Search

We retrospectively assessed the longitudinal changes of rheumatoid arthritis under rituximab therapy by use of quantitative and dynamic contrast-enhanced 3-T magnetic resonance (MR) imaging of the metacarpophalangeal joints of 10 patients at baseline and 26 weeks (n = 10). Additional studies were available at 12 weeks (n = 9) and at 52 weeks (n = 5). Clinical activity was assessed by use of the 28-joint disease activity score (DAS28). MR imaging was used to assess volumes of synovial enhancement, osseous enhancement, and erosions and early rapid enhancement. DAS28 and serum C-reactive protein trended down over time and were significantly lower at 26 weeks. Volume of synovial enhancement and early rapid enhancement showed a significant minimum at 26 weeks and increased thereafter. The erythrocyte sedimentation rate paralleled these two trends. Osseous enhancement did not significantly change over time. Erosions showed a significant progression. Trends of DAS28 and erosions were significantly different (P = 0.0075). In conclusion, our preliminary results suggest that rituximab is associated with a decrease of the inflammatory activity of synovitis with a minimum at 26 weeks and increasing activity thereafter suggesting recurrence. Our results further suggest subclinical progression of erosions with an inverse relationship to decreasing disease activity scores. Further studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

The CT and MRI scans of a 70-year-old male patient revealed a mass in the pancreatic head and a 2.8-cm peripancreatic lymph node. Under steroid therapy the mass did not show regression. Finally, a pancreatoduodenectomy was performed. Histologically, Rosai-Dorfman disease (RDD) was diagnosed. RDD is a rare histiocytic disorder with usually nodal but sometimes also extranodal involvement. Herein we report a rare case of extranodal RDD with intrapancreatic localization.

Aim: To compare the diagnostic value of liver perfusion computed tomography (PCT) and biphasic contrast-enhanced CT (bpCECT) for detection and characterization of hepatocellular carcinoma (HCC), and to identify potential causes for inter-modal discrepancies., Patients and Methods: In this retrospective study, 162 cases with a total of 325 HCC-typical lesions were evaluated using both PCT and bpCECT (mean time between examinations=15 days, range=0-13 days). HCC diagnosis was performed by multi-modality imaging including lesion growth at follow-up. For PCT, a total acquisition time of 40 s (26 measurements) each 1.5 s using 80 kV and 100 mAs, as well as 50 ml iodine contrast agent (at 5 ml/s) covering the entire liver was used. Mean arterial liver perfusion (ALP), portal venous perfusion (PVP) and hepatic arterial index (HPI) for both tumor and non-involved liver parenchyma; mean blood flow, blood volume and k-trans for tumor were quantified. Tumor localization, and size were registered. bpCECT consisted of unenhanced, arterial (30-33 s delay), and portal-venous (70-75 s) phases performed using 120 kV, 200-250 mAs, thin-slice reformates (<1 mm), 100 ml contrast agent (at 3 ml/s) followed by 50 ml saline flush. Finally, we divided the results according to detection by PCT only (i.e. missed by pbCECT), and by both PCT and pbCECT., Results: PCT detected 272 lesions compared to 217 with bpCECT only. HCCs in liver segments 4 and 5 were significantly better detected by PCT (p<0.005). Furthermore, PCT detected significantly smaller HCCs than did bpCECT (p<0.001). Lesions detected by both methods had significantly higher mean ALP (p=0.03) and HPI (p=0.02), and lower mean PVP (p=0.01). Tumor blood flow, blood volume and k-trans proved not to be significant for lesion detection. The mean ALP, HPI, and PVP in inconspicuous cirrhotic liver were also not significant for lesion detection. The PVP (tumor) /HPI (liver) ratio of detected lesions was significantly higher for PCT alone (p=0.04). Pretreated, still vital lesions were better detected by bpCECT., Conclusion: Detection of smaller HCC lesions, lesions located in liver segments 4 and 5, as well as lesions presenting lower ALP and HPI, and higher PVP (tumor) /HPI (liver) ratio was better using both methods, emphasizing the important role of PCT., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: The aim of this study was to compare the performance of 2 approved computer-aided detection (CAD) systems for detection of pulmonary solid nodules (PSNs) in an oncologic cohort. The first CAD system is based on a conventional machine learning approach (VD10F), and the other is based on a deep 3D convolutional neural network (CNN) CAD software (VD20A)., Methods and Materials: Nine hundred sixty-seven patients with a total of 2451 PSNs were retrospectively evaluated using the 2 different CAD systems. All patients had thin-slice chest computed tomography (0.6 mm) using 100 kV and 100 mAs and a high-resolution kernel (I50f). The CAD images generated by VD10F were transferred to the PACS for evaluation. The images generated by VD20A were evaluated using a Web browser-based viewer. Finally, a senior radiologist who was blinded for the CAD results examined the thin-slice images of every patient (ground truth)., Results: A total of 2451 PSNs were detected by the senior radiologist. CAD-VD10F detected 1401 true-positive, 143 false-negative, 565 false-positive (FP), and 342 true-negative PSNs, resulting in sensitivity of 90.7%, specificity of 37.7%, positive predictive value of 0.71, and negative predictive value of 0.70. CAD-VD20A detected 1381 true-positive, 163 false-negative, 337 FP, and 570 true-negative PSNs, resulting in sensitivity of 89.4%, specificity of 62.8%, positive predictive value of 0.80, and negative predictive value 0.77, respectively. The rate of FP per scan was 0.6 for CAD-VD10F and 0.3 for CAD-VD20A., Conclusions: The new deep learning-based CAD software (VD20A) shows similar sensitivity with the conventional CAD software (VD10F), but a significantly higher specificity., Competing Interests: Conflicts of interest and sources of funding: M.S.H. has received institutional research support from Siemens Healthineers Germany and GE USA. He is a scientific advisor of Siemens Healthineers Germany and has received speaker’s honorarium from Siemens Healthineers Germany and GE USA. R.G. is an employee of Siemens Healthcare AG, Germany. For the remaining authors, none were declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Longitudinal assessment of changes in apparent diffusion coefficient (ADC)-values in multiple myeloma (MM) patients and their potential role for classifying disease activity., Methods: Retrospective analysis of whole-body-MRI data in 73 stage III MM patients undergoing systemic treatment. Bone marrow involvement was evaluated using a standardized unenhanced 4-sequences whole-body-MRI protocol. We measured ADC-values in focal lesions (FL) and diffusely involved bone marrow (DIBM) areas. Response to treatment was based on the course of hematologic parameters. The time points of MRI-examinations were baseline, 1st (mean, 3 months), 2nd (mean, 10 months), and 3rd (mean, 18 months) follow up (FU)., Results: Mean IgG and IgA serum values at baseline were 2.1 mg/dl and 1.8 mg/dl, respectively. Patients were classified into responders (n = 59) and non-responders (n = 34). Some patients were re-enrolled for new treatment regimens as they became therapy-refractory. Patterns of medullary involvement were focal (n = 44), diffuse (n = 61) and mixed (n = 30). In FL, a subgroup of myeloma patients undergoing short-term 1st FU experienced a significant increase in ADC in responders (p = 0.001), but not in non-responders (p = 0.9). In the further course of the study, ADC levels decreased continuously in responders (p = 0.02) and increased slightly in non-responders (p = 0.8). In patients with DIBM, ADC values decreased in the responders (p < 0.001) and in the non-responders (p = 0.78). An ADC cut-off value of 0.5-0.6 × 10 -3  mm 2 /s for diagnosing inactive disease at follow-up proved unreliable., Conclusions: In myeloma-patients with lower tumor burden, the longitudinal course of ADC-values is predictable only for FL whereas for DIBM ADC-changes considerably overlap between responders and non-responders and are not indicative for assessment of the disease activity., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The undifferentiated embryonic sarcoma of the liver (UESL) is a rare, aggressive tumor mainly affecting children. Since UESL has no specific clinical symptoms or imaging characteristics, many cases of UESL are diagnosed late. The paraneoplastic leukemoid reaction (PLR) is a very rare concomitant of oncological patients associated with poor prognosis. This report describes the clinical course of a patient combining these two rare entities and describes the diagnostic challenges and dynamics of paraneoplastic syndrome., Case Presentation: We report a case of UESL in a 46-year-old male who became clinically conspicuous due to pronounced B symptoms. CT and MRI showed a suspicious unifocal liver lesion. As the histological analysis of a tissue sample did not reveal a clear result, an 18F-FDG-PET-CT examination was performed. In addition to a high glucose metabolism of the liver lesion, an increased glucose metabolism in the entire bone marrow was observed. This finding was considered as pronounced paraneoplasia and laparotomy with liver segment resection followed. Immediately after resection of the tumor the paraneoplastic symptoms completely declined and the patient showed no signs of recurrence in the 1-year follow-up., Conclusions: Although UESL is rare and predominantly affects children, this diagnosis should always be considered for unclear unifocal cystic liver lesions, regardless of the patient's age, as appropriate treatment has a good prognosis.

