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Around 20% of Hodgkin lymphoma (HL) patients are refractory to first-line therapy with ABVD (adriamycin-bleomycin-vinblastine-dacarbazine) or relapse after complete remission. Salvage regimens frequently have delayed courses or require dose-reduction because of haemotoxicity. We evaluated the IVOx (ifosfamide-etoposide-oxaliplatin) salvage regimen in terms of response rate, toxicity and stem-cell mobilization. Thirty-four patients with relapsed/refractory HL after anthracycline-containing chemotherapy prospectively received IVOx, consisting of ifosfamide (1500 mg/m(2) days 1-3), etoposide (150 mg/m(2) days 1-3) and oxaliplatin (130 mg/m(2) day 1). Patients <65 years old received high-dose therapy followed by autologous stem-cell transplantation (HDT-ASCT). Response was assessed by computed and positron-emission tomographies. Overall and complete response rates were 76% and 32%, respectively, after 2 cycles. Three episodes of febrile neutropenia occurred, and three patients required dose-reductions. Twenty-six patients underwent HDT-ASCT. With median follow-up at 5 years, the 5-year overall and event-free survival rates were 74% and 63%, respectively. IVOx is a well-tolerated outpatient regimen for relapsed HL, that does not hamper stem-cell mobilization, achieves good response rates and compares favourably with previously published salvage regimens., (© 2011 Blackwell Publishing Ltd.)

Context: Hereditary renal cancers (HRCs) comprise approximately 3-5% of renal cell carcinomas (RCCs)., Objective: Our aim was to provide an overview of the currently known HRC syndromes in adults., Evidence Acquisition: Data on HRC syndromes were analysed using PubMed and Online Mendelian Inheritance in Man with an emphasis on kidney cancer, clinical criteria, management, treatment, and genetic counselling and screening., Evidence Synthesis: Ten HRC syndromes have been described that are inherited with an autosomal dominant trait. Eight genes have already been identified (VHL, MET, FH, FLCN, TSC1, TSC2, CDC73, and SDHB). These HRC syndromes involve one or more RCC histologic subtypes and are generally bilateral and multiple. Computed tomography and magnetic resonance imaging are the best imaging techniques for surveillance and assessment of renal lesions, but there are no established guidelines for follow-up after imaging. Except for hereditary leiomyomatosis RCC tumours, conservative treatments favour both an oncologically effective therapeutic procedure and a better preservation of renal function., Conclusions: HRC involves multiple clinical manifestations, histologic subtypes, genetic alterations, and molecular pathways. Urologists should know about HRC syndromes in the interest of their patients and families., (Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Immunocompromised patients with influenza are at higher risk of pneumonia and death. However, risk factors for progression to pneumonia still need evaluation., Methods: Retrospective study in immunocompromised patients with influenza-related respiratory infections. Risk factors for pneumonia were identified by multivariable logistic regression., Results: We identified 100 immunocompromised patients infected with influenza (68 hematological malignancies, 11 HIV, 21 iatrogenic immunosuppression). Immunofluorescence was positive in 95% of patients, mainly on nasopharyngeal aspirates (84%). Influenza A virus was involved in 80% of patients. Associated infection was documented in 34 patients. All patients presented with upper respiratory tract infection and 53 progressed to pneumonia. Thirty-two patients were critically ill, 11 received mechanical ventilation, and 10 died. All the patients who died had pneumonia. Patients with pneumonia were older (46y (36-63) vs. 33y (13-51), P=0.003) and more often had influenza A (89% vs. 70%, P=0.04) and associated infection (56% vs. 9%, P<0.0001). Factors independently associated with progression to pneumonia were influenza A (OR 5.54, 95% CI [1.16-26.47]) and hematological malignancies (OR 3.85, 95% CI [1.1-14.5])., Conclusions: In our cohort of hospitalized immunocompromised patients, influenza progresses to pneumonia in more than half the patients. Patients with hematological malignancies and influenza A infection are at higher risk for pneumonia and should be included in preemptive antiviral therapy trials., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Diffusion-weighted imaging is helpful to further characterize lesions that remain indeterminate after morphological and dynamic MR evaluation. Suspicious lesions are hyperintense on diffusion-weighted images with corresponding low ADC values, indicating restricted diffusion and hypercellularity. Benign lesions and tumors responding to treatment usually have no diffusion restriction. ADC maps are useful for T2W hyperintense lesions that could mask the presence of restricted diffusion. Image fusion is sometimes needed to accurately localize enhancing lesions on ADC maps. For indeterminate lesions, a hypocellular appearance suggests a lower ACR category whereas the presence of restricted diffusion suggests a higher category.

