Clinical Status and Treatment of Liver Metastasis of Differentiated Thyroid Cancer Using Tyrosine Kinase Inhibitors.

BACKGROUND: Treatment of patients with liver metastasis of differentiated thyroid carcinoma (DTC) has not been sufficiently defined, because liver metastasis of DTC has been described mostly as case reports. Additionally, such patients are considered end-of-treatment responders. A relatively new approach using tyrosine kinase inhibitors (TKIs) may provide opportunities to manage systemic metastasis. This study aims to define the clinical features of DTC patients with liver metastasis and evaluate the benefits of TKIs. METHODS: We retrospectively analyzed clinical features of 29 patients (mean age 67.8 years) diagnosed with liver metastasis of DTC at our institution between January 1981 and May 2017. RESULTS: All patients had distant metastasis at other organ sites upon diagnosis of liver metastasis; 41% of them developed new metastasis afterward. Management after diagnosis of liver metastasis comprised palliative care (48%), radioactive iodine therapy (28%), and TKI therapy (24%). The median survival after diagnosis of liver metastasis was only 4.8 months. Survival rates were significantly better in patients with performance statuses between 0 and 2 on the Eastern Cooperative Oncology Group scale at diagnosis of liver metastasis (n = 22, 76%) treated with TKI compared to those who were not (P = 0.017; log-rank test; hazard ratio 0.19). One-year survival rates were 71.4 and 26.7% for patients treated with or without TKI, respectively. CONCLUSIONS: Patients with liver metastasis had poor clinical prognosis. When other distant metastases existed at diagnosis of liver metastasis, TKI therapy was considered an effective therapeutic option for patients with liver metastasis of DTC.

Pediatric differentiated thyroid carcinoma: trends in practice and outcomes over 40 years at a single tertiary care institution.

BACKGROUND: This study aims to analyze changes in characteristics, practice and outcomes of pediatric differentiated thyroid cancer (DTC) at our tertiary care institution. METHODS: Patients <21 years of age diagnosed between 1973 and 2013 were identified. Clinicopathological data, treatment and outcomes were obtained by a retrospective review. RESULTS: Thirteen males and 68 females were divided into Group A (n=35, diagnosed before July 1993) and Group B (n=46, diagnosed after July 1993). Group B was more likely to undergo neck ultrasound (US) (70% vs. 23%, p<0.0001) and fine-needle aspiration (FNA) biopsy (80% vs. 26%, p<0.0001). Patients in Group B more often underwent total thyroidectomy as a definitive surgical treatment (87% vs. 69%, p=0.04). There was no difference in radioactive iodine use. Recurrence-free survival was similar. CONCLUSIONS: Increased use of US and FNA has affected initial surgical management in the latter part of the study, possibly due to extension of adult DTC guidelines. The effects of the new pediatric DTC guidelines need further study.

LONG-TERM OUTCOMES AND PROGNOSTIC FACTORS IN PATIENTS WITH DIFFERENTIATED THYROID CANCER AND DISTANT METASTASES.