Purpose:  The purpose of this study was to analyze imaging findings in hepatic epithelioid hemangioendothelioma (HEHE) with a particular focus on contrast-enhanced ultrasound (CEUS)., Materials and Methods:  This retrospective multicenter study included 10 patients with histologically proven HEHE from 5 European centers. All existing ultrasound images/videos were independently analyzed by 2 experienced examiners (DEGUM level III, internal medicine) using a standardized evaluation form. Patterns of contrast enhancement were correlated with computed tomography (CT), magnetic resonance imaging (MRI), and pathological findings., Results:  B-mode ultrasound, CEUS, CT, and MRI were performed in 90 %, 70 %, 100 %, and 90 % of patients, respectively. Multifocal HEHE could be observed in 80 % with affection of both liver lobes in 70 %. Analysis of CEUS revealed 3 characteristic patterns that correlated well with contrast patterns on CT and MRI: (a) peripheral nodular enhancement with centripetal fill-in and wash-out in the portal venous and late venous phase (PVLP), (b) rim-like arterial enhancement with wash-out in the PVLP, and (c) inversed target sign with/without wash-out in the PVLP. Wash-out in the PVLP as a sign suspicious of malignancy was observed in 6/7 patients (85.7 %)., Conclusions:  Knowledge of the different characteristic CEUS patterns is of importance to avoid misdiagnosis due to resemblance of patterns A and B to the much more common focal liver lesions hemangioma and intrahepatic cholangiocarcinoma. Of importance, sonographers should be aware that wash-out in the PVLP might be absent in some patients., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Development of diffuse large B-cell lymphoma in chronic lymphocytic leukemia, so-called Richter transformation (RT), occurs in 2-5% of patients and is associated with poor outcome. The clinical features of RT are fairly non-specific and unable to discriminate transformation from other mimics. In case of clinically suspected RT, a CT/MRT is recommended, and FDG-PET/CT may help to select the site of biopsy. Radiological features suggestive of RT have been defined, but there are only limited data about their predictive value, and histological confirmation is still considered the gold standard for RT diagnosis. We retrospectively analyzed 34 patients with clinically suspected RT and available radiological and histological data. A histopathological diagnosis of RT with concordant clinical and radiological findings was obtained in 13 patients. In 18 patients, CT did not show features of transformation, concordant with lack of RT in the biopsy. Of interest, a distinct lymphoma other than DLBCL was identified in two of these cases. A false-positive radiological diagnosis of RT was rendered in two patients, including a case of Herpes simplex virus lymphadenitis. In conclusion, our findings confirm the central role of tissue biopsy in the diagnostic work up in case of clinically suspected RT.

