Background The optimal strategy for patients with colorectal liver metastases (CRLM) is unclear. The Precision1 prospective, observational trial assessed whether pre-operative functional imaging and whole genome sequencing (WGS), could enhance individualized decision-making. Methods Patients with CRLM considered for hepatectomy were recruited. In addition to standard staging, patients underwent a quantitative multiparametric MRI (mpMRI) scan, to assess liver function. Use of mpMRI to aid surgical decision-making, was prospectively recorded, as were short-term clinical outcomes in patients who underwent hepatectomy. In the first 45 patients, WGS was performed on blood and liver tumour samples collected per-operatively. Results 95 mpMRI scans were performed in 84 patients, who underwent 87 resections. The mpMRI scan affected surgical decision-making in 41% (39/95) of scans, with 11 undergoing dual-vein embolization, 16 undergoing more conservative parenchymal-sparing surgery, 11 having more extensive surgery, and one patient following a low calorie diet pre-operatively. There were significant (Clavien-Dindo grades 3/4) complications in 5% of patients, no Grade C post-hepatectomy liver failure, and zero 90-day mortality. WGS suggested additional therapeutic options and prognostic factors for 22 of 35 (63%) evaluable patients. Conclusion Precision1 shows mpMRI can aid surgical decision-making, and optimise clinical outcomes. WGS provides additional information, to further enhance personalised decision-making.

Background: Optimisation of the future liver remnant (FLR) is crucial to outcomes of extended liver resections. This study aimed to assess the quality of the FLR before and after dual vein embolization (DVE) by quantitative multiparametric MRI. Methods: Of 100 patients with liver metastases recruited in a clinical trial (Precision1:NCT04597710), ten consecutive patients with insufficient FLR underwent quantitative multiparametric MRI pre- and postDVE (right portal and hepatic vein). FLR volume, liver fibro-inflammation (corrected T1) scores and fat percentage (proton density fat fraction, PDFF) were determined. Patient metrics were compared by Wilcoxon signed-rank test and statistical analysis done using R software. Results: All patients underwent uncomplicated DVE with improvement in liver remnant health, median 37 days after DVE: cT1 scores reduced from median (interquartile range) 790 ms (753-833 ms) to 741 ms (708-760 ms) p = 0.014 [healthy range <795 ms], as did PDFF from 11% (4-21%), to 3% (2-12%) p = 0.017 [healthy range <5.6%]. There was a significant increase in median (interquartile range) FLR volume from 33% (30-37%)% to 49% (44-52%), p = 0.002. \Conclusion: This non-invasive and reproducible MRI technique showed improvement in volume and quality of the FLR after DVE. This is a significant advance in our understanding of how to prevent liver failure in patients undergoing major liver surgery.

Abstract Background The incidence of postoperative pulmonary complications (PPCs) after open liver surgery is high. Risk factors include age, body mass index, ex- or current smoker, and chronic lung disease. Early postoperative chest physiotherapy (CP), an essential part of any enhanced recovery protocol (ERP), can reduce PPCs, length of stay and healthcare costs. This study evaluated the uptake of CP after open liver surgery and resultant outcomes, following a quality improvement (QI) intervention. Method The project design involved two audit cycles: cycle 1 (C1) and cycle 2 (C2), each of five months duration, of consecutive patients undergoing open liver surgery, before and after a QI intervention (intensive preoperative patient education, poster campaign, increased engagement with physiotherapists regarding the importance of timely CP. Patients undergoing laparoscopic resections were excluded. Outcome measures included whether patients received postoperative CP at all, if so on which post-operative day (POD), for what duration, patient location, incidence of PPCs, and the length of postoperative stay. Statistical analysis was performed using (r 4-4.1) software, using the Chi-squared or Fisher’s Exact test. Results Despite more smokers/ex-smokers in C1(24%) versus C2(8%,p=0.04), only 18/50(36%) C1 patients received CP on POD1, versus 20/36(57%) in C2(p=0.07). Sixteen(32%) C1 patients received no postoperative CP, versus 7(19%) in C2(p=0.19). There were non-significant decreases in PPCs in C2(8%), versus C1(20%)(p=0.13). Three of four patients developing pneumonia in C1, and both those in C2, had no POD1 CP. Wards with higher physiotherapist:patient ratios had more POD1 CP: in C1 12/19(63%)[6/31(20%), p=0.001], and C2 14/15(93%)[6/20(30%) p=0.0001]. Median hospital stay was unchanged (4 days). Conclusion This QI project shows that even with an established enhanced recovery programme, the provision of postoperative chest physiotherapy is not universal. However, it can be improved with an education programme for both healthcare workers and patients.