OBJECTIVE: Distant metastatic spread is the most frequent cause of thyroid cancer-related death. The objective of this study was to evaluate overall and disease-related survival of patients with differentiated thyroid cancer (DTC) and distant metastases (DM) attending a single medical center and to investigate variables predictive of better long-term outcomes. METHODS: The Rabin Medical Center Thyroid Cancer Registry was searched for patients with DM from DTC. RESULTS: The cohort included 138 patients (58.7% female) diagnosed at age 54.7 ± 19.5 years. Mean primary tumor size was 33.9 ± 26 mm. Most patients (57.7%) were stage T3/T4; 48.7% had extrathyroidal extension; 53.5% had lymph node metastases. Histopathology yielded papillary and follicular thyroid carcinoma in 66.7% and 13.8%, respectively, and intermediate/poorly differentiated carcinoma in 19.6%. All but 2 patients underwent total thyroidectomy, and 133/138 (96.4%) received radioactive iodine (RAI) therapy. DM were synchronous in 55.1%. The mean follow-up was 8.2 years from detection of metastases. The common sites of metastases were the lungs (85.6% of patients), bones (39.9%), brain (5.8%) and liver (3.6%). At last follow-up, resolution was documented in 24.6% of patients, improvement/stable disease in 31.6%, and structurally progressive disease in 43.4%. By the end of the study, 40.6% of patients died, 23.2% of DTC. Improved overall survival and disease progression were associated with younger age, lung-only DM, and metastatic RAI avidity. CONCLUSION: Patients with DTC and DM treated by standard-of-care approaches frequently achieve favorable long-term outcomes. Novel therapies might be necessary in only a minority of these patients, and the reported prognostic factors can aid in their identification. ABBREVIATIONS: CR = complete response; DM = distant metastases; DTC = differentiated thyroid cancer; ETE = extra-thyroidal extension; M0 = detected during follow-up; M1 = detected at diagnosis; MSKCC = Memorial Sloan Kettering Cancer Center; NED = no evidence of disease; OS = overall survival; PFS = progression free survival; PTC = papillary thyroid cancer; RAI = radioactive iodine; Tg = thyroglobulin.

Role of salvage targeted therapy in differentiated thyroid cancer patients who failed first-line sorafenib.

CONTEXT: Sorafenib, a tyrosine kinase inhibitor, is a common first-line therapy for advanced differentiated thyroid cancer (DTC). However, responses are not durable and drug toxicity remains a problem. OBJECTIVE: The objective of the study was to determine the efficacy of salvage therapy after first-line sorafenib failure. DESIGN: This was a retrospective review at M. D. Anderson Cancer Center from January 2005 to May 2013. PATIENTS: The study included patients with metastatic DTC who received salvage therapy after their initial sorafenib failure (group 2). PATIENTS who received first-line sorafenib only (group 1) were evaluated for comparison of overall survival (OS). OUTCOME MEASURES: Progression-free survival, best response, and median OS were measured. RESULTS: Sixty-four patients with metastatic, radioactive iodine refractory DTC were included; 35 were in group 1 and 25 were in group 2, and the groups were well balanced. Median OS of all 64 patients receiving first line sorafenib was 37 months; median OS was significantly longer with salvage therapy compared with sorafenib alone (58 vs 28 months, P = .013). In group 2, 17 patients were evaluable for best response, although two patients had toxicity with sorafenib, which was discontinued before restaging. Best responses with first-line sorafenib were partial response in 2 of 15 (13%), stable disease in 10 of 15 (67%), and progressive disease in 3 of 15 (20%) patients. With salvage therapy, partial responses were seen in 7 of 17 (41%) and stable disease in 10 of 17 (59%) patients. Median progression-free survival was 7.4 months with first-line sorafenib and 11.4 months with salvage therapy. Salvage therapy included sunitinib (n = 4), pazopanib (n = 3), cabozantinib (n = 4), lenvatinib (n = 3), and vemurafenib (n = 3). CONCLUSIONS: Other targeted agents are effective salvage treatments after sorafenib failure, despite similar mechanisms of action, and should be offered to patients who are able to receive salvage therapy.

Resection margins and prognosis in locally invasive thyroid cancer.

BACKGROUND: Invasive thyroid cancer is rare, and the extent of surgery controversial. The purpose of this study was to present and evaluate therapeutic prognostic factors. METHODS: We conducted a retrospective single-center study of differentiated thyroid carcinoma invading the larynx, trachea, and/or esophagus treated surgically with macroscopic complete resection. RESULTS: Forty-six patients (average age, 57 years; average follow-up, 4 years) were included. Free margins (R0) were obtained for 22 of 46 (49%) and microscopic residual tumor was present after surgery (R1) for 24 (51%). Ten-year actuarial local control was 100% for R0 and 75% for R1 (p = .08). Five-year local control was lower for recurrent tumors versus inaugurally invasive disease (63% vs 87%; log-rank p = .011). Five-year and 10-year actuarial disease-specific survival (DSS) was correlated with preoperative distant metastases (100% and 87%, respectively, for M0 vs 68% and 34% for M1; p = .01). CONCLUSION: A trend toward lower local control was observed for R1 versus R0. The morbidity of surgery should be weighed against the prognosis if metastases are present.

