Italian consensus recommendations for a biomarker-based aetiological diagnosis in mild cognitive impairment patients.

BACKGROUND AND PURPOSE: Biomarkers support the aetiological diagnosis of neurocognitive disorders in vivo. Incomplete evidence is available to drive clinical decisions; available diagnostic algorithms are generic and not very helpful in clinical practice. The aim was to develop a biomarker-based diagnostic algorithm for mild cognitive impairment patients, leveraging on knowledge from recognized national experts. METHODS: With a Delphi procedure, experienced clinicians making variable use of biomarkers in clinical practice and representing five Italian scientific societies (neurology - Società Italiana di Neurologia per le Demenze; neuroradiology - Associazione Italiana di Neuroradiologia; biochemistry - Società Italiana di Biochimica Clinica; psychogeriatrics - Associazione Italiana di Psicogeriatria; nuclear medicine - Associazione Italiana di Medicina Nucleare) defined the theoretical framework, relevant literature, the diagnostic issues to be addressed and the diagnostic algorithm. An N-1 majority defined consensus achievement. RESULTS: The panellists chose the 2011 National Institute on Aging and Alzheimer's Association diagnostic criteria as the reference theoretical framework and defined the algorithm in seven Delphi rounds. The algorithm includes baseline clinical and cognitive assessment, blood examination, and magnetic resonance imaging with exclusionary and inclusionary roles; dopamine transporter single-photon emission computed tomography (if no/unclear parkinsonism) or metaiodobenzylguanidine cardiac scintigraphy for suspected dementia with Lewy bodies with clear parkinsonism (round VII, votes (yes-no-abstained): 3-1-1); 18 F-fluorodeoxyglucose positron emission tomography for suspected frontotemporal lobar degeneration and low diagnostic confidence of Alzheimer's disease (round VII, 4-0-1); cerebrospinal fluid for suspected Alzheimer's disease (round IV, 4-1-0); and amyloid positron emission tomography if cerebrospinal fluid was not possible/accepted (round V, 4-1-0) or inconclusive (round VI, 5-0-0). CONCLUSIONS: These consensus recommendations can guide clinicians in the biomarker-based aetiological diagnosis of mild cognitive impairment, whilst guidelines cannot be defined with evidence-to-decision procedures due to incomplete evidence.

Role of [18F]-FDG-PET/MDCT in evaluating early response in patients with Hodgkin's lymphoma.

PURPOSE: The authors evaluated the prognostic role of 18-fluoro-fluorodeoxyglucose positron emission tomography/multidetector computed tomography ([(18)F]-FDG PET/MDCT) in treating patients with Hodgkin's lymphoma (HL). MATERIALS AND METHODS: We retrospectively evaluated 132 patients with HL studied with PET/MDCT before the start of chemotherapy (CTX) for staging purposes and again after two CTX cycles with [doxorubicin (Adriblastin), bleomycin, vinblastine, dacarbazine (ABVD_] (interim PET/MDCT), at least 30 days after the end of the last CTX cycle and/or 3 months after the end of radiotherapy, if delivered (final PET-MDCT). RESULTS: Interim PET-MDCT was negative in 104/132 patients (79%), and their final PET-MDCT showed complete remission in 102/104 (98%) of cases, with disease recurrence/persistence in two (2%). In the remaining 28 (21%) patients, interim PET-MDCT revealed an early response in 68% of cases and chemoresistance with disease progression in 32% of cases; in these 28 patients, final PET-MDCT showed a lack of response to treatment in 43% of cases (43%) and complete remission in 57% of cases. Statistical analysis of these data showed that interim PET-MDCT had a negative predictive value of 98% and a positive predictive value of 42%, with values of sensitivity, specificity and diagnostic accuracy of 85.7%, 86.4% and 86.4%, respectively. CONCLUSIONS: Interim PET-MDCT has a reliable prognostic role in diagnosis and treatment of patients with HL, as it helps predict which patients are more likely to achieve a complete response at the end of treatment. PET/MDCT may also lead to a change in treatment, with reduced treatment-related toxic effects and significantly reduced total costs.

MR-PET fusion imaging in evaluating adnexal lesions: a preliminary study.

