Radiologists' recommendations for additional imaging (RAI) in the inpatient setting.

OBJECTIVE: The aim of our study was to measure the rate of radiologists' additional recommended imaging examinations (RAI) at a hospital-based inpatient setting and to estimate the influence on RAI of clinical variables. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board. Inpatients CT and US examinations interpreted by fifteen radiologists between October and December 2016 were studied. Information about RAI from radiology report texts was extracted manually. The analytic data set included the interpreting radiologists' years of experience, patient age, patient gender, radiologist gender, ordering service and "clinical question to be answered" as collected from the radiology request forms. RESULTS: Of the 1996 US and CT examinations performed between October and December 2016 in the inpatient setting, 34% (683 examinations) had a radiologists' RAI. The largest proportion of RAI was for chest CT, followed by PET-CT, abdominal CT and abdominal MRI. Patient age and gender had no impact on RAI. Radiologists' years of experience were inversely correlated to RAI. "Pneumonia" showed the highest rate of RAI due to follow-up of lung nodules. CONCLUSION: A high percentage of RAI resulted from CT and US radiologists' reports. The largest proportion of RAI was for chest CT, followed by PET-CT, abdominal CT, and abdominal MRI. Radiologists' years of experience play an important role in the number of the requested RAI. Further studies with a larger cohort of radiologists are needed to confirm the role of radiologists' experience in RAI. Also, follow-up studies are warranted to assess the number of RAI that are actually acted upon by the referring physicians.

Inappropriateness of diagnostic imaging examinations in the inpatient setting: a case study research.

OBJECTIVE: The purpose of our study was to audit the clinical appropriateness of the prescriptions of whole body CT (WB-CT), PET-CT and chest X-rays (CXRs) performed at Tor Vergata University Hospital in the inpatient setting. MATERIALS AND METHODS: WB-CT, PET-CT and CXRs examinations were retrospectively analysed in the period between January and December 2014. CXR examinations were divided into bedside CXRs and traditional CXRs. The appropriateness of the examinations was defined according the American College of Radiology Appropriateness Criteria. Inappropriate examinations were divided into six inappropriateness categories in accordance with the European Union Medical Imaging Guidelines. RESULTS: Appropriateness was suboptimal for all analysed techniques CXRs (A = 38%, I = 62%); bedside CXRs (A = 45%, I = 53%); WB-CT (A = 45%, I = 55%); PET-CT (A = 48%, I = 52%). With respect to WB-CT the highest rate of inappropriate imaging prescriptions came from the haematology clinical operative unit (OU) (44%) and emergency medicine (33%); with respect to PET-CT, the thoracic surgery OU (53%) and haematology OU (48%) showed the most inappropriate prescriptions. For CXRs, the percentage of inappropriateness was consistently distributed among all surgical OUs. For bedside CXRs, the largest inappropriate prescribers were the emergency medicine OU (48%), the cardiac surgery OU (58%), the intensive care OU (67%) and anaesthesia resuscitation OU (78%). The most represented classes of inappropriateness were 2, 3, 4 and 6. CONCLUSIONS: The elimination of inappropriate prescriptions would result in an annual savings of approximately 390,000 Euro. An implementation plan to increase prescription appropriateness is under development by our group.

Synovial fluid from patients with rheumatoid arthritis modulates monocyte cell-surface phenotype.

OBJECTIVES: To investigate the ability of synovial fluid from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) to modulate cell-surface phenotype, function and viability of monocytes. METHODS: Monocytes from healthy donors were incubated with synovial fluid from patients with RA or OA. These were then cultured with autologous healthy CD4+ T-cells. Immunoglobulin-like transcript 4 (ILT4) and CD86 were evaluated on stimulated monocytes and CD4+ T-cells via fluorescence activated cell sorting. RESULTS: Monocytes incubated with synovial fluid from patients with RA (SF-RA; n = 12) had significantly lower ILT4 and higher CD86 levels than those incubated with synovial fluid from patients with OA (SF-OA; n = 12) or medium alone. In patients with RA, there was a significant negative correlation between ILT4 and disease activity score (DAS; r = -0.699), and a positive correlation between CD86 and DAS (r = 0.626). T-cells costimulated with monocytes cultured with SF-RA produced significantly more interferon-γ and tumour necrosis factor-α than those costimulated with monocytes cultured with SF-OA or controls. CONCLUSIONS: Soluble mediators in SF-RA could contribute to modulating inflammation and local effectiveness of the immune response.

