Small Subcutaneous Soft Tissue Tumors (<5 cm) Can Be Sarcomas and Contrast-Enhanced Ultrasound (CEUS) Is Useful to Identify Potentially Malignant Masses.

Subcutaneous masses smaller than 5 cm can be malignant, in contrast with the international guidelines. Ultrasound (US) and magnetic resonance imaging (MRI) are useful to distinguish a potentially malignant mass from the numerous benign soft tissue (ST) lesions. Contrast-enhanced ultrasound (CEUS) was applied in ST tumors, without distinguishing the subcutaneous from the deep lesions. We evaluated CEUS and MRI accuracy in comparison to histology in differentiating malignant from nonmalignant superficial ST masses, 50% smaller than 5 cm. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) with their 95% confidence intervals (CI) were calculated. Of malignant cases, 44.4% measured ≤5 cm. At univariate analysis, no statistically significant differences emerged between benign and malignant tumors in relation with clinical characteristics, except for relationship with the deep fascia (p = 0.048). MRI accuracy: sensitivity 52.8% (CI 37.0, 68.0), specificity 74.1% (CI 55.3, 86.8), PPV 73.1% (CI 53.9, 86.3), and NPV 54.1% (CI 38.4, 69.0). CEUS accuracy: sensitivity 75% (CI 58.9, 86.3), specificity 37% (CI 21.5, 55.8), PPV 61.4% (CI 46.6, 74.3), and NPV 52.6% (CI 31.7, 72.7). CEUS showed a sensitivity higher than MRI, whereas PPV and NPV were comparable. Also, masses measuring less than 5 cm can be malignant and referral criteria for centralization could be revised.

Technical and clinical feasibility of contrast-enhanced ultrasound evaluation of long bone non-infected nonunion healing.

PURPOSE: To assess the technical feasibility of contrast-enhanced ultrasound (CEUS) in the monitoring of non-infected long bone nonunion healing. METHODS: Twenty-five patients (16 males; mean age: 40.4 ± 11.7) with long bone nonunion were treated using surgery and mesenchymal stem cells and platelet-rich plasma. They performed CEUS up to 15 days before, 7 days, 4 and 8 weeks after treatment. To categorize the angiogenesis around the fracture site, the microvascular blood flow from CEUS was classified into four categories, depending on the portion of the investigated area that was involved in the neovascularization process: grade 0 = 0%; grade 1 = 0-30%; grade 2 = 30-70%; grade 3 = 70-100%. Nonparametric Friedman and Wilcoxon statistics were used. RESULTS: Before treatment, neovascularization was graded as 0 in 15/25 patients, as 1 in 10/25. Vascularity significantly increased over time (P < 0.001), namely: 1 (25th-75th percentile = 1-2) at 7 days; 2 (1-2) at 4 weeks; 3 (0-2) at 8 weeks. All patients but one showed early progressive increase in neovascularization well identified with CEUS at the fracture site. CONCLUSION: CEUS is a feasible method to monitor healing in patients with long bone nonunion.

In Achilles tendinopathy, the neovascularization, detected by contrast-enhanced ultrasound (CEUS), is abundant but not related to symptoms.

PURPOSE AND HYPOTHESIS: Mid-portion Achilles tendinopathy is characterized by a proliferation of small vessels, called neovascularization, which can be demonstrated by power Doppler sonography (PD). Neovascularization can be correlated with diagnosis and consequent therapies focused on vascular supply. Published data regarding the relationship between neovascularisation and symptoms, such as pain and disability, are contradictory. The hypothesis that contrast-enhanced ultrasound (CEUS) could detect with more sensibility than PD the new vessel ingrowth in human degenerated Achilles tendons and therefore the correlation of neovascularization with pain and disability, was evaluated. METHODS: Thirty consecutive patients of recalcitrant Achilles tendinopathy were studied with ultrasound greyscale (US), PD, CEUS and magnetic resonance imaging. Neovascularization was recorded as percentage on the whole extension of examined area. The vascularization time was recorded as venous and arterial type. Imaging data were classified both concurrently with the examination and in a secondary blinded assessment; any difference in the subjective assessment was discussed and a consensus view formed. Pain and disability were assessed by Western Ontario McMaster Universities Arthritis Index (WOMAC) and EuroQuality of life 5-dimension-5-level questionnaire and visual analogue scale (EQ-VAS). All results were analysed with suitable statistical methods. RESULTS: 76.7% of cases were degenerated; 23.3% had also partial discontinuity of the fibres. PD detected vascularization in 54% of cases, whereas CEUS in 83% of cases: in 13 cases, PD did not detect vascularization. The vascularization time was rapid (< 20 s, arterial type) in 60% of cases. WOMAC pain mean value is 6.4 and SD 3.4; WOMAC total score mean value is 21.6 and SD 12.8. EQ-VAS mean value is 56 and SD 18.3. No statistically significant correlation emerged between vascularization and pain/disability. CONCLUSIONS: CEUS showed a greater ability to detect neovessels than PD in chronic Achilles tendinopathies. Nevertheless in 30 consecutive tendinopathies, no correlation between pain/disability and neovascularization was found: the role of multiple neovessels continue to be unclear. The possibility to discriminate arterial from venous vessels ('vascularization time') could be useful to understand the pathophysiology of tendinopathies and its healing process. STUDY TYPE: Diagnostic study. LEVEL OF EVIDENCE: II.

