Clinical impact of the new SIAPEC-IAP classification on the indeterminate category of thyroid nodules.

BACKGROUND: The increasing frequency in the diagnosis of thyroid nodules has raised a growing interest in the search for new diagnostic tools to better select patients deserving surgery. In 2014, the major Italian Societies involved in the field drafted a new cytological classification, to better stratify pre-surgical risk of thyroid cancer, especially for the indeterminate category, split into TIR3A and TIR3B subclasses, associated to different therapeutic decisions. MATERIALS AND METHODS: This retrospective cross-sectional survey analyzed thyroid fine-needle aspiration biopsy performed at our outpatient clinic before and after the introduction of the new SIAPEC-IAP consensus in May 2014. RESULTS: 8956 thyroid nodules were included in the analysis: 5692 were evaluated according to the old classification and 3264 according to the new one. The new criteria caused the overall prevalence of TIR3 to increase from 6.1 to 20.1%. Of those, 10.7 and 9.4% were included in the TIR3A and TIR3B subgroups, respectively. Each of the 213 TIR3B nodules underwent surgery and 86 (40.4%) were diagnosed as thyroid cancer, while among the 349 TIR3A nodules, only 15 of the 60 that underwent surgery were found to be thyroid cancer. CONCLUSIONS: This analysis shows that the new SIAPEC-IAC criteria significantly increased the proportion of the overall TIR3 diagnosis. The division of TIR3 nodules into two subgroups (A and B) allowed a better evaluation of the oncologic risk and a better selection of patients to be referred to surgery.

Comparison between 99mTc-sestamibi scintimammography and X-ray mammography in the characterization of clusters of microcalcifications: a prospective long-term study.

BACKGROUND: The early diagnosis of non-palpable breast cancer is the object of recent developments in the imaging procedures employed for screening purposes. In some patients, the presence of microcalcifications (MC) is the only indication of tumor. Although X-ray mammography (MRx) has high sensitivity in detecting MC, its specificity is however too low for diagnostic purposes. The aim of this study was to compare (99m)Tc-sestamibi scintimammography (SMM) and MRx in the differential diagnosis between benign and malignant clusters of MC and to assess the possible incremental value of SMM on specificity. PATIENTS AND METHODS: A total of 283 consecutive women (mean age 53+/-8 years) with MC identified on X-ray mammograms underwent SMM. Scintigraphic images were acquired 10 minutes after the i.v. injection of (99m)Tc-sestamibi (740 MBq). Planar images of both breasts were simultaneously obtained in the lateral prone position and in the anterior and oblique projections using a dual head camera. Sixty-nine women underwent surgery, whereas the remaining 214 patients had completely negative follow-up for 5 years (a 5-year follow-up period is considered the "gold standard" for diagnosing benign lesions). RESULTS: Histology demonstrated 32/69 primary breast carcinomas (prevalence of disease: 11% of all the 283 patients) and 37/69 benign lesions. The receiver operating characteristic (ROC) statistical technique was employed to compare the diagnostic value of Mrx alone to that of combined MRx and SMM. The detected difference between the areas under the MRx ROC curve (area=0.72, standard error 0.052) and the MRX and SMM ROC curve (area=0.86, standard error 0.039) was statistically significant (p<0.01). Moreover, the combination of MRx and SMM provided a significant improvement of the negative predictive value (NPV=98%) for MC with low-suspicion of malignancy at MRx. CONCLUSION: SMM can be considered as a complementary tool in the pre-operative work-up of patients with breast lesions. Furthermore, the high negative predictive value of this technique, makes it especially valuable in the perspective of reducing the number of negative breast biopsies or unnecessary surgical interventions.

Indications for breast magnetic resonance imaging. Consensus document "Attualità in senologia", Florence 2007.

