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The multiorgan ex vivo perfused liver–kidney model allows studying the hepatic pathophysiology and purifying waste products. We tested if the addition of the kidney first followed by the liver (KL circuit) produces better results compared to the classic liver-first approach (LK). Intact livers and kidneys were obtained post mortem from ten female domestic white pigs, five experiments were conducted with the KL circuit and five with the LK. Bile, urine production, arterial blood gases, glucose, renal and liver tests were collected hourly during the perfusions. The KL circuit had values more close to physiological ranges, more stable over time and showed less variability compared to the LK circuit for urine production, glucose, PH, anion gap, lactate, urea, sodium, potassium and Alanine Transaminase (ANOVA test for repeated measures p < 0.05). The KL circuit produced a more physiological and reliable biochemical milieu.

Background Electrolytic ablation (EA) destroys tissues through extreme pH changes in the local microenvironment. An ex vivo perfused liver model was used to assess the systemic effects of EA on the acid–base balance without the influence of compensatory organs (lungs and kidneys). Methods Eleven pigs were perfused extracorporeally at 39°C with autologous blood; 4 also underwent EA after 1 hour of reperfusion. Arterial blood samples were obtained hourly. Results pH and CO2 levels did not change throughout the experiments. A significant increase of HCO3-, anion gap, base excess, and lactate was present after the third hour. No differences were observed between EA experiments and controls. Conclusions EA does not alter the acid–base balance even when the confounding influence of compensatory organs is removed. Such findings should be considered when planning ablations in patients with renal failure or respiratory diseases in which EA could avoid undesirable metabolic changes.

The addition of a kidney to the ex vivo liver perfused model may facilitate the circuit homeostatic balance of important biochemical parameters (i.e. pH changes, urea and creatinine, or glucose levels) but might also increase the inflammatory reaction produced. In this study, we compared the production of various cytokines between liver-kidney and liver-alone circuits. Seven livers were harvested from female pigs and perfused for 6 h. In five additional experiments, a kidney was also harvested and connected in parallel. Blood samples for interleukins (IL) 1, 2, 4, 6, 8, 10, and 12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were collected before perfusion and at hours 1, 2, 4 and 6 postperfusion. In the combined liver-kidney circuit, a significant increase was present only for IL-6 and IL-8, but this did not differ significantly from those recorded in the liver-alone circuit. All other cytokines were not modified from baseline levels. The addition of a kidney to the perfusion circuit does not stimulate a greater inflammatory reaction than that of the liver alone and therefore further confirms the safety of the experimental setups in view of more delicate experiments requiring strict homeostatic conditions.

Background Multimodal recovery programmes decrease hospital stay. The objective of this systematic review was to assess how single-modality evidence-based care principles, regarding postoperative analgesia and postoperative nausea and vomiting (PONV) prophylaxis, combine to achieve this. Methods A systematic review of randomised controlled trials was performed. Relevant trials compared postoperative epidural analgesia/parenteral opioid analgesia/ paracetamol/non-steroidal anti-infl ammatory drugs (NSAIDs) and postoperative antiemetics. The effect on recovery was evaluated in terms of length of hospital stay, pain intensity, duration of gastrointestinal dysfunction and incidence of PONV. Results Twenty-three trials were included. Epidural anaesthesia failed to reduce length of stay or the incidence of PONV when compared to controls. Pain intensity and time to fi rst bowel movement were reduced (p

Background This review examines histological modifications obtained after liver radiofrequency ablation (RFA). Methods A literature search has been undertaken for all pre-clinical and clinical studies involving RFA and in which ablation zones have been excised for a complete histological examination. Results Two main histological areas are present, a central zone of coagulative necrosis and a peripheral rim of congestion and extravasation. Both corresponded to specific microscopic characteristics that evolved over time and that are influenced by the proximity of patent vessels and the liver perfusion status. Viable cells are not present in the central zone but have been described in the ischemic peripheral rim where they survive the ischemia and inflammation process. These correspond in clinical studies to residual viable tumor cells that lead to failure of the procedure. Conclusions Histological changes following RFA are complex and interactions take place at both a cellular and tissue level. Changes in the peripheral zone must be considered in future studies in order to extend the volume of reliable tumor destruction and increase the effectiveness of the procedure.

