Potential use of contrast-enhanced ultrasound (CEUS) in the detection of metastatic superficial lymph nodes in melanoma patients.

PURPOSE: Malignant melanoma represents a significant and growing public health burden worldwide. Ultrasonography is the most useful diagnostic modality for regional lymph nodal staging. Because any focal areas of cortical lobulation or thickening-swelling should also be considered as a sign of metastases, we are going to report the usefulness of contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of benign or malignant lymph nodes in patients with malignant melanoma based on blood stream patterns and investigate the diagnostic capability. PATIENTS AND METHODS: After the excision of cutaneous melanoma with positive excision margins but with negative sentinel lymph node, 540 patients underwent US of superficial lymph nodes. The inclusion criteria for CEUS consisted of both major signs (absence of the echogenic hilus, round shape, and peripheral capsular vascularity) and minor ones (the presence of focal cortical thickening). The diagnostic capability was evaluated by comparing the cytological findings with the enhancement pattern on CEUS.  RESULTS: US in combination with CEUS correctly classified 534/540 patients. CEUS applied to lymph nodes with focal cortical thickening on grayscale US confirmed great sensitivity (0.98) and specificity (0.99) but above all, it showed a markedly improved accuracy of 0.99. The likelihood ratios confirmed the good performance of the methods used. CONCLUSION: CEUS increases the diagnostic accuracy of US in the differential diagnosis of benign and malignant LNs but it also allows us, when possible, to avoid unnecessary invasive operations such as LN FNAC. Moreover, CEUS may guide FNAC in the case of focal cortical thickening on the basis of hypoperfusion, with a reduction in the number of false negatives and much earlier detection of nodal metastatic foci.

Role of multidetector CT angiography and contrast-enhanced ultrasound in redefining follow-up protocols after endovascular abdominal aortic aneurysm repair.

PURPOSE: Contrast-enhanced ultrasonography (CEUS) is an appealing alternative to computed tomography angiography (CTA) for the follow-up of patients who underwent endovascular abdominal aortic aneurysm repair (EVAR). We sought to evaluate the accuracy of CEUS compared with a particularly tailored protocol of CTA performed with a 64-row multidetector CT. MATERIALS AND METHODS: The study prospectively enrolled 88 consecutive patients for CEUS and CTA imaging during follow-up after EVAR, yielding 142 paired examinations. The outcome is represented by three main goals: identification and characterisation of endoleaks, evaluation of graft patency and measurement of aneurysm diameter. Triple-phase CTA was the gold standard. RESULTS: Sensitivity and specificity of CEUS compared with CTA in endoleak and graft patency evaluation were 91.89% and 100% and 72% and 100%, respectively. A very high correlation between CTA and CEUS diameter measurements was established. CEUS did not appear superior to CTA in endoleak detection, probably because a tailored CTA protocol with a delayed phase (180 s) allows detection of low-flow endoleaks. CONCLUSIONS: Patient management was not different following CEUS and CTA results. CTA cannot yet be completely replaced, but several limitations (radiation exposure, contrast agent) encourage redefining the routine follow-up imaging modality. We suggest an algorithm of surveillance alternating CTA and CEUS.

Synovial colony-stimulating factor-1 mRNA expression in diffuse pigmented villonodular synovitis.