PURPOSE: The objective of this preliminary study was to examine the effects of combined magnetic resonance/positron emission tomography (MR-PET) evaluation in the morphofunctional characterisation of ovarian lesions. MATERIALS AND METHODS: From June 2008 to September 2010, we evaluated 24 patients (mean age 44±10 years; range 24-74) with ovarian lesions incidentally detected on ultrasonography (US) and/or multislice computed tomography (CT). All patients underwent MR imaging of the pelvis and total-body CT-PET. PET and MR images were subsequently fused at postprocessing using specific anatomical criteria. Results were compared with the histological examination. RESULTS: Of the 24 examined lesions, 19 were malignant and five were benign on histological examination. MR, CT-PET and MR-PET sensitivity was 84%, 74% and 94%, respectively and specificity 60%, 80% and 100%, respectively. Positive (PPV) and negative predictive (NPV) values were 93% and 44% for CT-PET, 89% and 50% for MR and 100% and 83% for MR-PET, respectively. CONCLUSIONS: Pelvic MR-PET fusion imaging provides advantages in terms of sensitivity and especially specificity compared with MR imaging or CT-PET alone. The added value of this fusion imaging modality lies in combining the benefits of the morphological evaluation provided by MR imaging and the metabolic assessment provided by PET.

Cortical metabolic changes and clinical outcome in normal pressure hydrocephalus after ventriculoperitoneal shunt: Our preliminary results. / Cambios metabólicos corticales y resultado clínico en la hidrocefalia normotensiva después de la derivación ventrículo-peritoneal: nuestros resultados preliminares.

INTRODUCTION: Our objective was to evaluate the cortical metabolic changes and clinical outcome in patients affected by idiopathic normal pressure hydrocephalus (iNPH) after a placement of ventriculoperitoneal (VP) shunt. MATERIALS AND METHODS: 10 patients affected by suspected iNPH underwent a CSF hydrodynamics evaluation based on a lumbar infusion test (LIT). The main selection criterion for surgery was based on intracranial elasticity (IE)>0.30. All subjects with an IE>0.30 underwent a PET scan with 18 fluorodeoxiglucose (18F-FDG) at baseline (PET1) and 1 month after surgery (PET2). Furthermore, the same patients were submitted to clinical evaluation before and 1 month after surgery through neuropsychological tests and gait analysis. RESULTS: An overall number of 20 18F-FDG PET scans were performed in all the enrolled patients. As compared to PET1, PET2 showed an increase in glucose consumption in the left frontal and left parietal lobe in PET2 as compared to PET1 (P<.001). All the enrolled patients presented a significant increase in neuropsychological scores (i.e Frontal Assessment Battery and Montreal Cognitive Assessment) and have clinically improved at gait analysis. A significant correlation was found between the increase of cortical glucose consumption in the left parietal area and the cognitive improvement as detectable by neuropsychological assessment. CONCLUSIONS: Improvement in 18F FDG PET glucose metabolism could be considered a useful imaging marker for the assessment of iNPH response to VP shunting.

Pathological classification of DCIS and planning of therapeutic management.

BACKGROUND: Ductal intraepitelial neoplasia (DIN) represents a spectrum of disease that may progress from usual hyperplasia to ductal carcinoma in situ (DCIS) grade 3. The aim of the study was to asses the correlation between the DIN classification and the surgical treatment including sentinel lymph node biopsy (SLNB). PATIENTS AND METHODS: In this retrospective study, 229 patients with DIN had undergone conservative or radical surgical treatment and SLNB in cases of DIN1C-DIN3. RESULTS: Breast conservative surgery was the definitive treatment in 80% of the cases. The H&E evaluation of excised sentinel nodes was negative for metastatic disease; nevertheless the immunohistochemical (IHC) evaluation revealed the presence of metastatic cells in 6 patients (3.7%). CONCLUSION: In cases of DIN lesions SLNB is not indicated. The only reason SLNB should be considered is when there is an evidence of invasive foci at definitive histology or when radical mastectomy is proposed.

Accuracy of early and delayed FDG PET-CT and of contrast-enhanced CT in the evaluation of lung nodules: a preliminary study on 30 patients.

