Multimodal radionuclide shuntography for device patency: New procedural tips for anuncommon historical technique.

Cerebrospinal fluid (CSF) shunting is an established long-term treatment option for hydrocephalus, and is one of the most commonly performed neurosurgical procedures in western countries.Despite advances in CSF shunt design and management, its failure rates remain high and is most commonly due to obstruction and infection.Cerebrospinal fluidshunt failure diagnosis should be prompt and accurate in establishing timely if its revision is appropriate. Radionuclide shuntography with technetium-99m-diethylenetriaminepetaacetic acid (99mTc-DTPA) is a useful technique for evaluation CSF shunts and management of patients presenting with shunt-related problems, in particular it can avoid unnecessary replacement interventions. Although its execution and interpretation require specific skills, we suggest its execution for the evaluation of device's patency. We here describe the radionuclide shuntography performed with recent hybrid multimodal technologies, with a procedure customized to a complicated patient with hydrocefalus and neoplastic disease. We suggest considering radionuclide shuntography in association with conventional imaging and strongly recommend the additional performance of single photon emission computed tomography/computed tomography (SPECT/CT) because it also provides valuable information to complete the interpretation of planar images.

[18F]FDG PET/CT in head and neck squamous cell carcinoma: a head-to-head between visual point-scales and the added value of multi-modality imaging.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) represents the 6th leading cancer worldwide. In most cases, patients present a locally advanced disease at diagnosis and non-surgical curative treatment is considered the standard of care. Nowadays, [18F]FDG PET/CT is a validated tool in post-treatment evaluation, with a high level of evidence. However, to standardize imaging response, several visual scales have been proposed with none of them approved yet. The study's aim is a head-to-head comparison between the diagnostic performance of the Hopkins criteria, the Deauville score, and the new proposed Cuneo score, to establish their prognostic role. Secondly, we investigate the possible value of semiquantitative analysis, evaluating SUVmax and ΔSUVmax of the lymph node with the highest uptake on the restaging PET scan. Moreover, we also considered morphological features using the product of diameters measured on the co-registered CT images to assess the added value of hybrid imaging. METHODS: We performed a retrospective analysis on histologically proven HNSCC patients who underwent baseline and response assessment [18F]FDG PET/CT. Post-treatment scans were reviewed according to Hopkins, Deauville, and Cuneo criteria, assigning a score to the primary tumor site and lymph nodes. A per-patient final score for each scale was chosen, corresponding to the highest score between the two sites. Diagnostic performance was then calculated for each score considering any evidence of locoregional progression in the first 3 months as the gold standard. Survival analysis was performed using the Kaplan-Meier method. SUVmax and its delta, as well as the product of diameters of the lymph node with the highest uptake at post-treatment scan, if present, were calculated. RESULTS: A total of 43 patients were finally included in the study. Sensitivity, specificity, PPV, NPV, and accuracy were 87%, 86%, 76%, 92%, and 86% for the Hopkins score, whereas 93%, 79%, 70%, 96%, and 84% for the Deauville score, respectively. Conversely, the Cuneo score reached the highest specificity and PPV (93% and 78%, respectively) but the lowest sensitivity (47%), NPV (76%), and accuracy (77%). Each scale significantly correlated with PFS and OS. The ROC analysis of the combination of SUVmax and the product of diameters of the highest lymph node on the restaging PET scan reached an AUC of 0.822. The multivariate analysis revealed the Cuneo criteria and the product of diameters as prognostic factors for PFS. CONCLUSIONS: Each visual score statistically correlated with prognosis thus demonstrating the reliability of point-scale criteria in HNSCC. The novel Cuneo score showed the highest specificity, but the lowest sensibility compared to Hopkins and Deauville criteria. Furthermore, the combination of PET data with morphological features could support the evaluation of equivocal cases.

The eye is a common site of granulomatosis with polyangiitis. A collaborative study.