Clinical utility of KAP-1 expression in thyroid lesions.

Although there are evidences of the involvement of KAP-1 in other tumors, data on differentiated thyroid carcinomas (DTC) are still lacking. We aimed to evaluate KAP-1 clinical utility in the diagnosis and prognosis of DTC. We used both visual immunohistochemistry and a semiquantitative analysis to evaluate KAP-1 expression in 230 thyroid carcinomas and 131 noncancerous thyroid nodules. There were 43 follicular carcinomas (FC) and 187 papillary thyroid carcinomas (PTC), including 130 classic (CPTC), 4 tall cells (TCPTC), and 53 follicular variants (FVPTC). Patients were followed up for 53.8 ± 41 months. They were classified as free-of-disease (142 cases) or poor outcome (25 cases--10 deaths), according to their serum Tg levels and image evidences. KAP-1 was identified in 78 % PTC, 75 % TCPTC, 74 % FC, 72 % FVPTC, 55 % FA, 44 % hyperplasia, and 11 % normal thyroid tissues. A ROC analysis identified malignant nodules with 69 % sensitivity and 75 % specificity, using a cutoff of 73.19. In addition to distinguishing benign from malignant thyroid tissues (p < 0.0001), KAP-1 expression differentiated CPTC from nodular hyperplasia (p < 0.0001), CPTC from FA (p = 0.0028), FVPTC from hyperplasia (p = 0.0039), and FC from hyperplasia (p = 0.0025). Furthermore, KAP-1 was more expressed in larger tumors (>4 cm; p = 0.0038) and in individuals who presented recurrences/metastases (p = 0.0130). We suggest that KAP-1 may help diagnose thyroid nodules, characterize follicular-patterned thyroid lesions, and identify individuals with poor prognosis.

Delay to curative surgery greater than 12 weeks is associated with increased mortality in patients with colorectal and breast cancer but not lung or thyroid cancer.

BACKGROUND: Surgery for cancer is often delayed due to variety of patient-, provider-, and health system-related factors. However, impact of delayed surgery is not clear, and may vary among cancer types. We aimed to determine the impact of the delay from cancer diagnosis to potentially curative surgery on survival. METHODS: Cohort study based on representative sample of patients (n = 7,529) with colorectal, breast, lung and thyroid cancer with local or regional disease who underwent potentially curative surgery as their first therapeutic modality within 1 year of cancer diagnosis. They were diagnosed in 2006 and followed for mortality until April 2011, a median follow-up of 4.7 years. RESULTS: For colorectal and breast cancers, the adjusted hazard ratios (95 % confidence intervals) for all-cause mortality comparing a surgical delay beyond 12 weeks to performing surgery within weeks 1-4 after diagnosis were 2.65 (1.50-4.70) and 1.91 (1.06-3.49), respectively. No clear pattern of increased risk was observed with delays between 4 and 12 weeks, or for any delay in lung and thyroid cancers. Concordance between the area of the patient's residence and the hospital performing surgery, and the patient's income status were associated with delayed surgery. CONCLUSIONS: Delays to curative surgery beyond 12 weeks were associated with increased mortality in colorectal and breast cancers, suggesting that health provision services should be organized to avoid unnecessary treatment delays. Health care systems should also aim to reduce socioeconomic and geographic disparities and to guarantee equitable access to high quality cancer care.

Comprehensive MicroRNA expression profiling identifies novel markers in follicular variant of papillary thyroid carcinoma.

