Transcript Thyroid CA [ PPT ]

Current concepts in
Thyroid : BRAF & Beyond
Professor Ravi Kant
FRCS (England), FRCS (Ireland),
FRCS(Edinburgh), FRCS(Glasgow), MS, DNB,
FAMS, FACS, FICS,
Professor of Surgery
Thyroid = shield
What is new in Thyroid
• Why
• Molecular
• The labels
• Isotope
• The good, the
bad & the ugly
• Vasallo’s index • Artery
•
Nerve
• Recombinant
• Drain ?
TSH
• MCT
5 Common Cancers in Saudi
Female Adult Citizens 2004
Type
1 Breast
%
24.3
n
783
2 Thyroid
9.9
320
3 Colo-rectal
4 NHL
8.7
6.3
281
203
5 Other skin
3.8
123
History: 1600 AD
• Surgery on Thyroid is unwise.
History: Kocher 1900
• Meticulous
• ▲ incidence of ▼PTH in
Postop
• ▲ incidence of ▼T4 in
Postop
• Noble prize in 1908
for Surgery on
Thyroid
History: NO ►Yes
Better understanding of
• Anatomy
• Anaesthesia
• Physiology
• Antibiotics
What is new in Thyroid
•
•
•
•
•
? Thyroid CA
Molecular
The labels
Vasallo’s index
Recombinant
TSH
• Isotope
• The good, the
bad & the ugly
• Artery
• Nerve
• Drain ?
• MCT
Molecular aspects: Advantage
•
•
•
•
•
Etiology
Accurate diagnosis
Tailor the Rx
New Rx
Prognosis
MAPK pathway ► DTC
• (Mitogen activated protein kinase)
• MAPK ► 79% of Papillary CA
(Fagin 2004)
• MAPK ►cell growth & proliferation
Gardner
• APC Adenomatous polyposis coli
Cowden’s
• PTEN
• Phosphatase and tensin homolog
Carney’s
• Protein kinase
• cAMP Cyclic adenosine
monophosphate dependent,
regulatory, type I, alpha, PRKARIA
Werner’s
• RECQL2
Follicular CA & Chromosomal
aberrations:
• No study
• Karyotyping
• CGH
(Comparative genomic
hybridization)
• LOH
( Loss of hetrozygosity)
 Wressman & Bhuvanesh Singh.
SOCNA 2008 Jan p 4
0%
60%
75%
75%
Genetic factors reside on
Chromosomal loci
•
•
•
•
1q21
2q21
14q32
19p13.2
Papillary (%) i
CPTC FVPTC TCV PDPTC
Recurrence 10
10
40
50
Death
5
5
25
40
BRAF
40
5
60
70
RAS
5
40
p53
5
5
50
30
40
Papillary (%) ii
CPTC
FVPTC TCV
PDPTC
Recurrence 10
10
40
50
Death
5
5
25
40
CTNNB
5
5
PTEN
24
24
PPARy
0
30
25
24
50
BRAF
•  RAI response
•  Aggressive disease
• Not in Follicular cancer
Papillary
•
•
•
•
Classical
Follicular variant
Trans Classical variant
Poorly differentiated
Follicular (%) i
FTA MIFTC WIFTC PDFTC
Recurrence 0
10
40
60
Death
0
10
40
60
BRAF
0
0
0
0
RAS
30
40
50
60
p53
0
5
5
40
Follicular (%) ii
FTA
MIFTC WIFTC PDFTC
Recurrence
0
10
40
60
Death
0
10
40
60
CTNNB
0
0
0
25
PTEN
31
55
55
PPARy
30
40
40
Follicular
•
•
•
•
Adenoma
Minimal Invasive
Widely invasive
Poorly differentiated
Anaplastic (%) i
Recurrence
100
Death
100
BRAF
0
RAS
70
p53
80
Anaplastic (%) ii
Recurrence
100
Death
100
CTNNB
65
PTEN
58
PPARy
0
Wressman & Singh SOCNA 2008 Jan p
1-35
PPAR -y (Peroxidase Proliferator
activated receptor gamma
• for 3p25
• Follicular adenoma & carcinoma
• Responsible for cancer formation
and aggressiveness
• = √ aggressive Rx ▲
RAS = mitogen activated protein
kinase signalling pathway (MAPK)
• Receptor tyrosine kinase= EGFR &
erbb2
• ▲MAPK ► RAS protein ►A-RAFB-RAF, C-RAF
• B-RAF
• BRAF = Ugly Papillary CA = Total
thyroidectomy
Never co-exist but Part of MAPK
• RET/PTC for Papillary
• BRAF
for Papillary
• RAS
for Follicular
• 50% of Follicular CA have RAS
(Trovisco 2006)
AKT activation
• p13K-AKT signaling
• Uses the PTEN pathway
• √ √ √ √ √ role in prognosis
P53 pathway
B-catenin pathway
Molecular therapeutics
• ▼ EGFR for tyrosine kinase
pathway (Gefinitib)
• ▼ Tyrosine kinase (Vandetanib)
• ▼ RET
• ▼ VGEF
• ▼ RAS
• ▼ BRAF (Sorafenib)
Molecular therapeutics
•
•
•
•
•
•
▼ MEK (CI-1040) (? With RAI)
▼ RAS (farnesyl transferase inhibitor)
▼ AKT (KP372-1)
▼ p13-K (LY 294002)
▼ RET (pyrazolo-pyrimidine)
▼ p53 (ONYX-15)
Wreesman& Singh. SOCNA 2008; Jan 21-22
Molecular: Summary
• Papllary►Anaplastic
• Follicular ►Anaplastic
MCT
MCT
• Chase with Knife
• Hardly any role of CT/RT
• Chase with knife
MCT: Overview-1
Sporadic NxMEN
MEN-2A MEN-2B
42-45
43-45
24-27
15-20
Gender M=F
M=F
M=F
M=F
LN+
40-50
10-20
14
38
M+
12
0
0-3
20
Age
MCT: Overview-2
Sporadic NxMEN
MEN-2A MEN-2B
