Sofra M.,Italian National Cancer Institute |
Fei P.C.,San Gallicano Dermatology Institute |
Fabrizi L.,Italian National Cancer Institute |
Marcelli M.E.,Italian National Cancer Institute |
And 4 more authors.
Journal of Experimental and Clinical Cancer Research | Year: 2013
Background: Although surgery and anesthesia induce immunesuppression, remains largely unknown whether various anesthetic techniques have different immunosuppressive effects on cancer patients. Therefore, the aim of this study was to investigate the influence of total intravenous anesthesia with target-controlled infusion (TIVA-TCI) and balanced inhalation anesthesia (BAL) on the peri-operative levels of inflammatory cytokines and regulatory T cells (Tregs) in patients with bladder cancer undergoing surgery. Methods. Twenty eight consecutive patients with bladder cancer who underwent radical cystectomy were prospectively randomized into two groups to receive TIVA-TCI (n = 14) or BAL (n = 14). Before the induction of anesthesia (T0), 6-8 hours (T1) post-surgery, and 5 days post-surgery (T2), Tregs and serum levels of interleukin -1beta (IL-1β), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin -2 (IL-2), interleukin -6 (IL-6), and interleukin -10 (IL-10) were measured. Results: In the peri-operative period all cancer patients showed a marked and significant increase in IL-6. Moreover, TIVA-TCI patients also showed a higher increase in IFN-γ, whereas in BAL patients Tregs were reduced by approximately 30% during surgery. The incidence of infections, metastases, and death was similar in both groups. Conclusions: The increase in the Th1 response in the TIVA-TCI group and the reduction in Tregs in the BAL group seem to balance the immunosuppressive effect induced by IL-6. Therefore TIVA-TCI and BAL can be both used in major surgery in patients with bladder cancer without worsening the outcome. © 2013 Sofra et al.; licensee BioMed Central Ltd.
PubMed | University of Padua, Santa Maria Annunziata Hospital, Italian National Cancer Institute, University of Turin and 5 more.
Type: Journal Article | Journal: European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology | Year: 2016
Cutaneous metastases represent a therapeutic challenge. An increasing body of experience suggests that electrochemotherapy (ECT) provides effective tumor control, although its evidence basis should be strengthened.This prospective, multicenter, observational study enrolled patients with superficial metastases, who underwent ECT at 10 centers between 2008 and 2013. Outcomes included adherence to European Standard Operating Procedures of ECT (ESOPE), tumor response, local progression-free survival (LPFS), toxicity and patient-reported outcomes (PROs, EORTC QLQ-C30 plus an 8-item questionnaire).We enrolled 376 eligible patients. Tumor histotype distribution was as follows: melanoma, 56%; squamous cell carcinoma, 11%; Kaposi sarcoma, 11%; breast carcinoma, 8%; basal cell carcinoma, 6%; soft tissue sarcomas, 3%; others, 5%. We registered 1304 target tumors (median size 1cm). Treatment adhered to ESOPE in 88% of patients as to the route of drug administration, and in 70% as to electrode application. The procedure was mainly performed under sedation (64.6%) and by using intravenous chemotherapy (93.4%). Tumor response rate at 60 days was 88% (complete, 50%). Small tumor size predicted complete response achievement (OR 2.24, p=0.003), higher LPFS (HR 0.68, p=0.004) and improved PROs (Global Health Status, p<0.001; wound bleeding, p<0.001; healing, p=0.002; and aesthetics, p<0.001). Skin toxicity (grade 3, 7.8%) was lower in patients with tumors <2cm (p0.001). One-year LPFS was 73.7% (95%CI 68.4-78.3).ECT represents a valuable skin-directed therapy across a range of malignancies. The most frequently applied treatment modality is intravenous chemotherapy under sedation. Small tumor size predicts durable tumor control, fewer side-effects and better PROs.
