Search

Circulating tumor cells (CTCs) in the blood of cancer patients have been demonstrated to be of prognostic value regarding metastasis and survival. The CellSearch(®) system has been certified for the detection of CTCs and as a prognostic tool in patients with metastatic breast, colon and prostate cancer. Few studies have evaluated the detection of CTCs originating from esophagogastric or pancreatic cancer with the CellSearch(®) system. In the present small pilot study, a total of 16 patients with either esophagogastric (n=8) or pancreatic (n=8) adenocarcinomas at various disease stages were randomly screened and included. A total of 7.5 ml of blood was drawn from each patient and analyzed for CTCs using the CellSearch(®) device. CTCs could be detected in 1 out of 8 patients (12.5%) with esophagogastric and in 7 out of 8 patients (87.5%) with pancreatic cancer. The preliminary data obtained from this observational feasibility study suggested that the CellSearch(®) system may become a valuable tool for the detection of CTCs in patients with pancreatic adenocarcinoma, whereas the usefulness in patients with early-stage esophagogastric adenocarcinoma may be limited. This study clearly points towards a requirement for larger studies focusing on patients with pancreatic adenocarcinoma at various disease stages and assessing CTCs, whereas patients with esophagogastric adenocarcinomas should be part of further pilot studies.

RATIONALE Perioperative myocardial ischemia is common in high-risk patients. The use of interventional revascularisation or even thrombolysis is limited in this patient subset due to exceedingly high bleeding risks. Blockade of voltage-gated sodium channels (VGSC) with lidocaine had been suggested to reduce infarct size and cardiomyocyte cell death in ischemia/reperfusion models. However, the impact of lidocaine on cardiac function during sustained ischemia still remains unclear. METHODS Sustained myocardial ischemia was induced by ligation of the left anterior descending artery in 12-16 weeks old male BALB/c mice. Subcutaneous lidocaine (30 mg/kg) was used to block VGSC. Cardiac function was quantified at baseline and at 72h by conventional and speckle-tracking based echocardiography to allow high-sensitivity in vivo phenotyping. Infarct size and cardiomyocyte cell death were assessed post mortem histologically and indirectly using troponin measurements. RESULTS Ischemia strongly impaired both, global systolic and diastolic function, which were partially rescued in lidocaine treated in mice. No differences regarding infarct size and cardiomyocyte cell death were observed. Mechanistically, and as shown with speckle-tracking analysis, lidocaine specifically improves residual contractility in the ischemic but not in the remote, non-ischemic myocardium. CONCLUSION VGSC blockade with lidocaine rescues function of ischemic myocardium as a potential bridging to revascularisation in the setting of perioperative myocardial ischemia.

BACKGROUND During times of organ scarcity and extended use of liver grafts, protective strategies in transplantation are gaining importance. We demonstrated in the past that volatile anesthetics such as sevoflurane attenuate ischemia-reperfusion injury during liver resection. In this randomized study, we examined if volatile anesthetics have an effect on acute graft injury and clinical outcomes after liver transplantation. METHODS Cadaveric liver transplant recipients were enrolled from January 2009 to September 2012 at 3 University Centers (Zurich/Sao Paulo/Ghent). Recipients were randomly assigned to propofol (control group) or sevoflurane anesthesia. Postoperative peak of aspartate transaminase was defined as primary endpoint, secondary endpoints were early allograft dysfunction, in-hospital complications, intensive care unit, and hospital stay. RESULTS Ninety-eight recipients were randomized to propofol (n = 48) or sevoflurane (n = 50). Median peak aspartate transaminase after transplantation was 925 (interquartile range, 512-3274) in the propofol and 1097 (interquartile range, 540-2633) in the sevoflurane group. In the propofol arm, 11 patients (23%) experienced early allograft dysfunction, 7 (14%) in the sevoflurane one (odds ratio, 0.64 (0.20 to 2.02, P = 0.45). There were 4 mortalities (8.3%) in the propofol and 2 (4.0%) in the sevoflurane group. Overall and major complication rates were not different. An effect on clinical outcomes was observed favoring the sevoflurane group (less severe complications), but without significance. CONCLUSIONS This first multicenter trial comparing propofol with sevoflurane anesthesia in liver transplantation shows no difference in biochemical markers of acute organ injury and clinical outcomes between the 2 regimens. Sevoflurane has no significant added beneficial effect on ischemia-reperfusion injury compared to propofol.