Introduction: Islet autotransplantation requires access to the portal vein or tributaries. We originally infused islets into the liver via the middle or right colic veins, but since 2005 we have used the recanalised umbilical vein. Here, we describe the technique, the advantages and the early results achieved. Materials and Methods: After removal of the pancreas and restoration of the biliary and enteric continuity, the ligamentum teres is transected. The obliterated umbilical vein is identified and recanalised with Bakes dilators giving access to the left portal vein. A Vygon® Nutricath ‘S’ 11-Fr catheter is inserted and used for the islet infusion. If the ligamentum teres is to be exteriorised for postoperative measurements or subsequent access, it is pulled through a 10-mm laparoscopic port in the epigastrium, sutured to the skin and covered with a dressing. Results: We have used this approach in 17 patients and exteriorised the falciform ligament in 4. There have been no intra- or postoperative complications. Conclusions: The recanalised umbilical approach is safe and allows for venous sampling and postoperative measurements of the portal pressure. Under local anaesthetic, the umbilical vein can be approached above the umbilicus and exteriorised if repeated transplants are required for allograft patients.

Background Variations in the porcine hepatic vasculature may contribute to the outcome of experiments based on liver perfusion models. We studied the hepatic artery (HA), variations of its branches, and the correlation with the resultant perfusion. Materials and Methods Nineteen animals were used. After 6 h of perfusion, dissection of the HA and its branches was conducted up to the insertion in the liver parenchyma. Data about the macroscopic appearance of lobes and the pattern of branching were recorded. Results In all cases, the HA bifurcated into two constant branches, one for the LL/LM lobes (further divided in two vessels for each lobe) and one for the RM lobe. Five main patterns were identified involving vessels for the RL and the CL lobes. Two variations produced complete and uniform perfusion of the entire liver in all cases, while in the remaining cases, only part of them were completely perfused. Conclusions Some variants of the porcine HA and its branches are associated with the risk of incomplete perfusion if the perfusion cannula placement does not take the individual hepatic arterial anatomy into account. Understanding of the hepatic arteries branching patterns is essential when ex vivo perfusion models are being established.

Electrolytic ablation (EA) is a treatment that destroys tissues through electrochemical changes in the local microenvironment. This review examined studies using EA for the treatment of liver and pancreatic tumours, in order to define the characteristics that could endow the technique with specific advantages compared with other ablative modalities.Literature search of all studies focusing on liver and pancreas EA.A specific advantage of EA is its safety even when conducted close to major vessels, while a disadvantage is the longer ablation times compared to more frequently employed techniques. Bimodal electric tissue ablation modality combines radiofrequency with EA and produced significant larger ablation zones compared to EA or radiofrequency alone, reducing the time required for ablation. Pancreatic EA has been investigated in experimental studies that confirmed similar advantages to those found with liver ablation, but has never been evaluated on patients. Furthermore, few clinical studies examined the results of liver EA in the short-term but there is no appropriate follow-up to confirm any survival advantage.EA is a safe technique with the potential to treat lesions close to major vessels. Specific clinical studies are required to confirm the technique's safety and eventually demonstrate a survival advantage.

Background: A number of methods are available for the drainage of pancreatic pseudocysts, including percutaneous, endoscopic and open approaches. In Leicester, we developed a combined radiological and endoscopic technique (predating the use of endoscopic/ultrasound) to allow drainage of pancreatic pseudocysts into the stomach. The aim of the study was to evaluate the long-term results of this approach. Methods: This is a retrospective study of patients undergoing combined endoscopic/ultrasound-guided percutaneous stenting between 1994 and 2007. Data were extracted from case records and our computerised radiology database. Results: Thirty-seven combined endoscopic/ultrasound-guided procedures were undertaken. Median patient age was 52 years (range 26–84 years). Nineteen pseudocysts were secondary to acute pancreatitis and 18 were in patients with chronic pancreatitis. The diameter of pseudocysts on pre-procedure imaging ranged from 4 to 21 cm (median 11 cm). Median duration of hospital stay was 7 days (range 1–44 days) and 30-day mortality was 0%. Stents were inserted in 70.3% of patients (n= 26). Of those patients stented during the combined procedure, three developed infection of the pseudocyst, necessitating open cystgastrostomy within the first month. During a mean follow-up period of 41 months, two patients developed recurrent pseudocysts which were successfully drained with a further combined procedure (16 and 43 months). Repeat imaging in the remainder of patients failed to show any evidence of a persistent or recurrent pseudocyst beyond 2 months. Conclusion: Combined radiological and endoscopic drainage is safe, cost-effective and highly efficient in preventing recurrent pseudocyst formation.

