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Neuroendocrine tumours (NET) diagnosis has represented a major challenge in the past decades. The introduction of somatostatin receptor scintigraphy in the diagnostic work-up led to a significant improvement of accuracy. However with the advent of positron emission tomography (PET) that presents a higher spatial resolution as compared to the gamma camera and an array of different radiotracers, it is now possible to image NET with an even higher accuracy. In fact, PET imaging of NET is a rapidly evolving field closely connected to the development of novel beta-emitting radiopharmaceuticals. NET can be easily visualized on PET scans using an array of both metabolic and receptor-based tracers. [18F]DOPA and [68Ga]DOTA-peptides (DOTA-TOC, DOTA-NOC, DOTA-TATE) are very promising to image well differentiated NET and were reported to be superior to other imaging modalities (computed tomography [CT], somatostatin receptor scintigraphy). On the contrary, the role of [18F]FDG is limited in well differentiated NET, due to their low glucose metabolism and growth rate, while it still can provide valuable information in less differentiated tumours. On-going studies are investigating the potential role of new imaging agents (bombesin, GLP-1, CCK) that specifically bind to receptors expressed on NET cells.

Multichannel impedance pH monitoring has shown that weakly acidic refluxes are able to generate heartburn. However, data on the role of different pH values, ranging between 4 and 7, in the generation of them are lacking. The aim of this study was to evaluate whether different pH values of weakly acidic refluxes play a differential role in provoking reflux symptoms in endoscopy-negative patients with physiological esophageal acid exposure time and positive symptom index and symptom association probability for weakly acidic refluxes. One hundred and forty-three consecutive patients with gastroesophageal reflux disease, nonresponders to proton pump inhibitors (PPIs), were allowed a washout from PPIs before undergoing: upper endoscopy, esophageal manometry, and multichannel impedance pH monitoring. In patients with both symptom index and symptom association probability positive for weakly acidic reflux, each weakly acidic reflux was evaluated considering exact pH value, extension, physical characteristics, and correlation with heartburn. Forty-five patients with normal acid exposure time and positive symptom association probability for weakly acidic reflux were identified. The number of refluxes not heartburn related was higher than those heartburn related. In all distal and proximal liquid refluxes, as well as in distal mixed refluxes, the mean pH value of reflux events associated with heartburn was significantly lower than that not associated. This condition was not confirmed for proximal mixed refluxes. Overall, a low pH of weakly acidic reflux represents a determinant factor in provoking heartburn. This observation contributes to better understand the pathophysiology of symptoms generated by weakly acidic refluxes, paving the way toward the search for different therapeutic approaches to this peculiar condition of esophageal hypersensitivity.

BACKGROUND: Despite being a relatively rare disease, the incidence of malignant pleural mesothelioma (MPM) is expected to increase over the next two decades due to the long time interval elapsing between exposure to causative factors, mainly asbestos, and disease onset. Early disease stages have been reported to benefit from radical surgery. In more advanced disease stages, a multimodality treatment, including various combinations of chemotherapy, external radiotherapy and surgery, may provide some favourable results though the prognosis remains poor. In this regard, an accurate pre-treatment staging plays an important role in offering patients a more appropriate therapeutic planning. In some preliminary studies, (18)F-FDG PET has proven to be able to provide useful information for staging purpose, especially for the detection of metastatic spread to lymph nodes and distant sites. MATERIAL AND METHODS: In the present study, we investigated 15 consecutive patients with histologically proven MPM by means of conventional 2-mm thickness whole-body CT scan with and without contrast medium in comparison with wholebody (18)F-FDG PET/CT fusion imaging. RESULTS: (18)F-FDG PET/CT did not provide additional information about the primary tumour (T) compared to CT scan, but identified a higher number of metastatic mediastinal lymph nodes (N) in 6 patients (40% of cases) and unknown metastatic disease to distant sites (M) in 3 patients (20% of cases). On the basis of PET/CT findings, treatment planning was changed in 5 patients (33.3% of cases). CONCLUSIONS: Our data show that (18)F-FDG PET/CT fusion imaging can play a relevant role in the staging and treatment planning of MPM patients.