BACKGROUND: Ocular manifestations of granulomatosis with polyangiitis (GPA) have been reported in a limited number of studies and with largely variable frequency. Here we report on the clinical, diagnostic, and therapeutic features of a cohort of 63 GPA patients, with particular regard to 22 of them with ophthalmic involvement (35%). METHODS: Clinical manifestations, results of immunological findings, histopathological pictures, imaging data, Birmingham Vasculitis Activity Score, therapeutic regimens, and outcomes were retrospectively analyzed. At diagnosis, in addition to a structured clinical assessment, all patients underwent a comprehensive ophthalmologic examination. RESULTS: The most frequently involved organs were kidneys, lungs, ear/nose/throat, and eyes. Ocular manifestations were bilateral in 32%. The three most commonly diagnosed ophthalmologic manifestations were scleritis (36%), retro-orbital pseudotumor or orbital mass (23%), and episcleritis (13%). Ocular and systemic involvement were simultaneously present at onset in 41% of the patients; systemic involvement was followed by ocular lesions in 36%; ocular inflammation was followed by systemic manifestations in 18%; and an orbital mass in the absence of systemic disease characterized 5%. Glucocorticoids plus cyclophosphamide and glucocorticoids plus rituximab were the combined therapies most frequently employed during remission induction and remission maintenance, respectively. Persistent ophthalmologic and extra-ocular remissions were achieved in 77 and 64% of the patients, respectively. One to three systemic relapses were diagnosed in 7 patients (31.8%). At the last follow-up, a visual outcome 20/40 or better in 31 (70%) of 44 eyes was determined. CONCLUSIONS: The eye was involved in over one third of our patients with GPA. Increased awareness, early diagnosis, and multi-specialty collaboration are critical in achieving a favorable outcome of GPA.

The prognostic power of inflammatory indices and clinical factors in metastatic castration-resistant prostate cancer patients treated with radium-223 (BIO-Ra study).

PURPOSE: To combine peripheral blood indices and clinical factors in a prognostic score for metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223 dichloride ([223Ra]RaCl2). PATIENTS AND METHODS: Baseline neutrophil-to-lymphocyte ratio (NLR), derived NLR (donor), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), Eastern Cooperative Oncology Group performance status (ECOG PS), Gleason score (GS) group, number of bone metastases, prostate-specific antigen (PSA), alkaline phosphatase (ALP), line of therapy, previous chemotherapy, and the presence of lymphadenopathies were collected from seven Italian centers between 2013 and 2020. Lab and clinical data were assessed in correlation with the overall survival (OS). Inflammatory indices were then included separately in the multivariable analyses with the prognostic clinical factors. The model with the highest discriminative ability (c-index) was chosen to develop the BIO-Ra score. RESULTS: Five hundred and nineteen mCRPC patients (median OS: 19.9 months) were enrolled. Higher NLR, dNLR, PLR, and SII and lower LMR predicted worse OS (all with a p < 0.001). The multivariable model including NLR, ECOG PS, number of bone metastases, ALP, and PSA (c-index: 0.724) was chosen to develop the BIO-Ra score. Using the Schneeweiss scoring system, the BIO-Ra score identified three prognostic groups (36%, 27.3%, and 36.6% patients, respectively) with distinct median OS (31, 26.6, and 9.6 months, respectively; hazard ratio: 1.62, p = 0.008 for group 2 vs. 1 and 5.77, p < 0.001 for group 3 vs. 1). CONCLUSIONS: The BIO-Ra score represents an easy and widely applicable tool for the prognostic stratification of mCRPC patients treated with [223Ra]RaCl2 with no additional costs.

Prevalence of interstitial pneumonia suggestive of COVID-19 at 18F-FDG PET/CT in oncological asymptomatic patients in a high prevalence country during pandemic period: a national multi-centric retrospective study.

PURPOSE: To assess the presence and pattern of incidental interstitial lung alterations suspicious of COVID-19 on fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) ([18F]FDG PET/CT) in asymptomatic oncological patients during the period of active COVID-19 in a country with high prevalence of the virus. METHODS: This is a multi-center retrospective observational study involving 59 Italian centers. We retrospectively reviewed the prevalence of interstitial pneumonia detected during the COVID period (between March 16 and 27, 2020) and compared to a pre-COVID period (January-February 2020) and a control time (in 2019). The diagnosis of interstitial pneumonia was done considering lung alterations of CT of PET. RESULTS: Overall, [18F]FDG PET/CT was performed on 4008 patients in the COVID period, 19,267 in the pre-COVID period, and 5513 in the control period. The rate of interstitial pneumonia suspicious for COVID-19 was significantly higher during the COVID period (7.1%) compared with that found in the pre-COVID (5.35%) and control periods (5.15%) (p < 0.001). Instead, no significant difference among pre-COVID and control periods was present. The prevalence of interstitial pneumonia detected at PET/CT was directly associated with geographic virus diffusion, with the higher rate in Northern Italy. Among 284 interstitial pneumonia detected during COVID period, 169 (59%) were FDG-avid (average SUVmax of 4.1). CONCLUSIONS: A significant increase of interstitial pneumonia incidentally detected with [18F]FDG PET/CT has been demonstrated during the COVID-19 pandemic. A majority of interstitial pneumonia were FDG-avid. Our results underlined the importance of paying attention to incidental CT findings of pneumonia detected at PET/CT, and these reports might help to recognize early COVID-19 cases guiding the subsequent management.

