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Oncological outcomes for patients with well differentiated thyroid cancer
Nixon, I.J.
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Nixon, I. J. (2013). Oncological outcomes for patients with well differentiated thyroid cancer
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Download date: 18 Jun 2017
Chapter 4
Thyroid Isthmusectomy for
Well Differentiated Thyroid Cancer
Iain J Nixon, MD, Frank L. Palmer, BA, Monica M Whitcher, BA, Ashok R Shaha, MD,
Jatin P Shah, MD, Snehal G Patel, MD, Ian Ganly, MD, PhD
Ann Surg Oncol 2011; 18(3): 767-770
Abstract
Background
The American Thyroid Association guidelines do not mention isthmusectomy as an
appropriate procedure for thyroid cancer. Despite this, a small number of patients present
with lesions isolated to the thyroid isthmus, which can be excised without exploring the
trachesophageal grooves or total thyroidectomy. The aim of this study was to analyse
outcomes in patients treated with isthmusectomy for small well differentiated thyroid
cancer (WDTC) at our institution.
Methods
Nineteen patients with WDTC managed by isthmusectomy were identified from a database
of 1810 patients (1%) with WDTC managed by surgery in Memorial Sloan Kettering Cancer
Center, between 1986-2005. Demographic, surgical, pathological and outcomes data were
analyzed.
Results
Six patients were male and 13 female. The median age was 46 years (range 28-83 years).
All patients had a solitary nodule confined to the thyroid isthmus. The median size of
lesion was 1cm (range 0.4-3cm). Eighteen patients had a pathologically T1 disease (pT1),
1 patient had a pT2 lesion. Two patients had papillary carcinoma detected in peri-thyroid
lymph nodes (pN1a).
There were no complications of recurrent laryngeal nerve palsy or hypocalcaemia.
With a median follow up of 124 months (range 53-276), the 10 year disease specific
survival was 100% and 100% local and regional 10 year recurrence free survival.
Conclusion
54
Our results suggest that isthmusectomy alone may be sufficient treatment in selected
patients with small WDTC limited to the isthmus. This procedure has the benefit of
avoiding dissection of the recurrent laryngeal nerve and parathyroid glands thus limiting
post operative complications.
The place of thyroid isthmusectomy in the management of thyroid cancer is unclear. Neither
the current American Thyroid Association1 nor the British Thyroid Association guidelines2
mention isthmusectomy as an appropriate procedure in the setting of thyroid cancer. Despite
this, a small number of patients will present with malignant disease isolated to the thyroid
isthmus, which can be excised without exploring the trachesophageal grooves. This approach
has the attraction of reducing the potential for damage to the recurrent laryngeal nerves and
parathyroid glands, as well as reducing operating time.
Of the few reports in the literature on thyroid isthmusectomy3-6, most series include only
small numbers of malignant lesions. Of the malignant lesions, most patients were treated
with completion thyroidectomy after isthmusectomy. The aim of our study was to analyse the
outcomes of patients treated with thyroid isthmusectomy alone for localized well differentiated
thyroid cancer over a 20 year period at our institution. This is the largest series reporting on the
role of isthmusectomy alone in the management of thyroid cancer confined to the isthmus.
Chapter 4 Cyclooxygenase-2 inhibition inhibits c-Met kinase activity and Wnt activity in colon cancer.
Introduction
55
Methods and Patients
Following approval by the Institutional Review Board, nineteen patients with well differentiated
thyroid cancer managed by thyroid isthmusectomy alone were identified from a database of
1810 patients (1%) with well differentiated thyroid cancer managed by surgery in Memorial
Sloan Kettering Cancer Center, between 1986-2005. Patients who underwent initial treatment
elsewhere prior to referral or those who were considered unresectable at the time of referral
were excluded. Data was extracted from the electronic medical record and entered into an
Excel spreadsheet for analysis.