Kinase inhibitors have been proposed as novel therapeutic agents in different forms of solid tumours. The Food and Drug Administration (FDA) approved the use of Sorafenib, an oral multikinase inhibitor, for advanced renal carcinoma and unresectable hepatocellular carcinoma. On-going studies are investigating the efficacy of Sorafenib in other solid tumours such as melanoma and non-small cells lung carcinoma and pre-clinical models showed the efficacy of treatment with Sorafenib in murine models of renal cells carcinoma, breast cancer, colon carcinoma and melanoma. To our knowledge, Sorafenib has never been employed in human lymphoma. The aim of the present study was to assess the efficacy of Sorafenib in murine models of human anaplastic large cells lymphoma (ALCL) and Hodgkin lymphoma (HD).Sorafenib cytotoxicity was assessed in vitro and growth inhibition (IC50) was calculated. Cells were assayed for Caspase-3 to measure apoptosis. Human ALCL and HD xenografts in NOD/SCID mice were monitored by small animal positron emission tomography (PET) and computed tomography (CT) over time. Tumour bearing animals were randomly selected to receive treatment with Sorafenib or no treatment. Pathology was available in all cases.Sorafenib efficacy on cells proliferation and apoptosis (IC50: HD=0.0343 mg/L; ALCL=0.319 mg/L) was confirmed in vitro. Caspase-3 production showed a dose-dependent trend reaching significantly higher values for 0.046 mg/L and 0.465 mg/L drug concentrations in both cell lines. In vivo experiments showed a progressive increase of tumour lesions metabolism and dimensions regardless treatment.Sorafenib showed a good cytotoxic effect in vitro especially on human HD cell line, but these findings were not confirmed in vivo. The strong discrepancy between in vitro and in vivo results suggests that further studies are needed to better acknowledge the biodistribution and metabolism of Sorafenib in NOD/SCID mice. Factors influencing drug availability at tumour site or differences in the downstream pathways may be responsible for the scarse effect of treatment.

Objective. Dabigatran, a direct inhibitor of thrombin, represents an effective alternative to warfarin. Despite the good tolerance and predictable pharmacokinetic profile, dabigatran may be associated to adverse reactions, including gastrointestinal disorders. Here we report on a case of hepatotoxicity along with an extensive revision of the available literature on dabigatran induced liver injury Methods & results. An 84 years old man attended the Emergency Department after experiencing fatigue for a few days. He suffered from atrial fibrillation and had been initiated on dabigatran (110 mg bid) in the last four weeks. Clinical examination revealed tachycardia, scleral icterus in the absence of signs of chronic hepatic disease. Blood chemistry showed altered liver function tests: AST 809 IU/L, ALT 1629 IU/L, total bilirubin 2.42 mg/dL, gGT 381 IU/L, ALP 388 IU/L, LDH 552 IU/L. Screening laboratory investigations for infectious, autoimmune or metabolic hepatotoxic pathology were unremarkable. The abdominal ultrasound examination excluded vascular causes, revealing non-homogeneous echo-structure consistent with mild hepatic steatosis. At admission to our Geriatric ward dabigatran was discontinued and fondaparinux was introduced. Resolution of the hepatitis and normalization of blood chemistry was observed within two weeks. Few cases are described regarding hepatotoxicity likely caused by the recent onset of treatment with dabigatran. Conclusions. DOACs associated hepatotoxicity is rare but potentially harmful and should be kept in mind, especially in comorbid patients with unexplained liver injury. The mechanism of liver injury during dabigatran therapy is unknown and, not related to cytochrome P450 enzymes since the drug does not affect CYP450 activity.

This paper proposes an online evolutive procedure to optimize the Material Removal Rate in a turning process considering a stochastic constraint. The usual industrial approach in finishing operations is to change the tool insert at the end of each machining feature to avoid defective parts. Consequently, all parts are produced at highly conservative conditions (low levels of feed and speed), and therefore, at low productivity. In this work, a framework to estimate the stochastic constraint of tool wear during the production of a batch is proposed. A simulation campaign was carried out to evaluate the performances of the proposed procedure. The results showed that it was possible to improve the Material Removal Rate during the production of the batch and keeping the probability of defective parts under a desired level.

This paper addresses the numerical thermal characterization of a 3D turning process of a SAF 2507 stainless steel. A thermographic test campaign was conducted to measure the temperature distribution at the tool-workpiece interface. The campaign was accommodated by means of a L18 fractional factorial design of experiment. The 3D turning process was simulated using the software TWS Advantedge. The heat transfer numerical coefficients were calibrated against experimental measures to obtain temperature values as accurate as possible. A statistical methodology frame work was adopted to study the dependence of the coefficients from the machining parameters. A heat transfer surrogate model was then built and next experimentally validated.

Corticosteroids have been widely used for acute respiratory distress syndrome (ARDS), but their role in the early phase of SARS-CoV-2 infection is controversial. Our study aimed to determine the effectiveness of early corticosteroid therapy (ECT) in preventing the progression of disease, reducing the escalation of care and improving clinical outcome in older patients hospitalized for COVID-19 pneumonia. A total of 90 subjects (47.7% women; mean age = 82.3 ± 6.7 years) were enrolled. ECT was administered to 33 out of 90 patients before the hospitalization. At admission, no difference was detected in median SOFA score (2, IQR:2 vs. 2, IQR: 2). We found a significant difference in mean PaO2/FiO2 ratio during the first week of hospitalization between ECT patients and controls (F = 5.49, p = 0.002) and in mean PaO2/FiO2 ratio over time (F = 6.94, p < 0.0001). We detected no-significant differences in terms of in-hospital mortality and transfer to ICU between ECT patients and controls (27.1% vs. 22.8%, respectively, p = 0.63). ECT was associated with worse clinical outcomes, showing no benefit in attenuating the progression of the disease or reducing the escalation of care. These findings are crucial given the current pandemic, and further studies are needed to provide additional data on the optimal timing of initiating corticosteroid treatment.

