Benign liver lesions are common and can pose a diagnostic challenge due to difficulty in differentiating them from malignant hepatic lesions. Most benign liver lesions are asymptomatic and are frequently detected incidentally during investigations for other conditions. Liver function tests are usually normal or only mildly deranged. Diagnosis is principally established by abdominal ultrasound, contrast-enhanced computed tomography, and magnetic resonance imaging together with hepatobiliary contrast agents and magnetic resonance cholangiography. Biopsy, if required in diagnosis of benign liver tumours, should be done sparingly due to the potential risk of bleeding or tumour seeding from malignant lesions. Some benign liver lesions are precursors to malignant lesions, while others have no risk of malignancy. Management strategies may vary from simple reassurance, lifestyle advice and surveillance imaging, through to complex hepatic resections or even liver transplantation in rare cases. Awareness of the natural history, clinical presentation and management strategies will ensure appropriate initial diagnostic work-up and prompt referral to a specialist hepatobiliary unit.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the authors over questions of data integrity and reproducibility. Following an investigation undertaken by the University of Liverpool into research misconduct by Dr Daniel Antoine (https://news.liverpool.ac.uk/2018/07/06/research-misconduct-update/), the remaining authors elected to reanalyze independent samples of the human serum from the patient cohorts originally studied. The human serum analysis had been undertaken by Daniel Antoine at the University of Liverpool for this manuscript (REF PMID: 26344055). The coauthors were unable to reproduce the findings of the human serum analysis (doi: https://doi.org/10.1101/2021.04.02.437789) and therefore no longer have confidence in the human data component of this manuscript. The authors requested that this paper be retracted in 2019, and the Editors of Gastroenterology agree that this manuscript should be retracted. Dr Daniel Antoine played no part in any other aspects of this manuscript, and the authors have confidence in all other data.

Abstract Background 20 years ago acute surgical services were re-organised in our region to deliver subspecialist care of upper-gastrointestinal emergencies. Improved outcomes were reported as a result. Currently the unit has 24-hour availability for interventional and diagnostic radiology, emergency endoscopy and a specialist oesophago-gastric consultant surgeon. The aims of this study are to determine if, a decade after a major service re-organisation, any further improvements have been achieved in short-term outcomes and to provide long-term survival figures for this group of patients. Methods All patients admitted during a 62-month period from January 2010-February 2015, corresponding in duration and exactly a decade later than the previous report following service re-organisation, were identified from a prospectively compiled database. Results 287 patients were admitted during the study period. 235 patients were admitted with ulcer perforation and 52 patients underwent surgery for bleeding. Perforation. 8 patients (8/235, 3.4%) received end of life care. 37 patients (37/235, 15.7%) had initial conservative management. 191 (191/235, 81.3%) patients underwent operation (includes 1 patient with failed conservative management). 18 patients (18/191, 9.4%) died post-operatively. No patients selected for conservative management died. Within 5 years following discharge a further 34 patients died. 50% (17/34) of these were due to cancer. Actual 5-year survival was 73.3% (165/225, 10 patients lost to follow up). Comparing with the period following subspecialisation, overall in-hospital mortality was 10.4% vs 11.1% (14/135 vs 26/235) p=0.84, in-hospital mortality following surgery 7.9% vs 9.4% (9/114 vs 18/191) p=0.65 and in-hospital mortality following conservative management 23.8% vs 0% (5/21 vs 0/36) p=0.005. Bleeding. In-hospital mortality was 25% (13/52). This was not significantly different from the rate reported following service reorganisation, 23.5% (12/51) vs 25% (13/52) p=0.86. Within 5 years following discharge a further 12 patients died. 58% (7/12) of these were due to cancer. Actual 5-year survival was 51.9% (27/52 patients alive). Conclusions This study demonstrates that no improvement in surgical outcome in patients with complicated peptic ulcer disease has been achieved despite the delivery of what may be considered an optimal service. A significant improvement in outcome in patients selected as suitable for conservative management has been seen. 5-year survival figures for patients admitted with either perforation or bleeding are poor with cancer the most common cause of death within 5 years following discharge.

