Myocardial bridging of the left anterior descending coronary artery and anomalous origin of circumflex coronary artery: preoperative assessment with MDCT.
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Adult↗
Biomedical subjects
Ferruccio Fazio
Publications and source records attributed to Ferruccio Fazio.
A reappraisal of the role of vesicourethral anastomosis biopsy in patient candidates for salvage radiation therapy after radical prostatectomy.
BACKGROUND AND PURPOSE: To investigate the usefulness of vesicourethral anastomotic biopsy (VUBx) in patients who are candidates for salvage radiotherapy (SalvRT) after radical prostatectomy (RRP). MATERIAL AND METHODS: From 1992 to 2001, 98 patients with a PSA failure (PSAf) after RRP underwent SalvRT to the prostatic bed (median dose 70 Gy). In 50/98 patients the VUBx was positive, in 26 negative; 22 patients underwent SalvRT without a prior VUBx. The prognostic impact on biochemical disease-free survival (bNEDs) of histologic confirmation of the local failure was evaluated retrospectively. RESULTS: In the 40 patients with pre-RT PSA < or = 0.9 ng/mL, no additional prognostic information derived from the VUBx, while, for higher PSA values, a positive histology resulted as a covariate independently predictive of post-RT outcome (5-year bNEDs: 74% vs 42% in the 35 and 23 patients with a positive or negative/not performed VUBx, respectively, P=.03), together with pT, pre-RT PSA < or = 1.5 ng/mL, and PSA doubling time. CONCLUSIONS: In case of PSAf after RRP, VUBx before SalvRT seems unnecessary for PSA < or = 0.9 ng/mL. For higher values, a positive VUBx seems to always justify a SalvRT, which may not be recommendable, given the nonnegligible risk of an already micrometastatic disease, if the biopsy results are negative.
Aged↗
Post-therapy surveillance of patients with uterine cancers: value of integrated FDG PET/CT in the detection of recurrence.
PURPOSE: The purpose of this study was to prospectively determine the diagnostic accuracy of PET/CT in the detection of recurrence in patients with treated uterine cancers. METHODS: Twenty-five women, ranging in age from 37 to 79 years (mean 58.9 years), who underwent primary surgical treatment for either a cervical or an endometrial cancer met the inclusion criterion of the study, which was suspicion of recurrence based on results of routine follow-up procedures. PET/CT was performed after administration of 18F-fluorodeoxyglucose (FDG); two readers interpreted the images in consensus. Histopathological findings or correlation with results of subsequent clinical and imaging follow-up examinations served as the reference standard. Diagnostic accuracy of PET/CT was reported in terms of the proportion of correctly classified patients and lesion sites. RESULTS: Tumour recurrence was found at histopathological analysis or follow-up examinations after PET/CT in 14 (56%) of the 25 patients. Patient-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy of PET/CT for detection of tumour recurrence were 92.9%, 100.0%, 100.0%, 91.7% and 96.0%, respectively. Lesion site-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy of PET/CT were 94.7%, 99.5%, 94.7%, 99.5% and 99.0%, respectively. CONCLUSION: This preliminary study shows that PET/CT may be an accurate method for the evaluation of recurrence in patients who have been treated for uterine cancers and are undergoing follow-up.
Adult↗
Fluvoxamine treatment and D2 receptors: a pet study on OCD drug-naïve patients.
Changes in D(2) receptors during antidepressant therapy have been reported in patients with major depressive disorder using PET/SPET. The aim of this study was to evaluate modifications in D(2) receptors that might occur in patients affected by obsessive-compulsive disorder (OCD) during serotonin reuptake sites inhibitors (SSRIs). To this purpose, we measured the in vivo binding of [(11)C]raclopride ([(11)C]Rac)in the brain of a group of OCD naïve patients before and after the repeated administration of the inhibitor SSRI fluvoxamine. Eight patients with a Diagnostic and Statistical Manual of Mental Disorders IVth edition diagnosis of OCD completed the study undergoing a PET scan and a complete clinical evaluation before and during treatment with fluvoxamine. Patients have been compared also with a group of nine age-matched normal volunteers. Fluvoxamine treatment significantly improved clinical symptoms and increased [(11)C]Rac binding potential (BP) in the basal ganglia of OCD patients (7.5+/-5.2, 6.9+/-6.9, and 9.9+/-9.3% in dorsal caudate, dorsal putamen, and ventral basal ganglia, respectively; p<0.01) to values closer to those observed in the group of normal subjects. Chronic treatment with fluvoxamine induces a slight but significant increase in striatal [(11)C]Rac BP of previously drug-naïve OCD patients. The modifications in D(2) receptor availability might be secondary to fluvoxamine effects on serotoninergic activity.
