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.

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.

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.

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.

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.

A Randomized Controlled Trial Comparing Epidural Analgesia Versus Continuous Local Anesthetic Infiltration Via Abdominal Wound Catheter in Open Liver Resection.

AIM: To compare outcomes following open liver resection (OLR) between patients receiving thoracic epidural (EP) versus abdominal wound catheters plus patient-controlled analgesia (AWC-PCA). METHOD: Patients were randomized 1:1 to either EP or AWC-PCA within an enhanced recovery protocol. Primary outcome was length of stay (LOS), other variables included functional recovery, pain scores, peak flow, vasopressor and fluid requirements, and postoperative complications. RESULTS: Between April 2015 and November 2017, 83 patients were randomized to EP (n = 41) or AWC-PCA (n = 42). Baseline demographics were comparable. No difference was noted in LOS (EP 6 d (3-27) vs AWC-PCA 6 d (3-66), P = 0.886). Treatment failure was 20% in the EP group versus 7% in the AWC-PCA (P = 0.09). Preoperative anesthetic time was shorter in the AWC-PCA group, 49 minutes versus 62 minutes (P = 0.003). EP patients required more vasopressor support immediately postoperatively on day 0 (14% vs 54%, P = <0.001) and day 1 (5% vs 23%, P = 0.021). Pain scores were greater on day 0, afternoon of day 1 and morning of day 2 in the AWC-PCA group however were regarded as low at all time points. No other significant differences were noted in IV fluid requirements, nausea/sedation scores, days to open bowels, length of HDU, and postoperative complications. CONCLUSION: AWC-PCA was associated with reduced treatment failure and a reduced vasopressor requirement than EP up to 2 days postoperatively. While the use of AWC-PCA did not translate into a shorter LOS in this study, it simplified patient management after OLR. EP cannot be routinely recommended following open liver resections.

Impact of blood transfusion on outcomes following resection for colorectal liver metastases in the modern era.

BACKGROUND: Evidence suggests that perioperative blood loss and blood transfusions are associated with poorer long-term outcomes in patients undergoing other oncological surgery. The aim of this study was to determine the long-term outcomes of patients requiring a blood transfusion post-hepatectomy for colorectal liver metastases (CRLM). METHODS: This is a retrospective review from 2005 to 2012. Overall survival (OS) and recurrence-free survival (RFS) were assessed using Kaplan-Meier curves. Red blood cell transfusion (RBCT) and other clinic-pathological parameters were handled as covariates for Cox regression analysis. RESULTS: Six hundred and ninety patients were included. Median follow-up was 33 months. Sixty-four (9.3%) patients required a perioperative RBCT. RBCT was a predictor for decreased OS (median 41 versus 49 months, P = 0.04). However, on multivariate regression analyses preoperative chemotherapy, post-operative complications and Clinical Risk Score were independently associated with reduced OS, though RBCT was not. There was no association between RBCT and RFS (median 15 versus 17 months, P = 0.28). CONCLUSIONS: RBCT is not independently associated with a poorer OS.

A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota.

OBJECTIVE: Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). DESIGN: A randomised, open-label, cross-over trial of 8 weeks' treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week 'washout' period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry. RESULTS: Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or ß diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium, Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects. CONCLUSION: Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure. TRIAL REGISTRATION NUMBER: ISRCTN18662143.

Radical operation for hilar cholangiocarcinoma in comparable Eastern and Western centers: Outcome analysis and prognostic factors.