Elewski B.E.,University of Alabama at Birmingham |
Draelos Z.,Dermatology Consulting Services |
Dreno B.,University of Nantes |
Jansen T.,University of Duisburg - Essen |
And 2 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2011
Background The absence of specific histological or serological markers, the gaps in understanding the aetiology and pathophysiology of rosacea, and the broad diversity in its clinical manifestations has made it difficult to reach international consensus on therapy guidelines. Objectives The main objective was to highlight the global diversity in current thinking about rosacea pathophysiology, classification and medical features, under particular consideration of the relevance of the findings to optimization of therapy. Methods The article presents findings, proposals and conclusions reached by the ROSacea International Expert group (ROSIE), comprising European and US rosacea experts. Results New findings on pathogenesis provide a rationale for the development of novel therapies. Thus, recent findings suggest a central role of the antimicrobial peptide cathelicidin and its activator kallikrein-5 by eliciting an exacerbated response of the innate immune system. Cathelicidin/kallikrein-5 also provide a rationale for the effect of tetracyclines and azelaic acid against rosacea. Clinically, the ROSIE group emphasized the need for a comprehensive therapy strategy - the triad of rosacea care - that integrates patient education including psychological and social aspects, skin care with dermo-cosmetics as well as drug- and physical therapies. Classification of rosacea into stages or subgroups, with or without progression, remained controversial. However, the ROSIE group proposed that therapy decision making should be in accordance with a treatment algorithm based on the signs and symptoms of rosacea rather than on a prior classification. Conclusion The ROSIE group reviewed rosacea pathophysiology and medical features and the impact on patients and treatment options. The group suggested a rational, evidence-based approach to treatment for the various symptoms of the condition. In daily practice this approach might be more easily handled than prior subtype classification, in particular since patients often may show clinical features of more than one subtype at the same time. © 2010 European Academy of Dermatology and Venereology.
PubMed | University of Amsterdam, University of Nottingham, Ghent University, University Paris Est Creteil and 3 more.
Type: Journal Article | Journal: The Journal of investigative dermatology | Year: 2016
The clinical assessment of vitiligo involves an estimation of the affected body surface area. The most commonly used method is the palm of hand 1% rule as integrated in the Vitiligo Area Scoring Index. However, this method can be challenging and time consuming. In this study, we introduce a global Vitiligo Extent Score (VES). In the first part of the study, this measurement instrument was developed and subsequently optimized during a pilot scoring session. In a subsequent stage, the inter- and intrarater reliability of the instrument were tested. Live scoring showed an excellent interrater reliability for the VES (intraclass correlation VES: 0.924 vs. Vitiligo Area Scoring Index: 0.846). Subsequent scoring on pictures was comparable with the live evaluation and demonstrated an excellent intrarater reliability. A high intraclass correlation forthe VES (intraclass correlation VES: 0.923 vs. Vitiligo Area Scoring Index: 0.757) was also found in anadditional subgroup of patients with extensive vitiligo. Moreover, user-friendliness and timing were scored veryfavorably. In conclusion, this measurement instrument allows us to monitor accurately andeasily theaffected body surface area in a standardized way. Moreover, our results provide evidence that the VEScan be proposed as a promising tool to measure the vitiligo extent in clinical trials and in daily practice.
Solivetti F.M.,San Gallicano Dermatology Institute |
Solivetti F.M.,Irccs Instituto Dermosifilopatico Of Santa Maria E San Gallicano Ifo |
Elia F.,Irccs Instituto Dermosifilopatico Of Santa Maria E San Gallicano Ifo |
Graceffa D.,Irccs Instituto Dermosifilopatico Of Santa Maria E San Gallicano Ifo |
Di Carlo A.,San Gallicano Dermatology Institute
Journal of Experimental and Clinical Cancer Research | Year: 2012
Background: 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. Methods. 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. © 2012 Solivetti et al.
Koudriavtseva T.,Regina Elena Cancer Institute |
Sbardella E.,Regina Elena Cancer Institute |
Trento E.,San Gallicano Dermatology Institute |
Bordignon V.,San Gallicano Dermatology Institute |
And 2 more authors.
