Daniela Prosperi

Can Sequential 18F-FDG PET/CT Replace WBC Imaging in the Diabetic Foot?

White blood cell (WBC) scintigraphy is considered the nuclear medicine imaging gold standard for diagnosing osteomyelitis in the diabetic foot. Recent papers have suggested that the use of 18F-FDG PET/CT produces similar diagnostic accuracy, but clear interpretation criteria have not yet been established. Our aim was to evaluate the role of sequential 18F-FDG PET/CT in patients with a high suspicion of osteomyelitis to define objective interpretation criteria to be compared with WBC scintigraphy. Methods: Thirteen patients whom clinicians considered positive for osteomyelitis (7 with ulcers, 6 with exposed bone) were enrolled. The patients underwent 99mTc-exametazime WBC scintigraphy with acquisition times of 30 min, 3 h, and 20 h and sequential 18F-FDG PET/CT with acquisition times of 10 min, 1 h, and 2 h. A biopsy or tissue culture was performed for final diagnosis. Several interpretation criteria (qualitative and quantitative) were tested. Results: At final biopsy, 7 patients had osteomyelitis, 2 had soft-tissue infection without osteomyelitis, and 4 had no infection. The best interpretation criterion for osteomyelitis with WBC scintigraphy was a target-to-background (T/B) ratio greater than 2.0 at 20 h and increasing with time. A T/B ratio greater than 2.0 at 20 h but stable or decreasing with time was suggestive of soft-tissue infection. A T/B ratio of no more than 2.0 at 20 h excluded an infection. Thus, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for osteomyelitis were 86%, 100%, 100%, 86%, and 92%, respectively. For 18F-FDG PET/CT, the best interpretation criterion for osteomyelitis was a maximal standardized uptake value (SUVmax) greater than 2.0 at 1 and 2 h and increasing with time. A SUVmax greater than 2.0 after 1 and 2 h but stable or decreasing with time was suggestive of a soft-tissue infection. An SUVmax less than 2.0 excluded an infection. 18F-FDG PET at 10 min was not useful. Using these criteria, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for osteomyelitis were 43%, 67%, 60%, 50%, and 54%, respectively. Combining visual assessment of PET at 1 h and CT was best for differentiating between osteomyelitis and soft-tissue infection, with a diagnostic accuracy of 62%. Conclusion: 18F-FDG PET/CT, even with sequential imaging, has a low diagnostic accuracy for osteomyelitis and cannot replace WBC scintigraphy in patients with diabetic foot.

Central and peripheral dopamine transporter reduction in Parkinson's disease

Abstract Objective: Previous reports showed the reduction of dopamine transporter immunoreactivity in peripheral blood lymphocytes in Parkinsons disease. In this work, we sought to investigate the possible correlation between central and peripheral dopamine transporter immunoreactivity values in a group of 11 drug-naive patients with Parkinsons disease. Methods: Densitometric measurements of dopamine transporter immunoreactivity in peripheral blood lymphocytes was accomplished as described recently, using a monoclonal antidopamine transporter antibody. Dopamine transporter binding in the caudate and putamen nuclei was measured by means of 123I-fluopane single-photon emission computed tomography in the same patients. Results: The results failed to show any significant correlation between dopamine transporter immunoreactivity in peripheral blood lymphocytes and the caudate or putamen dopamine transporter binding. Moreover, dopamine transporter immunoreactivity in peripheral blood lymphocytes was reduced also in the single patient with normal striatal dopamine transporter binding. Discussion: These results indicate the lack of correlation between central and peripheral dopamine transporter reduction in Parkinsons disease, using the methodologies applied herein. They therefore suggest that the two phenomena are unlikely to share a common pathogenetic mechanism.