The liver has a complex hormonal and nervous control mechanism leading to difficulty in the interpretations of its responses to chronic hypoxia. Theoretically an ex vivo perfused model of the liver should, by dissociating the organ from the extrinsic regulatory mechanisms, allow a better and unequivocal analysis of changes obtained.Twelve livers were harvested from female pigs and perfused for 6 h. Hypoxia was produced by means of isovolemic hemodilution with hemoglobin and hematocrit reduced to 40% of the baseline value. The extracorporeal circuit included a centrifugal pump, heat exchanger, and oxygenator. Every hour, physiological parameters (arterial/portal venous pressures and flows) were measured and blood samples were collected for the analysis of hemoglobin, red blood cells, hematocrit, lactate, glucose, albumin, alanine aminotransferase, alkaline phosphatase, and total bilirubin, arterial and venous blood gases. The arterio-venous oxygen and carbon dioxide differences, and the hepatic metabolic rate for oxygen, were also calculated. Primary endpoint of the study was the glucose response of the liver to acute hypoxia. Secondary endpoints were eventual changes of markers for hepatic viability and functionality.Most parameters showed significant variability during the first h of perfusion but subsequently normalized and remained stable at baseline values for the following 5 h. A strong and significant hyperglycemic response was present throughout the experiment (P0.001). Lactate rose steadily throughout the study period and after 6 h of perfusion there was a significant deviation from initial values (P0.05). Albumin did not change significantly throughout the study although a trend towards decreasing values was observed (Friedman test, P = NS). After an initial rise in levels of alanine transaminase and alkaline phosphatase following perfusion (P0.01), values remained constant without any further increase.Following reperfusion in an ex vivo model, the liver reacts to low oxygen concentrations mobilizing glycogen deposits. This mechanism depends on an intrinsic sensibility of hepatocytes to hypoxia, as demonstrated by the ex vivo liver perfusion. These findings improve our knowledge in organ preservation for liver transplantation.

EWS is frequently used to monitor acute admissions requiring emergency surgery. This study examined preoperative early warning scoring (EWS) and its ability to predict mortality and critical care admission. Postoperative EWS was also evaluated as a predictor of mortality.Preoperative EWS, age, physiologic and operative severity (POSSUM) scores, ASA grade, and serology were compared in 280 patients undergoing emergency surgery.Two hundred eighty patients were identified with a mortality of 15%. Among the physiological scoring systems, ASA grade and POSSUM scores were the best predictors of mortality (AUC values of 0.81). EWS, APACHE II, and age were the next best predictors (AUC values of 0.70). Postoperative APACHE II and EWS both predicted mortality. EWS on day 2 postoperatively was the best overall predictor of mortality of all the variables studied (AUC value of 0.83). Survival between patients with "improving or stable" EWS and those with "deteriorating or failing to improve" EWS was also found to be significantly different (P0.001). In addition, both EWS on admission and EWS 1 h preoperatively were found to predict critical care requirement postoperatively (AUC value of 0.78).EWS can predict the need for critical care admission and mortality following emergency surgery. In particular, the progression of EWS preoperatively, that is, whether scores improve or deteriorate, is a highly significant factor in predicting survival following emergency surgery. These findings support the use of EWS in monitoring the acute surgical patient.

Introduction: The aim of this review is to summarize the available evidence for changes in bile composition following liver surgery and assess their use in predicting post-operative complications. Materials and Methods: A literature search was undertaken for all studies focusing on bile composition, bile volume and analysis. Articles were selected from MEDLINE, Embase and the Cochrane Central Register of Controlled Trials databases up to May 2009. Results: Low values of pre-operative bilirubin diglucuronide predict reduced post-operative liver function and the occurrence of jaundice. Low concentrations of hepatocyte growth factor and interleukin-6 in bile following surgery are associated with the subsequent development of liver failure and are probably surrogate markers for situations where the resultant hepatic regeneration is inadequate. Conclusions: Analysis of the composition and quality of bile is probably underused as a tool for the pre-operative screening and early post-operative monitoring of patients at high risk of developing liver failure following major hepatobiliary procedures.

Pain control is one of the most challenging aspects in the management of chronic pancreatitis. Total pancreatectomy can successfully relieve the intractable abdominal pain in these patients but will inevitably result in insulin-dependent diabetes. Islet autotransplantation aims to preserve, as far as possible, the insulin secretory function of the islet cell mass thereby reducing (or even removing) the requirement for exogenous insulin administration after a total pancreactomy. Despite the relatively small number of centres able to perform these procedures, there are important technical variations in the details of their approaches. The aim of this review is to provide details of the current surgical practice for total pancreatectomy combined with islet autotransplantation, and outline the potential advantages and disadvantages of the variations adopted in each centre.

Neuroendocrine tumours of the pancreas (PNETs) represent 1-2% of all pancreatic tumours. The terms 'islet cell tumours' and 'carcinoids' of the pancreas should be avoided. The aim of this review is to offer an overview of the history and diagnosis of PNETs followed by a discussion of the available treatment options.A search on PubMed using the keywords 'neuroendocrine', 'pancreas' and 'carcinoid' was performed to identify relevant literature over the last 30 years.The introduction of a revised classification of neuroendocrine tumours by the World Health Organisation (WHO) in 2000 significantly changed our understanding of and approach to the management of these tumours. Advances in laboratory and radiological techniques have also led to an increased detection of PNETs. Surgery remains the only treatment that offers a chance of cure with increasing number of non-surgical options serving as beneficial adjuncts. The better understanding of the behaviours of PNETs together with improvements in tumour localisation has resulted in a more aggressive management strategy with a concomitant improvement in symptom palliation and a prolongation of survival.Due to their complex nature and the wide range of therapeutic options, the involvement of specialists from all necessary disciplines in a multidisciplinary team setting is vital to provide optimal treatment of this disease.