Cured % 14-30
70-80
56-100
0
Dead % 30
0
0-17
50
Mutation Met918→ Cystei Cystein Met918
Thr
neEC eECDN → Thr
DNM M
Mutation Met768
→ Asp
MCT: Associate Diseases
Sporadic
-
Nx-MEN
-
MEN-2A
MEN-2B
Pheo,PTH Pheo,PTH
Marfanoid
body
Neuromas
oral &eye
Ganglione
uromas-GI
Investigations:
•
•
•
•
Provocative
Nuclear Medicine
Localisation
Genetic Screening
Investigations:
Serum Calcitonin
• Provocative
- Ca gluconate
- Pentagastrin
• Localisation
-Venous
sampling
-/+ provocative
Investigations:
Serum Calcitonin
Current:
Monomeric form of Calcitonin by
Immunoluminometric assay & not
RIA
*Engelbach J Clin Endocrinol Metab 2000
May; 85(5):1890-4)
Localisation studies
(Kebebew E, Arch 2000, August,; 135(8):895-901)
Investigation
US
Sensitivity (%)
88
CT
86
MRI
91
Dimercaptosuc
cinic acid Scan
100
Nuclear Medicine
• √ Somatostatin Receptor
Scintigraphy
• √ MIBG
• √ Anti-CEA antibody
• √ Anti-Calcitonin antibody
• X I-131, Tech, Thallium
PET
• Positive where MIBG fails
• Detect early Lung lesions not
detected by other methods.
• F-18 FDG PET more useful than
MIBG scan in detecting metastases
(Lind P , Acta Med Austriaca 2000; 27(2):3841)
PET
PET > CT, MRI, Isotope
(Diehl M. Eur J Nucl 2001)
FDG PET In Thyroid
• 18F-FDG PET of thyroid nodules with inconclusive
cytologic results. [J Nucl Med. 2006]
• 18F-fluorodeoxyglucose uptake in thyroid from positron
emission tomogram (PET) for evaluation in cancer
patients: high prevalence of malignancy in thyroid PET
incidentaloma. [Laryngoscope. 2005]
• 18F-FDG-PET in the follow-up of thyroid cancer. [Acta
Med Austriaca. 2003]
• Diagnostic accuracy and prognostic value of 18F-FDG
PET in Hurthle cell thyroid cancer patients. [J Nucl
Med. 2006]
• Role of [18F]fluorodeoxyglucose positron emission
tomography in follow-up of differentiated thyroid
cancer. [Endocr Pract. 2006]
Somatostatin Scintigraphy
• Better than other isotope
• Poor for < 1cm
• Poor for Liver lesions
Genetic: RET 98%in familial
• Autosomal dominant
• Tyrosine kinase protooncogene RET
• + in 98% in familial group
• Axon 10 & 11, 13-16
Treatment
• No role of Chemo/ RT
• No role of RAI
• Chase with Knife
• Genetic abnormality
based surgery in preclinical phase
Treatment = the knife
• Total thyroidectomy +
central node dissection in
all ++++
• + mRND if
1. >1cm tumor or
2. central compartment is +ve
Genetic abnormality based
surgery-1
• No abnormality in basal or
stimulated Calcitonin
• Worst out come correlated with
*Met918-------Thor
*Glu-768---- --Asp
Genetic abnormality based
surgery-2
• Good outcome associated with
“Mutations in cysteines in extra
cellular domain near membrane”
as in
*Familial Non MEN
*MEN II A
Genetic abnormality based
surgery-3
• Mutations in cysteines in extracellular domain near membrane→
• Diagnosed on molecular genetic
screening in infants &young children
• No abnormality in basal or
stimulated Calcitonin ►SURGERY
Genetic abnormality based
surgery-4
• Mutations in cysteines in extracellular domain near
membrane→ ►SURGERY =
• Total Thyroidectomy + Total
Parathyroidectomy + Parathyroid
auto graft
Genetic abnormality based
surgery-5. The beneficial
gene
• On the contrary 611 codon or exon
13 mutation is a mild one and gene
carriers may live up to 70 years of
age without intervention.
• Presence of this gene without other
endocrine tumor may not require
surgery.
(Hansen HS , Cancer 2000, Aug 15;89(4):863-867)
Genetic abnormality based
surgery-6: Protocol
• MEN II B – Surgery in first year of
life, As the course is aggressive.
• MEN II A- Surgery delayed up to
5yrs, As the course is indolent.
*Wells SA Jr: World J Surg 2000 Aug;24(8);952-956
*Dolan SJ: Ann R Coll Surg Engl 2000 May;
82(3):156-161
*Krueger JE, Am J Surg Pathol 2000 June; 24(6):8538
Prophylactic Thyroidectomy
• Prophylactic Thyroidectomy in Multiple
Endocrine Neoplasia Type 2A
Skinner M. A., Moley J. A., Dilley W. G.,
Owzar K., DeBenedetti M. K., Wells S. A. Jr.
N Engl J Med 2005; 353:1105-1113,
Sep 15, 2005.
