1. Controversies in the Management of Differentiated Thyroid Carcinoma
Dimyati Achmad
Department of Surgery, Faculty of Medicine Padjadjaran University/
Hasan Sadikin Hospital, Bandung Indonesia

2. Introduction
Thyroid carcinoma is the most frequent malignancy of the endocrine system
The incidence has increased sharply in three decades
Almost 90% of thyroid carcinoma are well-differentiated thyroid carcinoma

3. Differentiated Thyroid Carcinoma (DTC)
Is categorized into:
Papillary thyroid carcinoma (85%)
Folliculare thyroid carcinoma (10%)
Hurtle cell carcinoma (3%)
Slow growing tumor
Good prognosis

4. LOW RISK HIGH RISK AMES Age Males < 41 y, female < 51 y
Metastases
No distant metastases
Distant metastases
Extent
Intrathyroidal papillary or follicular with minor capsule invasion
Extrathyroidal papillary or follicular with major invasion
Size
< 5 cm
> 5 cm
Definition
A: Any low-risk age group without metastases
B: High-risk age without metastases and with low-risk extent and size
A: Any patient with metastases
B: High-risk age with either high-risk extent and size

5. Debated Issue Includes :
Until today, the management
of DTC are still in controversy
Debated Issue Includes :
The extent of primary surgical resection and / or need for the extent of regional lymph node dissection
The role of post operative radio iodine remnant ablation
The role of B-RAF mutation in management of papillary thyroid carcinoma

6. The Extent of Primary Surgical Resection
Based on high risk and low risk criteria from prognostic scoring system, the controversial issue especially, in the management of low risk case. Some group of surgeons performed only thyroid lobectomy, whether performed total thyroidectomy.

7. The Guidelines of American Thyroid Association 2009:
Thyroid cancer > 1 cm → recommended to perform total / near total thyroidectomy.
Thyroid cancer < 1 cm, is a low risk, unifocal intrathyroidal papillary carcinoma and in the absence of prior head and neck irradiation → recommended to perform only thyroid lobectomy.

8. Neck Dissection
Central – compartment (level VI) neck dissection should included in total thyroidectomy, especially:
Patients with clinically present central or lateral neck lymph node enlargement.
Advanced primary tumors.

9. Lateral neck compartement (level II-V) lymph node dissection:
Should be perfomed for patients with lateral cervical lymph node enlargement which is prove have metastatic by histopathological examination.

10. The Role of Post Operative Radio Iodine Remnant Ablation

11. The goals of the treatment are to destroy any residual thyroid tissue
to prevent locoregional recurrence
and to facilitate surveillance
with whole-body iodine scans
and/or adjusment thyroglobulin value.

12. Major Factors Impacting Decision Making in Radioiodine Remnant Ablation
Expected benefit
Factors
Description
Decreased
risk of
death
reccurence
May facilitate initial staging and follow up
RAI ablation usually recommended
Strength of
evidence T1
1 cm or less, intrathyroidal or microscopic multifocal No
Yes E
1-2 cm, intrathyroidal
Conflicting dataa
Selective usea I T2
> 2-4 cm intrathyroidal C T3
> 4 cm
< 45 years old B
> 45 years old
Any size, any age, minimal extrathyroidal extension
Inadequate dataa T4
Any size with gross extrathyroidal extension
Nx,N0
No metastatic nodes document N1
Conflicting data M1
Distant metastasis present A

13. Gross extrathyroidal extension and distant metastasis present → radioiodine ablation is usually recommended
In low risk case no recommended for radioiodine ablation

14. The Role of B-RAF Mutation in the Management of Papillary Thyroid Carcinoma

15. Extrathyroidal Invasion
VEGF
VEGF-C
HGF
Mutant B-RAF Protein
RET
Met
RAS
HYPOXIA
RAF
MEK
HIF-1α
ERK
ERK
B-RAF
Mutation
HIF-1α-1β
C-MET
ECM
C-JUN
C-FOS
VEGF
VE6F-C
Proliferation ↑
Extrathyroidal Invasion
Lymph node
metastases

16. The recent explosion of knowledge regarding the molecular and cellular pathogenesis of cancer has led to the development of range of targeted therapies
Efficacy has already been demonstrated for several agents including Sorafenib as tyrosine kinase inhibitor

17. Extrathyroidal Invasion
VEGF
VEGF-C
HGF
Mutant B-RAF Protein
Met X
HYPOXIA
MEK
SORAFENIB
HIF-1α
ERK
ERK
B-RAF
Mutation
HIF-1α-1β
C-MET
ECM
C-JUN
C-FOS
VEGF
VE6F-C
Proliferation
Extrathyroidal Invasion

18. Some of the researchers are recommended to undergo sorafenib utilization But, there is no guideline of management papillary thyroid carcinoma, describe the role of tyrosine kinase inhibitor

19. Conclusion
The management of differentiated thyroid carcinoma remains controversial
The choice for management of differentiated thyroid carcinoma:
Total thyroidectomy, radioiodine ablation and thyroxine suppresion therapy.

20. Lateral neck compartement lymph node dissection should be perfomed for patients with lateral cervical lymph node enlargement which is prove have metastatic by histopathological examination.
In papillary thyroid carcinoma with B-RAF mutation are recommended to undergo Sorafenib utilization as Tyrosine Kinase Inhibitor (TKI).

21. THANK YOU