Pre-operative determination of the risk of liver dysfunction has come under criticism with regards to its usefulness in clinical practice. Opinion is split between centres which use such tests uniformly on all patients and those where clinical judgment alone is used. Published data would not suggest any difference in mortality, morbidity or liver failure rates between these groups. This review outlines and presents the evidence for pre-operative quantification of functional liver remnant volume.

Ablation of liver tissue produces in situ tumoural antigens and elicits specific immune responses. The aim of this review is to examine the available data about the local and systemic responses produced and to compare differences between the methods available. A literature search was undertaken for all papers focusing on immune responses following ablative therapy of the liver, including experimental and clinical studies. Following ablative procedures, the cellular response is elicited by the presentation of antigens by dendritic cells to specific CD4(+) T cells, which in turn stimulate natural killer or CD8(+) cytotoxic cells. The local release of intracellular debris activates Kupffer cells to produce cytokines, which, in the immediate vicinity, activate monocytes/macrophages or specific T cells that respond and produce systemic reactions such as fever, thrombocytopaenia or shock. The immune responses elicited by cryotherapy, both cellular and cytokine, seem far greater than those produced by radiofrequency or microwave ablation, probably as a consequence of the peculiar mechanism of cell death of the former (disruptive necrosis). This mechanism is considered central to the pathogenesis of cryoshock. Ablative techniques stimulate the immune system and provide an easy way to achieve in vivo vaccination against tumoural antigens. Immunomodulatory approaches have the potential to augment the initial immune stimulation and this combined approach could pave the way to a more selective and specific method of treating liver tumours.

Peri-ampullary and hepatic malignancies will frequently present with obstructive jaundice. For unresectable tumors, effective and lasting decompression of the biliary tree is essential to improve quality of life and survival. An overview of present treatment modalities for palliation of obstructive jaundice is provided, including a systematic review of the English literature regarding the optimum choice of palliation.

Sclerosing cholangitis is an autoimmune condition characterized by lymphocytic infiltration within the biliary epithelium leading to multifocal stricturing of the biliary tree. Primary sclerosing cholangitis (PSC) is the most common type encountered clinically. However, a similar process may occur in conjunction with autoimmune pancreatitis (AIP), known as AIP-associated sclerosing cholangitis (AIP-SC). This subtype is associated with an elevated IgG4 level and the presence of a number of autoantibodies. AIP-SC shows good response to steroid treatment, distinguishing it clinically from PSC. The authors report a case of AIP-SC in a patient who had previously undergone a biliary bypass for AIP-induced chronic pancreatitis. The presentation of jaundice and grossly elevated tumor marker, CA19.9, raised the concern of malignancy. The uncertainty of the diagnosis was resolved when AIP-SC was confirmed on liver biopsy, with a concomitantly elevated serum IgG4 level. The disease went into remission with steroid treatment.

Microwave (MW) ablation therapy is a local treatment by which tumours are destroyed by coagulation from the passage of MWs into cells. The aim of this review is to examine histological results obtained from preclinical and clinical studies. A literature search was undertaken for all studies focusing on MW therapy and in which lesions were excised for a complete histopathological examination after treatment. Two main zones were described after ablative therapy (central and transitional). Both corresponded to specific microscopic characteristics and evolved over time in a precise manner. No viable cells even up to 6 cm in diameter were demonstrated in 93% of lesions after treatment. Microwave therapy is a reliable technique under a variety of clinical situations. Future investigations are needed to compare MW with other ablative techniques to identify factors that influence the effectiveness of the various techniques and to determine specific indications.

