Minimal Extrathyroid Extension (mETE) as the Only Risk Factor in Patients with Papillary Thyroid Carcinoma (PC): Its Clinical Impact on Recurrence and Outcome during Long-Term Follow-Up.

Minimal extrathyroid extension (mETE) effect on papillary thyroid carcinoma (PC) prognosis is still debated even more so now that this factor has been removed in the 8th AJCC Edition, supporting the hypothesis that mETE is not associated with aggressive tumors. We retrospectively enrolled 91 PC patients (Group 1) submitted to total thyroidectomy and radioiodine ablation. At the time of the primary tumor surgery, mETE was ascertained in all patients with no other risk factors, such as multifocality, vascular invasion, neck and distant metastases, and aggressive histological variants. As controls, 205 consecutive matched PC patients (Group 2) without mETE and the aforementioned risk factors were enrolled. During the follow-up (average 8 years), 16/91 (17.58%) Group 1 patients and 15/205 (7.32%) Group 2 patients developed metastases (p = 0.0078). Cox regression analysis showed an increased risk of metastases in patients with mETE (HR: 2.58 (95% CI 1.28-5.22) p = 0.008). Disease-free survival (DFS) was significantly lower in patients with mETE than in controls (p = 0.0059). The present study seems to demonstrate that mETE can be associated with an aggressive PC and can be considered, even alone without other risk factors, an independent factor of unfavorable DFS. Thus, by excluding mETE in the 8th AJCC Edition, patient care and management could be compromised.

Hashimoto's Thyroiditis and Papillary Thyroid Carcinoma: A Follow-Up Study in Patients with Absence of Aggressive Risk Factors at the Surgery of the Primary Tumor.

Hashimoto's thyroiditis (HT) is often associated with papillary thyroid carcinoma (PC); it is still a matter of controversy whether the behavior of carcinoma is more aggressive or not. During the follow-up, we retrospectively enrolled 97 patients with PC/HT after thyroidectomy without risk factors at the surgery of the primary tumor, such as multifocality/multicentricity, extrathyroid tumor extension, vascular invasion, neck and distant metastases, and aggressive histological variants. HT diagnosis was confirmed by histology and serum thyroid antibodies. Tumor size was ≤10 mm in 64 cases (microcarcinomas); 206 matched PC patients after thyroidectomy without HT and risk factors were enrolled as controls, totaling 122 microcarcinomas. During follow-up, metastases occurred in 15/97 (15.5%) PC/HT cases, eight microcarcinomas, and in 16/206 (7.8%) without HT, eight microcarcinomas (p = 0.04). Considering both PC/HT and PC patients without HT who developed metastases, univariate analysis showed an increased risk of metastases in patients with HT coexistence, OR: 2.17 (95% CI 1.03-4.60) p = 0.043. Disease-free survival (DFS) was significantly (p = 0.0253) shorter in PC/HT than in the controls. The present study seems to demonstrate that HT is not a cancer protective factor in PC patients given the less favorable outcomes and significantly shorter DFS. HT may also represent an independent recurrence predictor without other risk factors.

A Comparative Follow-Up Study of Patients with Papillary Thyroid Carcinoma Associated or Not with Graves' Disease.

Whether papillary carcinoma (PC) behavior is more aggressive in Graves' disease (GD) patients than PC cases without GD is controversial. We retrospectively enrolled 33 thyroidectomized PC/GD patients during long-term follow-up, 23/33 without risk factors at surgery, and 18/33 microcarcinomas; 312 PC euthyroid-matched patients without risk factors served as controls. A total of 14/33 (42.4%) PC/GD patients, 4 with and 10 without risk factors at diagnosis, 6 with microcarcinoma, underwent metastases during follow-up. In controls, metastases in 21/312 (6.7%) were ascertained. Considering 10/23 PC/GD patients and 21/312 controls without risk factors who developed metastases, univariate analysis showed that there was an increased risk of metastasis appearance for PC/GD cases (p < 0.001). Disease-free survival (DFS) was significantly (p < 0.0001, log-rank test) shorter in PC/GD patients than in controls. Significantly more elevated aggressiveness in 6/18 PC/GD patients with microcarcinoma than in controls was also ascertained with shorter DFS. Thus, in the present study, PC/GD had aggressive behavior during follow-up also when carcinoma characteristics were favorable and some cases were microcarcinomas. GD and non-GD patient comparison in the cases without risk factors at diagnosis showed an increased risk to develop metastases in GD during follow-up, suggesting that GD alone might be a tumor aggressiveness predictive factor in these cases.