OBJECTIVES: To delineate the molecular mechanisms underlying the process of the diffuse-type giant cell tumours, also called pigmented villonodular synovitis, a rare, aggressive condition of the synovium, the knee synovial tissue expression of colony-stimulating factor-1 gene, as detected by real-time polymerase chain reaction, was compared between patients affected with pigmented villonodular knee synovitis and knee meniscal tears, or persistent gonoarthitis. METHODS: Multiple synovial biopsies of the knee were performed by arthroscopy in five consecutive patients affected by diffuse pigmented villonodular knee synovitis and in 12 patients affected by knee meniscal tears (n. 6) or persistent active gonarthritis (n. 6), recruited from the patients attending the Rheumatology Day Surgery Outpatient Clinic of the University of Padova Hospital. The ethics committee approved the study protocol and the participants signed consent statements after being informed about the content of the study. The diagnosis was made on the basis of a histological examination. The colony-stimulating factor-1 gene expression was assessed by reverse transcription followed by real-time polymerase chain reaction. RESULTS: The detection by RT-PCR of synovial colony-stimulating factor-1 mRNA showed a wide spectrum of expression in the three groups of distinct knee joint disease affected patients, with significantly higher level of colony-stimulating factor-1 mRNA expression in synovial tissue of pigmented villonodular synovitis, in comparison to that of knee meniscal injuries and persistent gonoarthritis patients. CONCLUSIONS: Our findings point out to an important role of colony-stimulating factor-1 in pigmented villonodular knee synovitis disease process and support the idea that colony-stimulating factor-1/colony-stimulating factor-1 receptor interaction may represent a potential therapeutic target of this disease.

Quality control of ultrasound transducers: analysis of evaluation parameters and results of a survey of 116 transducers in a single hospital.

PURPOSE: The aim of this study was to develop a quality control programme for ultrasound equipment and assess equipment performance at a single hospital. MATERIALS AND METHODS: We tested 116 transducers by means of a phantom; ultrasound quality control tests were done on parameters from B-mode images, and each parameter was rated according to a three-point score as good, sufficient or poor. RESULTS: Surface transducers showed worse performance in terms of image uniformity, with 7/55 (13%) transducers rated poor, and depth of penetration, with 24/55 (44%) transducers, rated sufficient or poor. The 3.5-MHz transducers showed worse performance in lateral resolution, with 18/48 (38%) rated poor, and particularly in focusing, with 40/48 (83%) classified as poor. In addition, the 3.5-MHz transducers proved less accurate in vertical distance accuracy than in horizontal distance, with 31/48 (64%) considered sufficient. No significant geometric distortions of masses were identified, although 4/116 (3%) transducers failed to visualise two masses. CONCLUSIONS: The first goal of an ultrasound quality control programme is to establish specific parameters to evaluate equipment performance and, should results be below recommended action levels, implement corrective measures.

MRI in the assessment of muscular pathology: a comparison between limb-girdle muscular dystrophies, hyaline body myopathies and myotonic dystrophies.

PURPOSE: The continuous discovery of new subtypes of neuromuscular disorders demands more accurate imaging analyses. We set out to establish the specific patterns of muscular involution using magnetic resonance imaging (MRI). MATERIALS AND METHODS: A systematic clinical evaluation based on the Medical Research Council scale and MRI was completed in ten patients with calpainopathy [limb-girdle muscular dystrophy (LGMD)-2A], 16 with dysferlinopathy (LGMD-2B), ten with hyaline body myopathy (HBM), six with myotonic dystrophy (MD) types 1 and 5 with MD type 2. Severity of fibroadipose degeneration was specifically staged using T1-weighted sequences. Turbo inversion recovery magnitude (TIRM) sequences were used to assess oedema-like changes. RESULTS: T1 scans showed recurrent patterns of fibroadipose replacement, whereas TIRM images revealed differences in oedema-like changes between the various diseases. In LGMD, the posterior compartments are more vulnerable to degeneration. In HBM, fatty muscle degeneration and oedema are allocated to muscles of the posterior compartments of the leg. In MD, fatty muscle degeneration and oedematous changes are allocated to muscles of the anterior thigh and posterior lower leg. CONCLUSIONS: Imaging examination suggests a characteristic pattern of muscle involvement. MRI represents an important diagnostic technique useful in differential diagnosis, thanks to the distinctive patterns observed in the distribution of muscular changes between the different muscular diseases.

Differential diagnosis of benign and malignant thyroid nodules at elastosonography.

