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Objective The aim of the present study was to evaluate the impact of a multidisciplinary approach in patients' selection with advanced ovarian cancer (AOC) for different therapeutic strategies. Methods Patients referred at our institution between 2009 and 2012 for AOC were included. Primary multidisciplinary evaluation was performed in all patients. Different strategies included: 1. patients referred to primary neoadjuvant chemotherapy (NACT) and interval surgery (IDS) (group A); 2. patients considered for surgical exploration. After surgical exploration, patients were either considered for primary debulking (PDS; group B), or NACT (group C). Results A total of 363 patients were included. Of 38 patients (10.5%) in group A, 24 (63%) had sovradiaphragmatic/multiple liver metastases; 14 (37%) were excluded for PDS for anestehesiologic/medical reasons. Of 325 (89.5%) considered for surgical exploration, 295 (91%; group B) had primary surgery with debulking intent (N: 277) and were cytoreduced to no macroscopic disease (R0: N:200; 68%) o minimal RD

Objectives To compare the clinical and oncologic outcomes of robotic radical hysterectomy (RRH) vs abdominal radical hysterectomy (ARH) in patients with cervical carcinoma. Methods A retrospective analysis of women who underwent radical hysterectomy for cervical cancer from December 2006 to December 2014 at European Institute of Oncology was performed. Patients who underwent RRH were compared with women operated on by ARH. The groups were matched by age, body mass index, tumor size, International Federation of Gynecology and Obstetrics stage, comorbidity, previous neoadjuvant chemotherapy, histology type, and tumor grade. Results A total of 203 and 104 women who underwent RRH and ARH, respectively, were analyzed. Baseline characteristics, stage of disease, histology type, and grade of differentiation were similar between groups. Surgical time was significantly shorter in the ARH group (208 vs 282 minutes, P ⩽ 0.001). Robotic radical hysterectomy was associated with significantly less estimated blood loss (219 vs 104 mL, P = 0.001) and with significantly shorter hospital stay (5.2 vs 3.9 days, P ⩽ 0.001). Abdominal radical hysterectomy was correlated with a significantly higher number of lymph nodes removed (25.8 vs 22, P = 0.003). None of the robotic procedures required conversion to laparotomy. A significantly higher number of patients in ARH required postoperative transfusion (11 [10.5%] vs 6 [2.9%], P = 0.006). Lower extremity lymphedema was significantly higher in ARH (28 [27.5%] vs 17 [8.3%], P = 0.001). Recurrence rates as well as progression-free survival and overall survival were similar between groups at a median follow-up of 41.64 months. Conclusions Robotic radical hysterectomy is safe and feasible and is associated with improved clinical outcomes. Although longer follow-up is needed, early data show equivalent oncologic outcomes compared with other surgical modalities.

Randomly evolving systems composed by elements which interact among each other have always been of great interest in several scientific fields. This work deals with the synchronization phenomenon, that could be roughly defined as the tendency of different components to adopt a common behavior. We continue the study of a model of interacting stochastic processes with reinforcement, that recently has been introduced in Crimaldi et al. (2016, arXiv:1602.06217). Generally speaking, by reinforcement we mean any mechanism for which the probability that a given event occurs has an increasing dependence on the number of times that events of the same type occurred in the past. The particularity of systems of such stochastic processes is that synchronization is induced along time by the reinforcement mechanism itself and does not require a large-scale limit. We focus on the relationship between the topology of the network of the interactions and the long-time synchronization phenomenon. After proving the almost sure synchronization, we provide some CLTs in the sense of stable convergence that establish the convergence rates and the asymptotic distributions for both convergence to the common limit and synchronization. The obtained results lead to the construction of asymptotic confidence intervals for the limit random variable and of statistical tests to make inference on the topology of the network given the observation of the reinforced stochastic processes positioned at the vertices., Comment: 40 pages

Objective: Isoflurane is a volatile anesthetic that has a vasodilating effect on cerebral vessels producing a cerebral blood flow increase. Furthermore, it has been shown in animal studies that isoflurane, when used as a preconditioning agent, has neuroprotective properties, inducing tolerance to ischemia. However, it is not routinely used in neurointensive care because of the potential increase in intracranial pressure caused by the rise in cerebral blood flow. Nevertheless, subarachnoid hemorrhage patients who are at risk for vasospasm may benefit from an increase in cerebral blood flow. We measured regional cerebral blood flow during intravenous sedation with propofol and during sedation with isoflurane in patients with severe subarachnoid hemorrhage not having intracranial hypertension. Design: The study is a crossover, open clinical trial (NCT00830843). Setting: Neurointensive care unit of an academic hospital. Patients: Thirteen patients with severe subarachnoid hemorrhage , (median Fisher scale 4), monitored on clinical indication with intracranial pressure device and a thermal diffusion probe for the assessment of regional cerebral blood flow. An intracranial pressure >18 mm Hg was an exclusion criterion. Interventions: Cerebral and hemodynamic variables were assessed at three steps. Step 1: sedation with propofol 3–4 mg/ kg/hr; step 2: after 1 hr of propofol discontinuation and isoflurane 0.8%; step 3: after 1 hr of propofol at the same previous infusion rate. Cerebral perfusion pressure and arterial Pco 2 were maintained constant. Mean cerebral artery flow velocity and jugular vein oxygen saturation were measured at the end of each step. Measurements and Main Results: Regional cerebral blood flow increased significantly during step 2 (39.3 ± 29 mL/100 hg/min) compared to step 1 (20.8 ± 10.7) and step 3 (24.7 ± 8). There was no difference in regional cerebral blood flow comparing step 1 vs. step 3. No significant difference in intracranial pressure, mean cerebral artery transcranial Doppler velocity, PaCO 2 , cerebral perfusion pressure between the different steps. Conclusions: Isoflurane increases regional cerebral blood flow in comparison to propofol. Intracranial pressure did not change significantly in the population not affected by intracranial hypertension. (Crit Care Med 2012; 40:2797–2804)