Angiogenesis is the process of activating dormant endothelial cells to form new vessels, after stimulation and it is essential in tumor growth. In many types of cancer, angiogenesis results from the activation of oncogenes that stimulate the production of Vascular Endothelial Growth Factor (VEGF). However, these newly formed vessels have a great number of abnormalities: increased density of fragile and hyper-permeable microvessels, arterial-venous shunts, caliber abnormalities and flow instabilities susceptible to flow direction inversion according to interstitial pressure. Anti-angiogenic treatments inhibit VEGF activity, perceived as structural and functional normalization of the microvascular pattern, such as reduced density of microvessels and restored morphology of the remaining ones. Conventional imaging techniques are not sensible to these changes, at best they show tumor size stabilization, hence the need of new techniques. Microvascularization imaging can be achieved by detecting functional disturbances to blood flow and not by showing the microvasculature per se. These techniques are based in quantifying the enhancement in tumor due to the passage of contrast agent after injection or protons labeled by a magnetic field. Through these measurements, one can derive interstitial and blood volumes as well as the tissue perfusion and capillary wall permeability. Microvascular imaging has greatly benefited from the improvements seen in CT and MRI equipment allowing large volume coverage with high spatial and temporal resolutions as from the evolutions in the methods to calculate, present and compare maps of the microcirculation and it's heterogeneity. However, software to analyze microvascularization are still rare, limiting the technique's application and validation in large scale. Nevertheless, imaging of the microcirculation is useful throughout the care of the oncological patient: it can reinforce the suspicious nature of a lesion, suggest anti-angiogenic treatment efficacy in hypervascular lesions, and show early treatment response before morphological changes as in RECIST criteria.

Purpose: To assess the value of whole body CTA, as a complement to head CTA, in the management of brain-dead patients as potential organ donors. Materials and Methods. A total of 27 consecutive brain-dead patients admitted in a center authorized in the harvesting of organs between October 2006 and January 2008 were included. The imaging protocol used was the protocol recommended by the French Society of Neuroradiology, with additional arterial phase helical acquisition of the chest, abdomen and pelvis, and parenchymal phase helical acquisition of the abdomen and pelvis. The imaging findings were then correlated to the surgical reports after organ harvesting., Results: CTA readily demonstrates tissue lesions, a contraindication to harvesting (14 cases, including one false positive), and anatomical variants of the vascular system (7 arterial variants and 3 venous variants) and liver (8 patients)., Conclusion: CTA, the gold standard paraclinical examination for brain death assessment, allows, in a single examination, the identification of contraindications to organ harvesting that may modify the surgical approach and even avoid unnecessary mobilisation of the transplant team. It may also provide valuable preoperative evaluation by detecting anatomical variants of the liver and kidneys.

Objective: We describe a coaxial introducer provided with an additional blunt-tip stylet that allows safe access to difficult-to-reach lymph nodes in the chest, abdomen, and pelvis under CT control., Conclusion: Once the thoracic, abdominal, or pelvic wall is crossed by the introducer fitted with the sharp-tip stylet, the blunt-tip stylet replaces the sharp stylet for further progression in the fat toward the target. The soft-tip stylet carries a smaller risk of inadvertent perforation displacing vital structures.

