Fish oil supplement use modifies the relationship between dietary oily fish intake and plasma n-3 PUFA levels: an analysis of the UK Biobank.

Observational evidence linking dietary n-3 PUFA intake and health outcomes is limited by a lack of robust validation of dietary intake using blood n-3 PUFA levels and potential confounding by fish oil supplement (FOS) use. We investigated the relationship between oily fish intake, FOS use and plasma n-3 PUFA levels in 121 650 UK Biobank (UKBB) participants. Ordinal logistic regression models, adjusted for clinical and lifestyle factors, were used to quantify the contribution of dietary oily fish intake and FOS use to plasma n-3 PUFA levels (measured by NMR spectroscopy). Oily fish intake and FOS use were reported by 38 % and 31 % of participants, respectively. Increasing oily fish intake was associated with a higher likelihood of FOS use (P < 0·001). Oily fish intake ≥ twice a week was the strongest predictor of high total n-3 PUFA (OR 6·7 (95 % CI 6·3, 7·1)) and DHA levels (6·6 (6·3, 7·1). FOS use was an independent predictor of high plasma n-3 PUFA levels (2·0 (2·0, 2·1)) with a similar OR to that associated with eating oily fish < once a week (1·9 (1·8, 2·0)). FOS use was associated with plasma n-3 PUFA levels that were similar to individuals in the next highest oily fish intake category. In conclusion, FOS use is more common in frequent fish consumers and modifies the relationship between oily fish intake and plasma n-3 PUFA levels in UKBB participants. If unaccounted for, FOS use may confound the relationship between dietary n-3 PUFA intake, blood levels of n-3 PUFAs and health outcomes.

Randomised, placebo-controlled, phase 3 trial of the effect of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on colorectal cancer recurrence and survival after surgery for resectable liver metastases: EPA for Metastasis Trial 2 (EMT2) study protocol.

INTRODUCTION: There remains an unmet need for safe and cost-effective adjunctive treatment of advanced colorectal cancer (CRC). The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is safe, well-tolerated and has anti-inflammatory as well as antineoplastic properties. A phase 2 randomised trial of preoperative EPA free fatty acid 2 g daily in patients undergoing surgery for CRC liver metastasis showed no difference in the primary endpoint (histological tumour proliferation index) compared with placebo. However, the trial demonstrated possible benefit for the prespecified exploratory endpoint of postoperative disease-free survival. Therefore, we tested the hypothesis that EPA treatment, started before liver resection surgery (and continued postoperatively), improves CRC outcomes in patients with CRC liver metastasis. METHODS AND ANALYSIS: The EPA for Metastasis Trial 2 trial is a randomised, double-blind, placebo-controlled, phase 3 trial of 4 g EPA ethyl ester (icosapent ethyl (IPE; Vascepa)) daily in patients undergoing liver resection surgery for CRC liver metastasis with curative intent. Trial treatment continues for a minimum of 2 years and maximum of 4 years, with 6 monthly assessments, including quality of life outcomes, as well as annual clinical record review after the trial intervention. The primary endpoint is CRC progression-free survival. Key secondary endpoints are overall survival, as well as the safety and tolerability of IPE. A minimum 388 participants are estimated to provide 247 CRC progression events during minimum 2-year follow-up, allowing detection of an HR of 0.7 in favour of IPE, with a power of 80% at the 5% (two sided) level of significance, assuming drop-out of 15%. ETHICS AND DISSEMINATION: Ethical and health research authority approval was obtained in January 2018. All data will be collected by 2025. Full trial results will be published in 2026. Secondary analyses of health economic data, biomarker studies and other translational work will be published subsequently. TRIAL REGISTRATION NUMBER: NCT03428477.

Ursodeoxycholic acid in the management of symptomatic gallstone disease: systematic review and clinician survey.