Epithelial ovarian carcinoma (EOC) is an aggressive neoplasm, which mainly disseminates to organs of the peritoneal cavity, an event mediated by molecular mechanisms that remain elusive. Here, we investigated the expression and functional role of neural cell adhesion molecule (NCAM), a cell surface glycoprotein involved in brain development and plasticity, in EOC. NCAM is absent from normal ovarian epithelium but becomes highly expressed in a subset of human EOC, in which NCAM expression is associated with high tumour grade, suggesting a causal role in cancer aggressiveness. We demonstrate that NCAM stimulates EOC cell migration and invasion in vitro and promotes metastatic dissemination in mice. This pro-malignant function of NCAM is mediated by its interaction with fibroblast growth factor receptor (FGFR). Indeed, not only FGFR signalling is required for NCAM-induced EOC cell motility, but targeting the NCAM/FGFR interplay with a monoclonal antibody abolishes the metastatic dissemination of EOC in mice. Our results point to NCAM-mediated stimulation of FGFR as a novel mechanism underlying EOC malignancy and indicate that this interplay may represent a valuable therapeutic target. © 2011 EMBO Molecular Medicine.

HtrA1 belongs to a family of serine proteases found in organisms ranging from bacteria to humans. Bacterial HtrA1 (DegP) is a heat shock-induced protein that behaves as a chaperone at low temperature and as a protease at high temperature to help remove unfolded proteins during heat shock. In contrast to bacterial HtrA1, little is known about the function of human HtrA1. Here, we report the first evidence that human HtrA1 is a microtubule-associated protein and modulates microtubule stability and cell motility. Intracellular HtrA1 is localized to microtubules in a PDZ (PSD95, Dlg, ZO1) domain-dependent, nocodazole-sensitive manner. During microtubule assembly, intracellular HtrA associates with centrosomes and newly polymerized microtubules. In vitro, purified HtrA1 promotes microtubule assembly. Moreover, HtrA1 cosediments and copurifies with microtubules. Purified HtrA1 associates with purified alpha- and beta-tubulins, and immunoprecipitation of endogenous HtrA1 results in coprecipitation of alpha-, beta-, and gamma-tubulins. Finally, downregulation of HtrA1 promotes cell motility, whereas enhanced expression of HtrA1 attenuates cell motility. These results offer an original identification of HtrA1 as a microtubule-associated protein and provide initial mechanistic insights into the role of HtrA1 in theregulation of cell motility by modulating microtubule stability. HtrA1 belongs to a family of serine proteases found in organisms ranging from bacteria to humans. Bacterial HtrA1 (DegP) is a heat shock-induced protein that behaves as a chaperone at low temperature and as a protease at high temperature to help remove unfolded proteins during heat shock. In contrast to bacterial HtrA1, little is known about the function of human HtrA1. Here, we report the first evidence that human HtrA1 is a microtubule-associated protein and modulates microtubule stability and cell motility. Intracellular HtrA1 is localized to microtubules in a PDZ (PSD95, Dlg, ZO1) domain-dependent, nocodazole-sensitive manner. During microtubule assembly, intracellular HtrA associates with centrosomes and newly polymerized microtubules. In vitro, purified HtrA1 promotes microtubule assembly. Moreover, HtrA1 cosediments and copurifies with microtubules. Purified HtrA1 associates with purified alpha- and beta-tubulins, and immunoprecipitation of endogenous HtrA1 results in coprecipitation of alpha-, beta-, and gamma-tubulins. Finally, downregulation of HtrA1 promotes cell motility, whereas enhanced expression of HtrA1 attenuates cell motility. These results offer an original identification of HtrA1 as a microtubule-associated protein and provide initial mechanistic insights into the role of HtrA1 in theregulation of cell motility by modulating microtubule stability.

Resistance to chemotherapy presents a serious challenge in the successful treatment of various cancers and is mainly responsible for mortality associated with disseminated cancers. Here we show that expression of HtrA1, which is frequently downregulated in ovarian cancer, influences tumor response to chemotherapy by modulating chemotherapy-induced cytotoxicity. Downregulation of HtrA1 attenuated cisplatin- and paclitaxel-induced cytotoxicity, while forced expression of HtrA1 enhanced cisplatin- and paclitaxel-induced cytotoxicity. HtrA1 expression was upregulated by both cisplatin and paclitaxel treatment. This upregulation resulted in limited autoproteolysis and activation of HtrA1. Active HtrA1 induces cell death in a serine protease-dependent manner. The potential role of HtrA1 as a predictive factor of clinical response to chemotherapy was assessed in both ovarian and gastric cancer patients receiving cisplatin-based regimens. Patients with ovarian or gastric tumors expressing higher levels of HtrA1 showed a higher response rate compared with those with lower levels of HtrA1 expression. These findings uncover what we believe to be a novel pathway by which serine protease HtrA1 mediates paclitaxel- and cisplatin-induced cytotoxicity and suggest that loss of HtrA1 in ovarian and gastric cancers may contribute to in vivo chemoresistance.

