François Jamar

Magnetic Resonance Imaging of the Axial Skeleton for Detecting Bone Metastases in Patients With High-Risk Prostate Cancer: Diagnostic and Cost-Effectiveness and Comparison With Current Detection Strategies

PURPOSE To evaluate the diagnostic performance, costs, and impact on therapy of one-step magnetic resonance imaging (MRI) of the axial skeleton (MRIas) for detecting bone metastases in patients with high-risk prostate cancer (PCa). PATIENTS AND METHODS Sixty-six consecutive patients with high-risk PCa prospectively underwent MRIas in addition to the standard sequential work-up (SW) of bone metastases (technetium-99m bone scintigraphy [BS] completed with targeted x-rays [TXR] in patients with equivocal BS findings and with MRI obtained on request [MRIor] in patients with inconclusive BS/TXR findings). Panel review of initial and 6-month follow-up MRI findings, BS/TXR, and all available baseline and follow-up clinical and biologic data were used as the best valuable comparator to define metastatic status. Diagnostic effectiveness of MRIas alone was compared with each step of the SW. Impact of MRIas screening on patient management and costs was evaluated. RESULTS On the basis of the best valuable comparator, 41 patients (62%) had bone metastases. Sensitivities were 46% for BS alone, 63% for BS/TXR, 83% for BS/TXR/MRIor, and 100% for MRIas; the corresponding specificities were 32%, 64%, 100%, and 88%, respectively. MRIas was significantly more sensitive than any other approach (P < .05, McNemar). MRIas identified metastases in seven (30%) of 23 patients considered negative and eight (47%) of 17 patients considered equivocal by other strategies, which altered the initially planned therapy. Economic impact was variable among countries, depending on reimbursement rates. CONCLUSION MRIas is more sensitive than the current SW of radiographically identified bone metastases in high-risk PCa patients, which impacts the clinical management of a significant proportion of patients.

Can Whole-body Magnetic Resonance Imaging with Diffusion-weighted Imaging Replace Tc 99m Bone Scanning and Computed Tomography for Single-step Detection of Metastases in Patients with High-risk Prostate Cancer?

BACKGROUND Technetium Tc 99m bone scintigraphy (BS) and contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of the pelvis and abdomen are universally recommended for detecting prostate cancer (PCa) metastases in cancer of all stages. However, this two-step approach has limited sensitivity and specificity. OBJECTIVE Evaluate the diagnostic accuracy of whole-body MRI (WBMRI) as a one-step screening test for PCa metastases. DESIGN, SETTING, AND PARTICIPANTS One hundred consecutive PCa patients at high risk for metastases prospectively underwent WBMRI, CT, and BS completed with targeted x-rays (BS/TXR) in case of equivocal BS. Four independent reviewers reviewed the images. MEASUREMENTS This study compares the diagnostic performance of WBMRI, CT, BS, and BS/TXR in detecting PCa metastases using area under the curve (AUC) receiver operator characteristics. A best valuable comparator (BVC) approach was used to adjudicate final metastatic status in the absence of pathologic evaluation. RESULTS AND LIMITATIONS Based on the BVC, 68 patients had metastases. The sensitivity of BS/TXR and WBMRI for detecting bone metastases was 86% and 98-100%, respectively (p<0.04), and specificity was 98% and 98-100%, respectively. The first and second WBMRI readers respectively identified bone metastases in 7 and 8 of 55 patients with negative BS/TXR. The sensitivity of CT and WBMRI for detecting enlarged lymph nodes was similar, at 77-82% for both; specificity was 95-96% and 96-98%, respectively. The sensitivity of the combination of BS/TXR plus CT and WBMRI for detecting bone metastases and/or enlarged lymph nodes was 84% and 91-94%, respectively (p=0.03-0.10); specificities were 94-97% and 91-96%, respectively. The 95% confidence interval of the difference between the AUC of the worst WBMRI reading and the AUC of any of the BS/TXR plus CT lay within the noninferiority margin of ±10% AUC. CONCLUSIONS WBMRI outperforms BS/TXR in detecting bone metastases and performs as well as CT for enlarged lymph node evaluation. WBMRI can replace the current multimodality metastatic work-up for the concurrent evaluation of bones and lymph nodes in high-risk PCa patients.

Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity

Significance Alcohol-dependent subjects frequently develop emotional symptoms that contribute to the persistence of alcohol drinking. These subjects are also characterized by gastrointestinal disturbances. In this study, we showed that alcohol-dependent subjects with altered intestinal permeability had also altered gut-microbiota composition and activity and remained with high scores of depression, anxiety, and alcohol craving after a short-term detoxification program. These results are consistent with the existence of a gut–brain axis in alcohol dependence, in which the gut microbiota could alter the gut-barrier function and influence behavior in alcohol dependence. Therefore, this study opens a previously unidentified field of research for the treatment and the management of alcohol dependence, targeting the gut microbiota. Alcohol dependence has traditionally been considered a brain disorder. Alteration in the composition of the gut microbiota has recently been shown to be present in psychiatric disorders, which suggests the possibility of gut-to-brain interactions in the development of alcohol dependence. The aim of the present study was to explore whether changes in gut permeability are linked to gut-microbiota composition and activity in alcohol-dependent subjects. We also investigated whether gut dysfunction is associated with the psychological symptoms of alcohol dependence. Finally, we tested the reversibility of the biological and behavioral parameters after a short-term detoxification program. We found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol craving after 3 wk of abstinence, which may be important psychological factors of relapse. Moreover, subjects with increased gut permeability also had altered composition and activity of the gut microbiota. These results suggest the existence of a gut–brain axis in alcohol dependence, which implicates the gut microbiota as an actor in the gut barrier and in behavioral disorders. Thus, the gut microbiota seems to be a previously unidentified target in the management of alcohol dependence.

EANM/SNMMI Guideline for 18F-FDG Use in Inflammation and Infection

1Department of Nuclear Medicine, Universite Catholique de Louvain, Brussels, Belgium; 2Department of Nuclear Medicine, Cambridge Biomedical Campus, Cambridge, United Kingdom; 3Nuclear Medicine, Istituto Clinico Humanitas, Milan, Italy; 4Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah; 5Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee; 6Department of Nuclear Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; 7Department of Nuclear Medicine, Rambam Health Care Campus, Haifa, Israel; 8Nuclear Medicine Department, Hospital Universitario de Bellvitge, Barcelona, Spain; and 9Nuclear Medicine Unit, Faculty of Medicine and Psychology, University “Sapienza,” Rome, Italy

Inadequate detection of accessory spleens and splenosis with laparoscopic splenectomy. A shortcoming of the laparoscopic approach in hematologic diseases

AbstractBackground: The ultimate goal of surgery for hematological disorders is the complete removal of both the spleen and accessory spleens in order to avoid recurrence of the disease. Whereas splenectomy by open surgery provides excellent results, the validity of laparoscopic splenectomy in this regard remains unknown. Objective: The purpose of this study was to evaluate the detection of accessory spleens during laparoscopic splenectomy for hematologic diseases. Methods: We therefore evaluated the pre-, intra-, and postoperative detection of accessory spleens in a consecutive series of 18 patients treated by elective laparoscopic splenectomy for hematological diseases by using computed tomography (CT) and denatured red blood cell scintigraphy (DRBCS). Results: Preoperative CT, DRBCS, and laparoscopic exploration detected 25%, 25%, and 75% of accessory spleens, respectively. At time of laparoscopy, 16 accessory spleens were detected in seven of the 18 patients (41%). In two patients (11%), laparoscopic exploration failed to detect accessory spleens, whereas preoperative CT (one case) and DRBCS (one case) did reveal them. Postoperatively, during a mean follow-up of 28 months (median, 24; range, 12–44 months), nine patients (50%) showed persistence of splenic tissue by DRBCS, and three of them had signs of disease recurrence. Conclusions: This prospective clinical study suggests that elective laparoscopic surgery for hematological diseases does not allow complete detection of accessory spleens. Moreover, after such a laparoscopic approach, residual splenic tissue is detectable in half of the patients during the follow-up.

Yttrium-90 TOF PET scan demonstrates high-resolution biodistribution after liver SIRT

The decay of Y has a minor branch to the 0 excited state [1], followed by an internal ee creation which happens in 32 out of one million decays [2]. Consequently, Y PET scan was proposed in order to assess the biodistribution [3] of Y-labelled therapeutic agents. A 61-year-old woman was referred for treatment of chemorefractory colorectal liver metastasis. Based on the pretreatment evaluation (including a diagnostic FDG PET/CT scan on day 1, and a prophylactic embolization of the right gastric and gastroduodenal arteries followed by a Tc-MAA SPECT/CT scan on day 8), 1.3 GBq of Y-labelled SIR-Spheres were administered by sequential catheterization of both liver lobes (day 15). Subsequently, a 30-min Y TOF PET/CT scan was performed using a Philips GEMINI TF camera. In order to prevent saturation of the detectors, a copper ring of 2.5 mm thickness was inserted into the gantry to absorb the bremsstrahlung x-rays. The TOF data were reconstructed with attenuation and scatter correction using Philips RAMLA software (eight iterations, three subsets). An additional 20 min bremsstrahlung Y-SPECT was acquired using a Trionix XLT20 triple head camera (medium energy collimator, 30% window centred on 90 keV). Data were reconstructed using OSEM (four iterations, six subsets). As illustrated, despite the differences in their respective uptake mechanism, Y-PET better reflects the tumour heterogeneity assessed by FDG PET/CT (a necrotic core surrounded by active tumour margins) than traditional bremsstrahlung Y-SPECT. This gain in resolution should therefore contribute to increasing the accuracy of the dose distribution into the tumours and their surrounding healthy tissues.

