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Context Ultrasonography (US) is considered the most sensitive tool for imaging persistent or recurrent papillary thyroid cancer (PTC) in the neck. Objective To clarify the usefulness of routine neck US in low- and intermediate-risk patients with PTC with no evidence of disease 1 year after thyroidectomy. Design Retrospective analysis of prospectively recorded data. Setting Academic center. Patients Two hundred twenty-six patients with PTC with sonographically normal neck lymph nodes and unstimulated serum thyroglobulin (Tg) levels that were either undetectable ( Interventions Yearly assessment: unstimulated serum Tg level, anti-Tg-antibody (TgAb) titer, TSH levels, and ultrasound examination of neck lymph nodes. Main Outcome Measures Rates of ultrasonographic lymph node abnormalities at the 3-year and last follow-up visits. Results In patients with an undetectable Tg level at the 1-year evaluation, sonographically suspicious neck lymph nodes were found in 1.2% of patients at 3 years and in 1.8% at the last visit [negative predictive values (NPVs) of 1-year Tg < 0.2 ng/mL: 98.8% (95% CI 95.8% to 99.9%) and 98.2% (95% to 99.6%), respectively]. Similar NPVs emerged for low detectable 1-year Tg levels [98.2% (90.3% to 99.9%) and 94.5% (84.9% to 98.9%) at the 3-year and last visits, respectively]. Seventy-five percent of the nodal lesions were likely false positive; none required treatment. Conclusions Low- and intermediate-risk patients with PTC with negative ultrasound findings and unstimulated Tg levels

Context Current guidelines recommend a selective use of radioiodine treatment (RAI) for papillary thyroid cancer (PTC). Objective This work aimed to determine how policy changes affect the use of RAI and the short-term outcomes of patients. Methods A retrospective analysis of longitudinal data was conducted in an academic referral center of patients with nonaggressive PTC variants; no extrathyroidal invasion or limited to soft tissues, no distant metastases, and 5 or fewer central-compartment cervical lymph node metastases. In cohort 1, standard treatments were total thyroidectomy and RAI (May 2005-June 2011); in cohort 2 decisions on RAI were deferred for approximately 12 months after surgery (July 2011-December 2018). Propensity score matching was used to adjust for sex, age, tumor size, lymph node status, and extrathyroidal extension. Intervention included immediate RAI or deferred choice. Main outcome measures were responses to initial treatment during 3 or more years of follow-up. Results In cohort 1, RAI was performed in 50 of 116 patients (51.7%), whereas in cohort 2, it was far less frequent: immediately in 10 of 156 (6.4%), and in 3 more patients after the first follow-up data. The frequencies of structural incomplete response were low (1%-3%), and there were no differences between the 2 cohorts at any follow-up visit. Cohort 2 patients had higher rates of “gray-zone responses” (biochemical incomplete or indeterminate response). Conclusion Selective use of RAI increases the rate of patients with “uncertain” status during early follow-up. The rate of structural incomplete responses remains low regardless of whether RAI is used immediately. Patients should be made aware of the advantages and drawbacks of omitting RAI.

Background and Objectives: The surgical choice treatment of the breast cancer mostly depends on the stage of the disease. In the last years, breast cancer surgery has moved from being destructive to being more respectful of the anatomical and physiological integrity of the gland. The aim of the breast surgery should be finalized to obtain the best aesthetic and functional results, respecting the principles of oncologic radicality. The present study is a retrospective analysis aimed to evaluate the long-term outcomes of a conservative technique like the nipple-sparing mastectomy. Materials and Methods: We observed 894 patients with a median age of 47.5 years old, underwent nipple-sparing mastectomy between 2002&ndash, 2017. The data acquired include population and tumor characteristics, patient reconstructive outcomes, including locoregional, regional, and distant metastases, other variables, among nipple&ndash, areola complex necrosis and infection were collected. Results: The complications detected were considered as &ldquo, early&rdquo, within 1 month later the nipple-sparing mastectomy or &ldquo, late&rdquo, after this time. The overall complications rate (early and late) and the overall survival and the relapses detected by this study were comparable with those reported in the literature. In order to identify factors that correlate with complications, either early or later, it has been processed an evaluation of the univariate analysis showing adjuvant chemotherapy as the only predictive factor for late complications, while we encountered no predictors for early complications. Conclusions: The present study adds to the data already present in literature, demonstrating that the nipple-sparing mastectomy is a safe procedure, providing good oncological and aesthetic results in patients carefully selected.

A preoperative neck ultrasound (US) is recommended for all patients with suspected thyroid cancer, to identify features potentially changing surgical extent. The extrathyroidal extension (ETE) is considered an indication for total thyroidectomy, but there is limited consensus on its US definition, and the interobserver reliability is low. This study aimed to evaluate the predictive value of neck US for ETE before surgery and to estimate the diagnostic performance of different US findings, evaluated during real-time examinations. Patients referred to surgery between November 1, 2015, and May 31, 2019, for a suspicious thyroid cancer underwent a preoperative neck US, with systematic assessment for ETE. Three definitions were tested: very restrictive (capsular disruption with suspicious images of surrounding tissues invasion), restrictive (including also capsular abutment with evidence of capsular disruption), and nonrestrictive (capsular abutment is sufficient). Histopathology report of ETE involving at least soft tissues was considered positive. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. The study cohort included 128 patients, with 102 (79.7%) confirmed malignancies, and 44 (43.1%) histological ETE. The nonrestrictive definition had good sensitivity (86.4%) but low specificity (29.8%), with an NPV of 80.6%; the restrictive definition had higher specificity (81%), while the very restrictive had specificity and PPV of 100%. A more extensive surgical approach should not be based on US suspicion of ETE alone, with the possible exception of gross invasion appearance. The absence of any sign of ETE, on the other hand, has a substantial negative predictive value.