BACKGROUND Ablative therapies (AT) are widely utilized as bridging treatment for liver transplantation (LT) candidates with hepatocellular carcinoma (HCC) who are on the transplant waiting list to minimize dropout rate. We aimed to investigate whether AT could be considered a primary treatment modality for LT candidates with single, small HCC lesions. MATERIAL AND METHODS We retrospectively investigated the outcomes of patients with AT for single HCC lesions as primary treatment or bridging to LT between 2010 and 2017, compared with surgical resection (SR) during the same time period as control. Univariate and multivariate survival analyses were performed. Matched analysis, after propensity score matching (PSM), was performed to minimize the selection bias confounding effect on outcomes. RESULTS Of 162 patients identified, 92 received AT and 70 had SR. PSM identified 38 paired matches in each group. Overall survival (OS) and disease-free survival (DFS) before matching showed comparable outcomes for each treatment after 1, 3, and 5 years. Multivariate analysis using Cox regression models adjusting the study confounders showed lesion size (>30 mm), not treatment received, was associated with worse DFS (hazard ratio, 2.21 [95% confidence interval, 1.14-4.28]). In the matched groups, OS and DFS were equivalent and consistent with the whole-cohort survival outcomes. Explant histopathology of patients having AT as a bridge to LT showed complete pathological response in 85.7% of patients. CONCLUSIONS This study supports the use of AT with curative intent for single ≤3-cm HCCs, particularly in LT candidates, with salvage transplantation kept as a backup in case of recurrence.

Laparoscopic liver resection (LLR) is increasingly common worldwide but its suitability in patients with cirrhosis is not clearly defined. There are minimal data in the western literature on this topic and previous work has compared LLR to open hepatectomy rather than to LLR in non‐cirrhotic patients. This study compared short‐term outcomes of LLR in cirrhotic patients to LLR in non‐cirrhotic patients.

Prehabilitation prior to major surgery has increased in popularity over recent years and aims to improve pre-operative conditioning of patients to improve post-operative outcomes. The beneficial effect of such protocols is not well established with conflicting results reported. This review aimed to assess the effect of prehabilitation on post-operative outcome after major abdominal surgery.

INTRODUCTION Stoma formation following colorectal resection is often anticipated prior to surgery. Becoming independent with stoma handling can sometimes delay discharge beyond achievement of discharge criteria. The aim of this study was to assess the impact of preoperative stoma training on length of stay. METHODS Patients undergoing colorectal resection within an enhanced recovery after surgery (ERAS) programme were prospectively entered into a database. Retrospective analysis was performed of those who received a stoma as part of their operation. Patients who underwent preoperative stoma training were compared with those who had conventional postoperative training. The primary outcome measure was length of hospital stay. Secondary outcome measures included overall morbidity, stoma related morbidity, ERAS milestone achievement and readmission rates. RESULTS The median length of stay was improved in the patients receiving preoperative stoma training (8 days [interquartile range: 6-10] vs 9 days [interquartile range: 7-19.5], p=0.025). No statistically significant difference was observed in overall morbidity rates, stoma specific morbidity, ERAS milestones or readmission rates. CONCLUSIONS Preoperative stoma training can reduce length of stay and could be employed routinely for patients who are planned to have colorectal surgery. Such training can be incorporated within ERAS pathways.

Effective analgesia following open oesophagogastric (OG) resection is considered a key determinant of recovery. This review aimed to compare epidural to alternative analgesic techniques in patients undergoing major open resection for OG cancer.

Background: Resting energy expenditure (REE) is the major component of total energy expenditure. REE is traditionally performed by indirect calorimetry (IC) and is not well investigated after liver surgery. A mobile device (SenseWear Armband [SWA]) has been validated when estimating REE in other clinical settings but not liver resection. The aims of this study are to validate SWA vs IC, quantify REE change following liver resection, and determine factors associated with REE change. Materials and Methods: Patients listed for open liver resection prospectively underwent IC and SWA REE recordings pre- and postoperatively. In addition, the SWA was worn continuously postoperatively to estimate daily REE for the first 5 postoperative days. To determine acceptability of the SWA, validation analysis was performed. To assess REE change, peak postoperative REE was compared with preoperative levels. Factors associated with REE change were also analyzed. Results: SWA showed satisfactory validity compared with IC when estimating REE, although postoperatively, the 95% levels of agreement (-5.56 to 3.18 kcal/kg/d) may introduce error. Postoperative REE (median, 23.5 kcal/kg/d; interquartile range [IQR], 22.6-25.7 kcal/kg/d) was significantly higher than predicted REE (median, 19.7 kcal/kg/d; IQR, 19.1-21.0 kcal/kg/d; P < .0001). Median REE rise was 11% (IQR, -1% to 25%). Factors associated with REE rise of >11% were age (P = .017) and length of operation (P = .03). Conclusions: SWA offers a suitable alternative to IC when estimating postoperative REE, but the magnitude of the error (8.74 kcal/kg/d) could hinder its accuracy. REE quantification after liver resection is important to identify patients who could be prone to energy imbalance and therefore malnutrition.