The Diagnostic Usefulness of 131I-SPECT/CT at Both Radioiodine Ablation and during Long-Term Follow-Up in Patients Thyroidectomized for Differentiated Thyroid Carcinoma: Analysis of Tissue Risk Factors Ascertained at Surgery and Correlated with Metastasis Appearance.

131I Single-photon emission computerized tomography/computerized tomography (SPECT/CT) in the management of patients thyroidectomized for differentiated thyroid carcinoma (DTC) was further investigated. Retrospectively, 106 consecutive DTC patients were enrolled at the first radioiodine ablation, 24 at high risk (H), 61 at low risk (L) and 21 at very low risk (VL). 131I whole-body scan (WBS) and SPECT/CT were performed after therapeutic doses using a hybrid dual-head gamma camera. At ablation, SPECT/CT correctly classified 49 metastases in 17/106 patients with a significantly (p < 0.001) more elevated number than WBS which evidenced 32/49 foci in 13/17 cases. In this case, 86/106 patients could be monitored in the follow-up including 13/17 cases with metastases already at post-therapeutic scans. SPECT/CT after radioiodine diagnostic doses more correctly than WBS ascertained disease progression in 4/13 patients, stable disease in other 4/13 cases and disease improvement in the remaining 5/13 cases. Further 13/86 patients with only residues at post-therapeutic scans showed at SPECT/CT 16 neck lymph node (LN) metastases, three unclear and 13 occult at WBS. Significant involvement of some tissue risk factors with metastasis appearance was observed, such as minimal extrathyroid tumor extension and neck LN metastases. These risk factors should be carefully considered in DTC patient follow-up where 131I-SPECT/CT routinely use is suggested as a support tool of WBS.

123I-Ioflupane SPECT and 18F-FDG PET Combined Use in the Characterization of Movement and Cognitive Associated Disorders in Neurodegenerative Diseases.

BACKGROUND: Both movement (MD) and cognitive (CD) disorders can occur associated in some neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). OBJECTIVE: We further investigated the usefulness of 123I-Ioflupane SPECT and 18F-FDG PET combined use in patients with these disorders in the early stage. METHODS: We retrospectively enrolled twenty-five consecutive patients with MD and CD clinical symptoms of recent appearance. All patients had undergone neurologic examination, neuropsychological tests, and magnetic resonance imaging. 123I-Ioflupane SPECT was performed in all cases, followed by 18F-FDG PET two weeks later. In the two procedures, both qualitative (QL) and quantitative (QN) image analyses were determined. RESULTS: In patients with both 123I-Ioflupane SPECT and 18F-FDG PET pathologic data, associated dopaminergic and cognitive impairments were confirmed in 56% of cases. Pathologic SPECT with normal PET in 16% of cases could diagnose MD and exclude an associated CD, despite clinical symptoms. On the contrary, normal SPECT with pathologic PET in 28% of cases could exclude basal ganglia damage while confirming CD. QN 123I-Ioflupane SPECT analysis showed better performance than QL since QN correctly characterized two cases of MD with normal QL. Moreover, correct classification of normal metabolism was made only by QN analysis of 18F-FDG PET in four cases, despite suspect areas of hypometabolism at QL. CONCLUSION: The combined use of these imaging procedures proved a reliable diagnostic tool to accurately identify and characterize MD and CD in early stage. QN analysis was effective in supporting QL evaluation, and its routine use is suggested, especially with inconclusive QL.

Neck lymph node metastasis detection in patients with differentiated thyroid carcinoma (DTC) in long-term follow-up: a 131I-SPECT/CT study.

BACKGROUND: The identification of neck lymph node (LN) metastases represents a very important issue in the management of patients with differentiated thyroid carcinoma (DTC). To this purpose, in the present study, we used 131I-SPECT/CT as a diagnostic imaging procedure. METHODS: A consecutive series of 224 DTC patients with ascertained neck radioiodine-avid foci at 131I-SPECT/CT during long-term follow-up was evaluated. All patients had already undergone total thyroidectomy and radioiodine therapy and had been classified as follows: 62 at high risk (H), 64 at low risk (L) and 98 at very low risk (VL). 131I-Whole body scan (WBS) followed by SPECT/CT was performed in all cases. RESULTS: In the 224 patients, 449 neck iodine avid foci were ascertained at SPECT/CT, while 322 were evidenced at WBS in 165/224 patients. WBS classified as residues 263/322 foci and as unclear 59/322 foci; among the former foci SPECT/CT correctly characterized 8 LN metastases and 3 physiologic uptakes and among the latter, it pinpointed 26 LN metastases, 18 residues, and 15 physiologic uptakes. SPECT/CT also classified 127 foci occult at WBS as 59 LN metastases and 68 residues. Globally, SPECT/CT identified 93 LN metastases in 59 patients (26 H, 20 L, 13 VL), while WBS evidenced 34 in 25 cases. All 13 VL patients, T1aN0M0, 5 of whom with LN near sub-mandibular glands, had thyroglobulin undetectable or < 2.5 ng/ml. Globally, SPECT/CT obtained an incremental value than WBS in 45.5% of patients, a more correct patient classification changing therapeutic approach in 30.3% of cases and identified WBS false-positive findings in 8% of cases. CONCLUSIONS: 131I-SPECT/CT proved to correctly detect and characterize neck LN metastases in DTC patients in long-term follow-up, improving the performance of planar WBS. SPECT/CT routine use is thus suggested; its role is particularly relevant in patients with WBS inconclusive, VL, T1aN0M0 and with undetectable or very low thyroglobulin levels.

