Techniques for liver parenchymal transection: a meta-analysis of randomized controlled trials

Background:

Different techniques of liver parenchymal transection have been described, including the finger fracture, sharp dissection, clamp–crush methods and, more recently, the Cavitron ultrasonic surgical aspirator (CUSA), the hydrojet and the radiofrequency dissection sealer (RFDS). This review assesses the benefits and risks associated with the various techniques.

Methods:

Randomized clinical trials were identified from the Cochrane Library Trials Register, MEDLINE, EMBASE, Science Citation Index Expanded and reference lists. Odds ratio (ORs), mean difference (MDs) and standardized mean differences (SMDs) were calculated with 95% confidence intervals based on intention-to-treat analysis or available-case analysis.

Results:

We identified seven trials including a total of 556 patients. Blood transfusion requirements were lower with the clamp–crush technique than with the CUSA or hydrojet. The clamp–crush technique was quicker than the CUSA, hydrojet or RFDS. Infective complications and transection blood loss were greater with the RFDS than with the clamp–crush method. There was no significant difference between techniques in mortality, morbidity, liver dysfunction or intensive therapy unit and hospital stay.

Conclusions:

The clamp–crush technique is more rapid and is associated with lower rates of blood loss and otherwise similar outcomes when compared with other methods of parenchymal transection. It represents the reference standard against which new methods may be compared.     

Current protective strategies in liver surgery

During liver resection surgery for cancer or liver transplantation,the liver is subject to ischaemia (reduction in blood flow) followed by reperfusion (restoration of blood flow),which results in liver injury [ischemiareperfusion (IR) or IR injury]. Modulation of IR injury can be achieved in various ways. These include hypothermia,ischaemic preconditioning (IPC) (brief cycles of ischaemia followed by reperfusion of the organ before the prolonged period of ischaemia i.e. a conditioning response),ischaemic postconditioning (conditioning after the prolonged period of ischaemia but before the reperfusion),pharmacological agents to decrease IR injury,genetic modulation of IR injury,and machine perfusion (pulsatile perfusion). Hypothermia decreases the metabolic functions and the oxygen consumption of organs. Static cold storage in University of Wisconsin solution reduces IR injury and has prolonged organ storage and improved the function of transplanted grafts. There is currently no evidence for any clinical advantage in the use of alternate solutions for static cold storage. Although experimental data from animal models suggest that IPC,ischaemic postconditioning,various pharma-cological agents,gene therapy,and machine perfusion decrease IR injury,none of these interventions can be recommended in clinical practice. This is because of the lack of randomized controlled trials assessing the safety and efficacy of ischaemic postconditioning,gene therapy,and machine perfusion. Randomized controlled trials and systematic reviews of randomized controlled trials assessing the safety and efficacy of IPC and various pharmacological agents have demonstrated biochemical or histological improvements but this has not translated to clinical benefit. Further well designed randomized controlled trials are necessary to assess the various new protective strategies in liver resection.     

Ischemic preconditioning triggers nuclear translocation of thioredoxin and its interaction with Ref-1 potentiating a survival signal through the PI-3-kinase-Akt pathway

Thioredoxin (Trx-1), a key mediator of cellular redox homeostasis and cell survival, is implicated in redox signaling in the ischemic myocardium. To investigate further its mechanism of action, Trx expression in rat heart was suppressed by direct injection of small hairpin RNA against Trx-1 (shRNA-Trx-1). Forty-eight hours after treatment, hearts were excised for isolated working-heart preparation. A group of hearts was preconditioned (PC) by subjecting them to four cyclic episodes of 5-min ischemia, each followed by 10 min of reperfusion. All the hearts, PC or non-PC, were subjected to 30-min ischemia followed by 2 h of reperfusion. As expected, the PC hearts exhibited improved ventricular function, reduced infarct size, and cardiomyocyte apoptosis. Also in PC hearts, an increase was noted in Trx-1 and other cardioprotective and redox-regulated proteins like Ref-1, phospho-Akt, and NF-kappaB DNA-binding activity. PC also caused nuclear translocation of Trx-1 and Ref-1 followed by their association. However, in hearts treated with shRNA-Trx 1, the cardioprotective effects of PC were abolished along with a concomitant decrease in nuclear localized Trx-1 and Ref-1, along with a decrease in phospho-Akt and NF-kappaB. These results demonstrate that PC triggers translocation of Trx-1 into the nucleus, where it becomes associated with Ref-1 and performs redox signaling through the activation of NF-kappaB and an increase in prosurvival signal inducer phospho-Akt.     