Recent studies report promising results regarding extracorporeal magnetic separation-based blood purification for the rapid and selective removal of disease-causing compounds from whole blood. High molecular weight compounds, bacteria and cells can be eliminated from blood within minutes, hence offering novel treatment strategies for the management of intoxications and blood stream infections. However, risks associated with incomplete particle separation and the biological consequences of particles entering circulation remain largely unclear. This article discusses the promising future of magnetic separation-based purification while keeping important safety considerations in mind.

BACKGROUND The body is dependent on the exogenous supply of omega-3 polyunsaturated fatty acids (n3-PUFA). These essential fatty acids are key players in regulating metabolic signaling but also exert anti-inflammatory and anti-carcinogenic properties. The liver is a major metabolic organ involved in fatty acid metabolism. Under experimental conditions, n3-PUFA exert beneficial effect on hepatic steatosis, regeneration and inflammatory insults such as ischemic injury after surgery. Some of these effects have also been observed in human subjects. However, it is unclear whether perioperative administration of n3-PUFA is sufficient to protect the liver from ischemic injury. Therefore, we designed a randomized controlled trial (RCT) assessing n3-PUFA (pre-) conditioning strategies in patients scheduled for liver surgery. METHODS/DESIGN The Omegaven trial is a multi-centric, double-blind, randomized, placebo- controlled trial applying two single doses of Omegaven or placebo on 258 patients undergoing major liver resection. Primary endpoints are morbidity and mortality one month after hospital discharge, defined by the Clavien- Dindo classification of surgical complications (Ann Surg 240(2):205-13, 2004) as well as the Comprehensive Complication Index (CCI) (Ann Surg 258(1):1-7, 2013). Secondary outcome variables include length of Intensive Care Unit (ICU) and hospital stay, postoperative liver function tests, fatty acid and eicosanoid concentration, inflammatory markers in serum and in liver tissue. An interim analysis is scheduled after the first 30 patients per randomization group. DISCUSSION Long-term administration of n3-PUFA have a beneficial effect on metabolism and hepatic injury. Patients often require surgery without much delay, thus long-term n3-PUFA uptake is not possible. Also, lack of compliance may lead to incomplete n3-PUFA substitution. Hence, perioperative Omegaven™ may provide an easy and controllable way to ensure hepaative application of tic protection

INTRODUCTION In a recent randomized controlled trial our group has demonstrated in 102 patients that late post-conditioning with sevoflurane performed in the intensive care unit after surgery involving extracorporeal circulation reduced damage to cardiomyocytes exposed to ischemia reperfusion injury. On the first post-operative day the sevoflurane patients presented with lower troponin T values when compared with those undergoing propofol sedation. In order to assess possible clinical relevant long-term implications in patients enrolled in this study, we performed the current retrospective analysis focusing on cardiac and non-cardiac events during the first 6 months after surgery. METHODS All patients who had successfully completed the late post-conditioning trial were included into this follow-up. Our primary and secondary endpoints were the proportion of patients experiencing cardiac and non-cardiac events, respectively. Additionally, we were interested in assessing therapeutic interventions such as initiation or change of drug therapy, interventional treatment or surgery. RESULTS Of 102 patients analyzed in the primary study 94 could be included in this follow-up. In the sevoflurane group (with 41 patients) 16 (39%) experienced one or several cardiac events within 6 months after cardiac surgery, in the propofol group (with 53 patients) 19 (36%, p=0.75). Four patients (9%) with sevoflurane vs. 7 (13%) with propofol sedation had non-cardiac events (p=0.61). While a similar percentage of patients suffered from cardiac and/or non-cardiac events, only 12 patients in the sevoflurane group compared to 20 propofol patients needed a therapeutic intervention (OR: 0.24, 95% CI: 0.04-1.43, p=0.12). A similar result was found for hospital admissions: 2 patients in the sevoflurane group had to be re-admitted to the hospital compared to 8 in the propofol group (OR 0.23, 95% CI: 0.04-1.29, p=0.10). CONCLUSIONS Sevoflurane does not seem to provide protection with regard to the oc

