C-Met/miR-130b axis as novel mechanism and biomarker for castration resistance state acquisition.

Although a significant subset of prostate tumors remain indolent during the entire life, the advanced forms are still one of the leading cause of cancer-related death. There are not reliable markers distinguishing indolent from aggressive forms. Here we highlighted a new molecular circuitry involving microRNA and coding genes promoting cancer progression and castration resistance. Our preclinical and clinical data demonstrated that c-Met activation increases miR-130b levels, inhibits androgen receptor expression, promotes cancer spreading and resistance to hormone ablation therapy. The relevance of these findings was confirmed on patients' samples and by in silico analysis on an independent patient cohort from Taylor's platform. Data suggest c-Met/miR-130b axis as a new prognostic marker for patients' risk assessment and as an indicator of therapy resistance. Our results propose new biomarkers for therapy decision-making in all phases of the pathology. Data may help identify high-risk patients to be treated with adjuvant therapy together with alternative cure for castration-resistant forms while facilitating the identification of possible patients candidates for anti-Met therapy. In addition, we demonstrated that it is possible to evaluate Met/miR-130b axis expression in exosomes isolated from peripheral blood of surgery candidates and advanced patients offering a new non-invasive tool for active surveillance and therapy monitoring.

A microRNA code for prostate cancer metastasis.

Although the development of bone metastasis is a major detrimental event in prostate cancer, the molecular mechanisms responsible for bone homing and destruction remain largely unknown. Here we show that loss of miR-15 and miR-16 in cooperation with increased miR-21 expression promote prostate cancer spreading and bone lesions. This combination of microRNA endows bone-metastatic potential to prostate cancer cells. Concomitant loss of miR-15/miR-16 and gain of miR-21 aberrantly activate TGF-ß and Hedgehog signaling, that mediate local invasion, distant bone marrow colonization and osteolysis by prostate cancer cells. These findings establish a new molecular circuitry for prostate cancer metastasis that was validated in patients' cohorts. Our data indicate a network of biomarkers and druggable pathways to improve patient treatment.

Human HMGA2 protein overexpressed in mice induces precursor T-cell lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a neoplasia of thymocytes characterized by the rapid accumulation of the precursors of T lymphocytes. HMGA2 (high-mobility group AT-hook 2) gene expression is extremely low in normal adult tissues, but it is overexpressed in many tumors. To identify the biological function of HMGA2, we generated transgenic mice carrying the human HMGA2 gene under control of the VH promoter/Eµ enhancer. Approximately 90% of Eµ-HMGA2 transgenic mice became visibly sick between 4 and 8 months due to the onset and progression of a T-ALL-like disease. Characteristic features included severe alopecia (30% of mice); enlarged lymph nodes and spleen; and profound immunological abnormalities (altered cytokine levels, hypoimmunoglobulinemia) leading to reduced immune responsiveness. Immunophenotyping showed accumulation of CD5+CD4+, CD5+CD8+ or CD5+CD8+CD4+ T-cell populations in the spleens and bone marrow of sick animals. These findings show that HMGA2-driven leukemia in mice closely resembles spontaneous human T-ALL, indicating that HMGA2 transgenic mice should serve as an important model for investigating basic mechanisms and potential new therapies of relevance to human T-ALL.

Apparent diffusion coefficient obtained by magnetic resonance imaging as a prognostic marker in glioblastomas: correlation with MGMT promoter methylation status.

OBJECTIVE: To evaluate whether apparent diffusion coefficient (ADC) values can predict the status of MGMT of glioblastoma multiforme (GBM) and correlate with overall survival (OS) and progression-free survival (PFS). METHODS: This retrospective study included 47 patients with pathologically proven glioblastoma. All of them underwent MR DWI study before surgery (mean time 1 week) and the status of methylguanine-DNA-methyltransferase (MGMT) promoter methylation was searched for. Minimum apparent diffusion coefficient (ADC) values were evaluated. OS and PSF parameters were calculated, and Student's t-test, Kaplan-Meier curves, linear and Cox regression were performed. RESULTS: Twenty-five patients showed positive methylation of the MGMT promoter. Patients showing MGMT promoter methylation had higher minimum ADC values, and they survived longer than those without MGMT promoter methylation. The median ADCmin value of 0.80 represents the cutoff value able to distinguish between methylated and un-methylated patients. Patients showing minimum ADC values higher than 0.80 survived longer than patients with minimum ADC values lower than 0.80. A linear correlation between minimum ADC values vs. the OS and PFS was observed. CONCLUSIONS: Minimum ADC values in glioblastoma multiforme could be used as a preoperative parameter to estimate the status of MGMT promoter methylation and the survival of patients.