A National Multicenter Study on overall survival in elderly metastatic castrate-resistant prostate cancer patients treated with Radium-223.

BACKGROUND: Radium-223 prolongs overall survival (OS) and delays time to the first symptomatic skeletal events in patients with symptomatic metastatic castration-resistant prostate cancer (mCRPC). There is a lack of evidence on the safety and efficacy of Radium-223 treatment in the very elderly population. AIMS: Aim of this multicentre study is to analyze mCRPC patients treated with Radium-223 in terms of OS and to assess whether there are differences between young and elderly, as well as to verify efficacy and safety in patients ≥ 75 years of age. METHODS: 430 mCRPC patients of six Italian Centres were analyzed in this multicenter retrospective study. At baseline and after each cycle were collected clinical and diagnostic patients' parameters. The whole cohort was divided into two groups based on the age of the patients (< 75 years old and ≥ 75 years old). RESULTS: 47% of the patients were < 75 years old and 53% were ≥ 75 years old. The primary outcome, OS, does not show significant differences between the two subgroups if other basal parameters are considered. Considering clinical covariates in univariate models (p < 0.05) several clinical aspects have an impact on OS, except for age (p = 0.072). Age continues to have no significant impact on the OS (p = 0.274) even in multivariate models in the two groups. The toxic effects are similar in the two groups. CONCLUSIONS: Radium-223 prolongs survival in both younger and older patients at the same baseline condition and is a good option in the symptomatic mCRPC setting compared to other agents.

Safety culture to improve accidental event reporting in radiotherapy.

BACKGROUND AND PURPOSE: The potential for unintended and adverse radiation exposure in radiotherapy (RT) is real and should be studied because RT is a highly complex, multistep process, which requires input from numerous individuals from different areas and steps of the RT workflow. The 'Incident' (I) is an event the consequence of which is not negligible from the point of view of protection or safety. A 'near miss' (NM) is defined as an event that is highly likely to happen but did not occur. The purpose of this work is to show that through systematic reporting and analysis of these adverse events, their occurrence can be reduced. MATERIALS AND METHODS: Staff were trained to report every type of unintended and adverse radiation exposure and to provide a full description of it. RESULTS: By 2018, 110 worksheets had been collected, with an average of 6.1 adverse events per year (with 780 patients treated per year, meaning an average incident rate of 0.78%). In 2001-2009, 37 events were registered (13 I and 24 NM), the majority of them were in the decision phase (12/37), while in 2010-2013, there were 42 (1 I and 41 NM) in both the dose-calculation and transfer phase (19/42). In 2014-2018, 31 events (1 I and 30 NM) were equally distributed across the phases of the RT process. In 9/15 cases of I, some checkpoint was introduced. CONCLUSION: The complexity of the RT workflow is prone to errors, and this must be taken into account by encouraging a safety culture. The aim of this paper is to present the collected incidents and near misses and to show how organization and practice were modified by the acquired knowledge.

18F-FDG PET/CT in GIST treatment response evaluation beyond Imatinib.

Positron emission tomography/computed tomography (PET/CT) represents a reliable promising tool in treatment response evaluation of new therapies beyond Imatinib in gastrointestinal stromal tumors (GIST). This narrative review aims to discuss the literature about the role of fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT in evaluating response in new tyrosine kinase inhibitors (TKI) and radiotherapy (RT) in GIST patients. A comprehensive literature search was performed to retrieve original studies published on PubMed, Scopus and Google Scholar databases. Eighteen studies including 382 patients with GIST were selected. Main findings of included studies are presented. Fluorine-18-FDG PET/CT may enhance performance in GIST management providing significant information in evaluation of treatment response and representing a strong predictor of clinical outcome.

Is whole body low dose CT still necessary in the era of 18F-FDG PET/CT for the assessment of bone disease in multiple myeloma patients?

