W. Chung

Contrast-enhanced ultrasound in the preoperative, intraoperative and postoperative assessment of liver lesions.

The use of contrast agents (CA) with liver ultrasound (US) has gained recently an established role for the diagnosis of various hepatic diseases due to their safety, high versatility and low costs (contrast‐enhanced ultrasound: CEUS). The purpose of this review is to provide a state‐of‐the‐art summary of the available evidence for their use in the characterization of focal liver lesions. A published work search was conducted for all preclinical and clinical studies involving CA on hepatic US imaging. CEUS increases the sensitivity for lesion detection and the specificity to differentiate between benign and malignant diseases due to the enhanced visualization of the tumor microcirculation. Results achieved seem at least equivalent to those of spiral computed tomography or magnetic resonance imaging. The association of CA with intraoperative ultrasound has changed the surgical approach in 25% of patients and guarantees complete ablations by a single session in most of them. CEUS provides detailed information about tumor vasculature, improves the preoperative characterization and therefore the therapeutic strategy, and can evaluate the intraoperative completeness of the ablation.

Targeted microbubbles in the experimental and clinical setting.

BACKGROUND Microbubbles have improved ultrasonography imaging techniques over the past 2 decades. Their safety, versatility, and easiness of use have rendered them equal or even superior in some instances to other imaging modalities such as computed tomography and magnetic resonance imaging. Herein, we conducted a literature review to present their types, general behavior in tissues, and current and potential use in clinical practice. METHODS A literature search was conducted for all preclinical and clinical studies involving microbubbles and ultrasonography. RESULTS Different types of microbubbles are available. These generally improve the enhancement of tissues during ultrasonography imaging. They also can be attached to ligands for the target of several conditions such as inflammation, angiogenesis, thrombosis, apoptosis, and might have the potential of carrying toxic drugs to diseased sites, thereby limiting the systemic adverse effects. CONCLUSIONS The use of microbubbles is evolving rapidly and can have a significant impact on the management of various conditions. The potential for their use as targeting agents and gene and drug delivery vehicles looks promising.

The autologous normothermic ex vivo perfused porcine liver-kidney model: improving the circuit's biochemical and acid-base environment

BACKGROUND The ex vivo porcine liver perfused model isolates the organ from extrinsic regulatory mechanisms, facilitating an improved understanding of the organ physiology and reaction to various conditions. We have assessed the influence of the addition of a porcine kidney to the circuit. METHODS Eight livers were harvested and perfused for 6 hours. In 5 additional experiments a kidney also was connected in parallel. Hourly arterial blood gases were collected to analyze glucose, acid base, and renal parameters. The primary end point was an evaluation of the influence of the kidney on glucose, pH, and electrolyte levels. RESULTS In the combined porcine liver-kidney circuit all the parameters significantly improved compared with the liver circuit alone. This was particularly evident for glucose values because normoglycemia was reached by the end of the perfusion, and for pH and electrolyte values that were maintained at initial levels. CONCLUSIONS The addition of a porcine kidney to the perfusion circuit improves the biochemical milieu. This might produce more consistent and reliable results, particularly during studies requiring a steady-state environment.

Cellular and plasma uptake of parenteral omega-3 rich lipid emulsion fatty acids in patients with advanced pancreatic cancer

BACKGROUND & AIMS Omega-3 rich fatty acids (n-3FA) have powerful anti-inflammatory and anti-neoplastic properties. Previous studies have investigated plasma and cellular uptake of oral and parenteral n-3FA regimens. These have shown that n-3FA undergo rapid uptake into cells which is sustained for the length of the treatment course. The aim of this study was to investigate long-term uptake of prolonged, regular treatment courses of parenteral n-3FA which has not been previously reported. METHODS As part of a phase II single-arm trial, patients with advanced pancreatic cancer were treated with gemcitabine plus parenteral n-3FA rich lipid emulsion (up to 100 g) each week for three consecutive weeks with a subsequent rest week. This was repeated for up to six months in total for each patient. Pre-treatment serum and erythrocyte cell membrane (ECM) pellet samples were obtained each week for the entire treatment course of each patient. Post-treatment samples were obtained for the first two cycles only to assess rapid uptake. Fatty acid methyl esters (FAME) were produced and analysed using gas chromatography. FAME proportions as a total of sample lipid composition for each class were plotted and the results analysed using a linear regression coefficient model. RESULTS There was rapid and significant uptake of EPA and DHA FAME into plasma Non-Esterified Fatty Acids (NEFA) and EPA into ECM pellets in post-treatment samples (median increase of 1.06%, 0.65% and 0.05% respectively). There was significant reduction in n-6 fatty acid FAMEs and DHA in ECM pellets (decrease of 0.31% and 0.8% respectively- p = 0.031 for all). There was significant sustained uptake of EPA and DHA FAME into ECM pellets over the cohorts pooled treatment course with corresponding reduction in the n-6:n-3 ratio. CONCLUSIONS Prolonged regular parenteral n-3FA administration results in rapid and sustained cellular uptake. This regimen is appropriate for therapies aimed at increasing n-3FA content of cellular membranes and reduction of the n-6:n-3 ratio.