The capacity of the liver to convert the metabolic input received from the incoming portal and arterial blood into the metabolic output of the outgoing venous blood has three major determinants: The intra-hepatic blood flow, the transport of metabolites between blood vessels (sinusoids) and hepatocytes and the metabolic capacity of hepatocytes. These determinants are not constant across the organ: Even in the normal organ, but much more pronounced in the fibrotic and cirrhotic liver, regional variability of the capillary blood pressure, tissue architecture and the expression level of metabolic enzymes (zonation) have been reported. Understanding how this variability may affect the regional metabolic capacity of the liver is important for the interpretation of functional liver tests and planning of pharmacological and surgical interventions. Here we present a mathematical model of the sinusoidal tissue unit (STU) that is composed of a single sinusoid surrounded by the space of Disse and a monolayer of hepatocytes. The total metabolic output of the liver (arterio-venous glucose difference) is obtained by integration across the metabolic output of a representative number of STUs. Application of the model to the hepatic glucose metabolism provided the following insights: (i) At portal glucose concentrations between 6-8 mM, an intra-sinusoidal glucose cycle may occur which is constituted by glucose producing periportal hepatocytes and glucose consuming pericentral hepatocytes, (ii) Regional variability of hepatic blood flow is higher than the corresponding regional variability of the metabolic output, (iii) a spatially resolved metabolic functiogram of the liver is constructed. Variations of tissue parameters are equally important as variations of enzyme activities for the control of the arterio-venous glucose difference.

Background: To determine morphological and functional cardiovascular magnetic resonance (CMR) patterns in histopathologically confirmed myocardial involvement in patients with systemic sclerosis (SSc)., Methods: Twenty patients (6 females; mean age 41 ± 11 years) with histopathologically proven cardiac involvement in SSc in the years 2008-2016 were retrospectively evaluated. Morphological, functional and late gadolinium enhancement (LGE) images were acquired in standard angulations at 1.5 T CMR. Pathologies were categorized: 1) Pericardial effusion; 2) pathologic left (LV) or right ventricular (RV) contractility (hypokinesia, dyssynchrony, and diastolic restriction); 3) reduced left (LV-EF) and right ventricular ejection fraction (RV-EF); 4) fibrosis and/or inflammation (positive LGE); 5) RV dilatation. 95 % confidence intervals (CI) were calculated for appearance of pathologic EF and RV dilatation., Results: Seven patients (35 %) had positive CMR findings in three categories, 9 patients (45 %) in four categories and 4 patients (20 %) in five categories. The distribution of pathologic findings was: minimal pericardial effusion in 7 patients (35 %), moderate pericardial effusion >5 mm in nine patients (45 %); abnormal LV or RV contractility in 19 patients (95 %), reduced LV or RV function in 14 patients (70 %; 95 % CI: 51-88 %), pathologic LGE in all patients, RV dilatation in 6 patients (30 %; 95 % CI: 15-54 %)., Conclusions: CMR diagnosis of myocardial involvement in SSc requires increased attention to subtle findings. Pathologic findings in at least three of five categories indicate myocardial involvement in SSc.

Gout is a true crystal deposition arthropathy caused by the precipitation of monosodium urate into joints and periarticular soft tissues. It is the most common inflammatory arthropathy in men and women of older age with a male-to-female ratio of 3 to 8:1. The disease may progress from asymptomatic hyperuricemia through symptomatic acute gout attacks with asymptomatic periods into chronic symptomatic tophaceous gout. Although invasive arthrocentesis and demonstration of monosodium urate crystals on polarized light microscopy is definitive for the diagnosis of gout, dual-energy computed tomography (CT) allows for noninvasive visualization and reproducible volume quantification of monosodium urate crystals. Based on the high diagnostic performance, dual-energy CT has been included in the 2015 American College of Rheumatology/European League Against Rheumatism Collaborative Initiative Classification Criteria for Gout. Increasing evidence indicates the usefulness of dual-energy CT to guide the management of patients with suspected gout and monitor the effectiveness of urate-lowering medical therapy., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Renal cell carcinoma (RCC) is an immunogenic tumor for which immunotherapeutic approaches could be associated with clinically relevant responses. It was recently shown, that induction of T-cell responses against multiple tumor-associated antigen (TAA) epitopes results in prolonged overall survival in RCC patients. In 2003-2005, we performed a phase I/II trial testing an mRNA-based vaccine formulation consisting of a mixture of in vitro transcribed RNA coding for six different TAAs (MUC1, CEA, Her2/neu, telomerase, survivin, MAGE-A1) in 30 metastatic RCC (mRCC) patients. In the first 14 patients, vaccinations were applied i.d. on days 0, 14, 28, and 42. In the consecutive 16 patients, an intensified protocol consisting of i.d. injections (daily on days 0-3, 7-10, 28, and 42) was used. After the respective induction periods, patients in both cohorts were vaccinated monthly until tumor progression. At survival update performed in July 2015, one of the 30 patients was still alive. One patient was lost to follow-up. Median survival of 24.5 mo (all patients) and 89 mo (favorable risk patients) exceeded predicted survival according to Memorial Sloan Kettering Cancer Center (MSKCC) risk score. Impressively, long-term survivors displayed immunological responses to the applied antigens while vice versa no patient without detectable immune response had survived more than 33 mo. The current survival update shows a clear correlation between survival and immunological responses to TAAs encoded by the naked mRNA vaccine. This is one of the first vaccination studies and the only RNA trial that reports on safety and efficacy after a follow-up of more than 10 y.