Glomerular filtration rate: assessment with dynamic contrast-enhanced MRI and a cortical-compartment model in the rabbit kidney.

To describe the use of MRI and a cortical‐compartment model to measure the glomerular filtration rate (GFR), and compare the results with those obtained with the Patlak‐Rutland model.

Feasibility of 90Y TOF PET-based dosimetry in liver metastasis therapy using SIR-Spheres

Purpose90Y-labelled compounds used in targeted radiotherapy are usually imaged with SPECT by recording the bremsstrahlung X-rays of the β decay. The continuous shape of the X-ray spectrum induces the presence of a significant fraction of scatter rays in the acquisition energy window, reducing the accuracy of biodistribution and of dosimetry assessments.MethodsThe aim of this paper is to use instead the low branch of e− e+ pair production in the 90Y decay. After administration of 90Y-labelled SIR-Spheres by catheterization of both liver lobes, the activity distribution is obtained by 90Y time-of-flight (TOF) PET imaging. The activity distribution is convolved with a dose irradiation kernel in order to derive the regional dosimetry distribution.ResultsEvaluation on an anatomical phantom showed that the method provided an accurate dosimetry assessment. Preliminary results on a patient demonstrated a high-resolution absorbed dose distribution with a clear correlation with tumour response.ConclusionThis supports the implementation of 90Y PET in selective internal radiation therapy of the liver.

Role of intestinal permeability and inflammation in the biological and behavioral control of alcohol-dependent subjects

BACKGROUND AND AIMS Mood and cognition alterations play a role in the motivation for alcohol-drinking. Lipopolysaccharides are known to stimulate inflammation that was shown to induce mood and cognitive changes in rodents and humans. Enhanced intestinal permeability and elevated blood LPS characterize alcohol-dependent mice. However, no data have been published in non-cirrhotic humans. Our first goal was to test whether intestinal permeability, blood LPS and cytokines are increased in non-cirrhotic alcohol-dependent subjects before withdrawal and if they recover after withdrawal. Our second goal was to test correlations between these biochemical and the behavioral variables to explore the possibility of a role for a gut-brain interaction in the development of alcohol-dependence. METHODS Forty alcohol-dependent-subjects hospitalized for a 3-week detoxification program were tested at onset (T1) and end (T2) of withdrawal and compared for biological and behavioral markers with 16 healthy subjects. Participants were assessed for gut permeability, systemic inflammation (LPS, TNFα, IL-6, IL-10, hsCRP) and for depression, anxiety, alcohol-craving and selective attention. RESULTS Intestinal permeability and LPS were largely increased in alcohol-dependent subjects at T1 but recovered completely at T2. A low-grade inflammation was observed at T1 that partially decreased during withdrawal. At T1, pro-inflammatory cytokines were positively correlated with craving. At T2 however, the anti-inflammatory cytokine IL-10 was negatively correlated with depression, anxiety and craving. CONCLUSION Leaky gut and inflammation were observed in non-cirrhotic alcohol-dependent subjects and inflammation was correlated to depression and alcohol-craving. This suggests that the gut-brain axis may play a role in the pathogenesis of alcohol-dependence.

OctreoTherTM: Ongoing Early Clinical Development of a Somatostatin-Receptor-Targeted Radionuclide Antineoplastic Therapy

OctreoTherTM (90Y-DOTA-D-Phe1-Tyr3-octreotide, a.k.a. 90Y-SMT 487) consists of a somatostatin peptide analogue (Tyr3-octreotide), coupled with a complexing moiety (DOTA), and labeled with a tightly bound beta-emitter (yttrium-90). By targeting somatostatin receptor-positive tumors (as imaged by OctreaScan®) it may deliver a tumoricidal dose of radiation. Phase I clinical trials, conducted in patients with neuroendocrine tumors, established the safety and tolerability of the dose selected for further study and demonstrated the capacity of OctreoTher to deliver radiation doses to tumors that resulted in significant neuroendocrine tumor shrinkage. Novartis-sponsored phase II studies will soon begin to test the efficacy of OctreoTher in breast and small cell lung cancer. A fixed-dose regimen of 120 mCi/cycle × 3 cycles administered with concomitant amino acid infusion has been chosen for the study. Phase I data and published literature support that this fixed dose regimen will be safely tolerated.