A Vallance

Double bypass for inoperable pancreatic malignancy at laparotomy: postoperative complications and long-term outcome.

INTRODUCTION Between 4% and 13% of patients with operable pancreatic malignancy are found unresectable at the time of surgery. Double bypass is a good option for fit patients but it is associated with high risk of postoperative complications. The aim of this study was to identify pre-operatively which patients undergoing double bypass are at high risk of complications and to assess their long-term outcome. METHODS Of the 576 patients undergoing pancreatic resections between 2006 and 2011, 50 patients who underwent a laparotomy for a planned pancreaticoduodenectomy had a double bypass procedure for inoperable disease. Demographic data, risk factors for postoperative complications and pre-operative anaesthetic assessment data including the Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM) and cardiopulmonary exercise testing (CPET) were collected. RESULTS Fifty patients (33 men and 17 women) were included in the study. The median patient age was 64 years (range: 39–79 years). The complication rate was 50% and the in-hospital mortality rate was 4%. The P-POSSUM physiology subscore and low anaerobic threshold at CPET were significantly associated with postoperative complications (p=0.005 and p=0.016 respectively) but they were unable to predict them. Overall long-term survival was significantly shorter in patients with postoperative complications (9 vs 18 months). Postoperative complications were independently associated with poorer long-term survival (p=0.003, odds ratio: 3.261). CONCLUSIONS P-POSSUM and CPET are associated with postoperative complications but the possibility of using them for risk prediction requires further research. However, postoperative complications following double bypass have a significant impact on long-term survival and this type of surgery should therefore only be performed in specialised centres.

Sustained Isoprostane E2 Elevation, Inflammation and Fibrosis after Acute Ischaemia-Reperfusion Injury Are Reduced by Pregnane X Receptor Activation

Liver grafts donated after cardiac death are increasingly used to expand the donor pool but are prone to ischaemic-type biliary lesions. The anti-inflammatory effects of the activated pregnane X receptor have previously been shown to be beneficial in a number of inflammatory liver conditions. However, its role in reducing peri-portal inflammation and fibrosis following ischaemia-reperfusion injury has not been investigated. Hepatic injury and its response to pregnane X receptor activation was examined after partial hepatic ischaemia-reperfusion injury induced by surgically clamping the left and middle lobar blood vessels in rats. Molecular and pathological changes in the liver were examined over the following 28 days. Ischaemia-reperfusion injury resulted in transient cholestasis associated with microvillar changes in biliary epithelial cell membranes and hepatocellular injury which resolved within days after reperfusion. However, in contrast to chemically-induced acute liver injuries, this was followed by sustained elevation in isoprostane E2, peri-portal inflammation and fibrosis that remained unresolved in the ischaemic reperfused lobe for at least 28 days after clamping. Administration of pregnenolone-16α-carbonitrile—a rodent-specific pregnane X receptor activator—resulted in significant reductions in cholestasis, hepatic injury, ischaemic lobe isoprostane E2 levels, peri-portal inflammation and fibrosis. Hepatic ischaemia-reperfusion injury therefore results in inflammatory and fibrotic changes that persist well beyond the initial ischaemic insult. Drug-mediated activation of the pregnane X receptor reduced these adverse changes in rats, suggesting that the pregnane X receptor is a viable drug target to reduce ischaemic-type biliary lesions in recipients of liver transplants donated after cardiac death.

PTH-136 Activation of the pregnane X receptor (PXR) reduces the risk of early allograft dysfunction following liver transplantation

Introduction There has been increasing interest in the pregnane X receptor (PXR) in recent years as a promising drug target for the treatment of inflammatory liver disease. Our group has previously demonstrated that activation of the PXR reduces oxidative stress and fibrosis in a rat model of liver ischaemia-reperfusion injury. The aim of this study was to investigate the effect of PXR activation on early graft function in clinical liver transplantation. Method Data was collected retrospectively for all patients receiving liver transplants in a major transplant centre in the UK over the past three years. Patients were divided into high and low PXR activation groups based on the potency and number of PXR-activating drugs administered over the first week of transplantation. Early allograft dysfunction (EAD) was measured using a validated scoring system and was compared between the two groups in addition to graft and patient survival. Results Eighty three patients were considered eligible for inclusion in this study (n = 43 and 40 in the low and high PXR activation groups respectively). The incidence of EAD was significantly higher in the low PXR activation group (30.2% vs. 10% in the high PXR activation group; P < 0.05). No significant differences in graft or patient survival were demonstrated in this small cohort. Conclusion Activation of the PXR resulted in a reduction in EAD following liver transplantation in the clinical setting; consistent with our previous results in the animal model. Our findings have important implications for the potential reduction of graft loss following DCD liver transplantation. Disclosure of interest None Declared.