Background: The heterogeneity of splenic computed tomography (CT) attenuation is still not fully understood. A differentiation of these enhancement patterns and other conditions such as diffuse spleen infiltration can be challenging., Purpose: To understand the underlying physiological mechanisms of flow heterogeneity in normal and cirrhosis patients by quantifying perfusion parameters such as blood flow (BF), blood volume (BV), time to peak (TTP), flow extraction product (K(trans)), and mean transit time (MTT) using dynamic contrast-enhanced CT (DCE-CT)., Material and Methods: Sixteen patients without splenic or hepatic disease and 16 patients with liver cirrhosis were retrospectively analyzed. Perfusion assessment included rapidly and slowly enhancing areas of the spleen, the entire splenic volume, as well as intra- and inter-observer reliability analysis., Results: Significant differences between rapidly and slowly enhancing areas were found in controls for BF (109.8 mL/100 mL/min vs. 63.5 mL/100 mL/min), BV (37.1 mL/100 mL vs. 18.9 mL/100 mL), MTT (10.1 s vs. 13.0 s), but not for TTP (17.6 s vs. 18.6 s) and K(trans) (40.3 mL/100 mL/min vs. 44.7 mL/100 mL/min). In cirrhotic patients, differences proved significant for BF (90.5 mL/100 mL/min vs. 58.7 mL/100 mL/min), BV (17.5 mL/100 mL vs. 8.8 mL/100 mL), but not for K(trans) (60.9 mL/100 mL/min vs. 50.5 mL/100 mL/min), TTP (18.8 s vs. 20.0 s), and MTT (11.4 s vs. 14.2 s). Differences between rapidly enhancing areas in controls and cirrhotic patients reached a significant level for BV and K(trans)., Conclusion: Preliminary results suggest that DCE-CT-based splenic perfusion measurements enable detection of different blood flow kinetics presumed to represent the complex and characteristic architecture of splenic vascular channels. It is the separate analysis of flow kinetics through the rapidly enhancing channels that allow for additional differentiation between controls and patients with portal hypertension., (© The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Purpose: Our objective was a multifunctional imaging approach of chronic sclerodermatous graft-versus-host disease (ScGVHD) and its course during therapy using PET/MRI., Methods: We performed partial-body PET/CT and PET/MRI of the calf in 6 consecutively recruited patients presenting with severe ScGVHD. The patients were treated with different immunosuppressive regimens and supportive therapies. PET/CT scanning started 60.5 ± 3.3 minutes, PET/MRI imaging 139.5 ± 16.7 minutes after (18)F-FDG application. MRI acquisition included T1- (precontrast and postcontrast) and T2-weighted sequences. SUV(mean), T1 contrast enhancement, and T2 signal intensity from region-of-interest analysis were calculated for different fascial and muscular compartments. In addition, musculoskeletal MRI findings and the modified Rodnan skin score were assessed. All patients underwent imaging follow-up., Results: At baseline PET/MRI, ScGVHD-related musculoskeletal abnormalities consisted of increased signal and/or thickening of involved anatomical structures on T2-weighted and T1 postcontrast images as well as an increased FDG uptake. At follow-up, ScGVHD-related imaging findings decreased (SUV(mean) n = 4, mean T1 contrast enhancement n = 5, mean T2 signal intensity n = 3) or progressed (SUV(mean) n = 3, mean T1 contrast enhancement n = 2, mean T2 signal intensity n = 4). Clinically modified Rodnan skin score improved for 5 follow-ups and progressed for 2. SUV(mean) values correlated between PET/CT and PET/MRI acquisition (r = 0.660, P = 0.014), T1 contrast enhancement, and T2 signal (r = 0.668, P = 0.012), but not between the SUV(mean) values and the MRI parameters., Conclusions: PET/MRI as a combined morphological and functional technique seems to assess the inflammatory processes from different points of view and provides therefore in part complementary information.

Purpose: The aim of this study was to investigate correlations between glucose metabolism as determined by [(18)F]FDG PET/CT and tumour perfusion as quantified by volume perfusion CT in primary tumours and mediastinal lymph nodes (MLN) of patients with non-small-cell lung cancer (NSCLC)., Methods: Enrolled in the study were 17 patients with NSCLC. [(18)F]FDG uptake was quantified in terms of SUVmax and SUVavg. Blood flow (BF), blood volume (BV) and flow extraction product (K(trans)) were determined as perfusion parameters. The correlations between the perfusion parameters and [(18)F]FDG uptake values were subsequently evaluated., Results: For the primary tumours, no correlations were found between perfusion parameters and [(18)F]FDG uptake. In MLN, there were negative correlations between BF and SUVavg (r = -0.383), BV and SUVavg (r = -0.406), and BV and SUVmax (r = -0.377), but not between BF and SUVmax, K(trans) and SUVavg, or K(trans) and SUVmax. Additionally, in MLN with SUVmax >2.5 there were negative correlations between BF and SUVavg (r = -0.510), BV and SUVavg (r = -0.390), BF and SUVmax (r = -0.536), as well as BV and SUVmax (r = -0.346)., Conclusion: Perfusion and glucose metabolism seemed to be uncoupled in large primary tumours, but an inverse correlation was observed in MLN. This information may help improve therapy planning and response evaluation.

Background: This study evaluated efficacy and safety of pemetrexed in patients with refractory soft tissue sarcoma., Methods: Patients received pemetrexed intravenously at a dose of 500 mg/m² every 21 days until progression or unacceptable toxicity. The primary endpoint was objective tumor response., Results: Fourty-eight of 53 screened patients were included and received a total of 200 cycles (median 2; range 1-30). Median age was 53 years (range, 20-81). The observed toxicity profile was favorable. NCI-CTC hematologic grade 3/4 toxicity consisted of neutropenia in 13 %, anemia in 15 %, and febrile neutropenia in 4 % of patients of patients, respectively. Non-hematologic CTC grade 3/4 toxicity consisted of elevated ASAT/ALAT in 10 %, hyperglycemia in 6 %, infection with or without neutropenia in 6 %, nausea in 2 % and stomatitis in 2 % of patients. No other grade 3 toxicities and no treatment-related toxic deaths were observed. Overall response as defined by RECIST was 5 %, 16 patients experienced stable disease (40 %). The estimated 3- and 6-months progression-free rates were 33.3 % and 14.6 %, respectively., Conclusions: In patients with refractory STS, pemetrexed is well tolerated and moderately effective. The confirmed objective response rate in STS is low, however, disease stabilizations are seen in a high proportion of patients (ClinicalTrials.gov NCT00427466).

