Review of Review of Central Compartment Dissection inCentral Compartment Dissection in

Papillary Carcinoma of ThyroidPapillary Carcinoma of Thyroid

Joint Hospital Surgical Grand RoundJoint Hospital Surgical Grand Round22ndnd February 2013 February 2013

Dr. WY KwanDr. WY KwanUnited Christian HospitalUnited Christian Hospital

OutlineOutlineIntroductionIntroductionLymph node metastasis in papillary carcinoma of Lymph node metastasis in papillary carcinoma of

thyroid (PTC)thyroid (PTC)Pattern and significancePattern and significance

Central compartment dissection (CCD)Central compartment dissection (CCD)Principles and definitionPrinciples and definitionBenefits and complications of prophylactic CCDBenefits and complications of prophylactic CCDCurrent guidelines on prophylactic CCDCurrent guidelines on prophylactic CCDExtent of dissectionExtent of dissection

ConclusionConclusion

Thyroid CancerThyroid CancerThe most common endocrine malignancyThe most common endocrine malignancy~ 650 new cases in 2010 in HK~ 650 new cases in 2010 in HK

Papillary thyroid carcinoma (PTC):Papillary thyroid carcinoma (PTC):the most common histological subtype ~ 80%the most common histological subtype ~ 80%

Hong Kong Cancer Registry. http://www3.ha.org.hk/cancereg/Statistics.html#cancerfacts

Lymph Node Metastasis in Lymph Node Metastasis in PTCPTC

Cervical lymph nodes are the principle Cervical lymph nodes are the principle sites of metastasissites of metastasis

20% - 80% of patients with PTC20% - 80% of patients with PTCCentral compartment > Lateral Central compartment > Lateral

compartmentcompartment

White ML et al. Central lymph node dissection in differentiated thyroid cancer. World J Surg 2007;5:895-904

IIB

IIA

VA

VB

III

IBIA

IV

VI

VII

American Thyroid Association Surgery Working Group et al. Consensus statement on the terminology and classification of central neck dissection for thyroid cancer. Thyroid 2009;11:1153-8.

Central Central compartment compartment = Level VI= Level VI

Lateral Lateral compartmentcompartment= Levels II - V= Levels II - V

Patterns of LN MetastasisPatterns of LN Metastasis

Ipsilateralcentral compartment

Contralateralcentral compartment

Ipsilaterallateral compartment

Contralaterallateral compartment

Mediastinalcompartment

Thyroid Gland

Significance of LN Metastasis Significance of LN Metastasis In The Central Compartment?In The Central Compartment?

AMESAMES-- AAge, ge, MMetastasis, etastasis, EExtrathyroidal xtrathyroidal extension, extension, SSizeize

AGESAGES-- AAge, ge, GGrade, rade, EExtrathyroidal extension, xtrathyroidal extension, SSizeize

MACISMACIS-- MMetastasis, etastasis, AAge, ge, CCompleteness of ompleteness of resection, resection, IInvasion nvasion

(extrathyroidal), (extrathyroidal), SSize (modification of ize (modification of the AGES system)the AGES system)

TNMTNM staging- staging- T Tumor, umor, NNode, ode, MMetastasis etastasis

LN Status NOT Included In Most LN Status NOT Included In Most Prognostic Scoring Systems for Prognostic Scoring Systems for

PTCPTC

LN metastasis in PTC LN metastasis in PTC probably associatedprobably associated with a higher rate of with a higher rate of loco-regional recurrenceloco-regional recurrence

↑↑no.no. of LN metastasis in central compartment of LN metastasis in central compartment ↑↑ risks of lateral compartment metastasis as risks of lateral compartment metastasis as

wellwell

Significance ofSignificance ofLN MetastasisLN Metastasis

Hay ID et al. Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery. 1992;112;6:1139-46. discussion 1146-1147Spires JR et al. Metastatic papillary carcinoma of the thyroid: the significance of extranodal extension. Head Neck 1989;11: 242-246