Clinical and Experimental Immunology | Year: 2014
Natalizumab, an anti-alpha4 integrin monoclonal antibody inhibiting the adhesion of lymphocytes to the endothelium, is a widely accepted drug treatment for relapsing-remitting multiple sclerosis (RRMS). A peripheral increase of T and B lymphocytes has already been observed as an early treatment effect. This retrospective observational study was aimed to evaluate the peripheral lymphocyte subsets during a long-term treatment follow-up. We included 23 RRMS patients treated with natalizumab for at least 24-48 months who had pretreatment lymphocyte evaluation. Baseline values of lymphocyte subsets and CD4/CD8 ratio did not differ significantly from the 23 matched healthy subjects. The periodic (every 3-6 months) assessment of immune cell subsets was performed by flow cytometry on peripheral blood collected before drug injection. Therapy with natalizumab was confirmed to be effective during the observational period. For all patients, the increase in lymphocytes during natalizumab therapy compared to baseline at every assessment was significantly higher compared to that of overall white blood cells (2·1- and 1·3-fold, respectively, P<0·0001). Both T cell subsets were proportionally modified and the CD4/CD8 ratio did not change significantly, while B cells increased significantly compared to T and NK cells (3·2-, 1·88- and 1·92-fold, respectively, P<0·0001). These changes remained constant throughout the 25-48-month period of therapy. In conclusion, effective natalizumab treatment of RRMS patients was associated with the persistence of its biological effects through a stable increase of peripheral lymphocytes, mainly B cells, and an unchanged proportion of T cell subsets in long-term follow-up. © 2014 British Society for Immunology.
Solivetti F.M.,San Gallicano Dermatology Institute |
Elia F.,San Gallicano Dermatology Institute |
Latini A.,San Gallicano Dermatology Institute |
Cota C.,San Gallicano Dermatology Institute |
And 2 more authors.
Journal of Experimental and Clinical Cancer Research | Year: 2011
Background: 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. Methods. 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. Results: 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). Conclusions: 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. © 2011 Solivetti et al; licensee BioMed Central Ltd.
Briganti S.,San Gallicano Dermatology Institute |
Flori E.,San Gallicano Dermatology Institute |
Mastrofrancesco A.,San Gallicano Dermatology Institute |
Kovacs D.,San Gallicano Dermatology Institute |
And 4 more authors.
Experimental Dermatology | Year: 2013
Azelaic acid (AzA) has been used for the treatment for inflammatory skin diseases, such as acne and rosacea. Interestingly, an improvement in skin texture has been observed after long-time treatment with AzA. We previously unrevealed that anti-inflammatory activity of AzA involves a specific activation of PPARγ, a nuclear receptor that plays a relevant role in inflammation and even in ageing processes. As rosacea has been considered as a photo-aggravated disease, we investigated the ability of AzA to counteract stress-induced premature cell senescence (SIPS). We employed a SIPS model based on single exposure of human dermal fibroblasts (HDFs) to UVA and 8-methoxypsoralen (PUVA), previously reported to activate a senescence-like phenotype, including long-term growth arrest, flattened morphology and increased synthesis of matrix metalloproteinases (MMPs) and senescence-associated β-galactosidase (SA-β-gal). We found that PUVA-treated HDFs grown in the presence of AzA maintained their morphology and reduced MMP-1 release and SA-β-galactosidase-positive cells. Moreover, AzA induced a reduction in ROS generation, an up-modulation of antioxidant enzymes and a decrease in cell membrane lipid damages in PUVA-treated HDFs. Further evidences of AzA anti-senescence effect were repression of p53 and p21, increase in type I pro-collagen and abrogation of the enhanced expression of growth factors, such as HGF and SCF. Interestingly, PUVA-SIPS showed a decreased activation of PPARγ and AzA counteracted this effect, suggesting that AzA effect involves PPARγ modulation. All together these data showed that AzA interferes with PUVA-induced senescence-like phenotype and its ability to activate PPAR-γ provides relevant insights into the anti-senescence mechanism. © 2013 John Wiley & Sons A/S.
