Hyperthermic isolated liver perfusion with melphalan and bevacizumab.

Whereas surgical resection is the only curative treatment for liver tumors, effective treatment for isolated unresectable lesions when there is tumor progression in spite of several lines of chemotherapy remains to be found. We report herein two cases of patients treated by a 1-hour Hyperthermic Isolated Liver Perfusion (HILP) with a combination of melphalan and bevacizumab leading to complete response. The first patient had liver metastases secondary to previously resected malignant glucagonoma and the second, recurrent hepatocellular carcinoma. We used bevacizumab in association with melphalan for HILP because of the additional effect of an anti-VEGF antibody in these highly vascularized tumors and its locally restricted delivery to the isolated hepatic vascular compartment despite of its classic contraindication in association with surgery. The protocol was approved by the Ethics Committee. Enhanced CT scans during follow-up showed complete tumor necrosis as early as the second postoperative day. Patients had 27 and 7 months disease-free survival and 48 and 41 months overall survival after HILP, for neuroendocrine liver metastases and HILP plus liver transplantation for HCC respectively. Under very specific conditions, bevacizumab in HILP can provide excellent tumor response in hopeless clinical cases of liver tumors.

[Cardiac surgery without transfusion in 2005]. / Chirurgie cardiaque sans transfusion en 2005. A propos d'une série de 200 témoins de Jehovah opérés.

PURPOSE: Between January 1991 and October 2003, 200 Jehovah Witnesses adult patients underwent elective cardiac surgery. To asses the impact on continuing progress of blood saving protocols and the increasing operative risk of patients proposed to surgery, we have re-assessed our results in this specific population. METHODOLOGY: Files of the first 100 patients operated upon between 1991 and 1998 were reviewed, and compared to the following 100 ones treated between 1998 to today. All patients were scored using the Euroscore model. RESULTS: In the latest series, patients are older (68 vs 51) and 13% underwent an iterative procedure, although there was none in the first series. Three deaths occurred after one month at the beginning of our experience, only one in the latest series. Operative risk factors had distinctly deteriorated, with more redux, and ejection fraction lower than 35%. Major progress to maintain morbi-mortality stability were multifactorial: preoperative erythropoietin in order to reach an haemoglobin minimal value of 14 g/dL, Cornell University protocol, mini-ECC, warm blood cardioplegia, ultra-early extubation. CONCLUSION: Cardiac surgery without transfusion can be realised with an equivalent risk to that of classical surgery, despite an operative risk aggravation, due to the association of recent conservative techniques.

End-to-side anastomosis using a new sutureless vascular prosthesis.

Performing a conventional vascular anastomosis during minimally invasive surgery remains a technically difficult and time-consuming task. The purpose of our study was to assess the efficacy of a new sutureless vascular prosthesis. Through a left thoracotomy, a short segment of the descending aorta was bypassed in eight sheep. Our Dacron prosthesis had a cuff at one extremity. The cuff was introduced into the artery through an arteriotomy and attached to the arterial wall with clips. Surgery was performed on the sheep again 12-15 weeks later, and the prosthesis was retrieved for macroscopic and microscopic examination. At surgery, insertion of the prosthesis was easy, fast, and safe. A 3-4 mm space between each clip was required for proper attachment. At the second surgery, all prostheses were completely patent and there were no anastomotic stenoses or aneurysms. This new sutureless vascular prosthesis was easy and safe in its placement and might prove useful for video assisted vascular aortic surgery.

Endoscopic coronary artery bypass grafting with the aid of robotic assisted instruments.

OBJECTIVE: The development of endoscopic coronary artery bypass grafting has been limited because of poor visualization and increased technical difficulties in carrying out operations through ports. We investigated whether the use of robotic assisted instruments could minimize these difficulties. METHODS: After a period of technical development and training on cadavers (n = 8) with the Intuitive Surgical system (Intuitive Surgical, Inc, Mountain View, Calif), the first clinical application in coronary artery surgery was performed in 4 male patients (mean age 59 +/- 6 years) with the indication of grafting the left internal thoracic artery to the left anterior descending coronary artery. Robotic assisted 3-dimensional endoscopes and instruments were introduced into the left side of the chest through 3 intercostal ports. The Heartport system (Heartport, Inc, Redwood City, Calif) was used for arresting the heart during the anastomosis. RESULTS: In 2 patients, the harvesting of the left internal thoracic artery was completed endoscopically with robotic assisted instruments and the anastomosis to the left anterior descending artery was performed through a minithoracotomy with conventional instruments. In 2 other patients, the entire operation was completed endoscopically with robotic assisted instruments. Early postoperative coronary angiography demonstrated the patency of the grafts in all cases. At 6-month follow-up, all patients were free of symptoms. CONCLUSIONS: Robotic assisted instruments make endoscopic coronary bypass possible and open a new era in minimally invasive surgery.