Reducing the risk of early allograft dysfunction in liver transplant recipients by activation of the pregnane x receptor (PXR)

Introduction: Hypothermic machine perfusion improves outcomes fromkidney transplantation, and molecular analyses of hypothermic machineperfusate (HMP) have the potential to identify biomarkers of organ viabilityprior to transplantation. Effective prediction of organ-specific outcomes prior totransplantation offers enormous advantages to the transplant surgeon, andmay increase the organ donor pool by allowing use of the ever-increasing‘extended criteria donors (ECD)’. MicroRNAs (miRNAs) have considerablepotential for use as biomarkers of numerous pathological processes, includingkidney disease. Our previous analysis of urine samples from renal transplantpatients with delayed graft function identified miRNAs miR-10a, -21, -29a, -221and -429 as potential biomarkers of kidney injury. This study aimed todetermine if expression of these miRNAs predicted early transplant outcomes.Methods: HMP samples were taken after 15 min, 1 and 2 h of perfusion for11 kidneys (ECD/DCD) placed on the LifePortprior to transplantation.Following RNA extraction using miRNeasy Mini Kits (Qiagen), cDNA wasgenerated using the High Capacity Reverse Transcription kit (Life Technolo-gies) and RT-qPCR was carried out using specific TaqMan microRNAdetection assays (Life Technologies). Clinical data including demographicsand eGFR at 6 months post transplantation were collected.Results: MiRNAs were readily detected and found to be stable in the HMPmedium from the 11 kidneys (ECD/DCD) included in this study. Expression ofmiR-10a, -21, -29a, -221 and -429 in HMP after 1 h of perfusion correlatedsignificantly with eGFR at 6 months post transplantation.Conclusion: MicroRNAs are emerging as important biomarkers in thecontext of kidney injury and transplantation. This study shows that expressionmiR-10a, -21, -29a, -221 and -429 in HMP is predictive of early outcomesfollowing kidney transplantation. Further studies are underway to confirm thesein larger cohorts

Hepatic artery embolisation for liver metastases from neuroendocrine disease

The 2013 Alpine Liver and Pancreatic Surgery meeting was held in Madonna di Campiglio, Italy. The meeting was organised by the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland. The following abstracts were selected for presentation at the meeting.

OC-022 Embolisation of inflow to allow safer liver resection—is more, better?

Introduction Portal vein embolisation (PVE) is now an established technique to increase the future liver volume/remnant (FLR) prior to liver resection. For those patients where hypertrophy is still considered insufficient complete uni-lateral embolisation incorporating both portal and hepatic artery embolisation (HAE) has been less frequently reported. The aim of this study was to evaluate the feasibility of sequential PV/HA embolisation to increase the FLR prior to liver resection. Methods All HPB patients are discussed at a weekly MDT meeting to decide on appropriate management decisions including the necessity for FLR augmentation. PVE is performed by initially obtaining a portogram by percutaneous trans-hepatic puncture. Selective embolisation of the necessary portal veins are then performed using a combination of coils and glue etc. Embolisation of Segment 4 PV branches are performed on a selective basis. HA embolisation is performed by mapping arterial inflow and selectively embolising the desired segments planned for resection while carefully preserving the FLR. The aim of this study was to evaluate the feasibility/safety of PVE with sequential HAE over a 5-year period (January 2006–May 2011). Results 50 patients (M:F = 38:12) underwent a right PVE; 33 (66%) progressed to liver resection. Reasons for inoperability (34%) following PVE (n=17) were (1) Small FLR, (n=6) all underwent HAE (with five proceeding to liver resection) (2) extra-hepatic disease (n=7) (3) progression of hepatic disease (n=4). The median FLR of those who progressed to resection following PVE, by CT volumetry, was 384.5 cc (330–490), significantly more than those who did not 237 cc (110–280) p=0.03. HAE increased the FLR by a further 99.8 cc (range 80.5–130 cc). An R0 resection was achieved in 25 patients (76%), including 4/5 (80%) of sequential patients. Following PVE and sequential embolisation; 9/33 (27%) and 3/5 (60%) suffered serious complications (Clavien-Dindo 3 or 4). There were six post operative deaths including 5/33 (15%) after PVE and 1 (20%) following sequential embolisation respectively. Conclusion PVE is an increasingly used technique to increase the FLR allowing a significant proportion of patients an R0 resection despite initially being considered inoperable. Nevertheless at least 20% of patients will also have progression of disease. Patients who do not achieve adequate hypertrophy can potentially have HA embolisation to increase the FLR by a further 100 cc but perhaps at the expense of increasing post-operative complications. Competing interests None declared.

