Serum levels of osteopontin predict diabetes remission after bariatric surgery.

AIM: Bariatric surgery has been shown to effectively improve glycaemic control in morbidly obese subjects. However, the molecular bases of this association are still elusive and may act independently of weight loss. Here, our retrospective study has investigated the inflammatory molecule osteopontin (OPN) as a potential predictor of type 2 diabetes mellitus (T2DM) remission. METHODS: Baseline serum levels of OPN were analyzed in 41 T2DM patients who underwent bariatric surgery. Anthropometric measures and biochemical variables, including insulin sensitivity indices (HOMA2), were assessed at baseline and at 1 and 3 years after surgery. RESULTS: At baseline, patients who experienced T2DM remission had increased waist circumference, body weight and BMI, and higher serum OPN, compared with non-remitters. Patients with and without T2DM remission improved their lipid and glucose profiles, although insulin resistance indices were only improved in the T2DM remission group. In the overall cohort of both T2DM remission and non-remission patients, baseline circulating levels of OPN significantly correlated with reductions of body weight and BMI over time, and insulin sensitivity improved as well. However, only the HOMA2-%S remained independently associated with serum OPN on multivariate linear regression analysis (B: 0.227, 95% CI: 0.067-0.387, ß = 0.831; P = 0.010). Baseline values of OPN predicted 3-year T2DM remission independently of body weight loss, lower BMI and duration of diabetes (OR: 1.046, 95% CI: 1.004-1.090; P = 0.033). CONCLUSION: Although larger studies are still needed to confirm our preliminary results, pre-operative OPN serum levels might be useful for predicting 3-year T2DM remission independently of weight loss in patients undergoing bariatric surgery.

Spinal Cord Stimulation in Failed Back Surgery Syndrome: Effects on Posture and Gait-A Preliminary 3D Biomechanical Study.

We studied 8 patients with spinal cord stimulation (SCS) devices which had been previously implanted to treat neuropathic chronic pain secondary to Failed Back Surgery Syndrome. The aim of our study was to investigate the effects of SCS on posture and gait by means of clinical scales (Short Form Health Survey-36, Visual Analogue Scale for pain, and Hamilton Depression Rating Scale) and instrumented evaluation with 3D Gait Analysis using a stereophotogrammetric system. The latter was performed with the SCS device turned both OFF and ON. We recorded gait and posture using the Davis protocol and also trunk movement during flexion-extension on the sagittal plane, lateral bending on the frontal plane, and rotation on the transversal plane. During and 30 minutes after the stimulation, not only the clinical scales but also spatial-temporal gait parameters and trunk movements improved significantly. Improvement was not shown under stimulation-OFF conditions. Our preliminary data suggest that SCS has the potential to improve posture and gait and to provide a window of pain-free opportunity to optimize rehabilitation interventions.

Imaging of mesothelioma of tunica vaginalis testis.

OBJECTIVES: To describe the imaging findings in a series of patients with mesothelioma of the tunica vaginalis testis. METHODS: We reviewed clinical data, imaging findings and follow-up information in a series of 10 pathology-proven cases of mesothelioma (all had US; 2 had MR) of the tunica vaginalis. RESULTS: A variety of patterns could be observed, the most common (5/10) being a hydrocele with parietal, solid and hypervascular vegetations; one patient had a septated hydrocele with hypervascular walls; one had multiple, solid nodules surrounded by a small, physiological quantity of fluid; one a cystic lesion with thick walls and vegetations compressing the testis; two had a solid paratesticular mass. MR showed multiple small nodules on the surface of the tunica vaginalis in one case and diffuse thickening and vegetations in the other one; lesions had low signal intensity on T2-w images and were hypervascular after contrast injection. CONCLUSIONS: A preoperative diagnosis of mesotheliomas presenting as solid paratesticular masses seems very difficult with imaging. On the contrary, the diagnosis must be considered in patients in whom a hydrocele with parietal vegetations is detected, especially if these show high vascularity. KEY POINTS: Mesotheliomas of the tunica vaginalis are rare, often challenging to diagnose preoperatively. Most common finding is a complex hydrocele with hypervascular parietal vegetations. Septated hydrocele, nodules without hydrocele, a thick-walled paratesticular cyst are less common. Preoperative diagnosis may allow aggressive surgical approach and, possibly, a better prognosis.