BACKGROUND: Follicular variant of papillary thyroid carcinoma (FVPTC) shares features of papillary (PTC) and follicular (FTC) thyroid carcinomas on a clinical, morphological, and genetic level. MicroRNA (miRNA) deregulation was extensively studied in PTCs and FTCs. However, very limited information is available for FVPTC. The aim of this study was to assess miRNA expression in FVPTC with the most comprehensive miRNA array panel and to correlate it with the clinicopathological data. METHODS: Forty-four papillary thyroid carcinomas (17 FVPTC, 27 classic PTC) and eight normal thyroid tissue samples were analyzed for expression of 748 miRNAs using Human Microarray Assays on the ABI 7900 platform (Life Technologies, Carlsbad, CA). In addition, an independent set of 61 tumor and normal samples was studied for expression of novel miRNA markers detected in this study. RESULTS: Overall, the miRNA expression profile demonstrated similar trends between FVPTC and classic PTC. Fourteen miRNAs were deregulated in FVPTC with a fold change of more than five (up/down), including miRNAs known to be upregulated in PTC (miR-146b-3p, -146-5p, -221, -222 and miR-222-5p) and novel miRNAs (miR-375, -551b, 181-2-3p, 99b-3p). However, the levels of miRNA expression were different between these tumor types and some miRNAs were uniquely dysregulated in FVPTC allowing separation of these tumors on the unsupervised hierarchical clustering analysis. Upregulation of novel miR-375 was confirmed in a large independent set of follicular cell derived neoplasms and benign nodules and demonstrated specific upregulation for PTC. Two miRNAs (miR-181a-2-3p, miR-99b-3p) were associated with an adverse outcome in FVPTC patients by a Kaplan-Meier (p < 0.05) and multivariate Cox regression analysis (p < 0.05). CONCLUSIONS: Despite high similarity in miRNA expression between FVPTC and classic PTC, several miRNAs were uniquely expressed in each tumor type, supporting their histopathologic differences. Highly upregulated miRNA identified in this study (miR-375) can serve as a novel marker of papillary thyroid carcinoma, and miR-181a-2-3p and miR-99b-3p can predict relapse-free survival in patients with FVPTC thus potentially providing important diagnostic and predictive value.

Life expectancy is reduced in differentiated thyroid cancer patients ≥ 45 years old with extensive local tumor invasion, lateral lymph node, or distant metastases at diagnosis and normal in all other DTC patients.

OBJECTIVE: Differentiated thyroid carcinoma (DTC) generally has a good prognosis. As yet, however, it is unclear whether life expectancy is reduced in these patients and, if so, to what extent. The aim of this study was to determine how the all-cause mortality rate in DTC patients compares to that of the general population. DESIGN: A prospective database study was conducted. PATIENTS: The study included 2011 DTC patients treated in our hospital from 1980-2011. All patients received total thyroidectomy with subsequent (131)I ablation, except for those with an isolated papillary microcarcinoma. Survival data for the general German population were obtained from the German Federal Statistics Agency and matched to our DTC population for age and sex. RESULTS: Patients who were at least 45 yr old at diagnosis and had extensive perithyroidal invasion (UICC/AJCC TNM system, 7th edition, stages IVa and IVb), lateral cervical lymph node metastases (TNM stage IVa), or distant metastases (TNM stage IVc) showed a clearly reduced life expectancy [relative cumulative survival rate (observed:expected) for stage IVc after 20 yr, 0.295; 95% confidence interval, 0.033-0.556]. In patients over 60 yr of age at diagnosis, the loss of life expectancy was (much) greater than for those aged 45-59 yr in all groups. Life expectancy was not reduced in patients with TNM stages I, II, or III (86% of patients). CONCLUSION: Life expectancy is not significantly reduced in 86% of DTC patients; only patients at least 45 yr old with extensive local invasion, lateral lymph node metastases, and/or distant metastases (TNM stages IVa, IVb, and IVc) at diagnosis showed a clearly lower life expectancy.

Deaths due to differentiated thyroid cancer: a South Island, New Zealand experience: 1984-2009.