Objectives: To evaluate intraobserver and interobserver agreement of manually encompassed lung lesions for perfusion measurements using volume-perfusion computed tomography (VPCT)., Materials and Methods: Institutional review board approval and informed consent were obtained. HIPAA guidelines were followed. A 65-s dynamic study was acquired with scan parameters 80 kV, 60 mAs (80 mAs for patients ≥ 70 kg), 128 × 0.6mm collimation. Blood flow (BF), blood volume (BV) and K(trans) parameters were determined by syngo volume perfusion CT body with 88 lesions analyzed retrospectively., Results: Within-subject coefficients of variation for intraobserver agreement (range 6.59-12.82%) were superior to those for interobserver agreement (range 21.75-38.30%). Size-dependent analysis revealed lower agreements for lesions <4 cm as compared to larger lesions. Additionally, agreements of the upper, middle and lower lung zones were different., Conclusions: Intraobserver agreement was substantial for VPCT lung cancer perfusion measurements encouraging the use for tumor characterization and therapy response monitoring. Interobserver agreement is limited and unexperienced readers should be trained before using this new method., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Systemic mastocytosis comprises a group of clonal disorders of the mast cell that most commonly involves the skeletal system. Imaging can be helpful in the detection and characterization of the osseous manifestations of this disease. While radiography and bone scans are frequently used for this assessment, low-dose multidetector computed tomography and magnetic resonance imaging can be more sensitive for the detection of marrow involvement and for the demonstration of the various disease patterns. In this article, we review the pathophysiological and clinical features of systemic mastocytosis, discuss the role of imaging for staging and management, and illustrate the various cross-sectional imaging appearances. Awareness and knowledge of the imaging features of this disorder will increase the accuracy of image interpretation and can contribute important information for management decisions.

Rationale and Objectives: The aim of this study was to assess splenic perfusion in patients with spleen involvement in malignant hematologic diseases and liver cirrhosis and in controls without hepatosplenic disease using volume perfusion computed tomography., Materials and Methods: Between October 2009 and December 2011, 14 hematologic patients with known spleen involvement were recruited. An additional 17 consecutive patients without known splenic or liver disease were enrolled as controls, as well as 29 patients with liver cirrhosis and portal hypertension. A 40-second volume perfusion computed tomographic scan of the upper abdomen was performed. Analysis included measurement of splenic volume, blood flow (BF), blood volume (BV), K(trans), and mean transit time (MTT)., Results: In lymphoma patients, mean splenic volume and perfusion parameters were as follows: splenic volume, 1125.34 mL; BF, 61.24 mL/100 mL/min; BV, 16.53 mL/100 mL; K(trans), 37.00 mL/100 mL/min; and MTT, 12.42 seconds. All perfusion values of patients with lymphoma and cirrhosis differed significantly, except for BV, compared to controls. For patients with lymphoma, significant correlations were found between splenic volume and BF (r = -0.683, P = .000), splenic volume and BV (r = -0.525, P = .002), and splenic volume and MTT (r = 0.543, P = .001). During treatment, significant correlations between the diameters of nodular lymphoma target lesions, splenic volume, and the perfusion parameters were present for splenic volume (r = 0.601, P = .002), BF (r = -0.777, P = .000) and BV (r = -0.500, P = .011)., Conclusions: Volume perfusion computed tomography represents a novel tool for the assessment of splenic perfusion. Preliminary results in patients with spleen involvement reveal lower perfusion values compared to controls or patients with cirrhosis. Therefore, this technique might provide additional information in clinical routine., (Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.)

Unlabelled: The aim of this study was to investigate correlations between glucose metabolism registered by (18)F-FDG PET/CT and tumor perfusion quantified by volume perfusion CT and immunohistochemical markers Ki67 and microvessel density (MVD) in patients with non-small cell lung cancer (NSCLC)., Methods: Between February 2010 and April 2011, 24 consecutive patients (21 women, 3 men; mean age ± SD, 67.6 ± 6.8 y; age range, 55.6-81.3 y) with histologically proven NSCLC (14 adenocarcinoma, 9 squamous cell lung carcinoma [SCC], and 1 mixed adenocarcinoma and SCC) underwent (18)F-FDG PET/CT and additional volume perfusion CT. Maximum standardized uptake value (SUV(max)), mean SUV, and the metabolic tumor volume were used for (18)F-FDG uptake quantification. Blood flow (BF), blood volume (BV), flow extraction product (K(trans)), and standardized perfusion value (SPV) were determined as CT perfusion parameters. Both perfusion parameters and (18)F-FDG uptake values were subsequently related to the histologic subtypes, proliferation marker Ki67, MVD according to CD34 staining, and total tumor volume., Results: Mean SUV, SUV(max), and the metabolic tumor volume (mL) were 5.8, 8.7, and 32.3, respectively, in adenocarcinoma and 8.5, 12.9, and 16.8, respectively, in SCC. Mean BF (mL/100 mL/min), mean BV (mL/100 mL), and K(trans) (mL/100 mL/min) were 35.4, 7.3, and 27.8, respectively, in adenocarcinoma and 35.5, 10.0, and 27.8, respectively, in SCC. Moderate correlations were found between the (18)F-FDG PET/CT parameters and Ki67 as well as between CT perfusion parameters and MVD but not vice versa. For all tumors, the following correlations were found: between SUV(max) and Ki67, r = 0.762 (P = 0.017); between SUV(max) and MVD, r = -0.237 (P = 0.359); between mean BF and Ki67, r = -0.127 (P = 0.626); and between mean BF and MVD, r = 0.467 (P = 0.059). Interestingly, correlations between the BF-metabolic relationship and total tumor volume were higher in SCC (r = 0.762, P = 0.017) than in adenocarcinoma (r = -0.0791, P = 0.788)., Conclusion: (18)F-FDG uptake correlates with Ki67, whereas BF, BV, and K(trans) correlate with MVD. Therefore, (18)F-FDG uptake and perfusion parameters provide complementary functional information. An improved tumor profiling will be beneficial for both prognosis and therapy response evaluation in these tumors.