Background and objective: Acute renal failure is a serious complication of cardiac surgery. We studied the long-term survival and quality of life of patients requiring renal replacement therapy after cardiac surgery, since they represent a heavy burden on hospital resources and their outcome has never been adequately evaluated. Methods: Out of 7846 consecutive cardiac surgical patients, 126 (1.6%) required postoperative renal replacement therapy: their preoperative status and hospital course was compared with patients who had no need of postoperative renal replacement therapy. A multivariate analysis identified predictors of renal replacement therapy. Longterm survival and quality of life was collected in patients who had renal replacement therapy and in casematched controls. Results: Hospital mortality in the study group was 84/126 (66.7%) vs. 118/7720 (1.5%) in the control population (P < 0.001). Patients who underwent renal replacement therapy and were discharged from the hospital (42 patients) had a reasonable long-term outcome: at 42 +/- 23 months, 30 out of 42 patients were alive, with only 3 patients complaining of limitations in daily activities. Predictors of in-hospital renal replacement therapy were: emergency surgery, preoperative renal Impairment, intra-aortic balloon pumping, reoperation for bleeding, previous cardiac surgery, female gender, low ejection fraction, bleeding > 1000 mL, chronic obstructive pulmonary disease and age. Conclusions: This study confirms that the in-hospital mortality of patients requiring renal replacement therapy is high and shows a low long-term mortality with reasonable quality of life in patients discharged from hospital alive.

PURPOSE: To prospectively evaluate the accuracy of integrated positron emission tomography (PET) and computed tomography (CT) for depiction of persistent ovarian carcinoma after first-line treatment, with use of histologic findings as the reference standard. MATERIALS AND METHODS: Thirty-one women (mean age, 55.9 years) with ovarian carcinoma treated with primary cytoreductive surgery and followed up with platinum regimen chemotherapy were included. All 31 patients were scheduled for surgical second-look. Before surgical second-look, all patients underwent fluorodeoxy-glucose (FDG) PET/CT. At PET/CT, three main categories of persistent disease were considered for data analysis: lymph nodal lesion, peritoneal lesion, and pelvic lesion. In all patients, imaging findings were compared with results of histologic examination after surgical second-look to determine the diagnostic accuracy of PET/CT in the evaluation of disease status. The kappa statistic (Cohen kappa) was used for statistical analysis. RESULTS: Seventeen (55%) of 31 patients had persistent tumor at histologic analysis after surgical second-look, and fourteen (45%) had no histologically proved tumor. The total number of lesions that was positive for tumor cells at histologic analysis was 41 (lymph nodes, n = 16; peritoneal lesions, n = 21; pelvic lesions, n = 4); maximum diameter of these lesions was 0.3-3.2 cm (mean, 1.7 cm). A correlation was found between PET/CT and histologic analysis (kappa = 0.48). The overall lesion-based sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT were 78%, 75%, 77%, 89% and 57%, respectively. In the detection of a tumor, a size threshold could be set at 0.5 cm, as this was the largest diameter of a lesion missed at PET/CT. CONCLUSION: Integrated PET/CT depicts persistent ovarian carcinoma with a high positive predictive value. (C) RSNA, 2004.

We construct a response adaptive design, described in terms of a two-color urn model, targeting fixed asymptotic allocations. We prove asymptotic results for the process of colors generated by the urn and for the process of its compositions. An application of the proposed urn model is presented in an estimation problem context.

Objectives The aim of the study is to evaluate the response to neoadjuvant chemotherapy (NACHT) of patients with recurrent cervical cancer who were poor candidates for pelvic exenteration (PE), and the impact on DFS and OS. Methods A retrospective data collection extracted from medical records of 61 patients submitted to pelvic exenteration was performed: 30 underwent up-front exenterative procedure whereas 31 received NACHT. Results The median tumor size was significantly (P = 0.0006) larger in the NACHT group compared to the up-front PE one (43.9 mm vs 28 mm), and a significant (P = 0.04) higher percentage of patients (45 vs 20%) had lateral pelvic wall invasion in the NACHT group. No statistically significant difference in early and late complications was observed in the two groups. Median overall survival in study population was 42.9 months (95% CI: 22.2, 180.8). Median overall survival times as well as recurrence free survival times were not significantly different between NACHT (42.9 months and 36.1 months for OS and DFS respectively) vs. No NACHT (111.9 months and 48.1 months for OS and DFS respectively). There was an overall significant difference in DFS between negative and positive margins but the curves were similar for NACHT and up-front PE groups stratified by resection margin status. Conclusions In our series, though small and retrospective, NACHT prior to PE represents a feasible therapeutic option without intra-operative and early post-operative mortality or worsening of early and late complication rate and with acceptable long-term survival and DFS for recurrent cervical cancer patients who are poor candidates for up-front pelvic exenteration. © 2013 Elsevier Inc.