AIM: To assess differentiated thyroid cancer (DTC) deaths from the northern half of New Zealand's South Island. METHODS: Retrospective review of Christchurch Hospital Thyroid Clinic and Oncology Department clinical records of resident patients who died of differentiated thyroid cancer of follicular cell origin over the 25-year period 1984-2009. RESULTS: During the 25-year study period 25 patients died from differentiated thyroid cancer. All patients (17 female, 8 male) were Caucasian, with median age 65 years (47-86 years) at presentation. Most (24/25) patients presented with advanced (15 Stage IV, 9 Stage III) disease. Three patients initially presented with cervical lymphadenopathy and four patients with distant metastases--three patients with bone metastases, and one with a pleural effusion. The pathological classification of the tumours included 14 papillary cancers (four were follicular variants), six follicular cancers and five Hurthle cell cancers. The majority of primary tumours were large (>4 cm) and 11 were locally invasive. However one patient had a small (1.3 cm) papillary cancer and presented with a pleural effusion. Surgical removal of the primary tumour was attempted in 24 of the 25 patients, 18 received postoperative radioiodine 131I therapy, and three had external beam radiation therapy. The median survival from diagnosis was 5.5 years (0.2-22 years) with two Stage IV patients (both with Hurthle cell cancers) dying within 4 months. The majority of patients died of metastatic disease but seven died of local disease. CONCLUSIONS: During the 25-year study period, 25 patients died of differentiated thyroid cancer which approximates to one DTC death per year in our region. The median age at diagnosis was 65 years with no patients <45 years of age, and the female to male ration was 2.1:1. Most patients presented with advanced disease--7 patients (28%) had distant metastases. Hurthle cell cancers were over-represented (20%) in our series.

Reevaluating the prognostic significance of age in differentiated thyroid cancer.

OBJECTIVE: To determine the impact of age on disease-specific survival in differentiated thyroid cancer. STUDY DESIGN: Retrospective analysis of a large population database. Setting Surveillance, Epidemiology, and End Results (SEER) database/multiple settings. SUBJECTS AND METHODS: The SEER database was examined to identify patients diagnosed with either papillary or follicular carcinoma of the thyroid between the years 1988 and 2003. Information obtained included patient age, sex, tumor type, size, extension, and nodal or distant metastases. Kaplan-Meier survival analyses were used to estimate disease-specific survival based on patient age range, and the log-rank test was used to assess for statistical differences between survival curves. A multivariate analysis was performed including the variables listed above to determine disease-specific hazard ratios of death for various age cutoffs. RESULTS: A total of 42,209 patients were identified. Patients 45 years and older had significantly worse survival than younger patients (P < .0001). A significant decrease in disease-specific survival was first seen in patients aged 35 years and older, and survival continued to steadily decrease with each additional decade of age (P < .001). Patients aged 35 years and older were 14 times more likely to die from differentiated thyroid cancer than patients younger than 35 years. CONCLUSION: Increasing age is associated with poorer survival in differentiated thyroid cancer. This relationship represents a continuum with an initial decrease in survival starting at age 35 years that continues to decline with further advancing age.

Thyroid lobe ablation with radioactive iodine as an alternative to completion thyroidectomy after hemithyroidectomy in patients with follicular thyroid carcinoma: long-term follow-up.