CEUS Time Intensity Curves in the Differentiation Between Leydig Cell Carcinoma and Seminoma: A Multicenter Study.

PURPOSE: Ultrasound (US) is the main imaging technique in the assessment of testicular masses, as it has proved to be highly accurate in the visualization of these pathologies. Identification of a Leydig cell tumor is essential since the lesion is benign in 90% of cases. The aim of this multicenter study is to assess the effectiveness of contrast-enhanced ultrasound (CEUS) in differentiating Leydig cell tumors from seminoma using qualitative and quantitative features. MATERIALS AND METHODS: From February 2011 to December 2013, 31 patients (mean age: 34 years; range: 25 - 52) were recruited for this prospective study. Three of them were monorchid. Therefore, a total of 59 testicles were assessed. All patients underwent grayscale US, color Doppler ultrasound (CDUS), CEUS and orchiectomy. The paired one-tailed Student's t-test was carried out to differentiate between Leydig cell tumors and seminomas. RESULTS: 31 lesions suspicious for malignancy were hypoechoic on grayscale US while they did not show a typical pattern on CDUS. CEUS qualitative analysis, based on contrast enhancement pattern, during the arterial and venous phases, did not allow discrimination of Leydig cell tumors from seminoma. Quantitative analysis of time-intensity curves (TICs) demonstrated that only three parameters presented statistical significance, i. e. wash-in rate (WiR) p = 0.014, peak enhancement (PE) p = 0.001 and time to peak (TTP) p = 0.003. CONCLUSION: The vascular bed of a Leydig cell tumor is wider and the blood flow velocity is higher than that of a seminoma due to more regular neovascularization. In contrast, a seminoma presents large areas of necrosis due to irregular neovascularization. This explains the different PE and WiR values. Further studies involving larger patient populations are mandatory to confirm these encouraging preliminary results.

Growing indications for CEUS: The kidney, testis, lymph nodes, thyroid, prostate, and small bowel.

Contrast enhanced ultrasonography (CEUS) is increasingly used for non-hepatic applications as well, so that nearly all organs have been investigated. Among them, there is a growing clinical use for a variety of pathologies of the kidney, testis, and small bowel. The possibility to differentiate benign from malignant nodes in cancer patients has been investigated. A new application is in the detection of sentinel nodes after intradermal microbubble injection. The need to distinguish thyroid nodules eligible for fine needle aspiration cytology has led to the use of CEUS in thyroid examinations as well. The potential of CEUS for prostate cancer detection has been extensively investigated, with encouraging initial results. Early promise, however, has not been fulfilled. New perspective regards evaluation of the extent of prostate tissue devascularization following ablative treatments.

The use of CEUS in the diagnosis of retinal/choroidal detachment and associated intraocular masses - preliminary investigation in patients with equivocal findings at conventional ultrasound.