[123I]Metaiodobenzylguanidine (MIBG) Cardiac Scintigraphy and Automated Classification Techniques in Parkinsonian Disorders.

PURPOSE: To provide reliable and reproducible heart/mediastinum (H/M) ratio cut-off values for parkinsonian disorders using two machine learning techniques, Support Vector Machines (SVM) and Random Forest (RF) classifier, applied to [123I]MIBG cardiac scintigraphy. PROCEDURES: We studied 85 subjects, 50 with idiopathic Parkinson's disease, 26 with atypical Parkinsonian syndromes (P), and 9 with essential tremor (ET). All patients underwent planar early and delayed cardiac scintigraphy after [123I]MIBG (111 MBq) intravenous injection. Images were evaluated both qualitatively and quantitatively; the latter by the early and delayed H/M ratio obtained from regions of interest (ROIt1 and ROIt2) drawn on planar images. SVM and RF classifiers were finally used to obtain the correct cut-off value. RESULTS: SVM and RF produced excellent classification performances: SVM classifier achieved perfect classification and RF also attained very good accuracy. The better cut-off for H/M value was 1.55 since it remains the same for both ROIt1 and ROIt2. This value allowed to correctly classify PD from P and ET: patients with H/M ratio less than 1.55 were classified as PD while those with values higher than 1.55 were considered as affected by parkinsonism and/or ET. No difference was found when early or late H/M ratio were considered separately thus suggesting that a single early evaluation could be sufficient to obtain the final diagnosis. CONCLUSIONS: Our results evidenced that the use of SVM and CT permitted to define the better cut-off value for H/M ratios both in early and in delayed phase thus underlining the role of [123I]MIBG cardiac scintigraphy and the effectiveness of H/M ratio in differentiating PD from other parkinsonism or ET. Moreover, early scans alone could be used for a reliable diagnosis since no difference was found between early and late. Definitely, a larger series of cases is needed to confirm this data.

Qualitative and Quantitative Analyses of Brain 18Fluoro-Deoxy-Glucose Positron Emission Tomography in Primary Progressive Aphasia.

BACKGROUND: A primary progressive aphasia (PPA) diagnosis is generally based on clinical criteria, but often symptoms and signs may overlap in the different forms. Recent data have evidenced that brain 18fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) could support the clinical diagnosis, since specific metabolic patterns are described for the different variants. AIMS: We further evaluated the usefulness of 18F-FDG PET, by both visual qualitative (QL) and quantitative (QN) methods in the initial diagnosis of PPA, focusing on the classification of different variants. Moreover, we also analyzed the role of 18F-FDG PET in clarifying the association of PPA with the early phase of Alzheimer's disease (AD) or frontotemporal (FTD) dementias. METHODS: We consecutively enrolled 35 patients with clinical symptoms of aphasia, suspect of or attributable to PPA. Patients were classified into two groups: 18 cases with clinical symptoms of aphasia but normal neuropsychological tests and an unclear classification of a specific PPA variant (group A) and 17 cases with clinical and neuropsychological signs attributable to PPA with an uncertain differential diagnosis between AD and FTD (group B). All patients underwent brain 18F-FDG PET/CT, and images were evaluated both by QL and QN, the latter applying an automated analysis program that produced brain regional metabolicmaps and normal age-matched control group comparative analysis (zscore). RESULTS: 18F-FDG PET showed different patterns of bilateral cortical hypometabolism in the two groups. The combined use of QL and QN permitted to achieved a correct PPA variant diagnosis in 8 of 18 (44.4%) cases of group A and in 14 of 17 (82.3%) of group B, while only QN could support the correct classification of PPA variants in 10 of 18 (55.6%) cases of group A and in 3 of 17 (17.7%) cases of group B in whom the procedure better localized the hypometabolic areas. CONCLUSIONS: Brain 18F-FDG PET had an elevated performance in the early diagnosis of PPA variants and in the advanced PPA AD/FTD classification. QL clarified the development of AD or FTD in advanced PPA cases and supported the differential diagnosis of a PPA variant in a few early cases. QN 18F-FDG PET evaluation better contributed to the early diagnosis of an unclear metabolic pattern. To correctly identify all cases, patients with diffuse cortical hypometabolism were also included. Larger series are necessary to confirm these data.