BACKGROUND: Symptomatic gallstones are common. Ursodeoxycholic acid (UDCA) is a bile acid that dissolves gallstones. There is increasing interest in UDCA for symptomatic gallstones, particularly in those unfit for surgery. METHOD: A UK clinician survey of use and opinions about UDCA in symptomatic gallstones was performed, assessing clinicians' beliefs and perceptions of UDCA effectiveness. A systematic review was performed in accordance with the PRISMA guidelines. PubMed, MEDLINE, and Embase databases were searched for studies of UDCA for symptomatic gallstones (key terms included 'ursodeoxycholic acid'; 'UDCA'; 'biliary pain'; and 'biliary colic'). Information was assessed by two authors, including bias assessment, with independent review of conflicts. RESULTS: Overall, 102 clinicians completed the survey, and 42 per cent had previous experience of using UDCA. Survey responses demonstrated clinical equipoise surrounding the benefit of UDCA for the management of symptomatic gallstones, with no clear consensus for benefit or non-benefit; however, 95 per cent would start using UDCA if there was a randomized clinical trial (RCT) demonstrating a benefit. Eight studies were included in the review: four RCTs, three prospective studies, and one retrospective study. Seven of eight studies were favourable of UDCA for biliary pain. Outcomes and follow-up times were heterogenous, as well as comparator type, with only four of eight studies comparing with placebo. CONCLUSION: Evidence for UDCA in symptomatic gallstones is scarce and heterogenous. Clinicians currently managing symptomatic gallstone disease are largely unaware of the benefit of UDCA, and there is clinical equipoise surrounding the benefit of UDCA. Level 1 evidence is required by clinicians to support UDCA use in the future.

Incidence and risk factors for anastomotic bile leakage in hepatic resection with bilioenteric reconstruction - A international multicenter study.

BACKGROUND: Anastomotic leak (AL) after bilioenteric reconstruction (BR) is a feared complication after bile duct resection, especially in combination with liver resection. Literature on surgical outcome is sparse. This study aimed to determine the incidence and risk factors for AL after combined liver and bile duct resection with a focus on operative or endoscopic reinterventions. METHODS: Data from consecutive patients who underwent liver resection and BR between 2004 and 2018 in 11 academic institutions in Europe were collected from prospectively maintained databases. RESULTS: Within 921 patients, AL rate was 5.4% with a 30d mortality of 9.6%. Pringle maneuver (p<0.001),postoperative external biliary (p=0.007) and abdominal drainage (p<0.001) were risk factors for clinically relevant AL. Preoperative biliary drainage (p<0.001) was not associated with a higher rate of AL. AL was more frequent in stented patients (76.5%) compared to PTCD (17.6%) or PTCD+stent (5.9%,p=0.017). AL correlated with increased incidence of postoperative liver failure (p=0.036), cholangitis, hemorrhage and sepsis (all p<0.001). CONCLUSION: This multicenter data provides the largest series to date of LR with BR and could help in the management of these patients which are often challenging and hampering the patients' postoperative course negatively.

Does ALT Correlate with Survival After Liver Resection for Colorectal Liver Metastases?

Background: The pringle manoeuvre is commonly used during hepatectomy, which may cause ischaemia-reperfusion injury and transient liver dysfunction. Post-operative liver transaminases are often used to assess ischaemia-reperfusion injury, although there is conflicting evidence on survival outcomes. The primary aim was to assess post-operative alanine aminotransferase (ALT) with survival outcomes. Secondary aims were to assess ALT level with the length of stay and overall complications. Methods: Post-operative day 2 ALT levels of five times the upper limit of normal (i.e. 280 U/L) were considered as clinically significant transaminitis. Kaplan-Meier survival curves were studied using log-rank analysis to identify the predictors of overall survival (OS) and recurrence-free survival (RFS). Results: Out of 752 patients who underwent hepatectomy, 527 (70.1%) patients had low ALT (<280 U/L) and 225 (29.9%) patients had high ALT on day 2 post-op. Post-operative ALT did not affect OS (P = 0.883) or RFS (P = 0.063). Factors associated with a worse OS and RFS on multivariate analysis were pre-operative chemotherapy, number of tumours and largest tumour size (>4 cm). A high post-operative ALT was not associated with the increased length of stay or more complications. Conclusions: Post-operative ALT does not affect survival outcomes post-hepatectomy for colorectal liver metastases.

