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1.  HF ultrasound vs PET-CT and telethermography in the diagnosis of In-transit metastases from melanoma: a prospective study and review of the literature 
Over the past several years the incidence of cutaneous melanoma has rapidly increased. This tumor develops often in-transit metastases that significantly reduce patient survival at 5 years. To improve prognosis and quality of life in patients with melanoma metastases, a mini invasive procedure like electrochemotherapy (ECT) is adopted to remove superficial tissue lesions. To detect the melanoma metastases, high frequency (HF) ultrasound (US) is used. This technique, though, can be time-consuming and it needs an expert operator and a high performing machine. Therefore, we asked whether the US could be replaced or integrated with other less time-consuming techniques such as 18-FDG positron emission tomography/computed tomography (PET-CT) and telethermography (TT).
Fifteen patients (4 males and 11 females - age range: 63–91) affected whit advanced stage melanoma were enrolled. They presented 52 in-transit metastases as detected by the three techniques used, HF-US, PET/CT and TT within 30 days before ECT.
All the 52 lesions were detected by HF-US (100%), 24/52 were detected by PET-CT (42,6%) and 15/52 were detected by TT (27,7%). PET-CT reported 3.7% false positives, while no false positive were reported by TT.
As US detected 100% lesions, compared to the other two techniques used, US, along with clinical examination, has still to be considered as gold standard in the diagnosis of metastatic lesions. US, associated with an exhaustive anamnesis and accurate clinical examination, cannot be replaced by either PET-CT or TT. When US performing devices and experienced operators are not available, though, it is highly recommended to integrate US with at least one of the other techniques. Under certain circumstances, as in the case of obese and non-collaborating patients or in patients with lymphatic stasis, these techniques should be integrated to obtain exact in-transit metastases evaluation.
PMCID: PMC4246525  PMID: 25420445
High frequency-ultrasound; 18F-FDG PET-CT; Telethermography; Cutaneous melanoma; In transit-metastases; Electrochemotherapy
2.  The role of ultrasound and ultrasound-guided fine needle aspiration biopsy of lymph nodes in patients with skin tumours 
Radiology and Oncology  2014;48(1):29-34.
The primary aim of this study was to evaluate the diagnostic accuracy of ultrasound (US) in the study of superficial lymph nodes during the follow-up of patients surgically treated for skin tumours. The secondary objective was to compare positive cytological results with histological reports.
Patients and methods
From 2004 to 2011, 480 patients (male/female: 285/195; median age 57 years; prevalent skin tumour: melanoma) underwent US-guided fine-needle aspiration biopsy (FNAB) of suspicious recurrent lymph nodes. An expert radiologist first performed US testing of the lymph nodes, expressing either a negative or positive outcome of the test. Subsequently, US-guided FNAB was performed. FNAB positive patients were subjected to lymphadenectomy; the patients who tested negative underwent the follow-up.
The size of lymph nodes was ≤ 2 cm in 90% of cases. Out of the 336 (70%) US “positive” patients, 231 (68.8%) were FNAB positives. Out of the 144 (30%) US “negatives”, 132 (91.7%) were FNAB negatives. The sensitivity and specificity of the US were 95% and 55.7%, respectively; the negative predictive value was 91.7% and the positive predictive value was 68.8%. Definitive histological results confirmed FNAB positivity in 97.5% of lymphadenectomies.
US is a sensitive method in the evaluation of superficial lymph nodes during the follow-up of patients with skin tumours. High positive predictive value of cytology was confirmed.
PMCID: PMC3908844  PMID: 24587776
skin tumours; ultrasound; fine needle aspiration biopsy, follow-up
3.  Clinical and Contrast-Enhanced Ultrasound Echography Outcomes in Psoriatic Arthritis Patients after One Year of Continuous Therapy with Anti-TNF Drugs 
ISRN Dermatology  2014;2014:932721.
Background. We wanted to verify retrospectively the proportion of patients with psoriatic arthritis who were in remission after 1 year of continuous therapy with either etanercept or adalimumab. Remission was defined as the absence of both clinical and contrast-enhanced ultrasound (CEUS) findings suggestive of joint inflammation. Patients and Methods. The data of twenty-five patients with psoriatic arthritis were available for the clinical and CEUS evaluations before and after 1 year of continuous therapy with etanercept or adalimumab. The count of swollen (ACR66), tender (ACR68), and active inflamed joints (AJC) was used to measure the severity of joint involvement. PASI was used to score the severity of psoriasis. HAQ, DLQI, VAS pain, and VAS itching were administered to each patient before starting therapy and every 3 months, up to 1 year. Results. Eight (32%) out of twenty-five patients were in remission after 1 year of therapy with etanercept or adalimumab. A significant reduction of all clinical variables analysed was seen during the course of therapy. Conclusion. Although a significant proportion of patients achieved remission of arthritis after 1 year of effective anti-TNF therapy, the majority of them continued to have either clinical or CEUS findings suggestive of persistence of joint inflammation.