Sternal wound infection revisited

Abstract.Sternal wound infections (SWIs) can be subdivided into two types, superficial or deep, that require different treatments. The clinical diagnosis of superficial SWI is normally easy to perform, whereas the involvement of deep tissues is frequently difficult to detect. Therefore, there is a need for an imaging study that permits the assessment of SWIs and is able to distinguish between superficial and deep SWI. The present work was a prospective study aiming to evaluate the role of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) labelled leucocyte scan in SWI management. Twenty-eight patients with suspected SWIs were included in the study. On the basis of clinical examination they were subdivided into three groups: patients with signs of superficial SWI (group 1), patients with signs of superficial SWI and suspected deep infection (group 2) and patients with suspected deep SWI without superficial involvement (group 3). Ten patients previously submitted to median sternotomy, but without suspected SWI, were also included in the study as a control group (group 4). All patients with suspected SWI had bacteriological examinations of wound secretion, if present. In addition 99mTc-HMPAO labelled leucocyte scan was performed in all patients. The patients of groups 1, 2 and 3 were treated on the basis of the clinical signs and microbiological findings, independently of the scintigraphic results. The patients of group 4 did not receive treatment. The final assessment of infection was based on histological and microbiological findings or on long-term clinical follow-up. Sensitivity, specificity, accuracy and positive and negative predictive values for scintigraphic and non-scintigraphic results were calculated. In the diagnosis of superficial and deep SWI, clinical and microbiological examination (combined) yielded, respectively, a sensitivity of 68.7% and 100%, a specificity of 77.3% and 80.8%, an accuracy of 73.7% and 86.8%, a positive predictive value of 68.7% and 70.6% and a negative predictive value of 77.3% and 100%. The scintigraphic results obtained in superficial SWI yielded a sensitivity of 56.2%, a specificity of 90.9%, an accuracy of 76.3%, a positive predictive value of 81.8% and a negative predictive value of 74.1%, while, by contrast, in deep SWI all of these values were 100%. Therefore, one can conclude that 99mTc-HMPAO labelled leucocyte scan permits accurate diagnosis of deep SWI, solving the main clinical problem in this field. In the present study the categorisation of patients without taking into account 99mTc-HMPAO labelled leucocyte planar scan findings caused a non-negligible number of cases of superficial SWI to be treated as though they were deep SWI. This ”overestimation” led to unnecessary surgery, increased and prolonged use of antibiotics with more (higher) toxicity and additional expense.

Tc-99m Exametazime-Labeled Leukocyte Scans in the Study of Infections in Skull Neurosurgery

Diagnosis and follow-up of skull infections are usually performed by neurologic examination, laboratory tests and instrumental diagnostic methods such as computed tomography (CT) and magnetic resonance imaging (MRI). These have, however, shown some limitations for specificity. The aim of the current study was to evaluate the overall contribution of Tc-99m exametazime-labeled leukocyte imaging scan Tc-99m hexamethylpropyleneamine (HMPAO) labeled white blood cells (WBC) in the diagnosis and management of infections in skull neurosurgery. Thirty-four patients were subdivided into 4 groups on the basis of the suspected pathology: intracerebral lesions on CT or MRI (group A, n = 20), suspected postsurgical infections (group B, n = 6), suspected deep infection of the surgical wound (group C, n = 4), and suspected infection of the ventriculoperitoneal shunt (group D, n = 4). All patients underwent CT, MRI, and Tc-99m HMPAO WBC imaging. Patients in group C also underwent bacteriologic and culture examinations of wound secretions if present. In positive cases in group A, Tc-99m HMPAO WBC imaging was repeated. The scintigraphic results were compared with histologic findings in patients who underwent surgery and with the results of a 12-month clinical follow-up in the remaining patients. Tc-99m HMPAO WBC scans correctly detected the infections in all groups. Furthermore, such imaging proved to be able to document recovery from the disease in all of the assessed cerebral abscesses. This study may have an important role both in the diagnosis and in the management of infections in skull neurosurgery, which, it is hoped, will be confirmed in the future.

New SPECT and PET Radiopharmaceuticals for Imaging Inflammatory Diseases: A Meta-analysis of the Last 10 Years

Modern molecular nuclear medicine is rapidly developing in the field of imaging of chronic inflammatory diseases, and many new radiopharmaceuticals have been recently described and tested in animals and man. These can detect early pathophysiological changes before the development of anatomical changes and, often, before clinical onset of symptoms. This field includes new radiopharmaceuticals for SPECT and PET use to define new strategies for imaging immune cells as well as tissue modifications induced by the inflammatory process. In this review, we present the results of a meta-analysis based on radiopharmaceuticals (for SPECT or PET) that are not commercially available and that have been used, at least once, in humans in the last 10 years.