OBJECTIVE: Whole body low dose computed tomography (WBLDCT) is the first-choice imaging modality to identify bone involvement in multiple myeloma (MM). Because the unenhanced LDCT co-registered to positron emission tomography (PET) (LDCT/PET) has similar technical characteristics to WBLDCT, we aimed to assess its reliability in the detection of bone disease, for employing fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT as unique multimodality imaging method in MM patients. SUBJECTS AND METHODS: Thirty three consecutive MM patients were prospectively enrolled and evaluated with WBLDCT to assess bone involvement. In addition, patients underwent 18F-FDG PET/CT using a disease-tailored optimized LDCT protocol. To compare both methods, skeletal anatomical regions were identified and a per-region and per-patient analysis were performed using Cohen's k test. Low dose computed tomography/PET sensitivity, specificity and accuracy were also calculated. RESULTS: The two imaging modalities resulted highly concordant considering both patient-based (k=0.841) and region-based analysis; some discrepancies were observed in dorsal spine (k=0.809) and thorax (k=0.756). Low dose computed tomography/PET sensitivity, specificity and accuracy were 89.4%, 98.3% and 93.5%, respectively. CONCLUSION: Low dose computed tomography co-registered PET has comparable performance to WBLDCT. If confirmed on a lager sample, these encouraging results suggest the possibility to use this multimodal hybrid imaging as the only method for MM evaluation, rather than both exams, providing both morphologic and metabolic information in one session with impact on patient compliance, health care spending and especially radiation exposure.

Typical and atypical PET/CT findings in non-cancerous conditions.

Nuclear Medicine multimodality imaging, such as positron emission tomography/computed tomography PET/CT, refers to metabolic tissue characteristics integrated with anatomical details. Fluorine-18-fluorodeoxyglucose (18F-FDG) is the most diffuse radiopharmaceutical and its application is spreading beyond the area of oncology. The causes of high 18F-FDG uptake that were once considered false positives have been identified and the new knowledge about them led to non-cancerous pathologies that can be studied by 18F-FDG PET/CT. This technique, due to the inflammatory cells high avidity of 18F-FDG, can be useful in studying a variety of inflammatory and infectious systemic conditions. Studies performed in patients with fever of unknown origin (FUO) indicate that 18F-FDG PET/CT offer a great advantage of detecting malignancy, inflammation and infection at the same time both in adults and children. Furthermore, the 18F-FDG PET/CT has proved useful in the study of specific organs such as the heart and brain that represent separate topics also for the development of new specific radiopharmaceuticals. In all the non-oncologic conditions 18F-FDG PET/CT imaging may offer an "all-in-one" procedure, thanks also to its panoramic whole-body acquisition, as an alternative to other diagnostic procedures, reducing the number of unnecessary investigations. The 18F-FDG PET/CT finding of the simultaneous presence of radiopharmaceutical uptake for multiple disease interconnect to different medical disciplines. It is important to describe unexpected occasional typical or atypical PET/CT findings to the growth of scientific and medical community; it can be the starting point to the enlargement of PET/CT indications for a better and wider comprehension of the human system. To recognize unexpected occasional findings is very important a well knowledge of many aspects: physiological biodistribution, diagnostic imaging instrumentations and techniques, pathological aspects of the different neoplastic diseases, patient story, such as previous therapy, and its comorbidity. An unexpected occasional finding can lead to suggest further tests or investigations in order to have a wider comprehension of patients' clinical situation and they are easily explainable when we have a physician's approach towards patient.

Medical radiological procedures: which information would be chosen for the report?

AIMS AND OBJECTIVES: The aim of this study was to properly define the information regarding patient exposure to Ionizing Radiations in the radiological report, according to the European Directive 2013/59/EURATOM (EU 2013/59 art.58(b)). For this purpose, we evaluated the results from other Member States EU 2013/59 transpositions and from Guidelines recommendation published by International Organizations involved in diagnostic radiology. A practical way for implementing art.58 is also traced. MATERIALS AND METHODS: Dosimetric quantities, such as exposure, absorbed dose and effective dose which may be included in radiological report, were first analyzed; then, in order to define international state of art of Member States EU 2013/59 transposition, a Web research using French, English, Spanish and German key words was performed. RESULTS: EU 2013/59 transposition for 5 Member States was reported. Especially regarding art.58, a European project reports that few European countries (11 of 28) have identified the dose metrics to be used in radiological report. Scientific organizations supporting clinical radiologists and medical physicists have published Guidelines reporting parameters useful to quantify the radiation output and to assess patient dose. CONCLUSIONS: Our research revealed that there is not a shared interpretation of patient exposure information to be included in radiological report. Nevertheless, according to scientific community, authors believe that the exposure is the most appropriate information that could be included in radiological report. Alternatively, but with more expensiveness, a risk index based on effective dose could be used. Moreover, the systematic exposure information recorded could be useful for dose estimates of population from medical exposure.

The new lens dose limit: implication for occupational radiation protection.