Over 50% of newly diagnosed thyroid nodules are either cytologically benign or presumed to be benign on the basis of low-suspicion sonographic findings. The strategies used for their long-term surveillance are based mainly on the estimated residual risk of malignancy calculated with various ultrasonographic classification systems (e.g., Thyroid Image Reporting and Data Systems [TIRADS]). We conducted a longitudinal study to evaluate the temporal stability of the initial risk estimates computed with five widely used systems and to determine whether risk class increases during follow-up are indeed predictive of malignancy.We re-analyzed data prospectively collected at a single academic referral center on 232 patients (age: 54.1 ± 13.7 years) with 432 asymptomatic, sonographically or cytologically benign thyroid nodules at baseline (T0) and 122 new nodules that were present five years later (T5). At both time points, the sonographically estimated risk of malignancy was calculated as recommended by the American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi, the American College of Radiologists' TIRADS, the American Thyroid Association's 2015 practice guidelines, the European Thyroid Association's TIRADS (EU-TIRADS), and the TIRADS of the Korean Society of Thyroid Radiology (K-TIRADS).For 57 to 127 (13.2-29.4%) of the original nodules, depending on the system used, the estimated malignancy risk increased over the 5-year interval. Of the nodules whose baseline risk had not warranted cytological assessment, very few (6.3-8.3%) met the criteria for cytology at the 5-year evaluation. Biopsy was indicated for only 4 to 8 (3.3-6.6%) of the new nodules based on T5 risk estimates. Despite these changes, none of the 232 patients was ever diagnosed with a cancer.Ultrasound-based risk classes of presumably benign thyroid nodules remain fairly stable over time, and changes warranting biopsy are rare indeed. The appearance of new nodules is a frequent event, but very few (5%) are classified as high risk, and only the 3-7% meet the criteria for cytological assessment. Collectively, these findings support the view that patients with presumably benign thyroid nodules can be safely followed with less intensive protocols.

PURPOSE: To assess the diagnostic performance and the potential as a teaching tool of S-detect in the assessment of focal breast lesions. METHODS: 61 patients (age 21-84 years) with benign breast lesions in follow-up or candidate to pathological sampling or with suspicious lesions candidate to biopsy were enrolled. The study was based on a prospective and on a retrospective phase. In the prospective phase, after completion of baseline US by an experienced breast radiologist and S-detect assessment, 5 operators with different experience and dedication to breast radiology performed elastographic exams. In the retrospective phase, the 5 operators performed a retrospective assessment and categorized lesions with BI-RADS 2013 lexicon. Integration of S-detect to in-training operators evaluations was performed by giving priority to S-detect analysis in case of disagreement. 2 × 2 contingency tables and ROC analysis were used to assess the diagnostic performances; inter-rater agreement was measured with Cohen's k; Bonferroni's test was used to compare performances. A significance threshold of p = 0.05 was adopted. RESULTS: All operators showed sensitivity > 90% and varying specificity (50-75%); S-detect showed sensitivity > 90 and 70.8% specificity, with inter-rater agreement ranging from moderate to good. Lower specificities were improved by the addition of S-detect. The addition of elastography did not lead to any improvement of the diagnostic performance. CONCLUSIONS: S-detect is a feasible tool for the characterization of breast lesions; it has a potential as a teaching tool for the less experienced operators.

Aim of this study was to evaluate the association between body mass index (BMI) and aggressive features of differentiated thyroid cancer (DTC) in a prospective cohort. Patients with DTC were prospectively enrolled at a tertiary referral center and grouped according to their BMI. Aggressive clinic-pathological features were analyzed following the American Thyroid Association Initial Risk Stratification System score. The cohort was composed of 432 patients: 5 (1.2%) were underweight, 187 (43.3%) normal weight, 154 (35.6%) overweight, 68 (15.7%) grade 1 obese, 11 (2.5%) grade 2 obese and 7 (1.6%) grade 3 obese. No single feature of advanced thyroid cancer was more frequent in obese patients than in others. No significant correlation was found between BMI, primary tumor size (Spearman’s ρ − 0.02; p = 0.71) and ATA Initial Risk Stratification System score (ρ 0.03; p = 0.49), after adjustment for age. According to the multivariate logistic regression analysis, male gender and pre-surgical diagnosis of cancer were significant predictors of cancer with high or intermediate–high recurrence risk according to the ATA system (OR 2.06 and 2.51, respectively), while older age at diagnosis was a protective factor (OR 0.98), and BMI was not a predictor. BMI was a predictor of microscopic extrathyroidal extension only (OR 1.06). Obesity was not associated with aggressive features in this prospective, European cohort of patients with DTC.

Guidelines recommend thyroid-stimulating hormone (TSH) suppression before the first response to treatment assessment in papillary thyroid cancer (PTC) patients. The aim of this study was to assess the rate of structural disease (SD) in low- and intermediate-risk PTC patients according to TSH levels measured 1 year after primary treatment.A consecutive, prospective series of low- and intermediate-risk PTC patients with 3-years follow-up was collected. TSH, thyroglobulin (Tg), antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) 1 and 3 years after primary treatment were analyzed. Recurrence risk and disease status at 1 year were defined according to the American Thyroid Association (ATA) guidelines and as the presence or absence of SD after 3 years. Patients were grouped according to TSH level at 1 year: group 1, TSH0.1 μUI/mL; group 2, TSH 0.1 to 0.5 μUI/mL; group 3, 0.5 to 2 μUI/mL; and group 42 μUI/mL.This study included 263 patients (70.9% female, median age 47.2 years) of whom the risk of recurrence was low in 170 (65%), intermediate-low in 63 (24%), and intermediate-high in 30 (11%). The response to initial treatment at 1 year was excellent in 149 (57%), biochemical incomplete in 18 (7%), indeterminate in 84 (32%), and structural incomplete in 12 (4%). Group 1 consisted of 53 (20%) patients, group 2 of 85 (32%), group 3 of 61 (23%), and group 4 of 64 (24%). The rate of SD at 1 and 3 years from primary treatment was not significantly different between TSH groups.TSH suppression before the first response to treatment assessment does not appear to influence the rate of SD evaluated 1 and 3 years after primary treatment.ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; LT4 = levothyroxine; PTC = papillary thyroid cancer; SD = structural disease; Tg = thyroglobulin; TgAb = antithyroglobulin antibodies; TSH = thyroid-stimulating hormone; US = ultrasonography.