Functional Imaging in the Follow-Up of Enteropancreatic Neuroendocrine Tumors: Clinical Usefulness and Indications

Context Functional imaging tests (FITs) detecting somatostatin receptor expression [i.e., somatostatin receptor scintigraphy, 68Ga-DOTA positron emission tomography/computed tomography (CT)] have a pivotal role in the diagnosis of neuroendocrine tumors (NETs), although their indication during follow-up still needs to be clarified. Objective Investigate the role of FITs after diagnosis of metastatic enteropancreatic NETs, identifying patients who might benefit from these exams. Design Multicenter retrospective analysis of metastatic enteropancreatic NETs. Setting Analysis of imaging tests performed between January 1995 and December 2015 in Rome, Berlin, Milan, Marburg, or Graz. Subjects One hundred forty-three patients with metastatic pancreatic NETs and small intestine NETs, at least 2-year follow-up, and positive FITs. Interventions Patients had received CT every 6 months (unless clinical conditions and tumor behavior required shorter intervals) and FIT every 12 months. Main Outcome Measures Clinical usefulness of FITs, defined as changes in patient management (indication to biopsy, medical therapy, surgery, or further imaging tests) due only to FITs. Results FITs affected management in 73.4% of patients, mostly when G2 vs G1 [odds ratio (OR), 2.40; 95% confidence interval (CI), 1.09 to 5.27; P = 0.03]. Changes were observed in a 12-month time frame especially with pancreatic NETs vs small intestine NETs (OR, 2.89; 95% CI, 1.09 - 7.67; P = 0.03) or metastases since diagnosis vs developed during follow-up (OR, 4.00; 95% CI, 1.43 to 11.17; P < 0.01). Conclusions FITs used in addition to CT in the follow-up of stage IV enteropancreatic NETs improve patient management (especially for G2 tumors). Follow-up program should be tailored according to tumor features.

Clinical Usefulness of 18F‐Fluorodeoxyglucose Positron Emission Tomography in the Diagnostic Algorithm of Advanced Entero‐Pancreatic Neuroendocrine Neoplasms

BACKGROUND The role of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the diagnostic algorithm of entero-pancreatic neuroendocrine neoplasms (EP NENs) is unclear because most available data derive from heterogeneous populations in terms of tumor biology and disease status at time of examination. The aim of this study was to determine the ability of 18F-FDG PET to identify patients with more aggressive disease among those with advanced EP NENs. Subjects, Materials, and Methods . Patients with advanced EP NENs and known disease status (progressive disease [PD] or stable disease [SD]) according to imaging procedures, who received 18F-FDG PET and computed tomography scans during a time frame of 1 month, were included. RESULTS A total of 93 patients, including 69 patients with pancreatic NENs and 24 patients with small-intestine NENs, were included. At the time of study entry, 64 patients (68.8%) had PD, and the remaining 29 patients (31.2%) had SD. A total of 62 patients (66.7%) had positive 18F-FDG PET, whereas 18F-FDG PET was negative in the remaining 31 patients (33.3%). Overall, 18F-FDG PET sensitivity and specificity to detect PD were 90.6% and 86.2%, respectively, resulting in a diagnostic accuracy of 89.2%. A positive 18F-FDG PET was significantly associated with PD at the time of study entry (p < .0001 at multivariate analysis). Although a higher proportion of 18F-FDG PET-positive examinations were observed in patients with higher tumor grade (p = .01), 53.8% of patients with grade 1 neuroendocrine tumors (NETs) had positive 18F-FDG PET, and 37.5% of patients with grade 2 NETs had negative 18F-FDG PET. Overall survival was significantly shorter in 18F-FDG PET-positive patients (median: 60 months) in comparison with 18F-FDG PET-negative patients (median not reached; p = .008). CONCLUSION 18F-FDG PET has a high diagnostic accuracy to identify progression of disease with unfavorable clinical outcome in patients with advanced EP NENs. Knowledge of disease status and G grading are key factors for physicians to better select patients for whom 18F-FDG PET is clinically useful. IMPLICATIONS FOR PRACTICE The findings of the present study may help physicians dealing with advanced neuroendocrine neoplasms to select patients for whom 18F-fluorodeoxyglucose positron emission tomography is useful to predict poor clinical outcome.