BackgroundThe aim of surgical approach in advanced ovarian cancer should be the complete removal of all visible disease. Our purpose was to compare perioperative features and postoperative complications, and secondarily oncological outcomes, between patients who underwent splenectomy and those who did not at the time of surgery.Materials and MethodsThirty-three subjects underwent splenectomy, and we selected 99 controls with similar surgical characteristics but who did not undergo splenectomy. Data collected included perioperative details and follow-up data.ResultsLonger operating time (33 minutes longer;P= 0.02), larger estimated blood loss (812 mL more;P= 0.03), higher rate of intraoperative blood transfusions (78.8% vs 42.4%;P< 0.01), and intensive care unit stay (1.4 vs 0.5 days;P< 0.01) as well as higher pneumonia rate (2% vs 0%;P= 0.01) were observed in the splenectomy group. Disease-free and overall survival rates were 30.3% and 66.6%, respectively, in the splenectomy group, and 33.3% and 59.6%, respectively, in the control group.ConclusionsSplenectomy at the time of primary cytoreductive surgery for advanced ovarian cancer may contribute to achieve complete cytoreduction with low perioperative complication rate. This procedure seems to be an acceptable and rational intervention to increase the survival rates of those patients.

Objective: The aim of the study was to determine the impact of rectosigmoid resection, at the time of primary cytoreductive surgery, on morbidity and survival of patients with advanced ovarian cancer. Methods: We performed a retrospective medical chart review of patients who underwent rectosigmoid resection for ovarian, tubal and peritoneal cancers between 1998 and 2008 at the IEO in Milan and JHMI in Baltimore. Perioperative and follow-up data were collected. Results: A total of 238 patients were identified; 180 (75%) had stages IIC-IIIC and 58 (25%) had stage IV. Complete cytoreduction was achieved in 41% of the cases. Stapled coloproctostomy was performed in 98% while hand sewn in only 2%; a protective ileostomy and colostomy were necessary (constructed) in 2 (0.8%) and 5 (2%) cases respectively. The complications associated to rectosigmoid resection were anastomotic leakage in 7 (3%) patients and pelvic abscess in 9 (3.7%). Fifty percent of patients recurred during the study period, but only 5% of them showed a relapse at the level of the pelvis whereas 8% presented with abdominal recurrence associated with pelvic disease as well. The median overall survival time among patients with complete cytoreduction was 72 months compared with 42 months among the rest of patients (p = 0.002). Conclusions: Rectosigmoid colectomy may significantly contribute to achieve a complete primary cytoreduction for advanced stage ovarian, tubal and peritoneal cancers. Pelvic complete debulking accomplished by rectosigmoid resection could be associated with a lower rate of pelvic recurrence as well. © 2012 Elsevier Inc. All rights reserved.

BackgroundStandard approach for medically stable advanced ovarian cancer patients should be primary cytoreduction following platinum-based chemotherapy. The aim of surgical effort should be the complete removal of all visible disease. Our objective was to compare perioperative features, postoperative complications, and secondarily oncological outcomes of patients who underwent diaphragmatic stripping with those who underwent diaphragmatic resection for advanced ovarian cancer.MethodsOne hundred twelve cases were identified, among them 79 underwent diaphragmatic stripping and 33 underwent diaphragmatic full-thickness resection. Data collected included patients’ age, all perioperative details and pathological findings, International Federation of Gynecology and Obstetrics stage, adjuvant therapy, and follow-up data.ResultsLarger residual tumors (mean, 5.1 vs 1.6 mm, respectively;P< 0.01) but shorter operating time (25 minutes shorter operative time,P= 0.07) were observed in the stripping group. Higher postoperative pleural effusions rates (63.6% vs 37.9%,P= 0.01), but no differences in the remaining complications, were observed in the resection group. After a mean of 31 months of follow-up, disease-free survival rates were 27.8% in the stripping group and 39.4% in the resection group (P= 0.04). No significant differences were observed for overall survival.ConclusionsDiaphragmatic surgery at the time of primary cytoreductive surgery for advanced ovarian cancer may contribute to the achievement of complete cytoreduction with low perioperative complication rate; full-thickness resection is preferable if peritoneum stripping will not achieve a complete removal of the disease.

Objective To determinate the impact of maximal cytoreductive surgery on progression free survival (PFS), overall survival (OS) rates and morbidity, in patients with advanced epithelial ovarian or fallopian tube cancer. Methods We reviewed all medical records of patients with stages IIIC–IV epithelial ovarian and fallopian tube cancer that were managed at our institution between January 2001 and December 2008. The following information was collected: demographics, tumor characteristics, operative information, surgical outcomes and peri-operative complication. Results A total of 288 patients with advanced epithelial ovarian and fallopian tube cancer were referred to our institution between January 2001 and December 2008, 259 consecutive patients were enrolled in the study. After a median follow-up of 29.8 months, the PFS and OS were 19.9 and 57.6 months, respectively. At univariate analysis, factors significantly associated with decreased PFS included: age greater than median (> 60 years), stage IV, presence of ascites > 1000 cc, presence of diffuse peritoneal carcinomatosis and diameter of residual disease. This was confirmed also at multivariate analysis with age greater than 60 years (P = 0.025), stage IV vs IIIC (P = 0.037) and any residual disease (P = 0.032) having an independent association with worse PFS. Conclusions Our study seems to demonstrate that a more extensive surgical approach is associated with prolonged disease-free interval and improved survival in patients with stages IIIC–IV epithelial ovarian and fallopian tube cancer. Moreover all patients with no residual tumor seem to have the best prognosis and in view of these results we believe that the goal of primary surgery should be considered as leaving no macroscopic disease.

In this chapter, we briefly review some opinion dynamics models starting from the classical Schelling model and other agent-based modelling examples. We consider both discrete and continuous models and we briefly describe different approaches: discrete dynamical systems and agent-based models, partial differential equations based models, kinetic framework. We also synthesized some comparisons between different methods with the main references in order to further analysis and remarks.