Adult↗
Paclitaxel and concomitant radiotherapy in high-risk endometrial cancer patients: preliminary findings.
BACKGROUND: There is still much debate about the best adjuvant therapy after surgery for endometrial cancer (EC) and there are no current guidelines. Radiotherapy (RT) alone does not seem to improve overall survival. We investigated whether concomitant Paclitaxel (P) and RT gave better clinical results. METHODS: Twenty-three patients with high-risk EC (stage IIB, IIIA, IIIC or IC G3 without lymphadenectomy or with aneuploid tumor) underwent primary surgery and were then referred for adjuvant therapy. P was given at a dose of 60 mg/m2 once weekly for five weeks during RT, which consisted of a total radiation dose of 50.4 Gy. Three further weekly cycles of P at a dose of 80 mg/m2 were given at the end of RT. Overall survival and disease-free survival were calculated from the time of surgery. Patterns of failure were recorded by the sites of failure. RESULTS: A total of 157 cycles of P were administered both during radiotherapy and consolidation chemotherapy. Relapses occurred in five patients (21.7%). Median time to recurrence was 18.6 months (range 3-28). Survival rate for all the patients was 78.2%. Overall survival for the patients who completed chemo-radiation was of 81%. In this group median time to recurrence was 19.2 months (range 3-28). All recurrences were outside the radiation field. Mortality rate was 14.2%. CONCLUSION: This small series demonstrates pelvic radiotherapy in combination with weakly P followed by three consolidation chemotherapy cycles as an effective combined approach in high risk endometrial carcinoma patients.
Aged↗
Significant improvement in normal tissue sparing and target coverage for head and neck cancer by means of helical tomotherapy.
PURPOSE: In order to explore the potential of helical Tomotherapy in the treatment of head and neck cancers (HNC), a planning study comparing our routinely delivered IMRT technique (dynamic MLC Varian 600CD Linac, inversely optimised by the Helios/Eclipse system) against two different Tomotherapy planning approaches was performed. MATERIALS AND METHODS: In the first Tomotherapy plan (TOMO-a), we merely applied the same constraints used for the IMRT-Linac technique; in the second one (TOMO-b), we tried to stress the sparing of parotids and mandible while keeping PTV coverage and spinal cord Dmax similar to their values in the TOMO-a plan. Five patients with locally advanced oropharinx (n=3), hypopharinx (n=1) and larynx (n=1) cancer were considered. For each patient, CTV1 including neck nodes and the tumour was defined and was expanded with a margin of 0.5 cm (PTV1); then, CTV2 including high risk nodes and CTV3 including only T were defined and the corresponding PTV2/PTV3 were defined by a 0.5 cm expansion. IMRT and Tomotherapy planning were optimised to deliver 54 Gy in 30 fractions on PTV1 and 16.2 Gy in 9 fractions on PTV3; in the case a PTV2 was defined, 15 Gy were concomitantly delivered while delivering 16.2 Gy on PTV3. Separated plans for the two phases (Phase 1: first 30 fractions; Phase 2: last 9 fractions) were compared in terms of dose-volume histograms (DVH) and dose statistics on PTVs and OARs. RESULTS: When considering Phase 1, Tomotherapy improved the homogeneity of the dose distribution within PTV1 while delivering the same prescribed dose (assessed to be the median dose to PTV): the fraction of PTV1 receiving more than 95% of the prescribed dose (V95%) increased from 90% (IMRT) to 96-97% for Tomotherapy plans. Dmax within PTV1 decreased from 60.3 Gy (IMRT) to 57.4 Gy (TOMO-a) and 58.7 Gy (TOMO-b). Spinal cord Dmax decreased from 31.6 Gy (IMRT) to 26.5 Gy (TOMO-a) and 24.6 Gy (TOMO-b). No attempts to further reduce spinal cord Dmax were done. Mean dose to the parotids decreased from 26.1 Gy (IMRT) to 25.1 Gy (TOMO-a) and 20.8 Gy (TOMO-b). Mandible was significantly better spared with Tomotherapy: mean dose decreased from 34.9 Gy (IMRT) to 34.0 Gy (TOMO-a) and 30.7 Gy (TOMO-b). When considering phase 2, the average gains (TOMO-b vs IMRT) were more modest and depended on the location of PTV2/PTV3. CONCLUSIONS: Preliminary findings obtained in a sequential approach for HNC suggest that Tomotherapy has the potential to significantly improve the therapeutic ratio with respect to a conventional IMRT delivery method.
