Veneto Institute of Oncology IRCCS

Padova, Italy

Veneto Institute of Oncology IRCCS

Padova, Italy
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Ciccarese F.,University of Padua | Ciminale V.,University of Padua | Ciminale V.,Veneto Institute of Oncology IRCCS
Frontiers in Oncology | Year: 2017

Reactive oxygen species (ROS) are important signaling molecules that act through the oxidation of nucleic acids, proteins, and lipids. Several hallmarks of cancer, including uncontrolled proliferation, angiogenesis, and genomic instability, are promoted by the increased ROS levels commonly found in tumor cells. To counteract excessive ROS accumulation, oxidative stress, and death, cancer cells tightly regulate ROS levels by enhancing scavenging enzymes, which are dependent on the reducing cofactor nicotinamide adenine dinucleotide phosphate (NADPH). This review focuses on mitochondrial ROS homeostasis with a description of six pathways of NADPH production in mitochondria and a discussion of the possible strategies of pharmacological intervention to selectively eliminate cancer cells by increasing their ROS levels. © 2017 Ciccarese and Ciminale.

PubMed | 6 Medical Oncology Unit, University of Rome La Sapienza, National Cancer Institute, Metabolism and Nutrition Unit and 3 more.
Type: Journal Article | Journal: Journal of Cancer | Year: 2016

Malnutrition is a frequent problem in cancer patients, which leads to prolonged hospitalization, a higher degree of treatment-related toxicity, reduced response to cancer treatment, impaired quality of life and a worse overall prognosis. The attitude towards this issue varies considerably and many malnourished patients receive inadequate nutritional support. We reviewed available data present in the literature, together with the guidelines issued by scientific societies and health authorities, on the nutritional management of patients with cancer, in order to make suitable and concise practical recommendations for appropriate nutritional support in this patient population. Evidence from the literature suggests that nutritional screening should be performed using validated tools (the Nutritional Risk Screening 2002 [NRS 2002], the Malnutrition Universal Screening Tool [MUST], the Malnutrition Screening Tool [MST] and the Mini Nutritional Assessment [MNA]), both at diagnosis and at regular time points during the course of disease according to tumor type, stage and treatment. Patients at nutritional risk should be promptly referred for comprehensive nutritional assessment and support to clinical nutrition services or medical personnel with documented skills in clinical nutrition, specifically for cancer patients. Nutritional intervention should be actively managed and targeted for each patient; it should comprise personalized dietary counseling and/or artificial nutrition according to spontaneous food intake, tolerance and effectiveness. Nutritional support may be integrated into palliative care programs. Alternative hypocaloric anti-cancer diets (e.g. macrobiotic or vegan diets) should not be recommended as they may worsen nutritional status. Well-designed clinical trials are needed to further our knowledge of the nutritional support required in different care settings for cancer patients.

PubMed | University of Padua, Albert Ludwigs University of Freiburg, Leiden University, University of Groningen and 12 more.
Type: | Journal: Head & neck | Year: 2016

Endolymphatic sac tumors (ELSTs) are, with a prevalence of up to 16%, a component of von Hippel-Lindau (VHL) disease. Data from international registries regarding heritable fraction and characteristics, germline VHL mutation frequency, and prevalence are lacking.Systematic registration of ELSTs from international centers of otorhinolaryngology and from multidisciplinary VHL centers registries was performed. Molecular genetic analyses of the VHL gene were offered to all patients.Our population-based registry comprised 93 patients with ELST and 1789 patients with VHL. The prevalence of VHL germline mutations in apparently sporadic ELSTs was 39%. The prevalence of ELSTs in patients with VHL was 3.6%. ELST was the initial manifestation in 32% of patients with VHL-ELST.Prevalence of ELST in VHL disease is much lower compared to the literature. VHL-associated ELSTs can be the first presentation of the syndrome and mimic sporadic tumors, thus emphasizing the need of molecular testing in all presentations of ELST. 2015 Wiley Periodicals, Inc. Head Neck 38: 673-679, 2016.