Plasma from patients exposed to ischemia reperfusion contains clastogenic factors and stimulates the chemiluminescence response of normal leukocytes.

Clastogenic factors (CFs) are released by cells exposed to superoxide radicals and are found in various situations of oxidative stress. Certain of their components stimulate further superoxide production by competent cells, as shown with cytochrome c assay in previous work. In the present study, we report CF formation after ischemia reperfusion in patients undergoing coronary bypass surgery. Plasma ultrafiltrates, collected 20 min after reperfusion, had clastogenic properties in contrast to those collected before ischemia. We also show that the luminol-enhanced chemiluminescence response of neutrophils from healthy persons is increased when these cells are exposed to CF-containing postreperfusion samples from patients. Light emission was reduced to control values in the presence of superoxide dismutase. The burst of oxyradicals upon reperfusion is probably the initiating event of CF formation, which in turn leads to further oxyradical generation. This amplification process may explain why detectable levels of CF need a delay of at least 10 min. The activated state of neutrophils in ischemia reperfusion is at once a consequence and a source of CFs. Individual variation in the persistence of this clastogenic and leukocyte-activating material was observed. Therefore, antioxidants for prevention of ischemia reperfusion injury should be continued during the postoperative course.

[Assessment of effectiveness of a reperfusion solution in heart surgery]. / Evaluation de l'efficacité d'une solution de reperfusion en chirurgie cardiaque.

Technics of myocardial protection used in cardiac surgery have been dramatically improved with the use of cardioplegic solutions. These solutions (particularly blood cardioplegic solutions) are routinely administered during open heart surgery. When unclamping the aorta, reperfusion of the ischemic heart with oxygenated blood induces reperfusion injury. Consequently, solutions capable of reducing cellular damage due to reperfusion have been designed. The effectiveness of a reperfusion solution was assessed by a randomized double-blind study including 14 patients with coronary disease. Five biochemical and physiological parameters were measured: coronary resistance, oxygen uptake, total adenine nucleotides, malonaldehyde and lactate. The solution attenuated the reperfusion phenomenon: coronary resistance remained stable, oxygen uptake was increased at the beginning of reperfusion, the pool of nucleotides was preserved and lactate production was reduced. A new study on a larger number of patients is mandatory to establish the place of this reperfusion solution in myocardial protection, particularly in the case of prolonged ischemic time.

Cardioprotective effect of trimetazidine during coronary artery graft surgery.

Reperfusion injury remains the most uncontrolled phenomenon during cardiac surgery. Potential myocardial protection by trimetazidine was tested in a double blind placebo controlled study on 19 patients undergoing aorto-coronary bypass surgery. The trimetazidine group was composed of 10 patients and the placebo group of 9 patients. Pretreatment was started three weeks before surgery with 1 tablet (trimetazidine 20 mg) t.i.d. and the same drug was added to the cardioplegic solutions (trimetazidine: 10(-6) M). The cross clamping time was 41.1 +/- 3.8 minutes in the trimetazidine group and 39.8 +/- 2.3 minutes in the placebo group. Metabolic measurements showed that the increase of malondialdehyde measured in the coronary sinus 20 minutes after reperfusion was significantly (p = 0.014) less in the trimetazidine group (from 1.60 +/- 0.11 to 1.79 +/- 0.2 mumol/L-1) than in the placebo group (from 1.17 +/- 0.11 to 2.84 +/- 0.58 mumol/L-1). Myosin was present 4 hours after surgery in all patients in the placebo group and in 5 of the 10 of the trimetazidine group (p = 0.036). Haemodynamic measurements showed that patients pretreated with trimetazidine had a better ventricular function, as assessed by the stroke work index (SWI) significantly (p = 0.01) higher in the trimetazidine group (0.0391 +/- 0.0029 g/min/m2/beta) than in the placebo group (0.0282 +/- 0.0026 g/min/m2/beat), the evolution of SWI during surgery was not significantly different between the two groups. Thus trimetazidine seems to reduce ischaemia-reperfusion damage during cardiac surgery; moreover pretreatment with trimetazidine allows the patient to face the operation with better ventricular function.