Intravenous Oncolytic Vaccinia Virus Therapy Results in a Differential Immune Response between Cancer Patients.

Pexa-Vec is an engineered Wyeth-strain vaccinia oncolytic virus (OV), which has been tested extensively in clinical trials, demonstrating enhanced cytotoxic T cell infiltration into tumours following treatment. Favourable immune consequences to Pexa-Vec include the induction of an interferon (IFN) response, followed by inflammatory cytokine/chemokine secretion. This promotes tumour immune infiltration, innate and adaptive immune cell activation and T cell priming, culminating in targeted tumour cell killing, i.e., an immunologically 'cold' tumour microenvironment is transformed into a 'hot' tumour. However, as with all immunotherapies, not all patients respond in a uniformly favourable manner. Our study herein, shows a differential immune response by patients to intravenous Pexa-Vec therapy, whereby some patients responded to the virus in a typical and expected manner, demonstrating a significant IFN induction and subsequent peripheral immune activation. However, other patients experienced a markedly subdued immune response and appeared to exhibit an exhausted phenotype at baseline, characterised by higher baseline immune checkpoint expression and regulatory T cell (Treg) levels. This differential baseline immunological profile accurately predicted the subsequent response to Pexa-Vec and may, therefore, enable the development of predictive biomarkers for Pexa-Vec and OV therapies more widely. If confirmed in larger clinical trials, these immunological biomarkers may enable a personalised approach, whereby patients with an exhausted baseline immune profile are treated with immune checkpoint blockade, with the aim of reversing immune exhaustion, prior to or alongside OV therapy.

Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anticancer Immunity in Patients.

Improving the chances of curing patients with cancer who have had surgery to remove metastatic sites of disease is a priority area for cancer research. Pexa-Vec (Pexastimogene Devacirepvec; JX-594, TG6006) is a principally immunotherapeutic oncolytic virus that has reached late-phase clinical trials. We report the results of a single-center, nonrandomized biological end point study (trial registration: EudraCT number 2012-000704-15), which builds on the success of the presurgical intravenous delivery of oncolytic viruses to tumors. Nine patients with either colorectal cancer liver metastases or metastatic melanoma were treated with a single intravenous infusion of Pexa-Vec ahead of planned surgical resection of the metastases. Grade 3 and 4 Pexa-Vec-associated side effects were lymphopaenia and neutropaenia. Pexa-Vec was peripherally carried in plasma and was not associated with peripheral blood mononuclear cells. Upon surgical resection, Pexa-Vec was found in the majority of analyzed tumors. Pexa-Vec therapy associated with IFNα secretion, chemokine induction, and resulted in transient innate and long-lived adaptive anticancer immunity. In the 2 patients with significant and complete tumor necrosis, a reduction in the peripheral T-cell receptor diversity was observed at the time of surgery. These results support the development of presurgical oncolytic vaccinia virus-based therapies to stimulate anticancer immunity and increase the chances to cure patients with cancer.

Omega-3 polyunsaturated fatty acids: moving towards precision use for prevention and treatment of colorectal cancer.

Data from experimental studies have demonstrated that marine omega-3 polyunsaturated fatty acids (O3FAs) have anti-inflammatory and anticancer properties. In the last decade, large-scale randomised controlled trials of pharmacological delivery of O3FAs and prospective cohort studies of dietary O3FA intake have continued to investigate the relationship between O3FA intake and colorectal cancer (CRC) risk and mortality. Clinical data suggest that O3FAs have differential anti-CRC activity depending on several host factors (including pretreatment blood O3FA level, ethnicity and systemic inflammatory response) and tumour characteristics (including location in the colorectum, histological phenotype (eg, conventional adenoma or serrated polyp) and molecular features (eg, microsatellite instability, cyclooxygenase expression)). Recent data also highlight the need for further investigation of the effect of O3FAs on the gut microbiota as a possible anti-CRC mechanism, when used either alone or in combination with other anti-CRC therapies. Overall, these data point towards a precision approach to using O3FAs for optimal prevention and treatment of CRC based on mechanistic understanding of host, tumour and gut microbiota factors that predict anticancer activity of O3FAs.