Objective. Intrahepatic infusion is the most common method of islet autotransplantation. Structural and functional changes within the liver may result from a number of factors, including embolization of the terminal branches of the portal vein, the effects of high insulin concentration on surrounding hepatocytes or responses to the death of admixed exocrine tissue. Awareness of the potential changes in the appearance of the liver on ultrasonography (USS), together with an assessment of liver function, is important in the postoperative surveillance of these patients. Methods. We retrospectively reviewed 83 patients who underwent total pancreatectomy between 1993 and 2006. Thirty-three patients had total pancreatectomy alone (control group) and 50 patients underwent total pancreatectomy and islet autotransplantation (islet group). The islets were infused into the left lobe of the liver through the middle colic or recannalated umbilical vein. All patients underwent USS as part of their hepaticojejunostomy surveillance (initially every 6 months and then yearly). Results. "Echogenic nodularity" of the liver was observed in 25% of the islet group of patients and in none of the control group patients (P=0.03). These USS changes occurred from 6 to 12 months after islet autotransplantation and were not associated with any significant loss of liver function or increase in insulin requirements. The islet group had significantly less insulin requirement compared with the control group (P

Background/Aims: Due to enhanced imaging modalities, pancreatic cysts are being increasingly detected, often as an incidental finding. They comprise a wide range of differing underl

The use of ex vivo perfused models can mimic the physiological conditions of the liver for short periods, but to maintain normal homeostasis for an extended perfusion period is challenging. We have added the kidney to our previous ex vivo perfused liver experiment model to reproduce a more accurate physiological state for prolonged experiments without using live animals. Five intact livers and kidneys were retrieved post-mortem from sacrificed pigs on different days and perfused for a minimum of 6 hr. Hourly arterial blood gases were obtained to analyze pH, lactate, glucose and renal parameters. The primary endpoint was to investigate the effect of adding one kidney to the model on the acid base balance, glucose, and electrolyte levels. The result of this liver-kidney experiment was compared to the results of five previous liver only perfusion models. In summary, with the addition of one kidney to the ex vivo liver circuit, hyperglycemia and metabolic acidosis were improved. In addition this model reproduces the physiological and metabolic responses of the liver sufficiently accurately to obviate the need for the use of live animals. The ex vivo liver-kidney perfusion model can be used as an alternative method in organ specific studies. It provides a disconnection from numerous systemic influences and allows specific and accurate adjustments of arterial and venous pressures and flow.

Local recurrence of cholangiocarcinoma at resection margins following surgery remains notoriously difficult to be distinguished (clinically and radiologically) from a benign anastomotic stricture. We report the case of a 65-year-old gentleman who presented with fluctuating obstructive jaundice 4 years following his extended right hepatectomy for a hilar cholangiocarcinoma. Although a whole body combined computed tomography–positron emission tomography (PET–CT) suggested no evidence of recurrent disease this was found and confirmed histologically during revision of his hepatico-jejunostomy. This emphasizes the potential false negative rate of PET–CT scanning in the assessment of recurrent cholangiocarcinoma.

Numerous techniques developed in medicine require careful evaluation to determine their indications, limitations and potential side effects prior to their clinical use. At present this generally involves the use of animal models which is undesirable from an ethical standpoint, requires complex and time-consuming authorization, and is very expensive. This process is exemplified in the development of hepatic ablation techniques, starting experiments on explanted livers and progressing to safety and efficacy studies in living animals prior to clinical studies. The two main approaches used are ex vivo isolated non-perfused liver models and in vivo animal models. Ex vivo non perfused models are less expensive, easier to obtain but not suitable to study the heat sink effect or experiments requiring several hours. In vivo animal models closely resemble clinical subjects but often are expensive and have small sample sizes due to ethical guidelines. Isolated perfused ex vivo liver models have been used to study drug toxicity, liver failure, organ transplantation and hepatic ablation and combine advantages of both previous models.

Ex vivo perfused porcine livers have been used for temporary support during acute liver failure. The aim of this study was to assess both the histological changes and temporal pattern of the changes that occur during extracorporeal liver perfusions and to correlate these with factors that may influence them. Five porcine livers were harvested, preserved in cold ice and reperfused for 6 h in an extracorporeal circuit using autologous normothermic blood. Tissue biopsies were collected hourly. The Ishak score was used to quantify hepatic necrosis, and immunohistochemistry was used to evaluate apoptosis and regeneration. Liver weight, perfusion parameters, arterial blood gases and blood samples were also collected. The Ishak score peaked immediately before and 4 h after the start of reperfusion. Scattered necrosis, microvesicular steatotic vacuolization, sinusoidal dilatation and red cell extravasation were present. Anion gap acidosis was associated with the Ishak score. An inverse correlation was present between liver regeneration and necrosis, and between liver weight and regeneration. No changes were observed for apoptosis. Among the inflammatory cytokines evaluated, interleukin-6 and -8 levels increased significantly during the perfusions. Hepatic necrosis was always present during the extracorporeal perfusions, followed a definite pattern and was inversely correlated with regeneration. Apoptosis did not increase over baseline levels. The meaning of these findings and their correlation with clinical outcomes during acute hepatic failures deserve further investigation.

