Abstracts

1) Diagnostic accuracy of fine-needle aspiration and frozen section in nodular thyroid disease. Mandell DL, Genden EM, Mechanick OtolaryngolHeadNeckSurg.2001May; 124(5):531-6.

OBJECTIVE: To assess the diagnostic accuracy of fine-needle aspiration (FNA) and frozen section (FS) in nodular thyroid disease. SETTING: Tertiary care academic medical center. STUDY DESIGN: Retrospective review of 139 consecutive patients undergoing surgery for nodular thyroid disease. FNA and FS sensitivity, specificity, and accuracy were calculated with respect to permanent section histology. RESULTS: Among 63 patients with an FNA interpreted as either benign (n = 38) or malignant (n = 25), FNA was accurate (sensitivity 89%, specificity 97%, accuracy 94%). FS identified only one case of carcinoma missed by FNA. Among 76 patients with a “suspicious” FNA, FS was reasonably accurate (sensitivity 67%, specificity 100%, accuracy 89%), but was deferred in 50% of cases. CONCLUSION: Given high FNA accuracy, more selective use of FS is suggested. SIGNIFICANCE: The study results will assist with intra-institutional patient counseling and intraoperative decision-making with respect to FNA and FS results in patients with nodular thyroid disease.To conclude, Intraoperative FS consultation is of great diagnostic value in cases of non-follicular carcinoma and in cases of indeterminate FNAC including “suspicious” FNAC. A confident diagnosis rendered on FS assists surgeon in making therapeutic decision. However its utility is limited, when it comes to the interpretation of encapsulated follicular neoplasms including hurthle cell neoplasms because of high deferral rates, numerous false negatives and occasional false positive cases.A pathologist should be aware of the entire spectrum of thyroid neoplasia & their mimics to be able to render accurate & quick diagnosis on FS. Only the one who understands fully the scope & limitations of FS, can play a vital role in the intraoperative management of thyroid Neoplasia.

2) Prognostic indicators in differentiated thyroid carcinoma. Dean DS, Hay ID. Cancer Control. 2000 May-Jun;7(3):229-39.

BACKGROUND: Thyroid cancer ranges from well-differentiated lesions with an excellent prognosis to anaplastic carcinoma, which is almost uniformly fatal. Thus, methods to assess the behavior of thyroid malignancies are necessary to arrive at appropriate treatment decisions. METHODS: We discuss the factors that affect the prognosis of patients with well-differentiated thyroid malignancies, including papillary, follicular, Hurthle cell, and medullary thyroid carcinomas. We also review the presentation, therapy, and outcome of patients seen at our center over a span of 50 years. These data have identified those prognostic factors that are predictive of survival and recurrence in differentiated thyroid cancer. RESULTS: Several classifications with different variables have been developed to define risk-group categories. Three widely used systems, in addition to the TNM staging system, include AGES, AMES, and MACIS. CONCLUSIONS: A better understanding of independently important prognostic variables will result in improved patient care and treatment.

3) Implications of prognostic factors and risk groups in the management of differentiated thyroid cancer. Shaha AR. Laryngoscope. 2004 Mar; 114(3):393-402.

OBJECTIVES/HYPOTHESIS: The outcome in differentiated thyroid cancer generally depends on the stage of the disease at the time of presentation; prognostic factors such as age, grade, size, extension, or distant metastasis; and risk groups (eg, low or high risk). The author has reviewed a large number of patients with differentiated thyroid cancer to analyze their hypothesis and to confirm that various risk groups have a major implication in relation to extent of the treatment and outcome. Differentiated thyroid cancers make up 90% of all thyroid tumors. The prognostic factors are well defined, such as age, size of the tumor, extrathyroidal extension, presence of distant metastasis, histological appearance, and grade of the tumor. The author has previously divided the risk groups into low-, intermediate-, and high-risk categories based on prognostic factors. The study describes the author’s treatment approach related to the extent of thyroidectomy and adjuvant therapy based on various risk groups and the long-term survival. STUDY DESIGN: Retrospective. METHODS: In a retrospective review of 1038 patients with differentiated thyroid carcinoma, various prognostic factors were studied by univariate and multivariate analysis. The significant prognostic factors were studied in detail and, based on these prognostic factors, the patients were divided into low-, intermediate- and high-risk groups. The survival curves were plotted by Kaplan-Meier method. RESULTS: The long-term survivals in low-, intermediate- and high-risk groups were 99%, 87%, and 57% respectively. Based on these risk groups, a decision tree was made regarding extent of thyroidectomy and adjuvant treatment. In the high-risk group and selected patients in the intermediate-risk group, aggressive surgery including removal of all gross disease and extrathyroidal extension with postoperative radioactive iodine ablation is recommended. In the low-risk group and selected patients in the intermediate-risk group, lobectomy appears to be satisfactory with excellent long-term outcome. The surgical treatment offers the best long-term results in low-risk patients, and the role of adjuvant treatment in this group is questionable. CONCLUSION: The decisions in the management of well-differentiated thyroid cancer should be based on various prognostic factors and risk groups. The long-term survival in the low-risk group is excellent, and consideration should be given to conservative surgical resection depending on the extent of the disease. In the high-risk group and selected patients in the intermediate-risk group, total thyroidectomy with radioactive ablation is warranted. A consideration may be given to external-beam radiation therapy in selected high-risk patients. It is apparent, based on the author’s clinical experience and critical retrospective analysis, that the author’s hypothesis that risk groups are extremely important in the long-term outcome of patients with differentiated thyroid cancer is correct. Based on various risk groups, the author currently is able to guide the treatment policies for thyroid cancer.