Data was collected on patient demographics, surgical details including extent of both thyroid
and neck surgery, and the presence of gross extra-thyroid extension or residual disease on
completion of surgery. Pathological details included tumor histology, size, and presence of
extra-thyroid extension. Outcomes data included local, regional or distant recurrence. The
presence of local or regional recurrence following treatment was based on cytological or
histopathological evidence of disease. Distant disease was determined by imaging studies
including radioiodine uptake scans and CT scans, or cytological and histopathological
evidence where available. Biochemical evidence of recurrence was not accepted as definitive,
as the use of thyroglobulin measurement was not routine practice during the early part of the
study period, and may be difficult to interpret in the presence of normal thyroid lobes.
Statistical analysis was performed using JMP statistical package (SAS Institute Inc. SAS Campus
Drive, Cary, NC 27513). Survival outcomes were analyzed using the Kaplan-Meier method.
56
The clinical and pathological characteristics are shown in Table 1.
Patient and Treatment Characteristics
Six patients were male and 13 female. The median age was 46 years (range 28-83 years). All
patients had a solitary nodule confined to the thyroid isthmus. Eighteen patients (95%) were
T1 and 1 patient (5%) was T2. Eighteen patients (95%) were clinically N0 and 1 patient (5%) was
clinically N1b. All patients were free of distant metastases.
Nine patients (47%) were first diagnosed with malignancy on pre-operative fine needle
aspiration (FNA), a further 3 patients (16%) were diagnosed at frozen section in the operating
room. Seven patients (37%) were diagnosed on final histopathological analysis.
The 1 patient with a palpable cervical lymph node had failed to respond to chemoradiotherapy for an oropharyngeal cancer, and had a suspicious nodule in the thyroid isthmus
on CT scan, which was positive for papillary carcinoma. The cervical node was found to contain
squamous cell carcinoma on histopathological analysis. This patient had isthmusectomy and
modified radical neck dissection. All remaining patients underwent thyroid isthmusectomy
alone. No patients received post-operative radio-iodine treatment.
Pathology
In 18 patients (95%) the diagnosis was papillary carcinoma. The remaining 1 patient (5%) had
follicular carcinoma.
The median size of lesion was 1cm (range 0.4-3cm). Eighteen patients had a pathologically
T1 disease (pT1), 1 patient had a pT2 lesion. Two patients had papillary carcinoma detected in
peri-thyroid lymph nodes, making them pN1a.
In two patients the surgical margin was microscopically positive. Two patients had microscopic
extra thyroid extension noted on histopathology with no evidence of extension seen during
surgery.
Following surgical excision 8 patients (42%) were classified as low risk, 9 as intermediate (47%)
and 2 were classified as high risk (11%) using the GAMES criteria.
Outcomes
There were no complications of recurrent laryngeal nerve palsy or hypocalcaemia. One patient
had a wound hematoma managed at the bedside without return to the operating room.
The median follow up was 124 months (range 53-276). During this time there were no disease
specific deaths (10 year disease specific survival 100%). The 10 year overall survival was 94%,
one patient died at 65 months of unrelated causes.
There were no regional or distant recurrences. One patient had a papillary carcinoma removed
from the right thyroid lobe at 124 months by uncomplicated completion thyroidectomy. That
patient was a low risk female, with a 1cm tumor without extra thyroid extension. No patient
with positive margins or microscopic extra thyroid extension had a local or regional recurrence.
Chapter 4 Cyclooxygenase-2 inhibition inhibits c-Met kinase activity and Wnt activity in colon cancer.
Results
57
Discussion
58
Outcomes for patients with well differentiated thyroid cancers are excellent with 20 year survival
rates of around 90%7-10. Current guidelines do not support surgical management of thyroid
cancer with procedures other than thyroid lobectomy, near-total and total thyroidectomy1,2.
