PD45-01\u2003ASSOCIATION OF LOCAL ANAESTHETIC WOUNDS INFILTRATION AND ULTRASOUND TRANSVERSUS ABDOMINAL PLANE (US-TAP) BLOCK IN PATIENTS UNDERGOING ROBOT-ASSISTED RADICAL PROSTATECTOMY: A DOUBLE-BLIND RANDOMIZED CONTROLLED TRIAL

INTRODUCTION AND OBJECTIVES: To determinate bene\ufb01ts of the association of local anaesthetic wounds in\ufb01ltration and US-TAPblock with ropivacaine on postoperative pain, early recovery and hospital stay in patients undergoing robot assisted radical prostatectomy (RARP). METHODS: The study is double-blinded randomized controlled trial. Our hypothesis was that the association of wound in\ufb01ltration and US-TAP block with Ropivacaine would decrease immediate postoperative pain and opioids use. Primary outcomes included postoperative pain and opioids demand during the hospital stay. Secondary outcomes were nausea/vomiting rate, stool passing time, use of pro-kinetics, length of hospital stay and 30-days readmission to the hospital for pain or other US-TAP-block related complications RESULTS: A total of 100 patients who underwent RARP were eligible for the analysis; 57 received the US-TAP block with 20 ml of 0.35% Ropivacaine (US-TAP-block group) and 43 did not receive USTAP block (no-US-TAP group). All the patients received the local wound anaesthetic in\ufb01ltration with 20 ml of 0.35% Ropivacaine. USTAP block group showed a decreased mean NRS (2.7vs1.8; p[0.04) and reduced use of opioid (8 vs 2; p[0.01) in the \ufb01rst 24 h. Moreover, we found a shorter mean LOS (4.7 vs 4.2; p[ 0.04) with a reduced use of pro-kinetics during the hospital stay (31 vs 12; p<0.001). No US-TAP-block related complications to were reported. CONCLUSIONS: Association of anaesthetic wound in\ufb01ltration and US-TAP block with Ropivacaine as part of a multimodal analgesic regimen can be safely offered to patients undergoing RARP and ePLND. It improves the immediate post-operative pain control, reducing opioids administration and is associated to a decreased use of pro-kinetics and shorter hospital stay

Prostate cancer peripheral blood NK cells show enhanced CD9, CD49a, CXCR4, CXCL8, MMP-9 production, and secrete monocyte-recruiting and polarizing factors.

Background. Natural killer (NK) cells are effector lymphocytes of the innate immunity. Two major NK cell subsets are mostly present in the peripheral blood (pNKs): the cytotoxic CD56dimCD16+ NK cell subset (90-95% of pNKs), and the low cytotoxic, highly cytokine-producing CD56brightCD16-/low NK cell subset (5-10% of pNKs). It has been demonstrated that NK cells in peripheral blood of patients with several tumors are altered. We have shown that in NSCLC and colon cancer, tumor associated circulating NK (pTA-NK) and tumor infiltrating NK (TI-NK) are skewed towards the CD56brightCD16-/low phenotype. We have detected the production of pro-inflammatory and pro-angiogenic cytokines and chemokines. Other groups are reporting similar observations. There is still a lack of knowledge concerning the phenotype of pNK cells in prostate cancer (PCa). Here, we phenotypically and functionally characterized peripheral blood NK (pNK) from PCa patients (PCa pTA-NKs) and investigated their production of soluble factors, with endothelial cells and macrophage stimulatory action. Methods. NK cell subset distribution was investigated in the peripheral blood of PCa patients, by multicolor flow cytometry (FC) for surface antigens expression. Protein arrays were performed to characterize the secretome on FACS-sorted pNK cells. Secreted products from FACS-sorted PCa TA-NKs were used to characterize their production of pro-inflammatory molecules. Secreted products from FACS-sorted PCa pTA-NKs were also used to stimulate endothelial cells and monocytes and macrophages, determining their ability to recruit and polarize them. Alterations of endothelial cells and monocytes, following exposure to secreted products from FACS-sorted PCa pTA-NKs, was assessed by RT-PCR. To confirm these observations, secreted products from 3 different PCa (PC-3, DU-145, LNCaP) cell lines were used to assess their effects on human NK cell polarization, by multicolor flow cytometry. Results. Circulating NK cells from prostate cancer patients have been studied before, mostly for their impaired lytic functions. However, here we are the first to report that circulating pNK cells from PCa patients acquire a CD56brightCD9+CD49a+CXCR4+ phenotype with pro-inflammatory properties. We observed a similar polarization of heathy-donor derived pNK cells exposed to secreted products of three different PCa cell lines. Increased production of CXCL8, CXCR4, MMP-9, pro-inflammatory and reduced production of TNF\u3b1, IFN\u3b3 and Granzyme-B was detected. PCa TA-NKs released factors able to support angiogenesis in vitro and increased the expression of CXCL8, ICAM-1 and VCAM-1 mRNA in endothelial cells, confirming a pro-inflammatory signature. Secretome analysis revealed the ability of PCa pTA-NKs to release pro-angiogenic cytokines/chemokines involved in monocyte recruitment and M2-like polarization. In experimental setting, secreted products from PCa pTA-NKs can recruit THP-1 monocyte and polarize THP-1-differentiated macrophage towards CD206/Arginase1/IL-10/CXCL8-expressing M2-like/TAMs. Conclusions. Our results show that PCa pTA-NKs are effector cells able to produce pro-inflammatory angiogenesis factors able to stimulate endothelial cells, attract monocytes and polarize macrophage to an M2-like type. Our data provides a rationale for the possible use of pNK profiling in clinical studies on PC