Conflicting dataConflicting data on the impact of LN metastasis on the impact of LN metastasis on on survivalsurvival

No prospective RCT availableNo prospective RCT available

Significance ofSignificance ofLN MetastasisLN Metastasis

Harwood J et al. Significance of lymph node metastasis in differentiated thyroid cancer. Am J Surg. 1978;136:107-112Lundgren CI et al. Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study. Cancer. 2006;106;3:524-531 Hay ID et al. Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery. 1992;112;6:1139-46. discussion 1146-1147Spires JR et al. Metastatic papillary carcinoma of the thyroid: the significance of extranodal extension. Head Neck 1989;11: 242-246

LN Dissection - LN Dissection - PrinciplesPrinciples

Compartment-oriented LN clearanceCompartment-oriented LN clearanceBerry picking not recommendedBerry picking not recommended

Pre-cricoid laryngeal

(Delphian) nodes

Paratracheal nodes

Pre-tracheal nodes

Central Compartment Dissection Central Compartment Dissection (CCD)(CCD)

Bilateral CCD Bilateral CCD Bilateral paratracheal LN Bilateral paratracheal LNIpsilateral CCD Ipsilateral CCD Ipsilateral paratracheal LN Ipsilateral paratracheal LN

LN Dissection - LN Dissection - DefinitionsDefinitions

Therapeutic-Therapeutic-Clearance of lymphatic tissues when there are Clearance of lymphatic tissues when there are

involved LNs preoperatively or intraoperativelyinvolved LNs preoperatively or intraoperatively

Prophylactic-Prophylactic-No suspicious LN preoperatively or intraoperativelyNo suspicious LN preoperatively or intraoperatively

Routine Routine ProphylacticProphylactic Central Central Compartment Dissection For Compartment Dissection For Patients with PTC?Patients with PTC?

Use Of USG In DetectingUse Of USG In DetectingLN Metastasis LN Metastasis

Sensitivity in detecting cervical LN Sensitivity in detecting cervical LN metastasis: 40 – 83%metastasis: 40 – 83%

Stulak JM et al. Value of preoperative ultrasonography in the surgical management of initial and reoperative papillary thyroid cancer. Arch Surg 2006;141;5:489-494. discussion: 494-496

Popadich et al, retrospective multicenter study Popadich et al, retrospective multicenter study (Australia, USA, UK)(Australia, USA, UK)

606 patients with PTC, clinically node –ve606 patients with PTC, clinically node –ve

Group A: Total thyroidectomyGroup A: Total thyroidectomyGroup B: Total thyroidectomy with routine CCDGroup B: Total thyroidectomy with routine CCD

Prophylactic CCD And Prophylactic CCD And Serum Thyroglobulin (Tg)Serum Thyroglobulin (Tg)

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;6:1048-57

Stim

ulat

ed T

hyro

glob

ulin

val

ues

Stim

ulat

ed T

hyro

glob

ulin

val

ues

ng/m

Lng

/mL

p = 0.025p = 0.025

NSNS NSNS

NS = Not statistically significantNS = Not statistically significantPopadich A et al. A multicenter cohort study of total thyroidectomy and routine central lymph node dissection for cN0 papillary thyroid cancer. Surgery. 2011;150;6:1048-57

Prophylactic CCD And Prophylactic CCD And Serum Thyroglobulin (Tg)Serum Thyroglobulin (Tg)

Prophylactic CCD And Prophylactic CCD And RecurrenceRecurrence

Meta-analysisMeta-analysis, 5 retrospective studies, 5 retrospective studies1264 patients, FU 6 months to 27 years1264 patients, FU 6 months to 27 years

Group A: Total thyroidectomy + prophylactic CCDGroup A: Total thyroidectomy + prophylactic CCDGroup B: Total thyroidectomy aloneGroup B: Total thyroidectomy alone