PURPOSE: The aim of our prospective study was to compare the diagnostic accuracy of early, delayed and dual-time-point positron emission tomography (PET) acquisition with contrast enhanced computed tomography (CT) within a PET-CT examination in the evaluation of pulmonary solitary nodules (SPNs). MATERIALS AND METHODS: Thirty patients were enrolled in the study. All the patients underwent a dual-time-point PET-CT examination. Whole-body PET images were acquired at 50 min after fluorine18-fluorodeoxyglucose ((18)F-FDG) administration (early), followed by a chest acquisition (delayed). Lung nodules with maximum standardised uptake value SUVmax > or =2.5 were considered malignant. SUVmax was calculated on early and delayed images; SUV increasing > or =10% (Delta SUVmax) was considered suggestive of malignancy. Absence of significant lung nodule enhancement (<15 Delta HU) at CT was considered strongly predictive of benignity. For the CT morphological assessment, the irregularity of the shape of each lesion was rated. PET-CT results were related to histological assays and clinical records. Diagnostic accuracy was assessed by area under the receiveroperarting characteristic (ROC) curves analysis. RESULTS: Early and delayed SUVmax of malignant nodules were significantly higher than those of benign disease. Early SUVmax sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 77%, 91%, 79.5% and 66.7%; delayed SUVmax corresponding values were 77%, 66%, 74% and 66%; dual-time-point SUVmax values were 83%, 67%, 75% and 74%; DeltaHU values were 94%, 34%, 67%, 96%; CT morphologic evaluation values were 61%, 46%, 60%, 47%. Area under the curve (AUC) for early SUVmax was 0.79, for delayed SUVmax 0.80, for dual-time-point SUVmax 0.85, for DeltaHU 0.63 and for CT morphologic assessment 0.58. CONCLUSIONS: In our small series of patients, early and delayed SUVmax showed comparable accuracies, whereas morphological and contrast enhanced CT evaluations showed the lowest accuracies. Dual-time-point SUVmax showed the largest AUC. However, dual-time-point SUVmax was most sensitive, whereas single-time-point SUVmax was most specific.

Hearing and cognitive impairment: a functional evaluation of associative brain areas in patients affected by Alzheimer's disease.

Auditory dysfunction observed in patients with cognitive diseases is probably due to the alteration of some brain areas involved in sound stimulus processing. The present study aimed to investigate differences in such processing and in connectivity of the primary auditory cortex in patients affected by Alzheimer's disease (AD) and in normal subjects. We examined 131 diagnosed AD patients and a control group (CG) of 36 normal subjects. After a complete clinical investigation, focused on hearing function, all subjects underwent a brain FDG PET/CT. AD subjects vs CG showed reduced glucose consumption in BA 6,7,8,39, whereas we did not find differences in the primary auditory cortex. In AD, connectivity analyses showed a positive correlation of the primary auditory cortex with BA 6,8,21,31,39,40,42 and a negative correlation with BA 19, cerebellum and basal ganglia. Our findings suggest that neurological evaluation of patients with hearing loss might allow earlier (preclinical) identification of those affected by cognitive impairment.

Aspects of cerebral plasticity related to clinical features in acute vestibular neuritis: a "starting point" review from neuroimaging studies.

Vestibular neuritis (VN) is one of the most common causes of vertigo and is characterised by a sudden unilateral vestibular failure (UVF). Many neuroimaging studies in the last 10 years have focused on brain changes related to sudden vestibular deafferentation as in VN. However, most of these studies, also due to different possibilities across diverse centres, were based on different times of first acquisition from the onset of VN symptoms, neuroimaging techniques, statistical analysis and correlation with otoneurological and psychological findings. In the present review, the authors aim to merge together the similarities and discrepancies across various investigations that have employed neuroimaging techniques and group analysis with the purpose of better understanding about how the brain changes and what characteristic clinical features may relate to each other in the acute phase of VN. Six studies that strictly met inclusion criteria were analysed to assess cortical-subcortical correlates of acute clinical features related to VN. The present review clearly reveals that sudden UVF may induce a wide variety of cortical and subcortical responses - with changes in different sensory modules - as a result of acute plasticity in the central nervous system.

D2-40 negative pyogenic granuloma-like Kaposi's sarcoma: Diagnostic features and histogenetic hypothesis of an uncommon skin tumor in HIV-negative patients.

Pyogenic granuloma-like Kaposi's sarcoma (PGLKS) is a recently described skin tumor showing features both of pyogenic granuloma (PG) and Kaposi's sarcoma (KS). The differential diagnosis is often challenging. We reviewed a series of 50 PG and 23 Ks located on distal extremities with the aid of an immunohistochemical panel comprising CD34, CD31, FVIII, SMA, D2-40, HHV8. After revision, 6/50 PG lesions previously diagnosed as PG, showed positive immunostaining for LNA1-HHV8 and focal positivity for CD31 and FVIII in the endothelial cells of the proliferating vessels, with some SMA positive pericytes. D2-40, a marker of lymphatic endothelium positive in KS, stained negatively. These lesions were renamed PGLKS. Of note, in our series, PGLKS represented the only form of KS localized in the hand; all the patients were HIV-negative, older than PG patients, with a prevalence for male gender. PGLKS and PG need a different management and a follow-up is advisable for PGLKS, as for the other variants of KS. To date, D2-40 negative immunostaining has not yet been reported in PGLKS and should not lead to a misdiagnosis of PG. The morphological similarities with PG and the immunohistochemical findings, showing a defective phenotype of the neoplastic cells, suggest a histogenetic hypothesis in which D2-40 negative PGLKS could represent an early stage of HHV8 infection of a pre-existing PG, whose vessels loose progressively their blood vascular markers but have not still acquired the lymphatic ones.