Context:The European Thyroid Association (ETA) has classified posttreatment cervical ultrasound findings in thyroid cancer patients based on their association with disease persistence/recurrence.Objective:The objective of the study was to assess this classification's ability to predict the growth and persistence of such lesions during active posttreatment surveillance of patients with differentiated thyroid cancer (DTC).Design:This was a retrospective, observational study.Setting:The study was conducted at a thyroid cancer center in a large Italian teaching hospital.Patients:Center referrals (2005–2014) were reviewed and patients selected with pathologically-confirmed DTC; total thyroidectomy, with or without neck dissection and/or radioiodine remnant ablation; abnormal findings on two or more consecutive posttreatment neck sonograms; and subsequent follow-up consisting of active surveillance. Baseline ultrasound abnormalities (thyroid bed masses, lymph nodes) were classified according to the ETA system. Patients were divided into group S (those with one or more lesions classified as suspicious) and group I (indeterminate lesions only). We recorded baseline and follow-up clinical data through June 30, 2015.Main Outcomes:The main outcomes were patients with growth (>3 mm, largest diameter) of one or more lesions during follow-up and patients with one or more persistent lesions at the final visit.Results:The cohort included 58 of the 637 DTC cases screened (9%). A total of 113 lesions were followed up (18 thyroid bed masses, 95 lymph nodes). During surveillance (median 3.7 y), group I had significantly lower rates than group S of lesion growth (8% vs 36%, P = .01) and persistence (64% vs 97%, P = .014). The median time to scan normalization was 2.9 years.Conclusions:The ETA's evidence-based classification of sonographically detected neck abnormalities can help identify papillary thyroid cancer patients eligible for more relaxed follow-up.

Context The prevalence of thyroid nodules in the general population is increasingly high, and at least half of those biopsied prove to be benign. Sonographic risk-stratification systems are being proposed as “rule-out” tests that can identify nodules that do not require fine-needle aspiration (FNA) cytology. Objective To comparatively assess the performances of five internationally endorsed sonographic classification systems [those of the American Thyroid Association, the American Association of Clinical Endocrinologists, the American College of Radiology (ACR), the European Thyroid Association, and the Korean Society of Thyroid Radiology] in identifying nodules whose FNAs can be safely deferred and to estimate their negative predictive values (NPVs). Design Prospective study of thyroid nodules referred for FNA. Setting Single academic referral center. Patients Four hundred seventy-seven patients (358 females, 75.2%); mean (SD) age, 55.9 (13.9) years. Main Outcome Measures Number of biopsies classified as unnecessary, false-negative rate (FNR), sensitivity, specificity, predictive values, and diagnostic ORs for each system. Results Application of the systems’ FNA criteria would have reduced the number of biopsies performed by 17.1% to 53.4%. The ACR Thyroid Imaging Reporting and Data System (TIRADS) allowed the largest reduction (268 of 502) with the lowest FNR (NPV, 97.8%; 95% CI, 95.2% to 99.2%). Except for the Korean Society of Thyroid Radiology TIRADS, all other systems exhibited significant discriminatory performance but produced significantly smaller reductions in the number of procedures. Conclusions Internationally endorsed sonographic risk stratification systems vary widely in their ability to reduce the number of unnecessary thyroid nodule FNAs. The ACR TIRADS outperformed the others, classifying more than half the biopsies as unnecessary with a FNR of 2.2%.

Background The mediastinal ectopic thyroid is very rare, accounting for less than 1% of all cases of ectopic thyroid tissue. The differential diagnoses with other diseases such as lymphomas, thymic tumors and dermoid cysts is mandatory, in fact each one, needs different management and treatment. Case presentation Here, we discuss a rare case of mediastinal ectopic thyroid presenting with a paratracheal mass laying on the right bronchus without symptoms. A 63-year-old male presented with an abnormal well-defined mass along the right paratracheal side, detected by chest x-ray. The CT scan confirmed the presence of a 6 × 8 cm heterogeneously enhanced mass, located behind the superior vena cava and left brachiocephalic artery, reaching azygos vein and right bronchus, without a mass effect. Taking into account the clinical importance of a mediastinal mass, we removed it surgically, through a double surgical approach consisting in a classical transverse cervicotomy for the left thyroid lobe, followed then by a longitudinal sternal splitting to remove the mediastinal mass and complete the thyroidectomy. Conclusions In case of mediastinal masses, the surgical excision is recommended, presenting the double advantage to clarify the diagnosis and to treat the pathology. As demonstrated in this case, a mediastinal ectopic thyroid should be taken into account in the differential diagnosis, considering its clinical importance.

This study was aimed at assessing the incidence and timing of thyroid nodules recurrence, defined as appearance of new benign or malignant nodules in contralateral lobe in patients with benign thyroid nodules or thyroid microcarcinoma treated with lobo-isthmectomy. Patient's characteristics and risk factors associated with this phenomenon were also investigated.A retrospective study was performed by evaluating 413 patients undergoing lobo-isthmectomy with a minimum follow-up of 1 year. Clinical characteristics, surgical interventions and complications, histological diagnosis, and thyroid function at last follow-up were collected.Single or multiple thyroid nodule recurrence equally occurred in 80 patients (23%) with a median time to relapse of ~ 5 years (range 0.3-34.5 years) after lobo-isthmectomy. Recurrence was significantly associated with younger age ( 46 years) and number of pregnancies in women. Development of hypothyroidism was not rare either (~ 10%) and appeared in 3-19 months; a preoperative TSH level 2.43 mIU/L was associated with the need of l-thyroxin replacement therapy after surgery. The most frequent surgical complication was transient hypoparathyroidism (4.6%), while the rate of permanent hypoparathyroidism significantly increased in patients submitted to completion thyroidectomy (5.3%).Thyroid nodules recurrence following lobo-isthmectomy is not a rare event and occurs within 5 years after surgery, more frequently in younger patients with family history of nodular goiter and in women with multiple pregnancies. Pre-surgical TSH levels may predict the development of post-surgical hypothyroidism, possibly improving the management of patients addressed to surgery.