PURPOSE: Ultrasound of the neck detects a large number of non-palpable thyroid nodules in the population, but it offers poor diagnostic accuracy (the presence of microcalcifications is the only statistically significant criterion indicative of malignancy). The aim of this study is to evaluate elastography, a technique which allows differentiation between pathological and normal tissue by determining its hardness and which could also prove useful in the characterisation of thyroid nodules. MATERIALS AND METHODS: In this prospective study, 51 thyroid nodules in 40 consecutive patients were examined (25 women, 15 men, mean age +/- SD, 54 +/- 13.4). Elastosonography was performed by real-time, free-hand technique, using Logos HiVision equipment with a 10 MHz transducer and lesions were classified and scored in 4 classes of hardness. All patients were also examined by grey scale high frequency ultrasound and colour Doppler. Final diagnoses were obtained from cytological and/or histological evaluation. RESULTS: Final diagnoses revealed 11 malignant and 40 benign nodules. Only in two cases ultrasound demonstrated signs useful for a differential diagnosis (intrinsic microcalcifications). Correct differentiation of malignant from benign nodules was obtained by elastosonography in 43 / 51 cases with 5 false positives (FP) and 3 false negatives (FN). Specificity, sensitivity and accuracy were 87.5 %, 81.8 % and 86.2 %, respectively. Predictive negative value (PNV) and predictive positive value (PPV) were 94.5 % and 64 % area under the curve (AUC) 0.86. CONCLUSION: Elastosonography provides an interesting contribution to the differentiation of malignant and benign thyroid nodules. Particularly worthy of mention is that an entirely elastic nodule pattern was observed only in relation to benign nodules, a result which would suggest that immediate recourse to FNAB might be avoided.

[Intra-articular treatment with the TNF-alpha antagonist, etanercept, in severe diffuse pigmented villonodular synovitis of the knee]. / Trattamento intra-articolare con l'antagonista del TNFalpha etanercept nella sinovite villo-nodulare pigmentosa diffusa del ginocchio.

Pigmented villonodular synovitis (PVNS) is a rare pre-malignant disease that require aggressive treatment as surgical synovectomy, eventually followed by radiosynovectomy. Nevertheless, the disease often reoccurs after these treatments. To determine the safety and efficacy of intra-articular (IA) TNFalpha blockade with etanercept (ETN), before extended arthroscopic synovectomy, in severe PVNS of the knee, two patients, (a 26-year-old man with B27+ undifferentiated spondylarthropathy and a 32-year-old femal with seronegative oligoarthritis), affected by diffuse knee PVNS (diagnosis made by histological examination), resistant to IA corticosteroid injections and to repeated arthroscopic synovectomy, were submitted, after protocol approval by human research committee and patient's written informed consent to intra-articular etanercept (IA-ETN) treatment with a different dosage schedule: 12.5 mg weekly IA-ETN injection for 4 weeks, followed by extended arthroscopic synovectomy and of 25 mg IA-ETN injection for 4 weeks, respectively. Previous DMARDs treatment was continued in stable appropriate doses. Any adverse events were recorded throughout the study. The following parameters were considered as clinical endpoints: 1) Knee Joint Index (KJI: range 0-14); 2) Thompson index (THI: range 0-9) At the study entry and at the end of follow-up, high frequency ultrasound grey scale synovial thickening (US-ST) was also assessed. No adverse events were observed due to IA-ETN and to arthroscopic synovectomy. Marked improvement of knee disease activity over time and sustained functional recover was obtained. US-ST evaluation before treatment initiation and at the end of follow-up confirmed the regression of knee joint synovial proliferation.

The impact of ultrasound scanning in the staging and follow-up of patients with clinical stage I cutaneous melanoma.