The clinical use of breast magnetic resonance (MR) imaging is increasing, especially for applications requiring paramagnetic contrast-agent injection. This document presents a synthetic list of acceptable indications with potential advantages for women according to evidence from the literature and the expert opinion of the panel that developed this statement. We generally recommend that breast MR imaging be performed in centres with experience in conventional breast imaging [mammography and ultrasonography (US)] and needle-biopsy procedures (under stereotactic or US guidance) as well as in breast MR imaging and second-look US for findings not revealed by conventional imaging performed before MR imaging. In our opinion, there is no evidence in favour of breast MR imaging as a diagnostic tool to characterise equivocal findings at conventional imaging when needle-biopsy procedures can be performed, nor for the study of asymptomatic, non-high-risk women with negative conventional imaging. After a description of technical and methodological requirements, we define the indications and limitations of breast MR imaging for surveillance of high-risk women, local staging before surgery, evaluation of the effect of neoadjuvant chemotherapy, breast previously treated for carcinoma, carcinoma of unknown primary syndrome, nipple discharge and breast implants.

Quantitative diffusion-weighted MR imaging in the differential diagnosis of breast lesion.

The role of diffusion-weighted magnetic resonance imaging (DWI) to differentiate breast lesions in vivo was evaluated. Sixty women (mean age, 53 years) with 81 breast lesions were enrolled. A coronal echo planar imaging (EPI) sequence sensitised to diffusion (b value=1,000 s/mm(2)) was added to standard MR. The mean diffusivity (MD) was calculated. Differences in MD among cysts, benign lesions and malignant lesions were evaluated, and the sensitivity and specificity of DWI to diagnose malignant and benign lesions were calculated. The diagnosis was 18 cysts, 21 benign and 42 malignant nodules. MD values (mean +/- SD x 10(-3) mm(2)/s) were (1.48 +/- 0.37) for benign lesions, (0.95 +/- 0.18) for malignant lesions and (2.25 +/- 0.26) for cysts. Different MD values characterized different malignant breast lesion types. A MD threshold value of 1.1 x 10(-3) mm(2)/s discriminated malignant breast lesions from benign lesions with a specificity of 81% and sensitivity of 80%. Choosing a cut-off of 1.31 x 10(-3) mm(2)/s (MD of malignant lesions -2 SD), the specificity would be 67% with a sensitivity of 100%. Thus, MD values, related to tumor cellularity, provide reliable information to differentiate malignant breast lesions from benign ones. Quantitative DWI is not time-consuming and can be easily inserted into standard clinical breast MR imaging protocols.

Contrast-enhanced MR imaging in patients with BI-RADS 3-5 microcalcifications.

PURPOSE: The aim of this study was to evaluate the role of magnetic resonance imaging (MRI) in patients with microcalcifications classed as Breast Imaging Reporting and Data Systems (BI-RADS) 3-5. MATERIALS AND METHODS: Fifty-five patients with mammographic microcalcifications classified as BI-RADS categories 3, 4 or 5 underwent MRI and biopsy with stereotactic vacuum-assisted biopsy (VAB). Our gold standard was microhistology in all cases and histology with histological grading in patients who underwent surgery. Patients with a microhistological diagnosis of benign lesions underwent mammographic follow-up for at least 12 months. MRI was performed with a 1.5-Tesla (T) unit, and T1 coronal three-dimensional (3D) fast low-angle shot sequences were acquired before and after injection of paramagnetic contrast agent (0.1 mmol/kg). MRI findings, according to the Fisher score, were classified into BI-RADS classes. In patients with cancer who underwent surgery, we retrospectively compared the extension of the mammographic and MRI findings with histological extension. RESULTS: Histology revealed 26 ductal in situ cancers (DCIS) and ductal microinvasive cancers (DCmic), three atypical ductal hyperplasias (ADH) and 26 benign conditions. Histological grading of the 26 patients with cancer revealed four cases of G1, 11 cases of G2 and 11 cases of G3. If we consider mammographic BI-RADS category 3 as benign and BI-RADS 4 and 5 as malignant, mammography had 77% sensitivity, 59% specificity, 63% positive predictive value (PPV), 74% negative predictive value (NPV) and 67.2% diagnostic accuracy. If we consider MRI BI-RADS categories 1, 2 and 3 as benign and 4 and 5 as malignant, MRI had 73% sensitivity, 76% specificity, 73% PPV, 76% NPV and 74.5% diagnostic accuracy. As regards disease extension, mammography had 45% sensitivity and MRI had 84.6% sensitivity. CONCLUSION: Mammography and stereotactic biopsy still remain the only techniques for characterising microcalcifications. MRI cannot be considered a diagnostic tool for evaluating microcalcifications. It is, however, useful for identifying DCIS with more aggressive histological grades. An important application of MRI in patients with DCIS associated with suspicious microcalcifications could be to evaluate disease extension after a microhistological diagnosis of malignancy, as it allows a more accurate presurgical planning.