Atrial cardiomyoplasty after Fontan-type procedures.

The purpose of right atrial cardiomyoplasty is to increase atrial-pulmonary flow in patients undergoing Fontan-type procedures. We developed two surgical techniques to bypass the right ventricle, followed by right atrial cardiomyoplasty with a stimulated latissimus dorsi muscle flap (LDMF). In 10 goats, the left LDMF was transferred into the chest by removal of the second rib. After sternotomy, the right atrial appendages of five goats (group 1) were connected to the distal main pulmonary artery with polytetrafluoroethylene tubing and the proximal pulmonary trunks were ligated. In the other five goats (group 2), under cardiopulmonary bypass, bioprosthetic valves were implanted into the inferior venae cavae. The tricuspid orifice was closed, and the atriopulmonary connection was performed. The left LDMF was sutured over the right atrium and stimulated using synchronous 30-Hz bursts of impulses delivered by a Medtronic Cardiomyostimulator. Hemodynamic studies were performed in the acute phase. Right atrial, pulmonary arterial, and aortic pressures were assessed. Cardiac output was measured using ultrasonic flow studies. LDMF stimulation restored pulsatile pressure patterns in the pulmonary artery and increased the cardiac output. These observations were more evident in the model with caval valvular implant. This functional "ventricularization" of the right atrium could improve long-term results after Fontan-type procedures and extend operative indications. Chronic experimental studies are necessary to evaluate the diastolic and systolic functions of the neo-right ventricle.

Induction of interleukin-1 production in patients undergoing cardiopulmonary bypass.

Systemic reactions resembling inflammation occur in patients undergoing cardiopulmonary bypass. We now report that interleukin-1, an endogenous pyrogen and a key mediator of inflammation, is transiently and consistently generated in vivo by circulating monocytes within hours after cardiopulmonary bypass. Interleukin-1 production was assessed by measuring interleukin-1 functional activity and interleukin-1 beta antigen concentration in cell lysates from monocytes of patients during and after bypass. There was no increase in intracellular interleukin-1 activity during bypass and within the first hours after bypass, possibly because of a suppressive effect of hypothermia on interleukin-1 production, as documented in vitro. Maximal generation of interleukin-1 was observed 24 hours after extracorporeal circulation, concomitantly with the occurrence of a peak in body temperature. The amount of interleukin-1 generated at that time was linearly correlated with the increase in patients' body temperature. The peak in interleukin-1 production followed by 20 hours the peak in complement activation as assessed by determining C3a desArg and C5a desArg concentrations in patients' plasma. These results indicate that interleukin-1 may be involved in the pathogenesis of adverse systemic reactions associated with cardiopulmonary bypass.

Clastogenic factor in ischemia-reperfusion injury during open-heart surgery: protective effect of allopurinol.

The hypothesis tested was that free radicals generated following ischemia and reperfusion in cardiac operations can produce clastogenic factor that results in chromosomal aberration. Fourteen randomized patients undergoing coronary artery bypass grafting were divided into two groups. In Group 1 (7 patients), myocardial protection was achieved using a cardioplegic solution without allopurinol. In Group 2 (7 patients), 100 mg of allopurinol (xanthine oxidase inhibitor) was added to the solution. In both groups, blood samples were taken from the coronary sinus before the aorta was clamped and 20 minutes after myocardial reperfusion was achieved. The blood samples were used to study the patients' chromosomes. The results were given as the percentage of chromosomal aberrations observed in 100 mitoses. There were no significant differences between the preischemic values in both groups and the postischemic values in Group 2. On the other hand, there was a significant difference between the postischemic values in Groups 1 and 2 (p less than 0.01). In conclusion, reperfusion following myocardial ischemia in cardiac operations can produce clastogenic aberrations. This clastogenic activity can be reduced by adding allopurinol to the cardioplegic solution.