4) Unilateral total lobectomy: is it sufficient surgical treatment for patients with AMES low-risk papillary thyroid carcinoma? Hay, Grant CS, Bergstralh EJ, Thompson GB et al Surgery. 1998 Dec; 124(6):958-64

BACKGROUND: This study was designed to compare CSM and recurrence rates after either unilateral lobectomy (UL) or bilateral lobar resection (BLR) in patients with PTC considered low risk by AMES criteria. METHODS: Outcome was studied in 1685 patients initially treated during 1940 through 1991 and followed for up to 54 postoperative years (mean, 18 years). One thousand six hundred fifty-six patients (98%) had complete primary tumor resection; 634 (38%) had involvement of regional nodes. One hundred ninety-five patients (12%) had UL; BLR accounted for 1468 (near-total 60%; total thyroidectomy 18%). RESULTS: Thirty-year rates for CSM and distant metastasis were 2% and 3%, respectively. Twenty-year rates for local recurrence and nodal metastasis were 4% and 8%, respectively. There were no significant differences in CSM or distant metastasis rates between UL and BLR (P > .2). After UL, 20-year rates for local recurrence and nodal metastasis were 14% and 19%, significantly higher (P = .0001) than the 2% and 6% rates seen after BLR. CONCLUSIONS: UL was not associated with higher CSM rates, but it was associated with a significantly higher risk of locoregional recurrence. Thus BLR probably represents a preferable initial surgical approach to patients with low-risk PTC.

5) Initial results from a prospective cohort study of 5583 cases of thyroid carcinoma treated in the United States during 1996. U.S. and German Thyroid Cancer Study Group. An American College of Surgeons Commission on Cancer Patient Care Evaluation study. Hundahl SA, Cady B, Cunningham MP et al. Cancer. 2000 Jul 1; 89(1):202-17.

METHODS: Over 1500 hospitals with CoC (The American College of Surgeons Commission on Cancer (CoC))-approved cancer programs were invited to participate in this prospective cohort study of U.S. thyroid carcinoma cases treated in 1996. Follow-up was conducted through the National Cancer Data Base. RESULTS: Of the 5584 cases of thyroid carcinoma, 81% were papillary, 10% follicular, 3.6% Hurthle cell, 0.5% familial medullary, 2.7% sporadic medullary, and 1.7% undifferentiated/anaplastic. The vast majority of patients with differentiated thyroid carcinoma presented with American Joint Committee on Cancer Stage I and II disease and relatively small tumors. For all histologies, near-total or total thyroidectomy constituted the dominant surgical treatment(77.4% of cases). Residual tumor after the surgical event could be documented in 11% of cases, hypocalcaemia in 10% of cases, and recurrent laryngeal nerve injury in 1.3% of cases. Complications were most frequently associated with total thyroidectomy combined with lymph node dissection. Adjuvant treatment, probably underreported in this study, consisted of hormonal suppression (50% overall) and radioiodine (50% overall). CONCLUSIONS:, This current PCE study offers a surveillance snapshot of current management of thyroid carcinoma in the U.S and showed that the majority of surgeons prefer total thyroidectomy as the initial treatment of differentiated thyroid carcinoma, all things standing equal.

6) Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Mazzaferri EL, Jhiang SM. Am J Med. 1994 Nov;97(5):418-28.