BTG2 loss and miR-21 upregulation contribute to prostate cell transformation by inducing luminal markers expression and epithelial-mesenchymal transition.

Prostate cancer is one of the leading causes of cancer-related death in men. Despite significant advances in prostate cancer diagnosis and management, the molecular events involved in the transformation of normal prostate cells into cancer cells have not been fully understood. It is generally accepted that prostate cancer derives from the basal compartment while expressing luminal markers. We investigated whether downregulation of the basal protein B-cell translocation gene 2 (BTG2) is implicated in prostate cancer transformation and progression. Here we show that BTG2 loss can shift normal prostate basal cells towards luminal markers expression, a phenotype also accompanied by the appearance of epithelial-mesenchymal transition (EMT) traits. We also show that the overexpression of microRNA (miR)-21 suppresses BTG2 levels and promotes the acquisition of luminal markers and EMT in prostate cells. Furthermore, by using an innovative lentiviral vector able to compete with endogenous mRNA through the overexpression of the 3'-untranslated region of BTG2, we demonstrate that in prostate tumor cells, the levels of luminal and EMT markers can be reduced by derepression of BTG2 from microRNA-mediated control. Finally, we show that the loss of BTG2 expression confers to non-tumorigenic prostate cells ability to grow in an orthotopic murine model, thus demonstrating the central role of BTG2 downregulaton in prostate cancer biology.

Clinical applications of dynamic susceptibility contrast perfusion-weighted MR imaging in brain tumours.

Magnetic resonance imaging (MRI) with a dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) sequence to study brain tumours provides information on the haemodynamic characteristics of the neoplastic tissue. Brain perfusion maps and calculation of perfusion parameters, such as relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV) and mean transit time (MTT) allow assessment of vascularity and angiogenesis within tumours of the central nervous system (CNS), thus providing additional information to conventional MRI sequences. Although DSC-PWI has long been used, its clinical use in the study of brain tumours in daily clinical practice is still to be defined. The aim of this review was to analyse the application of perfusion MRI in the study of brain tumours by summarising our personal experience and the main results reported in the literature.

Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer.

The interaction between cancer cells and microenvironment has a critical role in tumor development and progression. Although microRNAs regulate all the major biological mechanisms, their influence on tumor microenvironment is largely unexplored. Here, we investigate the role of microRNAs in the tumor-supportive capacity of stromal cells. We demonstrated that miR-15 and miR-16 are downregulated in fibroblasts surrounding the prostate tumors of the majority of 23 patients analyzed. Such downregulation of miR-15 and miR-16 in cancer-associated fibroblasts (CAFs) promoted tumor growth and progression through the reduced post-transcriptional repression of Fgf-2 and its receptor Fgfr1, which act on both stromal and tumor cells to enhance cancer cell survival, proliferation and migration. Moreover, reconstitution of miR-15 and miR-16 impaired considerably the tumor-supportive capability of stromal cells in vitro and in vivo. Our data suggest a molecular circuitry in which miR-15 and miR-16 and their correlated targets cooperate to promote tumor expansion and invasiveness through the concurrent activity on stromal and cancer cells, thus providing further support to the development of therapies aimed at reconstituting miR-15 and miR-16 in advanced prostate cancer.

Neurotrophin-3 modulates noradrenergic neuron function and opiate withdrawal.

Somatic symptoms and aversion of opiate withdrawal, regulated by noradrenergic signaling, were attenuated in mice with a CNS-wide conditional ablation of neurotrophin-3. This occurred in conjunction with altered cAMP-mediated excitation and reduced upregulation of tyrosine hydroxylase in A6 (locus coeruleus) without loss of neurons. Transgene-derived NT-3 expressed by noradrenergic neurons of conditional mutants restored opiate withdrawal symptoms. Endogenous NT-3 expression, strikingly absent in noradrenergic neurons of postnatal and adult brain, is present in afferent sources of the dorsal medulla and is upregulated after chronic morphine exposure in noradrenergic projection areas of the ventral forebrain. NT-3 expressed by non-catecholaminergic neurons may modulate opiate withdrawal and noradrenergic signalling.