PMCID: PMC3933554  PMID: 24653837
4.  Cutaneous melanoma follow-up: appropriateness of requests for ultrasound tests – the S.Gallicano National Referral Centre Experience 
Cutaneous melanoma is a malignant neoplasm with a constantly increasing incidence, the prognosis of which is largely dependent on early diagnosis. The appropriateness of requests for ultrasound (US) tests during melanoma follow-up of patients referred to our institute was evaluated.
Patients and methods
The requests for US tests of all patients referred to our institute over a four-month period were assessed. In order to correctly evaluate the appropriateness of requests, patients were split into two groups on the basis of melanoma thickness: > 1 mm (Group A) and < 1 mm (Group B).
546 patients were enrolled in our study out of a total of 1240 US tests performed. Out of 290 Group A patients, 104 patients (35%) did not meet the established congruity criteria. Group B was composed of 256 individuals, 92 patients (35.9%) of which were found to have at least one inappropriate request.
In our study, more than 30% of the requests for US tests were found to be inappropriate, to the detriment of those with a real need for diagnostic testing. This lengthens waiting lists and it may also increase public healthcare costs. Therefore, it is mandatory to adopt new, widely accepted and easily applicable guidelines.
PMCID: PMC3851827  PMID: 24422765
Cutaneous melanoma; Defensive medicine; Ultrasound test appropriateness
5.  Ultrasound morphology of inguinal lymph nodes may not herald an associated pathology 
Among patients undergoing follow-up after surgery for melanoma, ultrasound (US) very often reveals lymph nodes in groin area, that do not show clear characters of a metastatic lesion yet that have atypical US features, which could result in diagnostic uncertainty. We evaluated such lesions among a cohort of patients.
The study population consisted of patients who presented consecutively to our facility for a control between 1 January 2009 and 30 July 2010 and who had undergone surgery for a melanoma, at least 6 months earlier, in areas draining to lymph nodes of the groin but choosing – for this study - the opposite side to the natural drainage. The following parameters of the US performed on the lymph nodes were evaluated: number and size, aspects of the outline, including any extroflexion of the outline and contours morphology, homogeneity and thickness of the cortex and aspects of the hilus, characteristics of the vascularisation of the lymph node at color-power Doppler. A second US examination was performed on the same area after at least 12 months.
Results and conclusions
We found a very high number of patients (42/124) with lymph nodes that did not appear to be fully normal at US examination, particularly those with structural alterations in the hilus and slight loss of physiologic curvature of the outlines, with moderate thickening of the cortex. Of the 124 patients, who were followed for at least one year, 42 showed these characteristics, and none of these showed any progression to malignancy at follow-up. Based on these results, we can conclude that focusing excessively on such US findings could lead to the inappropriate performance of additional diagnostic tests, with a consequent increase in management costs and a worsening of the quality of life for these patients.
PMCID: PMC3551661  PMID: 23078807
Anatomical lymph nodes of the groin; Ultrasound; Melanoma; Cortical; Hilus
6.  AIDS-Kaposi Sarcoma and Classic Kaposi Sarcoma: are different ultrasound patterns related to different variants? 
Kaposi Sarcoma (KS) is a malignancy of endothelial skin cells with multifocal localization on the skin, lymph nodes and visceral organs. Although all clinical variants are associated with HHV-8 infection, specific differences in the clinical onset and in the natural history of AIDS-KS and Classic-KS have been described. The present randomised prospective-observational study aimed to investigate whether the ultrasound pattern and color Doppler flow imaging of vascularisation of skin lesions of patients with Classic KS (CKS) or AIDS-KS could provide useful information to the evaluation of clinical activity of the disease.
Cutaneous lesions of 24 patients with histologically confirmed KS were investigated using very high frequency ultrasound probes; 16 patients had CKS and 8 had AIDS-KS. HHV-8 infection was confirmed in all patients by investigating the specific humoral response to viral antigens. Immunological and virological parameters were also assessed to monitor HIV or HHV-8 viral infection. For each patient, a target skin lesion was selected on the basis of size (diameter from 0.4 to 2 cm). Each lesion was analyzed in terms of size, depth and color Doppler pattern.