Recent studies have revealed in normal thyroid tissue the presence of the transcript of several phosphodiesterases (PDEs), enzymes responsible for the hydrolysis of cyclic nucleotides. In this work, we analyzed the expression of PDE5 in a series of human papillary thyroid carcinomas (PTCs) presenting or not BRAF V600E mutation and classified according to ATA risk criteria. Furthermore, we tested the effects of two PDE5 inhibitors (sildenafil, tadalafil) against human thyroid cancer cells. PDE5 gene and protein expression were analyzed in two different cohorts of PTCs by real-time PCR using a TaqMan micro-fluid card system and Western blot. MTT and migration assay were used to evaluate the effects of PDE5 inhibitors on proliferation and migration of TPC-1, BCPAP, and 8505C cells. In a first series of 36 PTCs, we found higher expression levels of PDE5A in tumors versus non-tumor (normal) tissues. PTCs with BRAF mutation showed higher levels of mRNA compared with those without mutation. No significant differences were detected between subgroups with low and intermediate ATA risk. Upregulation of PDE5 was also detected in tumor tissue proteins. Similar results were obtained analyzing the second cohort of 50 PTCs. Moreover, all tumor tissues with high PDE5 levels showed reduction of Thyroglobulin, TSH receptor, Thyroperoxidase, and NIS transcripts. In thyroid cancer cells in vitro, sildenafil and tadalafil determined a reduction of proliferation and cellular migration. Our findings demonstrate for the first time an overexpression of PDE5 in PTCs, and the ability of PDE5 inhibitors to block the proliferation of thyroid cancer cells in culture, therefore, suggesting that specific inhibition of PDE5 may be proposed for the treatment of these tumors.

To assess the accuracy and reproducibility of ultrasonography classification systems in characterizing cytologically indeterminate thyroid nodules.We retrospectively identified 49 nodules that had been surgically resected owing to features classified as indeterminate according to 2010 Italian Consensus on Thyroid Cytology criteria. Three experienced sonographers independently reviewed original sonographic images of each nodule and classified it using the 2015 American Thyroid Association (ATA) guidelines and the Thyroid Imaging Reporting and Data System (TI-RADS) classification proposed by Korean radiologists; later, images were reviewed jointly to obtain consensus classifications of each nodule. Original cytology slides were similarly reviewed by three experienced cytopathologists, who reclassified the nodule (independently, then jointly) according to revised Italian Consensus on Thyroid Cytology (ICTC-2014) criteria. Consensus ICTC-2014, ATA, and TI-RADS classifications were analyzed against surgical histology reports to estimate each system's sensitivity, specificity, positive and negative predictive values.Of the 49 indeterminate nodules examined, 30 (61.2 %) were histologically benign. Consensus ICTC-2014 classification correctly classified malignant nodules with positive predictive value of 50 % and negative predictive value of 90 %. Sonographic classification of nodules as intermediate to high suspicion by ATA or TI-RADS category 4c displayed positive predictive value of 63 and 71 %, respectively; positive predictive values dropped to 44 and 42 % when lower positivity thresholds were used (ATA low suspicion, TI-RADS category 4a). Negative predictive values for ATA and TI-RADS were 91 and 74 %, respectively, with higher positivity thresholds and 100 % for both with lower thresholds. All systems displayed appreciable inter-observer variability (Krippendorff alphas: ATA 0.36, TIRADS 0.42, ICTC-2014 0.74).With stringent negativity cut-offs, American Thyroid Association and Thyroid Imaging Reporting and Data System assessment of cytologically indeterminate thyroid nodules allows high-confidence exclusion of malignancy.

PURPOSE To assess the best technique and the diagnostic accuracy of Quasistatic Ultrasound Elastography (QUE) in thyroid nodules. Interobserver agreement was also evaluated. MATERIALS AND METHODS A preliminary study of 50 patients with 54 thyroid nodules was performed with quantitative software in order to define the best cut-off value of different imaging methods. All patients underwent total thyroidectomy and histopathology findings served as the standard of reference. Thereafter, 154 nodules in 137 consecutive patients were prospectively evaluated by three operators. Findings at fine-needle aspiration cytology and histopathology (N = 60) served as the standard of reference. RESULTS The most accurate technique was the axial peri-intranodular measurement method which achieved an area under the ROC curve of 0.961 (95 %CI 0.848 - 1.00) and had an optimal cut-off value of 3.00. QUE in the differentiation of thyroid nodules showed for operator 1: sensitivity 90 % (95 %CI 73.5 - 97.9 %), specificity 92.7 % (95 %CI 86.7 - 96.6 %), LR+ 12.40 (6.54 - 23.50), LR- 0.11 (0.04 - 0.32) and accuracy 91.4 % (95 %CI 85.4 - 97.3 %); for operator 2: sensitivity 86.7 % (95 %CI 69.3 - 96.2 %), specificity 87.1 % (95 %CI 79.9 - 92.4 %), LR+ 6.72 (4.16 - 10.80), LR- 0.15 (0.06 - 0.38) and accuracy 86.9 % (95 %CI 80.0 - 93.7 %); for operator 3: sensitivity 80 % (95 %CI 61.4 - 92.3 %), specificity 83.9 % (95 %CI 76.2 - 89.9 %), LR+ 4.96 (3.20 - 7.70), LR- 0.24 (0.12 - 0.49) and accuracy 81.9 % (95 %CI 74.0 - 89.9 %). Interobserver agreement values between operator 1 and operator 2 (k = 0.79) (p

To assess whether ultrasound elastography (USE) with strain ratio increases diagnostic accuracy of Doppler ultrasound in further characterisation of cytologically Thy3 thyroid nodules. In two different university diagnostic centres, 315 patients with indeterminate cytology (Thy3) in thyroid nodules aspirates were prospectively evaluated with Doppler ultrasound and strain ratio USE before surgery. Ultrasonographic features were analysed separately and together as ultrasound score, to assess sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Receiver operating characteristic (ROC) curves to identify optimal cut-off value of the strain ratio were also provided. Diagnosis on a surgical specimen was considered the standard of reference. Higher strain ratio values were found in malignant nodules, with an optimum strain ratio cut-off of 2.09 at ROC analysis. USE with strain ratio showed 90.6 % sensitivity, 93 % specificity, 82.8 % PPV, 96.4 % NPV, while US score yielded a sensitivity of 52.9 %, specificity of 84.3 %, PPV 55.6 % and NPV 82.9 %. The diagnostic gain with strain ratio was statistically significant as proved by ROC areas, which was 0.9182 for strain ratio and 0.6864 for US score. USE with strain ratio should be considered a useful additional tool to colour-Doppler US, since it improves characterisation of thyroid nodules with indeterminate cytology. • Strain ratio measurements improve differentiation of thyroid nodules with indeterminate cytology • Elastography with strain ratio is more reliable than ultrasound features and ultrasound score • Strain ratio may help to better select patients with Thy 3 nodules candidate for surgery