Expression of the receptor activator of nuclear factor-kB ligand in peripheral blood mononuclear cells in patients with acute Charcot neuroarthropathy.

Introduction. The receptor activator of nuclear factor-kB (RANK), ligand (RANK-L) and osteoprotegerin (OPG) are implicated in the pathogenesis of acute Charcot neuroarthropathy (CN). Materials and Methods. This study aimed to investigate the expression of RANK-L and OPG in peripheral blood mononuclear cells (PBMC) from patients with acute CN. Results. We found that the expression of RANK-L was lower in patients with acute CN as compared with diabetic control subjects and healthy control participants; whereas OPG expression was not detected in patients and in both control groups. RANK-L expression at the onset of disease was inversely correlated with the index of polyunsaturation (PUI), a bone marrow MRS-derived measurable index that allows evaluation of disease activity in acute CN, and recovery time. Finally, the expression of RANK-L increased at the time of healing compared with the values found during the acute phase. Conclusions. In conclusion, our preliminary data provide a first step in applying analysis of RANK-L expression in peripheral blood cells to the diagnosis of acute CN. Based on our data we also suggest that analysis of RANK-L expression could be a complementary tool that can be employed to obtain quantitative parameters that may help clinicians to monitor disease activity in patients with acute CN.

Pre-treatment staging of multiple myeloma patients: comparison of whole-body diffusion weighted imaging with whole-body T1-weighted contrast-enhanced imaging.

BACKGROUND: Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells. Accurate staging is of pivotal importance in the management of MM. Advanced imaging techniques, such as magnetic resonance imaging (MRI), are increasingly used for the initial diagnosis and staging of MM. PURPOSE: To compare whole-body (WB) MR diffusion-weighted imaging with background body signal suppression (DWIBS) with (WB) MR fat-suppressed T1-weighted contrast-enhanced imaging (T1-CE) in the pre-treatment staging evaluation of multiple myeloma (MM) patients. MATERIAL AND METHODS: Thirty-six patients with MM were included in the study. T1-CE and DWIBS were performed using a 3 T scanner. The Durie-Salmon plus staging system was used. Kappa statistics was used to assess agreement. RESULTS: For all MM stages good to very good agreement was found for both T1-CE and DWIBS. The unweighted kappa statistic indicated a moderate, good and very good agreement between T1-CE and DWIBS for stages I, II, and III, respectively. In particular, in 67% of patients the MM staging according to T1-CE was not different from DWIBS. In the remaining 33% of patients, the MM stage obtained with T1-CE was lower than that provided by DWIBS. CONCLUSION: DWIBS and T1-CE were concordant in the majority of patients. In a minority of cases DWIBS evidenced areas of water restriction that did not correspond to contrast enhancement areas. Studies monitoring therapeutic response in relation to tumour burden and aggressiveness should be performed to assess the clinical relevance of DWIBS findings.

Comparative evaluation of percutaneous laser and radiofrequency ablation in patients with HCC smaller than 4 cm.

OBJECTIVE: This study was done to compare percutaneous laser ablation (PLA) and radiofrequency thermoablation (RFA) for the treatment of hepatocellular carcinoma (HCC) ≤ 4 cm, in patients with liver cirrhosis. MATERIALS AND METHODS: Thirty patients with single HCC ≤ 4 cm in diameter were randomly assigned to one of two treatments: 15 patients were treated with PLA, using a multifibre system connected to a neodymium yttrium-aluminium-garnet laser source; 15 patients were treated with RFA, using an expandable needle electrode. Patients were followed up for up to 12 months. RESULTS: A complete response was obtained in 87 % lesions treated with PLA and in 93 % lesions treated with RFA (p = ns). The overall local recurrence-free survival rates at 3, 6 and 12 months were comparable. However, a higher rate of recurrence was observed in the PLA group for lesions ≥ 21 mm (p = 0.0081). A postablation syndrome was documented in 13 patients (1 PLA; 12 RFA). Tumour necrosis factor-α was significantly higher in the RFA group (p < 0.05). CONCLUSIONS: RFA is more effective in the treatment of HCC compared to PLA for lesions ≥ 21 mm. However, PLA should be considered a viable treatment option for HCC ≤ 20 mm, in view of the lower incidence of complications.