Introduction Post-hepatectomy liver failure (PHLF), driven by insufficient volume and quality of the remnant liver following an operation, is a significant clinical problem that is currently underserved by pre-operative assessment methods. Clinical management and a patient’s recovery from post-operative liver related complications results in a protracted stay in hospital. Methods 91 patients with colorectal liver metastasis being considered for liver resection were recruited onto the Precision1 trial. The imaging report from an additional non-quantitative multiparametric MRI (mpMRI) scan was examined and used to alter surgical decision making. Patient outcomes were monitored and evaluated against a standard of care comparator dataset blinded to mpMRI scan results. Results Previously undiagnosed liver disease activity or elevated liver fat was detected using mpMRI in 23% of patients, whereas the liver health was unexpectedly good in 7% of patients; this resulted in a change to surgical plan in 29% of cases. The incidence of protracted (over 14 days) length of stay was reduced from 5% to 1% following the introduction of mpMRI reports into surgical decision-making process. Conclusion mpMRI is a safe method to evaluate liver health in patients being considered for liver resection. Surgical decision making can be altered to achieve a safer treatment strategy resulting in shorter hospital stays for patients. ### Competing Interest Statement JC, SK, JMB, RB are employees and shareholders at Perspectum Ltd. ### Clinical Trial NCT04597710 ### Clinical Protocols ### Funding Statement This study was funded by InnovateUK. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Brighton and Sussex Research Ethics Committee (REC Reference 20/PR/0222). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Liver biopsy remains the gold standard for the histological assessment of the liver. With clear disadvantages and the rise in the incidences of liver disease, the role of neoadjuvant chemotherapy in colorectal liver metastasis (CRLM) and an explosion of surgical management options available, non-invasive serological and imaging markers of liver histopathology have never been more pertinent in order to assess liver health and stratify patients considered for surgical intervention. Liver MRI is a leading modality in the assessment of hepatic malignancy. Recent technological advancements in multiparametric MRI software such as the LiverMultiScanTM offers an attractive non-invasive assay of anatomy and histopathology in the pre-operative setting, especially in the context of CRLM. This narrative review examines the evidence for the LiverMultiScanTM in the assessment of hepatic fibrosis, steatosis/steatohepatitis, and potential applications for chemotherapy-associated hepatic changes. We postulate its future role and the hurdles it must surpass in order to be implemented in the pre-operative management of patients undergoing hepatic resection for colorectal liver metastasis. Such a role likely extends to other hepatic malignancies planned for resection.

Introduction Liver resection is the only curative treatment for colorectal liver metastases (CLM). Resectability decision-making is therefore a key determinant of outcomes. Wide variation has been demonstrated in resectability decision-making, despite the existence of criteria. This paper summarises a study protocol to evaluate the potential added value of two novel assessment tools in assessing CLM technical resectability: the Hepatica preoperative MR scan (MR-based volumetry, Couinaud segmentation, liver tissue characteristics and operative planning tool) and the LiMAx test (hepatic functional capacity).Methods and analysis This study uses a systematic multistep approach, whereby three preparatory workstreams aid the design of the final international case-based scenario survey:Workstream 1: systematic literature review of published resectability criteria.Workstream 2: international hepatopancreatobiliary (HPB) interviews.Workstream 3: international HPB questionnaire.Workstream 4: international HPB case-based scenario survey.The primary outcome measures are change in resectability decision-making and change in planned operative strategy, resulting from the novel test results. Secondary outcome measures are variability in CLM resectability decision-making and opinions on the role for novel tools.Ethics and dissemination The study protocol has been approved by a National Health Service Research Ethics Committee and registered with the Health Research Authority. Dissemination will be via international and national conferences. Manuscripts will be published.Registration details The CoNoR Study is registered with ClinicalTrials.gov (registration number NCT04270851). The systematic review is registered on the PROSPERO database (registration number CRD42019136748).