Role of Diagnostic 131I SPECT/CT in Long-Term Follow-up of Patients with Papillary Thyroid Microcarcinoma.

Papillary thyroid microcarcinoma (PTMC) usually has a favorable prognosis but can also be aggressive, with neck and distant metastases. We evaluated the diagnostic role of 131I SPECT/CT in detecting metastases in PTMC patients during long-term follow-up and whether the procedure should be included in the current diagnostic protocol. Methods: We retrospectively studied 351 consecutive PTMC patients who had undergone thyroidectomy and radioiodine therapy; 21 were at high risk, 94 at low risk, and 236 at very low risk. During follow-up, the patients underwent diagnostic 131I whole-body scanning (WBS) followed by SPECT/CT. Results: WBS found 248 radioiodine-avid foci in 126 patients, and SPECT/CT found 298 in 139 patients, confirming all foci found on WBS. SPECT/CT also correctly classified 76 of the avid foci as unclear or wrongly classified on WBS. Globally, SPECT/CT detected and correctly classified 64 neoplastic lesions in 27 of 30 patients with metastases, and WBS evidenced 39 of 64 lesions, 28 of which were unclear or wrongly classified, in 16 of the 30 patients. Nineteen of 27 patients, including 13 at very low risk, had only neck metastases, 9 of 19 being T1aN0M0 with an undetectable thyroglobulin level. Three of 27 patients, including 1 at very low risk, had only distant metastases with an undetectable or very low thyroglobulin level. Five of 27 patients had neck and distant metastases with a thyroglobulin level <2.5 ng/mL in 1 case, between 2.5 and 10 in 3 cases, and >10 in the remaining case. SPECT/CT also reduced WBS false-positive results in 15 of 139 patients (10.8%). SPECT/CT had an incremental value over WBS in 38.1% of patients with positive findings and changed the classification and therapeutic management in 21.6%. Conclusion: Metastases occurred in 8.5% of patients during long-term follow-up. SPECT/CT performed better than WBS, particularly in patients at very low risk with inconclusive WBS results, a TNM stage of T1aN0M0, and an undetectable or very low level of thyroglobulin. Prolonged surveillance is justified in PTMC patients, and wider use of 131I SPECT/CT in the diagnostic protocol is suggested.

Intracranial Leptomeningeal Carcinomatosis: A Diagnostic Study with 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Leptomeningeal carcinomatosis (LC) diagnosis is based on cerebrospinal fluid (CSF) cytological analysis and contrast-enhanced magnetic resonance imaging (MRI); however, low sensitivity was evidenced in some cases delaying prompt and adequate treatments. Brain 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) was also employed in doubtful cases. We retrospectively described 4 suspected LC cases with uncertain or undetectable MRI and initially negative CSF cytology. Whole-body (WB) and brain 18F-FDG PET/computed tomography (CT) were used, the latter showing intracranial tracer uptakes suspected for LC in 3/4 cases. In 2 of these 3 cases, WB scan also evidenced spinal cord lesion and pulmonary tumor, respectively, while both procedures were true negative in the fourth case. CSF cytology became positive after repeated exams in the 3 PET/CT-positive cases. In 1 of these 3 patients, it was also confirmed at MRI, while it stayed negative in the remaining PET/CT-negative case with uncertain MRI. 18F-FDG PET/CT could be a useful supportive diagnostic tool in doubtful intracranial and spinal LC.

The role of molecular breast imaging in predicting complete tumor response to treatment and residual tumor extent following neoadjuvant therapy.