111In-pentetreotide scintigraphy in the detection of insulinomas: importance of SPECT imaging.

UNLABELLED: The aim of this study was to determine whether the systematic use of SPECT can increase the reported low sensitivity of somatostatin receptor scintigraphy (SRS) in detecting insulinomas. METHODS: Fourteen patients were evaluated. After 111In-pentetreotide injection (approximately 250 MBq intravenously), abdominal SPECT images were obtained at 4 h and multiple planar images were obtained at 4 and 24 h. MRI and CT were performed within 1 mo of SRS. Sixteen tumors were histologically verified after surgery in 14 patients. RESULTS: SPECT revealed 14 lesions in 12 patients (sensitivity, 87.5%), both planar SRS and MRI revealed 7 tumors in 7 patients (sensitivity, 43.8%), and CT revealed only 5 lesions in 4 patients (sensitivity, 31.3%). Moreover, in 4 patients SPECT was the only examination with positive findings. CONCLUSION: SPECT at 4 h is mandatory for preoperative detection of insulinomas using SRS because the images are more sensitive than planar images and are superior to images from other conventional methods.

Somatostatin receptor scintigraphy of malignant somatostatinoma with indium-111-pentetreotide.

This article describes the visualization of a pancreatic somatostatinoma and liver metastases using 111In-pentetreotide imaging in a patient with somatostatinoma syndrome. A 61-yr-old woman with gallbladder stones, diabetes, weight loss, diarrhea and steatorrhea, immunohistochemical diagnosis of somatostatinoma (liver biopsy) and high plasma values of somatostatin was studied by somatostatin receptor scintigraphy. Six sites of focal abnormal 111In-pentetreotide hyperfixation were found: three in the liver and three in the pancreatic area. This case report demonstrates that in vivo detection of somatostatinoma with somatostatin receptor imaging is possible in the presence of high levels of circulating somatostatin, suggesting that receptor downregulation has not occurred.

SPECT improves accuracy of somatostatin receptor scintigraphy in abdominal carcinoid tumors.

UNLABELLED: Abdominal carcinoid tumors are often small and difficult to localize. Somatostatin receptors have been detected in carcinoids, thus enabling their in vivo visualization by scintigraphy with 111In pentetreotide, a radiolabeled somatostatin analog. The aim of this study was to determine the value of 111In-pentetreotide SPECT in the detection of abdominal carcinoids and to compare these results with the outcomes from planar scans and conventional imaging techniques. METHODS: Eighteen patients with a present, or previously operated, abdominal carcinoid were evaluated. Abdominal SPECT scans were acquired 4 hr postinjection of 111In-pentetreotide and multiple planar views were performed at 4, 24, and 48 hr. RESULTS: No adverse reactions were observed after radiopharmaceutical injection. In 13 of 18 patients, abnormal sites of uptake were found by SPECT, which localized 9 abdominal extrahepatic lesions (in 7 patients) and 33 hepatic lesions (in 10 patients). No pathologic accumulation was seen in the five patients considered in complete remission after surgery. Planar scans visualized 5 abdominal extrahepatic sites (in 4 patients) and 21 liver tumor sites (in 7 patients), while conventional procedures detected 3 abdominal extrahepatic lesions (in 2 patients) and 30 hepatic lesions (in 7 patients). CONCLUSION: Indium-111-pentetreotide scintigraphy is a safe and practical procedure. SPECT appears to be more sensitive than planar scintigraphy and conventional methods to detect abdominal carcinoids; it can increase the number of visualized tumor sites and that of patients with positive findings and may therefore have a role not only in the mapping of tumor spread but also in therapeutic decisions.

Technetium-99m sestamibi imaging in the detection of axillary lymph node involvement in patients with breast cancer.

BACKGROUND: The status of the axillary lymph nodes is the most important prognostic factor in breast cancer, and the findings of axillary node dissection remain the gold standard for the patients staging and prognosis. The aim of this study was to evaluate the usefulness of Tc-99m sestamibi scintigraphy in the detection of axillary node involvement. MATERIALS AND METHODS: Forty-nine patients (age range: 32-72 years) with breast cancer were studied. Dynamic images (1-20 minutes post-injection of the radiopharmaceutical) followed by multiple planar views and tomographic images were performed. Final diagnosis was achieved by histology after surgery. RESULTS: Metastatic axillary lymph node involvement was present in 21 patients: sensitivity was 81% (17/21) for tomographic and 61.9% (13/21) for planar images; specificity was 92.9% (26/28) and 96.4% (27/28), respectively. CONCLUSIONS: Tc-99m sestamibi imaging is a promising noninvasive method to detect axillary node metastases in patients with breast cancer, tomography appears more sensitive than planar views.