Proton magnetic resonance spectroscopy in the evaluation of patients with acute Charcot neuro-osteoarthropathy.

OBJECTIVE: To evaluate whether bone marrow proton magnetic resonance spectroscopy (MRS) might provide a quantitative parameter able to assess disease activity in acute Charcot neuro-osteoarthropathy (CN). METHODS: Ten diabetic patients with stage 0 CN were prospectively evaluated at clinical onset and during treatment follow-up. The MRS lipid spectrum was analysed and a lipid polyunsaturation index (PUI) was calculated. Disease recovery was defined as the disappearance of bone marrow oedema as demonstrated on MRI short-tau-inversion-recovery (STIR) images. A 3-T MRI was used. RESULTS: Inter- and intra-individual PUI measurements generated reproducible results with approximately 7 % and 6 % variation respectively. Baseline PUI values were significantly higher in patients with acute CN compared with controls. Also, a significant positive correlation was observed between baseline PUI values and serum levels of IL-6 and TNF-α. During follow-up a gradual decrease in PUI was observed. The percentage reduction of PUI values at 3 months' follow-up with respect to baseline values showed a negative correlation with recovery time. CONCLUSIONS: Bone marrow MRS may provide a measurable index that allows progressive evaluation of disease activity in acute CN. MRS may be a complementary tool that can be used to guide clinicians in the management of acute CN patients. KEY POINTS: • Bone marrow MRS demonstrates lipid alterations in acute Charcot neuro-osteoarthropathy (CN). • Bone marrow MRS allows disease activity in acute CN to be evaluated. • MRS could become a new tool in the management of CN.

3-T Diffusion tensor imaging of the optic nerve in subjects with glaucoma: correlation with GDx-VCC, HRT-III and Stratus optical coherence tomography findings.

OBJECTIVES: To correlate diffusion-tensor imaging (DTI) of the optic nerve with morphological indices obtained by scanning laser polarimetry (GDx-VCC); confocal scanning laser ophthalmoscopy (Heidelberg III retinal tomograph; HRT-III) and optical coherence tomography (Stratus OCT). METHODS: Thirty-six subjects (12 with no eye disease and 24 with perimetrically diagnosed glaucoma) were examined. One eye for each participant was studied with 3-Tesla DTI (with automatic generation of mean diffusivity (MD) and fractional anisotropy (FA) values); GDx-VCC, HRT-III and OCT. Single and multiple regression analyses of all variables studied were performed. RESULTS: MD displayed the strongest correlation with linear cup/disc ratio (LCDR) from HTR-III (r=0.662), retinal nerve fibre layer (RNFL) thickness (avThickn) from OCT (r=-0.644), and nerve fibre index (NFI) from GDx (r=0.642); FA was strongly correlated with the LCDR (r=-0.499). In multiple regression analyses, MD correlated with LCDR (p=0.02) when all variables were considered; with avThickn (p<0.01) (analysis of all RNFL parameters); with NFI (p<0.01) (analysis of all GDx parameters); with avThickn (p<0.01) (analysis of OCT parameters); with LCDR (p=0.01) (analysis of HRT-III morphometric parameters) and with linear discriminant function (RB) (p=0.02) (analysis of HRT-III indices). As for FA, it correlated with avThickn (p=0.02) when we analysed the OCT parameters and with RB (p=0.01) (analysis of HRT-III indices). CONCLUSIONS: DTI parameters of the axonal architecture of the optic nerve show good correlation with morphological features of the optic nerve head and RNFL documented with GDx-VCC, HRT-III and OCT.

Differences between proximal versus distal intraorbital optic nerve diffusion tensor magnetic resonance imaging properties in glaucoma patients.

