatment and follow-up

26. Comparison Of Guidelines On Prophylactic CCD
American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi 2006
“should be performed if the surgeon has specific training” for and experience with thyroid surgical techniques
Papillary thyroid microcarcinoma (<1cm in max diameter) without LN involvement may avoid CCD
Latin American Thyroid Society 2009
“should be performed” for T3 / T4 tumours
Japanese Society of Thyroid Surgeons 2011
Routine central compartment dissection is recommended (Policy of RAI only in high risks patients)

27. Should We Perform Ipsilateral Or Bilateral Central Compartment Dissection?

28. Extent of CCD: Unilateral VS Bilateral
1 out of 4 patients with bilateral CCD done had +ve LN metastasis in contralateral central compartment
Risks of transient hypoparathyroidism
Unilateral CCD < Bilateral CCD
Sadowski BM, et al. Routine bilateral central lymph node clearance for papillary thyroid cancer. Surgery (4): ; discussion 703-5
Grodski S, Cornford L, Sywak M et al. Routine level VI lymph node dissection for papillary thyroid cancer: surgical technique. ANZ J Surg 2007;4:203-8

29. What If The Policy Of Prophylactic CCD Is Not Implemented?

30. Alternative Options Watchful waiting
Empirical radioactive iodine therapy
Regular clinical exam during follow-up
Surveillance USG of neck
Monitoring of thyroglobulin level

31. Conclusions Therapeutic LN dissection if LN metastasis confirmed
Prophylactic CCD helps in accurate staging of PTC but carries increased risks of transient hypoparathyroidism
Prophylactic CCD in high risks groups by experienced surgeons
Ipsilateral CCD could reduce morbidity of transient hypocalcaemia compared with bilateral CCD

32. Thank You!