A multi-center post-market clinical study to confirm safety and performance of PuraStat® in the management of bleeding during open liver resection.

BACKGROUND: PuraStat® is a non-bioactive haemostatic agent that has demonstrated efficacy in a number of different surgical procedures. We performed a prospective multi-centre post-market study to evaluate the efficacy and safety of PuraStat® in liver resections performed for metastatic tumors. METHODS: This was a prospective cohort study. Patients undergoing liver resection for metastatic tumor were screened for eligibility, and included if they were ≥18 years old, undergoing open liver resection, had normal liver function, and required application of PuraStat® for haemostasis where standard haemostatic techniques were either insufficient or impractical. The primary endpoint was "time to haemostasis" (TTH). Secondary endpoints included blood loss, total postoperative drainage volume, transfusion of blood products, and ease of use. RESULTS: Eighty patients were included for analysis in the intention to treat population. 207 bleeding sites were treated with PuraStat. Of these, 190 (91.7%) bleeding sites reached haemostasis after PuraStat® application. Mean TTH (mm:ss) was 1:01 (SD 1:06, range 0:09-6:55). Ease of use of the product was described as either "excellent" or "good" in 78 (98.8%) patients. No serious adverse events were identified. CONCLUSION: This study confirms the safety, efficacy and ease of use of PuraStat® in the management of bleeding in liver surgery.

Making large-scale surgical trials possible: collaboration and the role of surgical trainees.

BACKGROUND: Recruitment to surgical randomised controlled trials (RCTs) can be challenging. The Sunflower study is a large-scale multi-centre RCT that seeks to establish the clinical and cost effectiveness of pre-operative imaging versus expectant management in patients with symptomatic gallstones undergoing laparoscopic cholecystectomy at low or moderate risk of common bile duct stones. Trials such as Sunflower, with a large recruitment target, rely on teamworking. Recruitment can be optimised by embedding a QuinteT Recruitment Intervention (QRI). Additionally, engaging surgical trainees can contribute to successful recruitment, and the NIHR Associate Principal Investigator (API) scheme provides a framework to acknowledge their contributions. METHODS: This was a mixed-methods study that formed a component part of an embedded QRI for the Sunflower RCT. The aim of this study was to understand factors that supported and hindered the participation of surgical trainees in a large-scale RCT and their participation in the API scheme. It comprised semi-structured telephone interviews with consultant surgeons and surgical trainees involved in screening and recruitment of patients, and descriptive analysis of screening and recruitment data. Interviews were analysed thematically to explore the perspectives of-and roles undertaken by-surgical trainees. RESULTS: Interviews were undertaken with 34 clinicians (17 consultant surgeons, 17 surgical trainees) from 22 UK hospital trusts. Surgical trainees contributed to patient screening, approaches and randomisation, with a major contribution to the randomisation of patients from acute admissions. They were often encouraged to participate in the study by their centre principal investigator, and career development was a typical motivating factor for their participation in the study. The study was registered with the API scheme, and a majority of the trainees interviewed (n = 14) were participating in the scheme. CONCLUSION: Surgical trainees can contribute substantial activity to a large-scale multi-centre RCT. Benefits of trainee engagement were identified for trainees themselves, for local sites and for the study as a whole. The API scheme provided a formal framework to acknowledge engagement. Ensuring that training and support for trainees are provided by the trial team is key to optimise success for all stakeholders.

Randomised controlled trial to establish the clinical and cost-effectiveness of expectant management versus preoperative imaging with magnetic resonance cholangiopancreatography in patients with symptomatic gallbladder disease undergoing laparoscopic cholecystectomy at low or moderate risk of common bile duct stones (The Sunflower Study): a study protocol.