Aged↗
A simplified method to integrate metabolic images in stereotactic procedures using a PET/CT scanner.
We have developed a method that needs only the computed tomography (CT) indicator box to coregister positron emission tomography (PET) images and integrates this information with magnetic resonance imaging. The study was performed using a PET/CT scanner. A standard CT bed adapter was attached to the scanner couch. Then, the patient, with the Leksell G frame fixed, was positioned into the scanner with the CT indicator box. PET images were acquired using either [18F]fluorodeoxyglucose or [11C]choline as radioisotopes. After acquisition, CT and PET images were exported in DICOM 3 standard and transferred to a dedicated workstation via data link. Homemade software was implemented for multimodal image fusion. PET images were overwritten to their corresponding CT point values using a threshold algorithm, maintaining the stereotactic CT markers. The use of a CT indicator simplifies the procedure, because there is no need for a radioactive solution filling the indicator box. This method was tested first using a phantom and then in patients. The localization accuracy of the PET images is limited only by the slice thickness.
Aged↗
Synthesis, labeling, and biological evaluation of halogenated 2-quinolinecarboxamides as potential radioligands for the visualization of peripheral benzodiazepine receptors.
The previous exploration of the structure-affinity relationships concerning 4-phenyl-2-quinolinecarboxamide peripheral benzodiazepine receptor (PBR) ligands 6 showed as an interesting result the importance of the presence of a chlorine atom in the methylene carbon at position 3 of the quinoline nucleus. The subnanomolar PBR affinity shown by N-benzyl-3-chloromethyl-N-methyl-4-phenyl-2-quinolinecarboxamide (6b) suggested its chlorine atom to be replaced with other halogens in order to optimize the interaction of the quinolinecarboxamide derivatives with PBR and to develop suitable candidates for positron emission tomography (PET) or single photon emission computed tomography (SPECT) studies. The binding studies led to the discovery of fluoromethyl derivative 6a, which showed an IC50 value of 0.11 nM and is, therefore, one of the most potent PBR ligands so far described. Fluoromethyl derivative 6a has been labeled with 11C (t1/2=20.4 min, beta+=99.8%) starting from the corresponding des-methyl precursor (14) using [11C]CH3I in the presence of tetrabutylammonium hydroxide in DMF with a 35-40% radiochemical yield (corrected for decay) and 1.5 Ci/micromol of specific radioactivity. Ex vivo rat biodistribution and inhibition (following intravenous pre-administration of PK11195) studies showed that [11C]6a rapidly and specifically accumulated in PBR-rich tissues such as heart, lung, kidney, spleen, and adrenal, and at a lower level in other peripheral organs and in the brain. The images obtained in mouse with small animal YAP-(S)PET essentially confirmed the result of the ex vivo biodistribution experiments. The biological data suggest that [11C]6a is a promising radioligand for peripheral benzodiazepine receptor PET imaging in vivo.
Amides↗
Pre-symptomatic diagnosis in fatal familial insomnia: serial neurophysiological and 18FDG-PET studies.