BACKGROUND: Acute lung injury (ALI) is associated with high mortality due to the lack of effective therapeutic strategies. Mechanical ventilation itself can cause ventilator-induced lung injury. Pulmonary vascular barrier function, regulated in part by Src kinase-dependent phosphorylation of caveolin-1 and intercellular adhesion molecule-1 (ICAM-1), plays a crucial role in the development of protein-/neutrophil-rich pulmonary edema, the hallmark of ALI. Amide-linked local anesthetics, such as ropivacaine, have anti-inflammatory properties in experimental ALI. We hypothesized ropivacaine may attenuate inflammation in a "double-hit" model of ALI triggered by bacterial endotoxin plus hyperinflation via inhibition of Src-dependent signaling. METHODS: C57BL/6 (WT) and ICAM-1 (-/-) mice were exposed to either nebulized normal saline (NS) or lipopolysaccharide (LPS, 10 mg) for 1 hour. An intravenous bolus of 0.33 mg/kg ropivacaine or vehicle was followed by mechanical ventilation with normal (7 ml/kg, NTV) or high tidal volume (28 ml/kg, HTV) for 2 hours. Measures of ALI (excess lung water (ELW), extravascular plasma equivalents, permeability index, myeloperoxidase activity) were assessed and lungs were homogenized for Western blot analysis of phosphorylated and total Src, ICAM-1 and caveolin-1. Additional experiments evaluated effects of ropivacaine on LPS-induced phosphorylation/expression of Src, ICAM-1 and caveolin-1 in human lung microvascular endothelial cells (HLMVEC). RESULTS: WT mice treated with LPS alone showed a 49% increase in ELW compared to control animals (p = 0.001), which was attenuated by ropivacaine (p = 0.001). HTV ventilation alone increased measures of ALI even more than LPS, an effect which was not altered by ropivacaine. LPS plus hyperinflation ("double-hit") increased all ALI parameters (ELW, EVPE, permeability index, MPO activity) by 3-4 fold compared to control, which were again decreased by ropivacaine. Western blot analyses of lung homogenates

Background: A reduced oxygen supply puts patients at risk of tissue hypoxia, organ damage, and even death. In response, several changes are activated that allow for at least partial adaptation, thereby increasing the chances of survival. We aimed to investigate whether the arginine vasopressin marker, copeptin, can be used as a marker of the degree of acclimatization/adaptation in rats exposed to hypoxia. Methods: Sprague-Dawley rats were exposed to 10% oxygen for up to 48 hours. Arterial and right ventricular pressures were measured, and blood gas analysis was performed at set time points. Pulmonary changes were investigated by bronchoalveolar lavage, wet and dry weight measurements, and lung histology. Using a newly developed specific rat copeptin luminescence immunoassay, the regulation of vasopressin in response to hypoxia was studied, as was atrial natriuretic peptide (ANP) by detecting mid-regional proANP. Results: With a decreasing oxygen supply, the rats rapidly became cyanotic and inactive. Despite continued exposure to 10% oxygen, all animals recuperated within 16 hours and ultimately survived. Their systemic blood pressure fell with acute (5 minutes) hypoxia but was partially recovered over time. In contrast, right ventricular pressures increased with acute (5 minutes) hypoxia and normalized after 16 hours. No signs of pulmonary inflammation or edema were found despite prolonged hypoxia. Whereas copeptin levels increased significantly after acute (5 minutes) hypoxia and then returned to near baseline after 16 hours, mid-regional proANP levels were even further increased after 16 hours of exposure to hypoxia. Conclusion: Plasma copeptin is a sensitive marker of acute (5 minutes) exposure to severe hypoxia, and subsequent regulation can indicate recovery. Copeptin levels can therefore reflect clinical and physiological changes in response to hypoxia and indicate recovery from ongoing hypoxic exposure.