The aim of this single-center, open-label, randomized controlled study was to evaluate which formulation of vitamin D—between cholecalciferol and calcifediol—is most effective in the treatment of hypovitaminosis D in older adults. Demographic characteristics, clinical history, and comprehensive geriatric assessment were recorded at admission. Eligible patients were randomly assigned an equivalent vitamin D supplement, either with cholecalciferol or calcifediol, from the time of hospital admission to three months after discharge. Among the 140 older patients included (mean age 83 ± 6.6 years, 57.8% females), 69 received cholecalciferol and 71 received calcifediol. The mean plasma values of 25-hydroxyvitamin D3 (25OH-vitamin D3) found at the time of enrollment were 16.8 ± 9.9 ng/mL in patients receiving cholecalciferol and 18.8 ± 13.3 ng/mL in those treated with calcifediol (p = 0.31). At the three month follow-up, the mean concentration of 25OH-vitamin D3 was significantly higher in patients treated with calcifediol than in those receiving cholecalciferol (30.7 ± 8.4 vs. 45.4 ± 9.8 ng/mL, respectively; p < 0.001). Supplementation with either cholecalciferol or calcifediol effectively results in reaching the optimal circulating values of 25OH-vitamin D3 in older patients suffering from hypovitaminosis D. However, supplementation with calcifediol led to average circulating values of 25OH-vitamin D3 that were significantly higher (over 50%) than those obtained with cholecalciferol.

Nickel superalloys are used in all the applications where high temperature and corrosion resistance are required, for example in aerospace, nuclear and oil&gas fields. Often defined as difficult to cut, these alloys are currently the most used materials in production of turbines of aircraft jet engines, stator parts and combustion chambers. Machining of superalloys is characterised by low productivity, poor surface quality and short tool life because of the high temperature reached during the process. So cutting fluids are used to cool and lubricate the cutting area; however, conventional fluids are often expensive for the difficult in their disposal management and represent a considerable risk for workers' health. In the last years, in order to solve environmental sustainability issues tied to these processes, the cryogenic machining with liquid nitrogen (LN2) has been developed. The cryogenic cooling effect is particularly interesting in difficult to machine materials but it presents some problems, e.g, cryogenic fluid affects material thermomechanical behavior. A small number of studies explore this aspect and moreover, the cooling approach for effectively using cryogenic machining and dispensing method shall be identified. In this sense, FE simulation can be considered a valid support tool for the process understanding. Furthermore, in this work a 3D numerical model in TWS AdvantEdge FE machining code has been developed. This model has been calibrated and validated with a comparison between simulations results, in term of cutting forces and temperatures, and experimental data.

In the present work, the approach used for the optimization of the process capabilities for Oil&Gas components machining will be described. These components are machined by turning of stainless steel castings workpieces. For this purpose, a proper Design Of Experiments (DOE) plan has been designed and executed: as output of the experimentation, data about tool wear have been collected. The DOE has been designed starting from the cutting speed and feed values recommended by the tools manufacturer; the depth of cut parameter has been maintained as a constant. Wear data has been obtained by means the observation of the tool flank wear under an optical microscope: the data acquisition has been carried out at regular intervals of working times. Through a statistical data and regression analysis, analytical models of the flank wear and the tool life have been obtained. The optimization approach used is a multi-objective optimization, which minimizes the production time and the number of cutting tools used, under the constraint on a defined flank wear level. The technique used to solve the optimization problem is a Multi Objective Particle Swarm Optimization (MOPS). The optimization results, validated by the execution of a further experimental campaign, highlighted the reliability of the work and confirmed the usability of the optimized process parameters and the potential benefit for the company.

Forces and temperatures in specific orthogonal cutting conditions and calculated by finite element analysis, have been evaluated taking into account the uncertainty of some process conditions. A traditional deterministic approach, in machining simulations, is not able to explain the uncertain physical variations related to material characteristics (yield and tensile strenght, hardness, etc.) and tool/chip/workpiece interface conditions (friction and tool wear). During machining operations many different sources of non-controllable process variations usually display their effect leading to a degree of uncertainty in the final parts quality. Statistical tools and methods are increasingly being used in combination with FE numerical simulation, in order to take in account of the variability of the process. Then, if one of the purposes of process design is to study and model robustness or reliability of a given process in aleatory conditions, a CAE study might become a feasible way to do it. Today, the evaluation of the performances of a metal cutting process is possible using several commercial FEA packages. These software tools automatically allow the preventive evaluation of the robustness of technological decisions. In this work the authors, by means the integration between stochastic simulation tools and machining FE codes, have evaluated the process sensitivity to a random variation of uncontrollable parameters or conditions. Furthermore, a specific experimental and numerical activity has been performed in order to better understand the technical capabilities in terms of process simulation in stochastic conditions.