INTRODUCTION: Surgery to remove the gallbladder (laparoscopic cholecystectomy (LC)) is the standard treatment for symptomatic gallbladder disease. One potential complication of gallbladder disease is that gallstones can pass into the common bile duct (CBD) where they may remain dormant, pass spontaneously into the bowel or cause problems such as obstructive jaundice or pancreatitis. Patients requiring LC are assessed preoperatively for their risk of CBD stones using liver function tests and imaging. If the risk is high, guidelines recommend further investigation and treatment. Further investigation of patients at low or moderate risk of CBD stones is not standardised, and the practice of imaging the CBD using magnetic resonance cholangiopancreatography (MRCP) in these patients varies across the UK. The consequences of these decisions may lead to overtreatment or undertreatment of patients. METHODS AND ANALYSIS: We are conducting a UK multicentre, pragmatic, open, randomised controlled trial with internal pilot phase to compare the effectiveness and cost-effectiveness of preoperative imaging with MRCP versus expectant management (ie, no preoperative imaging) in adult patients with symptomatic gallbladder disease undergoing urgent or elective LC who are at low or moderate risk of CBD stones. We aim to recruit 13 680 patients over 48 months. The primary outcome is any hospital admission within 18 months of randomisation for a complication of gallstones. This includes complications of endoscopic retrograde cholangiopancreatography for the treatment of gallstones and complications of LC. This will be determined using routine data sources, for example, National Health Service Digital Hospital Episode Statistics for participants in England. Secondary outcomes include cost-effectiveness and patient-reported quality of life, with participants followed up for a median of 18 months. ETHICS AND DISSEMINATION: This study received approval from Yorkshire & The Humber - South Yorkshire Research Ethics Committee. Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN10378861.

Luminal Bioavailability of Orally Administered ω-3 PUFAs in the Distal Small Intestine, and Associated Changes to the Ileal Microbiome, in Humans with a Temporary Ileostomy.

BACKGROUND: Oral administration of purified omega-3 (ω-3) PUFAs is associated with changes to the fecal microbiome. However, it is not known whether this effect is associated with increased PUFA concentrations in the gut. OBJECTIVES: We investigated the luminal bioavailability of oral ω-3 PUFAs (daily dose 1 g EPA and 1g DHA free fatty acid equivalents as triglycerides in soft-gel capsules, twice daily) and changes to the gut microbiome, in the ileum. METHODS: Ileostomy fluid (IF) and blood were obtained at baseline, after first capsule dosing (median 2 h), and at a similar time after final dosing on day 28, in 11 individuals (median age 63 y) with a temporary ileostomy. Fatty acids were measured by LC-tandem MS. The ileal microbiome was characterized by 16S rRNA PCR and Illumina sequencing. RESULTS: There was a mean 6.0 ± 9.8-fold and 6.6 ± 9.6-fold increase in ileal EPA and DHA concentrations (primary outcome), respectively, at 28 d, which was associated with increased RBC ω-3 PUFA content (P ≤ 0.05). The first oral dose did not increase the ileal ω-3 PUFA concentration except in 4 individuals, who displayed high luminal EPA and DHA concentrations, which reduced to concentrations similar to the overall study population at day 28, suggesting physiological adaptation. Bacteroides, Clostridium, and Streptococcus were abundant bacterial genera in the ileum. Ileal microbiome variability over time and between individuals was large, with no consistent change associated with acute ω-3 PUFA dosing. However, high concentrations of EPA and DHA in IF on day 28 were associated with higher abundance of Bacteroides (r2 > 0.86, P < 0.05) and reduced abundance of other genera, including Actinomyces (r2 > 0.94, P < 0.05). CONCLUSIONS: Oral administration of ω-3 PUFAs leads to increased luminal ω-3 PUFA concentrations and changes to the microbiome, in the ileum of individuals with a temporary ileostomy. This study is registered on the ISRCTN registry as ISRCTN14530452.

Outcomes of liver resection for hepatocellular carcinoma in octogenarians.

