Isolated limb perfusion for the management limb threatening soft tissue sarcomas: The role of histological type on clinical outcomes.

BACKGROUND: Hyperthermic isolated limb perfusion (HILP) is an effective neoadjuvant treatment to avoid amputation in patients with locally advanced extremity soft tissue sarcomas (STS). We aimed to investigate whether STS histological type plays a role in predicting clinical outcomes. METHODS: This study reports a retrospective analysis of 125 patients with limb threatening STS (liposarcoma, n = 41; malignant peripheral nerve sheath tumor, n = 20; leiomyosarcoma, n = 20; miscellany, n = 44), who underwent HILP from 1990 through 2015 at our institution. The following endpoints were evaluated: tumor response (assessed by radiological imaging and histology), limb sparing rate, local progression-free survival (LPFS) and overall survival (OS). RESULTS: On average, overall (complete + partial) tumor response was significantly greater in patients affected with liposarcoma as compared to those with other histotypes (radiological response rate: 38/41, 92.7% vs 66/84, 78.6%, P-value: 0.048; mean histological necrosis: 83.6% vs 52.9%, P < 0.0001). Limb sparing rate was also higher among patients with liposarcoma as compared to other histotypes (39/41, 95.1% vs 62/84, 73.8%, P-value: 0.005). As regards survival, LPFS was similar across tumor types, whereas OS resulted significantly worse in patients with limb leiomyosarcoma (log-rank P-value: 0.009). CONCLUSIONS: HILP is a very effective treatment modality for limb threatening STS. In our series, liposarcoma appears to be the histological type most sensitive to HILP in terms of tumor response and thus limb sparing, which might help clinicians in the patient selection process.

Microscopic histological characteristics of soft tissue sarcomas: analysis of tissue features and electrical resistance.

Tissue electrical conductivity is correlated with tissue characteristics. In this work, some soft tissue sarcomas (STS) excised from patients have been evaluated in terms of histological characteristics (cell size and density) and electrical resistance. The electrical resistance has been measured using the ex vivo study on soft tissue tumors electrical characteristics (ESTTE) protocol proposed by the authors in order to study electrical resistance of surgical samples excised by patients in a fixed measurement setup. The measurement setup includes a voltage pulse generator (700 V, 100 µs long at 5 kHz, period 200 µs) and an electrode with 7 needles, 20 mm-long, with the same distance arranged in a fixed hexagonal geometry. In the ESTTE protocol, the same voltage pulse sequence is applied to each different tumor mass and the corresponding resistance has been evaluated from voltage and current recorded by the equipment. For each tumor mass, a histological sample of the volume treated by means of voltage pulses has been taken for histological analysis. Each mass has been studied in order to identify the sarcoma type. For each histological sample, an image at 20× or 40× of magnification was acquired. In this work, the electrical resistance measured for each tumor has been correlated with tissue characteristics like the type, size and density of cells. This work presents a preliminary study to explore possible correlations between tissue characteristics and electrical resistance of STS. These results can be helpful to adjust the pulse voltage intensity in order to improve the electrochemotherapy efficacy on some histotype of STS.

Calculating regional tissue volume for hyperthermic isolated limb perfusion: Four methods compared.

INTRODUCTION: Hyperthermic isolated limb perfusion (HILP) can be performed as an alternative to amputation for soft tissue sarcomas and melanomas of the extremities. Melphalan and tumor necrosis factor-alpha are used at a dosage that depends on the volume of the limb. Regional tissue volume is traditionally measured for the purposes of HILP using water displacement volumetry (WDV). Although this technique is considered the gold standard, it is time-consuming and complicated to implement, especially in obese and elderly patients. AIM: The aim of the present study was to compare the different methods described in the literature for calculating regional tissue volume in the HILP setting, and to validate an open source software. METHODS: We reviewed the charts of 22 patients (11 males and 11 females) who had non-disseminated melanoma with in-transit metastases or sarcoma of the lower limb. We calculated the volume of the limb using four different methods: WDV, tape measurements and segmentation of computed tomography images using Osirix and Oncentra Masterplan softwares. RESULTS AND CONCLUSION: The overall comparison provided a concordance correlation coefficient (CCC) of 0.92 for the calculations of whole limb volume. In particular, when Osirix was compared with Oncentra (validated for volume measures and used in radiotherapy), the concordance was near-perfect for the calculation of the whole limb volume (CCC = 0.99). With methods based on CT the user can choose a reliable plane for segmentation purposes. CT-based methods also provides the opportunity to separate the whole limb volume into defined tissue volumes (cortical bone, fat and water).