In 85 patients with intermediate to high risk cutaneous melanoma, concomitant palpation and ultrasound scanning (US) of the axillary and inguinal sites were performed in order to detect any locoregional lymph node metastases at pre-operative staging and postoperative monitoring. At 12 months follow-up, US identified 12 out of 13 (92%) histologically proven metastases, while palpation indicated metastatic disease in only 3 (23%) patients. Metastases were intranodal in 6 out of 12 cases detected with US, and extranodal in all the 3 cases identified by palpation, thus confirming that US is more effective than palpation in the early detection of lymph node metastases from melanoma. US was also more effective in discriminating all non-neoplastic lymph nodes: its overall specificity was 100% versus 85% for palpation. Thus, when carried out by well-trained radiologists, US is a very useful diagnostic tool for the surgical oncologist dealing with melanoma patients.

Sentinel node biopsy and ultrasound scanning in cutaneous melanoma: clinical and technical considerations.

1.5 mm and in all cases with two metastatic SNs, further positive additional nodes were found. The mean counts per 10 s (CP10S) ratio for SN and non-SN values was 5.62 (1.29-23.51) and 3.09 (1.03-10.99) in the intra-operative and extra-operative phases, respectively. US scanning and preoperative lymphoscintigraphy associated with PBD allows preoperative patient selection and accurate SN(s) identification. Breslow thickness and the number of metastatic SN(s), but not their type, are correlated with disease spread; CP10S contributed to the differentiation amongst the nodes and the determining of procedure's completion.

Therapy of acute pancreatitis in systemic lupus erythematosus with plasmapheresis and corticosteroids.

A 24-year-old woman with systemic lupus erythematosus had, after reduction of corticosteroid therapy, a severe relapse of the disease with hepatitis, nephritis and pleurisy. After admission to the hospital, she was given 60-80 mg/day of prednisone and acute pancreatitis developed on the third day. Plasmapheresis, followed by injection of 1 g of methylprednisolone, was started. This combined therapy induced a prompt and complete recovery in a few days.

The role of vascularization in the formation of echographic patterns of hepatic metastases: microangiographic and echographic study.

An experimental microangiograhic and echographic study was carried out on metastatic autopsy livers which were also examined histologically. Relationships between the echographic pattern and vascularization are explored. In most cases, hypervascular lesions correspond to hyperechogenic patterns, while hypovascular lesions furnish hypoechogenic images.

Infantile recurrent sialectatic parotitis: the role of sonography and sialography in diagnosis and follow-up.

The results of a clinical, sonographic and sialographic study in 10 children (aged 4-10 years) with recurrent sialectatic parotitis are presented. Alteration in the sonographic pattern of the parotid glands, consisting of multiple hypoechogenic areas in the parenchyma, were found in four cases; milder nonhomogeneity was seen in four cases, and an almost normal pattern in two cases. Sonographic follow-up in two children showed a parallel reduction in non-homogeneity with symptomatic improvement. A probable therapeutic action following sialography using fat-soluble contrast medium was observed in four of the 10 children. The familial nature of the disease, which has not previously been described, is documented.

Pancreatic cystadenocarcinoma: diagnostic problems.

Eleven cases of pancreatic cystadenocarcinoma were studied with respect to the differential diagnosis from that of pancreatic pseudocysts, using diagnostic ultrasound as the initial investigative technique. Most of the cases presented an ultrasonic picture that correlated well with the gross pathology, but this correlation was not reliable enough to be considered characteristic in differentiating such masses from pseudocysts. The authors divide the cystadenocarcinomas of the pancreas into four echographic classes. In all but one of the classes, diagnostic ultrasound was insufficient by itself to render an accurate diagnosis. In such cases other techniques, i.e. CT, tissue biopsy, and especially angiography, were required for a reliable diagnosis.

Ultrasonographic evaluation of superficial lymph node metastases in melanoma.