PURPOSE: To determine the long-term impact of medical and surgical treatment of well differentiated papillary and follicular thyroid cancer. METHODS: Patients with papillary and follicular cancer (n = 1,355) treated either in U.S. Air Force or Ohio State University hospitals over the past 40 years were prospectively followed by questionnaire or personal examination to determine treatment outcomes. Outcomes were analyzed by Kaplan-Meier survival curves and Cox proportional-hazard regression model. RESULTS: Median follow-up was 15.7 years; 42% (568) of the patients were followed for 20 years and 14% (185) for 30 years. After 30 years, the survival rate was 76%, the recurrence rate was 30%, and the cancer death rate was 8%. Recurrences were most frequent at the extremes of age (< 20 and > 59 years). Cancer mortality rates were lowest in patients younger than 40 years and increased with each subsequent decade of life. In a Cox regression model that excluded patients who presented with distant metastases, the likelihood of cancer death was (1) increased by age > or = 40 years, tumor size > or = 1.5 cm, local tumor invasion, regional lymph-node metastases, and delay in therapy > or = 12 months; (2) reduced by female sex, surgery more extensive than lobectomy, and 131I plus thyroid hormone therapy; and (3) unaffected by tumor histologic type. Following 131I therapy given only to ablate normal thyroid gland remnants, the recurrence rate was less than one third the rate after thyroid hormone therapy alone (P < 0.001). No patient treated in this way with 131I died of thyroid cancer. Following 131I therapy, whether given for thyroid remnant ablation or cancer therapy, recurrence and the likelihood of cancer death were reduced by at least half, despite the existence of more adverse prognostic factors in patients given 131I. At 30 years, the cumulative cancer mortality rate following 131I therapy, regardless of the reason for its use, was one third that in patients not so treated (P = 0.03). CONCLUSION: Over the long term, for tumors > or = 1.5 cm that are not initially metastatic to distant sites, near-total thyroidectomy followed by 131I plus thyroid hormone therapy confers a distinct outcome advantage. This therapy reduces tumor recurrence and mortality sufficiently to offset the augmented risks incurred by delayed therapy, age > or = 40 at the time of diagnosis, and tumors that are much larger than 1.5 cm, multicentric, locally invasive, or regionally metastatic.

7) Effects of thyroid hormone suppression therapy on adverse clinical outcomes in thyroid cancer. McGriff NJ, Csako G, Gourgiotis L et al. Ann Med. 2002;34(7-8):554-64.

BACKGROUND: Long-term thyroid hormone (TH) therapy aiming at the suppression of serum thyrotropin (TSH) has been traditionally used in the management of well differentiated thyroid cancer (ThyrCa). However, formal validation of the effects of thyroid hormone suppression therapy (THST) through randomized controlled trials is lacking. Additionally, the role - if any - of TSH effect at low ambient concentrations upon human thyroid tumorigenesis remains unclear. AIM: Evaluation of the effect of THST on the clinical outcomes of papillary and/or follicular ThyrCa. METHODS: By using a quantitative research synthesis approach in a cumulative ThyrCa cohort, we evaluated the effect of THST on the likelihood of major adverse clinical events (disease progression/recurrence and death). A total of 28 clinical trials published during the period 1934-2001 were identified; only 10 were amenable to meta-analysis. Causality was assessed by Hill criteria. RESULTS: Out of 4, 174 patients with ThyrCa, 2, 880 (69%) were reported as being on THST. Meta-analysis showed that the group of patients who received THST had a decreased risk of major adverse clinical events (RR = 0.73; Cl = 0.60-0.88; P < 0.05). Further, by applying a Likert scale, 15/17 interpretable studies showed either a ‘likely’ or ‘questionable’ beneficial effect of THST. Assessment of causality between TSHT and reduction of major adverse clinical events suggested a probable association. CONCLUSIONS: THST appears justified in ThyrCa patients following initial therapy. As most primary studies were imperfect, future research will better define the effect of THST upon ThyrCa clinical outcomes.

8) The evolving role of (131)I for the treatment of differentiated thyroid carcinoma. Robbins, Richard J, Schlumberger, Martin J J Nucl. Med 46(2005), pp28S-37S

Abstract : The use of radioactive iodine ((131)I) for the treatment of thyroid carcinoma has changed over the past 50 y. These changes are based on increasing awareness of the biophysical properties of (131)I and new discoveries concerning the biology of iodine handling by thyroid cells. The therapeutic administration of (131)I for thyroid remnant ablation and for metastases requires an appreciation of iodine clearance kinetics, of factors that can alter the occupancy time of (131)I within lesions, and of the role of thyroid-stimulating hormone in stimulating the sodium-iodide symporter.