AIM AND OBJECTIVES: The aim of this article was to explore the implications of the new Euratom dose limit for occupational radiation protection in the context of medical occupational radiation exposures. The European Directive 2013/59/Euratom takes into account the new recommendations on reduction in the dose limit for the lens of the eye for planned occupational exposures released in 2012 by the International Commission on Radiological Protection (ICRP 118). MATERIALS AND METHODS: Different dose-monitoring procedures and devices were considered. Occupational eye lens doses reported by previous studies were analyzed, mainly considering workers involved in interventional procedures with X-rays. The current status of eye lens radiation protection and the main methods for dose reduction were investigated. RESULTS: The analysis showed that the workers, potentially exceeding the new limit, are clinical staff performing interventional procedures with a relatively high X-ray dose. Regarding radiological protection issues, the considered literature reports that the proper use of personal protective equipment may reduce the eye lens absorbed dose. CONCLUSION: The evaluation of the occupational eye lens dose is essential to establish which method of personal dose monitoring should be preferred. Furthermore, education and training about the right use of personal protective equipment are important for medical staff working with ionizing radiation.

How often suspected pulmonary embolism is diagnosed and its main diagnostic characteristics, in an emergency nuclear medicine service? Four years experience.

OBJECTIVE: Acute pulmonary embolism (APE) is an emergency condition and its treatment must be immediate. Nevertheless, the diagnosis of APE is diffcult because its symptoms and risk factors are not specific. We present our 4 years experience on this subject. SUBJECTS AND METHODS: We retrospectively studied 2178 lung perfusion scintigraphies (LPS). Of them 1846 were performed to patients suspected for APE admitted to the emergency departments of the University Polyclinic of Bari and examined immediately by our Nuclear Medicine Department. Contingency tables and odds ratio (OR) were used to estimate the relation between symptoms, risk factors, D-dimers dosage, other imaging diagnostic tools and LPS results. RESULTS: Lung perfusion scintigraphy was positive for APE in 309/1846 (16.7%) patients which then were treated successfully. In 89.5% of these, 309 patients D-dimer dosage was previously examined and was increased in 97.7% of them, but was not predictive of APE (OR=1.04, P=1). Among all symptoms, a low diagnostic capacity was found for cough (OR=1.25, P=0.066) and for chest pain (OR=0.95, P=649). On the contrary, dyspnea was a significant symptom correlated with positive LPS (OR=1.78, P<0.001). The presence of risk factors was predictive of positive LPS and positively correlated with the number of positive 2 oglin lesions in LPS. x2loglin=6.472, P=0.011). Lung perfusion scintigraphy positive for APE were significantly associated with computed tomography pulmonary angiography and/or chest X-ray results (x =9.618, P=0.022). CONCLUSION: Lung perfusion scintigraphy could early diagnose APE in 16.7% of the cases (referred to our Nuclear Medicine Emergency Service) and exclude APE in 83.3% of these cases. Immediate treatment or release of these patients from the emergency department was thus possible. LPS has a key role in the early diagnosis but even more in exclusion of APE, optimizing the management of patients who do not require admission to intensive care. Our four-year and large-scale experience, based on clinical and resource optimization, support the need of Nuclear Medicine Units to perform LPS as emergency in on-call 24 hrs service.

Use of amyloid PET/CT with 18F-Florbetaben in the management of patients with Alzheimer's disease.

INTRODUCTION AND AIM: Amyloid PET/CT is an "in vivo" imaging that may radically change management of Alzheimer's disease (AD) thanks to its ability to identify AD at the earliest stage. A diagnosis of dementia is currently made in terms of probability and is based on clinical evaluation (neuropsycological tests) as well as on the results of morphological imaging investigations (MRI) that can be supported by biohumoral (CSF analysis), and functional imaging only in the case of uncertain diagnosis of disease. The present study aimed to evaluate the role of amyloid PET/CT in the management of patients with suspicion of AD, through comparison with instrumental and clinical evaluation. METHODS: 38 consecutive patients with suspicion of AD (23 female, 15 male; median age 63 years old, range 46-72), who performed 18F-florbetaben PET/CT, were retrospectively reviewed. All of them performed a previous instrumental evaluation. A subgroup of patients (24/38) were evaluated with Mini Mental State Examination (MMSE). Cohen's K test was used as a measure of agreement between previous instrumental examinations/clinical evaluation and beta-amyloid PET results. RESULTS: Twenty-five/38 (65.8%) amyloid PET/CT scans resulted positive for amyloid deposition. Among the four target regions, precuneus was the most frequently involved. Previous instrumental evaluation was: MRI in 26/38 patients (24/26 positive for atrophy), CT in 9/38 (8/9 positive for atrophy), perfusion SPECT in 12/38 (8/12 areas of hypo-perfusion), 18F-FDG PET/CT in 2/38 (1/2 hypometabolism in frontal cortex). The agreement between previous instrumental examinations and beta-amyloid PET results was low (K= 0.084). In the subgroup of 24/38 patients, MMSE was scored positive (MMSE<24) in 14/24 (58.4%) and negative (MMSE>24) in 10/24 (41.6%). The agreement between clinical evaluation (MMSE) and beta-amyloid PET results was fair (K= 0.217). CONCLUSION: The low agreement between amyloid PET/CT and previous clinical and instrumental assessments that we found in our study suggests that the amyloid PET/CT provides additional and early information. To perform an early and differential diagnosis of AD could have a great impact on the patient's management and cost of care in order to perform the correct therapeutic interventions and to allow family members to manage adequately the patient's demanding care.

