Recent clinical data show that the risk of coronary thrombosis after antiplatelet drugs withdrawal is much higher than that of surgical bleeding if they are continued. In secondary prevention, aspirin is a lifelong therapy and should never be stopped. Clopidogrel is regarded as mandatory until the coronary stents are fully endothelialized, which takes 3 months for bare metal stents, but up to 1 yr for drug-eluting stents. Therefore, interruption of antiplatelet therapy 10 days before surgery should be revised. After reviewing the data on the use of antiplatelet drugs in cardiology and in surgery, we propose an algorithm for the management of patients, based on the risk of myocardial ischaemia and death compared with that of bleeding, for different types of surgery. Even if large prospective studies with a high degree of evidence are still lacking on different antiplatelet regimens during non-cardiac surgery, we propose that, apart from low coronary risk situations, patients on antiplatelet drugs should continue their treatment throughout surgery, except when bleeding might occur in a closed space. A therapeutic bridge with shorter-acting antiplatelet drugs may be considered.

The increasing number of patients with coronary artery disease undergoing major non-cardiac surgery justifies guidelines concerning preoperative evaluation, stress testing, coronary angiography, and revascularization. A review of the recent literature shows that stress testing should be limited to patients with suspicion of a myocardium at risk of ischaemia, and coronary angiography to situations where revascularization can improve long-term survival. Recent data have shown that any event in the coronary circulation, be it new ischaemia, infarction, or revascularization, induces a high-risk period of 6 weeks, and an intermediate-risk period of 3 months. A 3-month minimum delay is therefore indicated before performing non-cardiac surgery after myocardial infarction or revascularization. However, this delay may be too long if an urgent surgical procedure is requested, as for instance with rapidly spreading tumours, impending aneurysm rupture, infections requiring drainage, or bone fractures. It is then appropriate to use perioperative beta-block, which reduces the cardiac complication rate in patients with, or at risk of, coronary artery disease. The objective of this review is to offer a comprehensive algorithm to help clinicians in the preoperative assessment of patients undergoing non-cardiac surgery.

In patients with severe mitral regurgitation due to mitral valve prolapse, 3D echo allowed a precise localization and an accurate quantification of the prolapsing portion of the leaflets. This technique can provide refinements in the surgical planning of mitral valve repair and in the selection of candidates for this intervention.

Purpose As no curative treatment for advanced pancreatic and biliary cancer with malignant ascites exists, new modalities possibly improving the response to available chemotherapies must be explored. This phase I study assesses the feasibility, tolerability and pharmacokinetics of a regional treatment of gemcitabine administered in escalating doses by the stop-Xow approach to patients with advanced abdominal malignancies (adenocarcinoma of the pancreas, n = 8, and cholangiocarcinoma of the liver, n = 1). Experimental design Gemcitabine at 500, 750 and 1,125 mg/m 2 was administered to three patients at each dose level by loco-regional chemotherapy, using hypoxic abdominal stop-Xow perfusion. This was achieved by an aorto-caval occlusion by balloon catheters connected to an extracorporeal circuit. Gemcitabine and its main metabolite 2Ј,2Ј-diXuorodeoxyuridine (dFdU) concentrations were measured by high performance liquid chromatography with UV detection in the extracorporeal circuit during the 20 min of stop-Xow perfusion, and in peripheral plasma for 420 min. Blood gases were monitored during the stop-Xow perfusion and hypoxia was considered stringent if two of the following endpoints were met: pH · 7.2, pO 2 nadir ratio ·0.70 or pCO 2 peak ratio ¸1.35. The tolerability of this procedure was also assessed. Results Stringent hypoxia was achieved in four patients. Very high levels of gemcitabine were rapidly reached in the extracorporeal circuit during the 20 min of stop-Xow perfusion, with C max levels in the abdominal circuit of 246 ( §37%), 2,039 ( §77%) and 4,780 ( §7.3%) g/ml for the three dose levels 500, 750 and 1,125 mg/m 2 , respectively. These C max were between 13 ( §51%) and 290 ( §12%) times higher than those measured in the peripheral plasma. 123Similarly, the abdominal exposure to gemcitabine, calculated as AUC t0-20 , was between 5.5 ( §43%) and 200 ( §66%)-fold higher than the systemic exposure. Locoregional exposure to gemcitabine was statistically higher in presence of stringent hypoxia (P < 0.01 for C max and AUC t0-20 , both normalised to the gemcitabine dose). Toxicities were acceptable considering the complexity of the procedure and were mostly hepatic; it was not possible to diVerentiate the respective contributions of systemic and regional exposures. A signiWcant correlation (P < 0.05) was found between systemic C max of gemcitabine and the nadir of both leucocytes and neutrophils. Conclusions Regional exposure to gemcitabine-the current standard drug for advanced adenocarcinoma of the pancreas-can be markedly enhanced using an optimised hypoxic stop-Xow perfusion technique, with acceptable toxicities up to a dose of 1,125 mg/m 2 . However, the activity of gemcitabine under hypoxic conditions is not as Wrmly established as that of other drugs such as mitomycin C, melphalan or tirapazamine. Further studies of this investigational modality, but with bioreductive drugs, are therefore warranted Wrst to evaluate the tolerance in a phase I study and later on to assess whether it does impr...