Background Borderline ovarian tumors (BOTs) are a histological category of epithelial ovarian tumors and 70% of them are early diagnosed (stage I). Since early stage is the most important prognostic factor, restaging procedure could be justified. This study aims to evaluate the role of restaging surgery in the management of patients with borderline ovarian tumors referred to our Institution after being incompletely surgically staged in other hospitals. Materials and methods We retrospectively reviewed the charts of patients with BOT who were referred to our centre to undergo restaging procedure. From December 1995 to May 2008, 186 patients were treated for BOT and 70 patients met the inclusion criteria. Data collected included patients' age, primary and re-staging surgery details, FIGO stage after first and second procedure, pathological findings, and follow-up data. Results FIGO stage after primary surgery was IA in 46 patients (68.6%), IB in 7 patients (10.4%), IC in 12 patients (17.9%, 6 due to ruptured cyst), IIA in 1 patient (1.4%), IIB in 1 patient (1.4%), III B in 2 patients (2.8%), and IIIC in 1 patient (1.4%). Among stage I patients (representing 97% of all patients), 12.3% (8 patients) were up-staged. The upstaging rate among serous tumors was 16.2%, and 4% among mucinous tumors. The mean follow-up time was 60.4 months from restaging surgery (SD 30.6 months). We observed 8 primary recurrences of the disease and 3 second recurrences. Conclusions There were no differences in terms of overall survival between patients who were upstaged and those who were not. Restaging procedure does not seem to have a significant impact on the management of patients diagnosed with borderline ovarian tumors, especially in mucinous subtype and apparent FIGO stage higher than I.

Background and objective Patients undergoing off-pump coronary artery bypass grafting (CABG) may need emergent institution of cardiopulmonary bypass (CPB) for circulatory collapse during the operation. Our aim was to evaluate outcome in such patients and identify preoperative and intraoperative risk factors. Methods This is an observational study in a University Hospital setting. In the period June 2001-July 2003, data from 988 consecutive patients undergoing CABG in our institution were prospectively collected. No interventions were made. Prolonged hospital stay (>7 days), hospital mortality, temporal trends and risk factors for conversion from off-pump to on-pump surgery were studied. Results Fifty-four patients with emergency operations and six with associated carotid artery surgery were excluded. Of the remaining 928 patients, 450 (48.5%) were planned for off-pump surgery. Thirty-seven (8.2%) of them required conversion to CPB on an emergency basis. These patients had higher mortality (5.4%) than the off-pump group (1.5%) and the CPB group (0.4%), P = 0.02. The incidence of prolonged hospital stay was also higher (conversion group = 27%, off-pump group = 12.3%, CPB group = 17.6%; P = 0.02). We did not identify any perioperative characteristics significantly associated with the risk of requiring conversion. The conversion rate was uniformly distributed over the study period. Conclusions Patients who are emergently converted to CPB during attempted off-pump procedures are at higher risk of death and prolonged hospital stay; this population should be included in comparative studies as "intention to treat" in the off-pump group.

Background: There is evidence that cancer is immunogenic under certain situations. IL-2 is described to stimulate an effective antitumor immune response in vitro and in vivo. The ability of cancer patients to undergo surgical resection is still the most important prognostic factor for many solid tumors, including gastric adenocarcinoma. The host immune system may be further compromised by surgical procedures leading to a generalized state of immunodepression in the post-operative period. The aim of this randomized case-control study is to evaluate the effects of pre-operative low-dose IL-2 treatment on patients with gastric adenocarcinoma who undergo surgery. Methods: Sixty-eight patients with gastric adenocarcinoma were enrolled in the study and randomized in two groups: 36 patients were pre-treated with IL-2 and 32 underwent surgery without any treatment. Total peripheral WBC, neutrophils, CD3+ T, CD4+ T, CD8+ T and NK cells were obtained before and after surgery, at different times. Peritumoral infiltration was analyzed on all surgical specimens. Overall survival and relapse-free survival were studied with a median follow-up of 51 months. Results: Low-dose IL-2 treatment resulted in an increase peritumoral lymphocytic and eosinophilic infiltrations and in a minor decrease in CD3+ T and CD4+ T cells after surgery (P < 0.05). A stepwise multivariate analysis revealed that overall survival and relapse-free survival were affected only by stage of tumor and age of patients. Conclusions: According to our data low-doses of IL-2 administered pre-operatively to patients with gastric cancer activate peripheral and peri-tumoral lymphocytes but did not affect prognosis. © 2007 Society of Surgical Oncology.