BACKGROUND: There is a dearth of information about operative outcomes in patients ≥80 years for hepatocellular carcinoma (HCC) from Western institutions. We compare the result of HCC resections in patients <80 years vs. patients ≥80 years from our institution in the UK. METHODS: We conducted a retrospective review of all patients undergoing liver resections for HCC between 2005 and 2015. Demographics, comorbidities, morbidity, mortality and survival were compared between the two age groups. RESULTS: 200 patients underwent resection for HCC in this time period. Nineteen patients were ≥80 years and 181 were <80 years. Comorbidities measured by the Charlson Comorbidity Index were significantly higher in the ≥80 group (p < 0.0001). There was no significant difference in the extent of resection in the two groups. Morbidity and mortality between the <80 years and the ≥80 years group were not significantly different (morbidity 27% vs.16%; p = 0.29) (mortality 7% vs. 0%; p = 0.11). The one-year (83.4% vs. 88.2%; p = 0.83), five-year (56.3% vs. 55.8%; p = 0.83) and the overall survival rate rates (887 days vs. 1035 days; p = 0.66) were not significantly different between the groups. DISCUSSION: Liver resection should not be precluded based on age alone; with good outcomes in patients ≥80 years justifying surgery.

The impact of age on post-operative liver function following right hepatectomy: a retrospective, single centre experience.

BACKGROUND: An increasing number of patients undergoing liver resection are of advancing age. The impact of ageing on liver regeneration and post-operative outcomes following a major resection are uncertain. We aimed to investigate risk factors for patients who developed Post Hepatectomy Liver Failure (PHLF) following right hepatectomy with age as the primary risk-factor. METHOD: Patients undergoing right hepatectomy between July 2004-July 2018 were included. ROC analysis was performed to identify at which age PHLF development-risk increased. Secondary endpoints were length of stay (LOS), complications, and cost. RESULTS: 332-patients were included. ROC demonstrated a cut-off age of 75-years in which PHLF risk increased. >75 there was an increased risk of PHLF (35% >75yrs vs. 7% <75yrs (p = <0.001), OR = 8.8 (95% CI = 3.6-21)) There was no difference between the age groups for any other PHLF risk factor. Patients >75yrs had longer LOS (11-days vs. 7-days (p = 0.04). Patients who developed PHLF had increased hospital costs: £10,987.50 (£6175-£46,050) vs. £2575 (£900-£46,050 p = 0.01). CONCLUSIONS: Patients >75yrs have increased risk of developing PHLF after right hepatectomy, contributing to increased mortality and economic burden. Pre-operatively identifying patients at-risk of PHLF is important to consider liver volume optimization strategies and improve outcomes.

Ablation or Resection for Colorectal Liver Metastases? A Systematic Review of the Literature.

Background: Successful use of ablation for small hepatocellular carcinomas (HCC) has led to interest in the role of ablation for colorectal liver metastases (CRLM). However, there remains a lack of clarity about the use of ablation for colorectal liver metastases (CRLM), specifically its efficacy compared with hepatic resection. Methods: A systematic review of the literature on ablation or resection of colorectal liver metastases was performed using MEDLINE, Cochrane Library, and Embase until December 2018. The aim of this study was to summarize the evidence for ablation vs. resection in the treatment of CRLM. Results: This review identified 1,773 studies of which 18 were eligible for inclusion. In the majority of the studies, overall survival (OS) and disease-free survival (DFS) were significantly higher and local recurrence (LR) rates were significantly lower in the resection groups. On subgroup analysis of solitary CRLM, resection was associated with improved OS, DFS, and reduced LR. Three series assessed the outcome of resection vs. ablation for technically resectable CRLM, and showed improved outcome in the resection group. In fact, there were no studies showing a survival advantage of ablation compared to resection in the treatment of CRLM. Conclusions: Resection remains the "gold standard" in the treatment of CRLM and should not be replaced by ablation at present. This review supports the use of ablation only as an adjunct to resection and as a single treatment option when resection is not safely possible.

Variation in the Use of Resection for Colorectal Cancer Liver Metastases.