Objective: The purposes of this review are to summarize the indications for MDCT arthrography of the shoulder, highlight the features of MDCT acquisition, and describe the normal and abnormal MDCT arthrographic appearances of the shoulder., Conclusion: MDCT arthrography is a valid alternative for shoulder imaging of patients with contraindications to MRI or after failed MRI. MDCT arthrography is accurate for assessment of a variety of shoulder abnormalities and, with further validation, may become the imaging test of choice for evaluation of the postoperative shoulder.

Purpose: To report the safety and diagnostic performance of magnetic resonance (MRI)--guided core biopsy of osseous lesions in children with chronic recurrent multifocal osteomyelitis (CRMO) that were visible on MRI but were occult on radiography and computed tomography (CT)., Materials and Methods: A retrospective analysis of MRI-guided osseous biopsy performed in seven children (four girls and three boys; mean age 13 years (range 11 to 14) with CRMO was performed. Indication for using MRI guidance was visibility of lesions by MRI only. MRI-guided procedures were performed with 0.2-Tesla (Magnetom Concerto; Siemens, Erlangen, Germany; n = 5) or 1.5-T (Magnetom Espree; Siemens; n = 2) open MRI systems. Core needle biopsy was obtained using an MRI-compatible 4-mm drill system. Conscious sedation or general anesthesia was used. Parameters evaluated were lesion visibility, technical success, procedure time, complications and microbiology, cytology, and histopathology findings., Results: Seven of seven (100%) targeted lesions were successfully visualized and sampled. All obtained specimens were sufficient for histopathological analysis. Length of time of the procedures was 77 min (range 64 to 107). No complications occurred. Histopathology showed no evidence of malignancy, which was confirmed at mean follow-up of 50 months (range 28 to 78). Chronic nonspecific inflammation characteristic for CRMO was present in four of seven (58%) patients, and edema with no inflammatory cells was found in three of seven (42%) patients. There was no evidence of infection in any patient., Conclusion: MRI-guided osseous biopsy is a safe and accurate technique for the diagnosis of pediatric CRMO lesions that are visible on MRI only.

The aim of this phase I/II nonrandomized trial was to assess feasibility, safety as well as immunological and clinical responses of a mRNA-based vaccination in patients with stage IV renal cell cancer using granulocyte-macrophage colony stimulating factor (GM-CSF) as adjuvant. Intradermal injections of in vitro transcribed naked mRNA, which was generated using plasmids coding for the tumor-associated antigens mucin 1(MUC1), carcinoembryonic (CEA), human epidermal growth factor receptor 2 (Her-2/neu), telomerase, survivin, and melanoma-associated antigen 1 (MAGE-A1) were performed in 30 enrolled patients. In the first 14 patients (cohort A) vaccinations were administered on days 0, 14, 28, and 42 (20 µg/antigen) while in the consecutive 16 patients (cohort B) an intensified protocol consisting of injections at days 0-3, 7-10, 28, and 42 (50 µg/antigen) was used. In both cohorts, after this induction period, vaccinations were repeated monthly until tumor progression analyzed by Response Evaluation Criteria In Solid Tumors criteria (RECIST). Vaccinations were well tolerated with no severe side effects and induced clinical responses [six stable diseases (SD) and one partial response in cohort A and nine SD in cohort B]. In cohort A, 35.7% survived 4 years (median survival 24 months) compared to 31.25% in cohort B (median survival 29 months). Induction of CD4(+) and CD8(+) T cell responses was shown for several tumor-associated antigens (TAA) using interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) and Cr-release assays.

Objective: The purpose of our study was to test the hypothesis that real-time MRI-guided, selective injection procedures of the temporomandibular joints are feasible, accurate, and safe when performed on a clinical open-bore 1.5-T MR system., Materials and Methods: A retrospective analysis of 67 injection procedures of the temporomandibular joints (55% [37/67] were therapeutic injections, 27% [18/67] were diagnostic injections, and 18% [12/67] were arthrocentesis procedures), performed in 31 patients (58% [18/31] female, 42% [13/31] male; mean age, 14 years; age range, 3-34 years), was made. Seven of 38 (18%) subjects had two temporally separate procedures. Determinations of skin entry points, puncture, and injection were performed under real-time MRI. Data were assessed for rate of successful injections, quantitative and qualitative image quality, time requirements, and occurrence of complications., Results: Drug delivery was successful in all procedures. The quality of real-time FLASH 2D MR images was sufficient in all cases. Real-time MRI proved to be helpful to achieve high rates of intraarticular injections. Contrast-to-noise ratios were sufficiently high for good delineation of relevant structures. Average length of time was 25 minutes (range, 16-53 minutes). No major complications occurred., Conclusion: We accept the hypothesis that real-time MRI-guided selective injection procedures of the temporomandibular joints are feasible, accurate, and safe when performed on a clinical open-bore 1.5-T MR system.

Objective: The purposes of this study were single-center analysis of the incidence of pathologic fractures in patients with multiple myeloma undergoing bisphosphonate therapy and correlation of the occurrence of pathologic fractures with the course of disease., Materials and Methods: One hundred ninety-one patients with multiple myeloma consecutively underwent unenhanced whole-body low-dose MDCT in parallel with hematologic follow-up. Only patients undergoing at least two whole-body low-dose MDCT examinations were included in this retrospective study, resulting in 561 survey intervals. The median analysis period per patient was 23 months (range, 3-53 months). Fracture incidence and the relation between newly occurring fractures and course of the disease were assessed., Results: Forty-nine pathologic fractures were detected in 49 of the 561 survey intervals (8.7%) and in 36 of the 191 patients (19%). Fractures were found on MDCT images irrespective of disease course. They were found in 25 of 202 intervals (12.4%) of progressive disease, in 14 of 171 intervals (8.2%) of disease remission, and in 10 of 188 intervals (5.3%) of stable disease. The overall calculated annual incidence of pathologic fractures in patients with multiple myeloma was 14%. Eleven patients had more than one fracture, all of which were vertebral compression fractures. Three patients had three episodes of bone fracture, and eight patients had two episodes., Conclusion: Pathologic fractures in patients with multiple myeloma undergoing bisphosphonate therapy occur independently of myeloma activity and therefore should not be considered a sign of disease progression.

