Raffaele Liuzzi

18F-FDG PET/CT, 99mTc-MIBI, and MRI in evaluation of patients with multiple myeloma.

New imaging techniques have been introduced to assess the extent and severity of disease in multiple myeloma (MM) patients. The aim of our study was to compare newer imaging modalities—such as 18F-FDG PET/CT, 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy, and MRI—to assess their relative contribution in the evaluation of MM patients at diagnosis. Methods: Thirty-three newly diagnosed patients with MM were prospectively studied. Diagnosis and staging were made according to standard criteria. All patients underwent whole-body 18F-FDG PET/CT, whole-body 99mTc-MIBI, and MRI of the spine and pelvis within 10 d, and imaging findings were compared. Results: 18F-FDG PET/CT was positive in 32 patients (16 focal uptake, 3 diffuse uptake, 13 focal and diffuse uptake), 99mTc-MIBI was positive in 30 patients (6 focal, 11 diffuse, 13 focal and diffuse uptake), and MRI of the spine and pelvis was positive in 27 patients (6 focal, 13 diffuse, 8 focal and diffuse uptake). 18F-FDG PET/CT showed a total of 196 focal lesions (178 in bones and 18 in soft tissues), of which 121 were in districts other than the spine and pelvis, whereas 99mTc-MIBI visualized 63 focal lesions (60 in bones and 3 in soft tissues), of which 53 were in districts other than the spine and pelvis. In the spinal and pelvic regions, 18F-FDG PET/CT detected 75 focal lesions (35 in spine and 40 in pelvis), 99mTc-MIBI visualized 10 focal lesions (1 in spine and 9 in pelvis), and MRI detected 51 focal lesions (40 in spine and 11 in pelvis). Conclusion: In whole-body analysis, 18F-FDG PET/CT performed better than 99mTc-MIBI in the detection of focal lesions, whereas 99mTc-MIBI was superior in the visualization of diffuse disease. In the spine and pelvis, MRI was comparable to 18F-FDG PET/CT and 99mTc-MIBI in the detection of focal and diffuse disease, respectively. Because myelomatous lesions may often occur out of spinal and pelvic regions, MRI should be reserved to the evaluation of bone marrow involvement of these districts, whereas 18F-FDG PET/CT can significantly contribute to an accurate whole-body evaluation of MM patients. Finally, whole-body 99mTc-MIBI, despite its limited capacity in detecting focal lesions, may be an alternative option when a PET facility is not available.

Sonographic hepatic-renal ratio as indicator of hepatic steatosis: comparison with 1H magnetic resonance spectroscopy

The aim of this study was to determine the diagnostic performance of ultrasound (US) in the quantitative assessment of steatosis by comparison with proton magnetic resonance spectroscopy ((1)H-MRS) as a reference standard. Three liver echo-intensity indices were derived: US hepatic mean gray level, hepatic-renal echo-intensity ratio (H/R), and hepatic-portal blood echo-intensity ratio. The (1)H-MRS degree of steatosis was determined as percentage fat by wet weight. Regression equations were used to estimate quantitatively hepatic fat content. The hepatic fat content by (1)H-MRS analysis ranged from 0.10% to 28.9% (median value, 4.8%). Ultrasound H/R was correlated with the degree of steatosis on (1)H-MRS (R(2)= 0.92; P < .0001), whereas no correlation with (1)H-MRS was found for hepatic mean gray level and hepatic-portal blood echo-intensity ratio. A receiver operating characteristic curve identified the H/R of 2.2 as the best cutoff point for the prediction of (1)H-MRS of at least 5%, yielding measures of sensitivity and specificity of 100% and 95%, respectively. In this pilot study, US H/R exhibits high sensitivity and specificity for detecting liver fatty changes. Our results indicate that quantitative evaluation of hepatic fat content can be performed using US H/R and could therefore be a valuable analytic tool in clinical investigation.