IntroductionRadiogenomic analysis of patients being considered for liver resection is seldom performed in the clinic despite recent evidence indicating that quantitative MRI could improve posthepatectomy outcomes. Meanwhile, the increasingly accessible results from whole genome sequencing reporting on clinically actionable genetic biomarkers are yet to be fully integrated into the clinical care pathway.Methods and analysisA prospective observational cohort study of up to 200 participants is planned, recruiting adults with primary or secondary liver cancer being considered for liver resection at Hampshire Hospitals NHS Foundation Trust. The data will be evaluated to address the primary endpoint to calculate the proportion of participants in which the results from whole genome sequencing would have resulted in a change in clinical management. Participants will be offered an additional non-invasive quantitative MRI scan prior to the operation and the impact of the imaging results on treatment decision-making will be evaluated.Ethics and disseminationThis study was reviewed by the NHS Health Research Authority and given favourable opinion by the Brighton and Sussex Research Ethics Committee (REC reference: 20/PR/0222). Research findings will be discussed with a patient and public involvement and engagement group, presented at relevant scientific conferences and published in open access journals.Trial registration numberNCT04597710

Abstract Background The COVID-19 outbreak in January 2020 rapidly became a pandemic, adversely impacting elective cancer services in the UK. This study describes the pandemic-driven changes to existing admission and enhanced recovery protocols, which allowed the Unit to maintain a liver resection service, and evaluates their impact on patient safety. Methods During the pandemic, all patients undergoing liver resection in this Unit isolated for 14 days prior to their admission, with COVID-19 testing 48 hours pre-admission. Patients were admitted on the day of surgery to the day surgery unit, a designated COVID-free environment. They underwent liver surgery, recovery and post-operative care, all within the day surgery unit. Using a prospectively collected database, short-term outcomes of consecutive patients undergoing elective hepatectomy during the COVID-19 pandemic (April - June 2020) were retrospectively compared to patients during the same period in 2019. Results During the pandemic, 24 patients underwent hepatectomy compared to 34 patients in 2019. There was no statistical difference in demographics, indications for surgery, intra-operative parameters or complications between these periods. The median post-operative length of stay (LOS) was significantly shorter during the pandemic [3 (IQR: 3-4) days vs. 4 (IQR; 4-7) days, p = 0.015], as was the overall LOS [4 (IQR: 4-6) days vs. 6 (IQR; 5-9) days, p = 0.006]. No patient contracted COVID-19 per-operatively. Conclusions Patient pathway changes during a pandemic enabled safe liver surgery to be undertaken with improved outcomes – a model that is transferrable to other Units.

Background: Routine chemical venous thromboembolism (VTE) prophylaxis for liver surgery remains controversial, and often delayed post-operatively due to perceived bleeding risk. This study asked whether patients undergoing hepatectomy for colorectal metastases (CRM) were at risk from VTE pre-operatively, and the impact of hepatectomy on that risk.Methods: Single-centre prospective observational cohort study of patients undergoing open hepa-tectomy for CRM, comparing pre-, peri-and post-operative haemostatic variables.Results: Of 336 hepatectomies performed October 2017-December 2019, 60 resections in 57 patients were recruited. There were 28 (46.7%) major resections, with median (interquartile range [IQR]) blood loss 150.0 (76.3-263.7) mls, no blood transfusions, post-operative VTE events or deaths. Patients were prothrombotic pre-operatively (high median factor VIIIC and increased thrombin generation velocity index), an effect exacerbated post-hepatectomy. Major hepatectomies had a significantly greater median drop in Protein C, rise in Factor VIIIC and von Willebrand Factor, versus minor resections (p = 0.001, 0.005, 0.001 respectively). Patients with parenchymal transection times greater than median (40 min), had significantly increased median (IQR) PMBC-TFmRNA expression [1.65(0.93-2.70)2ddCt], versus quicker transections [0.99(0.69-1.28)2ddCt, p = 0.020].Conclusions: Patients with CRM are prothrombotic pre-operatively, an effect exacerbated by hepa-tectomy, particularly longer, complex resections, suggesting chemical thromboprophylaxis be consid-ered early in the patient pathway.