Impact of pre-treatment variables on the completion of 223radium-dichloride therapy in mCRPC patients with bone metastases.

INTRODUCTION: Radium-223 dichloride (223Ra) is an alpha-particle-emitter radiopharmaceutical, approved for metastatic castration-resistant prostate cancer (mCRPC) patients with symptomatic bone metastases and no visceral involvement. Its administration is based on a schedule of intravenous injection (55kBq/kg) every four weeks for up to six cycles. Because the biological effectiveness of 223Ra-therapy is dose-dependent, the main goal is to complete the entire treatment to achieve a better patient outcome. This study aims to identify potential pre-treatment variables that could impact on 223Ra-treatment completion and then be used to improve the clinical and supportive management of mCRPC patients. MATERIALS AND METHODS: 30 consecutive mCRPC patients (mean age 77 years old), who were admitted for Ra223-therapy at our Department from February 2016 to October 2018, were enrolled for the analysis. The population was grouped as patients who completed 223Ra-therapy (group Ra223-C) and patients who do not (group 223Ra-U). For each group, we analyzed the effects of potential pre-treatment variables (age, Gleason Score, tumor burden, "Time From Diagnosis To 223Ra therapy", type and number of previous treatments, hemoglobin level, Alkaline Phosphatase, Prostate Specific Antigen and pain) on the Ra223-therapy completion. Statistical analysis was performed to evaluate the association between the completion of 223Ra therapy and the variables examined. RESULTS: 16/30 (53%) patients were 223Ra-C, conversely 14/30 (47%) patients were 223Ra-U because of an early interrupted treatment. A statistically significant association was found only with tumor burden: 68.7% of patients who completed 223-therapy had less than 20 bone metastases (χ2=4.821, p=0.028). CONCLUSION: Our preliminary analysis demonstrates that the high tumor burden represents the most important pre-treatment factor that could affect treatment completion and that needs to be considered before starting 223Ra-therapy to achieve a better outcome in mCRPC patients.

The paleoradiology importance in the study of relics: the unique densitometric analysis of a bone relic of Saint Nicholas.

INTRODUCTION: DXA have greatly contributed to the development of paleoradiology, a branch of diagnostic imaging that allows to obtain information about human remains in contexts of archaeological and/or forensic interest. In this manuscript we report the unique experience of DXA performed on the relic of a Saint; in particular we analyzed a skeletal fragment of St. Nicholas, kept in the Basilica of Bari (Italy) since 1087. MATERIALS AND METHODS: The bone to be examined consisted of the posterior arch of the ninth left rib that was 12cm long, 1.2cm maximum width and 1.7cm thick at the body. The data acquired from the densitometric study were performed using the anthropometric measures reported in historical records of St. Nicholas' life: sex (male), age (75 years), weight (70kg), height (167cm), and ethnicity (Caucasian). In addition to the examination of the relic, a comparison assessment was made with the rib of a healthy 60 years old man (height of 170cm, without known skeletal pathologies). This sample had a length of 19cm, maximum width at the head 1cm, and 0.7cm thick at the body. The analysis of bone fragments is different from the analysis of bones in the context of the human body (where soft tissues are placed around the skeleton); for this reason, one of the most critical issues was to create a support that would allow the analysis of bone fragments. We simulated conditions similar to those occurring in patients: a density scale was established, using a specific plexiglass phantom on which the bone fragments to be examined were placed. From the analysis it was calculated the parameter bone mineral density (BMD), express in g/cm2, that indicates the relation between mass of bone mineral content and area of examined bone segment. BMD data was compared to a range normalized by age, sex and ethnicity (BMD-N). RESULTS: The results of the scannnig of St. Nicholas' rib showed a BMD of 0.97g/cm2 with a BMD-N between 0.77 and 1.08g/cm2. Simultaneous measurements of the relic compared with a reference rib showed highlighted BMD of 0.84g/cm2 for the relic and 0.50g/cm2 for the reference rib. The St. Nicholas data are 168% higher than reference bone. All our measurements of the relic indicated a high bone mineral density, most likely due to the presence of a high concentration of calcium salts. A relatively higher mineral density of the relic was seen compared to the healthy subject's rib. From the history of St Nicholas' life, we know of the long imprisonment at the age of 51 in damp and unhealthy environment. The results of this study suggest that a good bone mineral density was maintained by the Saint even in old age. An additional element that can influence bone mineral density is diet, certainly different during the time of St. Nicholas. The good bone densitometry indicates that the Saint maintained a proper diet, with a generally fair state of health. CONCLUSION: For this first DXA analysis of the rib relic of Saint Nicholas was necessary a long and complex experimental work to modify standard technique procedure to particular and unusual sample and Create specific supports and complementary instruments. Perform DXA analysis on relics permit to obtain additional information to living conditions, economical situation, behaviours, diet, diseaes, conservations conditions of remains, change of life style in different age. Our experimental work, the first of its kind, creates the way to analyze precious relics that often include only few bone fragments and data obtained by our work can be useful for a better management and movement of fragile relics. We ourselves are working on a new challenge for the analysis of bone finds from shipwrecks found at the bottom of the sea.