Local recurrence rates:Local recurrence rates:Group A: 2.02%Group A: 2.02% Odds ratio= 1.05 (CI 0.48-2.31) Odds ratio= 1.05 (CI 0.48-2.31)Group B: 3.92%Group B: 3.92% Not SignificantNot Significant

“ “ the available studies have substantial the available studies have substantial limitations…”limitations…”

Zetoune T et al Prophylactic central neck dissection and local recurrence in papillary thyroid cancer; a meta-analysis Ann Surg Oncol. 2010; 17:3287-93

Prophylactic CCD and Prophylactic CCD and SurvivalSurvival

Comparative study from SwedenComparative study from Sweden562 patients, 13-year FU562 patients, 13-year FU

Disease-specific mortality rateDisease-specific mortality rate in in CCD (CCD (1.6%1.6%) VS no CCD () VS no CCD (1.9%1.9%))

Tisell LE et al. Improved survival of patients with papillary thyroid cancer after surgical microdissection. World J Surg 1996. 20:854–859.

Complication Rates Of Total Complication Rates Of Total Thyroidectomy +/- CCDThyroidectomy +/- CCD

Transient RLN injury: 1% to 13%Transient RLN injury: 1% to 13%Permanent RLN injury: 0% to 3.6%Permanent RLN injury: 0% to 3.6%

Transient hypoparathyroidism: 14% to 60%Transient hypoparathyroidism: 14% to 60%Permanent hypoparathyroidism: 0% to 11% 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;10:1954-9.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;6:1095-100Sywak M et al. Routine level six lymphadenectomy reduces postoperative thyroglobulin levels in papillary thyroid cancer. Surgery 2006;140:1000–1005Roh 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.

Complications Of CCDComplications Of CCDMeta-analysisMeta-analysis from UK, 5 studies, 1132 patients from UK, 5 studies, 1132 patients

For For every 7.7 CCDevery 7.7 CCD performed with thyroidectomy, there performed with thyroidectomy, there was was one extra case of temporary hypocalcaemiaone extra case of temporary hypocalcaemia when when compared to thyroidectomy alonecompared to thyroidectomy alone

“…“…..There is ..There is no increased permanent morbidityno increased permanent morbidity by by performing the procedure at the same time as performing the procedure at the same time as thyroidectomy.”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

Prophylactic CCD: Prophylactic CCD: Continuous DebatesContinuous Debates

ProsPros LN metastasis have a LN metastasis have a negative negative

effecteffect on patient outcome on patient outcome LN metastasis in the central LN metastasis in the central

neck neck cannot be reliably cannot be reliably identifiedidentified preoperatively or at preoperatively or at operationoperation

Accurate Accurate stagingstaging and guides and guides RAI treatmentRAI treatment

NoNo increased risks of increased risks of permanent complicationspermanent complications

ReduceReduce morbidity of morbidity of reoperation reoperation for central neck recurrencefor central neck recurrence

ConsCons Increased risks of Increased risks of

temporary temporary hypoparathyroidismhypoparathyroidism

Survival benefit Survival benefit not not certaincertain

A Lack Of High Level A Lack Of High Level EvidenceEvidence

Given the low rates of recurrenceGiven the low rates of recurrence5840 patients would have to be recruited 5840 patients would have to be recruited

in an RCT to achieve adequate statistical in an RCT to achieve adequate statistical powerpower

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;3:237-44.

Current Guidelines On Current Guidelines On Prophylactic Central Prophylactic Central Compartment Dissection?Compartment Dissection?