• Prophylactic Thyroidectomy in MEN-2A — A
Stitch in Time?
Moore F. D., Dluhy R. G.
N Engl J Med 2005; 353:1162-1164,
Sep 15, 2005. Editorial
MIBG-palliation
• 1311- MIBG
(metiodobenzylguanidine)
• PR or Disease stabilisation only,
• Not curative
(Castellani MR, QJ Nucl Med 2000 Mar; 44(1):7787)
* Diagnostic
role
Future Trend-1:
• CEA Ag targeting with 1311 & 90y
labeled MAbs.
• Gene therapy with herpes simples
viral thymidine kinase (HSVTK).
Future Trends-2:
• Cell specific sensitivity to
ganciclovir in MCT by adenovirus
mediated gene transfer of HSV TK
( Zhang R, DeGroot LJ, Thyroid 2000 April,10(4):313-9)
MCT
• Mutation study may render all
other investigations meaningless.
• Till than, Somatostatin receptor
Scintigraphy is superior
investigation.
• Gene mutation based surgery,
even in ABSENCE of raised basal
or provoked Calcitonin, at an early
age of 1year.
BRAF →Papillary carcinoma
Thanks
LN Dissection*
CHASE WITH KNIFE
T
in cm
T=1cm
Sampling of Ln Lateral to Jugular+
Central Node Dissection
1cm=11%
T=2 cm or More
MODIFIED RND
2cm=60%
What is new in Thyroid
• ? Thyroid CA
• Molecular
• The labels
• Isotope
• The good, the
bad & the ugly
• Vasallo’s index • Artery
•
Nerve
• Recombinant
• Drain ?
TSH
• MCT
Plummer’s
Syndrome
T3 toxicosis
Plummer’s disease
Toxic adenoma
Refetoff’s
T4 resistance
Jod Basedow
Iatrogenic ▲T4
Pendred’s
▼T4 + Deafness
(TPO defect)
Wolff-Chaikoff
effect
Hypothyroidism
caused by ingestion
of a large amount of
iodine
Lugol’s iodine
BABA
bilateral axillo
breast approach
Tubercle of
Zuckerkandl
95% RLN
identification
Berry’s ligament
Grave’s
HLA
Riedel’s
Can confuse with
Anaplastic
Hashimoto’s
Askanazy cells (E)
▲TPO
Adverse prognosis
Hurthle’ cell
Orphan Arnie
nucleus
Papillary
Lugol’s Iodine
• Lugol's iodine, also known as Lugol's solution, first
made in 1829, is a solution of iodine named after the
French physician J.G.A. Lugol. Lugol's iodine
solution is also used to protect the thyroid gland
from radioactive materials (e.g. "fallout"), and for
emergency disinfection of drinking water.[1]
• It consists of 5 g iodine (I2) and 10 g
potassium iodide (KI) in 100 ml distilled
water with a total iodine content of 130
mg/mL. Potassium iodide renders the elementary
iodine soluble in water through the formation of the
I3- ion.
Hurthle cell CA
• Ann Surg Oncol. 2002 Mar;9(2):197-203.
Hurthle cell carcinoma: a 60-year experience.
MSKCC Experience :Stojadinovic A, Shah
JP, Singh B, Shaha AR.
• Aggressive locally
The Endoscopic
thyroidectomy
•
•
•
•
Infra-clavicluar
Axillary
Lateral neck
Infra-mammary
Radioguided revision surgery
• Erbil Y. J Endocrinol Invest. 2005
Jul-Aug;28(7):583-8. Gamma
probe-guided surgery for revision
thyroidectomy: in comparison with
conventional technique.
Familial Thyroid Syndromes
Syndrome Gene CP
Thyroid
Cowden’
F,
Hu,P
FAP
Werner’s
PTEN Intestinal
hemartoma,
breast tumor
APC Colon polyp,
duodenal,
desmoid
WRN
P
P,F,A
MCT: Associate Diseases
Sporadic NxMEN
-
MEN-2A
MEN-2B
Pheo,
PTH
Pheo,PTH
Marfanoid
body
Neuromas
oral &eye
Ganglioneur
omas-GI
MEN 1
• Parathyroid
• Pancreas
• Pituitary
What is new in Thyroid
• ? Thyroid CA
• Molecular
• The labels
• Isotope
• The good, the
bad & the ugly
• Vasallo’s index • Artery
•
Nerve
• Recombinant
• Drain ?
TSH
• MCT
USG for Regional LN
• 7.5-20 mhZ for LN : 20-100 for
Virtual
• USG B scan-LN
• Vassallo index < 2 (Long : Trans)
• Hypoechoic central area
• Color Doppler-peripheral perfusion
• USG Guided FNAC +RT-PCR Tyro
• USG guided anchor wire for mets
√ USG of Thyroid & neck
• Rx changed in 39%
 MD Anderson, Kouvaraki MA, Shapiro. Surgery
2003;134:946-55
• Rx changed in 57% (USG by Surgeon)
 Solorzano CC. Am Surg 2004;70(7):576-80
• √ Guidelines: American Thyroid
Association
 Cooper DA, Doherty GM. Thyroid 2006;16:109-41
USG
• High specificity
• Low sensitivity (36.7% for lateral &
10.9% for central)
Ito Y. World J Surg 2004;28:498-50
Shimmamoto K. Eur J Radiol 1998;29:4-10
Hoang JK. Radiographics 2007;27:847-60
What is new in Thyroid
• ? Thyroid CA
• Molecular
• The labels
• Isotope
• The good, the
bad & the ugly
• Vasallo’s index • Artery
•
Nerve
• Recombinant
• Drain ?