The aims of the present work were to assess the diagnostic accuracy of ultrasonographic evaluation of superficial lymph nodes in patients with cutaneous melanoma and to describe the sonographic characteristics which permit early detection of neoplastic nodal involvement. Eighty-seven patients (89 lymph node sites) were studied for approximately a 3-year period, with a minimal surveillance time of 1 year. The ultrasonographic imaging equipment utilized were a 10 MHz scanner with a mechanical and one with 10 MHz electronic linear probe. The characteristics considered indicative of possible metastatic involvement were: round shape (short to long axis ratio > 0.5), no central hilus, nodular areas within the lymph node, sinuosity of the lymph node edges and lymph node with regular morphology and echostructure but with maximum diameter greater than 3 cm. Generally inguinal and axillary lymph nodes are larger than cervical ones. Of the 89 sites explored, 32 were considered 'suspect'. All 32 of these were subjected to cytology using ultrasound-guided, fine needle aspiration. The remaining 56 came in for a periodic control examination during a year. Thirteen of the 32 'suspect' lymph nodes proved positive at the pathologic examination. Two patients whose ultrasound diagnosis was negative developed metastases within 2 to 4 months (ultrasound false negatives). Our study indicates that there are sonographic features indicative of lymph node metastases from melanoma even in the early stages of the disease. Ultrasound scanning, therefore, is a useful diagnostic tool in the follow-up of melanoma patients, identifying which should be subjected to further testing with needle biopsy.

Sentinel node biopsy in cutaneous melanoma patients: technical and clinical aspects.

The role of the patent blue dye (PBD) technique and intraoperative probe-guided lymphoscintigraphy (LS) in detecting the sentinel node (SN) was investigated in a group of 130 consecutive stage I cutaneous melanoma patients. The preoperative workup included high-resolution US scanning and LS performed 15-18 hours before surgery. On the basis of preoperative LS, in the group of examined patients a total of 143 lymphatic drainage basins were identified and surgically explored: 41.6% in the axilla, 52.8% in the groin, and 5.6% in the head/neck. A total of 228 SNs were intraoperatively detected and removed; 110 lymphatic basins contained histologically negative SNs, while 33 basins had metastatic SNs. The sensitivity for SN detection using PBD alone was 93%, while it was 100% when PBD was combined with intraoperative LS. Preoperative and intraoperative LS appears to be a highly sensitive technique for SN detection in cutaneous melanoma patients. Furthermore, in view of the limited skin incision when radioguided surgery is performed, SN biopsy could be feasible under local anesthesia.

Temporary occlusion of the hepatic artery plus infusion and systemic chemotherapy for inoperable cancer of the liver.

Fourteen patients with diffuse tumors of the liver were treated with temporary occlusion of the hepatic artery (HA) by an external tourniquet followed by infusion and systemic chemotherapy. Three patients had primary neoplasms (one hepatocarcinoma and two cholangiocarcinomas) and eleven had metastatic disease (nine from carcinoma of the colon and rectum, one from retroperitoneal liposarcoma, and one from pulmonary small cell cancer). Infusion chemotherapy in all patients was based on 5-FU, Mitomycin and Vincristine. Systemic chemotherapy was FIVB in metastatic carcinoma and Adriamycin in primary liver tumors. All patients showed improvement of the performance status according to the Karnofsky Index. Objective response (OR) was present in 54% of cases. At present, median survival time in 12.5 months. Aggressive treatment combining hepatic ischemia with infusion and systemic polychemotherapy seems to provide an effective method of palliation in diffuse tumors of the liver. Delayed occlusion by an external tourniquet appears safer than intraoperative ligation of the HA.

Ultrasound monitoring of gestosis polycentric study.

In polycentric research we studied 62 selected cases of gestosis to evaluate which symptom is greatly correlated with the deficit of fetal growth. According to us, the earlier the syndrome appearance the clearer the deficit of fetal growth.

Contrast-enhanced ultrasound findings in soft-tissue lesions: preliminary results.