Bonamonte D.,University of Bari |
Cristaudo A.,San Gallicano Dermatology Institute |
Nasorri F.,Instituto Dermopatico dellImmacolata |
Carbone T.,Instituto Dermopatico dellImmacolata |
And 3 more authors.
Contact Dermatitis | Year: 2011
Background. Nickel contact allergy remains common in Western countries, and the dermatitis may require prolonged treatment. The development of new strategies aimed at improving the quality of life of affected individuals is needed. Objectives. To investigate the efficacy of oral hyposensitization in nickel-allergic individuals and how this affects in vitro T cell responsiveness to the metal. Methods. Twenty-eight nickel-allergic patients received a daily dose of 50 μg of elemental nickel (given as NiSO 4·6H 2O) in cellulose capsules for 3 months. Severity of clinical manifestations, in vivo nickel responsiveness and in vitro T cell responses to the metal were assessed after 1 and 3 months. Results. Twenty-six patients finished the study. In these patients, oral hyposensitization ameliorated clinical manifestations despite continued nickel exposures, and increased the threshold of skin responsiveness to nickel. The 12 enrolled patients in the immunological study showed decreased in vitro T lymphocyte responsiveness to the metal, in terms of both cell proliferation and cytokine release. In the 1-year follow-up, 50% of the patients experienced relapses of the clinical manifestations at sites of topical exposure to nickel. Conclusions. Our study suggested therapeutic efficacy of oral hyposensitization in allergic individuals. Placebo-controlled studies are required to confirm the results and determine the optimal therapeutic regimen for prolonged beneficial effects. © 2011 John Wiley & Sons A/S.
Koudriavtseva T.,Regina Elena Cancer Institute |
D'Agosto G.,San Gallicano Dermatology Institute |
Mandoj C.,Regina Elena Cancer Institute |
Sperduti I.,Regina Elena Cancer Institute |
Cordiali-Fei P.,San Gallicano Dermatology Institute
Neurological Sciences | Year: 2014
The exact prevalence and pathogenic role of antiphospholipid antibodies (aPL) in multiple sclerosis (MS) remain unclear. This observational laboratory-blinded study evaluated the rate of aPL positivity in healthy controls and MS patients in different disease phases to recognize their frequency and possible pathogenic meaning. Reactivity for anti-cardiolipin, anti-β2 glycoprotein I, anti-prothrombin, anti-annexin V (IgG and IgM) was studied by enzyme immunoassays in 60 healthy controls and 100 consecutive MS patients [58 relapsing–remitting (RR) patients in remission, 26 RR patients in relapse, and 16 secondary progressive patients]. The overall rate of positivity for at least one aPL was significantly higher in MS patients compared to controls (32 % vs. 7 %, respectively, p < 0.0001), and in relapsing phase compared to those remitting or secondary progressive (53.8, 20.7 and 37.5 %, respectively, p = 0.002). In the single aPL analysis, the rate of positivity was significantly higher in MS patients compared to controls for anti-prothrombin IgM (7 % vs. 0, p = 0.05), and in relapsing phase compared to remitting and secondary progressive phases for anti-β2 glycoprotein I IgM (26.9, 1.7, 6.3 %, respectively, p < 0.0001), anti-prothrombin IgM (15.4, 3.4, 6.3 %, respectively, p = 0.05) and IgG (19.2, 5.2, 0 %, respectively, p = 0.05). We showed a significant aPL increase in MS patients compared to healthy controls, particularly during disease relapse which was also associated with significantly higher values of anti-β2 glycoprotein I and anti-prothrombin. These data suggest that antiphospholipid antibody occurrence in multiple sclerosis could be related to modification of structure and function of proteins involved in the inflammatory–thrombotic processes during disease re-activation. © 2014, Springer-Verlag Italia.