There are no specific guidelines for management of thyroid cancers confined to the thyroid
isthmus. Although the majority of thyroid nodules present within the body of the lobes, a small
minority of patients will present with disease limited to the isthmus11. Lesions of the thyroid
isthmus occur in less than 10% of patients presenting with thyroid cancer, and may have a
higher incidence of both multifocality and capsular invasion than cancers presenting in the
lobes11. If, in this situation, the nodule is solitary, confined to the isthmus without evidence of
extra glandular extension, the patient may be suitable for thyroid isthmusectomy or wide field
isthmusectomy. Unlike excision of a thyroid lobe, isthmusectomy does not require exploration
of the trachesophageal groove or formal identification of the recurrent laryngeal nerve, which
may reduce risk to the parathyroid glands and the recurrent laryngeal nerve.
Although thyroid isthmusectomy is a recognised surgical procedure, few groups have reported
their experience with the procedure for thyroid cancer 3-6,12. In the majority of reports in which
a cancer is found after isthmusectomy, completion thyroidectomy is normally performed.
Perez-Ruiz et al report a series of 31 isthmusectomies including only 1 papillary carcinoma,
who proceeded to completion thyroidectomy 1 week later4. Similarly, Skilbeck et al report
their experience of 9 isthmusectomies for isolated isthmic lesions with indeterminate
cytology5. Two of their patients were finally diagnosed with malignancy and both patients
again proceeded to completion thyroidectomy. Maser et al report on 8 patients with benign or
indeterminate cytology from an isthmic nodule. Three of their patients were diagnosed with
malignancy on histopathology and all went on to completion thyroidectomy3. In Sugenoya et
al’s report on 19 well differentiated thyroid isthmus malignancies, four patients were treated
with isthmusectomy alone and all were alive with no evidence of recurrence 20 years following
surgery. This finding prompted the authors to recommend isthmusectomy as an appropriate
treatment for malignant lesions of the thyroid isthmus6.
We advocate isthmusectomy for an isolated lesion of the thyroid isthmus without evidence of
extraglandular spread on imaging or assessment in the operating room. Using these criteria
only 19 of 1811 patients (1%) were deemed suitable for isthmusectomy between 1986 and
2005.
All patients in this study had clinically apparent disease limited to the thyroid isthmus. In 1
patient suspected of having metastasis to the lateral neck, the metastatic malignancy was
from an aerodigestive tract primary rather than from the thyroid.
With a median follow up of over 10 years, disease specific survival and both regional and
distant recurrence free survival in our group was 100%. One patient died of unrelated causes
during the study period. One patient developed a papillary cancer in the residual thyroid tissue
and underwent uneventful completion thyroidectomy over 10 years following initial surgery.
We encountered no cases of hypocalcaemia or recurrent laryngeal nerve damage.
Chapter 4 Cyclooxygenase-2 inhibition inhibits c-Met kinase activity and Wnt activity in colon cancer.
Using our previously published risk stratification scheme, GAMES, 58% of patients were
classified as intermediate or high risk. Despite this, our results suggest that in carefully selected
patients, thyroid isthmusectomy can be effective treatment for well differentiated thyroid
cancer.
Thyroid isthmusectomy should be reserved for selected patients with a small thyroid tumor
with no major extrathyroidal extension or adherence to the surrounding structures. It should
be recognized that this is not a nodulectomy, it is an oncologic procedure with wide-field
isthmusectomy which encompasses all gross tumor and a surrounding portion of normal
thyroid tissue. Most of these patients are low or intermediate risk thyroid cancer patients who
do not require postoperative radioactive iodine ablation. The preoperative ultrasound should
be reviewed carefully to ensure there is no nodularity involving either lobe of the thyroid.
Postoperative follow-up is generally clinical follow-up along with sonographic evaluation and
thyroid function tests, etc. In our experience, this is a sound oncologic surgical procedure for
small tumors involving the isthmus of the thyroid.
59
Conclusion
Our results suggest that isthmusectomy alone may be sufficient treatment in selected patients
with small, well differentiated cancer limited to the thyroid isthmus. This procedure has the
added benefit of avoiding dissection of the recurrent laryngeal nerve and parathyroid glands
thus limiting post-operative complications of hoarseness and hypocalcaemia.