It is not uncommon for clinicians to encounter varying degrees of hepatic steatosis in patients undergoing resection for colorectal liver metastases (CRLM). Magnetic resonance imaging is currently the preferred investigation for identification and pre-operative planning of these patients. An objective assessment of liver quality and degree of steatosis is paramount for planning a safe resection, which is seldom provided by routine MRI sequences. We studied two patients who underwent an additional pre-operative multiparametric MRI scan (LiverMultiScanTM) as a part of an observational clinical trial (HepaT1ca, NCT03213314) to assess the quality of liver. Outcome was assessed in the form of post-hepatectomy liver failure. Both patients (Patient 1 and 2) had comparable pre-operative characteristics. Both patients were planned for an extended right hepatectomy with an estimated future liver remnant of approximately 30%. Conventional preoperative contrast MRI showed mild liver steatosis in both patients. Patient one developed post-hepatectomy liver failure leading to prolonged hospital stay compared to patient two who had uneventful post-operative course. Retrospective evaluation of multiparametric MRI scan revealed findings consistent with fibro-inflammatory disease and steatosis (cT1 829 ms, PDFF 14%) for patient 1 whereas patient two had normal parameters (cT1 735 ms, PDFF 2.4%). These findings corresponded with the resection specimen histology. Multiparametric MRI can objectively evaluate future liver health and volume which may help refine surgical decision-making and improve patient outcomes

The rapid outbreak of SARS-CoV-2 (COVID-19) necessitated National Health Service England to postpone all non-urgent elective surgery from 15 April 2020, with the number of cancelled operations weekly estimated at 43 307. Shortage of healthcare professionals and limited bed capacity were major hurdles in continuation of the resectional cancer service. The Society of Surgical Oncology recommended that surgery was still indicated for ‘aggressive hepatobiliary malignancies’, also stating that neoadjuvant chemotherapy, ablation or stereotactic radiotherapy could be considered for resectable liver metastases. A similar approach was suggested by an Italian group. The authors advocated liver surgery in selected patients with potentially curative disease, recognizing the challenges of reduced resources. This study analysed the impact of changes to previously established protocols by comparing short-term outcomes of patients undergoing elective liver resection during the pandemic with outcomes of a cohort treated in the same period in the previous year. Key changes were introduced in the patient pathway, with close communication between referring hospitals, local Gold Command, and the liver surgery team. All multidisciplinary team meetings were held virtually using Microsoft TeamsC (Microsoft, Redmond, Washington, USA) and follow-up consultations by telephone, to reduce face-to-face contact and nosocomial spread of the virus. The entire patient journey was contained within a separate unit, the Diagnosis and Treatment Centre. This ‘green’ area was reserved for elective work. Patients were instructed to self-isolate for 14 days and undergo COVID-19 testing 48 h before admission. Patients were preferably admitted on the day of surgery, regardless of distance travelled (up to 400 miles). All resections were performed by an open approach (UK Intercollegiate Guidance) owing to concerns raised over aerosols released during pneumoperitoneum. Theatre staff wore full personal protective equipment, including grade 3 filtering face piece masks as protection against aerosols generated from anaesthesia and the cavitron ultrasonic surgical aspirator used for parenchymal transection. Postoperative analgesia entailed intercostal nerve blockade using bupivacaine infusion and patientcontrolled analgesia, in accordance with published techniques. A total of 58 patients were included in this study, of whom 24 underwent liver resection during the 3-month study interval in 2020 and 34 patients over the same period in 2019. Decisionmaking and quality of care were not altered as there was no statistical difference in patient demographics, indications for surgery, complexity of procedures, perioperative characteristics (including blood loss), and major complications (Table 1). No patients contracted COVID-19 during the hospital stay. Median total duration of hospital stay during the COVID-19 pandemic was 4 (i.q.r. 4–6) days, 2 days shorter than in 2019 (P1⁄4 0.006), with the postoperative stay reduced to 3 (3–4) days, compared with 4 (4–7) days in 2019 (P1⁄4 0.015). Reasons for this included patient factors, admission on the day of surgery, and pushing the boundaries of an existing enhanced recovery protocol. During the pandemic, patients were notably keen not to stay longer in hospital than was clinically necessary. Drains, central line, and urinary catheter were often removed on the first postoperative day, as opposed to the second or third day previously, facilitating earlier mobilization, active engagement with physiotherapy, and enhanced psychological recovery. This study has highlighted the importance of robust perioperative protocols, changes in the admission pathway, and use of a pre-existing geographically separate facility, which allowed the hepatobiliary service to continue during the pandemic, ensuring avoidance of nosocomial COVID-19 transmission. Most importantly, patient selection was unbiased, care was not compromised, and duration of hospital stay was reduced. Using this model, liver resection could be performed safely in the pandemic and this can be replicated in other units.