TSH
• MCT
Recombinant Human TSH
Recombinant Human TSH-Assisted
Radioactive Iodine Remnant Ablation
Achieves Short-Term Clinical
Recurrence Rates Similar to Those of
Traditional Thyroid Hormone
Withdrawal
R. M. Tuttle, J. Nucl. Med., May 1, 2008;
49(5): 764 - 770.
rhTSH
• A Comparison of Short-term
Changes in Health-related Quality of
Life in Thyroid Carcinoma Patients
Undergoing Diagnostic Evaluation
with rhTSH Compared to Thyroid
Hormone Withdrawal
• Pamela R. Schroeder, Journal of Clinical
Endocrinology & Metabolism, 2006;
doi:10.1210/jc.2005-2064
Recombinant Human
Thyrotropin
• Radioiodine Ablation of Thyroid
Remnants after Preparation with
Recombinant Human Thyrotropin in
Differentiated Thyroid Carcinoma:
Results of an International,
Randomized, Controlled Study
• F. Pacini. The Journal of Clinical
Endocrinology & Metabolism 2006;91(3):926–
932
• doi: 10.1210/jc.2005-1651
Clinical Comparison of WholeBody Radioiodine Scan and
Serum Thyroglobulin After
Stimulation with Recombinant
Human Thyrotropin
• Bryan R. Haugen. THYROID 2002;
Volume 12, Number 1, 37-43.
TSH suppression Ξ DTC is TSH
dependent
• Aggressive Rx =undetectable TSH=
Bone loss & Atrial fibrillation & Angina
• Aggressive Rx Indication=High risk
DTC (stage 3 &4)(▲Survival)
(Biondi 2005)
• Stage II= TSH to remain subnormal or
low normal
(Jonkklaas 2006)
• Stage I= No effect on Survival of stage I
What is new in Thyroid
• ? Thyroid CA
• Molecular
• The labels
• Isotope
• The good, the
bad & the ugly
• Vasallo’s index • Artery
• Nerve
• Recombinant
TSH
• Drain ?
• MCT
Isotope
131 I
8 Day
Energy Δ Dose Absorb
ed rads
KeV
Ci
364
100 µ
75
123 I
13 Hr
159
100 µ
0.75
140
10 m
1.3
Isotope Half
life
99m Tc 6 Hr
Isotope
Isotope Emissi Tissue Δ
on
Stun β
131 I
βγ
+
123 I
γ
-
99m Tc γ
-
Rx
√
√
Isotope
Isotope Emissi Δ of
on
Mets
131 I
βγ
123 I
γ
99m Tc γ
√
Rx
√
Before 131-I Rx: Current
recommendation
• Thyrogen (Recombinant TSH)
• SOCNA 2008
Rx by
Isotope
Δ
Dose for Rx
m Ci
131- I
+ Thyroid
100
+ Capsule of
thyroid
150 - 300
+ Cervical LN
150-175
+ Lung, Bone,
Liver
>200
 Tg
• Major protein product of Thyroid
cell
• Not produced by any other cell of
the body
Remnant ablation
• TSH > 25-30 micro U/mL
• Urinary iodine <200 microg/L
PET
•
•
•
•
Sensitivity 93.7
Specificity 77.8
 sensitivity @  Tg /  TSH
( TSH→ rTSH or ▼ T4)
• SOCNA 2008 Jan
FDG PET in Thyroid surgery
• J Nucl Med. 2006 May;47(5):770-5.
Comment in: J Nucl Med. 2006
Sep;47(9):1555; author reply 15556. 18F-FDG PET reduces
unnecessary hemithyroidectomies
for thyroid nodules with
inconclusive cytologic results.
Summary 1
• Thyroid surgery is safe in
safe hands
• Surgeon is a risk factor
• Surgeon < 10 cases per year
= 4x ▲complications
 Sosa JA. Ann Surg 1998;3:320-30
Summary-2
• Superior pole vessels→use
modern energy resource and NEED
NOT LIGATE (by suture),
• Safe for nerve,
• Save time.
Summary-3
• Do NOT ligate Inferior thyroid
artery- Only bipolar coagulation of
branches on the capsule
Summary-4
• Individual in-situ control of
branches of inferior thyroid artery
on the capsule of thyroid
• by modern energy resources,
SAFE FOR NERVE
Summary-5
• MUST Identify nerve, use gadgets
(esp for Sup Br of Ext Laryngeal N)
Summary-6
• Must identify recurrent laryngeal
nerve at all times (Lahey’s clinic
policy is now universally accepted)
Summary-8
• ? Drain
Summary-9
• Molecular markers are the new way
forward BRAF for Papillary, RAS
for Follicular, MPAK for DTC
• Preferred surgery is Near total or
Total Thyroidectomy• The concept of Good , the bad and
the ugly is for selection of surgery
What is new in Thyroid
• ? Thyroid CA
• Molecular
• The labels
• Isotope
• The good, the
bad & the ugly
• Vasallo’s index • Artery
•
Nerve
• Recombinant
• Drain ?
TSH
• MCT
The concept of good, the bad &
the ugly
• From MSKCC New York
• Lancet Oncol. 2005 Jul;6(7):529-31.
Is total thyroidectomy the best
possible surgical management for
well-differentiated thyroid cancer?
Udelsman R, Shaha AR.