Objective: The purpose of this study was to evaluate the effects of volatile anesthesia versus total intravenous anesthesia on cardiac troponin release in off-pump coronary artery bypass grafting (OPCAB). Design: The authors performed a multicenter randomized controlled study to compare cardiac troponin release in patients receiving either volatile anesthetics or total intravenous anesthesia for cardiac surgery on the beating heart, which is an excellent model of human myocardial ischemia. Setting: Three university hospitals. Participants: The authors randomly assigned 57 patients to desflurane (volatile anesthetic) and 55 patients to propofol (intravenous anesthetic) in addition to an opiate-based anesthesia for OPCAB. Interventions: The 2 groups of patients received either desflurane (volatile anesthetic) or propofol in addition to an opiate-based anesthesia for OPCAB. Peak postoperative troponin I release was measured as a marker of myocardial necrosis. Prolonged hospitalization was considered as a secondary outcome. Measurements and Main Results: Patient mean age was 69 years, and 82% were men. There was a significant (p < 0.001) reduction in postoperative median (25th-75th percentiles) peak of troponin I in patients receiving volatile anesthetics, 1.2 (0.9-1.9) ng/dL, compared with patients receiving total intravenous anesthesia, 2.7 (2.1-4.0) ng/dL. This myocardial protection resulted in a reduced (p = 0.04) number (percentage) of patients requiring postoperative inotropes, 20 (35%) versus 31 (56%), and a reduced number (percentage) of patients submitted to prolonged hospitalization ( 7 days), 7 (12%) versus 20 (36%) in the 2 groups (p = 0.005). One patient receiving total intravenous anesthesia died within 30 days of surgery. Conclusions: Myocardial damage measured by cardiac troponin release could be reduced by volatile anesthetics during OPCAB. Because patients underwent cardiac surgery on the beating heart, these results could have implications for cardiac patients undergoing noncardiac surgery. (C) 2006 Elsevier Inc. All rights reserved.

Objective : Atrial fibrillation is the most common complication after coronary artery bypass graft surgery. This arrhythmia may lead to hemodynamic compromise, prolonged hospitalization, and increased risk for cerebral thromboembolism. Older age is the only variable consistently associated with the development of postoperative atrial fibrillation; however, no strong predictive model exists. The purpose of this study was to identify perioperative characteristics associated with new-onset atrial fibrillation in patients undergoing off-pump coronary artery bypass grafting. Design : Prospective, observational. Setting : University tertiary care hospital. Participants : One hundred sixty consecutive patients undergoing off-pump coronary artery bypass grafting. Interventions : None. Measurements and Main Results : Incidence of postoperative atrial fibrillation was the major outcome. Atrial fibrillation occurred in 33 patients (20.6%). Multivariate analysis identified reintervention (odds ratio 26.8), revascularization of the ramus medianus (odds ratio 3.9), and age (odds ratio 1.069 per year) as the only independent predictors of postoperative atrial fibrillation. All patients were in sinus rhythm at hospital discharge. One hospital death was noted. Conclusions : Despite the less invasive approach, the incidence of postoperative atrial fibrillation is high after off-pump coronary artery bypass grafting. Older age, grafting of the ramus medianus, and a redo operation were predictors of new-onset postoperative atrial fibrillation. It is possible that left atrial stretching with heart dislocation during revascularization of the lateral wall could lead to postoperative atrial fibrillation.

Objective: Atrial fibrillation is a common complication after cardiac surgery. Magnesium is an effective and safe antiarrhythmic agent for arrhythmias that develop after cardiac surgery. The authors performed a study to evaluate the role of perioperative magnesium for prophylaxis of atrial fibrillation after off-pump coronary artery surgery. Design: Randomized controlled study. Setting: University teaching hospital. Participants: One hundred sixty consecutive patients undergoing elective, isolated, off-pump coronary artery bypass grafting were prospectively randomized into 2 groups. Interventions: Patients in the magnesium group (n=80) received a 2.5-g (20 mEq) magnesium sulphate infusion intraoperatively over 30 minutes, and the placebo group (n=80) received normal saline solution. Measurements and main results: Postoperative atrial fibrillation occurred in 16 of 80 patients (20%) in the magnesium group and in 18 of 80 (22.5%) in the placebo group (p=0.9). Conclusion: The use of 2.5 g of intraoperative magnesium showed no effect in preventing atrial fibrillation after off-pump coronary artery bypass. (C) 2005 Elsevier Inc. All rights reserved. OBJECTIVE: Atrial fibrillation is a common complication after cardiac surgery. Magnesium is an effective and safe antiarrhythmic agent for arrhythmias that develop after cardiac surgery. The authors performed a study to evaluate the role of perioperative magnesium for prophylaxis of atrial fibrillation after off-pump coronary artery surgery.DESIGN: Randomized controlled study.SETTING: University teaching hospital.PARTICIPANTS: One hundred sixty consecutive patients undergoing elective, isolated, off-pump coronary artery bypass grafting were prospectively randomized into 2 groups.INTERVENTIONS: Patients in the magnesium group (n = 80) received a 2.5-g (20 mEq) magnesium sulphate infusion intraoperatively over 30 minutes, and the placebo group (n = 80) received normal saline solution.MEASUREMENTS AND MAIN RESULTS: Postoperative atrial fibrillation occurred in 16 of 80 patients (20%) in the magnesium group and in 18 of 80 (22.5%) in the placebo group (p = 0.9).CONCLUSION: The use of 2.5 g of intraoperative magnesium showed no effect in preventing atrial fibrillation after off-pump coronary artery bypass.

Background— Acute renal failure is a serious complication of cardiac surgery causing high morbidity and mortality. The aim of this study was to evaluate the usefulness of fenoldopam, a specific agonist of the dopamine-1 receptor, in patients at high risk of perioperative renal dysfunction. Methods and Results— A prospective single-center, randomized, double-blind trial was performed after local ethical committee approval and after written consent was obtained from 80 patients undergoing cardiac surgery. Patients received either fenoldopam at 0.05 μg/kg per minute or dopamine at 2.5 μg/kg per minute after the induction of anesthesia for a 24-hour period. All these patients were at high risk of perioperative renal dysfunction as indicated by Continuous Improvement in Cardiac Surgery Program score >10. Primary end point was defined as 25% creatinine increase from baseline levels after cardiac surgery. The 2 groups (fenoldopam versus dopamine) were homogeneous cohorts, and no difference in outcome was observed. Acute renal failure was similar: 17 of 40 (42.5%) in the fenoldopam group and 16 of 40 (40%) in the dopamine group ( P =0.9). Peak postoperative serum creatinine level, intensive care unit and hospital stay, and mortality were also similar in the 2 groups. Conclusions— Despite an increasing number of reports of renal protective properties from fenoldopam, we observed no difference in the clinical outcome compared with dopamine in a high-risk population undergoing cardiac surgery.