Objective: Using high resolution computed tomography (HRCT), to assess the lung involvement outcome after autologous hematopoietic stem cell transplant (AHSCT) in patients with scleroderma (systemic sclerosis, SSc)., Methods: HCRT scans prospectively performed before (n = 9 patients) and after (n = 47) AHSCT were blindly reviewed by 2 independent investigators using the Wells score., Results: After a median 60 months' followup, the overall disease extent score from HCRT scans decreased from 10 (0-45) to 4 (0-36) (p = 0.04) 6 months after AHSCT, and thereafter increased up to 36 months and stabilized; the modified Rodnan skin score fell (p < 0.05)., Conclusion: The extent of SSc lung involvement on HRCT rapidly but transiently regressed after AHSCT.

The law number 2005-370 of April 22, 2005, or "Leonetti law", is a very important law for patients' rights and management of the end of life. In spite of its importance, it seems to remain largely unknown to ordinary citizen and even health professionals. In this study, we evaluated the knowledge of this law among general practitioners from Isere (France), and looked at the best communication mode to channel information about the law. The analysis of the content of the 581 answers out of 1050 sent questionnaires (55,3%) confirms the poor knowledge about the law. General practitioners went through a self-evaluation about their knowledge: they estimate they had a rather low knowledge, with a median at 2 over 10. 23% had never heard about the law. Paradoxically, the objective evaluation of their knowledge gives more positive results (below 56,3% per question). However, their mistakes deal with important points of the law: traceability of decisions, trusted person, value of advanced directives, and collegial medical procedure. In addition to accompanying the patient and his family, the role of the general practitioner in respect to this law lies more specifically in helping patients who want to draft early directives or to designate a trusted person. In primary care, tough decisions concerning withholding or withdrawal of treatments should be made collaboratively.

Continuous labeling by flow-driven adiabatic inversion is advantageous for arterial spin labeling (ASL) perfusion studies, but details of the implementation, including inefficiency, magnetization transfer, and limited support for continuous-mode operation on clinical scanners, have restricted the benefits of this approach. Here a new approach to continuous labeling that employs rapidly repeated gradient and radio frequency (RF) pulses to achieve continuous labeling with high efficiency is characterized. The theoretical underpinnings, numerical simulations, and in vivo implementation of this pulsed continuous ASL (PCASL) method are described. In vivo PCASL labeling efficiency of 96% relative to continuous labeling with comparable labeling parameters far exceeded the 33% duty cycle of the PCASL RF pulses. Imaging at 3T with body coil transmission was readily achieved. This technique should help to realize the benefits of continuous labeling in clinical imagers., ((c) 2008 Wiley-Liss, Inc.)

Many of the regions with the earliest atrophy in Alzheimer's Disease (AD) do not show prominent deficits on functional imaging studies of flow or metabolism. This paradox may provide unique insights into the pathophysiology of AD. We sought to examine the relationship between function and atrophy in AD using MRI blood flow and anatomic imaging. 22 subjects diagnosed with AD, mean Mini Mental State Exam (MMSE) score 22.2, and 16 healthy elderly controls were imaged with a volumetric arterial spin labeling blood flow MRI technique and an anatomical imaging method using the identical spatial resolution, image orientation, and spatial encoding strategy. Cerebral blood flow (CBF) and gray matter (GM) maps derived from the imaging were transformed to a standard anatomical space. GM and CBF maps were tested for significant differences between groups. Additionally, images were tested for regions with significant mismatch of the CBF and GM differences between groups. CBF was significantly lower in the bilateral precuneus, parietal association cortex and the left inferior temporal lobe but was non-significantly increased in the hippocampus and other medial temporal structures. After correction for GM loss, CBF was significantly elevated in the hippocampus and other medial temporal structures. The hippocampus and other regions affected early in AD are characterized by elevated atrophy-corrected perfusion per cm(3) of tissue. This suggests compensatory or pathological elevation of neural activity, inflammation, or elevated production of vasodilators.