Can benchmarking be applied to radiation protection? And is it useful?

PURPOSE: Any program of protection from the ionizing radiations used for health care must ultimately lead to the total prevention of graduated effects and to the limitation of probabilistic effects to acceptable levels. The latter are the more dangerous because they may occur even at very low doses and involve the whole population including unexposed subjects; these effects may appear in the generations to come. The specific protection of the health of operators, patients, and the general population, depends on a series of physical-technical and bureaucratic-administrative factors. These must be known and applied based on precise reference standards, recommended or stated by law, as well as on appropriately regulated and controlled procedures. We chose to apply the benchmarking method to radiation protection in order to standardize and increase the efficacy of prevention and to plan, according to Deming's cycle, the continuous improvement of radiation protection performance. METHOD: Benchmarking is a qualitative intercomparison method widely used in business economics to improve performance referring to best practice and the best in class. When applied in a department where all the partners belong (internal benchmarking), the method features a subdivision into different (sub)processes integrated according to the logic of problem-solving. These stages are: planning: 1) identifying benchmarking issues; 2) identifying the participants; 3) deciding the data collection method; 4) data collection; analysis: 5) measuring the gap; 6) planning future performance; integration: 7) reporting the results; 8) setting the functional goals; action: 9) developing and implementing plans; 10) checking results and resetting the target. The gross subdivision of resources into human and structural permits to check the gap between an actual and an ideal setting separately. Thus, the procedures will give information on the human factor which will be periodically checked in loco relative to all active and passive conducts, while standards will be used to assess the available spaces, facilities and equipment, as well as the relative regular activity. Specific physical-technical and bureaucratic-administrative indices will be needed in both cases. RESULTS AND DISCUSSION: Solving the operators' doubts and consequently decreasing the statistical errors and/or the cases of incorrect performance has resulted in improved rendered quality, which will be further increased after the planned replacement of substandard or unsafe equipment. Meanwhile, the early application of equipment quality controls has helped rationalize and markedly decrease maintenance costs, which results in possible technologic investment to improve emergency imaging. Greater attention to their protection has made patients feel an improvement in received quality and has increased empathy in general. Total quality, as compared with the best practice, has increased thanks to the positive stimulus from standardization, emulation and sharing, and not only to the controls performed. It is difficult to evaluate the management indices, especially the performance efficacy, that is the relationship between radiation protection and results, because the work is in progress and we still lack the actual data on the decrease in accidents at work or occupational diseases of the operators. Moreover, the epidemiological data on radiation-induced conditions will be difficult to collect and interpret, which will make the dynamics of lawsuits for unwarranted or excessive exposure a useful and more readily available piece of information. Finally, relative to economic results, we would like to stress that no additional costs have been necessary to implement safety and quality in a setting involving, directly or indirectly, thousands of people. (ABSTRACT TRUNCATED)

Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities.

Brain-derived neurotrophic factor (BDNF) has trophic effects on serotonergic (5-HT) neurons in the central nervous system. However, the role of endogenous BDNF in the development and function of these neurons has not been established in vivo because of the early postnatal lethality of BDNF null mice. In the present study, we use heterozygous BDNF(+/-) mice that have a normal life span and show that these animals develop enhanced intermale aggressiveness and hyperphagia accompanied by significant weight gain in early adulthood; these behavioral abnormalities are known to correlate with 5-HT dysfunction. Forebrain 5-HT levels and fiber density in BDNF(+/-) mice are normal at an early age but undergo premature age-associated decrements. However, young adult BDNF(+/-) mice show a blunted c-fos induction by the specific serotonin releaser-uptake inhibitor dexfenfluramine and alterations in the expression of several 5-HT receptors in the cortex, hippocampus, and hypothalamus. The heightened aggressiveness can be ameliorated by the selective serotonin reuptake inhibitor fluoxetine. Our results indicate that endogenous BDNF is critical for the normal development and function of central 5-HT neurons and for the elaboration of behaviors that depend on these nerve cells. Therefore, BDNF(+/-) mice may provide a useful model to study human psychiatric disorders attributed to dysfunction of serotonergic neurons.