BACKGROUND: Radioactive iodine lobe ablation (RAI-L-ABL) is a possible alternative to completion thyroidectomy (C-Tx) for follicular thyroid carcinoma (FTC), but no long-term outcome data are available after lobe ablation. We analyzed the long-term outcome of lobe ablation in a series of patients with FTC. METHODS: This was a retrospective study of patients who were treated with lobe ablation between 1983 and 2008. Of 134 patients with FTC, 37 (27.6%) had lobe ablation with (131)I (30-32 mCi) (RAI-L-ABL), 68 (50.7%) had C-Tx, and 29 (21.6%) had initial total thyroidectomy (T-Tx). The main outcomes analyzed were (131)I uptake after lobe ablation, C-Tx or T-Tx, serum thyroglobulin (Tg), serum thyroid-stimulating hormone (TSH), long-term disease-specific mortality, and disease-free survival. RESULTS: After lobe ablation, radioiodine uptake was significantly lower for the RAI-L-ABL group (0.6%) than for the C-Tx group (2.0%, p<0.005) or T-Tx group (1.3%, p=0.054). Subsequent remnant ablation was performed in 12 of 37 (32%) patients in the RAI-L-ABL group, in 58 of 68 (85.3%) patients in the C-Tx group, and in 25 of 29 (86.2%) patients in the T-Tx group (p<0.01). With median follow-up of 95 months for the RAI-L-ABL group, 47 months for the C-Tx group, and 53 months for the T-Tx group, there was one death in the RAI-L-ABL group and one death in the T-Tx group. No other RAI-L-ABL patients had detectable disease, whereas patients in the C-Tx group and two patients in the T-Tx group had detectable disease (p=0.18). Long-term stimulated or suppressed Tg of <1 ng/mL were found in 87.5% of the RAI-L-ABL group (n=28), 86.3% of the C-Tx group (n=57), and 77.8% of the T-Tx group (n=21). Tg was detectable in 40.6% of the RAI-L-ABL group compared to 13.8% of C-Tx and 28.6% of T-Tx groups (p<0.05, between groups). CONCLUSIONS: RAI-L-ABL, C-Tx, and T-Tx are equally effective in achieving serum TSH concentrations of >25 mIU/L and preparing patients for conventional (131)I treatment and whole body scanning with similar long-term outcomes. However, persistent measurable Tg (range 0.2-2.2 ng/mL) is more common after RAI-L-ABL.

Papillary thyroid carcinoma with different histological patterns.

Tumor-node-metastasis (TNM) staging is the most commonly used model for evaluating therapeutic strategies for papillary thyroid cancer (PTC). Additionally, different histopathological patterns and variants of PTC have been reported to influence the prognosis of these patients. We reviewed the clinical presentation, cancer recurrence, and cancer-specific mortality of the most frequent histological patterns, including the follicular variant (FVPTC), insular pattern, tall cell pattern, diffuse sclerosing type, PTC with Hashimoto's thyroiditis, and multicentric PTC. The tall cell variant of PTC is a more aggressive variant than classical PTC and has a poor prognosis. The high expression of Muc 1 and type IV collagenase in these tumors may facilitate stromal degradation and increase the invasive potential. In contrast, approximately 18% of PTC patients have been identified as having FVPTC. FVPTC patients have a better survival rate than those with follicular thyroid cancer, and fewer instances of lymph node or soft tissue invasion than control patients with classical PTC. The diffuse sclerosing variant of PTC predominantly observed in young patients is a rare aggressive tumor that requires intensive treatment. Despite characteristic clinical and histological features that facilitate easy diagnosis, pre-operative fine needle aspiration cytological diagnosis of this variant is often challenging. Different histological variants of PTC with other histological patterns are important for predicting cancer recurrence. In addition to TNM staging, high-risk histological patterns of PTC require more aggressive follow-up examinations and postoperative adjuvant therapies.

Central nodal metastases in papillary thyroid carcinoma based on tumor histologic type and focality.

OBJECTIVE: To determine the risk of nodal metastases to the central compartment from differentiated papillary thyroid carcinoma (PTC) relative to known prognostic variables. DESIGN: A 7-year single-institutional retrospective review. SETTING: Tertiary academic center. PATIENTS: A total of 115 patients undergoing central neck dissection (CND) for PTC or follicular variant PTC (FVPTC). MAIN OUTCOME MEASURE: Number, location, and positivity of lymph nodes for malignant disease in the central compartment based on patient age, sex, extrathyroidal extension, and primary tumor size, histologic type, and focality. RESULTS: Eighty-seven percent of patients had PTC, and 13% had FVPTC. Bilateral (64%) or ipsilateral (36%) CND was performed in patients with PTC. Patients with FVPTC underwent only ipsilateral CND. There was no significant difference in the number of lymph nodes retrieved based on patient age or sex, histologic type of the primary tumor, size or focality, or surgeon or pathologist. Seventy-eight percent of patients with PTC had malignant lymph nodes in the ipsilateral (75%) or bilateral/contralateral (69%) central compartment. Ipsilateral nodal metastases directly correlated with tumor multifocality (r = 0.93; P = .001) and size (r = 0.89; P = .001). Bilateral nodal metastases directly correlated with tumor multifocality (r = 0.92; P = .001) but was independent of size (r = 0.56; P = .001). No malignant lymph nodes were identified in the central compartment of FVPTC. CONCLUSIONS: Malignant central nodal metastases occur with high frequency in PTC but not in FVPTC. The risk of metastases correlated with the size and multifocality of the primary tumor. Additional studies are warranted to determine the extent of CND in patients with and without known multifocal disease and to determine the role of CND in patients with FVPTC.