PubMed | Clinical Epidemiology, Oncology ASST settelaghi, University of Bologna, University of Piemonte Orientale and 13 more.
Type: Journal Article | Journal: The Lancet. Haematology | Year: 2016

The combination of rituximab, bendamustine, and cytarabine (R-BAC) was highly active in a pilot trial of mantle cell lymphoma, but its use was restricted by high haematological toxicity. We aimed to assess the efficacy and safety of an R-BAC regimen with low-dose cytarabine (RBAC500).In this multicentre, phase 2 trial, we recruited previously untreated patients with an established histological diagnosis of mantle cell lymphoma from 29 Fondazione Italiana Linfomi centres in Italy. Patients had to be older than 65 years and fit according to the comprehensive geriatric assessment, or aged 60-65 years if they were ineligible for high-dose chemotherapy plus autologous stem-cell transplantation and were fit or unfit. All patients received RBAC500 (rituximab 375 mg/mBetween May 2, 2012, and Feb 25, 2014, we enrolled 57 patients (median age 71 years, IQR 67-75). 54 (95%) patients received at least four RBAC500 cycles (three discontinued because of toxicity), and 38 (67%) completed six cycles. Two (4%) had disease progression (one after the fourth cycle and one after the sixth cycle). All 52 (91%, lower limit of one-sided 95% CI 85%) remaining patients achieved complete response at the end of treatment. 23 (40%, upper limit of one-sided 95% CI 53%) of 57 patients had at least one episode of relevant toxicity. The most frequent grade 3-4 haematological toxicities were neutropenia (149 [49%] of 304 cycles) and thrombocytopenia (158 [52%]). Most treatment-related non-haematological adverse events were of grade 1-2, with the most frequent ones being fatigue (14 [25%] patients), nausea or vomiting (12 [21%]), and infusion-related reactions or tumour lysis syndrome (12 [21%]). 41 (72%) patients required a dose reduction. 12 patients died during the study, but no deaths were related to treatment.RBAC500 is an effective treatment for elderly patients with mantle cell lymphoma and, despite not meeting our prespecified safety boundary, haematological toxicity was manageable with appropriate supportive care and dose reduction. Since maintenance therapy is not required, RBAC500 could be considered an option and should be studied in phase 3 trials.Fondazione Italiana Linfomi and Mundipharma.

PubMed | Institute Of Cancerologie, Mount Vernon Cancer Center, University of Barcelona, Clinical Epidemiology Unit and 9 more.
Type: Journal Article | Journal: Journal of the European Academy of Dermatology and Venereology : JEADV | Year: 2016

Management of melanoma during pregnancy can be extremely challenging. The reported incidence of melanoma in pregnancy ranges from 2.8 to 5.0 per 100 000 pregnancies. There are no guidelines for the management of melanoma during pregnancy.The survey was designed to investigate the opinions of melanoma physicians on decision making in relation to pregnancy and melanoma. A clinical scenario-based survey on management of pregnancy in melanoma was distributed all over Europe via the membership of the EORTC and other European melanoma societies.A total of 290 questionnaires were returned with a larger participation from southern Europe. A large heterogeneity was found for the answers given in the different clinical scenarios with 50% of the answers showing discordance, especially regarding sentinel lymph node biopsy during pregnancy. Discordant answers were also found for the counselling of women about a potential delay in getting pregnant after a high-risk melanoma (35% for a 2 year wait minimum vs. 57% no waiting needed), while for thin melanomas, as expected, there was more concordance with 70% of the physicians recommending no delay. Fifteen per cent of physicians recommended an abortion in stage II melanoma during the third month of pregnancy. Twenty per cent of the responders advised against hormonal replacement therapy in melanoma patients.The management of melanoma during pregnancy varies widely in Europe. At present, there is a lack of consensus in Europe, which may lead to very important decisions in women with melanoma, and guidelines are needed.

Colombo C.,University of Milan | Verga U.,Fondazione Cagranda Instituto Of Ricovero E Cura A Carattere Scientifico Irccs | Mian C.,University of Padua | Ferrero S.,University of Milan | And 11 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: The evaluation of basal calcitonin (bCT) and stimulated calcitonin (sCT) can be used for the diagnosis and follow-up of medullary thyroid cancer (MTC). Objective: The aim of this study was to evaluate the reliability of high-calcium (Ca) test and to identify gender-specific thresholds for MTC diagnosis. Patients: Patients with MTC in remission (n = 24) or in persistence (n = 18), RET gene mutations carriers (n = 14), patients with nodular goiter (n = 69), and healthy volunteers (n = 16) were submitted to pentagastrin and Ca (25 mg/kg) tests. Results: In all groups, the levels of calcitonin (CT) stimulated by either pentagastrin or Ca were significantly correlated. The prevalence of both C-cell hyperplasia (CCH) and MTC in women and men paralleled the increasing basal and peak CT levels in a gender-specific manner. Receiver operating characteristic plot analyses showed that the best levels of bCT to separate normal and CCH cases from MTC patients were above 18.7 pg/ml in females and above 68 pg/ml in males. Furthermore, Ca sCT above 184 pg/ml in females and above 1620 pg/ml in males had the highest accuracy to distinguish normal and CCH cases from patients with MTC. At the C-cell immunohistochemical examination, Ca sCT below 50 pg/ml corresponded to a mean number of 30 cells per 10 fields, whereas higher sCT associated with ameannumberof 400 cells per 10 fields, often displaying a diffuse and nodular distribution pattern. Conclusions: High-dose Ca test is a potent and well-tolerated procedure that can be applied worldwide at a low cost. Reference ranges for Ca sCT levels in different groups of patients and CT thresholds to diagnose CCH/MTC have been identified. Copyright © 2012 by The Endocrine Society.