[Assessment of microvascularization around the plaques in Peyronie's disease with Doppler color ultrasonography, power Doppler and ultrasonography contrast media]. / Valutazione della microvascolarizzazione intorno alla placca nella malattia di La Peyronie con eco color Doppler, power Doppler e mezzo di contrasto ecografico.

INTRODUCTION: The origin of Peyronie's disease remains obscure although the first report of this condition dates back to 1743. The disease prevalence in 388.6 in 100,000 population and little physiopathologic information is available. Repeated microtrauma to the tunica albuginea appears to favor the onset of inflammatory phenomena which result in fibrosis and calcification. The disease activity produces a microvascularization around the fibrocalcific plaques. We studied the evolution of the inflammatory process in Peyronie's disease relative to clinical symptoms, in order to optimize treatment follow-up. MATERIAL AND METHODS: We examined 20 patients with Peyronie's disease aged 34 to 56 years using a GE Sonora Logic 500 MD US scanner with linear probes of 7.5 and 13 MHz. The microvascularization around the plaques was studied with color and power Doppler investigations before contrast agent administration and with combined color and power Doppler after contrast agent administration. We injected Levovist (300 mg/mL) and 10 micrograms prostglandin E1 (PGE1). Examinations were repeated after 2-4 months in the patients with evidence of microvascularization around the plaques. RESULTS: US demonstrated fibrocalcific plaques in all the patients. The microvascularization around the plaques was seen with color Doppler in 3 cases (15%), with power Doppler in 5 cases (25%) and with contrast-enhanced color and power Doppler in 7 cases (35%). At 2-4 months' follow-up, we observed slight plaque enlargement and worsened symptoms in 5 of 7 patients (71%) with evidence of some microvascularization around the plaque. CONCLUSIONS: The plaque presence allows to define the condition and the microvascularization provides information on its evolution. The disease activity can be distinguished into 3 stages which can be related to the painful symptoms. US exhibits a better cost/benefit ratio than contrast-enhanced MRI.

[Follow-up chest radiography in surgical breast cancer patients]. / La radiografia del torace nel controllo delle pazienti operate per neoplasia della mammella.

PURPOSE: We investigated to what extent the diagnostic findings of chest radiography can improve prognosis and treatment in surgical breast cancer patients. We also reviewed the literature and our personal findings to choose the optimal follow-up frequency to meet therapeutical and management needs, including radiation protection. MATERIAL AND METHODS: We retrospectively reviewed 1556 chest radiographs of 195 surgical patients with M0 breast cancer performed January 1990 to December 1996. Patient's history and clinical data were accurately reviewed to investigate the relation between protocol type and results. The maximalist or intensive protocol featured 3 chest radiographs a year, even in the absence of any specific signs; the results were reviewed in terms of early diagnosis and prolongation of life. RESULTS: Only 13% of the examinations had been performed following a specific clinical indication, while 87% had been performed for a generic referral. Recurrences were found in 0.6% only of the latter examinations, which means that radiography provided no diagnostic improvement or important change in treatment in as much as 99.4% of cases. In 1997 radiographic follow-up was made triannual instead of biannual as it used to be. DISCUSSION AND CONCLUSIONS: In the absence of specific clinical indications, chest radiography can be performed in the two projections once a year. More aggressive protocols requiring more frequent examinations are not justified, as the patient's life expectancy is not increased. Yearly examinations permit to meet economic and management needs, with a better use of time, staff and materials. Moreover, the clinical-diagnostic yield is not affected by the skipping of unselected examinations. Finally, another pro is the technical thoroughness of the examination with orthogonal projections and the possibility to use ionizing radiations, which improves the management of clinical risks. Maximum radiologist-oncologist cooperation in clinical practice can improve both diagnostic efficiency and treatment efficacy, by reducing the population dose and rationalizing the use of human, instrumental, structural and financial resources.

Differential effect on TCR:CD3 stimulation of a 90-kD glycoprotein (gp90/Mac-2BP), a member of the scavenger receptor cysteine-rich domain protein family.