Electrolytic ablation (EA) destroys the liver by releasing toxic radicles and producing modifications in the local pH without increasing the tissue temperature. We assessed the histological changes produced by EA using an ex-vivo perfused model. Five porcine livers were harvested, preserved in ice and reperfused for six hours in an extracorporeal circuit using autologous normothermic blood. One hour after reperfusion EA was performed and liver biopsies collected at the end of the experiments. The main necrotic zone consisted of coagulative necrosis, sinusoidal dilatation and haemorrhage with an unusual morphological pattern. The coagulative necrosis and haemorrhage affected mainly the peripheral area of the lobule with relative sparing of the area surrounding the centrilobular vein. Contrasting with this sinusoidal dilatation appeared to be more prominent in the centrilobular area. EA produces patterns of tissue destruction that have not been observed with the more commonly used thermal techniques. Further studies should obtain more information about the influence of adjacent biliary and vascular structures so that appropriate clinical trials can be designed.

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.

The inflammatory response following hepatic ablation depends on different factors including the method used, the duration and intensity of the treatment and the presence or absence of ischemia. Debate continues about the use of different modalities and whether some aspects of the response may be advantageous by releasing immunological active substances. Little data have been published concerning the cytokine response elicited by hepatic electrolytic ablation (EA). Study of an ex vivo liver model could allow for the evaluation of this response without the influence of confounding systemic factors.Livers explanted from 11 pigs were perfused extracorporeally with normothermic autologous blood. Four of them underwent EA after 1 h of reperfusion. Serum samples were obtained up to 6 h after the reperfusion and assayed for IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IFN-gamma, TNF-alpha.Significant changes in the control group were observed for IL-6 after the second hour and IL-8 after the first hour compared with baseline levels (P0.001). In the EA group, IL-6 and IL-12 were raised after the second hour and IL-8 and IL-10 after the first hour (P0.001). The comparison between groups showed significant differences for IL-2, IL-4 (decreased in the EA group compared with controls), IL-10 and TNF-alpha (EA group increased compared with controls; P0.001).The ex vivo perfused liver model demonstrated changes in levels of IL-2, IL-4, IL-10 and TNF-alpha following hepatic EA.

Background Radiology reports provide specialist interpretation of images and relate these findings to the patient's symptoms and signs. This study compared ultrasound (USS) reports generated by radiologists and sonographers to determine if any significant or clinically relevant differences existed. Methods A retrospective analysis of 624 consecutive USS reports was carried out. The reports were assessed for the presence of a ‘disclaimer’ or ‘caveat’ pertaining to the quality of the images and were analysed with respect to the clarity of their wording and ability to answer the clinical request. Results The majority of sonographer USS reports contained a disclaimer regarding the quality of the USS images (57.1%) compared with a smaller proportion of radiologist scans (9.9%) (P

No conclusive evidence exists confirming the role of preoperative biliary drainage (PBD) in reversing the physiological disturbances resulting from biliary obstruction to improve outcome. This review examined the impact of PBD and the outcomes after surgery.A PubMed literature search was undertaken using the keywords preoperative, biliary, and drainage. The primary end points were the effect of PBD on mortality, morbidity, and bile cultures. The secondary outcome measures were PBD and pancreatic leakage, intra-abdominal abscess, sepsis/infectious complications, wound infection, hemorrhage, and bile leak rates. The impact of bile cultures positive for bacteria and the outcomes after surgery were also examined.Preoperative biliary drainage significantly increases wound and bile infection rates on meta-analysis (P0.0005) using a fixed and random effect model, but no adverse effect on mortality and morbidity was found. A bile culture positive for bacteria negatively impacts on both mortality and morbidity (P0.005) after surgery.Preoperative biliary drainage significantly increases the rates of bile culture positive for bacteria and the probability of wound infection. Bile cultures positive for bacteria adversely impact mortality and morbidity after surgery in jaundiced patients. Although no evidence has been found by this review that PBD directly increases mortality and morbidity, it is possible that in certain patients, PBD may deleteriously affect outcome by bacterial contamination of the bile.

In this review, we focus on studies that examined such prognostic indices in relation to predicting a fatal outcome from pancreatitis.Acute pancreatitis (AP) is a common emergency, and early identification of high-risk patients can be difficult. For this reason, a plethora of different prognostic variables and scoring systems have been assessed to see if they can reliably predict the severity of pancreatitis and/or subsequent mortality.All studies that focused on AP, including retrospective series and prospective trials, were retrieved and analysed for factors that could influence mortality. Articles that analysed factors influencing the severity of the disease or the manifestation of disease-related complications were excluded.58 articles meeting the inclusion criteria were identified. Among the various factors investigated, APACHE II seemed to have the highest positive predictive value (69%). However, most prognostic variables and scores showed high negative predictive values but suboptimal values for positive predictive power.Despite the proliferation of scoring systems for grading AP, none are ideal for the prediction of mortality. With the exception of the APACHE II, the other scores and indexes do not have a high degree of sensitivity, specificity and predictive values.