PURPOSE: To investigate whether contrast-enhanced ultrasound (CEUS) may help to diagnose retinal/choroidal detachment and may help to differentiate intraocular lumps in cases with equivocal features on conventional grayscale and Doppler modes. MATERIALS AND METHODS: The institutional review board approved this retrospective study. The need for informed consent was waived. A computerized data search was performed in the database of our institution for patients with vitreous hemorrhage who underwent CEUS of the eye to assess retinal/choroidal detachment and/or associated masses. This process yielded a total of 31 patients (18 men, 13 women, age range: 39 - 88 years) in whom CEUS was performed because the findings on conventional grayscale and Doppler modes were equivocal. CEUS was performed using low acoustic power contrast-specific modes. A 2.4 - 4.8  mL bolus of SonoVue was injected, followed by a saline flush. All examinations were digitally recorded for retrospective analysis. Confirmation of CEUS findings was obtained at surgery (n = 20) or with binocular indirect fundoscopy performed after clearance of the ocular media (n = 11). Two readers with different levels of ultrasound experience independently reviewed the imaging features. A five-degree scale ranging from definitely absent (score 1) to definitely present (score 5) was used to assess the presence or absence of retinal/choroidal detachment on conventional ultrasound modes alone and with the addition of CEUS. ROC curve analysis was performed to assess the diagnostic accuracy of both methods. The inter-reader agreement was also evaluated. In patients with associated intraocular lumps, conventional Doppler modes and CEUS were used to differentiate non-tumor masses from tumor masses. RESULTS: According to the reference standard, 13 patients had retinal detachment, 4 had choroidal detachment, and 3 had both retinal and choroidal detachment. There were 8 associated intraocular lumps (4 subretinal hemorrhages, 3 malignant melanomas, 1 metastasis). The inter-reader agreement was good (K = 0.644) and very good (K = 0.833) for conventional modes and CEUS, respectively. The diagnostic performance of CEUS was high for both readers (area ± standard error under the ROC curve: 0.966 ±â€Š0.031 and 0.900 ±â€Š0.055 for readers 1 and 2, respectively). There were 2 false-positive results and 1 false-negative result in patients with proliferative diabetic retinopathy. CEUS was effective in differentiating subretinal hemorrhage from hypovascular tumors. CONCLUSION: CEUS can be used as a problem-solving technique when conventional ultrasound modes are not diagnostic for retinal/choroidal detachment and when intraocular lumps cannot be characterized as tumor or non-tumor masses on conventional modes. The evaluation of patients with proliferative diabetic retinopathy, however, may be problematic.

Preoperative vascular mapping with multislice CT of deep inferior epigastric artery perforators in planning breast reconstruction after mastectomy.

PURPOSE: Our aim was to evaluate the usefulness of computed tomography angiography (CTA) in vascular mapping for planning breast reconstruction after mastectomy using a free flap made with the deep inferior epigastric perforators (DIEP). MATERIALS AND METHODS: We retrospectively evaluated 41 patients, mean age 57 years, scheduled for mastectomy. CTA was performed with a 64-row scanner (Aquilion 64, Toshiba Medical Systems, Japan), with injection of 100 ml of contrast medium (iomeprol 350 mgI/ml, Bracco, Italy) at 4.5 ml/s. Maximum intensity projection (MIP) and three-dimensional volume-rendering (VR) reconstructions were made to mark perforator positions. Presentation frequency, anatomy and artery opacification quality were evaluated. RESULTS: DIEP were always depicted (n=81) and subdivided according to Taylor's classification into type I (65%), type II (28%), and type III (7%). We observed a mean of three (range, 1-5) DIEP arteries on the right and two (range, 1-5) on the left side. The superficial inferior epigastric artery (SIEA) was depicted in 6/41 patients, bilaterally in three cases. Opacification was optimal in 30/41 cases, venous contamination due to late arterial phase in eight and low opacification due to early scan in three. CONCLUSIONS: Studying DIEP with CTA is useful in the surgical planning of breast reconstruction, even though it requires careful optimisation owing to the critical timing of opacification typical of that vascular district.

Role of US in acute scrotal pain.

BACKGROUND: The acute scrotum is a common emergency department (ED) presentation and can be defined as any condition of the scrotum or intrascrotal contents requiring emergent medical or surgical intervention. Although rarely fatal, acute scrotal pathology can result in testicle infarction and necrosis, testicular atrophy, infertility, and significant morbidity. METHODS: Scrotal US is best performed with a linear 7.5- to 12-MHz transducer. In addition to imaging in the longitudinal and transverse planes, it is helpful to obtain simultaneous images of both testes for comparison. Color Doppler is used to evaluate for abnormalities of flow and to differentiate vascular from nonvascular lesions. Attention to appropriate color Doppler settings to optimize detection of slow flow is critical. RESULTS: The evaluation of acute scrotal pain can be challenging for the clinician initially examining and triaging the patient. Acute scrotal conditions due to traumatic, infectious, vascular, or neoplastic etiologies can all present with pain as the initial complaint. Additionally, the laboratory and physical examination findings in such conditions may overlap; this, coupled with potential patient guarding and lack of collaboration, may result in a limited, non-specific physical examination. Therefore, scrotal ultrasound has emerged to play a central role in the evaluation of the patient presenting with acute scrotal pain. CONCLUSIONS: In conclusion, we are firmly convinced that a scrotal ultrasound should always be performed in the presence of acute scrotal pain. Moreover, urologist should be able to perform a scrotal ultrasound but, if imaging does not supply a clear diagnosis, surgical exploration is still mandatory.