Sickle cell diseases: What can nuclear medicine offer?

Sickle cell disease (SCD) is the best known haemoglobinopathy, caused by a mutation substituting valina for glutamic acid at position 6 of the beta-globin chain of adult hemoglobin A, resulting in hemoglobin S (HbS). The homozygous HbS disease (HbSS), an autosomal recessive disorder, is the most common form and the Mediterranean area, along with sub-Saharian African and India, have the highest prevalence (1%-15%). In particular, Sicily with a prevalence of 2%-5%, is among the most interested regions. However, migratory flows have led to a wider diffusion of the disease no longer confined to endemic areas. In Europe, the yearly estimate of affected births are 1,300 but more than 90% of children with SCD survive into adulthood thanks to screening programs and early available care; however, their lifespan remains shortened by two or three decades compared to general population. In Greece, the number of affected births surpassing 100,000 yearly and the total number of newborns carrying two deleterious genes, if no prevention measures are taken, is estimated to be about 120-130/year. Diagnosis of SCD is based on analysis of haemoglobin through protein electrophoresis or chromatography, that are cheap and widely available techniques, even if haemoglobin mass spectrometry and DNA analysis are techniques with high-throughput testing. Prenatal diagnosis is used in many European countries, so the number of affected newborns has significantly decreased during the last 3 years. Over the course of SCD, sickling process may cause acute and chronic abdominal pain due to vaso-occlusive crisis, bone pain often in long bones due to bone marrow infarction, chronic hemolytic anemia, splenic sequestration with rapid enlargement of the spleen, delayed sexual maturation and cholelithiasis, with important inter-indivuidual variability. Sickle hepatopathy reflects liver sickling process within hepatic sinusoids and includes gallstone disease, hepatic sequestration, hepatic sideroris, acute sickle cell hepatic crises (ASHC) and sickle cell intrahepatic cholestasis (SCIC). Clinically, it appears with fever, right upper quadrant pain, jaundice and increased serum liver function tests. These patients are repeatedly esposed to trasfused red cells that contributes to iron overload and may contribute to hepatic haemosiderosis. Increased bone turnover and resorption by osteoclasts and by marrow expansion due to activation of hematopoiesis. The hematopoietic system may expand physiologically. Computed tomography (CT) is an easily reproducible imaging method that allows the morphologic whole-body evaluation although with a high dose of radiation exposure and possible side effects from intravenous contrast media. Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive technique without radiation chosen to image cholangiopathy and may be followed by the execution of endoscopic retrograde cholangiopancreatography (ERCP) in case of gallstone disease. Otherwise it can be helpful in identifying extramedullary hematopoiesis sites. Dual-energy X-rays absorptiometry (DEXA) is performed to evaluate deficit of bone mineral density (BMD), in which reduction of osteoblastic activity, high risk for necrosis may induce to fragility fractures. We recently had the experience of a typical case of a 56 years old Albanian woman with SCD, with jaundice after a long history of recurrent vaso-occlusive crisis. She was submitted to splenectomy and cholecystectomy 5 years before and since then she was treated with hydroxyurea. Hemocromatosis was excluded by genetic analysis. Hepatic biopsy (Pearl's stain) showed sinusoidal dilatation and diffuse iron accumulation in hepatocytes and Kupffer cells. Endo-hepatic jaundice was observed in MRCP images. It was interesting that DEXA examination was within normal range in both right proximal femur. This may probably be due to the presence of sclerotic lesions in the vertebrae, as was seen in the CT images. Technetium-99m-methylen bisphosphonate (99mTc-MDP) skeletal scintigraphy is a higly sensitive whole-body diagnostic nuclear medicine technique able to evaluate early bone metabolic changes. Multimodality SPET/CT allows to correlate scintigraphic findings with anatomical images with higher sensitivity and specificity. The higher uptake of 99mTc-MDP in SCD patients is due to the activation of hematopoetic system and relies on the osteoblastic response to bone resorption as in our patient. The 99mTc-MDP scan may be better than fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to show sclerotic lesions. Technetium-99m nanocolloids bone marrow scintigraphy (BMS) provides information about the assessment of the reticulum-endothelial system (RES), the whole-body distribution of functional red bone marrow and the presence and the extent of extramedullary hematopoiesis, especially in liver, spleen and bone marrow. Fluorine-18-FDG PET/CT completes the whole-body assessment with an integrated multimodal approach with high spatial resolution that evaluates the metabolic activity and the standardized uptake value (SUV) in SCD patients. Modern genetic diagnosis and gene treatment give promise for having fewer cases of SCD in the future.