The aim of the present study was to investigate the usefulness of molecular breast imaging (MBI) in predicting complete tumor response to treatment and residual tumor extent following neoadjuvant therapy. A consecutive series of 43 female patients with large or locally advanced primary breast cancer, scheduled for surgery following neoadjuvant therapy, was retrospectively reviewed. Prior to surgery, all patients underwent MBI using a high­resolution semiconductor­based device for image acquisition. MBI data were correlated with surgical histopathological findings. Spearman's correlation coefficient was calculated to assess differences in residual tumor size with MBI and histopathological examination. From the images obtained using MBI, 7 patients were negative for residual tumors with pathological complete response (specificity, 100%) and positive in 34/36 patients with residual disease (sensitivity, 94.4%), including 26/27 patients with unifocal and 8/9 patients with multicentric/multifocal tumors, 5 of which exhibited multiple microscopic foci scattered in a fibrotic area. Overall accuracy was 95.3% and the positive predictive value (PPV) and negative predictive value (NPV) were 100 and 77.8%, respectively. MBI was false­negative in one patient with a 2.5­cm invasive ductal carcinoma located close to the chest wall and in one patient with microscopic foci of epithelial carcinoma. In the patients with unifocal residual tumors, correlation of tumor size between MBI and histopathology was r=0.981 (P<0.0001); however, MBI overestimated the number of lesions in one of these cases. In the patients with multifocal/multicentric tumors, MBI adequately assessed residual tumor extent in 5/8 positive cases, overestimating the number of lesions in one case and underestimating tumor extent in 2 further cases with microscopic foci scattered in a fibrotic area. MBI proved to be a highly accurate diagnostic tool in predicting complete tumor response to neoadjuvant therapy and residual tumor extent, correlating with surgical histopathological findings in 86% of overall cases. A positive result was always associated with the presence of residual disease and MBI tumor size was strongly correlated with histopathological analysis mainly in unifocal residual tumors.

123I-ioflupane SPET and 123I-MIBG in the diagnosis of Parkinson's disease and parkinsonian disorders and in the differential diagnosis between Alzheimer's and Lewy's bodies dementias.

Nuclear medicine procedures are widely used as "in vivo" biomarkers in a large number of brain diseases, especially in the diagnosis of Parkinson's disease (PD) and of parkinsonian disorders (pD). Furthermore, nuclear medicine is used in the differential diagnosis of dementias especially Alzheimer's disease (AD) and dementia with Lewy's bodies (LBD) which share many clinical symptoms and often LBD is misdiagnosed as AD. The differential diagnosis between these clinical entities is crucial for treatment since LBD also shares some clinical symptoms with parkinsonian disorders. We reviewed the most relevant papers that study the usefulness of both iodine-123-ioflupane studied by single photon emission tomography (123I-ioflupane SPET) and of 123I-metaiodobenzylguanidine (123I-MIBG) cardiac scintigraphy in the diagnosis of PD and pD and in the differential diagnosis between AD and LBD in order to contribute to the clinical practice of the diseases.

Non-functioning gastroenteropancreatic (GEP) tumors: a 111In-Pentetreotide SPECT/CT diagnostic study.

In a retrospective study performed in non-functioning GEP tumor patients we further investigated 111In-Pentetreotide SPECT/CT usefulness in diagnosis, staging and follow-up also evaluating whether the procedure may give more information than conventional imaging procedures (CIP), such as CT, MRI, US. We enrolled 104 consecutive patients with non-functioning GEP tumors, 30 in initial diagnosis and staging phases (IDS) and 74 in follow-up (FU). All patients underwent somatostatin receptor scintigraphy (SRS) whole body scan at 4, 24 and, if necessary, 48 hours followed by abdominal and chest SPECT/CT after 111In-Pentetreotide 148-222 MBq i.v. injection. The patients previously underwent 2 to 3 CIP. At both CIP and SPECT/CT, 34/104 patients were classified as no evidence of disease (NED); in 70/104 patients, neoplastic lesions were ascertained and 12 IDS and 17 FU were classified as not operable and treated with octeotride or chemotherapy. SPECT/CT and CIP were concordantly positive in 44 patients, while only CIP was positive in 6 cases and only SPECT/CT in 20. Both per-patient sensitivity and accuracy of SPECT/CT (91.4 and 94.2%, respectively) were higher than CIP (71.4 and 80.8%, respectively), but not significantly. Globally, 292 lesions were ascertained: 141 hepatic, 78 abdominal extra-hepatic and 73 extra-abdominal. CIP detected 191/292 (65.4%) lesions in 50 patients, while SPECT/CT 244/292 (83.6%) in 64, the difference being significant (p<0.0001). No false positive results were found at both SPECT/CT and CIP. Both SPECT/CT sensitivity and accuracy were higher than CIP in G1, G2, neuroendocrine carcinoma (NEC) and mixed adeno-neuroendocrine carcinoma (MANEC) patients, but significantly only for G1. Globally, SPECT/CT incremental value than CIP was 35.6%. SPECT/CT correctly modified CIP classification and patient management in 27.9% of cases, while it down-staged the disease than CIP in 9.6% of cases. However, the two procedures combined use could achieve the highest accuracy value. 111In-Pentetreotide SRS, acquired as SPECT/CT, showing high sensitivity and accuracy values, more elevated than CIP in the present study, can still have a wide employment in the routine diagnostic protocol of non-functioning GEP tumors with significant impact on patient management and therapy planning. The procedure is simple to perform, has limited cost and wide availability in all Nuclear Medicine Centers.