A novel role of the CX3CR1/CX3CL1 system in the cross-talk between chronic lymphocytic leukemia cells and tumor microenvironment.

Several chemokines/chemokine receptors such as CCR7, CXCR4 and CXCR5 attract chronic lymphocytic leukemia (CLL) cells to specific microenvironments. Here we have investigated whether the CX(3)CR1/CX(3)CL1 axis is involved in the interaction of CLL with their microenvironment. CLL cells from 52 patients expressed surface CX(3)CR1 and CX(3)CL1 and released constitutively soluble CX(3)CL1. One third of these were attracted in vitro by soluble CX(3)CL1. CX(3)CL1-induced phosphorylation of PI3K, Erk1/2, p38, Akt and Src was involved in induction of CLL chemotaxis. Leukemic B cells upregulated CXCR4 upon incubation with CX(3)CL1 and this was paralleled by increased chemotaxis to CXCL12. Akt phosphorylation was involved in CX(3)CL1-induced upregulation of CXCR4 on CLL. In proliferation centers from CLL lymph node and bone marrow, CX(3)CL1 was expressed by CLL cells whereas CX(3)CR1 was detected in CLL and stromal cells. Nurselike cells (NLCs) generated from CLL patient blood co-expressed surface CX(3)CR1 and CX(3)CL1, but did not secrete soluble CX(3)CL1. Only half of NLC cell fractions were attracted in vitro by CX(3)CL1. In conclusion, the CX(3)CR1/CX(3)CL1 system may contribute to interactions between CLL cells and tumor microenvironment by increasing CXCL12-mediated attraction of leukemic cells to NLC and promoting directly adhesion of CLL cells to NLC.

Cystic lesions and scrotal fluid collections in adults: Ultrasound findings.

The widespread use of scrotal ultrasonography (US) has led to increased detection of testicular and extratesticular pathologies. Cystic or encapsulated fluid collections are relatively common benign lesions that usually present as palpable testicular lumps. Most cysts arise in the epidydimis, but all anatomical structures of the scrotum can be the site of their origin. US may suggest a specific diagnosis for a wide variety of intrascrotal cystic and fluid lesions and appropriately guide therapeutic options. US should be used as an adjunctive diagnostic modality after clinical evaluation of a scrotal lesion associated or not with the presence of a lump.

High-resolution, three-dimensional, and contrast-enhanced ultrasonographic findings in diseases of the eye().

OBJECTIVES: To review the contrast-enhanced ultrasound (CEUS) and 3D ultrasound findings (3D-US) in various pathologies involving the eye and orbit and to compare them with high-resolution US (HRUS) findings. BACKGROUND: CEUS is a valid diagnostic tool for study several districts. There are numerous pathological conditions of the eye in which CEUS can be very helpful or detrimental. IMAGE FINDINGS: We review a wide range of ocular lesions, traumatic (retinal and choroidal detachments) and malignant (choroidal melanoma, tumors inside and outside the muscle cone) evaluated alternatively with CEUS and 3D and compare these findings with those obtained with HRUS. Dysthyroid orbitopathy is not included in this review. CONCLUSION: CEUS plays a central role in the differentiation of detached retina (vascular) and vitreous membranes (avascular). It is also helpful in the assessment of tumor of the eye, in planning treatment for choroidal melanoma, and in assessing orbital masses for neovascularization. HRUS is highly effective in the detection of traumatic and non-traumatic lesions of the eye, but it is less effective for the assessment of orbital lesions. The 3D module has increased the diagnostic value of CEUS. CEUS is cost-effective and can be used when CT and MR cannot be performed.