Objective: To investigate the release of cardiac biomarkers (troponin 1 and CK-MB) in patients undergoing coronary artery bypass graft (CABG) with or without cardiopulmonary bypass (CPB). Design: Prospective study. Setting: University tertiary hospital. Participants: Sixty-five consecutive patients undergoing coronary artery bypass grafting (greater than or equal to2 vessel disease, ejection fraction greater than or equal to0.35%, elective procedure). Interventions: Cardiac biomarkers were measured before surgery, at intensive care unit arrival, 4 and 18 hours after the end of the procedure. Measurements and Main Results: Cardiac biomarker release was higher in on-pump than in off-pump patients at every time point. On multivariate analysis, CPB (p < 0.0001), number of distal grafts (p = 0.005), and hypertension treatment (p = 0.03) were the only independent predictors of peak cardiac troponin release. Conclusions: Cardiac troponin 1 release after multivessel CABG is associated with the technique. Different values for the normal range should be considered. OPCABG is minimally invasive for the heart as far as myocardial marker release is concerned. (C) 2004 Elsevier Inc. All rights reserved.

Objective: The purpose of this study was to determine whether coronary artery bypass grafting (CABG) surgery on the beating heart (BH) is associated with reduction of R-wave potentials on the precordial leads on the surface electrocardiogram (ECG) as previously shown for CABG with cardiopulmonary bypass. Methods: Fifty-four patients undergoing CABG surgery at a single tertiary care university hospital were analyzed. Patients suffering a postoperative cardiac event (myocardial infarction) or nonspecific ECG changes were excluded. ECG results were recorded at arrival in the intensive care unit, after 4 and 18 hours postoperatively; simultaneously, myocardial cell damage biomarkers (CK-MB and cTnl) were assayed. A control group of 31 patients undergoing mitral valve repair was also evaluated. Results: Patients operated with the BH (OPCABG) technique did not show any decrease of R-wave amplitude at 0, 4, and 18 hours postoperatively; whereas those operated with CPB, both for coronary artery surgery and for mitral repair, had a similar extent and pattern of R-wave reduction. The release of myocardial necrosis markers was significantly lower in coronary artery patients operated with BH than in those operated with CPB; however, no statistically significant correlation between the ECG changes and release of myocardial cell damage markers was observed in any of the groups. Conclusions: The findings indicate, for the first time, that CABG surgery on the BH is not followed by any reduction of R-wave amplitude on precordial leads and confirms that the BH technique is associated with a lower release of myocardial cell damage markers. (C) 2004 Elsevier Inc. All rights reserved.

SummaryThe urokinase-type plasminogen activator receptor (uPAR) is involved in cell migration and tissue remodelling, as a receptor for pro-uPA, as a cell adhesion component, and in a soluble form as a chemoattractant. We have analyzed the presence and the molecular forms of uPAR and uPAR-fragments in urine of ovarian cancer patients in comparison with tumour tissue, ascites, and serum. Carcinoma tissue contained high levels of uPAR, but more abundantly the D2D3-fragment. Ascitic fluid contained similar ratio’s of suPAR fragments as corresponding tumour tissue, but serum only contained intact suPAR. Interestingly, urine contained predominantly the uPAR-fragments D1 and D2D3, and the pattern of these fragments was different in cancer patients as compared to healthy individuals. To confirm the hypothesis that circulating and urinary suPAR and suPAR-fragments originate from the tumour tissue, the presence of human suPAR (fragments) was analyzed in mice xenografted with human tumours. Indeed, high levels of urinary D1 fragment were found in mice carrying a tumour displaying cleaved uPAR on the cell surface, but little or no D1 was found in the urine from mice carrying a tumour with full-length uPAR. Mouse serum contained only intact suPAR. Our data demonstrate that the enhanced levels of suPAR fragments in the urine of cancer patients is likely to originate from uPAR expressed in the tumour tissue. Considering the biological activities that uPAR fragments display, the level and typing of uPAR fragments in urine might therefore be clinically more relevant than the plain serum uPAR content.

Objective: The appearance of new Q waves on the electrocardiogram (ECG) after cardiac surgery has been traditionally considered a sign of major myocardial tissue damage. The aim of this study was to investigate the clinical significance of new Q waves appearing following cardiac surgery and to correlate them with the release of myocardial cell damage biomarkers. Methods: 206 consecutive patients undergoing cardiac surgery were prospectively evaluated. A 12 lead ECG was recorded and cardiac troponin I and creatinekinase subtraction MB assayed the day before surgery, on arrival at the intensive care Unit. 4 and 18 h postoperatively and every morning until the fifth postoperative day. Results: The incidence of new Q waves was 7.3%. Patients with isolated ECG findings had an uneventful postoperative course; on the contrary, when ECG changes were coupled with the release of myocardial necrosis biomarkers, patients had a complicated postoperative course. Conclusions: The association of a new Q wave and high levels of myocardial necrosis biomarkers is strongly associated with postoperative cardiac events. On the contrary, the isolated appearance of a new Q wave has no impact on the postoperative cardiac outcome. (C) 2004 Elsevier B.V. All rights reserved.