Purpose: To describe whole-body magnetic resonance (MR) imaging appearance of chronic recurrent multifocal osteomyelitis (CRMO) and assess the role of MR imaging versus radiography in diagnosis of disease and correlation with clinical findings and laboratory data., Materials and Methods: Institutional review board approved this retrospective HIPAA-compliant study; informed consent was waived. T1-weighted, short inversion time inversion-recovery, and contrast material-enhanced T1-weighted whole-body MR imaging was performed and two-plane radiographs, clinical findings, and laboratory data were reviewed in 13 children (median age, 13 years) with CRMO. Lesion depiction, location, and characterization and extraskeletal abnormalities were evaluated. MR imaging findings were compared with clinical and laboratory data and radiographic results. Data analysis was performed, and diagnostic performance statistics of radiography, physical examination results, and serum inflammatory markers were calculated. General multilevel linear modeling framework was used. Odds ratios were calculated to estimate effect of age, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level on reliabilities. Associations of ESR and CRP level with total number of lesions were assessed (chi(2) test)., Results: MR imaging depicted 101 ill-defined edemalike osseous lesions. Most frequent anatomic sites were distal femur (21%, 21 of 101), proximal tibia (17%, 17 of 101), and distal tibia and fibula (14% each, 14 of 101). In tubular bones (70 anatomic sites), metaphysis (86%, 60 of 70) and epiphysis (67%, 47 of 70) were involved. Contiguous physeal relationship (89%, 66 of 74), periosteal reaction (48%, 48 of 101), and symmetric involvement (85%, 11 of 13) were present. MR imaging demonstrated multifocality in all patients. There were no extraskeletal abnormalities and no relationship between serum inflammatory markers and number of symptomatic anatomic sites (P = .472). Sensitivity for radiography was 0.13 (70 of 119); physical examination, 0.31 (52 of 299); and serum inflammatory markers, 0.15 (two of 13)., Conclusion: Whole-body MR imaging is useful for detection of CRMO, particularly in indeterminate cases, because it is more likely to show abnormalities.

A 67-year-old male patient with a pancreatic carcinoma and hepatic metastases was admitted with progressive dyspnea and anuria. Previously he had received five cycles of a palliative chemotherapy with gemcitabine and responded well with a reduction of the tumor mass. The laboratory results showed a distinct anemia, thrombocytopenia, an increase in creatinine and lactate dehydrogenase levels. With an additional finding of 21 per mille fragmentocytes in the periphery blood smear, we diagnosed a thrombotic microangiopathy (TMA). Until now the literature lacks well-defined therapy standards for this known but rare condition of gemcitabine. In a few case reports addressing the related microangiopathy of thrombotic thrombocytopenic purpura (TTP), which is characterised by a significant reduction of the von Willebrand factor (vWF) cleaving serum protease ADAMTS-13, encouraging results have been achieved by an immediate plasma exchange. Though ADAMTS-13 activity was not relevantly reduced in our patient, we still observed a rapid improvement of the clinical features as well as of LDH, thrombocytes and fragmentocytes under plasma exchange. The patient was discharged after one month in good clinical condition. Interestingly, during follow-up for further 21 months we found a continued stable status of the pancreatic carcinoma without any cytostatic therapy. In summary, this case provides evidence that the use of plasma exchange therapy in gemcitabine-associated TMA is justified.

This prospective multicentre phase II study characterises the toxicity and activity of first-line capecitabine and oxaliplatin combination therapy (CAPOX) in advanced biliary system adenocarcinomas. Patients received oxaliplatin (130 mg m(-2), day 1) plus capecitabine (1000 mg m(-2) b.i.d., days 1-14) every 3 weeks. Patients were stratified prospectively into two groups based on location of the primary (gallbladder carcinoma (GBC) or extrahepatic cholangiocarcinoma (ECC) versus intrahepatic mass-forming type cholangiocarcinoma (ICC)). Sixty-five patients were evaluable. The response rate in 47 patients with GBC/ECC was 27% (4% complete responses), and in 23 patients (49%) stable disease (SD) was encountered. In 18 patients with ICC, we observed no objective responses, but 6 patients (33%) had SD. Median survival was 12.8 months (95% CI, 10.0-15.6) for patients with GBC or ECC (GBC: 8.2 months; 95% CI, 4.3-11.7; ECC: 16.8 months; 95% CI, 12.7-20.5), and 5.2 months (95% CI, 0.6-9.8) for ICC patients. In both cohorts, therapy was well tolerated. The most common grade 3-4 toxicity was peripheral sensory neuropathy (11 patients). Our data suggest that the CAPOX regimen is a well-tolerated and active treatment option for advanced ECC and GBC but might produce poorer results for ICC.

We report a case of granulocytic sarcoma exclusively manifesting as diffuse intramuscular infiltration of the proximal upper and lower limb girdle and the torso muscles in a patient with previous history of acute myelogenous leukemia 5a. Whole-body CT showed widespread distribution of ill-defined intramuscular, homogeneously enhancing lesions. On whole-body MRI, lesions were homogeneously hyperintense on fat saturated T2-weighted images, isointense on T1-weighted images and strongly enhancing after intravenous gadolinium contrast administration. Histopathology revealed muscular infiltration of blast cells with identical immunochemistry to the initial manifestation of leukemia, diagnostic for an extramedullary relapse manifesting as granulocytic sarcoma. CT and MRI characteristics of this previously undocumented manifestation of granulocytic sarcoma should assist in the identification of such cases.