Knowing how and when the degenerative process starts is important in neurodegenerative diseases. We have addressed this issue in fatal familial insomnia (FFI) measuring the cerebral metabolic rate of glucose (CMRglc) with 2-[18F]fluoro-2-deoxy-D-glucose PET in parallel with detailed clinical, neuropsychological examinations and polysomnography with EEG spectral analyses. Nine asymptomatic carriers of the D178N mutation, 10 non-carriers belonging to the same family, and 19 age-matched controls were studied over several years. The CMRglc as well as clinical and electrophysiological examinations were normal in all cases at the beginning of the study. Four of the mutation carriers developed typical FFI during the study but CMRglc and the clinical and electrophysiological examinations remained normal 63, 56, 32 and 21 months, respectively before disease onset. The carrier whose tests were normal 32 months before disease onset was re-examined 13 months before the onset. At that time, selective hypometabolism was detected in the thalamus while spectral-EEG analysis disclosed an impaired thalamic sleep spindle formation. Following clinical disease onset, CRMglc was reduced in the thalamus in all 3 patients examined. Our data indicate that the neurodegenerative process associated with FFI begins in the thalamus between 13 and 21 months before the clinical presentation of the disease.
Adult↗
Positron emission tomography changes in PARK1 mutation.
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Adult↗
Bone metastases are infrequent in patients with newly diagnosed prostate cancer: analysis of their clinical and pathologic features.
OBJECTIVES: To investigate the clinical and pathologic characteristics of patients with bone metastases identified at the time of newly diagnosed prostate carcinoma at biopsy. METHODS: From November 2002 to May 2004, 1587 consecutive patients had a pathologic diagnosis of prostate cancer and underwent conventional technetium-99m methylene diphosphonate scintigraphy of the entire body. The clinical and pathologic features of those patients with positive bone scan findings (group 1) were compared with those of a subcohort of 372 patients with negative bone scan findings performed at the same nuclear medicine department (group 2). RESULTS: A retrospective complete data collection was available for 1242 of 1587 patients. Bone metastases were found in 31 patients (2.5%). As expected, patients with skeletal metastases had a significantly greater mean serum total prostate-specific antigen level, and a Gleason sum of 8 or 9 was significantly more frequent in the pathologic findings of these subjects. Group 1 patients had a significantly greater prevalence of previous nonprostate primary neoplasms (chi-square 12.74, df = 1, P = 0.0004) and reported a greater prevalence of current use of H2 blockers for the treatment and prevention of gastroesophageal reflux disorders (chi-square 37.52, df = 1, P < 0.0001) than did group 2 patients. CONCLUSIONS: Our data have confirmed that bone metastases are more frequent in patients with high prostate-specific antigen levels and poorly differentiated tumors at biopsy regardless of the patient's age. A history of previous nonprostate primary neoplasms and the use of H2 blockers seemed to be more prevalent in those patients with bone metastases at diagnosis.
Aged↗
PET and SPET molecular imaging: focus on serotonin system.
Emission tomography techniques and, in particular, positron emission tomography (PET) enable the in vivo study of several physiological and neurochemical variables in human subjects using methods originally developed for quantitative autoradiography. In particular, PET allows one to evaluate in human subjects: (a) the effect of specific neurochemical challenges on regional brain function at rest or under activation; (b) the activity of neurotransmitters and the regional expression of specific molecular targets during pathology including their modulation by drug treatment; (c) the kinetics of drug disposition and activity directly in the target organ. This is of primary interest in the field of biological psychiatry and in psychoactive drugs development, where it is particularly difficult to reproduce human diseases using animal models in view of the peculiarity of this field and the large heterogeneity of each psychiatric illness also inside the same clinical definition. The aim of this paper is to review the principal strategies and the main results of the use of PET or single photon emission tomography (SPET) molecular imaging for the in vivo study of serotonin receptors and the main results obtained from their application in the study of major depression.
Brain↗
Persistent renal hypertrophy and faster decline of glomerular filtration rate precede the development of microalbuminuria in type 1 diabetes.