Effects of enzyme replacement therapy in patients with Anderson-Fabry disease: a prospective long term cardiac magnetic resonance imaging study

Background: Anderson–Fabry disease is a multisystem X linked disorder of lipid metabolism frequently associated with cardiac symptoms, including left ventricular (LV) hypertrophy gradually impairing cardiac function. Evidence showing that enzyme-replacement therapy (ERT) can be effective in reducing LV hypertrophy and improving myocardial function in the long term is limited. Objective: This study aimed to assess the long-term effects of ERT with recombinant α-galactosidase A (agalsidase beta, Fabrazyme) on LV function and myocardial signal intensity in 11 patients with Anderson–Fabry disease. Patients: Eleven patients (eight males, three females) with varying stages of genetically confirmed Anderson–Fabry disease were examined by means of physical examination and magnetic resonance imaging before ERT with agalsidase beta at 1 mg/kg every other week (study 1) and after a mean treatment duration of 45 months (study 2). Results: At 45 months of treatment, LV mass and LV wall thickness had significantly reduced: 188 (SD 60) g versus 153 (47) g, and 16 (4) mm versus 14 (4) mm, respectively. Furthermore, a significant reduction in myocardial T2 relaxation times was noted in all myocardial regions, that is, interventricular septum 80 (5) ms versus 66 (8) ms, apex 79 (10) ms versus 64 (10) ms, and lateral wall 80 (8) ms versus 65 (16) ms. Changes in LV ejection fraction were not significant. Amelioration of clinical symptoms was observed in all patients. Conclusions: Long-term therapy with agalsidase beta at 1 mg/kg every 2 weeks was effective in significantly reducing LV hypertrophy, improving overall cardiac performance and ameliorating clinical symptoms in patients with Anderson–Fabry disease.

THYROID V30 PREDICTS RADIATION-INDUCED HYPOTHYROIDISM IN PATIENTS TREATED WITH SEQUENTIAL CHEMO-RADIOTHERAPY FOR HODGKIN'S LYMPHOMA

PURPOSE Hypothyroidism (HT) is a frequent late side effect of Hodgkins lymphoma (HL) therapy. The purpose of this study is to determine dose-volume constraints that correlate with functional impairment of the thyroid gland in HL patients treated with three-dimensional radiotherapy. METHODS AND MATERIALS A total of 61 consecutive patients undergoing antiblastic chemotherapy and involved field radiation treatment (median dose, 32 Gy; range, 30-36 Gy) for HL were retrospectively considered. Their median age was 28 years (range, 14-70 years). Blood levels of thyroid-stimulating hormone (TSH), free triiodo-thyronine (FT3), free thyroxine (FT4), and thyroglobulin antibody (ATG) were recorded basally and at different times after the end of therapy. For the thyroid gland, normal tissue complication probability (NTCP), dosimetric parameters, and the percentage of thyroid volume exceeding 10, 20, and 30 Gy (V10, V20, and V30) were calculated in all patients. To evaluate clinical and dosimetric factors possibly associated with HT, univariate and multivariate logistic regression analyses were performed. RESULTS Eight of 61 (13.1%) patients had HT before treatment and were excluded from further evaluation. At a median follow-up of 32 months (range, 6-99 months), 41.5% (22/53) of patients developed HT after treatment. Univariate analyses showed that all dosimetric factors were associated with HT (p < 0.05). On multivariate analysis, the thyroid V30 value was the single independent predictor associated with HT (p = 0.001). This parameter divided the patients into low- vs. high-risk groups: if V30 was ≤ 62.5%, the risk of developing HT was 11.5%, and if V30 was >62.5%, the risk was 70.8% (p < 0.0001). A Cox regression curve stratified by two levels of V30 value was created (odds ratio, 12.6). CONCLUSIONS The thyroid V30 predicts the risk of developing HT after sequential chemo-radiotherapy and defines a useful constraint to consider for more accurate HL treatment planning.

