D. Al-Leswas

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.

Pooled survival and response data from phase III randomized controlled trials for gemcitabine-based regimes in the treatment of advanced pancreatic cancer.

Although gemcitabine remains current first-line chemotherapy for patients with advanced pancreatic cancer, median survival times have not improved significantly since its introduction 15 years ago. Of the phase III trials which have investigated alternative regimens to single-agent gemcitabine, most have used combination regimens as the investigational arm. Accurate data on median overall, progression-free survival and objective response rates is important, for two principle reasons: advising patients about their prognosis and when powering phase II trials and evaluating the results of single-armed trials. This study aims to pool results from published randomized trials to date. Twenty-one randomized phase III trials involving a total of 6348 patients were identified from 1997 to 2010. Only one trial investigating a novel agent in combination with gemcitabine showed a significantly prolonged median and progression-free survival compared with single-agent gemcitabine. Pooled median and progression-free survivals for the single-agent gemcitabine arm involving 3171 patients across all studies were 6.15 and 3.3 months, respectively. Length of survival for patients with advanced pancreatic cancer remains disappointing. Further trials of novel agents to complement or replace gemcitabine are indicated.

Potential applications of fish oils rich in n -3 fatty acids in the palliative treatment of advanced pancreatic cancer

The palliative treatment of patients with advanced pancreatic cancer (APC) has undergone little advancement in the last 15 years. Novel therapies that have been investigated to extend survival have shown little benefit over existing chemotherapy regimens. Patients with APC often experience significant weight loss, which is one of the primary factors involved in declining quality of life. Recently, the ability of n-3 fatty acid rich oral preparations to attenuate or reverse tumour-related weight loss has been investigated in this patient group with encouraging results. Laboratory investigation has also yielded promising results suggesting a potential direct tumouricidal effect of n-3 fatty acids as well as the putative potentiation of existing chemotherapy regimes. The present review aims to examine the potential applications of fish oils rich in n-3 fatty acids in patients with APC, present a selection of the studies carried out to date and outline avenues of possible further clinical investigation.

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.

Hepatic haemangioma masquerading as the gallbladder in a case of gallbladder agenesis: a case report and literature review.

Gallbladder agenesis is uncommon. In contrast, liver haemangiomas are the most common type of benign liver lesions. We describe the first documented case of gallbladder agenesis where the clinical presentation was consistent with biliary colic, and radiological investigation suggested the presence of gallstones. Subsequent operative findings revealed a solitary haemangioma of the liver sited in the normal position of the gallbladder fossa but with absence of the gallbladder. It is important that clinicians should keep gallbladder agenesis in mind when the gallbladder appears abnormal on preoperative imaging studies and cannot be found at laparoscopy. As symptoms will improve in 98% of cases, it is very important to avoid unnecessary intervention in patients who have a negative laparoscopy. The clinical presentation, investigations, and operative findings are discussed with a review of other relevant reported cases in the literature.

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.