High tumor grade
• Tall cell
• Hurthle cell
• Poor tumor differentiation
Prognostic factors
TN AGES AMES MACIS MSKCC EORTC
M
Age
Size
+
+
Extra- +
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-
+
-
+
+
-
+
+
-
+
+
-
thy
M
G
R0
M/F
+
-
TNM Classification
Stage
I
II
III
IVA
IVB
Age in years
<45
Any T, Any N, M0
Any T, Any N, M1
Age
>45
T1, N0, M0
T2, N0, M0
T3, N0, M0
T1-3,N1a, M0
T4a, N0-1a, M0
T1-4a, N1b, M0
T4b, any N, M0
Any T, any N,M1
Differentiated Thyroid CA
%
Low Risk
High risk
Recurrence
10
45
Mortality
2-5
40-50
 Risk: (Papillary or Follicular
Thyroid Carcinoma) : Rx
• MSKCC→ Low risk→ Lobectomy +
Isthmus
Shah AR, Shah JP, Loree TR: Ann Surg
Oncol 1997;4:328-33
Shah AR. Laryngoscope 2004;114:393-402
• Many others → Total or near total
thyroidectomy even in Low risk
Risk factors : MSKCC
Age
Low Intermediate High
<45 <45
>45
>45
Tumor size cm
<4
<4
>4
>4
Extra thyroidal extension
M
-
+
-
+
+
-
+
High tumor
grade
+
-
+
-
Near Total or Total
Thyroidectomy preferred for DTC
• Sem in Oncol June 2008 vol 35, No
3 : 298-308
• Am Asso of Clinical
Endocrinologist (AACE)
• Am Asso of Endocrine Surgeons
(AAES)
• NCCN
• Am Thyroid Asso (ATA)
May Lobectomy or T/NT: ALL of
the following+
•
•
•
•
•
•
•
Age 15-45
Tumor < 4cm
No prior RT
No Neck LN
No extra-thyroid extension
No mets
Not aggressive variant
• NCCN 2009
Total/ Near total: Any of the
following+
•
•
•
•
•
•
•
Age <15 or >45
History of RT
Distant mets
Extrathyroidal extension
Tumor >4 cm
Cervoivcal LN +
Aggressive variant
• NCCN 2009
Lobectomy vs near Total or Total
thyroidectomy
• Survival same in both
• DFS  Near Total or T
• Recurrence (30%)  in Lobectomy
• Recurrence (1%)  in Total / NT
(Mazzaferri 2001)
• Near Total < 1gm tissue left after
Surgery
Access to thyroid- new
techniques
• Open
– Mini
– Video assisted
• Endoscopic
Minimal invasive
thyroidectomy
• Ikeda Y, Takami H, Sasaki Y, et al. Are
there significant benefits of minimally
invasive endoscopic thyroidectomy?
World J Surg 2004; 28(11):1075-8.
• Shimizu K, Tanaka S. Asian perspective
on endoscopic thyroidectomy -- a
review of 193 cases. Asian J Surg 2003;
26 (2):92-100.
• Takami HE, Ikeda Y. Minimally invasive
thyroidectomy. Curr Opin Oncol 2006;
18(1):43-7.
Small incision thyroidectomy
• Miccoli P.1999; 22(11):849-51.
• Miccoli P, Berti P, Materazzi G, et al.
Minimally invasive video-assisted
thyroidectomy: five years of experience.
J Am Coll Surg 2004; 199(2):243-8.
• Terris DJ, Gourin CG, Chin E. Minimally
invasive thyroidectomy: basic and
advanced techniques. Laryngoscope
2006; 116(3):350-6.
Minimal invasive
thyroidectomy
• Ujiki MB, Sturgeon C, Denham D, et
al. Minimally invasive videoassisted thyroidectomy for
follicular neoplasm: is there an
advantage over conventional
thyroidectomy? Ann Surg Oncol
2006; 13(2):182-6.
What is new in Thyroid
• ? Thyroid CA
• Molecular
• The labels
• Isotope
• The good, the
bad & the ugly
• Vasallo’s index • Artery
•
Nerve
• Recombinant
• Drain ?
TSH
• MCT
New Concepts:
Superior thyroid artery & vein
• Superior thyroid artery & vein need
not be ligated by sutures
• Use Modern Energy resources,
safe for nerve & artery, nerve &
vein
• Cricothyroid space- medial side
has a gift
box
New Concepts:
Inferior Thyroid Artery
• Do not ligate Inferior Thyroid
Artery Trunk
• Work on capsule of gland, much
away from trunk of inferior thyroid
artery
• Individual branch control by new
energy resources
• Sweep down parathyroid, & nerve
Do not ligate Inf thyroid artery
trunk
Inferior pole control : Veins
• No need to use sutures in time
honoured manner
• Use new energy resource
• Faster
• Safe
√ Deliberate identification of RLN
Rubin AD & Spiegel,JR. SOCNA
2008;Jan p 176
Lahey FH. SGO 1938;66:775-7
Lahey FH. SGO 1944;194:239-44
Lahey 10,000 thyroidectomies
Schwartz’ 8th edition 2005
Must identify the nerve
• Laryngoscope. 2002
Jan;112(1):124-33.
• Advantages of recurrent laryngeal
nerve identification in thyroidectomy
andparathyroidectomy and the
importance of preoperative and
postoperativelaryngoscopic
examination in more than 1000 nerves
at risk.
• Steurer M, Passler C, Denk DM,
Schneider B, Niederle B, Bigenzahn W.
Nerve: Must identify
• Identify recurrent laryngeal nerve
• Identify Superior laryngeal nerve
• Use new machines for
identification
Must identify the nerve
• Am J Surg. 1999 Jun;177(6):485-8.