Bone Involvement in Hodgkin's Lymphoma: Clinical Features and Outcome.

Hodgkin's lymphoma (HL) is now a highly curable disease, with an improving 5-year survival rate that has now reached 86%. At the time of presentation, HL is usually almost entirely confined to the lymph nodes. We performed a retrospective single-institution study of 384 cases with a median follow-up of 44 months, with the aim of identifying clinical and radiological characteristics and outcomes of patients with bone HL; 32 patients (8%) had primary bone involvement, always with concurrent nodal disease. These included 22 men (69%) and 10 women (31%) with the median age as 41 years. Advanced stages and nodular sclerosis histology prevailed among the subgroup. Radiographic features of bone HL are not specific but indicate a destructive malignant process with osteosclerosis and/or osteolysis. With current chemotherapeutic regimens, the long-term prognosis of patients with osseous HL appears good. The presence of bone lesions in HL should not be interpreted as implying a worse prognosis than without bone involvement.

Chronic coffee consumption and striatal DAT-SPECT findings in Parkinson's disease.

Coffee may interfere with the dopaminergic transmission, and this action would possibly enhance motor activity and exert an antidyskinetic effect in Parkinson's disease (PD). This study aimed to see whether coffee habit could be associated with change in striatal dopamine active transporter (DAT)-single photon emission computed tomography (SPECT) imaging in PD. A total of 83 PD patients (71 current coffee drinkers and 12 never drinkers) underwent a DAT-SPECT study, using [123I]FP-CIT as radionuclide. Socio-demographic and clinical information as well as smoking habit was collected at the time of imaging acquisition. The Unified Parkinson's Disease Rating Scale part III was used to evaluate disease severity. On multivariable analysis, chronic coffee consumption was not associated with any significant change in striatal uptake of the radionuclide. However, the number of years patients drunk coffee was correlated with a significant increase in age at PD onset (p < 0.001). Confirming a previous report, current cigarette smoking was associated with a reduction of radionuclide uptake in putamen and caudate (p < 0.001).

Therapeutic Potential of Autologous Adipose-Derived Stem Cells for the Treatment of Liver Disease.

Currently, the most effective therapy for liver diseases is liver transplantation, but its use is limited by organ donor shortage, economic reasons, and the requirement for lifelong immunosuppression. Mesenchymal stem cell (MSC) transplantation represents a promising alternative for treating liver pathologies in both human and veterinary medicine. Interestingly, these pathologies appear with a common clinical and pathological profile in the human and canine species; as a consequence, dogs may be a spontaneous model for clinical investigations in humans. The aim of this work was to characterize canine adipose-derived MSCs (cADSCs) and compare them to their human counterpart (hADSCs) in order to support the application of the canine model in cell-based therapy of liver diseases. Both cADSCs and hADSCs were successfully isolated from adipose tissue samples. The two cell populations shared a common fibroblast-like morphology, expression of stemness surface markers, and proliferation rate. When examining multilineage differentiation abilities, cADSCs showed lower adipogenic potential and higher osteogenic differentiation than human cells. Both cell populations retained high viability when kept in PBS at controlled temperature and up to 72 h, indicating the possibility of short-term storage and transportation. In addition, we evaluated the efficacy of autologous ADSCs transplantation in dogs with liver diseases. All animals exhibited significantly improved liver function, as evidenced by lower liver biomarkers levels measured after cells transplantation and evaluation of cytological specimens. These beneficial effects seem to be related to the immunomodulatory properties of stem cells. We therefore believe that such an approach could be a starting point for translating the results to the human clinical practice in future.