Electrical resistance of human soft tissue sarcomas: an ex vivo study on surgical specimens.

This paper presents a study about electrical resistance, which using fixed electrode geometry could be correlated to the tissue resistivity, of different histological types of human soft tissue sarcomas measured during electroporation. The same voltage pulse sequence was applied to the tumor mass shortly after surgical resection by means of a voltage pulse generator currently used in clinical practice for electrochemotherapy that uses reversible electroporation. The voltage pulses were applied by means of a standard hexagonal electrode composed by seven, 20-mm-long equispaced needles. Irrespective of tumor size, the electrode applies electric pulses to the same volume of tissue. The resistance value was computed from the voltage and current recorded by the pulse generator, and it was correlated with the histological characteristics of the tumor tissue which was assessed by a dedicated pathologist. Some differences in resistance values, which could be correlated to a difference in tissue resistivity, were noticed according to sarcoma histotype. Lipomatous tumors (i.e., those rich in adipose tissue) displayed the highest resistance values (up to 1700 Ω), whereas in the other soft tissue sarcomas, such as those originating from muscle, nerve sheath, or fibrous tissue, the electrical resistance measured was between 40 and 110 Ω. A variability in resistance was found also within the same histotype. Among lipomatous tumors, the presence of myxoid tissue between adipocytes reduced the electrical resistance (e.g., 50-100 Ω). This work represents the first step in order to explore the difference in tissue electrical properties of STS. These results may be used to verify whether tuning electric field intensity according to the specific STS histotype could improve tissue electroporation and ultimately treatment efficacy.

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.

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.

Adjuvant and neoadjuvant chemotherapy for soft tissue sarcomas.

Sarcomas of the soft tissue are a heterogeneous, rare and complex group of mesenchymal malignant tumors, accounting for less than 1% of all adult malignancies and about 10-15% of childhood cancer. Despite local disease control obtained with surgery and pre- or postoperative radiotherapy, roughly one half of patients with high-grade tumors experience metastatic disease. The adjunction of chemotherapy, either before or after resection, is not currently viewed as standard practice due to the lack of reproducible impact on survival. The 1997 SMAC meta-analysis based on individual data from randomized studies confirmed a significant impact of adjuvant chemotherapy on both local and metastatic relapse, without any significant benefit on survival. Further meta-analyses demonstrated a significant benefit also in overall survival. Yet, the latest adjuvant EORTC trial was disappointedly negative. To date, adjuvant chemotherapy may be recommended as a reasonable option for the high-risk individual patient who should be well informed on the possible risks and benefits of treatment. Also the indications for neoadjuvant chemotherapy remain controversial. A local benefit may be gained, facilitating surgery, but data on survival are limited and affected by a strong patient selection bias. In order to improve our knowledge on sarcomas and to offer patients the best of current standards, we strongly recommend that all patients be referred to a sarcoma multidisciplinary group, under whose supervision they could receive the correct combined-modality management as well as have access to new clinical trials appropriately stratified for risk and histological and/or molecular subtypes.

Metastatic malignant soft tissue myoepithelioma: a case report showing complete response after locoregional and systemic therapy.

We report on the case of a 61-year-old man with a soft tissue malignant myoepithelioma of the second toe of the right foot. After removal of the primary tumor, the patient developed in-transit metastases of the limb that we later treated with limb perfusion, using extracorporeal circulation with complete response. Following the appearance of lymph node metastases, the patient underwent inguinal, iliac and obturator lymphadenectomy. Subsequent pelvis metastases were treated with chemotherapy and radiotherapy, with complete response. Currently, after 3 years, the patient is alive and no evidence of any residual disease is apparent.