Psychobiological correlates of smoking in patients with erectile dysfunction.

Although it is clear that cigarette abuse is closely linked to sexual dysfunction, it is still unclear which are the psychobiological correlates of smoking among individuals with sexual dysfunction. The aim of the present study is the assessment of the organic, psychogenic and relational correlates of erectile dysfunction (ED) in outpatients with different smoking habits. We studied the psychobiological correlates of smoking behaviour in a consecutive series of 1150 male patients, seeking medical care for ED. All patients were investigated using a Structured Interview (SIEDY), which explores the organic, relational and intra-psychic components of ED, and a self-administered questionnaire for general psychopathology (MHQ). In addition, several biochemical and instrumental parameters were studied, to clarify the biological components underlying ED. Current smokers (CS) showed a higher activation of the hypothalamus-pituitary-testis axis (higher LH, testosterone and right testicular volume) and lower levels of both prolactin and TSH. Hormonal changes were reverted after smoking cessation. CS showed a higher degree of somatized anxiety and were more often unsatisfied of their occupational and domestic lifestyle. Smoking, as part of a risky behaviour, was significantly associated with abuse of alcohol and cannabis. Both CS and past smokers (PS) showed an impairment of subjective and objective (dynamic peak systolic velocity at penile duplex ultrasound) erectile parameters. This might be due to a direct atherogenic effect of smoking, a cigarette-induced alteration of lipid profile (higher triglyceride and lower HDL cholesterol in CS than in non-smokers or PS), or due to a higher use of medications potentially interfering with sexual function. This is the first comprehensive evaluation of the biological and intrapsychic correlates to the smoking habit. Our report demonstrates that smoking has a strong negative impact on male sexual life, even if it is associated at an apparently more sexual-favourable hormonal milieu.

The Italian multi-centre project on evaluation of MRI and other imaging modalities in early detection of breast cancer in subjects at high genetic risk.

This report presents the preliminary results of the first phase (21 months) of a multi-centre, non-randomised, prospective study, aimed at evaluating the effectiveness of contrast-enhanced magnetic resonance imaging (MRI), X-ray mammography (XM) and ultrasound (US) in early diagnosis of breast cancer (BC) in subjects at high genetic risk. This Italian national trial (coordinated by the Istituto Superiore di Sanità, Rome) so far recruited 105 women (mean age 46.0 years; median age 51.0; age range 25-77 years), who were either proven BRCA1 or BRCA2 mutation carriers or had a 1 in 2 probability of being carriers (40/105 with a previous personal history of BC). Eight cases of breast carcinomas were detected in the trial (mean age 55.3 years, median age 52.5; age range 35-70 years; five with previous personal history of BC). All trial-detected BC cases (8/8) were identified by MRI, while XM and US correctly classified only one. MRI had one false positive case, XM and US none. Seven "MRI-only" detected cancers (4 invasive, 3 in situ) occurred in both pre- (n = 2) and post-menopausal (n = 5) women. With respect to the current XM screening programmes addressed to women in the age range 50-69 years, the global incidence of BC in the trial (7.6%) was over ten-fold higher. The cost per "MRI-only" detected cancer in this particular category of subjects at high genetic risk was substantially lower than that of an XM-detected cancer in the general women population. These preliminary results confirmed that MRI is a very useful tool to screen subjects at high genetic risk for breast carcinoma, not only in pre-, but also in post-menopausal age, with a low probability of false positive cases.

Breast MR imaging screening in eight women proved or suspected to be carriers of BRCA1&2 gene mutations.