Purpose: To measure changes in tumor blood flow following treatment with PTK787/ZK 222584, a pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, and their association with clinical response in patients with metastatic renal cell carcinoma., Experimental Design: In 10 patients with metastatic renal cell carcinoma treated with PTK787/ZK 222584, tumor blood flow was evaluated by arterial spin labeling (ASL) magnetic resonance imaging before and 1 month on treatment. Changes in blood flow after 1 month of treatment were compared with bidimensional tumor response at 4 months of treatment using the Mann-Whitney test., Results: Changes in blood flow at 1 month and changes in tumor size measured at 4 months or at time of disease progression were significantly correlated (P=0.01). Patients with progressive disease within 4 months on treatment (n=4) had a nonsignificant increase in tumor blood flow at 1 month (+25+/-33%; P=0.43), whereas patients with stable disease or partial response at 4 months (n=6) had a significant decrease in tumor blood flow at 1 month (-42+/-22%; P=0.02)., Conclusion: These results suggest that decreasing tumor blood flow with PTK787/ZK 222584 therapy, as shown as soon as 1 month on therapy by ASL, may predict for a favorable clinical outcome. These data are consistent with a hypothetical functional role for tumor ischemia in the mechanism of response to anti-vascular endothelial growth factor therapy. ASL blood flow magnetic resonance imaging shows promise as an early predictor of clinical response to antiangiogenic therapies.

Malignant lymphomas are lymphoproliferative disorders arising in both lymphoid tissue and non-lymphoid organ systems. Treatment rarely is surgical, and currently relies on a combination of chemotherapy and radiation therapy. The role of imaging is to determine the spread of the disease, to identify targets and to assess therapeutic response. Imaging techniques mainly use morphological criteria, and may underestimate infiltrative disease, as observed in bones. The frequent presence of residual masses after treatment usually prevents classification of patients as complete response. Over time, positron emission tomography (PET) with F18-fluorodeoxyglucose (FDG) has become a prominent part of the workup at diagnosis and during follow-up. Recently, PET has been integrated in the revised response criteria for malignant lymphoma.

Objective: The aim of this study was to evaluate the regional effects of type 2 diabetes and associated conditions on cerebral tissue volumes and cerebral blood flow (CBF) regulation., Research Design and Methods: CBF was examined in 26 diabetic (aged 61.6 +/- 6.6 years) and 25 control (aged 60.4 +/- 8.6 years) subjects using continuous arterial spin labeling (CASL) imaging during baseline, hyperventilation, and CO2 rebreathing. Regional gray and white matter, cerebrospinal fluid (CSF), and white matter hyperintensity (WMH) volumes were measured on a T1-weighted inversion recovery fast-gradient echo and a fluid attenuation inversion recovery magnetic resonance imaging at 3 Tesla., Results: The diabetic group had smaller global white (P = 0.006) and gray (P = 0.001) matter and larger CSF (36.3%, P < 0.0001) volumes than the control group. Regional differences were observed for white matter (-13.1%, P = 0.0008) and CSF (36.3%, P < 0.0001) in the frontal region, for CSF (20.9%, P = 0.0002) in the temporal region, and for gray matter (-3.0%, P = 0.04) and CSF (17.6%, P = 0.01) in the parieto-occipital region. Baseline regional CBF (P = 0.006) and CO2 reactivity (P = 0.005) were reduced in the diabetic group. Hypoperfusion in the frontal region was associated with gray matter atrophy (P < 0.0001). Higher A1C was associated with lower CBF (P < 0.0001) and greater CSF (P = 0.002) within the temporal region., Conclusions: Type 2 diabetes is associated with cortical and subcortical atrophy involving several brain regions and with diminished regional cerebral perfusion and vasoreactivity. Uncontrolled diabetes may further contribute to hypoperfusion and atrophy. Diabetic metabolic disturbance and blood flow dysregulation that affects preferentially frontal and temporal regions may have implications for cognition and balance in elderly subjects with diabetes.