The potential complications and adverse events associated with (131)I are discussed. (131)I will continue to be a major weapon in the fight against metastatic thyroid carcinoma. Its future role will be modified by expanding knowledge of its relative risks and benefits.

9) A systematic review and metaanalysis of the effectiveness of radioactive iodine remnant ablation for well-differentiated thyroid cancer. Sawka A M, Thephamongkhol K, Brouwers M et al.
J Clin Endocrinol Metab 89 (2004), pp 3668-3676

Abstract : Radioactive iodine remnant ablation destroys residual thyroid tissue after surgical resection of papillary or follicular thyroid cancer. We systematically reviewed 1543 English references to determine whether remnant ablation decreases the risk of thyroid cancer-related death or recurrence after bilateral thyroideciomy for papillary or follicular thyroid cancer. In 13 cohort studies in which the analysis of thyroid cancer-related outcomes was statistically adjusted to a variable degree for prognostic factors or cointerventions, rates of recurrences of thyroid cancer-related outcomes were significantly decreased in the following: one of seven studies examining thyroid cancer-related mortality, three of six studies examining any tumor recurrence, three of three studies examining locoregional recurrence, and two of three studies examining distant metastases. Thyroid hormone suppressive therapy was not adjusted for in the majority of these analyses. In 18 cohort studies not adjusted for prognostic factors or interventions, the benefit off radioactive iodine ablation in decreasing the thyroid cancer-related mortality and any recurrence at 10 yr was inconsistent among centers. However, pooled analyses were suggestive of a statistically significant treatment effect of ablation for the following 10-yr outcomes: locoregional recurrence (relative risk of 0.31, 95% confidence interval, 0.2, 0.49) and distant metastases (absolute decrease in risk 3%, 95% confidence interval, risk decreases 1-4%). In conclusion, radioactive iodine ablation may be beneficial in decreasing recurrence of well-differentiated thyroid cancer; however, results are inconsistent among centers for some outcomes, and the incremental benefit of remnant ablation in low-risk patients treated with bilateral thyroidectomy and thyroid hormone suppressive therapy is unclear.

10) Comparison of administration of recombinant human thyrotropin with withdrawal of thyroid hormone for radioactive iodine scanning in patients with thyroid carcinoma.Ladenson PW, Braverman LE, Mazzaferri EL et al. N Engl J Med. 1997 Sep 25;337(13):888-96

BACKGROUND: To detect recurrent disease in patients who have had differentiated thyroid cancer, periodic withdrawal of thyroid hormone therapy may be required to raise serum thyrotropin concentrations to stimulate thyroid tissue so that radioiodine (iodine-131) scanning can be performed. However, withdrawal of thyroid hormone therapy causes hypothyroidism. Administration of recombinant human thyrotropin stimulates thyroid tissue without requiring the discontinuation of thyroid hormone therapy. METHODS: One hundred twenty-seven patients with thyroid cancer underwent whole-body radioiodine scanning by two techniques: first after receiving two doses of thyrotropin while thyroid hormone therapy was continued, and second after the withdrawal of thyroid hormone therapy. The scans were evaluated by reviewers unaware of the conditions of scanning. The serum thyroglobulin concentrations and the prevalence of symptoms of hypothyroidism and mood disorders were also determined. RESULTS: Sixty-two of the 127 patients had positive whole-body radioiodine scans by one or both techniques. The scans obtained after stimulation with thyrotropin were equivalent to the scans obtained after withdrawal of thyroid hormone in 41 of these patients (66 percent), superior in 3 (5 percent), and inferior in 18 (29 percent). When the 65 patients with concordant negative scans were included, the two scans were equivalent in 106 patients (83 percent). Eight patients (13 percent of those with at least one positive scan) were treated with radioiodine on the basis of superior scans done after withdrawal of thyroid hormone. Serum thyroglobulin concentrations increased in 15 of 35 tested patients: 14 after withdrawal of thyroid hormone and 13 after administration of thyrotropin. Patients had more symptoms of hypothyroidism (P<0.001) and dysphoric mood states (P<0.001) after withdrawal of thyroid hormone than after administration of thyrotropin.

CONCLUSIONS: Thyrotropin stimulates radioiodine uptake for scanning in patients with thyroid cancer, but the sensitivity of scanning after the administration of thyrotropin is less than that after the withdrawal of thyroid hormone. Thyrotropin scanning is associated with fewer symptoms and dysphoric mood states.