Scintimammography with technetium-99m tetrofosmin in suspected breast cancer.

BACKGROUND: Scintimammography with Tc-99m sestamibi has recently demonstrated a clinical usefulness in the evaluation of patients with breast lesions. The aim of this study was to assess the potential role of scintimammography using Tc-99m tetrofosmin in the detection of breast cancer. MATERIALS AND METHODS: Fifty-five patients (age range: 33-76 years) with suspicious breast abnormalities detected by mammography, and ten controls were examined. Dynamic images (1-20 min post-injection of the radiopharmaceutical) followed by three planar views were performed. Final diagnosis was achieved by hystology after surgery or excisional biopsy. RESULTS: A total of 59 breast lesions were considered. The sensitivity of Tc-99m tetrofosmin scintimammography for detection of primary breast cancer was 93.1% (27/29) and the specificity was 93.3% (28/30). No focal uptake was observed in both breasts of the control population. CONCLUSIONS: Tc-99m tetrofosmin scintimammography has high diagnostic accuracy in detecting breast cancer and may have a clinical role as complement to conventional mammography.

Immunoscintigraphy with a technetium-99m labelled anti-epithelial growth factor receptor antibody in patients with non-small cell lung cancer.

BACKGROUND: A variety of human tumours, including non-small cell lung cancer, overexpress epithelial growth factor (EGF) receptors. In this study we evaluated the feasibility of immunoscintigraphy with a technetium-99m-labelled monoclonal antibody directed towards the EGF receptor (MINT5). MATERIALS AND METHODS: The labelling with technetium-99m was performed using the glucoheptonate-iminothiolane method. Eight patients with non-small cell lung cancer were i.v. injected 740 MBq of MINT5. Neither side-effects, nor toxicity, nor HAMA response were observed. Each patient was submitted to total body planar images in anterior and posterior projections at 1-2 hours and at 4-6 hours after the injection. RESULTS: Uptake of MINT5 was mainly visible in liver, spleen and bone marrow; it proved stable in vivo. The primary lung cancer was imaged in 7 out of 8 patients and metastases were detected in 3 out of 3 cases. CONCLUSION: MINT5 is a safe and promising radiopharmaceutical for in vivo localization and biological characterization of non-small cell lung cancer.

A three center study on the diagnostic accuracy of 99mTc-MIBI scintimammography.

In order to assess specificity and sensitivity of the prone scintimammography (PSM) in a large series with 99m-Tc MIBI, we performed a three-center study; 420 patients were studied; after mammography all the patients were submitted to PSM and biopsy and/or operation. PSM was considered positive if hot spot within the breast was observed. In palpable masses sensitivity was 0.98 and specificity 0.89, non palpable masses showed a sensitivity of 0.62 and a specificity of 0.91. When the cancers were stratified for T category the sensitivity was 0.28 in T1a 0.26 in the group of T1a carcinomas, 0.56 in T1b 0.95 in T1c and 0.97 T2 tumors. Physical factors such as attenuation. Compton scattering from chest, as well as biological factors have a role in breast tumor imaging. In the tumors smaller than 1 cm biological factors are probably involved too.

Single photon emission computerized tomography increases the sensitivity of indium-111-pentetreotide scintigraphy in detecting abdominal carcinoids.

Somatostatin (sms) receptors have been identified in carcinoids (c), so enabling their visualization with 111In-pentetreotide scintigraphy. The aim of this study was to evaluate if single photon emission computerized tomography (SPECT) can increase the sensitivity of sms receptor scintigraphy in the detection of abdominal c. 26 patients (pts) with a present, or previously operated, abdominal carcinoid were submitted to SPECT over the abdomen and multiple planar views after the injection of 111In-pentetreotide. Magnetic resonance imaging and computed tomography were also performed. In 19 pts abnormal sites of uptake were found by SPECT which localized 13 abdominal extrahepatic (in 11 pts) and 45 hepatic lesions (in 15 pts). No pathologic accumulation was seen in 7 pts in complete remission after surgery. Planar images visualized 7 abdominal extrahepatic (in 6 pts) and 26 liver tumor sites (in 10 pts), conventional procedures detected 5 abdominal extrahepatic (in 4 pts) and 36 hepatic lesions (in 10 pts). 111In-pentetreotide SPECT is more sensitive than planar scanning and conventional methods to detect abdominal c, and so may play a major role in the early and accurate mapping of tumour spread.