Down-regulation of thyroid hormone receptor beta (THRβ) gene has been described in several human malignancies, including thyroid cancer. In this study, we analyzed THRβ mRNA expression in surgical specimens from a series of human papillary thyroid carcinomas (PTCs), characterized by their genotypic and clinical–biological features. Thirty-six PTCs were divided into two groups according to the 2009 American Thyroid Association risk classification (17 low, 19 intermediate), and each group was divided into subgroups based on the presence or absence of the BRAFV600E mutation (21 BRAF mutated, 15 BRAF wild type). Gene expression was analyzed using fluidic cards containing probes and primers specific for the THRβ gene, as well as for genes of thyroperoxidase (TPO), sodium/iodide symporter (NIS), thyroglobulin (Tg) and thyroid stimulating hormone receptor (TSH-R) and for some miRNAs involved in thyroid neoplasia and targeting THRβ. The mRNA levels of each tumor tissue were compared with their correspondent normal counterpart. THRβ transcript was down-regulated in all PTCs examined. No significant differences were found between intermediate- vs low-risk PTCs patients, and BRAF-mutated vs BRAF wild-type groups. THRβ expression was directly correlated with NIS, TPO, Tg and TSH-R, and inversely correlated to miR-21, -146a, -181a and -221 expression. Our results demonstrate that down-regulation of THRβ is a common feature of PTCs. While it is not associated with a more aggressive phenotype of PTC, it correlates with the reduction of all the markers of differentiation and is associated with overexpression of some miRNAs supposed to play a role in thyroid tumorigenesis.

The diffuse sclerosing variant (DSV) of papillary thyroid carcinoma is known for its high aggressiveness, high incidence of lymph node metastases, and high incidence of pulmonary metastases, and thus its consequently poorer prognosis. In this study, we undertook a retrospective analysis of papillary thyroid carcinomas to assess whether DSV can be considered a predictive factor for prognosis. We performed a retrospective evaluation of the Department's database of patients with papillary thyroid carcinoma who had undergone total thyroidectomy from January 1992 to December 2000. Group I consisted of 83 DSV patients and Group II was 168 pure papillary carcinoma (PC) patients. A significant prevalence of multinodular thyroid disorder on diagnosis was found for PC (P < 0.05), whereas with DSV, there was a significantly higher prevalence of post-thyroiditis nodular thyroid disorder than with PC (P < 0.001). The incidence of laterocervical lymph node pathology on diagnosis was significantly higher for DSV (P < 0.05). In 3.6 per cent of PC patients and 15.7 per cent of DSV patients, we observed recurrences in the regional lymph nodes (P < 0.001). We found 1.2 per cent distant metastases in PC patients and 7.2 per cent in DSV patients (P < 0.05). One PC patient (0.6%) and three DSV patients (3.6%) died of tumor-related causes (P < 0.05). Our study demonstrated that diffuse sclerosing carcinoma leads to a poorer prognosis to the extent that its classification as an autonomous clinical pathological entity is justified. In conclusion, we can state that DSV is a form of papillary thyroid tumor characterized by its higher aggressiveness, diffuse intrathyroid growth, and high incidence of lymph node and pulmonary metastasis. Ultimately, this means a poorer prognosis. In the presence of risk factors indicating a possible increase in biological aggressiveness, adequate postoperative treatment and close follow-up become essential.

During the last 20 years an ever increasing number of nonpalpable breast lesions (NPBL) have been identified. A cytohistological definition is required to establish the correct diagnostic classification of these lesions and the suitable therapy to be used. The Fine-Needle Aspiration Cytology (FNAC), the Advanced Breast Biopsy Instrumentation (ABBI) system or the Vacuum Assisted Core Biopsy (VACB) represent valid alternatives to the surgical excision with needle localisation. 591 NPBL have been included in the present study. The suspected grade of each lesion was then assigned according to the Breast Imaging Reporting and Data System (BI-RADS) of the American College of Radiology. All the BI-RADS 4 and 5, and all the BI-RADS 3 lesions, which after 6-month follow-up showed altered morphology, were sampled for cytological and/or histological examinations by FNAC, VACB or biopsy by ABBI system. The diagnostic algorithm used in this study obviated a surgical procedure in 574 women (97.1%), yielding a 73.9% decrease in the cost of diagnosis compared with surgical biopsy, and a 48.1% decrease in cost if all lesions had been histologically tested using ABBI or VACB procedure. Compared to surgical biopsy, VACB and ABBI system are less expensive, and have smaller emotional and aesthetical impact on patients; however they retain the same sensitivity and specificity.

Evaluation of the diagnostic efficacy and interobserver agreement of Q-elastography in the differentiation of benign from malignant thyroid nodules.A total of 344 thyroid nodules in 288 patients were examined with grey-scale and colour Doppler ultrasound (CDUS) and Q-elastography by two independent operators. Nodules with hypoechogenicity, poorly defined margins, microcalcifications, and intralesional vascularity were classified as suspicious. Diagnostic performances of CDUS features and Q-elastography for predicting thyroid malignancy were estimated using ROC analysis. Cytology or histopathology was the reference standard. Interobserver agreement in the evaluation of CDUS and Q-elastography was assessed using Cohen's k-statistic.Q-elastography showed excellent diagnostic performance for the prediction of thyroid malignancy, with sensitivity of 93 % and specificity of 92 % for operator 1 (best cutoff at 2.02), and sensitivity of 84 % and specificity of 79 % for operator 2 (best cutoff at 1.86). Performance of Q-elastography was superior to that of CDUS. Reproducibility of the findings was excellent for both Q-elastography and CDUS features as assessed with Cohen's k, which was highest for strain ratio measurements (0.95) and lowest for the echogenicity score (0.83).Q-elastography showed excellent performance. It is a valid and reproducible diagnostic method as well as a promising tool for identifying suspicious solid thyroid nodules needing cytological assessment and surgery.• Elastography is an additional tool for optimal characterisation of malignant thyroid nodules. • The use of semiquantitative elastographic evaluation increases the diagnostic performance, • The interobserver agreement of quantitative elastography can be considered to be good.