11) A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer.Haugen BR, Pacini F, Reiners C et al. J Clin Endocrinol Metab. 1999 Nov; 84(11):3877-85

Recombinant human TSH has been developed to facilitate monitoring for thyroid carcinoma recurrence or persistence without the attendant morbidity of hypothyroidism seen after thyroid hormone withdrawal. The objectives of this study were to compare the effect of administered recombinant human TSH with thyroid hormone withdrawal on the results of radioiodine whole body scanning (WBS) and serum thyroglobulin (Tg) levels. Two hundred and twenty-nine adult patients with differentiated thyroid cancer requiring radioiodine WBS were studied. Radioiodine WBS and serum Tg measurements were performed after administration of recombinant human TSH and again after thyroid hormone withdrawal in each patient. Radioiodine whole body scans were concordant between the recombinant TSH-stimulated and thyroid hormone withdrawal phases in 195 of 220 (89%) patients. Of the discordant scans, 8 (4%) had superior scans after recombinant human TSH administration, and 17 (8%) had superior scans after thyroid hormone withdrawal (P = 0.108). Based on a serum Tg level of 2 ng/mL or more, thyroid tissue or cancer was detected during thyroid hormone therapy in 22%, after recombinant human TSH stimulation in 52%, and after thyroid hormone withdrawal in 56% of patients with disease or tissue limited to the thyroid bed and in 80%, 100%, and 100% of patients, respectively, with metastatic disease. A combination of radioiodine WBS and serum Tg after recombinant human TSH stimulation detected thyroid tissue or cancer in 93% of patients with disease or tissue limited to the thyroid bed and 100% of patients with metastatic disease. In conclusion, recombinant human TSH administration is a safe and effective means of stimulating radioiodine uptake and serum Tg levels in patients undergoing evaluation for thyroid cancer persistence and recurrence.

12) Differentiated thyroid cancer. Impact of adjuvant external radiotherapy in patients with perithyroidal tumor infiltration (stage pT4).Farahati J, Reiners C, Stuschke M et al.Cancer. 1996 Jan 1; 77(1):172-80

BACKGROUND. The role of adjuvant external radiotherapy in the survival of patients with differentiated thyroid cancer (DTC) is controversial. To our knowledge, no attempt has been undertaken thus far to assess the impact of this therapy with respect to the papillary and follicular types of thyroid cancer as separate entities. METHODS. Between 1979 and 1992, 238 patients with differentiated papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) with Stage pT4 have been treated and followed in our clinic. One hundred sixty-nine patients free of metastases at the final staging, which was performed after the second radioiodine therapy, were included in this study. The standard treatment comprised total thyroidectomy, ablative radioiodine therapy, and thyroid-stimulating hormone-suppressive therapy with levothyroxin. Ninety-nine patients free of disease after the final staging received additional external radiotherapy to the neck (with a dose of 50-60 Gy), whereas the remaining 70 patients were treated with the standard treatment protocol only. Distributions of age, sex, and follow-up time were comparable in both irradiated and nonirradiated groups. Multivariate analysis of the influence of age, sex, histologic subtype, and lymph node status as well as of external radiotherapy on the time to first locoregional and distant failure (LDF), and the time to locoregional recurrence (LR), was accomplished using Cox’s proportional hazard model. RESULTS. In patients with DTC, external radiotherapy was a predictive factor for improvement of both LR (P = 0.004) and locoregional and distant failure (P = 0.0003). When the time to first locoregional and distant failure was calculated separately for patients with PTC and FTC, there was a significant difference in the PTC group in favor of irradiated patients (P = 0.0001), whereas there was no effect of external radiotherapy in the FTC group (P = 0.38). Further analyses disclosed that this effect was significantly present only in patients with PTC and lymph node involvement (P = 0.002), whereas those without lymph node involvement did not benefit from an additional adjuvant radiotherapy (P = 0.27). Because none of the patients younger than age 40 years died due to the disease nor had progressive disease during follow-up, we reassessed our results in patients older than age 40 years. The effect of external radiotherapy could be confirmed in this subgroup of patients (P = 0.0009) and in the subgroup of lymph node positive patients older than age 40 years with invasive PTC (P = 0.01). CONCLUSIONS. In addition to total thyroidectomy, treatment with radioiodine, and TSH-suppressive therapy with thyroid hormone, adjuvant external radiotherapy improves the recurrence-free survival in patients older than age 40 years with invasive PTC and lymph node involvement.