Conservative management of well-differentiated thyroid cancer.

BACKGROUND: Controversy exists over the optimal surgical treatment of well-differentiated thyroid cancer. Conservative surgical management reduces the risk of complications and maintains an overall survival rate equivalent to the more extensive approach. METHODS: We conducted a retrospective review of all patients with well-differentiated thyroid cancer greater than 1 cm (180 patients) who underwent surgery between 1982 and 2002 by a single general surgeon at our institution. The prevailing philosophy was to be as conservative as possible, and the predominant resection was lobectomy and isthmusectomy on the affected side. RESULTS: In total, 90% of patients were in a definable low-risk group: 75% had conservative surgery with 4 recurrences and no mortality, 25% had extensive surgery with 3 recurrences and no mortality. The other 10% were in a definable high-risk group: 90% had extensive surgery with 9 recurrences and 4 deaths. Overall, there were 22 sites of recurrence in 16 patients. There was no recurrence in the residual thyroid tissue, with a median follow-up of 10 years. Three recurrences occurred in the resected thyroid bed; each of these patients had undergone extensive surgery. Twelve recurrences were in lymph nodes; 67% of these patients had extensive surgery. All except 1 of 7 distant metastases occurred in the high-risk group, despite the patient having undergone extensive local surgery. Recurrence did not affect survival in the low-risk group. The extensive surgery group had a 3.4% incidence of recurrent laryngeal nerve injury and a 1.1% incidence of permanent hypocalcemia, with none in the conservative surgery group. CONCLUSION: Conservative surgery for low-risk patients with well-differentiated thyroid cancer appears to be sufficient and avoids complications without significantly increased risk for local, regional or distant recurrence.

Histology does not influence prognosis in differentiated thyroid carcinoma when accounting for age, tumour diameter, invasive growth and metastases.

OBJECTIVE: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) show considerable differences in disease stage at initial presentation. The aim of this study was to investigate whether there are differences in tumour-specific survival if initial staging is accounted for. DESIGN: Retrospective chart review study. PATIENTS: The study sample comprised 875 PTC and 350 FTC patients (856 females, 369 males, mean age 47.8 years) treated in our hospital from 1978 to 2002. All patients received total thyroidectomy with subsequent I-131 ablation except for those patients with an isolated papillary microcarcinoma. METHODS: Kaplan-Meier analyses and Cox-regression analyses were performed to assess the influence of histology on thyroid cancer-specific survival. RESULTS: FTC patients were on average older, more likely to be male, presented with a larger tumour and more frequently had multifocal carcinoma and distant metastases than PTC patients, whereas they presented less frequently with extrathyroidal invasion or lymph node metastases. Twenty-year tumour-specific survival in PTC was 90.6% and in FTC 73.7% (P<0.001). In multivariate analysis the presence of distant metastases (P<0.001), age (P<0.001), tumour size (P=0.001) and the presence of extrathyroidal invasion (P=0.007), but not histology (P=0.26), were independent determinant variables for tumour-specific survival. CONCLUSION: There is no difference in tumour-specific survival between PTC and FTC when accounting for the presence of metastases, age, tumour size and the presence of extrathyroidal invasion.