The current use of life-long follow-up in patients with papillary thyroid cancer (PTC) is based largely on the study of individuals diagnosed and treated in the latter half of the 20th century when recurrence rates were approximately 20% and relapses detected up to 20-30 years after surgery. Since then, however, diagnosis, treatment, and postoperative monitoring of PTC patients have evolved significantly.The objective of the study was to identify times to PTC recurrence and rates by which these relapses occurred in a more recent patient cohort.We retrospectively analyzed follow-up data for 1020 PTC patients consecutively diagnosed in 1990-2008 in 8 Italian hospital centers for thyroid disease. Patients underwent thyroidectomy, with or without radioiodine ablation of residual thyroid tissue and were followed up with periodic serum thyroglobulin assays and neck sonography.At the initial posttreatment (≤ 12 months) examination, 948 patients had no structural/functional evidence of disease. During follow-up (5.1-20.4 years; median 10.4 years), recurrence (cervical lymph nodes, thyroid bed) was diagnosed in 13 (1.4%) of these patients. All relapses occurred 8 or fewer years after treatment (10 within the first 5 years, 6 within the first 3 years). Recurrence was unrelated to the use/omission of postoperative radioiodine ablation.In PTC patients whose initial treatment produces disease remission (no structural evidence of disease), recurrent disease is rare, and it usually occurs during the early postoperative period. The picture of recurrence timing during the follow-up provides a foundation for the design of more cost-effective surveillance protocols for PTC patients.

Ectopic parathyroid adenomas represent a diagnostic challenge, since they are quite rare in clinical practice. We present a case of a 61 years old man with symptomatic hypercalcemia due to an ectopic parathyroid adenoma in the upper-anterior mediastinum that was not localized by the scintigraphy. Ultrasonography identified a nodule on the left upper-superior lobe of the thyroid gland, consistent with a parathyroid adenoma; scintigraphy showed two focuses of abnormal tracer uptake, one on the left upper-superior lobe of the gland and the other on the right inferior lobe of the gland. Patient underwent surgery to remove the adenoma on the left side, but postoperatively PTH and serum calcium level were still elevated. CT scan showed a mass of 27 x 22 mm in the upper anterior mediastinum, in front of the right emisoma of D2. The final surgery allowed us to remove the adenoma with a laterocervical approach. The histopathology was consistent with parathyroid adenoma.

Serum thyroglobulin (Tg) assays are considered fundamental in postoperative surveillance of differentiated thyroid cancer (DTC) patients. However, the postsurgical profile of Tg levels has never been specifically investigated in patients who do not undergo radioiodine remnant ablation (RRA).Our objective was to explore the evolution of Tg levels over time in DTC patients treated with total or near-total thyroidectomy without RRA.We retrospectively analyzed 290 consecutively diagnosed cases of low-risk (American Thyroid Association criteria) DTC treated with thyroidectomy alone and followed yearly with neck ultrasonography and serum Tg assays. We compared final Tg values in this group and a matched group of 495 RRA-positive patients. Temporal trends of serial Tg levels were also analyzed in 78 of the RRA-negative patients monitored with a high-sensitivity immunoradiometric assay.After follow-up of 2.5-22 yr (median 5 yr), final Tg levels were undetectable (1 ng/ml) in 274 of 290 RRA-negative patients (95%) and 492 of 495 RRA-positive controls (99%). In the subset of 78 RRA-negative patients, undetectable Tg levels (0.2 ng/ml) were recorded in 60% at the first postoperative evaluation (3-12 months) and in 79% after 5 yr. Tg levels increased in the single patient who experienced disease recurrence during the observation period.In most RRA-negative patients, postoperative serum Tg values spontaneously drop to undetectable levels within 5-7 yr after thyroidectomy. Thus, in later phases, Tg assays may be a valuable tool for follow-up even in patients who do not undergo RRA.

ObjectiveTyrosine kinase inhibitors (TKIs) are evaluated for treatment of radioiodine refractory thyroid cancer. Their effects in this setting are based on blockade of proangiogenic signaling mediated by receptors for vascular endothelial growth factors (VEGFs) and platelet-derived growth factors (PDGF). Most TKIs also block other cancer-relevant kinases, such as B-type Raf kinase (BRAF), which are constitutively activated in approximately half of papillary thyroid carcinomas (PTCs), but the impact of these effects is not clear.DesignThe aim of our study was to investigate the impact of BRAFV600E on proangiogenic gene expression and microvascular features of PTCs.MethodsmRNA levels for VEGFA, VEGF receptors, and coreceptors (VEGFRs 1, 2, and 3, neuropilin-1), and PDGF receptor β (PDGFRβ or PDGFRB) were measured with real-time PCR in BRAFV600E (n=55) and wild-type BRAF (BRAF-wt; n=35) PTCs. VEGF and VEGFR protein expression and microvessel densities (MVD) and lymphatic vessel densities (LVDs) were assessed by immunohistochemistry in 22 of the 90 PTCs (including 11 BRAFV600E cases). Angiogenic gene expression was also studied in vitro after induction/silencing of the BRAFV600E mutation in thyrocyte lines.ResultsTranscript levels of proangiogenic factors were significantly lower in BRAFV600E PTCs versus BRAF-wt PTCs (PVEGFA mRNA levels in thyroid cell lines decreased when BRAFV600E mutation was induced (P=0.01) and increased when it was silenced (P=0.01).ConclusionsCompared with BRAF-wt PTCs, those harboring BRAFV600E exhibit downregulated VEGFA, VEGFR, and PDGFRβ expression, suggesting that the presence of BRAF mutation does not imply a stronger prediction of response to drugs targeting VEGF and PDGFB signaling pathways.