nosis of peri-hilar cholangiocarcinoma. The objective of this study was to evaluate the utility of these models in determining prognosis for all patients presenting to a tertiary treatment centre with PHC. Methods: Three hundred and two patients diagnosed with PHC referred to a regional tertiary referral centre between 2008 and 2019 had their demographic and survival data retrospectively analysed from a prospectively held database linked to Hospital Episode Statistics and Somerset Cancer Registry data. One hundred and twenty seven patients were surgically explored. Eight-four patients underwent resection. One-hundred and seventy-four (57.6%) patients underwent palliative endoscopic therapy. Univariate and multivariate modelling was utilised to determine significant prognostic variables. Concordance Indices (C-Indices) were constructed for the prognostic models to determine internal validity within the cohort. Results: Multivariate analysis demonstrated that: pre-interventional ECOG status (p< 0.001); serum albumin (p< 0.001); bilirubin levels (p<0.001); CA 19-9 levels (p< 0.001) and resectional status (p< 0.001) were significant predictors of OS. Patients stratified by the MC scoring system to early-stage disease had a significantly longer OS compared to patients fulfilling late-stage criteria (p< 0.001). The predictive CIndices for the MC model obtained significance in discriminating OS for the entire cohort (p< 0.05) and un-resected patients (p< 0.05). Neither model attained significant concordance for accurately discriminating OS in post-resectional patients. Conclusions: The predictive performance of the stated prognostic models for OS have poor utility. Simple pre-interventional serological, functional and radiological variables appear to provide better prognostic indication of OS. Variables not incorporated in the AJCC registry have a significant effect upon post-resectional OS and require full incorporation in to model prognostication.

Introduction: The future liver performance (FLP) of an individual undergoing liver resection for cancer is critical for their survival and recovery. Here, we report the development and clinical testing of HepT1ca, a novel magnetic resonance image (MRI) technology that combines multiparametric MRI signal processing with automated anatomical liver segmentation to estimate FLP. Method: HepaT1ca combines iron-corrected T1 (cT1) mapping with a 3D U-net pipeline to automatically delineate the liver volume and Couinaud segments based on anatomical landmarks. HepaT1ca combines quantitative cT1 mapping with accurate estimation of the future liver remnant (FLR) volume to predict FLP. We evaluated the ability of HepaT1ca to predict post-operative morbidity, length of stay and regenerative capacity in a prospective 2-centre observational clinical trial (ClinicalTrials.gov NCT03213314). Results: 135 of 143 patients recruited and scanned underwent liver resection. 84% of participants had colorectal liver metastases; the remainder had primary liver cancer or other secondary cancers. The HepaT1ca score showed a significant linear correlation with the modified Hyder-Pawlik score, an indicator of post-operative morbidity (adjusted R2=0.26, P< 0.001), and liver regenerative performance (adjusted R2=0.46, P< 0.001). Furthermore, in patients with an FLR < 90%, a mean cT1 >795ms was associated with a longer duration of hospital stay (median (IQR) of 6.5 (5.3-12) vs. 5 (4-7.1); P=0.005). cT1 also correlated with histological measures of inflammation and hepatocyte ballooning. Conclusion: HepaT1ca is a non-invasive quantitative MRI technology for predicting FLP. HepT1ca informs individualised operative risk and augments patient and surgeon decision-making prior to liver resection.