This article reviews the therapeutic efficacy and complications of microwave ablation (MWA) in the treatment of primary and secondary liver malignancies. A PubMed search using keywords 'microwave', 'liver', 'malignancy', 'cancer' and 'tumour' was performed to identify articles related to MWA of liver malignancies published in English from 1975 to February 2008. MWA is an effective treatment options for both primary and secondary liver malignancies with survivals comparable with those of liver resections. Local recurrences can be managed with further ablation. Small tumour size, well-differentiated tumour and a reduced number of lesions are factors associated with good prognosis. Temporary occlusion of the portal venous and hepatic arterial flow may increase the size of ablation but the safety aspect requires further validation. MWA is a minimally invasive technique that has broadened the therapeutic option for patients with conventionally unresectable liver tumours with promising survival data. Future advances in the applicator design and treatment monitoring may further improve its efficacy and widen the indications.

Objectives Early Warning Scores (EWS) is a widely used scoring system monitoring patient progress, which we have previously shown to predict outcome from acute pancreatitis. This study examined EWS from a larger group of patients to confirm if this predictive value held true. Methods The EWS scores were compared with the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, modified organ dysfunction scores, Imrie scores, computed tomography grading scores, and Ranson criteria for 181 admissions with acute pancreatitis. The accuracy of EWS in predicting outcome was determined by receiver operator characteristics. Results A total of 181 patients were identified with acute pancreatitis. On day 1 of admission, APACHE II scores were the most accurate predictor of mortality with an area under curve (AUC) values of 0.876, closely followed by EWS (AUC, 0.827). By day 2 and 3 after admission, the EWS was the most accurate predictor of mortality (AUC, 0.910 and 0.934, respectively). The APACHE II was the second most accurate scoring system at 48 and 72 hours (AUC, 0.892 and 0.911, respectively). Conclusions The EWSs on days 2 and 3 after admission are sensitive and specific in predicting mortality from acute pancreatitis. It is as accurate as the APACHE II scores and easier to implement in daily practice.

Background: Untreated colorectal liver metastases (CLMs) have a dismal prognosis. Surgery remains the gold standard of treatment, but many patients will have inoperable disease at presentation. Until recently, the outlook for such patients was bleak. The purpose of this review was to report on available options in the treatment CLMs, which would be considered unresectable by conventional evaluation. Methods: Inclusion criteria were articles published in English-language journals reporting on either retrospective or prospective cohorts of patients undergoing treatment for conventionally inoperable CLM. Main outcome measures were survival, resectability rates, morbidity and mortality following treatment of the patients’ disease. Results: Improved chemotherapy regimes and other innovative treatments have opened up new options for such patients and may even render conventionally inoperable disease resectable. The aim of treatment should be down-staging of metastases to achieve resectability, however, other treatments such as ablation may be also be used (either alone or in conjunction with resection). Conclusion: A nihilistic attitude to the patient with seemingly inoperable liver metastases should be discouraged. Discussion of such patients at multi-disciplinary meetings is essential in order to plan and monitor treatments.

Introduction Early warning scores (EWS) is a physiological scoring system measured hourly. This study determined how progression of EWS affected outcome in acute pancreatitis. Methods The single worst EWS score for each 24 h period following admission was recorded for 110 patients with acute pancreatitis. Scores falling below 3 were defined as improving; scores which remained at 3 or rising were considered deteriorating. Results Deteriorating EWS values were associated with a greatly increased risk of mortality (p Conclusion Deteriorating EWS values within the 48 h from admission are associated with adverse outcome or death in acute pancreatitis. Measuring progression of EWS over 72 h from admission can further improve accuracy of this monitoring system for acute pancreatitis.

Background. There is no consensus regarding the optimum surgical approach to gallbladder cancer. This study reviews the management of gallbladder cancer in a single unit. Methods. Retrospective study of 73 consecutive patients diagnosed with gallbladder cancer. Twenty-three patients underwent surgery with curative intent (surgical group), 28 patients underwent exploratory surgery but had inoperable disease (surgically inoperable group) and 22 patients had inoperable disease radiologically (radiologically inoperable group). Within the surgical group, nine patients (cholecystectomy group) were diagnosed with gallbladder cancer after routine cholecystectomy. Results. The inoperable groups had significantly higher bilirubin and alkaline phosphatase (ALP) than the surgical group (p=0.02 and p68, white cell count (WCC)>7.6×109/L, platelet>345×109/L, bilirubin>16 mol/L, ALP >124 iu/L and sodium =137mmol/L were markers of inoperability. Age, haemoglobin and neutrophil:lymphocyte ratio (NLR) were predictors for survival following surgery (p=0.04, p=0.01 and p