Aurora-A kinase has recently been shown to be deregulated in thyroid cancer cells and tissues. Among the Aurora-A substrates identified, transforming acidic coiled-coil (TACC3), a member of the TACC family, plays an important role in cell cycle progression and alterations of its expression occur in different cancer tissues. In this study, we demonstrated the expression of the TACC3 gene in normal human thyroid cells (HTU5), and its modulation at both mRNA and protein levels during cell cycle. Its expression was found, with respect to HTU5 cells, unchanged in cells derived from a benign thyroid follicular tumor (HTU42), and significantly reduced in cell lines derived from follicular (FTC-133), papillary (B-CPAP), and anaplastic thyroid carcinomas (CAL-62 and 8305C). Moreover, in 16 differentiated thyroid cancer tissues, TACC3 mRNA levels were found, with respect to normal matched tissues, reduced by twofold in 56% of cases and increased by twofold in 44% of cases. In the same tissues, a correlation between the expression of the TACC3 and Aurora-A mRNAs was observed. TACC3 and Aurora-A interact in vivo in thyroid cells and both proteins localized onto the mitotic structure of thyroid cells. Finally, TACC3 localization on spindle microtubule was no more observed following the inhibition of Aurora kinase activity by VX-680. We propose that Aurora-A and TACC3 interaction is important to control the mitotic spindle organization required for proper chromosome segregation.

Although thyroglossal duct cysts represent a common developmental abnormality of the thyroid gland, malignant transformation is rare and occurs in only 1% of cases. This article describes four clinical cases observed at the Surgical Science Department of "La Sapienza" University of Rome between 1996 and 2000. Histologic examination indicated two pure papillary carcinomas, a sclerosing papillary carcinoma, and a follicular variant of papillary carcinoma. In all cases, treatment involved removal of the body of the hyoid bone and total thyroidectomy, which we associated with removal of the thyroglossal duct cyst. In one case, laterocervical lymphectomy was performed. Carcinoma multifocality was found in one patient. We recommend associating total thyroidectomy with removal of the tumor of the thyroglossal duct and of the body of the hyoid bone, because the carcinoma may be multifocal and there may be lymphatic invasion of the thyroid and to ensure a correct follow-up.

The objective of this study was to evaluate the value of a color-coded automated signal intensity curve software package for contrast-enhanced magnetic resonance mammography (CE-MRM) in patients with suspected breast cancer.Thirty-six women with suspected breast cancer based on mammographic and sonographic examinations were preoperatively evaluated on CE-MRM. CE-MRM was performed on a 1.5-T magnet using a 2D Flash dynamic T1-weighted sequence. A dosage of 0.1 mmol/kg of Gd-BOPTA was administered at a flow rate of 2 mL/s followed by 10 mL of saline. Images were analyzed with the new software package and separately with a standard display method. Statistical comparison was performed of the confidence for lesion detection and characterization with the 2 methods and of the diagnostic accuracy for characterization compared with histopathologic findings.At pathology, 54 malignant lesions and 14 benign lesions were evaluated. All 68 (100%) lesions were detected with both methods and good correlation with histopathologic specimens was obtained. Confidence for both detection and characterization was significantly (Por = 0.025) better with the color-coded method, although no difference (P0.05) between the methods was noted in terms of the sensitivity, specificity, and overall accuracy for lesion characterization. Excellent agreement between the 2 methods was noted for both the determination of lesion size (kappa = 0.77) and determination of SI/T curves (kappa = 0.85).The novel color-coded signal intensity curve software allows lesions to be visualized as false color maps that correspond to conventional signal intensity time curves. Detection and characterization of breast lesions with this method is quick and easily interpretable.

To evaluate the role of contrast-enhanced Magnetic Resonance Mammography (MRM) in the evaluation of the contralateral breast in patients with recently diagnosed breast cancer.Fifty patients with proved unilateral breast cancer, with a negative contralateral breast at physical examination, ultrasound and mammography, were studied with a 1.5 T magnet (Siemens, Vision Plus, Germany). A bilateral breast surface coil was used. Dynamic 3D Flash T1-weighted sequences were acquired in the axial plane before and 0, 2, 4, 6 and 8 minutes after the administration of 0.1 mmol/kg of Gd-BOPTA at a flow rate of 2 ml/s followed by 10 ml of saline. The level of suspicion was reported on a scale from 0 to 5 following the BI-RADS classification, based on lesion morphology and kinetic features. The results were compared with the histological findings after biopsy or surgery.Fourteen out of 50 patients (28%) had contralateral lesions identified on MRM. Biopsy was performed in four of them for suspicious lesions (BI-RADS 4) while 10 patients underwent surgery because of highly suggestive malignant lesions (BI-RADS 5). Histology diagnosed three fibroadenomas, 5 ductal carcinomas in situ, 2 lobular carcinomas in situ, 3 invasive ductal carcinomas and 1 invasive lobular carcinoma. Contrast-enhanced MRM yielded no false negative and three false positives.Our results demonstrate a very good accuracy of Magnetic Resonance Mammography in the detection of synchronous contralateral cancer in patients with newly diagnosed breast cancer. Therefore, contrast-enhanced MRM could be introduced to screen patients with proven breast cancer before they undergo surgery.

Aim of this study was to investigate the effects of implantation of different coronary drug-eluting stents on trafficking of central (T(CM)) or effector (T(EM)) memory T cells in the coronary sinus of patients with coronary artery disease (CAD) undergoing percutaneous coronary revascularization. Thirty-two patients presenting with stable coronary disease and angiographically proven stenosis of left descending coronary artery were randomly assigned to treatment with rapamycin-eluting, paclitaxel-eluting or bare metal stents. Heparinized blood samples were obtained from the coronary sinus either before or 20 min after stent implantation. Mononuclear cells were stained with mAbs specific for CD3, CD4, CD8, CD45R0, and CD27 molecules. Analysis of surface phenotype was performed by four-color flow cytometry and data on both CD4+ and CD8+ T(CM) and T(EM) cells were expressed either as absolute cell numbers/microL of blood or as percentages relative to the corresponding total memory T cell populations in the individual patients. We found that the number of CD8+ T(EM), as defined by CD3+CD45R0+CD8+CD27- phenotype, was significantly reduced in patients receiving a rapamycin-eluting stent as compared with basal values. Conversely, the number of CD8+ T(CM) (CD3+CD45R0+CD8+CD27+) was increased in the same treatment group after the revascularization procedure. No changes in the absolute number of CD4+ and CD8+ total (T(CM) plus T(EM)) memory T cells before and after the procedure were observed. These findings suggest that rapamycin eluted from medicated coronary stents rapidly induce a redistribution of memory CD8+ T lymphocyte subsets, with a significant decrease of T(EM) and a corresponding increase of T(CM) increase circulating within the coronary sinus. This anti-inflammatory effect could partially explain the reduction of coronary in-stent restenosis rate associated with the clinical use of this type of device.