Comparison Of Guidelines On Comparison Of Guidelines On Prophylactic CCDProphylactic CCD

National National Comprehensive Comprehensive Cancer Network Cancer Network (1/2013)(1/2013)

““Can be considered”:Can be considered”: age <15 or > 45 years; age <15 or > 45 years; radiation Hx; M1; extrathyroidal extension; radiation Hx; M1; extrathyroidal extension; tumour > 4cm; aggressive histological varianttumour > 4cm; aggressive histological variant

American Thyroid American Thyroid Association 2009Association 2009

““Ipsilateral/ bilateral CCD may be performed”,Ipsilateral/ bilateral CCD may be performed”, esp. T3 / T4 tumours. TT without CCD may esp. T3 / T4 tumours. TT without CCD may be appropriate for T1/T2 and noninvasive be appropriate for T1/T2 and noninvasive PTCPTC

British Thyroid British Thyroid AssociationAssociation20072007

Should be performedShould be performed if: male / age>45 / if: male / age>45 / tumour>4cm /extracapsular or extrathyroidal tumour>4cm /extracapsular or extrathyroidal extension/ suspicious nodes intraoperativelyextension/ suspicious nodes intraoperatively

European European Thyroid Thyroid Association 2006Association 2006

Controversial benefitsControversial benefits; No evidence to ; No evidence to improve recurrence or mortality; improve recurrence or mortality; may perform may perform to guide treatment and follow-upto guide treatment and follow-up

Comparison Of Guidelines On Comparison Of Guidelines On Prophylactic CCDProphylactic CCD

American American Association of Association of Clinical Clinical Endocrinologists Endocrinologists and Associazione and Associazione Medici Medici Endocrinologi Endocrinologi 20062006

““should be performed if the surgeon has should be performed if the surgeon has specific training”specific training” for and experience with for and experience with thyroid surgical techniquesthyroid surgical techniquesPapillary thyroid microcarcinoma (<1cm in Papillary thyroid microcarcinoma (<1cm in max diameter) without LN involvement may max diameter) without LN involvement may avoid CCDavoid CCD

Latin American Latin American Thyroid Society Thyroid Society 20092009

““should be performed”should be performed” for T3 / T4 tumoursfor T3 / T4 tumours

Japanese Society Japanese Society of Thyroid of Thyroid Surgeons 2011Surgeons 2011

RoutineRoutine central compartment dissection is central compartment dissection is recommended (Policy of RAI only in high recommended (Policy of RAI only in high risks patients)risks patients)

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

Extent of CCD:Extent of CCD:Unilateral VS BilateralUnilateral VS Bilateral

1 out of 4 patients with bilateral CCD done 1 out of 4 patients with bilateral CCD done had +ve LN metastasis in contralateral had +ve LN metastasis in contralateral central compartmentcentral compartment

Risks of transient hypoparathyroidismRisks of transient hypoparathyroidismUnilateral CCD < Bilateral CCDUnilateral CCD < Bilateral CCD

Sadowski BM, et al. Routine bilateral central lymph node clearance for papillary thyroid cancer. Surgery. 2009 146(4):696-703; discussion 703-5Grodski 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

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

Alternative OptionsAlternative Options1.1. Watchful waitingWatchful waiting2.2. Empirical radioactive iodine therapyEmpirical radioactive iodine therapy

Regular clinical exam during follow-upRegular clinical exam during follow-up Surveillance USG of neckSurveillance USG of neck Monitoring of thyroglobulin levelMonitoring of thyroglobulin level

ConclusionsConclusionsTherapeutic LN dissection if LN metastasis Therapeutic LN dissection if LN metastasis

confirmedconfirmedProphylactic CCD helps in accurate staging of PTC Prophylactic CCD helps in accurate staging of PTC

but carries increased risks of transient but carries increased risks of transient hypoparathyroidismhypoparathyroidism

Prophylactic CCD in high risks groups by Prophylactic CCD in high risks groups by experienced surgeonsexperienced surgeons

Ipsilateral CCD could reduce morbidity of transient Ipsilateral CCD could reduce morbidity of transient hypocalcaemia compared with bilateral CCDhypocalcaemia compared with bilateral CCD

Thank You!Thank You!