The risk of poor post-operative outcome and the benefits of surgical resection as a curative therapy require careful assessment by the clinical care team for patients with primary and secondary liver cancer. Advances in surgical techniques have improved patient outcomes but identifying which individual patients are at greatest risk of poor post-operative liver performance remains a challenge. Here we report results from a multicentre observational clinical trial (ClinicalTrials.gov NCT03213314) which aimed to inform personalised pre-operative risk assessment in liver cancer surgery by evaluating liver health using quantitative multiparametric magnetic resonance imaging (MRI). We combined estimation of future liver remnant (FLR) volume with corrected T1 (cT1) of the liver parenchyma as a representation of liver health in 143 patients prior to treatment. Patients with an elevated preoperative liver cT1, indicative of fibroinflammation, had a longer post-operative hospital stay compared to those with a cT1 within the normal range (6.5 vs 5 days; p = 0.0053). A composite score combining FLR and cT1 predicted poor liver performance in the 5 days immediately following surgery (AUROC = 0.78). Furthermore, this composite score correlated with the regenerative performance of the liver in the 3 months following resection. This study highlights the utility of quantitative MRI for identifying patients at increased risk of poor post-operative liver performance and a longer stay in hospital. This approach has the potential to inform the assessment of individualised patient risk as part of the clinical decision-making process for liver cancer surgery.

BACKGROUND:The interim analysis of the multicentre New EPOC trial in patients with resectable colorectal liver metastasis showed a significant reduction in progression-free survival in patients allocated to cetuximab plus chemotherapy compared with those given chemotherapy alone. The focus of the present analysis was to assess the effect on overall survival. METHODS:New EPOC was a multicentre, open-label, randomised, controlled, phase 3 trial. Adult patients (aged ≥18 years) with KRAS wild-type (codons 12, 13, and 61) resectable or suboptimally resectable colorectal liver metastases and a WHO performance status of 0-2 were randomly assigned (1:1) to receive chemotherapy with or without cetuximab before and after liver resection. Randomisation was done centrally with minimisation factors of surgical centre, poor prognosis cancer, and previous adjuvant treatment with oxaliplatin. Chemotherapy consisted of oxaliplatin 85 mg/m2 administered intravenously over 2 h, l-folinic acid (175 mg flat dose administered intravenously over 2 h) or d,l-folinic acid (350 mg flat dose administered intravenously over 2 h), and fluorouracil bolus 400 mg/m2 administered intravenously over 5 min, followed by a 46 h infusion of fluorouracil 2400 mg/m2 repeated every 2 weeks (regimen one), or oxaliplatin 130 mg/m2 administered intravenously over 2 h and oral capecitabine 1000 mg/m2 twice daily on days 1-14 repeated every 3 weeks (regimen two). Patients who had received adjuvant oxaliplatin could receive irinotecan 180 mg/m2 intravenously over 30 min with fluorouracil instead of oxaliplatin (regimen three). Cetuximab was given intravenously, 500 mg/m2 every 2 weeks with regimen one and three or a loading dose of 400 mg/m2 followed by a weekly infusion of 250 mg/m2 with regimen two. The primary endpoint of progression-free survival was published previously. Secondary endpoints were overall survival, preoperative response, pathological resection status, and safety. Trial recruitment was halted prematurely on the advice of the Trial Steering Committee on Nov 1, 2012. All analyses (except safety) were done on the intention-to-treat population. Safety analyses included all randomly assigned patients. This trial is registered with ISRCTN, number 22944367. FINDINGS:Between Feb 26, 2007, and Oct 12, 2012, 257 eligible patients were randomly assigned to chemotherapy with cetuximab (n=129) or without cetuximab (n=128). This analysis was carried out 5 years after the last patient was recruited, as defined in the protocol, at a median follow-up of 66·7 months (IQR 58·0-77·5). Median progression-free survival was 22·2 months (95% CI 18·3-26·8) in the chemotherapy alone group and 15·5 months (13·8-19·0) in the chemotherapy plus cetuximab group (hazard ratio [HR] 1·17, 95% CI 0·87-1·56; p=0·304). Median overall survival was 81·0 months (59·6 to not reached) in the chemotherapy alone group and 55·4 months (43·5-71·5) in the chemotherapy plus cetuximab group (HR 1·45, 1·02-2·05; p=0·036). There was no significant difference in the secondary outcomes of preoperative response or pathological resection status between groups. Five deaths might have been treatment-related (one in the chemotherapy alone group and four in the chemotherapy plus cetuximab group). The most common grade 3-4 adverse events reported were: neutrophil count decreased (26 [19%] of 134 in the chemotherapy alone group vs 21 [15%] of 137 in the chemotherapy plus cetuximab group), diarrhoea (13 [10%] vs 14 [10%]), skin rash (one [1%] vs 22 [16%]), thromboembolic events (ten [7%] vs 11 [8%]), lethargy (ten [7%] vs nine [7%]), oral mucositis (three [2%] vs 14 [10%]), vomiting (seven [5%] vs seven [5%]), peripheral neuropathy (eight [6%] vs five [4%]), and pain (six [4%] vs six [4%]). INTERPRETATION:Although the addition of cetuximab to chemotherapy improves the overall survival in some studies in patients with advanced, inoperable metastatic disease, its use in the perioperative setting in patients with operable disease confers a significant disadvantage in terms of overall survival. Cetuximab should not be used in this setting. FUNDING:Cancer Research UK.