The recurrent laryngeal nerve
related to thyroid surgery.Sturniolo
G, D'Alia C, Tonante A, Gagliano E,
Taranto F, Lo Schiavo MG.
RLN 95% identification
• Tubercle of ZuckerkandL
• Post lateral thickening of thyroid
Intra-operative nerve monitoring
• 29% off US surgeons use nerve
monitoring
• Endotracheal tube + integrated
surface electrode
Endotracheal nerve monitoring
Must recognise Ext br of
Superior Laryngeal Nerve
New Concepts:
Superior thyroid artery
& EBSLN
• Type 1
• Type 2
– Type 2a
– Type 2b
Ext Branch Sup Laryngeal N
Injury
• Type I
• Type II
• Type III
• Opera singer & Teacher
• Intraoperative monitoring
Nerve stimulator
– Thyroid. 2005 May;15(5):449-54.
Importance of the intraoperative
identification of the external branch
of the superior laryngeal nerve
during thyroidectomy:
electromyographic evaluation.
Hurtado-Lopez LM,
Nerve stimulator
– Indian J Med Sci. 2007 Jan;61(1):3-8. The
external laryngeal nerve in thyroid surgery: the
'no more neglected' nerve. Mishra AK
– Eur J Pediatr Surg. 2006 Dec;16(6):3925. The advantages and disadvantages of
nerve monitoring during thyroid surgery in
childhood. Meyer T, Hamelmann W,
Timmermann W, Meyer B, Hocht B.
Nerve stimulator-against
• Eur J Surg. 2001 Sep;167(9):662-5.
External laryngeal nerve in thyroid
surgery: is the nerve stimulator.
necessary? Aina EN
• Surgery. 2005 Mar;137(3):342-7
Recurrent laryngeal nerve palsy after
thyroidectomy with routine
identification of the recurrent laryngeal
nerve. Chiang FY, Wang LF,
Nerve stimulator-against
• World J Surg. 2006 May;30(5):806-12
Pitfalls of intraoperative neuromonitoring for
predicting postoperative recurrent laryngeal
nerve function during thyroidectomy. Chan
WF, Lo CY.
• Surgery. 2006 Dec;140(6):866-72;
discussion 872-3. Epub 2006 Sep 18 The
role of intraoperative neuromonitoring of
recurrent laryngeal nerve during
thyroidectomy: a comparative study on
Nerve stimulation
• Tomoda C, World J Surg. 2006
Jul;30(7):1230-3. Sensitivity and
specificity of intraoperative
recurrent laryngeal nerve
stimulation test for predicting
vocal cord palsy after thyroid
surgery.
Must identify the nerve
• Lahey Clinic policy for last 70
years
What is new in Thyroid
• ? Thyroid CA
• Molecular
• The good, the
bad & the ugly
• The labels
• Artery
• Nerve
• Vasallo’s index
•
Drain
?
• Recombinant
• Isotope
TSH
• MCT
What is new in Thyroid
• ? Thyroid CA
• Molecular
• The labels
• Isotope
• The good, the
bad & the ugly
• Vasallo’s index • Artery
•
Nerve
• Recombinant
• Drain ?
TSH
• MCT
Drain ?
Khanna J, Mohil RS. BMC Surg
2005;5:11
Lee SW, Choi EC, Lee YM.
Laryngoscope 2006;116(9):1632-5
Kristofferson A. BJS 1986;73(2):121-2
Corstan M. Meta-analysis. J
Otolaryngol 2005; 34(6):415-7
Potheir DD. J Laryngol Otol
2005;119(9):669-71 Meta-analysis
A drain has no effect on
hematoma incidence
• Hematoma 0.3-3%
Corstan M.. J Otolaryngol 2005;
34(6):415-7 Meta-analysis
Potheir DD. J Laryngol Otol
2005;119(9):669-71 Meta-analysis
Drain not required after
thyroidectomy
Suslu N, Vural S, Oncel M, Demirca
B, Gezen FC, Tuzun B, Erginel T,
Dalkilic G. Is the insertion of drains
after uncomplicated thyroid
surgery always necessary? Surg
Today. 2006 ;36(3):215-8.
Hemostasis
• Harmonic scalpel (Ethicon)
• Ligasure (Tyco)
Postop Drain ?
• Usually not required
• Especially with Ultrasonic
scalpel
• Remove < 12 h (De Groot)
• Examination: Drain=
√
Surgeon as a risk factor: Thyroid
• Surgeon < 10 cases per year = 4x
▲complications
Sosa JA. Ann Surg 1998;3:320-30
The lymph node dissection
• MRND =
• Modified radical neck dissction
• Save muscle (SCM), nerve (IX) and
vein (IJ)
New concepts:
•
•
•
•
•
Incision modifications
Endoscopic techniques
Nerve identification techniques
Hemostatsis control
No suture No ligation of any vessel
due to new energy resources
Incision
• Hold vessel bleed not before
platysma is completely divided
• Essential anatomy tip
Drain not required after
thyroidectomy
• BMC Surg. 2005 May 19;5:11. Is the
routine drainage after surgery for
thyroid necessary? A prospective
randomized clinical study
[ISRCTN63623153]. Khanna J,
Mohil RS, Chintamani, Bhatnagar
D, Mittal MK, Sahoo M, Mehrotra M
LA for Thyroidectomy
• Spanknebel K, Chabot JA, DiGiorgi
M, Cheung K, Lee S, Allendorf J,
Logerfo P.Related Articles,
Thyroidectomy using local
anesthesia: a report of 1,025
cases over 16 years.
J Am Coll Surg. 2005
Sep;201(3):375-85.