We studied the effects of a 90-kD glycoprotein (gp90/Mac-2BP) belonging to the scavenger receptor family, present in normal serum and at increased levels in inflammatory disease and cancer patients, on some T cell function parameters. Whereas the lymphocyte proliferative response to non-specific mitogens such as phytohaemagglutinin (PHA) and concanavalin A (Con A), but not pokeweed mitogen (PWM), was strongly reduced, probably due to the lectin-binding properties of gp90/Mac-2BP, the response to T cell receptor (TCR) agonists such as superantigens and allogeneic cells was potentiated. When lymphocytes were stimulated with different anti-TCR:CD3 MoAbs, both in soluble and solid-phase form, gp90/Mac-2BP was able to down-regulate the proliferative response to anti-CD3 MoAb, whereas the response to anti-TCR alphabeta MoAb was enhanced. A similar differential effect was observed when a MoAb against CD5 (another member of the scavenger receptor superfamily) was added to anti-CD3 or anti-TCR-stimulated cells; anti-CD5 MoAb strongly down-modulated the CD3-mediated response, whereas its presence in culture was associated with potentiation of the response to TCR alphabeta agonists. gp90/Mac-2BP was able per se to up-regulate Ca2+ levels in freshly isolated lymphocytes; moreover, its presence in culture was associated with increased Ca2+ mobilization following stimulation with anti-TCR alphabeta, but not anti-CD3 MoAb. These data indicate that gp90/Mac-2BP could be able to influence some immune responses, possibly through multiple homologous interactions with other members of the scavenger receptor family; moreover, our findings suggest that signalling through the different components of the TCR:CD3 complex may follow distinct activation pathways into the cells.

[The relationships between the specialist in radiology, the competent physician, the licensed physician and the qualified expert]. / Rapporti fra specialista in radiologia, medico competente, medico autorizzato ed esperto qualificato.

PURPOSE: To define the juridical figures of the medical specialist (in radiodiagnostics, radiotherapy, nuclear medicine), of the qualified doctor, of the physician authorized to radioprotection controls, and of the qualified expert. To analyze the role of these professionals and their working integration in the light of the regulations in force. To review the regulations referrable to nonspecialist physicians in the activities with ionizing radiation risks. To stress how patient radioprotection remains one of the major concerns of the radiologist, not only with the precautions he/she must take directly but also with the radioprotection policy he/she must promote in the different application fields and with the other specialists. DISCUSSION: Only the specialist (in radiodiagnostics, radiotherapy, nuclear medicine) can practice the specific relevant profession. The physicians working in public institutions in radiodiagnostics, radiotherapy, or nuclear medicine departments without the relative specialization will have to acquire it by 2007, the deadline of a specific moratorium (not indemnity) measure. Also the other medical specialists and nonspecialists using ionizing radiations for complementary activities to clinics are responsible for the radioprotection measures they take; particularly, nonspecialists will be allowed to work only if they get the relative specialization diploma. The medical specialist can interact with the authorized physician at three different levels: as the object of the regulation, he/she being exposed for professional reasons; as the promoter of the radioprotection of patients and the general population; as the person in charge and thus the direct responsible, together with the head of department and the management for the application of the regulations. Thence the need of effective consulting and collaboration between the two professionals. The same should apply also in full for the qualified expert, who is responsible for the physical control of radioprotection. CONCLUSIONS: The medical specialists is both the subject and the object of radioprotection regulations. For optimal collaboration with the other two professionals and to make the needed protection effective for patients and the population (as well as for the involved workers), he/she must be qualified enough and have sufficient technical-professional training, as well as a radioprotection-oriented attitude. In this respect the Italian Society of Medical Radiology (Società Italiana di Radiologia Medica: SIRM) plays a fundamental role.

Lymphoproliferative disease in human peripheral blood mononuclear cell-injected SCID mice. IV. Differential activation of human Th1 and Th2 lymphocytes and influence of the atopic status on lymphoma development.