123I-ioflupane brain SPECT and 123I-MIBG cardiac planar scintigraphy combined use in uncertain parkinsonian disorders.

We evaluated the clinical usefulness of the combined use of I-ioflupane brain single photon emission computed tomography (SPECT) and I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy in discriminating uncertain parkinsonism with vascular lesions in striatal nuclei at magnetic resonance imaging (MRI). Forty-three consecutive patients with uncertain parkinsonism and vascular lesions at MRI in striatal nuclei were retrospectively evaluated; the uncertain differential diagnosis was between Parkinson's disease and vascular parkinsonism (PD/VP) in 22 patients, between PD and other neurodegenerative parkinsonism (PD/PS) in 11 patients and between Lewy body dementia and Alzheimer disease (LBD/AD) in the remaining 10 cases. All patients underwent I-ioflupane SPECT with striatal dopaminergic activity determination as binding potentials (BP; cut-off: 3.3). I-MIBG cardiac planar scintigraphy was performed 2 weeks later, in early (15 minutes) and delayed (240 minutes) phases also calculating heart to mediastinum (H/M) ratio (cut-off: 1.56). I-Ioflupane uptake was normal in 9 patients with BP values >3.3, while it was reduced in 34/43 cases with BP values <3.3 at least in one of the striatal nuclei. I-MIBG uptake was normal in 21/43 patients (5 of whom with normal and 16 with I-ioflupane striatal defects) showing the H/M ratio >1.56 in all cases; the uptake was reduced in 22/43 cases, (4 of whom were normal and 18 were with I-ioflupane striatal defects) with the H/M ratio <1.56 in all cases. No statistical differences were found when early and delayed H/M ratios were mutually compared. Combining the 2 radioisotopic procedures, a more reliable diagnosis was achieved in 39/43 cases properly classifying 13 PD, 10 VP, 7 PS, 5 LBD, and 4 AD. However, the diagnosis remained uncertain in four patients with normal I-ioflupane and reduced I-MIBG uptake. The results of the present study confirmed that in uncertain parkinsonian syndromes associated with vascular lesions in striatal nuclei, brain I-ioflupane SPECT alone did not prove able to discriminate between the different forms of disease. Only the association with I-MIBG cardiac scintigraphy, also with the early acquisition alone, allowed the most appropriate diagnosis in 90.7% of our cases. However, patients with normal I-ioflupane and reduced I-I-MIBG uptakes need a close clinical and instrumental follow-up as sympathetic damage could precede striatal disorders in the early stage of PD and LBD.

Brain SPECT with Perfusion Radiopharmaceuticals and Dopaminergic System Radiocompounds in Dementia Disorders.

As well known, the increase in life expectancy and the better physical condition of people in western countries will lead in the next 20 years to a dramatic development of neurodegenerative diseases, especially of dementia that could be considered one of the most important problems in clinical, social and economic fields for the future. Therefore, the differential diagnosis of the various types of dementia is a critical step for patients, clinicians and researchers since an accurate "in vivo" diagnosis can lead to a better patients management. Neuroimaging techniques and in particular the most diffuse and affordable single photon emission computed tomography (SPECT) have provided useful information about dementia disorders and these methods, on the basis of the recent advances, will have an increasingly important role in research and clinical practice. The purpose of this article is to analyze the different SPECT techniques now available which proved clinically useful in correctly formulating the differential diagnosis of dementia.

111In-Pentetreotide SPECT/CT in Pulmonary Carcinoid.

AIM: We evaluated somatostatin receptor scintigraphy (SRS) with (111)In-pentetreotide incremental value in pulmonary carcinoid (PC) diagnosis compared to contrast enhanced Computed Tomography (ceCT). PATIENTS AND METHODS: We enrolled 81 patients with ascertained PC, 39 at initial staging and 42 in follow-up; the primary tumor had already been excised in 68 cases. Single Photon emission Computed Tomography (SPECT) images were reconstructed with the iterative method and fused with non-enhanced Computed tomography (CT) images. RESULTS: Primary PC or metastatic lesions were ascertained in 55/81 patients and SPECT/CT was positive in 50/55 cases, while ceCT was positive in 44/55. Comparing SPECT/CT with ceCT results, we found a sensitivity of 96 vs. 87.5%, and specificity of 92% vs. 97% for the detection of primary lesion or recurrent disease. A total of 198 lesions were ascertained at SPECT/CT, while 161 at ceCT, with values of sensitivity and specificity of 85.5% and 84.6% for SRS and 75.2% and 90.5% respectively. CONCLUSION: (111)In-Pentetreotide SPECT/CT proved to be more sensitive and accurate than ceCT, thus enhancing its role in evaluating patients with PC.