Thyroidectomy in LA
• Arch Surg. 2006 Feb;141(2):167-73.
• Local Anesthesia With Monitored
Anesthesia Care vs General Anesthesia
in Thyroidectomy: A Randomized
Study. Snyder SK,.
• Department of Surgery, Texas A&M
University System Health Science
Center College of Medicine, Scott &
White Clinic and Foundation, Temple,
Tex 76508, USA.
Daycare surgery
• Surgery. 1995 Dec;118(6):1051-3;
discussion 1053-4. Outpatient
thyroid and parathyroid surgery: a
prospective study of
feasibility,safety, and
costs.Mowschenson PM, Hodin
RA.Department of Surgery, Beth
Israel Hospital, Boston, Mass, USA.
Harmonic-1
• Head Neck. 2006 Nov;28(11):102831. Efficacy and safety of ultrasonically
activated shears in thyroid
surgery.Karvounaris DC, Antonopoulos
V, Psarras K, Sakadamis A.
• Arch Surg. 2002 Feb;137(2):137-42.
The use of the harmonic scalpel vs
conventional knot tying for vessel
Harmonic 2
• Chir Ital. 2004 Nov-Dec;56(6):843-8.
Usefulness of the ultrasonically
activated shears in total
thyroidectomy.Casadei R, Perenze B,
Vescini F, Piccoli L, Zanini N, Minni F.
Italy
• Ann Surg. 2000 Mar;231(3):322-8.
Ultrasonically activated shears in
thyroidectomies: a randomized
trial.Voutilainen PE, Haglund CH.
Harmonic 3
• Ann Chir. 2000 Jun;125(5):468-72.
[Evaluation of the Ultracision
ultrasonic dissector in thyroid
surgery.Prospective randomized
study]Belgium
• Acta Chir Belg. 2003 Jun;103(3):274-7.
Evaluation of the ultrasonic dissector
in thyroid surgery. A
Harmonic 4
• Laryngoscope. 2006 Jun;116(6):851-4.
Ultrasonic technology facilitates
minimal access thyroid surgery.Terris
DJ, Seybt MW, Gourin CG, Chin E.
• Surgery. 2005 Mar;137(3):337-41. A
randomized, prospective, parallel
group study comparing the Harmonic
Scalpelto electrocautery in
Harmonic 5
• Zhonghua Wai Ke Za Zhi. 2003
Oct;41(10):733-7. [Using ultrasonically
activated scalpels as major instrument
for vessel dividingand bleeding control
in minimally invasive video-assisted
thyroidectomy][Article in Chinese]Gao
L, Xie L, Li H, Shao Y, Ye XH, Hu Y,
Song CY.
Harmonic 6
• Laryngorhinootologie. 2003 Jul;82(7):514-9.
[Preliminary results for superficial
parotidectomy using the
ultrasonicallyactivated scalpel (Ultracision
Harmonic Scalpel)][Article in
German]Metternich FU, Sagowski C, Wenzel
S, Jakel T, Leuwer R, Koch U.
• Surg Endosc. 2003 Mar;17(3):442-51. Epub
2002 Oct 29. Laparoscopic cholecystectomy
by ultrasonic dissection without cystic duct
Harmonic advantages 1
• significant ▼ operating time 23-90 mts
• significant ▼ blood loss,
• significant ▼ in "transitory
hypoparathyroidism";
• ▼ postoperative analgesic
consumption
Harmonic advantages 2
• Save the nerve from collateral
damage
• Endocopic surgery
• No drain
• Better cosmesis due to small
incision
Extent:
• Total thyroidectomy is best
operation for thyrotoxicosis
England and Atkin BMJ.2007; 334:
710
Near Total thyroidectomy is
close to ideal
• [Retrospective analysis of the results
of surgical treatment of 407 patients
with differential thyroid gland cancer
over a period of 23 years] [Khirurgiia
(Sofiia). 2004]
• Completion thyroidectomy in patients
with thyroid cancer who initially
underwent unilateral operation. [Clin
Endocrinol (Oxf). 2004]
Near Total thyroidectomy is
close to ideal
• Total thyroidectomy: the treatment of
choice in differentiated thyroid carcinoma?
[Eur J Surg Oncol. 1985]
• The role of total thyroidectomy in the
management of differentiated thyroid
cancer. [Curr Opin Gen Surg. 1994]
Near Total thyroidectomy is
close to ideal
• Total thyroidectomy for differentiated
thyroid carcinoma: primary and secondary
operations. [Eur J Surg Oncol. 1998]
• [Retrospective analysis of the results of
surgical treatment of 407 patients with
differential thyroid gland cancer over a
period of 23 years] [Khirurgiia (Sofiia).
2004]
• Completion thyroidectomy in patients with
thyroid cancer who initially underwent
unilateral operation. [Clin Endocrinol
Medullary Thyorid CA
• Chase by knife
• No role of RT or Chemo or
Radoactive substance
Hurthle cell CA
• Ann Surg Oncol. 2002 Mar;9(2):197-203.
Hurthle cell carcinoma: a 60-year experience.
MSKCC Experience :Stojadinovic A, Shah
JP, Singh B, Shaha AR.