The workpiece distortion that occurs during machining, can lead to a large increase in the number of the scrap parts. Residual stresses are the main cause of these distortions and they are generally present in both forging and casting products. In order to obtain the desired microstructure and mechanical properties, the workpiece is subjected to heat treatment before being worked. Quenching produces residual stresses that exist throughout a large percentage of the casting or forging part. Distortion occurs as a result of removing stressed material from the workpiece. The component will re-equilibrate and distort as each layer of stressed material is machined away. This paper describes a procedure development for distortions numerical analysis on a SAF2507 casting bulk workpiece. A solubilization heat treatment has been simulated, in order to predict the bulk residual stresses distribution. Different metal cutting processes have been considered to measure the numerical distortions induced in the workpiece.

Ring Rolling is a complex hot forming process where different rolls are involved in the production of seamless rings. Since each roll must be independently controlled, different speed laws must be set; usually, in the industrial environment, a milling curve is introduced to monitor the shape of the workpiece during the deformation in order to ensure the correct ring production. In the present paper a ring rolling process has been studied and optimized in order to obtain anular components to be used in aerospace applications. In particular, the influence of process input parameters (feed rate of the mandrel and angular speed of main roll) on geometrical features of the final ring has been evaluated. For this purpose, a three-dimensional finite element model for HRR (Hot Ring Rolling) has been implemented in SFTC DEFORM V11. The FEM model has been used to formulate a proper optimization problem. The optimization procedure has been implemented in the commercial software DS ISight in order to find the combination of process parameters which allows to minimize the percentage error of each obtained dimension with respect to its nominal value. The software allows to find the relationship between input and output parameters applying Response Surface Methodology (RSM), by using the exact values of output parameters in the control points of the design space explored through FEM simulation. Once this relationship is known, the values of the output parameters can be calculated for each combination of the input parameters. After the calculation of the response surfaces for the selected output parameters, an optimization procedure based on Genetic Algorithms has been applied. At the end, the error between each obtained dimension and its nominal value has been minimized. The constraints imposed were the maximum values of standard deviations of the dimensions obtained for the final ring.

Residual stresses induced in the component by previous thermal/mechanical processes are compressive or tensile stresses having a zero resultant. In particular, they arise as consequence of thermo-mechanical processes (e.g. ring-rolling process), casting and heat treatments. When machining stressed components, volume removal leads to a re-arrangement of residual stresses, which inevitably causes distortions in the workpiece. If distortions are excessive, they can lead to a large number of scrap parts. This paper describes the development of a numerical procedure for the analysis of the distortions on a waspaloy turbine case, obtained by ring rolling process. A 3D model of ring rolling process has been set in the commercial software DEFORM 3D. Three different ring rolling strategies have been analyzed, in order to find the combination of process parameters which allows to obtain the best component in terms of geometrical precision. Then, the heat treatments (air cooling, solubilization, stabilization and aging) have been simulated to predict the bulk residual stresses distributions. Finally, the numerical distortions induced by machining have been simulated considering the material removal in some machining operations.

Taking into account the main importance of nickel-based superalloy in aerospace, marine and chemical industries concerning the production of high performance artifacts, in this paper experimental results of cutting forces, chip morphology, tool wear and temperatures were investigated during orthogonal machining of Waspaloy (45 HRC). All the experiments were performed in dry and lubricated cutting conditions, analyzing and comparing the collected results for a range of different cutting parameters: cutting speed and feed rate. The results show a good trends coherence, highlighting the influence of lubrication during machining.

To evaluate the sensitivity of 18-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) in patients with mucosa-associated lymphoid tissue (MALT) lymphoma. A total of 32 patients with a histological diagnosis of extra-nodal MALT lymphoma were referred to the PET Centers in the last 2 years (2003 - 2004) and scanned with 18F-FDG-PET following standard procedures. Overall, the results of 50 18F-FDG-PET scans performed in either active disease state or in complete remission were reviewed. Sites of primary disease included stomach, lung, parotid, skin, orbit, mandible, esophagus and uterus. This study retrospectively enrolled 26 patients with known active disease. 18F-FDG-PET was true positive (TP) in 21/26 patients and false negative (FN) in 5/26. Sensitivity of 18F FDG-PET for extra-nodal MALT was 81%. The data show that 18FDG-PET is a useful diagnostic tool in order to stage, restage or monitor disease in patients with extra-nodal MALT lymphoma.