Sentinel node biopsy in early breast cancer: lessons learned from more than 1000 cases at a single institution.

AIMS: The aims of this paper are to report the development of sentinel node biopsy (SNB) in breast cancer at a single institution and to discuss the relevant issues on SNB still to be elucidated. PATIENTS AND METHODS: From 1998 to 2010, 1021 SNBs with frozen section examination were carried out in patients with breast cancer. In the early period (1998-2002) SNB was always combined with axillary lymph node dissection (ALND). From 2002 onwards, only patients with a positive SNB result underwent ALND (late period). The characteristics of patients with infiltrating carcinoma (IC) and ductal carcinoma in situ (DCIS) and the histological status of the sentinel nodes were examined. The survival outcomes of node-negative patients were compared between patients submitted to SNB and ALND (ALND group) during the early period and patients who underwent only SNB during the late period (SNB group). RESULTS: The sentinel node was identified intraoperatively in 98.3% of cases. During the early period the overall accuracy of SNB was 97.0%. During the late period, 700 patients with IC and 140 with DCIS underwent SNB. In the IC group, 149 patients (21.3%) had sentinel node macrometastases and 36 (5.1%) micrometastases; of that subgroup, 21 underwent ALND and no other metastatic lymph nodes were found, and 15 underwent SNB only. Axillary recurrences were observed in 4 patients (0.77%) with negative SNB; none of these were among the patients with micrometastatic SNB. Two patients (1.4%) with DCIS had a positive SNB. In node-negative patients the 5-year overall survival was 96.7% in the ALND group and 96.5% in the SNB group (P = 0.63). The 5-year disease-free survival was 93.8% and 93.2% in the ALND and SNB groups, respectively (P = 0.77). CONCLUSIONS: Overall and disease-free survival in patients with a negative SNB result and no further axillary surgery were equal to those in patients with negative ALND. Intraoperative assessment of the sentinel node in expert hands has a low false-negative rate and allows immediate ALND in patients with sentinel node metastases, avoiding the need for a second operation. ALND for sentinel node micrometastases may be safely omitted in most patients with early stage breast cancer.

Breast scintigraphy with breast-specific γ-camera in the detection of ductal carcinoma in situ: a correlation with mammography and histologic subtype.

UNLABELLED: Ductal carcinoma in situ (DCIS) is a subtype of breast cancer encountered increasingly in clinical practice because of the widespread use of screening mammography. In the present study, we evaluated the usefulness of breast-specific γ-camera (BSGC) scintigraphy in DCIS identification, describing the scintigraphic findings and their correlation with mammography and histologic subtype. METHODS: Thirty-three women, aged 41-81 y, with surgically proven DCIS were retrospectively reviewed. Before surgery, all patients underwent breast scintigraphy using a high-resolution semiconductor-based BSGC, starting 10 min after intravenous injection of 740 MBq of (99m)Tc-tetrofosmin. All patients had previously undergone mammography. A definitive histologic diagnosis was obtained in all cases after scintigraphy, and the scintigraphic findings were correlated with mammography and histologic subtype. RESULTS: Mammography was positive in 30 of 33 patients (sensitivity, 90.9%), showing calcifications in 22 of 30 (73.3%), masses in 3 of 30 (10%), and masses plus calcifications in the remaining 5 of 30 (16.7%). Scintigraphy was positive in 31 of 33 patients (sensitivity, 93.9%), showing patchy irregular uptake in patients with calcifications and focal uptake in masses; sensitivity was higher in low- to intermediate-grade DCIS than in intermediate/high- and high-grade DCIS (100% vs. 91.3%), but the difference was not statistically significant. Two comedo-type DCIS (one 20-mm intermediate/high-grade and one 15-mm high-grade) with heterogeneously or highly dense breasts at mammography and one papillary low/intermediate-grade DCIS associated with Paget disease were true positive only at scintigraphy. Moreover, scintigraphy better assessed disease extent than did mammography in 5 additional patients. Two comedo-type DCIS (one 6-mm intermediate/high-grade and one 15-mm high-grade) were true positive only at mammography. The difference in sensitivity between scintigraphy and mammography was not statistically significant. The combined use of mammography and scintigraphy achieved 100% sensitivity. CONCLUSION: BSGC scintigraphy proved to be a highly sensitive diagnostic tool in the detection of DCIS, irrespective of histologic subtype, and with a scintigraphic pattern of uptake that correlated well with mammography findings. In our series, BSGC scintigraphy demonstrated a slightly higher sensitivity than mammography and a better assessment of local disease extent. Thus, BSGC scintigraphy should represent a useful adjunctive tool in breast cancer diagnosis.