Cappetta A.,Veneto Institute of Oncology IRCCS | Bergamo F.,Veneto Institute of Oncology IRCCS | Mescoli C.,University of Padua | Lonardi S.,Veneto Institute of Oncology IRCCS | And 2 more authors.
Pathology and Oncology Research | Year: 2012

Hepatoid adenocarcinoma is a rare extra hepatic neoplasm that displays morphological and phenotypic features similar to those of hepatocellular carcinoma. We report a case of a 75-year-old woman, presenting with abdominal pain and complaints of weakness and lost of appetite, who was found to have a mass on her right colon. She underwent right hemicolectomy for a pT3N2M0, stage IIIC colon cancer. The tumor phenotype and immunophenotype, as documented by alpha-fetoprotein immunoreaction positivity, were consistent with adenocarcinoma of hepatoid origin. The patient received FOLFOX-4 regimen as adjuvant treatment, relapsed after six cycles, then was switched to FOLFIRI regimen plus Bevacizumab and progressed after only four cycles. She died 1 month later, eight months after the diagnosis. The lack of any clinical benefit despite an aggressive and multimodal therapeutic strategy, raises a question about what should be targeted when we face this rare disease associated with a very poor prognosis. © 2011 Arányi Lajos Foundation.

Rossi C.R.,Veneto Institute of Oncology IRCCS | Vecchiato A.,Veneto Institute of Oncology IRCCS | Mastrangelo G.,University of Padua | Montesco M.C.,Veneto Institute of Oncology IRCCS | And 10 more authors.
Annals of Oncology | Year: 2013

Background: The impact of adherence to clinical practice guidelines (CPGs) for loco-regional treatment (i.e. surgery and radiotherapy) and chemotherapy on local disease control and survival in sarcoma patients was investigated in a European study conducted in an Italian region (Veneto).Patients and methods: The completeness of the adherence to the Italian CPGs for sarcomas treatment was assessed by comparing the patient's charts and the CPGs. Propensity score-adjusted multivariate survival analysis was used to assess the impact of CPGs adherence on patient clinical outcomes. Results: A total of 151 patients were included. Adherence to CPGs for loco-regional therapy and chemotherapy was observed in 106 out of 147 (70.2%) and 129 out of 139 (85.4%) patients, respectively. Non-adherence to CPGs for loco-regional treatment was independently associated with AJCC stage III disease [odds ratio (OR) 1.77, P = 0.011] and tumor-positive excision margin (OR 3.55, P = 0.003). Patients not treated according to the CPGs were at a higher risk of local recurrence [hazard ratio (HR) 5.4, P < 0.001] and had a shorter sarcoma-specific survival (HR 4.05, P < 0.001), independently of tumor stage. Conclusions: Incomplete adherence to CPGs for loco-regional treatment of sarcomas was associated with worse prognosis in patients with non-metastatic tumors.

PubMed | Research Institute Fujimori Kogyo Co., University of Padua and Veneto Institute of Oncology IRCCS
Type: Journal Article | Journal: Haemophilia : the official journal of the World Federation of Hemophilia | Year: 2016

The heterogeneity of von Willebrand disease (VWD) makes its diagnosis a difficult task.We report here on the usefulness of a microchip-based flow-chamber system, the total thrombus-formation analysis system (T-TAS), in the identification and characterization of VWD. Thirty VWD patients and 20 healthy subjects were studied with the T-TAS platelet (PL) and atherome (AR) microchips developed for the in vitro assessment of platelet thrombus formation and fibrin-rich platelet thrombus formation respectively.Samples from severe type 1 VWD, characterized by von Willebrand factor (VWF) levels below 10 U dLThe T-TAS appears to be sensitive mainly to plasma VWF concentration and the presence of large multimers. Failure of the PL and AR chips to become occluded points to a lack of large VWF multimers, or type 1 VWD with VWF levels below 10 U dL

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