Background: Analgesia after liver surgery remains controversial. A previous randomized trial of continuous wound infiltration versus thoracic epidural analgesia (TEA) after liver surgery (LIVER Trial) showed faster recovery time in the wound infiltration group but better early postoperative pain scores in the TEA group. High level evidence, however is limited and opinion remains divided. Methods: A randomized controlled trial of 100 patients undergoing open liver resection was performed from December 2012 to August 2014. The aim was to determine whether there is a difference in the functional recovery time between patients having continuous wound infiltration plus abdominal nerve blocks versus epidural after liver resection. Patients were randomized, by opaque sealed envelopes, to receive either wound catheter and nerve block (CWI) or TEA for 48 hours post-operatively. Primary outcome measure was functional recovery time. Secondary outcome measures were pain scores, complication rates, inflammatory mediators and central venous pressure (CVP) during transection. Results: 44 patients received TEA and 49 received CWI. Recovery time was 6.5 IQR 5–9.75 days (TEA) versus 5.75 IQR 4–7 (CWI) days (p = 0.04). Pain scores were equivalent between the two groups and there were no differences in morbidity, inflammatory response or CVP during transection. Conclusion: CWI offers a reduction in time to recovery and could be considered as first line analgesic modality after liver resection. TEA does not offer an advantage over CWI in terms of attenuation of the inflammatory response or pain scores.

Introduction: Enhanced Recovery After Surgery protocols have been implemented effectively after liver resection and provide benefits in terms of general morbidity rates. In order to optimise peri-operative care protocols and minimise morbidity, further investigation is required to identify factors associated with poor outcome after liver resection.Methods: A retrospective analysis of patients undergoing liver resection and enhanced recovery care between January 2006 and September 2012 was conducted. Data were collected on patient outcome and demographics, operative and pathological details. Univariate and multivariate analyses were performed to determine independent predictors of adverse outcome.Results: 603 patients underwent liver resection during the study period. Morbidity and mortality rates were 34.3% and 1.5% respectively. The only predictor of major morbidity was extended resection (OR 4.079; 95% CI 2.177-7.642).Conclusions: Extended resection is associated with major morbidity. When determining optimum perk operative care, ERAS protocols must incorporate care components that can mitigate against morbidity associated with extended resection.

Background & Aims Liver regeneration requires functional liver macrophages, which provide an immune barrier that is compromised after liver injury. The numbers of liver macrophages are controlled by macrophage colony-stimulating factor (CSF1). We examined the prognostic significance of the serum level of CSF1 in patients with acute liver injury and studied its effects in mice. Methods We measured levels of CSF1 in serum samples collected from 55 patients who underwent partial hepatectomy at the Royal Infirmary Edinburgh between December 2012 and October 2013, as well as from 78 patients with acetaminophen-induced acute liver failure admitted to the Royal Infirmary Edinburgh or the University of Kansas Medical Centre. We studied the effects of increased levels of CSF1 in uninjured mice that express wild-type CSF1 receptor or a constitutive or inducible CSF1-receptor reporter, as well as in chemokine receptor 2 (Ccr2)-/- mice; we performed fate-tracing experiments using bone marrow chimeras. We administered CSF1-Fc (fragment, crystallizable) to mice after partial hepatectomy and acetaminophen intoxication, and measured regenerative parameters and innate immunity by clearance of fluorescent microbeads and bacterial particles. Results Serum levels of CSF1 increased in patients undergoing liver surgery in proportion to the extent of liver resected. In patients with acetaminophen-induced acute liver failure, a low serum level of CSF1 was associated with increased mortality. In mice, administration of CSF1-Fc promoted hepatic macrophage accumulation via proliferation of resident macrophages and recruitment of monocytes. CSF1-Fc also promoted transdifferentiation of infiltrating monocytes into cells with a hepatic macrophage phenotype. CSF1-Fc increased innate immunity in mice after partial hepatectomy or acetaminophen-induced injury, with resident hepatic macrophage as the main effector cells. Conclusions Serum CSF1 appears to be a prognostic marker for patients with acute liver injury. CSF1 might be developed as a therapeutic agent to restore innate immune function after liver injury.