Liposomal drug delivery systems--clinical applications

Liposomes have been widely investigated since 1970 as drug carriers for improving the delivery of therapeutic agents to specific sites in the body. As a result, numerous improvements have been made, thus making this technology potentially useful for the treatment of certain diseases in the clinics. The success of liposomes as drug carriers has been reflected in a number of liposome-based formulations, which are commercially available or are currently undergoing clinical trials. The current pharmaceutical preparations of liposome-based therapeutic systems mainly result from our understanding of lipid-drug interactions and liposome disposition mechanisms. The insight gained from clinical use of liposome drug delivery systems can now be integrated to design liposomes that can be targeted on tissues, cells or intracellular compartments with or without expression of target recognition molecules on liposome membranes. This review is mainly focused on the diseases that have attracted most attention with respect to liposomal drug delivery and have therefore yielded most progress, namely cancer, antibacterial and antifungal disorders. In addition, increased gene transfer efficiencies could be obtained by appropriate selection of the gene transfer vector and mode of delivery.     

Hemodynamic effects of carvedilol infusion and the contribution of the sympathetic nervous system in rats with heart failure

We investigated the contribution of the sympathetic nervous system (SNS) in maintaining the blood pressure and in regulating the cardiac function during and after carvedilol administration in rats with heart failure (group F). Left ventricular end-diastolic pressure, percent functional shortening, and rates of intraventricular pressure rise were significantly changed by carvedilol infusion as compared with the basal values in group N (normal rats), but not in group F. The left ventricular end-diastolic pressure was elevated, corresponding to the enhancement of the plasma norepinephrine (NE) concentration caused by carvedilol infusion, in group N. The enhancement of the plasma NE concentration induced by carvedilol administration in group F was higher than that in group N. The value for the maximal hypertensive effect of NE intravenous infusion (Emax) was decreased, and the plasma NE concentration at half-maximal effect (EC50) was increased in group F as compared with the values in group N. These results indicate that the SNS (presynaptic) activity is increased and that the SNS receptor sensitivity in the cardiovascular regulation system is decreased in heart failure.     

Betaxolol improves the survival rate and changes natriuretic peptide expression in rats with heart failure

Growing evidence suggests that the autoimmune mechanism plays an important role in the pathogenesis of dilated cardiomyopathy. The purpose of this study was to evaluate the effect on the cardiac structure and function by the transfer of immunoglobulin G (IgG) and/or lymphocytes from rabbits immunized with a synthetic peptide corresponding to the sequence of the second extracellular loop of beta1-adrenoceptor (beta peptide) into severe combined immunodeficiency (SCID) mice. CB-17 SCID mice were injected intraperitoneally with 2 mg of IgG and/or 1 x 10(7) peripheral blood lymphocytes (PBL) from either rabbits immunized with both beta1 peptide and adjuvant (beta group), and adjuvant or rabbits with adjuvant only (N group). Thirty-five SCID mice were divided into seven groups: (1) N-IgG group; (2) N-PBL group; (3) N-IgG+PBL group; (4) beta-IgG group; (5) beta-PBL group; (6) beta-IgG+PBL group; and (7) control group. Morphological, serological and endocrinological studies were performed 70 days after the transfer. Results showed that heart weight and heart weight/body weight ratio in the beta-IgG+PBL group tended to be increased as compared with those in other groups. All mice in the beta-IgG group, two in the beta-PBL group and four in the beta-IgG+PBL group showed high titer of rabbit anti-beta1-adrenoceptor antibodies. Brain natriuretic peptide in the beta-IgG+PBL group showed a significant increase as compared with those in the control group and N-IgG+PBL. Pathohistologically, focal infiltration of inflammatory cells in the myocardium was observed in one mouse of the beta-IgG+PBL group. Rabbit CD3-positive T-lymphocytes in the myocardium were observed in two mice of the beta group. In conclusion, transfer of IgG and PBL from rabbits immunized with beta1 peptide was able to induce the early stages of myocardial damage in SCID mice. These data provide direct evidence that the autoimmune mechanism is important in the pathogenesis of dilated cardiomyopathy.     

Hemophilic pseudotumor of the first lumbar vertebra

Hemophilic pseudotumor involving the spine is extremely uncommon and presents a challenging problem. Preoperative planning, angiography, intra and perioperative monitoring with factor VIII cover and postoperative care for hemophilic pseudotumor is vital. Recognition of the artery of Adamkiewicz in the thoracolumbar junction helps to avoid intraoperative neurological injury. We report the case of a 26-year-old male patient with hemophilia A, who presented with a massive pseudotumor involving the first lumbar vertebra and the left iliopsoas. Preoperative angiography revealed the artery of Adamkiewicz arising from the left first lumbar segmental artery. Excision of pseudotumor was successfully carried out with additional spinal stabilization. At 2 years followup, there was no recurrence and the patient was well stabilized with a satisfactory functional status. Surgical excision gives satisfactory outcome in such cases.     

Delay to surgery prolongs hospital stay in patients with fractures of the proximal femur

Previous studies on the timing of surgery for fracture of the hip provide conflicting evidence as to the effect of prolonged delay before operation. We have prospectively reviewed 3628 such fractures in patients older than 60 years of age. Those for whom the delay was for medical reasons were excluded. Patients were followed up for one year or until death. Operation was undertaken within 48 hours in 95.2% and after this in 4.8%. A significant increase in length of stay was found in patients operated on after 48 hours when compared with those in the earlier group (21.6 vs 32.5 days). No increase in hospital stay was found for lesser delays.