60
1. Cooper, D.S., G.M. Doherty, B.R. Haugen, R.T. Kloos,
S.L. Lee, S.J. Mandel, E.L. Mazzaferri, et al. Revised
American Thyroid Association management
guidelines for patients with thyroid nodules
and differentiated thyroid cancer. Thyroid, 2009.
19(11): 1167-214.
2. Watkinson, J.C. The British Thyroid Association
guidelines for the management of thyroid cancer
in adults.Nucl Med Commun, 2004. 25(9): 897-900.
3. Maser, C., P. Donovan, and R. Udelsman. Thyroid
isthmusectomy: a rarely used but simple, safe, and
efficacious operation. J Am Coll Surg, 2007. 204(3):
512-4.
4. Perez-Ruiz, L., S. Ros-Lopez, M. Gudelis, J.A. LatasaGimeno, C. Artigas-Marco, and A. Pelayo-Salas.
Isthmectomy: a conservative operation for solitary
nodule of the thyroid isthmus. Acta Chir Belg,
2008. 108(6): 699-701.
5.Skilbeck, C., A. Leslie, and R. Simo. Thyroid
isthmusectomy: a critical appraisal. J Laryngol
Otol, 2007. 121(10): 986-9.
6. Sugenoya, A., K. Shingu, S. Kobayashi, H. Masuda,
S. Takahashi, T. Shimizu, H. Onuma, et al. Surgical
strategies for differentiated carcinoma of the
thyroid isthmus. Head Neck, 1993. 15(2): 158-60.
7. Hay, I.D., E.J. Bergstralh, J.R. Goellner, J.R. Ebersold,
and C.S. Grant. Predicting outcome in papillary
thyroid carcinoma: development of a reliable
prognostic scoring system in a cohort of 1779
patients surgically treated at one institution
during 1940 through 1989. Surgery, 1993. 114(6):
1050-7; discussion 1057-8.
8. Mazzaferri, E.L. and S.M. Jhiang. Long-term impact
of initial surgical and medical therapy on papillary
and follicular thyroid cancer.The American journal
of medicine, 1994. 97(5): 418-428.
9. Lin, H.W. and N. Bhattacharyya. Survival impact of
treatment options for papillary microcarcinoma of
the thyroid. Laryngoscope, 2009. 119(10): 1983-7.
10.Shaha, A.R., J.P. Shah, and T.R. Loree. Risk group
stratification and prognostic factors in papillary
carcinoma of thyroid. Ann Surg Oncol, 1996. 3(6):
534-8.
11.Lee, Y.S., J.J. Jeong, K.H. Nam, W.Y. Chung, H.S.
Chang, and C.S. Park. Papillary carcinoma located
in the thyroid isthmus. World J Surg, 2010. 34(1):
36-9.
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Chapter 4 Cyclooxygenase-2 inhibition inhibits c-Met kinase activity and Wnt activity in colon cancer.
References
61
Table 1. Clinical and pathological characteristics
Variables
N (%)
Age
<45y
9 (47%)
>45y
10 (53%)
Gender
Male
6 (32%)
Female
13 (68%)
N0
18 (95%)
N1b
1 (5%)
(Ultimately SCC)
M0
19 (100%)
M1
0
cN Stage
M Stage
Histology
Papillary Ca
18 (95%)
Follicular Ca
1 (5%)
Negative
17 (89%)
Positive
2 (11%)
T1
18 (95%)
T2
1 (5%)
Margins
pT Stage
62
Extra Thyroid Extension
None
17 (89%)
Microscopic
2 (11%)
pN Stage
N0
17 (89%)
N1a
2 (11%)
GAMES Criteria
Low
8 (42%)
Intermediate
9 (47%)
High
2 (11%)
GAMES is the method of risk stratification used in Memorial Sloan Kettering Cancer Center10