Hypericin photosensitization of tumor and metastatic cell lines of human prostate

We have investigated the photoactivating effect of hypericin on two cancer cell lines: PC-3, a prostatic adenocarcinoma non-responsive to androgen therapy and LNCaP, a lymphonodal metastasis of prostate carcinoma responsive to androgen therapy. The two cell lines are incubated for 24 h with hypericin at concentrations ranging from 0.001 to 0.3 microg/ml in cell culture medium. The cells are irradiated at 599 nm (fluence = 11 J/cm2) using a dye laser pumped by an argon laser. Hypericin exerts phototoxic effects on both cell lines, while it does not produce toxic effects in the absence of irradiation. These results suggest that photodynamic therapy (PDT) with hypericin could be an alternative approach to the treatment of prostatic tumors, and could be beneficial in tumors that are non-responsive to androgen therapy.

Multiple Sclerosis: Cerebral Circulation Time

PURPOSE To assess cerebral circulation times (CCTs) in patients with multiple sclerosis (MS) and control subjects by using contrast material-enhanced ultrasonography (US) to determine whether vascular abnormalities can be detected in this disease. MATERIALS AND METHODS This study was approved by the local ethics committee, and informed consent was obtained from all subjects. One hundred three patients with MS and 42 control subjects underwent extracranial and transcranial venous echo-color Doppler ultrasonography (US) and contrast-enhanced US. CCT was defined as the difference in arrival time of the US contrast agent bolus between the carotid artery and the internal jugular vein. The presence of chronic cerebrospinal venous insufficiency (CCSVI) was defined according to previously reported criteria for the extracranial and transcranial US techniques. Nonparametric statistics, including the Mann-Whitney U test and the Kruskal-Wallis analysis of variance, were used to compare contrast-enhanced US parameters between groups. RESULTS The longest and average CCTs were substantially prolonged in patients with MS compared with those in control subjects (median longest CCT in patients with MS, 6.47 seconds [range, 3.29-29.24 seconds]; that in control subjects, 5.54 seconds [range, 2.57-7.63 seconds]; P < .001; median average CCT in patients with MS, 5.76 seconds [range, 2.64-17.51 seconds]; that in control subjects, 5.01 seconds [range, 2.57-7.06 seconds]; P < .002). No correlation was found between CCTs and clinical parameters. The prevalence of CCSVI was higher in patients with MS than in control subjects (77% vs 28%, P < .0001). CCT was not significantly different between patients with MS who had CCSVI and patients with MS who did not (P = .182). CONCLUSION These results suggest that contrast-enhanced US with CCT assessment may have a role in the evaluation of cerebral blood flow in patients with MS and that a vascular impairment could be associated with MS. The finding of a prolonged CCT at contrast-enhanced US does not result from outflow impairment. Further studies are required to verify these observations and to clarify if CCT and CCSVI have any physiologic and clinical relevance in MS.

Dosimetric predictors of asymptomatic heart valvular dysfunction following mediastinal irradiation for Hodgkin’s lymphoma

PURPOSE To identify dose-heart-volume constraints that correlate with the risk of developing asymptomatic valvular defects (VD) in Hodgkins lymphoma (HL) patients treated with three-dimensional radiotherapy (RT). PATIENTS AND METHODS Fifty-six patients undergoing cytotoxic chemotherapy (CHT) and involved-field radiation treatment for HL were retrospectively analyzed. Electro-echocardiography was performed before CHT, after CHT, and after RT. For the entire heart, for right and left ventricle (RV, LV), right and left atrium (RA, LA) percentage of volume exceeding 5-30Gy in increment of 5Gy (V(x)), and dosimetric parameters were calculated using 1.6Gy fraction as reference. To evaluate clinical and dosimetric factors possibly associated with VD, univariate and multivariate logistic regression analyses were performed. RESULTS At a median follow up of 70.5 months, 32.1% of patients developed VD (regurgitation and/or stenosis): 25.0% developed mitral, 5.4% developed aortic, and 14.3% tricuspid VD. In particular the percentage of LA exceeding 25Gy (LA-V(25)) and the percentage of LV exceeding 30Gy (LV-V(30)) correlated with mitral and aortic VD with an odds ratio (OR) of 5.7 (LA-V(25)>63.0% vs. LA-V(25)≤63.0%) and OR of 4.4 (LV-V(30)>25% vs. LV-V(30)≤25%), respectively. RV-V(30) correlated with tricuspid VD (OR=7.2, RV-V(30)>65% vs. RV-V(30)≤65%). CONCLUSION LA-V(25), LV- and RV-V(30) prove to be predictors of asymptomatic alteration of valve functionality.