Effect of Tadalafil on prostate haemodynamics: preliminary evaluation with contrast-enhanced US.

PURPOSE: Phosphodiesterase-5 (PDE-5) inhibitors have an established role in the treatment of erectile dysfunction, but there is increasing evidence that these drugs are effective also for the treatment of lower urinary tract symptoms and benign prostatic hyperplasia (BPH). The mechanism of action of PDE-5 inhibitors in the prostate, however, is poorly understood. It is conceivable that these drugs act by reducing the smooth muscle tone of the organ, but this effect could produce vascular changes as well. The aim of this study was to investigate whether administration of Tadalafil, a PDE-5 inhibitor, in patients with BPH produces haemodynamic changes in the prostate that can be assessed using contrast-enhanced US (CEUS). MATERIALS AND METHODS: Twelve consecutive patients with BPH underwent transrectal CEUS before and 90 min after administration of 20 mg Tadalafil. CEUS was performed during bolus injection of SonoVue (4.8 ml) using a nondestructive US mode. The same scan plane, imaging parameters and technique were used before and after Tadalafil administration. Digital clips were recorded and processed using dedicated software (QontraXt v.3.60. Signal intensity (SI) changes in a region of interest (ROI) encompassing the entire prostate were fitted to a gammavariate curve. Changes in enhancement peak, time to peak (TTP), sharpness of the bolus transit and area under the curve (AUC) were considered for further analysis. RESULTS: After Tadalafil administration, the enhancement peak and AUC increased significantly (p<0.01), reflecting changes in prostate vascularity. TTP and sharpness did not change significantly. CONCLUSIONS: In patients with BPH, vascular changes are observed in the prostate after Tadalafil administration, which can be detected with CEUS.

Differential diagnosis between splenic nodules and peritoneal metastases with contrast-enhanced ultrasound based on signal-intensity characteristics during the late phase.

PURPOSE: This study was done to assess the enhancement characteristics of splenic implants and to evaluate whether contrast-enhanced ultrasound (CEUS) after SonoVue injection allows the differential diagnosis with peritoneal metastases. MATERIAL AND METHODS: Thirteen consecutive patients with splenosis and 13 consecutive patients with peritoneal metastases were investigated with CEUS after injection of 2.4 ml of SonoVue. Lesion enhancement was evaluated in real time for 240 s. All examinations were recorded digitally and analysed retrospectively. Frames were selected at different time intervals ranging from 0 to 4 min after injection. Average signal intensity was evaluated by measuring the average grey level in a region of interest encompassing the entire nodule. Results were evaluated using the Mann-Whitney test and interobserver variability using the Bland and Altmann method. RESULTS: Splenic grafts presented with intense enhancement and without significant washout. Metastases presented with variable enhancement and progressive washout. Signal intensity values were significantly higher for splenic grafts, starting from 40 s after microbubble administration. Starting from 90 s after injection, there was no overlapping between enhancement of splenic grafts and peritoneal metastases, and only splenic grafts showed a percent of enhancement higher than 60% of the maximum enhancement. CONCLUSIONS: CEUS after SonoVue injection may be considered a valuable alternative to scintigraphy for characterising peritoneal splenic grafts without radiation.

Comparison of conventional ultrasound and real-time spatial compound imaging in evaluation of patients with severe Peyronie's disease.

BACKGROUND: Real-time spatial compound imaging (C-US) is an ultrasound (US) method which effectively reduces image artifacts and noise. In contrast to conventional techniques, multiple frames are acquired from different viewing angles and combined to form a single compound image. PURPOSE: To evaluate whether C-US improves ultrasound evaluation of patients with severe Peyronie's disease. MATERIAL AND METHODS: 60 consecutive patients with severe Peyronie's disease underwent conventional US and C-US after intracavernous prostaglandin E1 injection. Corresponding images of the same scan plane were obtained with both methods, and subjective image quality was scored retrospectively using a four-point scale by two blinded readers with different experience in penile imaging. Readers focused on evaluation of the tunica albuginea, plaques, involvement of the penile septum, and overall image quality. Also, presence of large albugineal calcifications or microcalcifications was considered. To assess intrareader agreement, both readers repeated evaluation after a 1-month interval. Statistical analysis was performed using the Wilcoxon signed-rank test and McNemar test. Weighted kappa values were calculated to assess intra- and inter-reader agreement. RESULTS: Average scores were significantly higher for reader 1 (P<0.001). Both readers rated C-US better (P<0.001) than conventional US. Despite higher image quality scores, C-US was as effective as conventional grayscale US in assessing involvement of the penile septum. No differences were found between the two methods for visualization of large calcifications, while microcalcifications were better visible with compound imaging. Intrareader agreement was higher for the more experienced reader 1. CONCLUSION: C-US is subjectively superior to conventional US in evaluating patients with severe Peyronie's disease.