There is increasing evidence that the presence of a pre-operative systemic inflammatory response (SIR) independently predicts poor long-term outcome in patients with colorectal cancer (CRC). Socioeconomic deprivation was reported to correlate with the presence of the SIR and to independently predict poor outcome following primary CRC resection. The aim of this study was to determine the prognostic value of pre-operative systemic inflammatory biomarkers and socioeconomic deprivation in patients undergoing resection of colorectal liver metastases (CLM) and to examine correlations between these variables in this context.Clinicopathological data, including the Memorial Sloan-Kettering Cancer Centre Clinical Risk Score (CRS), were obtained from a prospectively maintained database for 174 patients who underwent hepatectomy for CLM between January 2000 and December 2005 at a single United Kingdom (UK) tertiary referral hepatobiliary centre. Inflammatory biomarkers (total and differential leucocyte counts, neutrophil-lymphocyte ratio, platelet count, haemoglobin, and serum albumin) were measured from routine pre-operative blood tests. Socioeconomic deprivation was measured using the Carstairs deprivation score.On multivariable analysis, poor CRS (3-5), high neutrophil count (6.0 x 10(9)/l) and low serum albumin (40g/dl) were the only independent predictors of shortened overall survival following metastasectomy, with neutrophil count representing the greatest relative risk of death. These factors were also the only independent predictors of shortened disease-free survival following hepatectomy. Socioeconomic deprivation was associated with neither systemic inflammation nor long-term outcome in this context.The presence of a pre-operative systemic inflammatory response, but not socioeconomic deprivation, independently predicts shortened survival following resection of CLM.

Despite extensive preoperative staging, a significant number of pancreatic cancers are unresectable at surgical exploration. Patients undergoing pancreatic exploration with a view to resection were studied and comparisons are then made between those undergoing resection and a bypass procedure to identify surrogate markers of unresectability. One hundred thirteen consecutive patients underwent pancreatic exploration for head-of-pancreas (HOP) adenocarcinoma with curative intent. Fifty-five underwent pancreaticoduodenectomy and 58 underwent a bypass procedure. Student's t test, receiver operator characteristics (ROC) and logistic regression were used to compare the predictive value of preoperative patient variables collected retrospectively. The bypass group had a significantly higher median CA19.9 than the resection group (P = 0.003). Platelet count and neutrophil-lymphocyte ratio (NLR) were also significantly different (P = 0.013 and P = 0.026, respectively). ROC analysis indicated that ageor =65, platelet count297 x 10(9)/l, CA19.9or =473 Ku/l, and CA19.9-bilirubin ratio were predictive variables for resectable disease. NLR and CA19.9-bilirubin ratio had specificity values of 92.9 and 97.0%, respectively. From logistic regression, a raised CA19.9 was found to be an independent risk factor for unresectable disease (P = 0.031). A significant proportion of patients with HOP adenocarcinoma are understaged preoperatively. Preoperative serology including platelet count, NLR, CA19.9, and CA19.9-bilirubin ratio may be used as additional discriminators of resectability particularly for high-risk patients.

Aims We have maintained a highly conservative policy in selecting patients with carcinoma of the head of pancreas for resection. This has been based on tumour size, evidence of lymph node involvement or local invasion outside of the gland at laparotomy, laparoscopy or CT imaging. This study investigated our survival rates following pancreatic resection and examined clinicopathological predictors of survival. Methods Sixty-two consecutive patients undergoing pancreatic resections for malignancy were identified from 1999 onwards. Thirty-three underwent resection for pancreatic ductal adenocarcinoma and were included in our analysis, the remainder included resections for ampullary adenocarcinoma ( n = 20) or other malignancies ( n = 9). Patient, tumour and operative characteristics were analysed to assess predictors of survival following resection (Kaplan–Meier survival curves). Results Median survival following resection for ductal pancreatic adenocarcinoma was 54 months (ampullary adenocarcinomas achieved a median survival of 62 months) and thirty-day mortality was 2.7% ( n = 1). Survival was not associated with any demographic or intraoperative factors, such as blood loss, operative duration or anaesthetic technique. Survival curves were significantly worse when perineural or vascular invasion was evident histologically ( p = 0.023 and 0.0023 respectively). Patients with positive lymph nodes had a significantly shorter survival ( p = 0.0030) especially when lymph node status was expressed as a percentage of total lymph node yield. If more than 20% of retrieved lymph nodes were positive for tumour, this was a clear predictor of survival ( p p = 0.0291). Conclusion Despite the advances made in the management of pancreatic cancer, tumour biology still dictates long-term survival. A highly selective surgical approach to the management of these patients results in good long-term survival.

We report the case of a 75-year-old woman who died of liver failure following coronary artery bypass grafting. The possibility of an association with leflunomide is discussed.