BACKGROUND: Extensive resection for hilar cholangiocarcinoma is the most effective treatment, but high morbidity and poor prognosis remain concerns. Previous data have shown marked differences in outcomes between comparable Eastern and Western centers. We compared the outcomes of the management for hilar cholangiocarcinoma at one Japanese and one British institution with comparable experience. METHODS: Of 298 consecutive patients with hilar cholangiocarcinoma evaluated at Hirosaki University Hospital, Japan and St. James's University Hospital, Leeds, UK, 183 underwent radical resection. Clinicopathologic variables and postoperative outcomes were compared. RESULTS: Significant differences were not observed between the Hirosaki and Leeds cohorts in overall outcomes despite several differences in the patient characteristics. Although there was a difference in 90-day mortality (2.5% vs 13.6%, respectively), disease-specific 5-year survival rates were 32.8% and 31.9%, respectively (P = .767). Multivariate analysis identified trisectionectomy (odds ratio = 2.32; P = .010), combined pancreatoduodenectomy (odds ratio = 7.88; P = .010), and perioperative blood transfusion (odds ratio = 1.88; P = .045) were associated with postoperative major complications, while preoperative biliary drainage associated with postoperative major complications, while preoperative biliary drainage (risk ratio = 2.21; P = .018), perioperative blood transfusion (risk ratio = 1.58; P = .029), lymph node metastasis (risk ratio = 2.00; P = .002), moderate/poorly differentiated tumor (risk ratio = 1.72; P = .029), microvascular invasion (risk ratio = 1.63; P = .046), and R1 resection (risk ratio = 1.90; P = .005) were risk factors for poor survival. CONCLUSION: Disease-specific survival and prognostic factors were similar in both centers. Meticulous operative technique to avoid perioperative blood transfusion may improve long-term survival.

A cost-effective analysis of fibrin sealants versus no sealant following open right hemihepatectomy for colorectal liver metastases.

BACKGROUND: There is paucity of data regarding the cost-effectiveness of fibrin sealants during liver surgery. This study aimed to assess the cost-effectiveness of fibrin sealants following right hemihepatectomy for colorectal liver metastases. METHOD: A prospectively maintained database between 2004 and 2013 was reviewed to identify patients who underwent a right hemihepatectomy with and without fibrin sealant application. Perioperative and post-operative outcomes were analysed to assess its cost-effectiveness. RESULTS: One hundred and sixty-three right hemihepatectomies were performed, of which 79 were in the fibrin sealant treatment group and 84 were in the no sealant group. No difference was seen between fibrin sealant and no sealant with regard to bile leak (P = 0.366), intra-abdominal collections (P = 0.200) and overall post-operative complications (P = 0.480). Operating costs were significantly cheaper in the no sealant group (P = 0.010). There was no difference seen in median post-operative stay between fibrin sealant versus no treatment (8 versus 9 days, P = 0.327), median total bed cost (£3900 versus £4300, P = 0.400), mean transfusion cost per patient (P = 0.201) and overall cost (£6706.15 versus £6555.80, P = 0.792). CONCLUSION: Fibrin sealant application to cut surface during liver surgery confers no cost benefit and their routine use may not be recommended.

The effect of Liver Transplantation on the quality of life of the recipient's main caregiver - a systematic review.

Liver transplantation (LT) is a transformative, life-saving procedure with life-long sequale for patients and their caregivers. The impact of LT on the patient's main caregiver can be underestimated. We carried out a systematic review of the impact of LT on the Health-Related Quality of Life (HRQL) of LT patients' main caregivers. We searched 13 medical databases from 1996 to 2015. We included studies with HRQL data on caregivers of patients following LT then quality assessed and narratively synthesized the findings from these studies. Of 7076 initial hits, only five studies fell within the scope of this study. In general, they showed caregiver burden persisted in the early period following LT. One study showed improvements, however, the other four showed caregiver's levels of stress, anxiety and depression, remained similar or got worse post-LT and remained above that of the normal population. It was suggested that HRQL of the patient impacted on the caregiver and vice versa and may be linked to patient outcomes. No data were available investigating which groups were at particular risk of low HRQL following LT or if any interventions could improve this. The current information about LT caregivers' needs and factors that impact on their HRQL are not adequately defined. Large studies are needed to examine the effects of LT on the patients' family and caregivers to understand the importance of caregiver support to maximize outcomes of LT for the patient and their caregivers.