PURPOSE: To analyze in vivo the diffusion tensor magnetic resonance imaging (DT-MRI) properties of the intraorbital optic nerve at two different levels: Proximal to the optic nerve head (ONH) and distal to the ONH at the level of the orbital apex in glaucoma patients. METHODS: Twenty-four patients with primary open-angle glaucoma were examined. The categorization into early and severe glaucoma was performed by Hodapp's classification. Fifteen healthy individuals served as controls. DT-MRI was performed with a 3T-MR unit. RESULTS: At early stage mean diffusivity (MD) values were higher at the proximal site with respect to the distal site. On the contrary, a decrease in fractional anisotropy (FA) was observed only relative to patient stage, independent of optic nerve site. Moreover, at early disease stage an increase in overall diffusivities, was evident at the proximal site, whereas at the distal site a decrease of the largest diffusivity and an increase in both the intermediate and smallest diffusivities were observed. FA and MD measured at the proximal site, had, respectively, the highest sensitivity and specificity in discriminating between healthy and glaucomatous eyes. CONCLUSIONS: Our study represents the first attempt to evaluate in vivo fiber integrity changes along the optic nerve with DT-MRI. Optic nerve degeneration appears to be a process that affects differently the proximal and the distal segments of the optic nerve. The complementary high sensitivity of FA with the high specificity of MD at the proximal site may provide reliable indexes for the identification of glaucomatous patients at early stages.

Liver elasticity in NASH patients evaluated with real-time elastography (RTE).

Liver elasticity as assessed by real-time elastography (RTE) has been shown to be correlated to liver fibrosis in various chronic liver diseases. The aim of our study was to assess the RTE performance in the evaluation of liver fibrosis in nonalcoholic steatohepatitis (NASH), as well as the histopathologic variables determining the eventual discordance between the RTE-predicted and the biopsy-proven fibrosis. Fifty-two consecutive biopsy proven NASH patients and 20 controls were studied. Liver tissue elasticity measurements were performed using the Hitachi EUB-8500 sonographer and the EUP-L52 Linear (3-7 MHz) probe. RTE liver tissue mean elasticity (TME) values were calculated and correlated to the histologic fibrosis, activity and steatosis scores. A decrease in TME was observed with increasing fibrosis (r = -0.75). Similarly, TME varied together consistently with steatosis (r = -0.3). In contrast, TME did not show any correlation with the severity of inflammation. Multiple regression analysis showed that fibrosis was the only variable able to significantly (p < 0.0001) modify TME values. The diagnostic accuracy of TME measurement for F > 0 evaluated by AUC-ROC analysis was 0.86. The diagnostic accuracy of TME measurement for F ≥ 2 was 0.92. We suggest that RTE could be used as a complementary imaging method to evaluate liver fibrosis in NASH patients. Future studies of larger patient cohorts are necessary for the validation of the technique.

Liver contrast enhanced ultrasound perfusion imaging in the evaluation of chronic hepatitis C fibrosis: preliminary results.

We wanted to determine whether liver contrast-enhanced ultrasound (CEUS)-derived peak signal intensity (PSI) and peak signal intensity/time (PIT) predict liver fibrosis in chronic hepatitis C (CHC). Forty-nine patients with CHC (METAVIR classification) and 10 control subjects were included in the study. After a bolus of 2.4 mL SonoVue (Bracco Imaging, Milan, Italy) solution was injected into a peripheral vein, the right lobe of the liver containing the right portal vein was scanned in a transverse section. Two-dimensional sonography was performed using the Philips iU22 ultrasound system (Philips Healthcare, Best, the Netherlands). A 1.0-5.0-MHz (C5-1) wideband convex transducer was used, applying the following settings in all cases. Regions of interest were manually drawn over the right liver lobe and over the portal vein (PV). Liver parenchyma PSI (LPpsi) and PIT (LPpit), portal vein PSI (PVpsi) and PIT (PVpit) were automatically calculated. δPSI was defined as the difference between PVpsi and LPpsi. A significant correlation was observed between PA(PSI) and fibrosis scores. When patients were stratified according to their LPpsi, a significant difference was achieved only between patients with fibrosis score 0-1 vs. 2-3 and 2 vs. 4. Statistically significant differences between all fibrosis scores, except 0 vs. 1 and 3 vs. 4 were observed when δPSI was used to stratify patients. Overall diagnostic accuracy of LPpsi and δPSI measurement for severe fibrosis by area under the receiving operator characteristic curve analysis was, respectively, 0.87 and 0.88. We suggest that liver CEUS perfusion could have the potential to be used as a complementary tool for the evaluation of liver fibrosis. However, further large-scale studies are required to accurately assess its accuracy in the evaluation of liver fibrosis.