The clinical impact of breast scintigraphy acquired with a breast specific γ-camera (BSGC) in the diagnosis of breast cancer: incremental value versus mammography.

We investigated the clinical impact of breast scintigraphy acquired with a breast specific γ-camera (BSGC) in the diagnosis of breast cancer (BC) and assessed its incremental value over mammography (Mx). A consecutive series of 467 patients underwent BSGC scintigraphy for different indications: suspicious lesions on physical examination and/or on US/MRI negative at Mx (BI-RADS 1 or 3), characterization of lesions suspicious at Mx (BI-RADS 4), preoperative staging in lesions highly suggestive of malignancy at Mx (BI-RADS 5). Definitive histopathological findings were obtained in all cases after scintigraphy: 420/467 patients had BC, while 47/467 patients had benign lesions. The scintigraphic data were correlated to Mx BI-RADS category findings and to histology. The incremental value of scintigraphy over Mx was calculated. Scintigraphy was true-positive in 97.1% BC patients, detecting 96.2% of overall tumor foci, including 91.5% of carcinomas ≤10 mm, and it was true-negative in 85.1% of patients with benign lesions. Scintigraphy gave an additional value over Mx in 141/467 cases (30.2%). In particular, scintigraphy ascertained BC missed at Mx in 31 patients with BI-RADS 1 or 3, including 26 patients with heterogeneously/high dense breast (19/26 with tumors ≤10 mm) and detected additional clinically occult ipsilateral or controlateral tumor foci (all <10 mm) or the in situ component sited around invasive tumors in 77 BC patients with BI-RADS 4 or 5, changing surgical management in 18.2% of these cases; moreover, scintigraphy ruled out malignancy in 33 patients with BI-RADS 4. BSGC scintigraphy proved a highly sensitive diagnostic tool, even in small size carcinoma detection, while maintaining a high specificity. The procedure increased both the sensitivity of Mx, especially in dense breast and in multifocal/multicentric disease, and the specificity as well as it better defined local tumor extension, thus guiding the surgeon to a more appropriate surgical treatment.

The usefulness of Tc-99m-tetrofosmin SPECT/CT in the detection of residual tumors and axillary lymph node metastases in breast cancer patients following neoadjuvant therapy.

Single photon emission computed tomography (SPECT)/CT is emerging as a useful diagnostic tool in several oncological fields. In this prospective study, we assessed the usefulness of Tc-99m-tetrofosmin SPECT/CT in the detection of both residual breast tumors and axillary lymph node metastases following neoadjuvant therapy. Thirty-seven consecutive breast cancer patients scheduled to surgery following neoadjuvant therapy preoperatively underwent a Tc-99m-tetrofosmin SPECT/CT study, using a dual head gamma camera integrated with a x-ray tube for low-dose CT, including both breasts and axillary regions in the field of view. Within 1 week of SPECT/CT, all 37 patients had breast surgery with associated axillary lymph node dissection in 33/37 cases. At surgery, 31/37 patients had breast residues (microscopic in 4/31 cases and macroscopic in 27/31 cases). Axillary lymph node metastases were ascertained in 19/33 cases (N1mi: 2 cases, N1a: 8 cases, N2a: 6 cases, N2b: 3 cases). SPECT/CT sensitivity, specificity, and accuracy in detecting residual tumors were 87%, 100%, and 89.2%, respectively; the corresponding values in detecting axillary lymph node metastases were 36.8%, 92.8%, and 60.6%. SPECT/CT missed breast cancer residues in 4/31 patients, including 2 cases with microscopic residual disease. Moreover, lymph node metastases were missed in 12/19 patients (10/12 with pN1mi or pN1a metastases), all with lymph nodes with post-therapy fibrotic changes and small deposits of metastases. Tc-99m-tetrofosmin SPECT/CT proved a useful diagnostic tool in the detection and in the localization of residual breast tumors following neoadjuvant therapy. The procedure lacked in sensitivity in identifying axillary lymph node metastases, especially in patients with a limited lymph node involvement. According to our data, SPECT/CT may guide the surgeon to the most appropriate breast surgical treatment and to eventually select the most suitable axillary lymph node sampling (axillary lymph node dissection or sentinel node biopsy).