¹8F-FDG uptake as a prognostic variable in primary differentiated thyroid cancer incidentally detected by PET/CT: a multicentre study.

PURPOSE: Our aim was to investigate the association between (18)F-fluorodeoxyglucose (FDG) uptake and event-free survival in patients in whom a differentiated thyroid cancer (DTC) was detected by (18)F-FDG positron emission tomography (PET)/CT. METHODS: Among 884 focal (18)F-FDG PET thyroid incidentalomas referred to our 4 Nuclear Medicine Departments, we investigated 54 patients in whom a DTC was confirmed and a clinical follow-up was available. The ratio between maximum standardized uptake value (SUVmax) of DTC and SUVmean of the liver (SUV ratio) was recorded for each scan. All patients underwent total thyroidectomy and (131)I remnant ablation. After a median follow-up of 39 months we assessed the outcome. The association between disease persistence/progression, (18)F-FDG uptake and other risk factors (T, N, M and histological subtype) was evaluated through univariate and multivariate analyses. RESULTS: Of the 54 patients, 39 achieved complete remission. The remaining 15 showed persistence/progression of disease. High (18)F-FDG uptake, i.e. SUV ratio ≥3, showed a low positive predictive value (48 %). Low (18)F-FDG uptake (SUV ratio < 3) displayed a high negative predictive value (93 %). The median of SUV ratios in T1-T2 (2.2), in M0 (2.7) and in non-virulent subtypes (2.7) were significantly lower (p < 0.03) than in T3-T4 (5.0), M1 (7.3) and virulent subtypes (6.0). Kaplan-Maier analysis showed a significant association between high (18)F-FDG uptake and disease persistence/progression (p = 0.001). When we adjusted risk estimates by using a multivariate Cox model, only T (p = 0.05) remained independently associated with disease persistence/progression. CONCLUSION: An intense (18)F-FDG uptake of the primary DTC is associated with persistence/progression of disease. However, when all other prognostic factors have been taken into account, (18)F-FDG uptake does not add further prognostic information.

Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study.

BACKGROUND: In the USA, about 30 200 well-differentiated thyroid carcinomas were diagnosed in 2007, but the prevalence of thyroid nodules is much higher (about 5% of the adult population). Unfortunately, the preoperative characterisation of follicular thyroid nodules is still a challenge, and many benign lesions, which remain indeterminate after fine-needle aspiration (FNA) cytology are referred to surgery. About 85% of these thyroid nodules are classified as benign at final histology. We aimed to assess the diagnostic effect of galectin-3 expression analysis in distinguishing preoperatively benign from malignant follicular thyroid nodules when FNA findings were indeterminate. METHODS: 544 patients were enrolled between June 1, 2003, and Aug 30, 2006. We used a purified monoclonal antibody to galectin-3, a biotin-free immunocytohistochemical assay, and a morphological and phenotypic analysis of FNA-derived cell-block preparations. Galectin-3-expression analysis was applied preoperatively on 465 follicular thyroid proliferations that were candidates for surgery, and its diagnostic accuracy was compared with the final histology. FINDINGS: 31 patients were excluded because they had small galectin-3-negative thyroid nodules; we did not have data for 47 patients; and one patient with an oncocytic nodule was excluded. 331 (71%) of the assessable 465 preoperative thyroid FNA samples did not express galectin-3. 280 (85%) of these galectin-3-negative lesions were classified as benign at final histology. Galectin-3 expression was detected, instead, in 134 of 465 (29%) thyroid proliferations, 101 (75%) of which were confirmed as malignant. The overall sensitivity of the galectin-3 test was 78% (95% CI 74-82) and specificity was 93% (90-95). Estimated positive predictive value was 82% (79-86) and negative predictive value was 91% (88-93). 381 (88%) of 432 patients with follicular thyroid nodules who were referred for thyroidectomy were correctly classified preoperatively by use of the galectin-3 test. However, 29 (22%) of 130 cancers were missed by the galectin-3 method. INTERPRETATION: Our findings show that if the option of surgery was based theoretically on galectin-3 expression alone, only 134 thyroid operations would have been done in 465 patients; therefore a large proportion (71%) of unnecessary thyroid surgical procedures could be avoided, although a number of galectin-3-negative cancers could be potentially missed. The galectin-3 test proposed here does not replace conventional FNA cytology, but represents a complementary diagnostic method for those follicular nodules that remain indeterminate.

Low triiodothyronine serum levels as a predictor of poor prognosis in burn patients.