Accuracy and role of contrast-enhanced CT in diagnosis and surgical planning in 88 soft tissue tumours of extremities.

OBJECTIVES: Soft tissue tumours (STT) require accurate diagnosis in order to identify potential malignancies. Preoperative planning is fundamental to avoid inadequate treatments. The role of contrast-enhanced computed tomography (CT) for local staging remains incompletely assessed. Aims of the study were to evaluate CT accuracy in discriminating active from aggressive tumours compared to histology and evaluate the role of CT angiography (CTA) in surgical planning. MATERIALS AND METHODS: This retrospective cohort series of 88 cases from 1200 patients (7 %) was locally studied by contrast-enhanced CT and CTA in a referral centre: 74 malignant tumours, 14 benign lesions. Contrast-enhancement patterns and relationship of the mass with major vessels and bone were compared with histology on surgically excised samples. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were evaluated in discriminating active from aggressive tumours. RESULTS: Sensitivity in differentiating aggressive tumours from active lesions was 89 %, specificity 84 %, PPV 90 %, NPV 82 %. The relationship between mass and major vessels/bone was fundamental for surgical strategy respectively in 40 % and in 58 % of malignant tumours. CONCLUSION: Contrast-enhanced CT and CTA are effective in differentiating aggressive masses from active lesions in soft tissue and in depicting the relationship between tumour and adjacent bones and major vessels. KEY POINTS: • Accurate delineation of vascular and bony involvement preoperatively is fundamental for a correct resection. • CT plays a critical role in differential diagnosis of soft tissue masses. • Contrast-enhanced CT and CT angiography are helpful in depicting tumoral vascular involvement. • CT is optimal for characterization of bone involvement in soft tissue malignancies.

Perfusion pattern and time of vascularisation with CEUS increase accuracy in differentiating between benign and malignant tumours in 216 musculoskeletal soft tissue masses.

INTRODUCTION: Musculoskeletal Soft Tissue Tumours (STT) are frequent heterogeneous lesions. Guidelines consider a mass larger than 5 cm and deep with respect to the deep fascia potentially malignant. Contrast Enhanced Ultrasound (CEUS) can detect both vascularity and tumour neoangiogenesis. We hypothesised that perfusion patterns and vascularisation time could improve the accuracy of CEUS in discriminating malignant tumours from benign lesions. MATERIALS AND METHODS: 216 STT were studied: 40% benign lesions, 60% malignant tumours, 56% in the lower limbs. Seven CEUS perfusion patterns and three types of vascularisation (arterial-venous uptake, absence of uptake) were applied. Accuracy was evaluated by comparing imaging with the histological diagnosis. Univariate and multivariate analysis, Chi-square test and t-test for independent variables were applied; significance was set at p<0.05 level, 95% computed CI. RESULTS: CEUS pattern 6 (inhomogeneous perfusion), arterial uptake and location in the lower limb were associated with high risk of malignancy. CEUS pattern has PPV 77%, rapidity of vascularisation PPV 69%; location in the limbs is the most sensitive indicator, but NPV 52%, PPV 65%. The combination of CEUS-pattern and vascularisation has 74% PPV, 60% NPV, 70% sensitivity. No correlation with size and location in relation to the deep fascia was found. CONCLUSION: US with CEUS qualitative analysis could be an accurate technique to identify potentially malignant STT, for which second line imaging and biopsy are indicated in Referral Centers. Intense inhomogeneous enhancement with avascular areas and rapid vascularisation time could be useful in discriminating benign from malignant SST, overall when the lower limbs are involved.

Accuracy of core-needle biopsy after contrast-enhanced ultrasound in soft-tissue tumours.