PURPOSE: Metastatic cancer of unknown primary origin is a syndrome characterised by a poor prognosis, with a typical survival rate from diagnosis of no longer than 1 year. Only 20-27% of primary tumours are identified by conventional radiological imaging. By contrast, it has been reported that 18F-fluorodeoxyglucose positron emission tomography (FDG PET) allows the identification of 24-40% of otherwise unrecognised primary tumours. To our knowledge, the studies on this topic have been conducted using 18F-FDG PET imaging alone. The aim of this study was to evaluate the potential additional diagnostic role of fused 18F-FDG PET-CT imaging for the detection of metastatic occult primary tumours. METHODS: The study population consisted of 21 consecutive patients with biopsy-proven metastatic disease and negative conventional diagnostic procedures. Each patient underwent a PET scan, carried out according to a standard procedure (6 h of fasting, i.v. injection of 370 MBq of 18F-FDG and image acquisition with a dedicated PET-CT scanner for 4 min per bed position). RESULTS: 18F-FDG PET-CT detected the occult primary tumour in 12 patients (57% of cases), providing a detection rate higher than that reported with any other imaging modality, including conventional 18F-FDG PET. CONCLUSION: The favourable results of this study need to be confirmed in larger patient populations with long-term follow-up.

In patients with heart failure and wide QRS complex, cardiac resynchronization therapy (CRT) is associated with improvement of symptoms and cardiac function. This study examined the effects of a 3-month period of CRT on left ventricular (LV) and right ventricular (RV) ejection fraction (EF) and on LV volumes, both at rest and during exercise. A CRT system was implanted in 15 patients with severe heart failure and wide QRS. Before implant and 3 months later, all patients underwent assessment of cardiac performance with equilibrium Tc 9 9 radionuclide angiography with imaging in the best septal left anterior oblique view. Exercise was performed on a bicycle ergometer. At 3 months, a significant improvement in New York Heart Association functional class was observed, and radionuclide angiography showed a significant decrease in LV volumes and a significant increase in LVEF at rest, as well as a significant increase in LVEF during exercise. The remodeling processes associated with CRT did not appear to include RV function, since RVEF did not improve, and changes in RVEF did not correlate with changes in LVEF, neither at rest nor during exercise.

To retrospectively evaluate the sensitivity, specificity and accuracy of (68)Ga-DOTA-NOC PET/CT and CT alone for the evaluation of bone metastasis in patients with neuroendocrine tumour (NET).From among patients with NET who underwent (68)Ga-DOTA-NOC PET/CT between April 2006 and November 2008 in our centre, 223 were included in the study. Criteria for inclusion were pathological confirmation of NET and a follow-up period of at least 10 months. PET and CT images were retrospectively reviewed by two nuclear medicine specialists and two radiologists, respectively, without knowledge of the patient history or the findings of other imaging modalities. PET data were compared with the CT findings. Interobserver agreement was evaluated in terms of the kappa score. Clinical and imaging follow-up were used as the standard of reference to evaluate the PET findings.PET was performed for staging (49/223), unknown primary tumour detection (24/223), restaging (32/223), restaging before radioimmunotherapy (1/223), evaluation during therapy (12/223), equivocal findings on conventional imaging (4/223 at the bone level; 61/223 at sites other than bone), and follow-up (40/223). A very high interobserver agreement was observed. CT detected at least one bone lesion in only 35 of 44 patients with a positive PET scan. In particular, PET showed more lesions in 20/35 patients, a lower number of lesions in 8/35, and the same number in 7/35. The characteristics of the lesions (sclerotic, lytic, mixed) on the basis of the CT report did not influence PET reading. PET revealed the presence of at least one bone metastasis in nine patients with a negative CT scan. Considering patients with a negative PET scan (179), CT showed equivocal findings at the bone level in three (single small sclerotic abnormality in two at the spine level, and bilateral small sclerotic abnormalities in the humeri, femurs and scapula). Clinical follow-up confirmed the PET findings in all patients; thus there were no false-positive or false-negative findings. Considering all patients, PET detected more lesions than CT (246 vs. 194). As compared to CT, on a patient basis PET showed a higher sensitivity (100% vs. 80%), specificity (100% vs. 98%), positive predictive value (100% vs. 92%), and negative predictive value (100% vs. 95%).In conclusion, (68)Ga DOTA-NOC PET was more accurate than CT for the identification of bone lesions and led to a change in clinical management in nine patients with a negative CT scan.