Soon after the onset of type 1 diabetes, renal hypertrophy and hyperfiltration become manifest, particularly among patients who will subsequently develop diabetic nephropathy. Whether these early renal dysfunctions are involved in the pathogenesis of diabetic nephropathy is currently unclear. We evaluated, during the same day, kidney volume and glomerular filtration rate (GFR) in 146 patients with type 1 diabetes and normal renal function. All the individuals were then monitored for a mean of 9.5 +/- 4.4 years for the development of microalbuminuria. Kidney volume and GFR were reevaluated in a subset of 68 patients 4 years after baseline. During follow-up, microalbuminuria developed in 27 of 146 diabetic patients. At baseline, kidney volume (312.8 +/- 52.6 vs. 281.4 +/- 46.1 vs. 236.8 +/- 41.6 ml/1.73 m(2), P < 0.05) but not GFR was increased in patients predisposed to microalbuminuria. Risk of progression was higher in patients with increased kidney volume (P = 0.0058). Patients predisposed to microalbuminuria showed a stable increase in kidney volume (P = 0.003), along with a faster decline of GFR (P = 0.01). Persistent renal hypertrophy and faster decline of GFR precede the development of microalbuminuria in type 1 diabetes. These findings support the hypothesis that renal hypertrophy precedes hyperfiltration during the development of diabetic nephropathy.
Adolescent↗
Lymph node metastasis in patients with clinical early-stage cervical cancer: detection with integrated FDG PET/CT.
PURPOSE: To prospectively determine the accuracy of combination positron emission tomography-computed tomography (PET/CT) in lymph node staging in patients with early-stage cervical cancer, with histopathologic results as the reference standard. MATERIALS AND METHODS: The study was institutional review board approved, and all patients gave informed consent. Forty-seven consecutive women aged 29-71 years with clinical stage IA or IB cervical carcinoma were included in the study. All 47 patients were scheduled for radical hysterectomy with pelvic lymph node dissection. Before surgery, all patients underwent fluorine 18 fluorodeoxyglucose (FDG) PET/CT. PET/CT findings were interpreted by two readers in consensus and then compared with histopathologic results. At histopathologic examination, the dissected lymph nodes were classified as nonmetastatic or metastatic. RESULTS: Fifteen (32%) patients had metastatic lymph nodes at histopathologic examination, and 32 (68%) had no histopathologically confirmed nodal metastasis. Of the total 1081 lymph nodes histopathologically sampled, 18 were found to be positive for malignant cells. The overall node-based sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT were 72% (13 of 18), 99.7% (1060 of 1063), 81% (13 of 16), 99.5% (1060 of 1065), and 99.3% (1073 of 1081), respectively. Corresponding values for PET/CT-based diagnosis of lymph nodes larger than 0.5 cm in diameter were 100% (13 of 13), 99.6% (675 of 678), 81% (13 of 16), 100% (675 of 675), and 99.6% (688 of 691), respectively. The overall patient-based sensitivity, specificity, PPV, NPV, and accuracy of PET/CT were 73% (11 of 15), 97% (31 of 32), 92% (11 of 12), 89% (31 of 35), and 89% (42 of 47), respectively. CONCLUSION: PET/CT proved to be valuable for lymph node staging in patients with early-stage cervical cancer, with short-axis diameter greater than 0.5 cm being the size threshold for accurate depiction of metastatic nodes.
Adult↗
11C-labeling of n-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]arylcarboxamide derivatives and evaluation as potential radioligands for PET imaging of dopamine D3 receptors.
The selective dopamine D(3) receptor ligands N-4-[4-[(2,3-dichlorophenyl)piperazin-1-yl]butyl]1-methoxy-2-naphthalencarboxamide (1) and N-4-[4-[(2,3-dichlorophenyl)piperazin-1-yl]butyl]-7-methoxy-2-benzofurancarboxamide (2) were labeled with (11)C (t(1/2) = 20.4 min) as potential radioligands for the noninvasive assessment of the dopamine D(3) neurotransmission system in vivo with positron emission tomography (PET). The radiosynthesis consisted in an O-methylation of the des-methyl precursors N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-1-hydroxy-2-naphthalenecarboxamide (3) and N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-7-hydroxy-2-benzofurancarboxamide (4) with [(11)C]methyl iodide using tBuOK/HMPA and KOH/DMSO, respectively. The radiotracers [(11)C]1 and [(11)C]2 were obtained in 35 min with over 99% radiochemical purity, 74 +/- 37 GBq/mumol of specific radioactivity, 13% and 26% radiochemical yield (EOB, decay-corrected). Distribution studies in rats demonstrated that the new tracers [(11)C]1 and [(11)C]2 cross the blood-brain barrier and localize in the brain. However, the kinetics of cerebral uptake did not reflect the regional expression of the D(3) receptors. Despite their in vitro pharmacological profile, [(11)C]1 and [(11)C]2 do not display an in vivo behavior suitable to image D(3) receptor expression using PET.