It is commonly admitted that the diagnosis of lymphomas can be assessed by the image-guided needle biopsy (IGNB) of deep lymph nodes. However, when peripheral lymph nodes are present, surgical dissection remains the standard strategy. The aim of this study was to evaluate the diagnostic yield of IGNB of peripheral lymph nodes in patients with suspected lymphomas. The records of 180 multisampling IGNBs of peripheral lymph nodes in 180 patients were reviewed. One hundred and twenty-three IGNBs were observed at first diagnosis and 57 at progression using large-cutting core-biopsy needles ranging between 18 G and 14 G in size. Immunohistochemistry studies were performed in all cases and at least one biopsy was systematically frozen. A diagnosis of lymphoma with sufficient information such that a therapeutic decision could be made was obtained in 146 of the 152 patients with lymphoproliferative disorders (96%). IGNB was equally effective in making the correct diagnosis of lymphoma at the time of original diagnosis than at relapse. The results did not depend on the biopsy site, lymph nodes size, or needle type. We recommend that IGNB may be performed as an initial procedure for the diagnosis of lymphomas either in the presence of peripheral or deep lymph nodes, as it avoids surgery.

Background: High-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) remain controversial for indolent lymphoma patients., Methods: The study was designed to evaluate the benefit of this strategy by retrospectively comparing for each patient the event-free survival (EFS) after ASCT with the duration of the disease phase just before the phase including ASCT (ie, the last qualifying phase, LQP)., Results: A total of 109 indolent lymphoma (mostly follicular lymphoma) patients were treated with HDT and ASCT. Before ASCT, patients experienced a median of 2 disease phases (range, 1-4). After a median 5-year follow-up from ASCT, overall survival was 67% and EFS was 43%. When each of the 92 patients experiencing recurrence was taken as her/his own control, EFS was longer after ASCT than the duration of LQP (62%, P < .01). During LQP, 86 patients (93%) experienced recurrence in less than 5 years, compared with only 58 (63%) who experienced recurrence in the 5 years after ASCT (P < .01)., Conclusion: HDT and ASCT can significantly increase EFS in comparison with the duration of the LQP for indolent lymphoma patients and can change disease course. This methodology has been found useful for evaluating new strategies, especially with monoclonal antibodies., ((c) 2006 American Cancer Society.)

This study analyzed the T2* effect of extracellularly distributed gadolinium contrast agents in arterial blood during tumor studies using T1-weighted sequences at high field strength. A saturation-prepared dual echo sequence with echo times of 1.5 and 3.5 ms was employed at 3 T to simultaneously characterize T1 and T2* of arterial blood during bolus administration of Gd-DTPA in 28 patients with body tumors. T2* effect and T1 effect of Gd-DTPA on image intensity of whole blood were calibrated in human blood samples with different concentrations of contrast agent. T2* was used to estimate concentration near the peak of the bolus. T1 was used to measure lower concentrations when T2* was not significant. T2* was measurable on calibration curves for Gd-DTPA concentrations higher than 4 mM. This concentration was exceeded in 18 patients. The mean signal intensity reduction because of T2* effect was estimated at 22+/-14% of the T2* compensated signal. Using T2* measurements reduced underestimations of peak arterial Gd-DTPA concentration (59 +/- 38%) and overestimation of permeability Ktrans (58%). The T2* effect of gadolinium contrast agents should therefore be accounted for when performing tumors study with T1-weighted sequences at high field strength.

To present a new compartmental analysis model developed to simultaneously measure tissue perfusion and capillary permeability in a tumor using MRI and a macromolecular contrast medium. Rhadomyosarcomas were implanted subcutaneously in 20 rats and studied by 1.5-T MRI using a fast gradient echo sequence (2D fast SPGR TR/TE/alpha 13 ms/1.2 ms/60 degrees ) after injection of a macromolecular contrast medium. The left ventricle and tumor signal intensities were converted into concentrations and modeled using compartmental analysis, yielding tumor perfusion F, distribution volume Vdistribution, volume transfer constant Ktrans, rate constant of influx kpe, and initial extraction (fraction) E. Tumor perfusion was F=43+/-29 ml.min-1.100 g-1. The permeability study allowed the measurement of kpe=0.37+/-0.12 min-1 and Ktrans=0.01+/-0.0031 min-1. The blood volume could be assimilated to the distribution volume (Vdistribution=2.9+/-1.01%) since the capillary leakage was small. The simultaneous assessment of perfusion and permeability allowed quantification of the initial extraction (fraction) E=2.34+/-1.05%. Quantification of both tumor perfusion and capillary leakage is feasible using MRI using a macromolecular blood pool agent. The method should improve tumor characterization.