Sentinel node biopsy for high-risk cutaneous nonanogenital squamous cell carcinoma: a preliminary result.

BACKGROUND: Certain patients with squamous cell carcinoma (SCC) have much higher rates of regional nodal metastases than is often reported. This study aims to further validate sentinel lymph node biopsy (SNB) for SCC and the outcome of these patients following SNB. METHODS: 20 patients with high-risk nonanogenital SCC who underwent SNB between 1998 and 2007 were retrospectively reviewed. SNB was performed under local or general anesthesia following lymphoscintigraphy and blue dye injection. RESULTS: The median follow-up from SNB was 24 months. Tumor location included the head and neck (n = 11), extremities (n = 9) and trunk (n = 1). One patient had a positive sentinel node. This patient developed parotid metastases 13 months after refusing a complete neck dissection and is alive with progressive disease after 31 months. Two patients developed regional recurrence after negative SNB (1 is alive and disease free, the other died of progressive disease). Of the remaining patients, 15 are alive and disease free, 1 died of another malignancy and 1 was lost to follow-up. CONCLUSION: SNB for high-risk SCC is feasible and allows early detection and treatment of nodal metastases. Currently, SNB for SCC is not a standard treatment and requires further investigation to determine which patients would benefit best from this procedure.

Can dedicated ambulances improve the efficiency of the neonatal emergency transport service?

OBJECTIVE: To assess whether dedicated ambulances would improve the efficiency of the neonatal emergency transport service (NETS). METHODS: The efficiency of NETS was investigated in the Lazio region, Italy, by comparing data collected during the first 6 months of 1997 (from 1 January to 30 June), with those collected during the same months of 2000, using NETS availability and time investment as indicators. The data yielded by the study were reported as number and percentage, and were analyzed by SPSS 10.1 software; chi2 analysis with Pearson's correction was used to assess the statistical significance of the differences between the two groups; p < 0.05 was considered statistically significant. RESULTS: Our investigation showed a reduced availability of the service in 2000, compared to 1997 (90.4% vs. 95%; p < 0.03). We also noted that in 2000 all dedicated ambulances remained off duty for 26 days, owing to engine failure. The response time and the total transfer time where much longer in 2000 than in 1997 (response time > 30 min in 8% vs. 3%, p < 0.008; total transfer time > 120 min in 37% vs. 30%, p < 0.04). CONCLUSIONS: The reduced efficiency in 2000 was mainly due to the lack of ambulances used to replace the dedicated ambulances. However, the type of ambulance that may provide the best replacement for NETS remains an unsolved question.

Antinuclear antibodies are not induced by PUVA treatment in patients with uncomplicated psoriasis.

BACKGROUND: Previous investigations of antinuclear antibody (ANA) prevalence in patients undergoing PUVA therapy reported contrasting results. However, ANA tests were performed on low-sensitivity substrates that do not allow investigation of anti-Ro (SS-A) antibodies. OBJECTIVE: We assessed ANAs on a highly sensitive substrate. METHODS: ANAs were assayed on HEp-2 cells at regular intervals in 238 patients with psoriasis who were treated with PUVA therapy for 1 to 5 years and in 118 untreated control subjects with psoriasis. In addition, radioimmunoassay and counterimmunoelectrophoresis studies of anti-DNA and anti-extractable nuclear antigen antibodies were performed. RESULTS: Low titers of ANA developed in three patients in at least two consecutive determinations and in 10 patients in a single determination despite continuing treatments. The positive conversion rate was not statistically significant. Radioimmunoassay counterimmunoelectrophoresis studies of anti-DNA and anti-extractable nuclear antigen antibodies were never positive. CONCLUSION: In our experience PUVA therapy does not represent a risk factor for the induction of anti-Ro antibodies and other ANAs.