With increasing application of positron-emission tomography (PET) imaging, familiarity with the applications of PET in genitourinary oncology, especially prostate-cancer (PCa) imaging, becomes important. PET studies provide functional information using radiolabeled tracers, with fluoro-dexoxy-glucose (FDG) being the most commonly used. Nevertheless FDG has limitations for evaluation of PCa patients and therefore alternative tracers are being investigated. To date, the best results have been obtained with 11C-choline and 11C-acetate PET, which seem to demonstrate similar values in this field. We review the current role of PET in PCa patients based on data published in the literature as well as our own experience. Most studies of PET imaging of PCa address three goals: a) detecting primary PCa; b) staging PCa; and c) assessing PCa recurrence. From available results, routine clinical use of 11C-choline PET cannot be recommended for detecting and staging primary PCa. At present, the only clinical indication for imaging PCa with 11C-choline-PET is evaluation of suspected recurrence after treatment.

(18)F-FDG PET value for the assessment of neuroendocrine tumours (NET) is limited. Preliminary studies indicate that somatostatin receptor PET using (68)Ga-DOTA-peptides is more accurate for disease assessment and provide additional data on receptor status, that are crucial for targeted radionuclide therapy. At present, however, few papers investigated the role of (68)Ga-DOTA-NOC PET in NET, especially in unusual situations. The purpose of the present study was to evaluate (68)Ga-DOTA-NOC for the evaluation of NET of uncommon presentation. Patients with biopsy-proven NET were scheduled for (68)Ga-DOTA-NOC PET; we excluded from further evaluation cases with most common NET tumours (gastro-entero-pancreatic and pulmonary localization of primary lesion, MEN syndromes, medullary thyroid carcinoma, pheochromocytomas). PET results were compared with findings of conventional imaging, including CT, ultrasonography, MR and somatostatin receptor scintigraphy; finally PET results were compared with follow-up data with respect to the impact on patient management. Fourteen patients were finally enrolled; primary tumours were located at uterine level (3 cases), prostate (3 cases), ovary (1 case), kidney (1 case), breast (1 case), ear (1 case); also 3 cases of paraganglioma (at neck, abdominal and mediastinum level) and 1 case of lymphoma were included. (68)Ga-DOTA-NOC PET was positive, showing at least 1 lesion, in 6/14 cases while 5 cases turned out negative and 2 inconclusive. On a clinical basis, (68)Ga-DOTA-NOC provided additional information in comparison to conventional imaging procedures in 7/14 cases, and was considered useful in 12/14 patients, with 8 patients in which (68)Ga-DOTA-NOC PET was determinant for patient's management. Although the number of patients studied is limited, our data show that (68)Ga-DOTA-NOC can be usefully applied for the evaluation of NET of uncommon presentation; in particular very promising results were obtained in paraganglioma. On the other hand, care has to be paid when studying lesions localized at sites of physiological concentration of the tracer, and in presence of inflammation.

Small-animal PET is acquiring importance for pre-clinical studies. In rodents, radiotracers are usually administrated via the tail vein. This procedure can be very difficult and time-consuming as soft tissue extravasations are very frequent and tail scars can prevent repeated injections after initial failure. The aim of our study was to compare the retro-orbital (RO) versus tail vein intravenous (i.v.) administration of (18)F-FDG and (11)C-choline in mice for small-animal PET studies.We evaluated four healthy female ICR CD1 mice according to the following protocol. Day 1: each animal underwent an i.v. injection of 28 MBq of (11)C-choline. PET scan was performed after 10 min and 40 min. Day 2: each animal received an RO injection of 28 MBq of (11)C-choline. A PET scan was performed after 10 min and 40 min. Day 3: each animal received an i.v. injection of 28 MBq of (18)F-FDG. A PET scan was performed after 60 min and 120 min. Day 4: each animal received an RO injection of 28 MBq of (18)F-FDG. A PET scan was performed after 60 min and 120 min. Administration and image acquisition were performed under gas anaesthesia. For FDG studies the animals fasted for 2 h and were kept asleep for 20-30 min after injection, to avoid muscular uptake. Images were reconstructed with 2-D OSEM. For each scan ROIs were drawn on liver, kidneys, lung, brain, heart brown fat and muscles, and the SUV was calculated. We finally compared choline i.v. standard acquisition to choline RO standard acquisition; choline i.v. delayed acquisition to choline RO delayed acquisition; FDG i.v. standard acquisition to FDG RO standard acquisition; FDG i.v. delayed acquisition to FDG RO delayed acquisition.The RO injections for both (18)F-FDG and (11)C-choline were comparable to the intravenous injection of F-FDG for the standard and delayed acquisitions.The RO administration in mice represents a technical advantage over intravenous administration in being an easier and faster procedure. However, its use requires high specific activity while its value in peptides and other receptor-specific radiopharmaceuticals needs further assessment.