The purpose of this study was to investigate the presence of risk factors for node metastases and to estimate survival in patients with cervical cancer, stages IB and LIA. In a retrospective study of 103 patients with cervical cancer stages IB and IIA, all treated with radical hysterectomy and adjuvant radiotherapy, we estimated survival curves according to different prognostic parameters. Mean follow-up time was 97 months. A significant difference between clinical pre-operative assessment and histological determination of real extent of the disease was evidenced. Pelvic lymph node metastases (P = 0.0005) significantly correlated with survival. This study shows that only lymph node involvement is an independent prognostic factor. Stage acts through nodal status in its impact on survival. A surgical-pathological staging in early stage cervical cancers is found to be more appropriate to correctly estimate patients' survival and prognosis.

Aim. A high postoperative peak of cardiac Troponin I is associated to an increased risk of morbidity and mortality after cardiac operations. The aim of this study was to investigate the release of cardiac Troponin I in different cardiac surgical procedures. Methods. This was a prospective, single-centre study performed at the IRCCS San Raffaele Hospital in Milan, Italy. The study group consisted of 194 consecutive patients undergoing cardiac surgery. For each of them creatinkinase MB and cardiac Troponin I were assayed preoperatively, at ICU arrival, 4 h and 18 h postoperatively. Results. Different cardiac surgical procedures were characterized by different release of cardiac biomarkers (P < 0.001, ANOVA test). Off-pump coronary artery bypass grafting (CABG) was associated to the smallest amount of myocardial injury while mitral valve replacement produced the largest amount of biomarkers release. Patients who suffered a postoperative cardiac event released more myocardial necrosis biomarkers; than those with an uneventful course (P=0.01). Conclusion. We showed that each type of cardiac operation has a peculiar amount of myocardial necrosis biomarkers: mitral valve replacement in particular is associated to the highest release of cardiac biomarkers.

Obiettivo. La quantità degli interventi sulla popolazione ultraottantenne sta costantemente aumentando. Abbiamo riesaminato la nostra casistica per identificare quali variabili siano associate a una peggior prognosi in questa popolazione ad alto rischio.Metodi. Abbiamo raccolto in un data base le variabili perioperatorie e l’outcome a breve termine di 109 pazienti ottuagenari consecutivi. I dati sono stati analizzati con statistica descrittiva. Abbiamo applicato analisi uni- e multivariate per identificare i fattori di rischio perioperatorio per la ventilazione meccanica prolungata e la permanenza in Terapia Intensiva.Risultati. I 109 ultraottantenni rappresentano l’1,8% di 4 940 interventi chirurgici effettuati presso un ospedale universitario dal gennaio 1998 al giugno 2001: 94 pazienti (86%) presentavano copatologie; 46 (42%) sono stati sottoposti a chirurgia valvolare, 38 (36%) a rivascolarizzazione coronarica, e 25 pazienti (22%) a procedura combinata o riparazione di arco aortico. Per 2 pazienti (1,8%) vi fu il decesso. Le complicanze postoperatorie includevano: infarto (10 pazienti, 9%), ictus (6 pazienti, 5%), terapia sostitutiva renale (1 paziente, 1%); 69 (63%) pazienti hanno avuto un periodo perioperatorio libero da eventi. Un’analisi multivariata ha mostrato che la durata del bypass cardiopolmonare era associata al prolungamento del tempo di intubazione tracheale e del tempo di permanenza in Terapia Intensiva. La patologia mitralica era associata a intubazione prolungata e un precedente intervento cardiochirurgico era associato a una prolungata permanenza in Terapia Intensiva.Conclusioni. Abbiamo studiato 109 ottuagenari che hanno avuto un eccellente immediato outcome postoperatorio e, sulla base della nostra esperienza, possiamo concludere che la chirurgia cardiaca può essere effettuata con sicurezza nella popolazione ultraottantenne. AIM: The number of cardiac operations in octogenarians is steadily increasing. A review of personal 4 years' experience is made in order to identify which variables are associated to a poor prognosis in this high risk population.METHODS: Perioperative variables and short-term outcome of 109 consecutive octogenarians were prospectively collected in a database. Data were analysed with descriptive statistics. Univariate and multivariate analyses were performed to identify preoperative risk factors for prolonged mechanical ventilation and ICU stay.RESULTS: The 109 octogenarians represented 1.8% of the 4 940 cardiac operations performed at our University Teaching Hospital in the period January 1998-June 2001: 94 patients had comorbidities (86%); 46 underwent valve surgery (42%), 38 had coronary artery bypass grafting surgery (36%), and combined procedures or aortic arch replacement were performed in 25 patients (22%). Two patients died (1.8%). Postoperative complications included: myocardial infarction (10 patients, 9%), stroke (6 patients, 5%), renal replacement therapy (1 patient, 1%). Sixty nine patients (63%) had an uneventful perioperative period (63%). On a multivariate analysis, cardiopulmonary bypass (CPB) time was associated with prolonged intubation and ICU stay; mitral pathology predicted prolonged intubation while previous cardiac surgery was associated with prolonged ICU stay.CONCLUSION: The 109 octogenarians studied had an excellent course in the immediate postoperative period. Therefore, on the basis of personal experience cardiac surgery could be safely performed in octogenarians.