Measurement of red blood cell eicosapentaenoic acid (EPA) levels in a randomised trial of EPA in patients with colorectal cancer liver metastases.

We investigated red blood cell (RBC) PUFA profiles, and the predictive value of RBC EPA content for tumour EPA exposure and clinical outcomes, in the EMT study, a randomised trial of EPA in patients awaiting colorectal cancer (CRC) liver metastasis surgery (Cockbain et al., 2014) [8]. There was a significant increase in RBC EPA in the EPA group (n=43; median intervention 30 days; mean absolute 1.26[±0.14]% increase; P<0.001), but not in the placebo arm (n=45). EPA incorporation varied widely in EPA users and was not explained by treatment duration or compliance. There was little evidence of 'contamination' in the placebo group. The EPA level predicted tumour EPA content (r=0.36; P=0.03). Participants with post-treatment EPA≥1.22% (n=49) had improved OS compared with EPA <1.22% (n=29; HR 0.42[95%CI 0.16-0.95]). RBC EPA content should be evaluated as a biomarker of tumour exposure and clinical outcomes in future EPA trials in CRC patients.

Relationship between primary colorectal tumour and location of colorectal liver metastases.

BACKGROUND: There is conflicting evidence regarding whether streamlining of blood flow within the portal vein influences the anatomical distribution of colorectal liver metastases (CRLM). This study assesses the relationship between primary tumour location and metastases location. METHODS: Patients were identified using a prospectively maintained database, and those with known site of primary colorectal tumour and hemiliver involvement were included. Site of metastases and segments affected were confirmed via review of the radiology reports. The location of primary colonic tumour was confirmed via review of clinical correspondence letters. RESULTS: A total of 2364 metastases were identified in 891 patients. Of these, 379 metastases were in the right lobe and 156 in the left lobe, with 356 having bilobar disease. There was no significant relationship between the distribution of CRLM and the site of primary disease (left colon versus right colon) (P = 0.819). However, when the segmental location of the metastases was considered, there is a statistically significant difference between the number of right-sided CRLM compared with left-sided CRLM (P < 0.001). CONCLUSIONS: Right-sided CRLM is more likely regardless of the primary location. Portal streaming may have an effect, although the natural anatomical 'angulation', particularly of the left portal vein branch is more likely to play a role.

Redefining major hepatic resection for colorectal liver metastases: Analysis of 1111 liver resections.

INTRODUCTION: A major hepatic resection is currently defined as resection of 3 or more segments. The aim of this study was to analyse the post-operative morbidity and mortality of hepatic resections in relation to the number of segments excised. PATIENTS AND METHODS: From January 2000 to December 2010, 1111 liver resections were performed for colorectal liver metastases (CRLM). Data were collected from a prospectively maintained database and analysed according to the extent of resection performed. RESULTS: 457 patients had 1-2, 362 had 3-4 and 292 had 5-6 segments resected respectively. In comparing 1-4 vs. 5-6 segments, overall morbidity (16.7% vs 40.7%; p < 0.001), hepatic failure (0.6% vs 10.6%; p < 0.001); mean hospital stay (8 vs 13.5 days; p = 0.000), mean ICU stay (4.4 vs 6.5 days; p = 0.01), 60-day mortality (0.7% vs 3.4%; p = 0.002), and 90-day mortality (0.7% vs 3.4%; p = 0.002) were significantly different. When analysing the 3-4 vs 5-6 segment resections, morbidity (21.8% vs 40.7%; p < 0.001), hepatic failure (1.4% vs 10.6%; p = 0.000), 60-day mortality (0.7% vs 3.4%; p = 0.002), and 90-days mortality (0.8% vs 3.4%; p = 0.023) remained statistically significant. CONCLUSIONS: Differences in outcome would suggest a revision of the current classification. Only when 5 or more segments are excised for CRLM should a liver resection be considered "major".