The aim of this study was to evaluate the efficacy of MR imaging for the early detection of breast tumor in women at high genetic risk compared to conventional strategies such as ultrasonography and mammography. This study included 8 women, 5 of which had undergone surgery for breast cancer. BRCA germ line mutations were detected in 7 women, one patient was enrolled for more than 50% probability to be carrier of BRCA mutation. RM imaging screening was negative in 7 patients and strongly indicative of a malignant lesion in one. The gold standard was surgery for the suspicious cases and follow-up with clinical examination and conventional imaging every six months for the others. MR imaging proved itself to be a reliable technique in familial breast cancer high risk women.

Clinical application of 5alpha-reductase inhibitors.

The inhibitors of 5alpha-reductase isoenzymes (1 and 2) can be schematically divided in three groups according they substrate specificity: a) pure or preferential inhibitor of 5alpha-reductase 1; b) pure or preferential inhibitor of 5alpha-reductase 2; c) dual inhibitors. Despite the fact that several steroidal and non-steroidal inhibitors have been synthesized and experimented in pharmacological models, only finasteride has been extensively used for clinical purposes. The largest application of finasteride in man has been human benign prostative hyperplasia (BPH). In addition, finasteride has been recently used for treatment of male baldness with a 50% of objective response. In women, finasteride has been used in some control trials for treatment of hirsutism with an objective favorable response. In conclusion, finasteride appears be useful for BPH, baldness and hirsutism (with caution) treatment. On the basis of experimental observations on distribution of 1 and 2 isoenzymes in human skin, scalp and prostate, the dual inhibitors should be more indicated for treatment of BPH and baldness. Similarly, the dual inhibitors seem indicated in attempting to prevent prostatic cancer. The pure 5alpha-reductase 1 inhibitors seem the ideal drugs for treatment of acne and hirsutism.

Tc 99m-Sestamibi scintimammography in the differentiation of benign and malignant breast microcalcifications.

The capability of the mammography-scintimammography combination to distinguish between benign and malignant isolated clusters of breast microcalcifications is discussed. Scintimammography using Tc 99m-Sestamibi was performed in 97 women with an isolated cluster of microcalcifications on mammograms. Seventy-two women had final histopathologic diagnoses (24 cancer and 48 benign pathology). The other 25 patients had follow-up to 3 years. The results of mammography, scintimammography and mammography-scintimammography combination were divided into five groups, based on the suspicion of malignancy. The sensitivity, specificity, false negative fraction, false positive fraction, predictive positive value, predictive negative value and diagnostic accuracy were calculated varying the diagnostic threshold. The Receiver Operating Characteristic (ROC) statistical technique was employed to compare the diagnostic value of mammography to mammography-scintimammography combination. The area under the ROC curves was calculated by the Wilcoxon statistic without any hypothesis on data distribution. The detected difference between areas under the mammography ROC curve (area=0.854, standard error=0.049) and mammography-scintimammography ROC curve (area=0.897, standard error 0.033) was statistically significant (P>0.05, one tail). The area under a ROC curve represents the probability that a randomly chosen diseased or non-diseased subject could be correctly classified. From this point of view this paper demonstrates that, if properly used, scintimammography can add to mammography in the characterization of an isolated cluster of microcalcifications, even if it is not able to replace FNAB and core biopsy.

Pheochromocytoma in Italy: a multicentric retrospective study.