Intraperitoneal transfer of PBMC from EBV+ donors into SCID mice leads to high human Ig levels in mouse serum and B cell lymphoproliferative disease. As these events depend on the activation of coinjected human T cells, we addressed the behavior of the Th1 and Th2 subsets in this model. Production of IFN-gamma, but not of Th2 cytokines such as IL-4, was detected in culture supernatants of PBMC stimulated in vitro with mouse splenocytes. Moreover, anti-CD3 stimulation of the human cells recovered from mice brought about IFN-gamma, but not IL-4, synthesis; on the other hand, PCR and in situ hybridization analysis of ex vivo-recovered cells disclosed the presence of mRNA for both cytokines following in vitro restimulation, thus suggesting posttranscriptional regulation of IL-4 gene expression. When SCID mice were inoculated with PBMC from atopic donors, whose Th1/Th2 profile displays an imbalance toward Th2 cells, tumor development rates were lower, and tumor latency was higher, compared with those in mice injected with PBMC from normal donors. Isotypic analysis of human Ig in mouse serum showed the exclusive presence of IFN-gamma-driven IgG subclasses; in addition, human IgE were low or undetectable in most cases. These findings indicate that following transfer into SCID mice, human Th1 lymphocytes undergo preferential activation, whereas Th2 function is down-regulated. Th1 lymphocytes probably are a major component in promoting EBV+ B cell expansion and tumor development; the individual Th1/Th2 profile could in part account for the as yet unexplained donor variability in tumor generation in this experimental model.

[Cystic dilatation of the seminal vesicles: which diagnostic approach?]. / Dilatazione cistica delle vescichette seminali: quale l'iter diagnostico?

PURPOSE: We investigated the frequency, clinical features, diagnostic course and therapy of congenital and acquired seminal vesicle cysts. MATERIAL AND METHODS: Seven vesicular cysts were found in adult subjects in 1995-1996. All diagnoses were made with suprapubic and transrectal US, CT and MRI. Vesiculo-deferentography was never used for diagnosis. Patient age and symptoms, cyst site, structure and dysembryogenetic associations were considered for diagnosis. RESULTS: All the patients were adult and all but one fertile. Age ranges were IV (43%), III and V (28.5%) decades. The cyst was congenital in 5 patients, associated with other dysplasias in 60% of them, and acquired in 2 patients. 57% of patients had urogenital symptoms and 2 patients (28.5%) had no clinical signs. US was performed for fertility tests in one patient. The left gland was always and exclusively involved; its size ranged 3.2 to 5.8 cm and its shape was characteristic only in 2 acquired cysts. DISCUSSION: Both abdominal and rectal US examinations were always performed and always reliably showed cyst site, origin, size and components. CT confirmed local findings and was also used to study the abdomen assessing renal presence and function. MRI permitted the best anatomical study with the multiplanar demonstration of the relationships between small pelvis structures. CONCLUSIONS: Congenital cysts and acquired distension of the seminal vesicles are uncommon findings also because they are difficult to diagnose. Diagnostic imaging reliably differentiates vesicular cysts from other cystic collections in that region, providing enough information to distinguish acquired from congenital forms, the former curable with drug treatment and the latter requiring more invasive therapy. Relative to site prevalence (100% in the left gland), we do not know if this was an aleatory finding or it indicated an actual congenital predisposition. US yields the indispensable diagnostic findings, but MRI should be always performed to ensure diagnosis, to study the abdomen and to plan possible surgery.

[Doppler color ultrasonography with contrast media in the study of eye and orbit neoplasms]. / L'eco color Doppler con mdc nello studio delle neoplasie dell'occhio e dell'orbita.

We investigated the diagnostic efficacy of the i.v. administration of a sonography (US) contrast agent to study eye and orbit tumors at different stages. We administered Levovist (Schering), an air microbubble stabilized by fatty acid, which is specific for angiographic indications. Baseline color Doppler US was performed on 24 selected patients and tumor vascularization patterns were classified into three classes. Color Doppler signal enhancement was assessed after contrast agent administration and the signal-to-noise ratio (SNR) was improved in 70% of cases, which helped identify vascular patterns and improved flowmetric accuracy. The Doppler effect was also improved and vascular signal was always enhanced. The SNR was improved also by the postcontrast detection of small vessels missed on baseline scans. Doppler signal enhancement was proportional to precontrast vascularization and depended on tumor size, with poor results in lesions < 5 mm. In contrast, vascular signal spots with increased postcontrast echogenicity sometimes caused excessive noise affecting the results. No correlation was found between signal enhancement and lesion histotype or between signal and lesion site. Treated lesions exhibited poorer contrast agent enhancement. The examination technique must be accurate and the various parameters set optimally, especially the velocity scale, gain and filtration; the unit must feature adequate recording capabilities (mm/s). To conclude, we believe that the routine use of i.v. US contrast agents will play a major role in improving diagnostic imaging in oculistics also thanks to the lack of untoward reactions and to the ease of contrast agent preparation.