OBJECTIVE: Percutaneous biopsies are gaining acceptance in the diagnosis of soft-tissue tumours. Sampling in the most representative area is not easy in sarcomas of huge dimension. We hypothesised that ultrasound (US) contrast medium could identify the representative area for focus core-needle biopsy (CNB) METHODS: This is a retrospective cohort series of 115 soft-tissue masses treated from January 2007 to November 2008. Accuracy of US-guided CNB after contrast-enhanced US (CEUS) was determined by comparing the histology of the biopsy with the definitive diagnosis in 105 surgically excised samples (42 benign, 63 malignant) and with the expected outcome in the remaining ten malignant cases not surgically treated. A myxoid component was present in 21 sarcomas (34.4%). RESULTS: Of samples, 94.8% were adequate for diagnosis with 97.1% sensitivity and 92.5% specificity. Sensitivity and specificity in specific histopathological subgroupings were 100%, and in grading definition they were 100% and 96.8%. DISCUSSION: US-guided CNB is safe and effective. US contrast medium depicts tumour vascular supply and identifies the representative area(s) for sampling. Sensitivity and specificity are also high in subgrouping and grading, including myxoid types. Discussion about biopsy is part of the essential multidisciplinary strategy for these tumours.

CEUS in abdominal trauma: multi-center study.

The objective of this study was to evaluate the concordance of US and contrast-enhanced US (CEUS) with CT in the assessment of solid organ injury following blunt trauma. Patients underwent complete US examination, including free fluid search and solid organ analysis. CEUS followed, using low-mechanical index techniques and SonoVue. CT was performed within 1 h. Among 156 enrolled patients, 91 had one or more abnormalities (n = 107) at CT: 26 renal, 38 liver, 43 spleen. Sensitivity, specificity, and accuracy for renal trauma at baseline US were 36%, 98%, and 88%, respectively, after CEUS values increased to 69%, 99%, and 94%. For liver baseline US values were 68%, 97%, and 90%; after CEUS were 84%, 99%, and 96%. For spleen, results were 77%, 96%, and 91% at baseline US and 93%, 99%, and 97% after CEUS. Per patient evaluation gave the following results in terms of sensitivity, specificity and accuracy: 79%, 82%, 80% at baseline US; 94%, 89%, and 92% following CEUS. CEUS is more sensitive than US in the detection of solid organ injury, potentially reducing the need for further imaging. False negatives from CEUS are due to minor injuries, without relevant consequences for patient management and prognosis.

Contrast enhanced gray-scale sonography in assessment of joint vascularity in rheumatoid arthritis: results from the IACUS study group.

The purpose of this study way to assess the value of contrast enhanced gray-scale ultrasound (CEUS) in detection of vascularity in joints of patients with rheumatoid arthritis (RA) in a multicenter study of the International Arthritis Contrast Ultrasound (IACUS) study group. We assessed 113 joints in 113 patients (44 men, 69 women; mean age 51+/-14 years) with clinical diagnosis of RA. Gray-scale ultrasound (US), power Doppler US (PDUS) and CEUS, using a low mechanical index US technique, was performed. CEUS was done by bolus administration of the contrast agent SonoVue (Bracco, Milan, Italy) with a dosage of 4.8-ml SonoVue flushed with 10 ml saline. Detection of joint vascularity was performed for differentiation of active synovitis from inactive intra-articular thickening (synovitis/effusion). With the use of US and PDUS, active synovitis could be differentiated from inactive intra-articular thickening in 68/113 joints (60.1%), whereas CEUS enabled differentiation in 110/113 (97.3%) joints (p<0.0001). Thickness measurement of active synovitis was significantly improved after contrast administration (p=0.008). In conclusion, CEUS improves the differentiation of active synovitis from inactive intra-articular thickening. Since CEUS has shown an ability to improve assessment of vascularized synovial proliferation in RA affected joints, this technique may have further potential in monitoring therapy.

A preliminary experience in the study of soft tissue superficial masses. Color-Doppler US and wash-in and wash-out curves with contrast media compared to histological result.

PURPOSE: A morphological analysis of wash-in and wash-out curves was carried out to assess their significance in the evaluation of superficial masses with US after the introduction of contrast medium, and to compare the findings with the histological analysis. MATERIALS AND METHODS: From April to December 2000 we studied 70 patients with palpable masses in different body sites. Each patient underwent US examination at baseline and after the introduction of Levovist contrast medium (Schering, Berlin, Germany), performed with an AU5 Harmonic device (Esaote Biomedica, Genoa, Italy), using linear probes with frequencies ranging from 7.5 to 13 MHz and software assessing wash-in and wash-out curves. All the patients underwent surgical excision of the mass. Histological confirmation of the nature of the mass was therefore available for all cases. RESULTS: Out of 70 examined patients, 43 had benign and 27 had malignant lesions. In cases of dubious interpretation of ultrasound and MR imaging, color Doppler US with contrast medium and the subsequent analysis of wash-in and wash-out curves exhibited a particular curve pattern indicating the nature of the lesion. DISCUSSION AND CONCLUSIONS: Based on the preliminary data gathered, we believe that the analysis of wash-in and wash-out curves can be useful and reliable in diagnosing an expansile soft tissue lesions. Because our study is still in its early stages and is based on a small number of cases, no conclusions can be drawn as yet but just an observation and description of data obtained.