The purpose of this study was to assess CT morphology of pneumocystis pneumonia (PcP) and cytomegalovirus (CMV) pneumonia for specific characteristic features, similarities as well as differences, which might contribute to an early diagnosis and, therefore, influence patient management 58 patients were included, 31 with CMV pneumonia and 27 with PcP. All patients with CMV pneumonia had underlying haematological malignancies (n = 31) mainly treated by haematopoietic cell transplantation (HCT) (n = 26). Patients with PcP had haematological malignancies (n = 17) treated by HCT in 6, solid tumours (n = 5) and corticosteroid therapy (n = 5). Thin section CTs were analysed retrospectively by two radiologists. 18 CT morphological criteria were evaluated for presence or absence. Significance was calculated by chi2 test. Interobserver correlation was tested by kappa-statistic (K) Only 5 of the 18 features were found to have significantly different frequencies in the two entities. Apical distribution (p<0.01), mosaic pattern (p<0.01) and homogeneous structure of ground-glass opacities (GGO) (p<0.05) were found more frequently in PcP (each K: 0.7-0.9), whereas small nodules or unsharp demarcation of GGO and consolidation were typical of CMV pneumonia (p<0.05). Peripheral sparing, consolidation and septal thickening inter alia were found equally in both groups In conclusion analysis of craniocaudal distribution, demarcation and structure of infiltrates may be helpful in prioritizing differential diagnosis of CMV pneumonia or PcP. However, some features thought typical for one or the other entities appear with similar frequency in both groups in HIV-negative patients.

We present a case of unusual distribution of red marrow in a patient with extramedullary acute myelogenous leukemia (AML). In adults, hematopoietic marrow is usually located in the axial skeleton and the proximal aspects of the limbs, except for the epiphyses. Nodular islets of red marrow located in the epiphyseal and distal parts of the limbs may mimic tumoral infiltration and be mistaken for chloroma in a patient with AML.

Objective: The purpose of our study was to assess the correlation between early high-resolution CT findings of cytomegalovirus (CMV) pneumonia in patients with blood disorders and their clinical outcomes., Conclusion: The initial high-resolution CT findings in immunocompromised patients with CMV pneumonia seem to predict the patient's outcome being unfavorable in those forms of disease beginning mostly bilaterally as diffuse or patchy ground-glass opacity followed by progressive air-space consolidation. Also, a change in the CT morphology of pulmonary lesions toward diffuse ground-glass opacity seems to correlate with an unfavorable disease course.

The Carney triad is a rare syndrome of unknown aetiology, with synchronous or metachronous appearance of rare neoplasms: gastrointestinal stromal tumours (GISTs), pulmonary chondromas and extra-adrenal paragangliomas. In most cases, the Carney triad is incomplete. The combination encountered typically, GISTs and pulmonary chondromas, was also seen in our patient, a 22-year-old woman. She was diagnosed with the triad after Billroth II gastrectomy for histologically proved gastric GISTs. The diagnosis of pulmonary chondromas was confirmed by transthoracic, computed tomography-guided needle biopsy. An oesophageal leiomyoma was resected 2 years after the initial diagnosis, on suspicion of paraganglioma. The clinical course of the patient has been uneventful since. The last follow-up was carried out 6 years after the initial diagnosis. On histological examination, the cells of gastric GIST were partly positive for CD34, whereas CD117 was expressed in all areas in variable intensity and S-100 protein was negative. The oesophageal tumour was classified as leiomyoma due to strong immunopositivity for smooth muscle actin and desmin, being negative for CD34 and CD117. Two different gastric GIST lesions as well as the oesophageal leiomyoma and normal tissue were analysed for activating mutations in common hot spots of KIT (exon 9 and 11) and platelet-derived growth factor receptor alpha (exon 18), but in all probes wild-type sequences were found. These results are in accordance with the first published analyses of GIST lesions from Carney patients.

A phase I trial was conducted to evaluate the feasibility, safety, and efficacy of a dendritic cell-based vaccination in patients with metastatic renal cell carcinoma (RCC). Autologous mature dendritic cells derived from peripheral blood monocytes were pulsed with the HLA-A2-binding MUC1 peptides (M1.1 and M1.2). For the activation of CD4(+) T-helper lymphocytes, dendritic cells were further incubated with the PAN-DR-binding peptide PADRE. Dendritic cell vaccinations were done s.c. every 2 weeks for four times and repeated monthly until tumor progression. After five dendritic cell injections, patients additionally received three injections weekly of low-dose interleukin-2 (1 million IE/m(2)). The induction of vaccine-induced T-cell responses was monitored using enzyme-linked immunospot and Cr release assays. Twenty patients were included. The treatment was well tolerated with no severe side effects. In six patients, regression of the metastatic sites was induced after vaccinations with three patients achieving an objective response (one complete response, two partial responses, two mixed responses, and one stable disease). Additional four patients were stable during the treatment for up to 14 months. MUC1 peptide-specific T-cell responses in vivo were detected in the peripheral blood mononuclear cells of the six patients with objective responses. Interestingly, in patients responding to the treatment, T-cell responses to antigens not used for vaccinations, such as adipophilin, telomerase, or oncofetal antigen, could be detected, indicating that epitope spreading might occur. This study shows that MUC1 peptide-pulsed dendritic cells can induce clinical and immunologic responses in patients with metastatic RCC.

Preoperative localization of gastrinomas, especially of extrapancreatic origin, remains a challenge to the radiologist. Most patients with extrapancreatic gastrinomas undergo surgery without preoperative identification of the primary tumor. The appropriate imaging modality to localize gastrinomas is under continuing debate. We report a case of a duodenal gastrinoma with regional lymph node metastases that presented with Zollinger-Ellison syndrome. The small primary tumor was detected noninvasively by dual-phase multidetector thin-section computed tomography with adequate bowel distention and confirmed by endoscopy and histopathologic examination. The case illustrates that appropriate computed tomographic technique and scanning protocol are crucial for success in localizing extrapancreatic gastrinoma.

In a young female patient originally coming from Albany, immunoproliferative small intestinal disease (IPSID) could be diagnosed as a cause for severe maladsorption. Considering clinical and histological criteria an early disease stage of IPSID could be diagnosed. Under the continuous treatment of doxycycline for more than 3 1/2 years, all disease manifestations like watery diarrhea, vomiting, pain in the upper abdomen and loss of weight disappeared. After discontinuation of the antibiotic therapy the patient reached a sustained response.