US, colour-Doppler US and fine-needle aspiration biopsy in the diagnosis of thyroid nodules.

PURPOSE: The purpose of this study was to correlate the diagnosis of benign or malignant thyroid nodules obtained with grey-scale ultrasound (US) and colour-Doppler US with the cytological findings after US-guided fine-needle aspiration (FNA). MATERIALS AND METHODS: Between January 2004 and June 2005, 516 thyroid nodules in 420 patients (181 solitary thyroid nodules and 239 multiple nodules) were prospectively evaluated with US, colour-Doppler US and US-guided FNA. The nodules were classified as sonographically benign, suspicious or malignant in accordance with established US criteria. Cytological findings were classified as inadequate, benign, indeterminate, suspicious or malignant. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of US and colour-Doppler US were evaluated using FNA as the reference procedure. RESULTS: The sensitivity, specificity, PPV, NPV and overall accuracy values of grey-scale US were 46%, 73%, 34%, 82% and 67%, respectively, for solitary thyroid nodules and 35%, 72%, 14%, 90% and 68%, respectively, for multiple nodules. The evaluation of nodule vascularity with colour-Doppler US produced a slight increase in sensitivity but a slight reduction in specificity. CONCLUSIONS: Thyroid nodules cannot be accurately characterised using grey-scale US or colour-Doppler US.

The radiologist and the cytologist in diagnosing thyroid nodules: results of cooperation.

PURPOSE: This study was done to evaluate the effectiveness of cooperation between the radiologist and the cytopathologist in ultrasound-guided fine-needle aspiration biopsy (FNAB) of thyroid nodules. MATERIALS AND METHODS: Since 1995, FNAB of thyroid nodules at our department has been performed under ultrasound guidance by the radiologist with a cytopathologist present on-site. The results of ultrasound-guided FNAB procedures performed at our department in 1995, 1999, and 2005 were retrospectively evaluated and compared with those of other departments in the Trieste Province where thyroid nodules are sampled by palpation-guided FNAB performed by a clinician. RESULTS: From 1995 to 2005, the number of ultrasound-guided FNAB procedures performed at our department rose steadily, whereas the number of inadequate samples fell progressively. In patients who underwent surgery, the number of discrepancies between the cytological findings and the final histological diagnoses decreased progressively. CONCLUSIONS: Ultrasound-guided FNAB performed by the radiologist with a cytopathologist present on-site is superior to palpation-guided FNAB. The results are optimised by cooperation between the radiologist and cytologist.

Ultrasonography of the pancreas. 3. Doppler imaging.

Ultrasonography is probably the most widely used medical imaging technique. In fact, its non-invasivity, portability, widespread distribution and good clinical results have made it the preferred method for a first imaging approach to patients in a large variety of clinical settings. Ultrasound technology is advancing rapidly, aimed to increase image quality. In particular, increased color-Doppler sensitivity is contributing to the diagnosis and staging of pancreatic disease. Doppler studies are in fact integral part of ultrasound examination of the pancreas evaluating the peripancreatic vascular structures enclose portal vein, splenic artery and vein, superior mesenteric artery and vein, aorta, and inferior vena cava. While flows in all peri-pancreatic vessels are well recognized, only few parenchymal vessels are usually appreciable in normal conditions. Anyway the increased Doppler sensitivity allows the visualization of smaller peri-pancreatic and intra-pancreatic vessels. This article will review the technical background underlying the clinical application of Doppler ultrasonography in pancreatic imaging, with particular emphasis to normal vascular anatomy of the pancreas, and to the main applications of Doppler techniques in the different pancreatic pathologies.