Combined pulmonary fibrosis and emphysema: 3D time-resolved MR angiographic evaluation of pulmonary arterial mean transit time and time to peak enhancement.

PURPOSE: To correlate conventional invasive pressure indexes of pulmonary circulation with pulmonary first-order arterial mean transit time (MTT) and time to peak enhancement (TTP) measured by means of three-dimensional time-resolved magnetic resonance (MR) angiography in patients with combined pulmonary fibrosis and emphysema (CPFE). MATERIALS AND METHODS: The study was institutional review board approved. All subjects involved in the study provided written informed consent. Eighteen patients with CPFE were enrolled in this study. Thirteen healthy individuals matched for age and sex served as control subjects. Three-dimensional time-resolved MR angiography was performed by using a 3.0-T MR imager. Regions of interest (ROIs) were drawn manually on first-order pulmonary arteries. Within the ROIs, signal intensity-versus-time curves reflecting the first pass of the contrast agent bolus in the pulmonary vessels were obtained. MTT and TTP were calculated. Pulmonary arterial pressure and pulmonary capillary wedge pressure were measured with a double-lumen, balloon-tipped catheter that was positioned in the pulmonary artery. The mean pulmonary arterial pressure (mPAP) and the pulmonary vascular resistance (PVR) were determined. RESULTS: MTT and TTP values were prolonged significantly in patients with CPFE compared with those in the control subjects (P < .001). Mean TTP and mean MTT correlated directly with mPAP and PVR index (P < .005). At multiple linear regression analysis, MTT was the only factor independently associated with PVR index and mPAP. CONCLUSION: Three-dimensional time-resolved MR angiography enables determination of pulmonary hemodynamic parameters that correlate significantly with the pulmonary hemodynamic parameters obtained with invasive methods and may represent a complementary tool for evaluating pulmonary hypertension in patients with CPFE.

Optic nerve and optic radiation neurodegeneration in patients with glaucoma: in vivo analysis with 3-T diffusion-tensor MR imaging.

PURPOSE: To evaluate, with high-field-strength diffusion-tensor (DT) magnetic resonance (MR) imaging, the axonal architecture of the optic nerves and optic radiations in patients with glaucoma and determine whether DT MR imaging-derived parameters correlate with disease severity. MATERIALS AND METHODS: The study was approved by the institutional review board. All participants provided written informed consent. Sixteen patients with primary open-angle glaucoma were examined. Glaucoma severity was clinically assessed with use of a six-stage system based on static threshold visual field parameters. Ten healthy individuals served as control subjects. DT MR imaging was performed with a 3-T MR unit. Mean diffusivity (MD) and fractional anisotropy (FA) maps were automatically created. Regions of interest were positioned on the MD and FA maps, and mean MD and mean FA values were calculated for each optic nerve and each optic radiation. RESULTS: The optic radiations and optic nerves of patients with glaucoma, as compared with control subjects, had significantly higher MD and significantly lower FA. The mean MD values for the optic nerves and the glaucoma stages varied consistently (r = 0.8087, P < .0001). A negative correlation between mean FA for the optic nerves and glaucoma stage (r = -0.7464, P < .0001) was observed. CONCLUSION: Glaucoma is a complex neurologic disease that affects optic nerves and optic radiations. The finding that DT MR imaging-derived MD and FA in the optic nerves correlate with glaucoma severity suggests that these parameters could serve as complementary indicators of disease severity.

Small breast cancers: in vivo percutaneous US-guided radiofrequency ablation with dedicated cool-tip radiofrequency system.