PWE-147 Colorectal liver metastasis (CRLM): increasing role of laparoscopic liver resection—a single unit comparative analysis

Introduction Laparoscopic liver resection (LLR) is becoming increasingly used to reduce the morbidity of open liver resection The aim of this study was to compare outcomes after LLR with that of open liver resection. Methods From April 2007 onwards all patients who underwent either left lateral sectionectomy, left hemi-hepatectomy, segmentectomy and non-segmental resection for CRLM were identified from a prospectively maintained HPB database (open and LLR). Those having right hepatectomy were excluded from analysis as there were too few laparoscopic procedures for meaningful analysis. Comparisons between groups were made in terms of complications (graded using the Clavien-Dindo classification), duration of hospital stay and overall survival (OS). Statistical analysis was performed using Fisher Exact test for categorical variables, Mann–Whitney U test for non-parametric continuous variables and overall survival (OS) plotted with Kaplan–Meier curves (SPSS V.19). Results 78 patients had LLR for various indications (colorectal n=43, non-colorectal n=17, benign n=18). During the same period 94 patients had open equivalent procedures for CRLM (including 4 conversions from a lap procedure). Female patients were more likely to have a LLR compared to open (47% females, 24% males p=0.01). Grade 3 and 4 complications were more seen in the open group (8.5% vs 4.7%), however grade 1 and 2 complications were slightly higher in the laparoscopic group (18.6% vs 17.1%) Median stay was 4 days in LLR group (range 1–23), 7 days (range 3–95) in open group, p<0.001. R1 resections were less during second era of the study in LLR and comparable to the open group. At 3 years 91% of LLR and 72% of open group were alive. OS was similar (p=0.4). Conclusion Laparoscopic liver resection has shown benefits in terms of lower morbidity in our series when comparing it to equivalent open procedures. Long term follow-up will be needed to see if there is real advantage in OS and outcome. Competing interests None declared.

PWE-145 Prognostic factors influencing survival after liver resection for colorectal metastasis

Introduction A variety of factors have been identified in the literature which influence survival following resection of colorectal liver metastases (CRLM). The aim of this study was to identify those factors which influence survival in patients undergoing resection of CRLM in a UK centre. Methods All patients having liver resection for CRLM during an 11-year period up to 2011 were identified from a prospectively maintained database and relevant clinical data retrieved from case records. Prognostic factors analysed included tumour size (>5 cm or <5 cm), lymph node status of primary tumour, margin positivity R1 (<1 mm) or R0, neo-adjuvant chemotherapy (for liver), tumour differentiation, number of liver metastasis (4 or more), preoperative CEA (>200 or <200) and whether metastases were synchronous (ie, diagnosed <12 months) or metachronous to the primary tumour. Overall survival (OS) was compared with Kaplan–Meier plots, log rank test. Multi-variate analysis was performed using Cox regression model (SPSS V.19). p<0.05 considered significant. Results 432 patients underwent resection of CRLM during this period (67% male; mean age 64.5 years). The overall 5-year survival in this series was 43%. A pre-op CEA>200 was present in 10% of patients and was associated with a poorer 5-year OS (24% vs 45%; p<0.001). A resection margin <1 mm was present in 16% of patients and this had a negative impact on 5 yr OS (15% vs 47%; p<0.001). Tumour differentiation, number, size, presence of biliary or vascular invasion, relationship to primary disease, nodal status of primary, or the use of neoadjuvant chemotherapy had no impact on OS. Multi-variate analysis identified only the presence of a positive resection margin (OR 1.75; p<0.05) and a pre-op CEA>200 (OR 1.88; p<0.01) as independent predictors of poorer OS. Conclusion Despite the wide variety of prognostic factors reported in the literature we were only able to identify a pre-op CEA>200 and the presence of tumour within 1 mm of the resection margin as being of value in predicting survival. These variables are likely to identify patients who may benefit from intensive follow-up to enable early adjuvant chemotherapy postoperatively. Competing interests None declared.