OBJECTIVES: There is currently no widely available, minimally invasive first-level examination that allows physicians to identify soft-tissue lesions that are likely to be malignant. The aim of this pilot study was to explore the potential suitability of dynamic contrast-enhanced ultrasound (DCE-US) for this purpose. MATERIALS AND METHODS: 23 patients were referred to the Veneto Oncological Institute for work-up of superficial soft-tissue lesions. Fourteen lesions were examined with CEUS and enhancement kinetics was analyzed. Subsequently, all lesions were surgically removed and subjected to histological analysis. RESULTS: The 14 lesions included in the study were histologically classified as malignant (n = 7) or benign (n = 7, including 3 schwannomas). A statistically significant difference between benign and malignant lesions was found in terms of mean times to peak enhancement intensity (p = 0.03) but not mean filling times (FT). When schwannomas were analyzed as a separate group, their mean FT was found to be significantly different from that of the other benign lesions (p = 0.001) and from that of the group comprising other benign lesions as well as malignant lesions (p < 0.005). CONCLUSIONS: CEUS with analysis of contrast-enhancement kinetics is a relatively low-cost, minimally invasive imaging technique, which appears to be a potentially effective first-level method for identifying suspicious soft-tissue masses.

Molecular pathways involved in synovial cell inflammation and tumoral proliferation in diffuse pigmented villonodular synovitis.

Diffuse-type tenosynovial giant cell tumors, also known as pigmented villonodular synovitis, are unique mesenchymal lesions that arise from the synovial tissue of the joints. They are predominantly intraarticular, aggressive, infiltrative processes, characterized by both inflammatory or neoplastic properties and local destructive progression. The pattern of synovial gene and protein expressions in pigmented villonodular synovitis, similar to those in activated macrophages in rheumatoid arthritis, and the phenotype of multinucleated giant cells, characteristic of osteoclasts, suggest that there is a common autocrine mechanism in osteoclast differentiation in both diseases and indicate the potential utility of tumor necrosis factor (TNF)-alpha blockade. High synovial colony stimulating factor 1 (CSF1) messenger RNA (m RNA) expression in pigmented villonodular synovitis, unrelated to a chromosomal translocation involving CSF1 locus, may indicate that there is a synergic paracrine loop mediated by TNF-alpha and CSF1, as shown in both inflammatory and neoplastic conditions. The effects of a new therapeutic approach consisting in intraarticular TNF-alpha blockade were studied in four pigmented villonodular synovitis knees. Knee injections produced a rapid reduction in clinical and sonographic indexes and immunohistological alterations, confirmed by arthroscopic synovectomy. A delayed relapse in one of the four knees and unaltered synovial CSF1 expression were other important findings. In the light of these observations, CSF1/CSF1R interaction probably represents a more sensible therapeutic target than TNF-alpha blockade in the diffuse form of pigmented villonodular synovitis.

The role of sonoelastography in the differential diagnosis of neck nodules.

Sonoelastography is an imaging technique that provides information on tissue elasticity. Its use as a diagnostic procedure is based on the premise that pathological processes like cancer alter the physical characteristics of the involved tissue. Ultrasonographic studies of the neck can reveal the nonpalpable thyroid nodules, but the nature of these lesions generally has to be established on the basis of FNAB findings. In our hands, sonoelastography displayed a diagnostic accuracy of 86.2% in identifying thyroid nodule malignancy, with positive and negative predictive values (PPV and NPV) of 64% and 94.5%, respectively. In the study of cervical lymph nodes, the results were less impressive (sensitivity 75%, specificity 80%, accuracy 77%, PPV 80%, NPV 70%), but the information obtained with this technique can in our opinion be a useful adjunct to sonographic findings. Indeed, in 5 lymph nodes with sonographic features consistent with malignancy, sonoelastography revealed diffuse elasticity that was indicative of benign disease, which was confirmed by pathological studies. Other nodular lesions of the neck can also be evaluated with sonoelastography, including enlarged parotid glands, but the data in the literature are too limited to allow hypotheses on the role of this imaging modality in this field. Sonoelastography is rapid and simple to perform, and it appears to be a potentially useful tool for the differential diagnosis of neck nodules. This is particularly true of thyroid nodules. Our experience with these lesions indicates that diffuse elasticity is strongly correlated with benign disease. If this finding is confirmed in larger studies, sonoelastography might be used to identify thyroid nodules that do not require immediate biopsy.