OBJECTIVE: Euthyroid sick syndrome is a common finding in critically ill patients with nonthyroidal illness, characterized by low serum levels of free triiodothyronine (fT3) with a peculiar increase in reverse T3 (rT3) and normal-to-low free thyroxine (fT4) as well as thyroid-stimulating hormone (TSH) levels. This condition has been proposed as a prognostic factor of worse outcome in critically ill patients, while no conclusive data are available in burns. METHODS: Since thyroid function testing is contained in our baseline laboratory tests at admission, we retrospectively evaluated fT3, fT4 and TSH in 295 consecutive burn patients admitted to the Burn Center of Turin from January 2002 to December 2006, comparing hormone levels in survivors and non-survivors. RESULTS: fT3 and TSH levels were significantly lower (p

Focus on high-risk DTC patients: high postoperative serum thyroglobulin level is a strong predictor of disease persistence and is associated to progression-free survival and overall survival.

INTRODUCTION: No parameters predicting recurrence are available for high-risk differentiated thyroid cancer (DTC) patients, and 2-year-follow-up is required to modify the initial prognostic classification. High thyroglobulin (Tg) levels before ¹³¹I-remnant-ablation, during L-thyroxine-withdrawal (ablation-Tg) have undetermined predictive/prognostic significance in low-risk DTC patients. Our study aimed to assess the positive predictive value (PPV) of ablation-Tg in high-risk DTC patients and to evaluate whether high ablation-Tg levels were associated with progression-free-survival (PFS) and overall survival (OS). PATIENTS AND METHODS: We selected 243 high-risk DTC patients. All patients underwent total thyroidectomy and ¹³¹I-remnant-ablation (initial therapy). Clinical data obtained during a median 5-year follow-up were used to assess the response and outcome. The association between disease persistence/recurrence after initial therapy, ablation-Tg, and other risk-factors (T, N, G, histology, and MACIS score) was evaluated through univariate and multivariate analyses, as was the association between PFS, OS ablation-Tg, and other risk factors. RESULTS: Ablation-Tg of 50 µg/L or greater displayed the highest PPV(97%) for disease persistence. In the univariate analysis, high levels of ablation-Tg were confirmed in patients with persistent disease after initial therapy: the higher the odds ratios, the higher the ablation-Tg levels. On multivariate analysis, ablation-Tg was the best predictive factor, especially on comparing patients with ablation-Tg levels of 50 µg/L or greater and those with ablation-Tg less than 2 µg/L (adjusted OR, 818). In a multivariate Cox model, ablation-Tg was the factor most closely associated with PFS (HR, 65.9). The prognostic value of ablation-Tg was confirmed by the overall-survival curves and adjusted risk estimates (adjusted HR=26.7). CONCLUSIONS: Ablation-Tg levels of 50 µg/L or greater are a valuable initial predictor of disease persistence/recurrence in high-risk DTC patients. A significant association emerged between high ablation-Tg levels of 50 µg/L or greater and both progression-free survival (PFS) and overall survival (OS).

99mTc-MIBI Imaging in the presurgical characterization of thyroid follicular neoplasms: relationship to multidrug resistance protein expression.

UNLABELLED: Recently, thyroid (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) scintiscanning has been proposed in an attempt to preoperatively identify thyroid malignancies, but discrepant results have been reported for oncocytic lesions. The aim of this study was to investigate the usefulness of visual and semiquantitative analyses of (99m)Tc-MIBI scintigraphy for preoperatively characterizing thyroid nodules with indeterminate cytologic diagnoses, segregating in advance nononcocytic variants from those that are oncocytic. This study also aimed to analyze the relationship between (99m)Tc-MIBI images and P-glycoprotein (P-gp)/multidrug resistance-associated protein-1 (MRP1) immunohistochemical expression. METHODS: Fifty-one consecutive patients with cold thyroid nodules cytologically diagnosed as nononcocytic or oncocytic follicular neoplasm were prospectively studied. Visual and semiquantitative (99m)Tc-MIBI scanning was performed and the diagnoses of the lesions were histologically proven by subsequent thyroidectomy. Immunohistochemical evaluation of P-gp and MRP1 was also performed on surgical samples. RESULTS: Visual and semiquantitative (99m)Tc-MIBI scintiscans showed a low specificity in preoperatively discriminating malignant oncocytic lesions. In nononcocytic nodules, the semiquantitative method was more accurate than the visual (94.44% and 77.78%, respectively). P-gp protein expression was negative in all thyroid lesions, whereas apical plasma membrane MRP1 expression was found in 78% of the lesions with a negative (99m)Tc-MIBI retention index, compared with 11% of lesions with a positive retention index, correlating most strongly with a negative (99m)Tc-MIBI RI in those cases with strong MRP1 apical expression. CONCLUSION: Semiquantitative (99m)Tc-MIBI scintigraphy is an adjunctive method to predict preoperatively the malignant behavior of nononcocytic follicular thyroid nodules indeterminate at fine-needle aspiration biopsy, with a potential impact on the definition of their clinical management. Moreover, the good correlation found between immunohistochemical apical expression of MRP1 and the scintigraphic findings supports the (99m)Tc-MIBI results and provides tissue information on the molecular mechanisms responsible for (99m)Tc-MIBI images in thyroid lesions.