OBJECTIVE: The aim of this study was to investigate variation in the frequency of resections for colorectal cancer liver metastases across the English NHS. BACKGROUND: Previous research has shown significant variation in access to liver resection surgery across the English NHS. This study uses more recent data to identify whether inequalities in access to liver resection still persist. METHODS: All adults who underwent a major resection for colorectal cancer in an NHS hospital between 2005 and 2012 were identified in the COloRECTal cancer data Repository (CORECT-R). All episodes of care, occurring within 3 years of the initial bowel operation, corresponding to liver resection were identified. RESULT: During the study period 157,383 patients were identified as undergoing major resection for a colorectal tumor, of whom 7423 (4.7%) underwent ≥1 liver resections. The resection rate increased from 4.1% in 2005, reaching a plateau around 5% by 2012. There was significant variation in the rate of liver resection across hospitals (2.1%-12.2%). Patients with synchronous metastases who have their primary colorectal resection in a hospital with an onsite specialist hepatobiliary team were more likely to receive a liver resection (odds ratio 1.22; 95% confidence interval, 1.10-1.35) than those treated in one without. This effect was absent in resection for metachronous metastases. CONCLUSIONS: This study presents the largest reported population-based analysis of liver resection rates in colorectal cancer patients. Significant variation has been observed in patient and hospital characteristics and the likelihood of patients receiving a liver resection, with the data showing that proximity to a liver resection service is as important a factor as deprivation.

Use of a modified Delphi approach to develop research priorities in HPB surgery across the United Kingdom.

BACKGROUND: Research prioritisation can help identify clinically relevant questions and encourage high-quality, patient-centred research. Delphi methodology aims to develop consensus opinion within a group of experts, with recent Delphi projects helping to define the research agenda and funding within several medical and surgical specialties. METHODS: All members of the Association of Upper Gastrointestinal Surgeons (AUGIS) were asked to submit clinical research questions using an online survey (Phase 1). Two consecutive rounds of Delphi prioritisation by multidisciplinary HPB healthcare professionals (Phase 2) were undertaken to establish a final list of the most highly prioritised research questions. A multidisciplinary steering committee analysed the results of each phase. RESULTS: Ninety-three HPB-focussed questions were identified in Phase 1, with thirty-seven questions of sufficient priority to enter a further prioritisation round. A final group of 11 questions considered highest priority were identified. The most highly ranked research questions related to treatment pathways, operative strategies and the impact of HPB procedures on quality of life, particularly for malignant disease. CONCLUSION: Expert consensus has identified research priorities within the UK HPB surgical community over the coming years. Funding applications, to establish well-designed, high quality collaborative research are now required to address these questions.

Segment 2/3 Hypertrophy is Greater When Right Portal Vein Embolisation is Extended to Segment 4 in Patients with Colorectal Liver Metastases: A Retrospective Cohort Study.

BACKGROUND: In patients with colorectal cancer liver metastases (CRLM), right portal vein embolisation (RPVE) is used to increase the volume of the future remnant liver (FRL) before major hepatic resection. It is not established whether embolisation of segment 4 in addition RPVE (RPVE + 4) induces greater hypertrophy of the FRL. Limitations of prior studies include heterogenous populations and use of hypertrophy metrics sensitive to baseline variables. METHODS: From 2010 to 2015, consecutive patients undergoing RPVE or RPVE + 4 for CRLM, who had not undergone prior major hepatic resection and in whom imaging was available, were included in a retrospective study. Data were extracted from hospital electronic records. Volumetric assessments of segments 2-3 were made on cross-sectional imaging before and after embolisation and corrected for standardised liver volume. RESULTS: Ninety-nine patients underwent PVE, and 60 met the inclusion criteria. Thirty-eight patients underwent RPVE, and 22 underwent RPVE + 4. Forty-five patients had undergone median 6 cycles of prior chemotherapy. Eighteen patients had FRL metastases at PVE, and 16 had undergone subsegmental metastasectomy in the FRL. Assessments of the degree of hypertrophy (DH) of segments 2/3 were made at median 35 (interquartile range 30-49) days after PVE. RPVE + 4 resulted in a significantly greater increase in DH than RPVE (7.7 ± 1.8% vs 11.3 ± 2.6%, p = 0.011). No confounding association between baseline variables and the decision to undertake RPVE or RPVE + 4 was identified. Median survival was 2.4 years and was not influenced by segment 4 embolisation. CONCLUSION: RPVE + 4 results in greater DH of segments 2/3 than RPVE in people with CLRM.