Incidental papillary microcarcinoma of the thyroid--factors affecting lymph node metastasis.

BACKGROUND AND AIMS: Despite the overall excellent prognosis for patients with thyroid papillary microcarcinoma (PMC), these tumors are associated with lymph node metastasis. The aim of this study is to identify the rate of lymph node metastasis and evaluate the clinical and pathological factors affecting metastasis in thyroid PMC. METHODS: Among 475 patients with papillary thyroid carcinoma treated between 1990 and 2003, 81 patients (17%) were diagnosed as PMC and the records of these patients were evaluated retrospectively. Clinicopathologic features were evaluated by univariate and multivariate analyses. RESULTS: According to age, metastases, extent, and size risk definition, all patients were in low-risk group. Lymph node metastases were determined in 12.3% of patients. Mean follow-up was 7 years (range from 28 to 192 months). Ten-year disease-free and overall survival rates were 97 and 100%, respectively. Both multifocality and thyroid capsular invasion were found to be independent risk factors for lymph node metastasis by multivariate analysis. CONCLUSION: Patients with thyroid PMC in low-risk group with multifocal tumors and with capsule invasion may have increased risk of lymph node metastasis, and must be considered in follow-up of the patients who have these factors.

[The role of lymphadenectomy in the treatment of differentiated thyroid cancer]. / Locul limfadenectomiei in tratamentul cancerului tiroidian diferentiat.

Papillary and follicular carcinoma represent almost 90% of the thyroid malignancies, being responsible for 70% of the mortality generated by thyroid cancer. Lymph node involvement, far more significant in the papillary form, increases the risk of local recurrence and affects long-term survival. Due to the lack of prospective randomised studies to assess the benefit of lymph node dissection in addition to total thyroidectomy, there is no consensus regarding the need of routine vs elective central compartment lymphadenectomy. Routine lymph node dissection of the central compartment is supported by the argument that it reduces the amount of neoplastic thyroid tissue and, therefore, optimises the effectiveness of radioiodine in DTC patients. Moreover, it provides an accurate staging by the detailed histopathological analysis and allows an optimal postoperative thyroid scanning. No additional morbidity of central lymphadenectomy is reported, compared to total thyroidectomy alone, if performed by a specialised surgeon. However, reinterventions for recurrence in the central compartment, carry a significantly higher risk of recurrent nerve and parathyroids damage. Unlike central compartment, it is generally agreed that lymphadenectomy of the lateral neck, as modified radical neck dissection, is employed when there is evidence of neoplastic lymph node involvement, wether macroscopic, imaging or by pathological data.

Survival in patients with papillary thyroid cancer is not affected by the use of radioactive isotope.

INTRODUCTION: Papillary cancer is the most common neoplasm of the thyroid. The mainstay of treatment is thyroidectomy, but most patients are additionally treated with radioactive iodine (RAI). Its utility is controversial. This study seeks to determine whether RAI use affects patient outcome and to identify specific cohorts of patients that benefit from its use. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database is a large-scale sample of approximately 14% of the US population. It was used to identify patients with papillary carcinoma of the thyroid. Statistical analyses were used to compare prognostic factors such as lymph node status, age, tumor size, and treatment with RAI. RESULTS: A total of 14,545 patients were identified in SEER as having papillary cancer of the thyroid. Multivariate analysis showed significantly worse outcome in patients with age>45 years, tumor size >2 cm, lymph node disease, and distant metastases. Multivariate analysis failed to show RAI significantly affecting mortality. Survival between those not treated with RAI was similar to those whose treatment included it (P = 0.9176). Subgroup analysis identified patients older than 45 years with primary tumors >2 cm and disease in the lymph nodes with distant metastatic disease as the only group positively affected by RAI. CONCLUSIONS: Despite its widespread use in the treatment of well-differentiated papillary cancer of the thyroid, RAI only affects a survival advantage in older patients with large primary tumors involving the lymph nodes and with distant spread. Treating other patient groups is costly and offers no improvement in outcome.