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Marina di Pisa, Italy

Piccioni F.,Intensive Care and Palliative Care | Casiraghi C.,University of Milan | Fumagalli L.,Intensive Care and Palliative Care | Kusamura S.,Fondazione Istituto Nazionale Dei Tumori | And 5 more authors.
International Journal of Surgery | Year: 2015

Purpose: To evaluate epidural analgesia role after cytoreductive surgery with peritonectomy combined with heated intraperitoneal chemotherapy. Methods: 101 patients were retrospectively studied (between 2008 and 2012) to evaluate epidural analgesia effectiveness, tolerability and safety in this surgical context through the assessment of pain, detection of adverse events (nausea, vomiting, itching), temporary motor block, respiratory failure and coagulation profile in the post-operative period. Results: The median duration of epidural analgesia was 5 [range 1-10] days. As regards pain relief, the median verbal numerical scale scores at rest and on movement were below 2 and 5 until the fifth post-operative day, respectively. 13% of patients suffered nausea, 4% vomit, and 1% itching. No bradycardia or respiratory failure event was reported. 9.9% of patients had hypotension episodes. Coagulation reached normality only 3-4 days after surgery. 5 risky accidental dislodgments of epidural catheter occurred (prothrombine time INR>1.5) without neurological complications. Conclusions: Epidural analgesia ensures adequate pain relief and is well tolerated by patients after cytoreductive surgery with peritonectomy combined with heated intraperitoneal chemotherapy. Hypotension is common in this context and careful monitoring of coagulation parameters, especially in the first 3 days after surgery, is advisable to reduce the risk of neuraxial complications. © 2015 Surgical Associates Ltd. Source

Camisaschi C.,Unit of Immunotherapy of Human Tumor | De Filippo A.,Unit of Immunotherapy of Human Tumor | Beretta V.,Unit of Immunotherapy of Human Tumor | Vergani B.,University of Milan Bicocca | And 9 more authors.
Journal of Investigative Dermatology | Year: 2014

Plasmacytoid dendritic cells (pDCs) at tumor sites are often tolerogenic. Although pDCs initiate innate and adaptive immunity upon Toll-like receptor (TLR) triggering by pathogens, TLR-independent signals may be responsible for pDC activation and immune suppression in the tumor inflammatory environment. To identify molecules that are potentially involved in alternative pDC activation, we explored the expression and function of lymphocyte activation gene 3 (LAG-3) in human pDCs. In this report, we showed the expression of LAG-3 on the cell surface of a subset of circulating human pDCs. LAG-3+ pDCs exhibited a partially mature phenotype and were enriched at tumor sites in samples from melanoma patients. We found that LAG-3 interacted with major histocompatibility complex class II (MHC-II) to induce TLR-independent activation of pDCs with limited IFNα and enhanced IL-6 production. This in vitro cytokine profile of LAG-3-activated pDCs paralleled that of tumor-associated pDCs analyzed ex vivo. By confocal microscopy, LAG-3+ pDCs detected in melanoma-invaded lymph nodes (LNs) stained positive for IL-6 and preferentially localized near melanoma cells. These results suggest that LAG-3-mediated activation of pDCs takes place in vivo at tumor sites, and it is in part responsible for directing an immune-suppressive environment. © 2014 The Society for Investigative Dermatology. Source

Bindi M.L.,Liver Transplant Anaesthesia and Critical Care Medicine | Miccoli M.,University of Pisa | Marietta M.,Haemostasis and Thrombosis Unit | Meacci L.,Liver Transplant Anaesthesia and Critical Care Medicine | And 8 more authors.
Vox Sanguinis | Year: 2013