Accurate assessment of liver health prior to undertaking resectional liver surgery or chemoembolisation for primary and secondary cancers is essential for patient safety and optimal outcomes. LiverMultiScan™, an MRI-based technology, non-invasively quantifies hepatic fibroinflammatory disease, steatosis and iron content. We hypothesise that LiverMultiScan™can quantify liver health prior to surgery and inform the risk assessment for patients considering liver surgery or chemoembolization and seek to evaluate this technology in an operational environment.

Background: The International Study Group for Liver Surgery (ISGLS) definition of post hepatectomy liver failure (PHLF) was developed to be consistent, widely applicable, and to include severity stratification. This international multicentre collaborative study aimed to prospectively validate the ISGLS definition of PHLF. Methods: 11 HPB centres from 7 countries developed a standardised reporting form. Prospectively acquired anonymised data on liver resections performed between 01 July 2010 and 30 June 2011 was collected. A multivariate analysis was undertaken of clinically important variables. Results: Of the 949 patients included, 86 (9%) met PHLF requirements. On multivariate analyses, age >= 70 years, pre-operative chemotherapy, steatosis, resection of >3 segments, vascular reconstruction and intraoperative blood loss >300 ml significantly increased the risk of PHLF. Receiver operator curve (ROC) analysis of INR and serum bilirubin relationship with PHLF demonstrated post-operative day 3 and 5 INR performed equally in predicting PHLF, and day 5 bilirubin was the strongest predictor of PHLF. Combining ISGLS grades B and C groups resulted in a high sensitivity for predicting mortality compared to the 50-50 rule and Peak bilirubin >7 mg/dl. Conclusions: The ISGLS definition performed well in this prospective validation study, and may be the optimal definition for PHLF in future research to allow for comparability of data.

Liver resection before primary cancer resection is a novel strategy advocated for selected patients with synchronous colorectal liver metastases (sCRLM). This study measured outcomes in patients with sCRLM following a liver‐first or classical approach, and used a validated propensity score.