• Aggressive locally
Prognostic factors: MSKCC
•
•
•
•
•
•
age,
size of the tumor,
extrathyroidal extension,
presence of distant metastasis,
histological appearance
grade of the tumor
Prognostic Factors
AGES ( Mayo
Clinic)
A Age
G Histological
Grade
E Extent of
Tumor
Staging System for Thyroid Carcinoma
Established by the American Joint Committee on Cancer
Stage
Papillary or follicular
Medullary,
age
any
Anaplastic,
age
Age < 45 yr
Age > 45
yr
I
M0
T1
T1
-
II
M1
T2-3
T2-4
-
III
-
T4 or N1
N1
-
IV
-
M1
M1
Any
any
EORTC: Risk group assignment
Age in years: + 12 if male, + 10 if
medullary,
+
10
if
poorly
differentiated follicular, + 45 if
anaplastic, + 10 if extending
beyond thyroid, + 15 if one
distant
metastasis,
+
multiple distant metastasis.
30
if
AMES: High risk if
•♀ > 50y
•♂ > 40 y
• Tumor > 5 cm (if older age)
• Distant metastases
• substantial extension beyond tumor
capsule (follicular) or gland capsule
(papillary).
AGES
•
•
•
•
•
•
0.5 x Age in yrs. (if > 40)
+ 1 (if grade 2)
+ 3 (if grade 3 or 4)
+ 1 (if extrathyroidal)
+ 3 (if distant spread)
+ 0.2 x max. tumor diameter
MACIS
• 3.1 (if age < 39 yr) or 0.08 x age (if
age > 40 yr),
• + 0.3 x tumor size (in cm),
• + 1 (if incompletely resected),
• + 1 (if locally invasive),
• + 3 (if distant metastases present).
Energy resources in thyroid
surgery
• Otolaryngol Head Neck Surg. 2005 Mar;132(3):487-9.
The use of Ligasure Vessel Sealing System in
thyroid surgery.Germany.
• Head Neck. 2005 Nov;27(11):959-62. Electrothermal
bipolar vessel sealing system is a safe and timesaving alternative to classic suture ligation in total
thyroidectomy.
• Asian J Surg. 2005 Apr;28(2):86-9. Use of the
electrothermal vessel sealing system versus
standard vessel ligation in thyroidectomy.Shen WT,
Baumbusch MA, Kebebew E, Duh QY
• G Chir. 2005 Oct;26(10):387-94. Major complications
What is new in Thyroid
• Molecular
• Drain ?
• The names
•
•
•
•
• Vasallo’s index
• Recombinant
TSH
• The good, the
bad & the ugly
Artery
Nerve
Isotope
MCT
MCT
Calcium-Pentagastrin Stimulation Testing
Skinner M et al. N Engl J Med 2005;353:1105-1113
Specific RET Mutations Associated with Multiple Endocrine Neoplasia and Variants
Machens A et al. N Engl J Med 2003;349:1517-1525
Treatment of the Single Nonmalignant Thyroid Nodule
Hegedus L. N Engl J Med 2004;351:1764-1771
Cross-Sectional Ultrasonogram Showing a Solid, Hypoechoic Nodule (Dark Gray) in the Right
Thyroid Lobe
Hegedus L. N Engl J Med 2004;351:1764-1771
Cumulative Risk of Medullary Thyroid Carcinoma among Carriers of Codon 634 Germ-Line RET
Mutations, According to the Presence or Absence of Nodal Metastases and Age
Machens A et al. N Engl J Med 2003;349:1517-1525
Progression to Medullary Thyroid Carcinoma in the First Two Decades of Life among Carriers of
Codon 634 RET Germ-Line Mutations
Machens A et al. N Engl J Med 2003;349:1517-1525
Progression to Medullary Thyroid Carcinoma in the First Two Decades of Life, According to the
Position of the RET Codon Domain
Machens A et al. N Engl J Med 2003;349:1517-1525
Specific RET Mutations Associated with Multiple Endocrine Neoplasia and Variants
Machens A et al. N Engl J Med 2003;349:1517-1525
Treatment of the Single Nonmalignant Thyroid Nodule
Hegedus L. N Engl J Med 2004;351:1764-1771
Scintigram of a Solitary Functioning Nodule in the Right Thyroid Lobe
Hegedus L. N Engl J Med 2004;351:1764-1771
Algorithm for the Cost-Effective Evaluation and Treatment of a Clinically Detectable Solitary
Thyroid Nodule
Hegedus L. N Engl J Med 2004;351:1764-1771
Clinical Findings Suggesting the Diagnosis of Thyroid Carcinoma in a Euthyroid Patient with a
Solitary Nodule, According to the Degree of Suspicion
Hegedus L. N Engl J Med 2004;351:1764-1771
Current and Proposed Restrictions on Work and On-Duty Hours in U.S. Commercial Aviation
Gaba D and Howard S. N Engl J Med 2002;347:1249-1255
Lugol’s Iodine
• Lugol's iodine, also known as Lugol's solution, first
made in 1829, is a solution of iodine named after the
French physician J.G.A. Lugol. Lugol's iodine
solution is also used to protect the thyroid gland
from radioactive materials (e.g. "fallout"), and for
emergency disinfection of drinking water.[1]
• It consists of 5 g iodine (I2) and 10 g
potassium iodide (KI) in 100 ml distilled
water with a total iodine content of 130
mg/mL. Potassium iodide renders the elementary
iodine soluble in water through the formation of the
I3- ion.
Thyroid cancer & regions:2004
Thyroid cancer 2004
Saudi Cancer data
• National Cancer Registry
• Cancer Incidence report Saudi
Arabia 2004 page 21, 44, 45
• Ministry of Health Publication
• Kingdom of Saudi Arabia
Pre-tibial myxedema
• Auto- antibodies
→ glycos-aaminglycan
→ Stimulated fibroblast
→ Deposition of Hyaluronic acid
(in dependent position)