The development of a multiorgan ex vivo perfused model: results with the porcine liver-kidney circuit over 24 hours.

We already developed an ex vivo liver-kidney model perfused for 6 h in which the kidney acted as a homeostatic organ to improve the circuit milieu compared to liver alone. In the current study, we extended the multiorgan perfusions to 24 h to evaluate the results and eventual pitfalls manifesting with longer durations. Five livers and kidneys were harvested from female pigs and perfused over 24 h. The extracorporeal circuit included a centrifugal pump, heat exchanger, and oxygenator. The primary end point of the study was the evaluation of the organ functions as gathered from biochemical and acid-base parameters. In the combined liver-kidney circuit, the organs survived and maintained an acceptable homeostasis for different lengths of time, longer for the liver (up to 19-23 h of perfusions) than the kidney (9-13 h of perfusions). Furthermore, glucose and creatinine values decreased significantly over time (from the 5th and 9th hour of perfusion onward). The addition of a kidney to the perfusion circuit improved the biochemical environment by removing excess products from ongoing metabolic processes. The consequence is a more physiological milieu that could improve results from future experimental studies. However, it is likely that long perfusions require some nutritional support over the hours to maintain the organs vitality and functionality throughout the experiments.

Extracorporeal machine perfusion of the pancreas: technical aspects and its clinical implications – a systematic review of experimental models

Pancreas or pancreatic islet transplantation is an important treatment option for insulin-dependent diabetes and its complications. However, as the pancreas is particularly susceptible to ischaemic-reperfusion injury, the criteria for pancreas and islet donation are especially strict. With a chronic shortage of donors, one critical challenge is to maximise organ availability and expand the donor pool. To achieve that, continuous improvement in organ preservation is required, with the aims of reducing ischaemia-reperfusion injury, prolong preservation time and improve graft function. Static cold storage, the only method used in clinical pancreas and islet cell transplant currently, has likely reached its plateau. Machine perfusion, hypothermic or normothermic, could hold the key to improving donor pancreas quality as well as quantity available for transplant. This article reviews the literature on experimental models of pancreas machine perfusion, examines the benefits of machine perfusion, the technical aspects and their clinical implications.

OP004 EVALUATION OF THE CYTOKINES RESPONSE TO OMEGA-3 FATTY ACIDS IN PATIENTS WITH SEVERE ACUTE PANCREATITIS: A RANDOMISED CONTROLLED TRIAL

Rationale: A progressive decrease of renal function has been described in patients on home parenteral nutrition (HPN) for benign intestinal failure. The occurrence of frequent and severe episodes of dehydration potentially causing chronic renal failure (CRF) on HPN, was considered an indication for intestinal transplantation (ITx ), even though ITx is the solid organ transplant at higher risk for developing CRF. We investigated the renal function before and after HPN or ITx in patients currently cared at the same Hospital. Methods: A cross-sectional and retrospective follow up study was carried out in patients meeting the following criteria: age >18 and 60 yrs, duration of treatment 6 months, living at home. Renal function was evaluated at time of enrollment (cross sectional) and was compared with that observed at time of starting HPN or ITx (retrospective follow up): serum creatinine concentration (mg/dL) and glomerular filtration rate (GFR), estimated according to the MDRD equation (ml/min/1.73m2). CRF was defined as GFR <60. Duration of follow up was from time of starting HPN or ITx to time of cross sectional. Analysis by Student’s T and X2 test. Results: Thirty-three HPN patients and 22 ITx recipients were enrolled. At starting treatment, mean creatinine was 0.82 and 0.83 (P= 0.88), mean GFR was 101 and 115 (p = 0.21), and frequency of CRF was 6% and 9% (P= 0.67), in HPN and ITx respectively. Mean duration of follow up was 101 months in HPN and 74 in ITx (p = 0.15). At time of cross sectional, creatinine was higher (P= 0.00), GFR was lower (P= 0.03), %decrease of GFR was higher (p = 0.00) and frequency of CRF was higher (p = 0.10) in ITx. The yearly decline of GFR was 2.8% in HPN and 14.5% in ITx (p = 0.02). Conclusion: The decrease of renal function and the risk of developing CRF are greater after ITx than during long-term HPN.