A case of pancreatic small cell neuroendocrine carcinoma associated with SIADH

To the Editor: W e read with interest the recent Pancreas article by Wu et al entitled “When to initialize enteral nutrition in patients with severe acute pancreatitis?” The timing for enteral nutrition initiation in severe pancreatitis is a relevant issue, but we believe that the study design does not allow answering the question. Indeed, this study evaluates essentially the impact of enteral nutrition in comparison to parenteral nutrition because 83% of the patients in “delayed enteral nutrition” group received exclusive parenteral nutrition. However, it is already well established that enteral nutrition was superior to parenteral nutrition to decrease infectious and surgical complications, as well as mortality in severe pancreatitis. On the other hand, the authors used the presence of necrosis to define the expected severity of acute pancreatitis. To date, it is accepted that the systemic inflammatory response syndrome is the better parameter to predict the expected severity of an acute pancreatitis. To assess comparability between the groups, SIRS and organ failure on admission are missing. The main objective of an early enteral nutrition during severe acute pancreatitis is to maintain the integrity of the gut barrier and then to prevent bacterial translocation. The choice made by the authors to use nasojejunal feeding tube placed by endoscopy could be debated. Authors give no information about energy supply within the first 48 hours, but we can assume that some days are necessary to reach the goal of 25 to 30 kcal/kg per day because of delay for the tube placement and the progressive feeding speed (initiated at 20 mL/h). In a recent randomized trial comparing the early nasojejunal tube feeding with an oral diet,

Functional imaging tests and CT scan: Detection of new metastases and clinical usefulness in digestive neuroendocrine neoplasms follow-up.

219 Background: Digestive Neuroendocrine Neoplasms (DNENs) express in up to 80% of cases somatostatin receptors (SSTRs), which can be detected by Functional Imaging Tests (FITs). FITs are needed at DNENs first diagnosis to define therapy but their role in follow-up (FU) is unclear. Moreover, with the introduction of targeted therapies, RECIST criteria are showing difficulties to assess tumor response to these drugs. The aim of this study was to evaluate, in metastatic DNENs FU, the diagnostic yield of FITs associated to Computed Tomography scan (CT) in terms of detecting new distant metastases (primary outcome) and of clinical usefulness (secondary outcome). Methods: Retrospective analysis of stage IV DNENs expressing SSTRs and with at least 24 month-FU. From 1995 to 2008 FIT performed was Octreoscan (OCT), subsequently it was 68Ga-DOTA- PET/CT (GaPET). CT was repeated every 6-12 months, FIT yearly. FU time was divided into 12 month-“units”, in which each patient had faced at least 1 CT and 1 FIT. Units w...

Abstract 3455: Functional imaging tests vs. computed tomography scan: detection of new metastases and clinical usefulness in digestive neuroendocrine neoplasms follow-up

Background: Digestive Neuroendocrine Neoplasms (DNENs) express in up to 80% of cases somatostatin receptors (SSTRs), that are detected by Functional Imaging Tests (FITs). FITs are needed at DNENs first diagnosis to define therapy but their role in follow-up (FU) is unclear. Moreover, with the introduction of targeted therapies, RECIST criteria are showing difficulties to assess tumor response to these drugs. The aim of this study was to compare the accuracy in detecting new distant metastases (primary outcome) and the clinical usefulness (secondary outcome) of FITs and Computed Tomography scan (CT) in metastatic DNENs FU. Methods Retrospective analysis of stage IV DNENs expressing SSTRs with at least 24 month-FU. From 1995 to 2008 FIT performed was Octreoscan (OCT), from 2008 to 2013 it was 68Ga-DOTANOC PET/CT (GaPET). CT was repeated every 6-12 months, FIT yearly. FU time was divided into 12 month-”units”, in which each patient had at least 1 CT and 1 FIT. Units were analyzed separately and then compared to each other. The gold standard adopted was the result of the imaging tests, the surgical and pathology findings collected for each patient during FU. Clinical usefulness was defined as appropriate changes in management (indication to new imaging test, therapy, surgery or biopsy) due to CT and/or FITs during FU. Results 323 units (median 3 per patient, range 2-7) derived from 99 patients included (66% metastatic since the first diagnosis). New lesions were detected by CT alone in 86.4% of cases, with a positive predictive value (PPV) of 93.3% and a negative predictive value (NPV) of 91.9%; adding OCT, the diagnostic yield was 10.34% (P Citation Format: Elettra Merola, Francesco Panzuto, Gabriele Capurso, Patrizia Kump, Rainer Lipp, Noemi Cicchese, Elsa Iannicelli, Daniela Prosperi, Patrizia Pizzichini, Maria Rinzivillo, Stefano Partelli, Anja Rinke, Massimo Falconi, Gianfranco Delle Fave. Functional imaging tests vs. computed tomography scan: detection of new metastases and clinical usefulness in digestive neuroendocrine neoplasms follow-up. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3455. doi:10.1158/1538-7445.AM2015-3455