The B-mode ultrasound patterns of skin lesions did not differ when comparing CKS patients to AIDS-KS patients, whereas the color Doppler signal, which is associated with vascular activity, was detected in the KS lesions of 6/8 AIDS-KS patients (75.0%) and in 2/16 CKS (16,7%); the latter two patients showed a clinically progressive and extensive disease stage (IV B).
Our preliminary results suggest that small cutaneous KS lesions - in both CKS and AIDS-KS patients- display similar B-mode ultrasound patterns ( hypoechoic, well defined, superficial lesions). However, the color Doppler signal, which is associated with endothelial activity and angiogenesis, which play a substantial role in KS progression, could constitute a useful tool for evaluating disease activity.
PMCID: PMC3095540  PMID: 21489270
7.  Epithelioma of Malherbe: new ultrasound patterns 
Calcifying epithelioma of Malherbe, or Pilomatricoma, is considered an uncommon cutaneous neoplasia, normally occurring in children as a solitary, firm, asymptomatic, hard, subcutaneous, slowly growing nodule on the face, neck, or proximal upper extremity. In literature, two Pilomatricoma ultrasound patterns are described: the totally calcified nodule and the hypoechoic nodule with internal calcific foci. High frequency ultrasound has not yet been applied for routine diagnosis of Pilomatricoma. The aim of the study was to retrospectively identify specific ultrasound features.
We retrieved 124 histologically Pilomatricoma cases: 28 patients with 32 lesions were preoperatively evaluated with ultrasound.
22/32 have shown a solid formation, hypoechoic, with a sharp outline. Of these 22, 10 lesions were completely calcifying and 12 partially calcified. In 3/32 lesions with uncertain diagnosis, ultrasounds showed a complex/mixed pattern with pseudo-fluid areas and microspots. 7/32 lesions with US different diagnosis included 3 complex lesions, 2 cystic lesions and 2 solid nodular lesions.
In addition to well-known ultrasound patterns (completely calcified and partially calcified) we identified three new, not yet described, patterns that constitute the 31% of the cases: complex, pseudocistyc and pseudotumoral.
PMCID: PMC2883973  PMID: 20444298
8.  Decreased levels of metalloproteinase-9 and angiogenic factors in skin lesions of patients with psoriatic arthritis after therapy with anti-TNF-α 
Inflammation represents an early and key event in the development of both the cutaneous psoriasis and psoriatic arthritis. Compelling evidences indicate that the production of TNF-α plays a central role in psoriasis by sustaining the inflammatory process in the skin as well as in the joints. Among the multiple effects produced by TNF-α on keratinocytes, the induction of matrix metalloproteinase-9 (MMP-9), a collagenase implicated in joint inflammatory arthritis which acts as an angiogenesis promoting factor, might represent a key mechanism in the pathogenesis of the disease. Aims of the present study were to investigate a) the role of MMP-9 in the development of psoriasis by assessing the presence of MMP-9 in lesional skin and in sera of psoriatic patients; b) the association of MMP-9 with the activity of the disease; c) the relationship between MMP-9 and TNF-α production.
Eleven psoriatic patients, clinically presenting joint symptoms associated to the cutaneous disease, were included in a therapeutic protocol based on the administration of anti-TNF-α monoclonal antibody (Infliximab). Sera and skin biopsies were collected before treatment and after 6 weeks of therapy. Tissues were kept in short term cultures and production soluble mediators such as TNF-α, MMP-9, MMP-2, VEGF and E-Selectin, which include angiogenic molecules associated to the development of plaque psoriasis, were measured in the culture supernatants by immunoenzymatic assays (ng/ml or pg/ml per mg of tissue). MMP-9 concentrations were also measured in the sera. The cutaneous activity of disease was evaluated by the Psoriasis Area and Severity Index (PASI).
Clinical and laboratory assessment indicated that all but one patients had a significant improvement of the PASI score after three months of therapy. The clinical amelioration was associated to a significant decrease of MMP-9 (P = 0.017), TNF-α (P = 0.005) and E-selectin (P = 0.018) levels, spontaneously released by lesional biopsies before and after therapy. In addition, significant correlations were found between the PASI measurements and TNF-α (r2 = 0.33, P = 0.005), MMP-9 (r2 = 0.25, P = 0.017), E-selectin (r2 = 0.24, P = 0.018) production. MMP-9 levels were significantly correlated with those of TNF-α (r2 = 0.30, P = 0.008). A significant decrease of MMP-9 in the sera, associated to the clinical improvement was also found.
Our findings show the existence of a direct relationship between MMP-9 and TNF-α production strongly suggesting that MMP-9 may play a key role in the skin inflammatory process in psoriasis.
PMCID: PMC1601955  PMID: 17022813

Results 1-8 (8)