Radiation therapy in primary orbital lymphoma: a single institution retrospective analysis

BackgroundPrimary orbital lymphoma is a rare disease that accounts for 10% of all orbital tumors. Radiotherapy on the orbital cavity is the treatment of choice for this unusual presentation of localized non-Hodgkins lymphoma (NHL). The aim of this study is to retrospectively evaluate the effectiveness and the toxicity of radiation treatment in patients with primary orbital lymphoma.MethodsForty-seven consecutive patients having primary orbital lymphoma treated in our department between May 1983 and September 2006 were investigated in a retrospective study. Either 60Co γ rays or 6 MV X rays were used to deliver daily fractions of 1.8 or 2.0 Gy, 5 times/week, with total doses ranging from 34.2 to 50 Gy. Forty-three patients had stage IE, three had stage II and one stage IV disease. Thirty-eight patients had marginal zone B-cell lymphoma, 5 diffuse large B cell lymphoma, 3 mantle cell lymphoma and 1 Burkitt lymphoma. Local control (LC), disease free survival (DFS), overall survival (OS) and late side effects were evaluated in all patients.ResultsWith a median follow up of 45 months, LC was obtained in 100% of patients. The estimated 5- and 7-year DFS rates were 75.8% and 55.3%, and the 5- and 7-year OS rates were 88.7% and 79.9% respectively. Acute toxicity was minimal. Late toxicity such as cataract, keratitis, retinopathy and xerophthalmia occurred respectively in 12 (25.5%), 5 (10.6%), 1 (2.1%), and 9 (19.1%) patients.ConclusionRadiotherapy is an effective and at the same time well tolerated treatment for primary orbital lymphoma.

MRI Characterization of Myocardial Tissue in Patients with Fabry's Disease

OBJECTIVE Fabrys disease is a multisystem X-linked disorder of lysosomal metabolism frequently associated with left ventricular (LV) hypertrophy. In this study, we aimed to assess whether myocardial T2 relaxation time determined by a black blood multiecho multishot MRI sequence could be used to evaluate cardiac involvement in patients with Fabrys disease. CONCLUSION Myocardial T2 relaxation time is prolonged in patients with Fabrys disease compared with that of hypertrophic patients and healthy control subjects. MRI may be useful for the characterization of myocardial tissue in patients with Fabrys disease.

Progression of Striatal and Extrastriatal Degeneration in Multiple System Atrophy: A Longitudinal Diffusion-Weighted MR Study

Diffusion‐weighted imaging has been largely used to detect and quantify early degenerative changes in patients with multiple system atrophy, but progression of neurodegeneration has been poorly investigated. We performed a serial diffusion‐weighted imaging study in a population of multiple system atrophy patients and analyzed the evolution of diffusion properties in striatal and extrastriatal brain regions. Diffusion‐weighted imaging was obtained in 11 multiple system atrophy patients at baseline and after a follow‐up of 11.7 ± 1.2 months, and Trace (D) changes in different brain regions were correlated with disease duration and severity. A significant increase in Trace (D) was observed at follow‐up in the putamen (P < .001), pons (P = .003), cerebellar white matter (P = .03), thalamus (P = .013), and frontal white matter (P = .021). Both Unified Multiple System Atrophy Rating Scale Part II and Unified Parkinsons Disease Rating Scale Part III scores significantly increased at follow‐up (P = .003), but percent changes of Unified Parkinsons Disease Rating Scale Part III and Unified Multiple System Atrophy Rating Scale Part II did not correlate with percent changes of Trace (D) values in any brain region. This longitudinal study provides new insights into the progression of neurodegeneration in different brain regions in multiple system atrophy. Our results confirm that abnormal diffusivity in the putamen is sensitive to change over time in multiple system atrophy patients and show for the first time a progression of Trace (D) alterations in specific extrastriatal regions. Diffusivity changes in these regions may be useful for monitoring disease progression even after a short follow‐up period.