QUESTIONS UNDER STUDY: The aim of this study was to evaluate two practices of airway management in patients undergoing head and neck cancer (HNC) resection and microvascular free tissue transfer (MFTT), and to assess the advantages and disadvantages of the two approaches. METHODS: Patients undergoing a delayed extubation approach (NO-TRACH group) and patients undergoing primary tracheotomy (PRIM-TRACH group) were retrospectively evaluated in terms of perioperative and postoperative outcome measures. RESULTS: Not performing routine tracheotomy was safe and no perioperative airway complications occurred. NO-TRACH patients were extubated after 1.1 ± 0.9 days (mean ± standard deviation) and secondary tracheotomy was necessary in three patients (13%). NO-TRACH patients revealed decreased duration of surgery (p <0.05) and showed trends to earlier resumption of oral feeding and decreased length of hospitalisation. Flap complication rates were similar in both groups, with an overall flap survival rate of 97.5% (n = 39/40). CONCLUSIONS: With appropriate postoperative care, carefully selected patients undergoing major HNC resections with MFTT can be safely managed without routine tracheotomy.

BACKGROUND Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a treatment option for selected patients with peritoneal carcinomatosis. There are limited data available on anaesthesia management and its impact on patients' outcome. Our aim was to retrospectively analyze and evaluate perioperative management and the clinical course of patients undergoing CRS/HIPEC within a three-year period. METHODS After ethic committee approval, patient charts were retrospectively reviewed for patient characteristics, interventions, perioperative management, postoperative course, and complications. Analysis was intervention based. Data are presented as median (range). RESULTS Between 2009 and 2011, 54 consecutive patients underwent 57 interventions; median anaesthesia time was 715 (range 370 to 1135) minutes. HIPEC induced hyperthermia with an overall median peak temperature of 38.1 (35.7-40.2)°C with active cooling. Bleeding, expressed as median blood loss was 0.8 (0 to 6) litre and large fluid shifts occurred, requiring a total fluid input of 8.4 (4.2 to 29.4) litres per patient. Postoperative renal function was dependent on preoperative function and the type of fluids used. Administration of hydroxyethyl starch colloid solution had a significant negative impact on renal function, especially in younger patients. Major complications occurred after 12 procedures leading to death in 2 patients. Procedure time and need for blood transfusion were associated with a significantly higher risk for major complications. CONCLUSIONS Cytoreductive surgery with HIPEC is a high-risk surgical procedure associated with major hemodynamic and metabolic changes. As well as primary disease and complexity of surgery, we have shown that anaesthesia management, the type and amount of fluids used, and blood transfusions may also have a significant effect on patients' outcome.

PURPOSE OF REVIEW Organ protection remains a primary objective in the anesthetic management of patients undergoing transplantation. An ongoing effort has been made to develop strategies to improve graft outcome and reduce postoperative morbidity and mortality, but trials have reported conflicting results. The aim of this review was to provide a comprehensive summary of the anesthetic management in transplant recipients and to identify current strategies for organ protection. RECENT FINDINGS Decreasing blood products requirements, intraoperative blood glucose control and adequate postoperative pain therapy may improve patient outcome. Vasopressors have been reported to reduce perioperative bleeding but might be associated with postoperative acute renal failure in liver transplantation. Early extubation may increase survival rates in recipients. These perioperative challenges, along with other protective strategies, have been addressed in 20 recently published studies: 10 randomized controlled trials, nine retrospective studies and one prospective study. SUMMARY This review identified several promising strategies ensuring organ protection and improving patient outcome after solid organ transplantation. However, as outcomes were difficult to compare, further evidence will be needed before drawing firm conclusions.