Dexamethasone -induced apoptosis of human monocytes exposed to immune complexes. Intervention of CD95- and XIAP-dependent pathways.

Monocytes and macrophages play a key role in the initiation and persistence of inflammatory reactions. The possibility to interfere with the survival of these cells, once recruited and activated at sites of inflammation, is an attractive therapeutic option. Although resting monocytes are susceptible to pharmacologically induced apoptosis, no data are available about the possibility to modulate the survival of activated monocytes. The present work was planned to investigate if dexamethasone is able to promote apoptosis of human monocytes activated by immune complexes. When monocytes were cultured with immune complexes, a dose-dependent inhibition of apoptosis was observed. Dexamethasone stimulated apoptosis of resting and activated monocytes in a dose-dependent manner. Both the immune complex inhibitory activity and dexamethasone stimulatory properties depend on NF-kappaB/XIAP and Ras/MEK/ERK/CD95 pathways. In fact, the exposure of monocytes to immune complexes increased NF-kB activation and XIAP expression, which in turn were inhibited by dexamethasone. On the other hand, immune complex-stimulated monocytes displayed a reduced expression of CD95, which is prevented by dexamethasone, as well as by MEK inhibitor U0126. Furthermore, anti-CD95 ZB4 mAb prevented dexamethasone-induced apoptosis in immune complex stimulated monocytes. Similarly, ZB4 inhibited dexamethasone-mediated augmentation of caspase 3 activity. The present findings suggest that Fc triggering by insoluble immune complexes result in the activation of two intracellular pathways crucial for the survival of monocytes: 1. Ras/MEK/ERK pathway responsible for the down-regulation of CD95 expression; 2. NF-kappaB pathway governing the expression of XIAP. Both the pathways are susceptible to inhibition by monocyte treatment with pharmacologic concentrations of dexamethasone.

Effect of different cytokines on mammaglobin and maspin gene expression in normal leukocytes: possible relevance to the assays for the detection of micrometastatic breast cancer.

In cancer patients, the ability to detect disseminated tumour cells in peripheral blood or bone marrow could improve prognosis and consent both early detection of metastatic disease and monitoring of the efficacy of systemic therapy. These objectives remain elusive mainly due to the lack of specific genetic markers for solid tumours. The use of surrogate tissue-specific markers can reduce the specificity of the assays and give rise to a clinically unacceptable false-positive rate. Mammaglobin (MAM) and maspin are two putative breast tissue-specific markers frequently used for detection of occult tumour cells in the peripheral blood, bone marrow and lymph nodes of breast cancer patients. In this study, it was evaluated whether MAM and maspin gene expression may be induced in the normal blood and bone marrow cells exposed to a panel of cytokines, including chemotactic factors (C5a, interleukin (IL)-8), LPS, proinflammatory cytokines (TNF-alpha, IL-1beta) and growth factors (IL-3, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor). The experimental data show that all cytokines included in the panel, except for IL-8, were able to induce maspin expression; on the contrary, MAM gene was never induced. These results suggest that MAM is more specific than maspin and that the possible interference of cytokines should be taken into account in interpreting molecular assays for detection of isolated tumour cells.

Primary and secondary malignancies of the penis: ultrasound features.

Cancer of the penis is a rare neoplasm in developed countries but worldwide represents a significant health problem. In this study, the ultrasonographic features of primary and secondary malignant lesions of the penis are described. Squamous cell carcinoma usually presents as a hypoechoic lesion with heterogeneous appearance. Invasions of the corpora cavernosa and the corpus spongiosum are appreciable. B-cell lymphoma presents as well-vascularized mass, a plaque, or ulcers in the penile skin. Penile metastases results from hematogenous or lymphatic spreading of distant tumors or, more frequently, as penile infiltration by tumors from adjacent organs. Diffuse corporeal or nodular involvement can result.