OBJECTIVE: To conduct an epidemiological study on pheochromocytoma in Italy. METHODS: Data on 284 patients with pheochromocytoma observed between 1978 and 1997 were collected from 18 Italian centers through a questionnaire reporting epidemiological, clinical, laboratory, radiological and surgical data. RESULTS: 53.6% of the patients were females and 46.4% were males. Thirty-two tumors were discovered as incidental adrenal masses. The most frequent referred symptoms were palpitations (58.1%), headache (51.9%), sweating (48. 8%) and anxiety (35.3%). Their association was present only in 15.5% of patients. Paroxysmal symptoms were reported in 67.1% and hypertensive crises in 59.7% of patients. Normal blood pressure (systolic and diastolic) was present both in the supine and upright positions in 21.1% of patients. Among laboratory assays, urinary vanylmandelic acid (VMA) was the most widely used (58.1%) and was the least sensitive (25% of false negative results). Basal plasma catecholamines were found to be normal in 11.3% of patients but were always elevated when sampled during a hypertensive paroxysm. A clonidine suppression test was performed in 38 patients with no adverse side effects. It gave a false negative response in 2 patients. A glucagon test was performed in 21 patients. It was interrupted for acute hypertension in 52.4% of patients. Only 5/21 patients were normotensive and had normal basal plasma catecholamines. In these patients the test gave a positive response in four (80%). CT (79.6%) and I-MIBG scintigraphy (68.5%) were the most widely used methods for tumor localization. CT sensitivity was 98.9% for intra-adrenal and 90.9% for extra-adrenal tumors. MIBG sensitivity was 88.5%. In the 263 patients who underwent surgery, the tumor was intra-adrenal in 89.4%, extra-adrenal in 8.5%, intra- and extra-adrenal in 2.1%, and bilateral in 11.0% of patients. Malignancy was reported in 9.9% of cases. Surgery caused remission of hypertension in 59.3%, improvement in 26.8%, and no changes in 13. 9% of patients. In the last group the interval between initial symptoms and diagnosis was significantly longer. CONCLUSIONS: The present study confirms that the clinical presentation of pheochromocytoma is variable and aspecific. Normotension is often present and often the tumor is discovered incidentally. An indication for the routine use of screening methods more sensitive than urinary VMA is strongly suggested. The clonidine test was found to be safe and should be preferred to the glucagon test which has to be restricted to very selected patients. CT and MIBG scintigraphy are almost always successful in localizing the tumor. Reversal of hypertension by surgery seems to depend on an early diagnosis.

[Correlation of ultrasound and galactography in the diagnosis of nipple discharge. Preliminary results]. / Correlazione tra ecografia e galattografia nella diagnostica della mammella secernente. Risultati preliminari.

INTRODUCTION: Several pathologic conditions involving the breast ductal tree can cause bloody or serous nipple discharge. Galactography plays a major clinical role in identifying and localizing intraductal masses, but its sensitivity in detecting cancer is certainly suboptimal. Presently high-frequency ultrasound (US) probes allow detection and guided biopsy of intraductal lesions. We compared the specific information provided by US and galactography in the discharging breast. MATERIAL AND METHODS: Thirty-three patients with discharging breast were submitted to both diagnostic examinations. US was performed with 13 MHz scanheads both before and after galactography. Galactography was performed with 30-31 G catheters to cannulate the discharging duct. Nonionic, water-soluble, sterile contrast material was administered. Postgalactography US was performed to investigate if it could yield further information. The final diagnosis was made at histology and 2 years' instrumental follow-up. RESULTS: Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were evaluated for both techniques. We considered a positive finding the detection of a lesion in general (be it papilloma, papillomatosis, or cancer), as well as the detection of carcinoma only. Sensitivity was 96% for galactography and 84% for US in the former case, versus 50% and 100%, respectively, in the latter. Postgalactography US added no major information. DISCUSSION AND CONCLUSION: US is more sensitive than galactography in cancer diagnosis and, it permits guided biopsy and preoperative localization of unpalpable ductal lesions. In our limited experience, US can be considered a complementary diagnostic tool to galactography in the discharging breast.

[Anterolateral fibrous impingement of the ankle. Report of 14 cases]. / Conflitto fibroso antero-laterale della caviglia. Descrizione di 14 casi.