PURPOSE: To evaluate in vivo the efficacy of a newly developed breast radiofrequency (RF) ablation system in human small invasive breast carcinomas in terms of induction of complete tumor necrosis, reproducibility of ablation lesion size and shape, and cosmetic outcome. MATERIALS AND METHODS: This study had institutional review board approval, and written informed consent was obtained. Thirty-four postmenopausal women (mean age, 53 years +/- 5 [standard deviation]; range, 49-62 years) with small (< or = 2 cm) biopsy-proved invasive ductal breast carcinomas were enrolled. RF energy was delivered through a 25-mm 15-gauge monopolar cool-tip needle electrode by using the temperature-controlled mode. Patients were divided into three groups according to their breast pattern as assessed at mammography. The volumetric size and geometry of the coagulation zone, together with ablation time, were determined. Histopathologic data were compared with postprocedural 3.0-T contrast material-enhanced magnetic resonance (MR) images. Cosmesis after RF ablation was assessed. Four weeks after RF ablation, patients underwent definitive surgery. RESULTS: All ablation procedures were performed successfully. For 97% of the procedures, nicotinamide adenine dinucleotide in its reduced form-diaphorase staining showed no evidence of viable cells. The mean induced ablation volume, as assessed with histologic analysis, was 12.50 cm(3) +/- 0.8. Tumor ablation volume on the postablation MR images showed good correlation with results of histopathologic analysis (r = 0.823, P < .005). No differences were observed in terms of duration of the procedure or ablation volume with respect to the glandular pattern of the breast (P > .05 for both). The general shape of the induced necrosis was close to a sphere in all cases. Cosmesis was excellent in 28 patients. CONCLUSION: A dedicated breast cool-tip RF ablation system can induce complete tumor necrosis and reproducible ablation volumes independently of breast glandular pattern, providing excellent cosmesis. Postablation MR images are a reliable tool in predicting histologic findings.

Evaluation of the severity of chronic hepatitis C with 3-T1H-MR spectroscopy.

OBJECTIVE: The purpose of this study was to compare the spectral characteristics of lipids, choline-containing compounds, and glutamine-glutamate complex assessed with (1)H-MR spectroscopy with the histologic findings in patients with chronic hepatitis C. SUBJECTS AND METHODS: Nine healthy controls and 30 patients with biopsy-proven hepatitis C virus-related liver disease participated in this prospective study. Degree of fibrosis and histologic activity were scored according to the METAVIR classification. The percentage of involved hepatocytes was used to grade steatosis. Hepatic spectra were obtained with a 3-T spectroscopic system. Tenfold cross-validated stepwise discriminant analysis was performed to classify disease severity on the basis of the spectroscopic findings. RESULTS: There was a strong correlation between (1)H-MR spectroscopically measured lipid concentration and the degree of steatosis at histologic examination (r = 0.9236, p < 0.0001). This finding enabled clear separation of groups according to degree of histologically determined steatosis. Variation in lipid concentration was consistent with the degree of steatosis (r = 0.7265, p < 0.0001) and stage of fibrosis (r = 0.8156, p < 0.0001). In univariate analysis, concentrations of both choline-containing compounds and glutamine-glutamate complex had a direct correlation with histologic grade (p < 0.0001) and degree of steatosis (p < 0.0001) but not with stage of fibrosis (p > 0.05). In multivariate analysis, the only factor independently associated with concentrations of choline-containing compounds and glutamine-glutamate complex was histologic grade. In cross-validated discriminant analysis based on choline-containing compound, glutamine-glutamate complex, and lipid resonance, 70% (21 of 30) of the histologic grade groups and 73% (22 of 30) of the steatosis groups were correctly classified. CONCLUSION: Hydrogen-1 MR spectroscopy can be an alternative to liver biopsy in the evaluation of steatosis and necroinflammatory activity in liver disease but is not useful for complete evaluation of hepatic fibrosis.

Percutaneous cryoablation of small hepatocellular carcinoma with US guidance and CT monitoring: initial experience.