BACKGROUND Robotic-assisted laparoscopic prostatectomy (RALP) gained much popularity during the last decade. Although the influence of intraoperative fluid management on patients' outcome has been largely discussed in general, its impact on perioperative complications and length of hospitalization in patients undergoing RALP has not been examined so far. We hypothesized that a more restrictive fluid management might lead to a shortened length of hospitalization and a decreased rate of complications in our patients. METHODS Retrospective analysis of data of 182 patients undergoing RALP at an University Hospital (first series of RALP performed at the center). RESULTS The amount of fluid administered was initially normalized for body mass index of the patient and the duration of the operation and additionally corrected for age and the interaction of these variables. The application of crystalloids (multiple linear regression model, estimate = -0.044, p = 0.734) had no effect on the length of hospitalization, whereas a negative effect was found for colloids (estimate = -8.317, p = 0.021). Additionally, a significant interaction term between age and the amount of colloid applied (estimate = 0.129, p = 0.028) was calculated. Evaluation of the influence of intraoperative fluid administration using multiple logistic regression models corrected for body mass index, duration of the surgery and additionally for age revealed a negative effect of crystalloids on the incidence of an anastomotic leak between bladder and urethra (estimate = -23.860, p = 0.017), with a significant interaction term between age and the amount of crystalloids (estimate = 0.396, p = 0.0134). Colloids had no significant effect on this particular complication (estimate = 1.887, p = 0.524). Intraoperative blood loss did not alter the incidence of an anastomotic leak (estimate = 0.001, p = 0.086), nor did it affect the length of hospitalization (estimate = 0.0001, p = 0.351). CONCLUSIONS In accordance to th

Volatile anesthetics are known to have immunomodulatory effects in conditions of organ injury. A recent study in an experimental sepsis model has shown remarkably improved survival when mice were exposed to volatile anesthetics. In the present study, we show that hexafluoroisopropanol - a water-soluble primary sevoflurane metabolite - has beneficial effects on the overall survival in a murine model of cecal ligation and puncture. Seven-day survival as well as tissue damage markers including transaminases and high mobility group box protein-1 were assessed as measures of end organ damage. In animals undergoing cecal ligation and puncture procedure hexafluoroisopropanol conditioning - but not late postconditioning 24 hours after sepsis induction - significantly increased survival rate (17% vs. 77%, p = 0.037) and attenuated secretion of organ damage markers. This study shows survival benefits by administration of the metabolite of a volatile anesthetic. If successfully translated, hexafluoroisopropanol might offer interesting therapeutic opportunities in the future treatment of abdominal sepsis.

BACKGROUND: Sepsis remains a leading cause of death in intensive care units. There is growing evidence that volatile anesthetics have beneficial immunomodulatory effects on complex inflammation-mediated conditions. The authors investigated the effect of volatile anesthetics on the overall survival of mice in a sepsis model of cecal ligation and puncture (CLP). METHODS: Mice (N = 12 per treatment group) were exposed to anesthetic concentrations of desflurane, isoflurane, and sevoflurane either during induction of sepsis or when the mice showed pronounced symptoms of inflammation. Overall survival, as well as organ function and inflammation was compared with the CLP group without intervention. RESULTS: With desflurane and sevoflurane conditioning (1.2 minimal alveolar concentration for 2 h immediately after induction of CLP) overall survival was improved to 58% and 83%, respectively, compared with 17% in the untreated CLP group. Isoflurane did not significantly affect outcome. Application of sevoflurane 24 h after sepsis induction significantly improved overall survival to 66%. CONCLUSIONS: Administration of the volatile anesthetics desflurane and sevoflurane reduced CLP-induced mortality. Anesthesia may be a critical confounder when comparing study data where different anesthesia protocols were used.