In a limited study, comprising only ten patients, we have previously reported that allogeneic irradiated RCC-cell-line cells, engineered to produce IL-2 (ACHN-IL-2), admixed with autologous metastatic formalin-treated tumour cells were used to vaccinate MRCC patients in progression of disease and also receiving IL-2 immunotherapy. The cells, admixed to autologous TC, were administered subcutaneously. We now report an extended study on thirty patients and one hundred thirty-one controls. Patients received 4-20 injections (mean 10 +/- 4), containing an average of 92 x 10(6) +/- 45 x 10(6) ACHN-IL-2 transfected cells (a minimum of 25 x 10(6), and a maximum of 200 x 10(6)). Autologous TC, admixed to allogeneic, were also administered by 4-16 s.c. injections (mean 7 +/- 3), i.e. a total of 12 x 10(6)-160 x 10(6) cells. Vaccination was administered during 73-1451 (307 +/- 316) days, and the follow-up continued for 1122 +/- 1240 days (106-5137). Throughout this period, the patients continued receiving the previously set immunotherapy treatment. No adverse side effects related to the treatment were noticed. One complete and four partial tumour responses were observed, as well as nine cases of stable disease. Thirteen patients died in the treated group (43%) and 63 (44%) in the control group. Responding patients resumed progression in 4-11 months and died 18 and 36 months after beginning the vaccine therapy. The Gehan Wilcoxon's test showed a significantly (P0.01) better survival in the vaccinated patients compared to that of the controls. Thus, we confirm, in an increased number of patients and an extensive follow-up, that our vaccination protocol is safe, devoid of adverse side effects, and promising.

The authors, on the basis of 3 cases of complicated diverticular disease, discuss the indications to surgery, considering the advantages and disadvantages of the various surgical techniques and examining in particular the rules for a correct operation with resection and primary or secondary anastomosis. As they performed a rectosigmoidectomy with primary high colorectal anastomosis, they report the reasons why they adopted the preservation and peeling of the inferior mesenteric artery (IMA).

Maspin expression in endometrial hyperplasia and endometrial endometrioid adenocarcinomas was assessed and its correlation with p53 and Ki-67 expressions and clinical outcome, as well as its potential to distinguish typical from atypical endometrial hyperplasia, were assessed in this study. Histological sections from 114 cases of endometrial endometrioid adenocarcinoma, 75 cases of endometrial hyperplasia (typical and atypical), and 23 normal endometrial tissue samples were examined. The most representative hematoxylin-eosin slides were selected and 2-3 micron-thick sections were cut for immunohistochemical staining with maspin, p53, and Ki-67 antibodies. While there was no maspin expression in normal endometrial cells, it was present in 14.5% of the patients with endometrial hyperplasia without atypia. Staining for maspin was positive in atypical hyperplasia and endometrial adenocarcinoma in, respectively, 45% and 49.1% of the cases studied. No statistically significant correlations were found between maspin and Ki-67 antibodies or p53 expression. Our findings showed that maspin expression, which generally correlates with a less aggressive behavior, is significantly higher in atypical hyperplasia and in endometrial endometrioid adenocarcinoma. Maspin positivity in endometrial hyperplasia could be used to identify pseudo-atypical hyperplasia and could be considered a potentially useful prognostic parameter in those cases in which adenocarcinomas are well differentiated.

Recently, several Authors have emphasized the relationship between oxidative stress and thyroid tumors. Several methods have been proposed in the literature for the measurement of oxidative stress in human tissues, although the high reactivity and short half life of reactive oxygen and nitrogen species make difficult their direct determination. Here we propose a novel approach for the determination of oxidative stress in human tissues, taking into account the relationship between free radicals and thyroid diseases.Our goal in this preliminary study, was to demonstrate the opportunity to use the coupling of the EPR-spin trapping technique with the hydroxylamine 1-hydroxy-3-carboxy-pyrrolidine, to detect oxidative stress in the human blood of patients with thyroid disease.Our preliminary findings confirm that this is a sensible, precise and valid method to study the oxidative stress and encourage us to continue the project.Our next goal will be to enroll patients affected by different thyroid diseases and to study the effect of some antioxidants in the management of the disease. This will allow to better understand the pathological path that binds the formation of reactive oxidizing species to the thyroid cancer and eventually to take into account the antioxidant therapy, as a possible additional "therapeutic weapon".

Background The aim of the study was to investigate whether p503S, p504S and p510S gene expression in peripheral-blood be useful as a diagnostic or prognostic marker of prostatic cancer. Methods Circulating cells were identified by reverse transcription-polymerase chain reaction (RT-PCR) to detect p503S, p504S and p510S mRNA in peripheral blood (PB) from 11 patients with treated prostatic carcinoma (CaP), 11 with newly-diagnosed untreated CaP and 20 with benign prostatic hyperplasia (BPH) (controls). Results RT-PCR amplified P503S in 7 of 11 untreated and 2 of 11 treated patients with CaP and 5 of 20 with BPH; p504S in 7 of 11 untreated and in 9 of 11 treated patients with CaP and 11 of 20 with BPH; whereas it amplified p510S in all subjects with CaP and in 15 of 20 with BPH. Conclusion These findings suggest that the investigated genes are poorly specific and probably of little use as diagnostic or prognostic prostatic markers in peripheral blood for monitoring disease progression and recurrence.