Amides↗
Basal ganglia and language: phonology modulates dopaminergic release.
Basal ganglia have been implicated in syntactic and phonological processes, but direct evidence has been scarce. Here, we used [11C]raclopride and positron emission tomography to measure modulations of the dopaminergic system induced by phonological or syntactic processing. Two significant effects were found. First, the level of accuracy in phonological processing significantly correlated with tracer binding potential in the left caudate nucleus. Second, the speed in phonological processing significantly correlated with tracer binding potential in the left putamen. Thus, a more accurate and fast phonological processing was associated with a reduced dopamine requirement in the left striatum. These findings show that the striatal dopaminergic system plays an essential role in grammatical processes that form the core of human language.
Acoustic Stimulation↗
Heterogeneity of brain glucose metabolism in mild cognitive impairment and clinical progression to Alzheimer disease.
BACKGROUND: Subjects with amnesic mild cognitive impairment (aMCI) may include patients at high risk for progression to Alzheimer disease (AD) and a population with different underlying pathologic conditions. OBJECTIVE: To evaluate the potential roles of positron emission tomography with fluorodeoxyglucose F 18 (18FDG-PET) and memory scores in identifying subjects with aMCI and in predicting progression to dementia. DESIGN, SETTING, AND PATIENTS: Sixty-seven patients at European centers for neurologic and AD care who were diagnosed as having aMCI each underwent an extensive clinical and neuropsychological examination and an 18FDG-PET study. Forty-eight subjects were followed up periodically for at least 1 year, and progression to dementia was evaluated. MAIN OUTCOME MEASURES: Brain glucose metabolism and memory scores. RESULTS: Fourteen subjects with aMCI who converted to AD within 1 year showed bilateral hypometabolism in the inferior parietal, posterior cingulate, and medial temporal cortex. Subjects with "stable" aMCI presented with hypometabolism in the dorsolateral frontal cortex. The severity of memory impairment, as evaluated by the California Verbal Learning Test-Long Delay Free Recall scores, correlated with the following brain metabolic patterns: scores less than 7 were associated with a typical 18FDG-PET AD pattern, and scores of 7 or higher were associated with hypometabolism in the dorsolateral frontal cortex and no progression to AD. CONCLUSION: These data provide evidence for clinical and functional heterogeneity among subjects with aMCI and suggest that 18FDG-PET findings combined with memory scores may be useful in predicting short-term conversion to AD.
Aged↗
Laterality of manual function in foraging and positional behavior in wild indri (Indri indri).
This research is based on the idea that some prosimian species are good models in which to test certain postulates of the "postural origins" theory proposed by MacNeilage and colleagues [Behavioral and Brain Sciences 10:247-303, 1987] to explain the evolution of hand preference within the order Primates. We investigated manual laterality in 16 wild indris (eight males and eight females, living in four social groups) in their habitat, the Madagascan tropical rain forest. Data were collected on two spontaneous behaviors: "branch-reach," an action that occurs during foraging, and "higher support," a posture typical of clingers and leapers. A total of seven subjects were significantly lateralized for branch-reach (two showed a right preference, and five showed a left preference). Four subjects were significantly lateralized for higher support, and all of them showed a right-hand preference. Most of the indris we studied showed no preference. Our research suggests that indri are at "level 1 of laterality" in the classification framework proposed by McGrew and Marchant [Yearbook of Physical Anthropology 40:201-232, 1997]. The data presented here are not discordant with the "postural origins" theory, as lateralized subjects are often in the direction predicted by MacNeilage and colleagues [Behavioral and Brain Sciences 10:247-303, 1987], but they are the minority.
Animals↗