Background: Although orthotopic liver transplantation (OLT) is nowadays considered standard practice at experienced centres, it can still be affected by a significant risk of massive bleeding and its related complications. Solvent/detergent plasma (S/D Plasma) has been proposed as an alternative to fresh frozen plasma (FFP) to curtail such complications. This study aimed at evaluating the efficacy of S/D Plasma in OLT patients by comparing it to FFP. Materials and Methods: Sixty-three OLT patients were randomized into two groups depending on whether they were transfused with FFP or S/D plasma. A thromboelastography-based protocol aimed at achieving and maintaining predetermined coagulation goals was used to guide plasma transfusions. At the beginning and the end of surgery, standard laboratory coagulation tests were performed together with the assessment of the VII, VIII, V, XII factors and S protein blood levels. Results: The two study groups equally achieved the thromboelastography goals but with a reduced amount of transfusions in the S/D plasma group (P < 0·0001). At the end of surgery, factors V and XII and S protein blood levels were lower in the S/D plasma patients who also showed lower INR, aPTT and antithrombin III levels. Conclusion: In cirrhotic patients undergoing OLT, the use of S\D plasma associated with thromboelastography allows the same clinical results but with a significant reduction in the amount of plasma transfusions. © 2013 International Society of Blood Transfusion. Source

Vittorio O.,CNR Institute of Neuroscience | Cirillo G.,University of Calabria | Iemma F.,University of Calabria | Di Turi G.,University of Pisa | And 7 more authors.
Pharmaceutical Research | Year: 2012

Purpose A polysaccharide-flavonoid conjugate was developend and proposed for the treatment of pancreatic ductal adenocarcinoma (PDAC). Methods The conjugate was synthesized by free radical grafting reaction between catechin and dextran. The chemical characterization of the conjugate was obtained by UV-Vis, 1H-NMR, FT-IR and GPC analyses, while the functionalization degree was determined by the Folin-Ciocalteu assay. The biological activity of the catechin-dextran conjugate was tested on two different cell lines derived from human pancreatic cancer (MIA PaCa-2 and PL45 cells), and the toxicity towards human pancreatic nestin-expressing cells evaluated. Results Both the cancer cell lines are killed when exposed to the conjugate, and undergo apoptosis after the incubation with catechin-dextran which resulted more effective in killing pancreatic tumor cells compared to the catechin alone. Moreover, our experimental data indicate that the conjugate was less cytotoxic to human pancreatic nestin-expressing cells which are considered a good model of non-neoplastic pancreatic cells. Conclusion The suitability of newly synthesized Dextran-Catechin conjugate in the treatment of PDAC was proved confirming the high potential application of the proposed macromolecula system in the cancer therapy. © Springer Science+Business Media, LLC 2012. Source

Anichini A.,Human Tumors Immunobiology Unit | Molla A.,Human Tumors Immunobiology Unit | Vegetti C.,Human Tumors Immunobiology Unit | Bersani I.,Human Tumors Immunobiology Unit | And 9 more authors.
Cancer Research | Year: 2010

CD8+ T cells at the earliest stage of effector generation have not been identified at tumor site of melanoma patients. Such early effectors, if present, should be characterized by a specific phenotype, distinct from that expressed at later stages of the antigen-induced differentiation program, by short-lived effector cells, memory precursors, and terminal effectors. Here, we show that neoplastic tissues from primary and metastatic lesions of melanoma patients contain a subset of CD8+ T cells expressing FOXP3. CD8 + FOXP3+ CD25+ T lymphocytes were found in tumor-invaded lymph nodes (TILN), s.c. metastases, and advanced primary lesions. Their frequency was significantly higher in TILN compared with tumor-free lymph nodes or with peripheral blood and in primary tumors compared with TILN. CD8+ FOXP3+ T cells did not express markers of regulatory [CTLA-4, CCL4, interleukin-10 (IL-10), transforming growth factor-β1], exhausted (PD-1), or senescent (CD57) CD8+ T lymphocytes. Instead, this subset showed an antigen-experienced "EM1" phenotype (CCR7 -. CD45RA- CD28+ CD27+) and exhibited a CD127-, KLRG1-, HLA-DR+, CD38 +, T-bet+, perforin+ "early effector" profile predicted by current models. CD8+ FOXP3+ T cells produced IFN-γ on short in vitro activation, recognized autologous tumor by CD107a mobilization, and expressed Ki-67 on ex vivo analysis. In response to autologous tumor plus IL-2/IL-15, the CD8+ FOXP3+ T cells proliferated promptly and showed competence for differentiation (downregulation of CD27 and upregulation of T-bet). These results suggest development of early phases of antitumor immunity even in advanced melanoma. Moreover, the CD8 + FOXP3+ "early effector" subset may be an invaluable tool for monitoring immunity at tumor site. ©2010 AACR. Source

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