The purpose of this study was to retrospectively determine the safety and effectiveness of percutaneous cryoablation, monitored with computed tomography (CT) and ultrasonographic (US) guidance, for the treatment of hepatocellular carcinoma (HCC). Four patients with small HCCs underwent one percutaneous cryoablation treatment session monitored with CT and US guidance. All patients underwent pretreatment blood chemistry testing and imaging evaluation. We treated lesions with simultaneous insertion of multiple 17-G cryoprobes (two or three) and defined technical success when the extension of a visible iceball was beyond 5 mm from the tumor margin. Intralesional enhancement or tumoral size increase was defined as local progression compared with that on images obtained immediately after ablation. We evaluated complications and follow-up (at 1, 3, and 6 months). All patients survived without short- or long-term complications. Cryoablation was technically successful in all patients at the end of the procedure. During follow-up two patients developed disease recurrence. One patient developed local tumor progression on the margin of the lesion; the other, a new HCC. In the case of local tumor progression a new elevation of alpha-fetoprotein (alphaFP) levels occurred at first follow-up control. In the other case levels of alphaFP remained stable during the first 3 months after the procedure, then demonstrated a progressive increase in alphaFP levels beginning at the fourth month, without tumor evidence during CT control at 3 months. We conclude that percutaneous cryotherapy with US guidance and CT monitoring is a feasible, safe, and effective for treatment of HCC. If local ablative procedures of hepatic lesions are to be performed, percutaneous cryoablation, not laparotomic, should be discussed as an alternative therapeutic measure. Longer follow-up should provide proof of the effectiveness of this technique.

Lipopolysaccharide desensitizes monocytes-macrophages to CD40 ligand stimulation.

Polymicrobial sepsis induces the suppression of macrophage function as determined by a reduction of pro-inflammatory cytokine production upon re-exposure to lipopolysaccharide (LPS) in vitro. Here, we examined whether macrophages were refractory to only LPS or if they were unable to respond to other stimuli such as CD40 ligand (CD40L). Monocytic cells exposed in vitro to LPS showed a dose-dependent reduction of their ability to produce interleukin-12 and tumour necrosis factor-alpha upon subsequent CD40L stimulation, as compared to cells stimulated with CD40L alone. Similarly, LPS interfered with the up-regulation of CD40, CD80 and CD86 induced by CD40L in monocytic cells. The effect of LPS on the response of monocytes to CD40L was similar whether these cells were directly exposed to LPS or cocultured with LPS-pretreated cells, indicating that soluble factors released by LPS stimulation could mediate tolerance to CD40L. We also show that the functional alterations induced by LPS in monocytes can be reversed by indomethacin, thus suggesting a role for inducible cyclooxygenase in mediating the LPS-induced hyporesponsive state of monocytes to CD40L. In conclusion, we propose that in vitro CD40L tolerance may be an appropriate model of monocyte alteration observed during septic immunosuppression and may help in the development of novel therapeutic strategies.

Anti-gene peptide nucleic acid targeted to proviral HIV-1 DNA inhibits in vitro HIV-1 replication.

Highly active antiretroviral therapy (HAART) is unlikely to affect reservoirs of HIV in latently infected cells. Anti-gene compounds, such as peptide nucleic acids (PNAs), which block transcriptional activity via sequence-specific invasion of double-stranded DNA may be an effective strategy to target cells harbouring proviral HIV DNA. Here we show that a PNA oligomer (PNA(HIV)), 15 bases in length, linked to a nuclear localization signal (NLS), substantially suppressed HIV-1 replication in chronically infected lymphocytes and macrophages and efficiently prevented mitogen-induced HIV-1 reactivation in lymphocytes, as determined by HIV-p24 antigen production in supernatants and FACS analysis for intracellular HIV accumulation. In contrast, a mismatched PNA did not show any effect on HIV expression. Semi-quantitative RT-PCR and quantitative real-time RT-PCR demonstrated a decrease of HIV RNA expression in infected cells treated by PNA(HIV) indicating that inhibition of HIV-1 replication occurred at the transcription step. In conclusion, the use of anti-gene PNA to target the HIV-1 proviral DNA in the quest for new antiretroviral agents appears quite promising.