PURPOSE: Anterolateral fibrous impingement of the ankle is one of the causes of post-traumatic pain in the foot. We investigated the comparative accuracy of US and MRI in this condition. MATERIAL AND METHODS: Fourteen patients were submitted to arthroscopy, plain radiography, US and MRI of the foot. The patients, all sportsmen, had a clinical history of sprains; the major symptoms were pain, swelling and clicking on foot dorsiflexion. RESULTS: US showed anterior talofibular ligament changes in all patients and mid-low-echogenicity synovial tissue filling the lateral malleolar gutter. MRI demonstrated a small mass of synovial tissue in the gutter in 8 patients, with mid-low signal intensity before Gd-DTPA and mid-low contrast enhancement after contrast administration and no abnormal findings in 6 patients. Arthroscopy showed a small firm mass of proliferative synovium in the lateral malleolar gutter in all patients. CONCLUSIONS: Fibrous impingement must be suspected in the sportsmen presenting typical symptoms after ankle trauma. US is poorly accurate in diagnosing this condition. MRI shows a small synovial mass in the lateral malleolar gutter in more than half the patients, but aspecific MR findings do not rule impingement our MR images must be acquired along the proper planes and with Gd-DTPA administration.

Comparison of the diagnostic performance of high-frequency ultrasound as a first- or second-line diagnostic tool in non-palpable lesions of the breast.

To compare the diagnostic performance of high-frequency ultrasound (HFU) as a first- or second-line diagnostic tool in non-palpable lesions (NPL) of the breast and to define the place of HFU in the diagnostic process, 89 women with this kind of lesion, previously detected by mammography, underwent HFU with 7.5-13 MHz transducers. The examinations were performed by two equally experienced operators of which only one (operator I) was aware of the mammographic findings. The mammographic examinations revealed the following non-palpable lesions: asymmetry-hyperdensity (17 cases), nodule (44 cases), stellate lesion (5 cases), microcalcifications (23 cases). Total sensitivity of HFU in the examinations performed by operator I was 83 %, while in the examinations performed by operator II (unaware of the mammographic findings) it was only 35 %. In all cases HFU allowed the operators to determine the basic features of the lesions. Our experience confirms that ultrasonography, even if performed with high frequency, cannot be proposed as a screening examination but may profitably be employed as a second-step technique to characterize NPL previously identified by mammography. This 'second-step' role can do the following: rule out true pathology (cases of false-positive mammography findings); furnish some basic features in the case of focal lesions; show other findings in the case of microcalcifications, such as microcysts, 'filled duct' appearance, parenchymal inhomogeneities and nodules; guide interventional procedures; and localize lesions preoperatively.

[Osteochondral lesions of the humeral head: the usefulness of echographic study]. / Lesioni osteocondrali della testa omerale: utilità dello studio ecografico.

PURPOSE: In the cranial humeral end, osteochondral injuries localize in a circular crown including part of the humeral head and part of the major and minor tuberosities. Since this region is easy to depict with US, we investigated the potentials of this technique in detecting osteochondral injuries. MATERIALS AND METHODS: Seventy-five osteochondral injuries found at 492 US examinations performed in 12 months with a 7.5 MHz linear probe were retrospectively reviewed. Clinical history taking was focused on the following: a) previous trauma or b) luxation-instability and c) if the patient was a sportsman devoted to activities requiring forced abduction-external rotation or adduction-internal rotation. Since the site of the head's humeral injury is an important clue for diagnosis, we subdivided the humeral circle into four ideal quadrants by two perpendicular lines with the main line passing through the bicipital groove. Then, each injury was ascribed to a quadrant. All patients were also submitted to radiography (at least two films) and to MRI; CT was performed in 12 patients. Ten patients underwent surgery. RESULTS: We found 34 Hill-Sachs lesions, 15 traumas, 9 arthrotic lesions, 7 cases of anterointernal and 4 of posterosuperior impingement, 4 cases of infraspinatus enthesopathy and 2 erosions due to perihumeral calcifications. In our experience, US was an accurate tool in the identification of humeral head conditions, which were confirmed at CT and/or MRI in all patients (no false positives). As for the injury nature, US diagnosis was confirmed in all Hill-Sachs lesions (34/34 cases), traumas (15/15 cases) and 50% of the cases of posterosuperior impingement (2/4 cases). These conditions made up about 2/3 of the whole cases (51/75 cases). US failed to establish the injury nature in the 9 arthrotic lesions, 7 cases of anterointernal impingement, 4 cases of infraspinatus enthesopathy and 2 erosions due to perihumeral calcifications. CONCLUSIONS: US can be suggested as the method of choice in the study of the osteochondral lining of the humeral head.