A 72-year-old man with monoclonal gammopathy of unknown significance presented with pain at the left hip level 4 years after radical prostatectomy for a malignant tumour. At the time of diagnosis of the primary tumour, the PSA level had increased to 7.4 ng/ml. Biopsy revealed a Gleason score of 4+3 and T2aN0M0 disease. Following radical prostatectomy (pathological stage pT3c, 1/15 positive lymph nodes, perineural infiltration), androgen deprivation was started promptly. At the onset of pain at the left hip level, PSA, MRI, bone scintigraphy and 11Ccholine PET/CT were performed owing to suspicion of recurrence of prostate cancer [1–4]. The anatomical imaging features (osteolytic lesion at the left ilium on MRI, negative total bone scintigraphy) and the low PSA level (

Metastatic cancers of unknown primary origin are characterised by a poor prognosis, with a survival rate from diagnosis of approximately 12 months. Conventional radiological imaging allows detection of 20%-27% of primary cancers, whereas the detection rate with positron emission tomography (PET) is 24%-40%. The aim of this study was to assess the role of 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) in the identification of occult primary cancers.The study population consisted of 38 consecutive patients with histologically proven metastatic disease and negative or nonconclusive conventional diagnostic procedures. All patients were studied by 18F-FDG PET performed according to the standard procedure (6 h of fasting, intravenous injection of 370 MBq 18F-FDG, and image acquisition with a PET/CT scanner for 4 min per bed position).18F-FDG-PET/CT detected the occult primary cancer in 20 cases (53%), showing higher sensitivity than that reported for any other imaging modality, including PET.The encouraging results, if validated by larger series, support the use of PET/CT in patients with carcinoma of unknown primary origin and negative conventional imaging results.

BACKGROUND: Integrated positron emission tomography/computed tomography (PET/CT) systems represent a major development allowing functional and anatomical information to be acquired in a single examination session and therefore providing a more accurate definition of suspected lesion characteristics. Together with the increasing number of clinical settings in which PET/CT scans have been advocated, however, pitfalls in image interpretation have been reported. METHODS: Four female subjects presenting a focal area of increased F-fluorodeoxyglucose (F-FDG) uptake with no evidence of a corresponding CT abnormality were included in the study. PET/CT scans were performed in all cases after the administration of 5.3 MBq . kg of F-FDG through a venous cannula. RESULTS: Focal high uptake of F-FDG was observed in lung lesions without anatomical counterparts on CT in four female cases. The only common feature to all was the paravenous injection of the radiotracer. CONCLUSION: The lesions detected by PET may be related to distal lung microembolism originating from the site of paravenous injection.

PURPOSE: Scintigraphic localisation of parathyroid glands is often unsuccessful in patients with renal failure on chronic haemodialysis who have secondary hyperparathyroidism (HPT). The purpose of this study was to investigate the use of (11)C-methionine PET/CT to detect hyperfunctioning parathyroid glands in patients with renal failure on chronic haemodialysis who had (99m)Tc-sestamibi-negative HPT. METHODS: (11)C-methionine PET/CT was performed in 18 patients (11 women and 7 men, aged 42-79 years; mean age 57.8 years) on haemodialysis for renal failure (2-14 years' duration), with normo-, hypo- or hypercalcaemia and HPT not localised by either dual-tracer (99m)Tc-pertechnetate/(99m)Tc-sestamibi subtraction scans or dual-phase (99m)Tc-sestamibi scans. RESULTS: In three of ten patients with normo- or hypocalcaemic HPT there was increased (11)C-methionine accumulation in one gland. Seven of eight patients with hypercalcaemic HPT showed increased uptake: in five of these patients increased (11)C-methionine accumulation was present in one gland, while in two it was demonstrated in two glands. All patients also had high-resolution ultrasound of the neck and were treated with subtotal parathyroidectomy, leaving a remnant of the smallest of the four glands. Regardless of their size, all glands with abnormal (11)C-methionine parathyroid uptake were removed, and all demonstrated parathyroid hyperplasia. All patients developed post-parathyroidectomy hypoparathyroidism and one patient with normocalcaemic HPT relapsed 8 months after surgery. CONCLUSION: These data suggest that (11)C-methionine PET/CT may be used to identify hyperfunctioning parathyroid glands in non-primary HPT, and especially hypercalcaemic HPT, when conventional (99m)Tc-sestamibi imaging is non-localising.

