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Cavallin F.,Veneto Oncology Institute IOV IRCCS | Scarpa M.,Veneto Oncology Institute IOV IRCCS | Alfieri R.,Veneto Oncology Institute IOV IRCCS | Cagol M.,Veneto Oncology Institute IOV IRCCS | And 3 more authors.
Anticancer Research | Year: 2014

Background: Esophageal carcinosarcoma (ESC) is a rare malignant lesion of the esophagus with controversial characteristics and prognostic factors. Patients and Methods: Seventeen consecutive patients with esophageal carcinosarcoma were referred to the Center for Esophageal Diseases located in Padua from January 1, 1980 to December 31, 2011. Clinical characteristics, pathological features, treatment and outcome were retrospectively analyzed in a prospectively collected database. Results: Five patients received palliative treatment and one refused surgery; they died of unresected tumor or progression of disease within 0.6-43.5 months after diagnosis. Eleven patients underwent surgical treatment with complete tumor resection; recurrence rate was 80%, leading to death within 2 years after surgery. Only two resected patients are currently alive and free of disease over 20 years after surgery. Conclusion: Our results did not support the better prognosis concept of esophageal carcinosarcoma and suggested the importance of radical esophagectomy with adequate lymph node dissection.

Valpione S.,Veneto Oncology Institute IOV IRCCS | Aliberti C.,Veneto Region Oncology Research Institute | Parrozzani R.,GB Bietti Foundation IRCCS | Bazzi M.,University of Padua | And 6 more authors.
Melanoma Research | Year: 2015

We retrospectively evaluated the benefit of transarterial chemoembolization with CPT-11 charged microbeads (TACE) in 58 of 141 uveal melanoma patients with liver metastases. This was a retrospective analysis of a prospectively maintained database ranging from September 1990 to April 2014. Statistical analyses adjusting for possible confounding effects of extent of liver metastases were carried out using the Cox regression model under the verified hypothesis of proportional hazards. Among 141 patients with liver metastases, 58 were treated with TACE as first-line therapy and 36 were dead at the time of the analysis; 83 patients received other first-line treatments (deaths = 83). The treatment with TACE conferred a survival advantage (median 16.5 vs. 12.2 months, respectively); when the two cohorts were analyzed comparing the two groups according to the percentage of liver involvement, there was significant evidence that patients with worse hepatic involvement benefited most from the treatment (liver metastases = 20-50%: hazard ratio = 0.50, P = 0.048 and liver metastases ≥50%: hazard ratio = 0.17, P = 0.009). Liver function tests (transaminases and γ-glutamyl-transpeptidase) and age were higher in the historic group, and LDH tended to show higher values. There were no high-grade toxicities with TACE. TACE seems to be a tolerable regimen that confers an improvement in the survival of uveal melanoma patients with liver metastases. Confirmation of the clinical efficacy of TACE is recommended in a phase III trial, possibly with the inclusion of a targeted therapy such as a MEK inhibitor. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Scarpa M.,Veneto Oncology Institute IOV IRCCS | Cardin R.,University of Padua | Bortolami M.,University of Padua | Kotsafti A.,Veneto Oncology Institute IOV IRCCS | And 10 more authors.
European Journal of Cancer | Year: 2013

Background: CD80 has been thought to play an active role in immunosurveillance as it has been found to be up-regulated in ulcerative colitis (UC) patients with dysplasia. The aim of the present study was to analyse early events in UC-related and non-inflammatory carcinogenesis with reference to CD80 expression to clarify what stimuli are involved in its up-regulation in these patients. Patients and methods: Sixty-two patients affected with UC, UC with dysplasia, UC and cancer, colonic adenoma, or colonic cancer and 11 healthy subjects were enroled in our study. Tissue samples were taken from surgical specimens during colonic resection or during colonoscopy. Mucosal mRNA expression of Toll-like receptor-4 (TLR4) and nuclear factor-kappaB (NF-κB) was quantified with Real Time RT-PCR. TLR4, β-catenin and p53 expressions were analysed by immunohistochemistry. Mucosal levels of activated NF-κB were measured with immunometric assays while 8-Hydroxydeoxyguanosine (8-OHdG) levels were quantified by high-performance liquid chromatography with electrochemical detection (HPLC-ED). Non-parametric tests were used for statistical analysis. Results: 8-OHdG mucosal levels were higher in the patients with UC + dysplasia with respect to those in the patients with UC only (p = 0.03). CD80 mRNA mucosal levels were directly correlated with 8-OHdG mucosal levels (τ = 0.26, p = 0.04), TLR4 protein expression (τ = 0.45, p < 0.01) and NF-κB mRNA expression and activity (τ = 0.24, p = 0.02; τ = 0.34, p = 0.02, respectively). CD80 protein expression, instead, was directly correlated with 8-OHdG mucosal levels (τ = 0.19, p = 0.05) and inversely correlated with TLR4 mRNA expression (τ = -0.25, p = 0.03). Conclusion: Oxidative DNA damage peaked in UC-related dysplasia and was found to be directly correlated to CD80 expression. The direct correlation between TLR4 protein expression and CD80 mRNA and the indirect correlation between CD80 protein and TLR4 mRNA expressions give substance to the hypothesis that they play a role in immunosurveillance. No significant correlations between CD80 expression and p53 and β-catenin accumulation during oncogenesis were, instead, observed. © 2012 Elsevier Ltd. All rights reserved.

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