It is now accepted that MR imaging does not present any biological risk for humans, even in cases of repeated exposure. However, several of the MR components (magnetic field, gradients, RF pulses, electrodes...) may cause some inconveniences to patients, most of them being reversible. However, severe accidents have been reported. Even though screening of patients for MR imaging eligibility is performed to identify patients with contra-indications to MRI, the lack of vigilance or the ignorance of certain basic safety requirements could lead to serious adverse effects, including death. The goal of this article is to review the various accidents reported with MRI, to explain their mechanism, and to describe means of prevention.

Rationale and Objective: This study sought to assess the feasibility of arterial spin labeling (ASL) blood flow (BF) magnetic resonance imaging (MRI) for the study of metastatic renal cell carcinoma (RCC) in the body, where the respiratory, cardiac, and peristaltic motions present challenges when applying ASL., Materials and Methods: ASL was performed using a background-suppressed single-section flow-alternating inversion recovery (FAIR) preparation and a single-shot fast spin-echo imaging sequence on a 3.0-T whole body imager. Tumor BF was evaluated for 26 patients with RCC metastatic to the liver, bone, lung, or lymph nodes before VEGF receptor inhibitor therapy. Two cases with tumor size change after treatment were also scanned 1 month after therapy. For validation, kidney cortex BF in five normal volunteers was measured with the same technique and compared with literature values., Results: ASL was successfully performed in all normal volunteers and in 20 of 26 patients. The six failures resulted from a systematic error, which can be avoided in future studies. For normal volunteers, measured kidney cortex BF was 275 +/- 14 mL/min/100 g, a value consistent with the literature. ASL determined tumor BF averaged across tumor volume and subjects was 194 mL/min/100 g (intersubject SD = 100), resulting in high perfusion signal and conspicuity of lesions. Bright signal was also seen in large vessels and occasionally in bowel. In the two cases studied 1 month after therapy, ASL perfusion changes were consistent with tumor size changes., Conclusion: With background suppression, ASL MRI is a feasible method for quantifying BF in patients with renal cell carcinoma. This technique may be useful for evaluating tumor response to antiangiogenic agents.

Macromolecular contrast-enhanced functional CT was performed to characterize early perfusion changes in hepatocellular carcinoma (HCC). Fourteen rats with chemically induced primary liver tumors ranging pathologically from hyperplasia to HCC and 15 control rats were investigated. Two dynamic CT scans using an experimental macromolecular contrast agent were performed on a single slice 11 and 18 weeks after tumor induction followed by pathological examination. A deconvolution mathematical model was applied, yielding the hepatic perfusion index (HPI), mean transit time (MTT), liver distribution volume (LDV) and arterial, portal and total blood flows (FA, FP, FT). Analysis was performed on one slice per rat, containing overall two hyperplasia, six dysplasia and 15 HCC. On the first scans, HCC at an early pathological stage had a low FP (-30%, P=0.002) but a normal arterial-portal balance. On the scan contemporary to pathology, HCC perfusion parameters showed an inversion of the arterial-portal balance (HPI +212%, P<0.0001), with a high FA (+56%, P=0.002) and a low FP (-69%, P<0.0001). Sensitivity and specificity of detection of HCC by perfusion CT were high (87 and 80%) on late scans; but also on the earlier scans (86 and 65%), even though only one (7%) was visible to the eye. Perfusion-CT allowed early detection of HCC. This technique could contribute in the detection and characterization of liver lesions in clinical studies.