Purpose: The aim of this study was to evaluate the significance of increased uptake of 18F-fluorodeoxyglucose (FDG) in patients with malignant lymphoma (ML) studied by positron emission tomography (PET). Methods: A total of 1,120 consecutive scans carried out in 848 patients were reviewed; all patients had a diagnosis of ML [574 non-Hodgkin’s lymphoma (NHL) and 274 Hodgkin’s disease (HD)] and were studied at completion of therapy, for suspected recurrence or during follow-up. PET was carried out after intravenous injection of 370 MBq of 18F-FDG; images were recorded after 60– 90 min. Patients were selected whose reports indicated areas of increased FDG uptake. PET findings were considered positive for lymphomatous localisation when uptake occurred at sites of previous disease, in asymmetrical lymph nodes or in nodes unlikely to be affected by inflammation (mediastinal, except for hilar, and abdominal). PET findings were adjudged negative for neoplastic localisations in the following instances: physiological uptake (urinary, muscular, thymic or gastrointestinal in patients without MALT), symmetrical nodal uptake, uptake in lesions unrelated to lymphoma that had already been identified by other imaging methods at the time of PET scan, uptake at sites atypical for lymphoma, very low uptake and non-focal uptake. PET findings were compared with the results of other diagnostic procedures (including CT and ultrasound), biopsy findings and follow-up data. Results: Overall, 354 scans (in 256 patients) showed increased FDG uptake (244 scans in NHL and 110 in HD): in 286 cases, FDG uptake was considered pathological and indicative of ML, in 41 cases the findings were described as uncertain or equivocal and in 37 cases, FDG uptake was considered unrelated to ML (in ten scans, concurrent findings of abnormal FDG uptake attributed to ML and uptake assigned to other causes were obtained) . Of the 286 patients with positive PET findings, 274 (95.8%) were found to have residual or recurrent ML (i.e. true positives). Four of the 41 patients with inconclusive findings turned out to have ML, while in 13 patients, pathological processes other than ML could be identified as the cause of FDG uptake. ML was excluded in all patients with findings reported as non-pathological (100% true-negative rate). Therefore, the false-positive rate in our series was about 5%. The main cause of increased FDG uptake mimicking ML was inflammation. Conclusion: Our data confirm that 18F-FDG-PET has very high but not absolute specificity for ML. As already suggested, increased FDG uptake may also be observed in patients without active disease; in most cases, however, non-pathological FDG accumulation is properly identified. Less frequently, inconclusive scans are encountered; these cases are usually caused by inflammation, which subsequently resolves.

Malignant Pleural Mesothelioma (MPM) is a relatively rare neoplasia characterized by a poor prognosis. Recent studies show that new therapeutic approaches can lead to an improvement in life quality and to a prolonged survival; therefore, proper evaluation of MPM before, as well as after, therapy, is needed. The aim of this study was to evaluate the impact of 18F-FDG photon emission tomography (PET) scan compared to computed tomography (CT) findings in patients affected by MPM, whether untreated or already treated. We studied 15 consecutive patients (13 male and 2 female) with a histological diagnosis of MPM, with a mean age of 69.9 years (range: 38-78 years old) and a recent total-body CT scan. Five (5) patients were studied for staging, while 10 patients were studied after therapy. An FDG PET scan was carried out 60 minutes after an intravenous (i.v.) injection of 370 MBq of 18F-FDG. For each patient, we compared the PET stage to the CT stage, and evaluated the role of PET in choosing a therapeutic approach. In 9 of 15 (60%) patients, there was no difference between the PET and the CT stage. In 2 of 15 (13%) patients, PET upstaged the disease, while in 4 of 15 (27%) patients PET downstaged MPM. According to these results, patient management was changed in 3 cases. Specifically, 1 patient was excluded from surgery, and 2 patients had different chemotherapy. These data suggest that PET is useful in the evaluation of MPM, giving additional data that can clarify doubtful CT findings, especially regarding lymph node involvement and distant lesions. In conclusion, FDG PET was found to play a worth-while role in patient management.

To evaluate the value of 18F-fluorodeoxy-glucose (FDG) positron emission tomography with computed tomography (PET/CT) in myeloma in patients presenting with a solitary plasmacytoma of bone (SPB).Fourteen consecutive patients studied since 2006, all having a diagnosis of SPB before PET/CT imaging took part in this study. In 3 patients PET/CT was performed for staging while in the remaining 11 it was used to monitor therapy. PET/CT was performed using a dedicated tomograph 60-90 minutes after intravenous injection of 53 MBq/kg of 18F-FDG and the results were compared to other diagnostic procedures [radiographs and magnetic resonance imaging (MRI)], biopsy, and other available follow-up data.In 8/14 patients, PET/CT scans showed previously unsuspected sites of increased FDG accumulation. In 6/8 patients, FDG uptake was considered pathologic, depicting myeloma involvement in bone, while in the remaining cases, findings were considered incidental and not related to myeloma. PET findings attributed to myeloma were confirmed (i.e. true positives) in 6/6 cases (100%) and in all patients with findings reported as non-pathologic, myeloma was excluded (100% true negatives).Our preliminary data in a small number of cases suggests that there are a group of patients with SPB (local disease) in whom FDG PET/CT may detect other unsuspected sites of bone involvement, upstaging the extent of the disease. In these cases, SPB may be a local manifestation of multiple myeloma where other sites of involvement have eluded detection by other less sensitive imaging modalities (i.e. skeletal surveys) or anatomically restricted imaging (i.e., less than total body MR or CT). Finding other sites of involvement have significant implications for appropriate treatment of myeloma.