Background: The effect of liver resection on acetaminophen metabolism and whether it is affected by residual liver volume is poorly understood.Methods: We investigated the effects of liver resection on acetaminophen metabolism in a single centre, prospective observational, case-control study of inpatients. Patients undergoing liver resection were administered therapeutic post-operative acetaminophen. Glutathione and urinary acetaminophen metabolites were measured over the first three post-operative days and compared between patients with low (Group A) and high (Group B) residual liver volume.Results: 41 patients (41% female, median age 62 [IQR 53-72] years) were included. Mean urinary cysteine levels increased significantly from post-operative day 1 to 2 (578.0 mg/day 95% CI 478.9-677.1 vs. 775.4 mg/day, 95% CI 625.7-925.1; p = 0.03). Group A (n = 11) had significantly higher median levels of cysteine (day 1, 464.3 mg/day [IQR 355.6-582.0]; day 3, 717.6 mg/day [IQR 423.5-1104.0]) compared to Group B (n = 11): day 1, 545.4 mg/day (IQR 346.9-843.5); day 3, 508.1 mg/day (IQR 390.8-788.4; p = 0.048). No significant difference was observed in glutathione or 5-oxoproline levels between the groups.Conclusion: Low residual liver volume results in altered acetaminophen metabolism, however, no evidence of glutathione deficiency was observed. Therapeutic acetaminophen is safe after major liver resection provided liver function is adequate. Crown Copyright (c) 2015 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. All rights reserved.

Postoperative analgesia following liver resection remains controversial. The traditional standard of care of thoracic epidural is increasingly questioned due to perceived associated complications and delays to recovery. Evidence supporting alternative analgesic techniques is emerging however best practice is not yet established. This review aimed to evaluate the literature to assess the optimum analgesic technique following liver resection. A systematic review was conducted of trials evaluating analgesic methods in open liver surgery. Primary outcome was the postoperative complication rate. Secondary outcomes were length of stay and pain scores. Fourteen trials matching the inclusion criteria were analysed. No difference was observed in systemic complication rates between analgesic modalities. Epidural was associated with prolonged length of stay when compared with continuous wound infiltration and intrathecal morphine. Epidural offered equivalent or superior pain scores when compared to alternative techniques. In summary current evidence suggests alternative analgesic modalities may provide favorable recovery outcomes following liver surgery but consistent evidence is limited. Epidurals provide superior pain relief to alternatives but this does not translate into reduced length of stay or complication rate following liver surgery.

Background: A liver resection under low central venous pressure (CVP) has become standard practice; however, the benefits beyond a reduction in blood loss are not well reported. Moreover, the precise method to achieve CVP reduction has not been established. A systematic review and meta-analysis of randomized controlled trials (RTCs) was performed to assess the effects of CVP on clinical outcome and to identify the optimum method of CVP reduction.Methods: EMBASE, Medline, PubMed and the Cochrane database were searched for trials comparing low CVP surgery with controls. The primary outcome was post-operative complications within 30 days. Secondary outcomes included estimated blood loss (EBL), blood transfusion rates and length of stay (LOS). Sub-group analysis was performed to assess the CVP reduction method on the outcome.Results: Eight trials were identified. No difference was observed in the morbidity rate between the high CVP and control groups [odds ratio (OR) = 0.96 (95% confidence interval (CI) 0.66, 1.40) P = 0.84, I-2 = 0%]. EBL [weighted mean difference (WMD) = -308.63 ml (95% CI -474.67, -142.58) P = < 0.001, I-2 = 73%] and blood transfusion rates [OR 0.65 (95% CI 0.44, 0.97) P = 0.040, I-2 = 37%] were significantly lower in the low CVP groups. Neither anaesthetic nor surgical methods of CVP reduction were associated with a reduced post-operative morbidity.Conclusion: Low CVP surgery is associated with a reduction in EBL; however, this does not translate into an improvement in post-operative morbidity. The optimum method of CVP reduction has not been identified.

BACKGROUND:Analgesia after liver surgery remains controversial. A previous randomized trial of continuous wound infiltration (CWI) versus thoracic epidural analgesia (TEA) after liver surgery (LIVER trial) showed a faster recovery time in the wound infiltration group but better early postoperative pain scores in the TEA group. High-level evidence is, however, limited and opinion remains divided. The aim was to determine whether there is a difference in functional recovery time between patients having CWI plus abdominal nerve blocks versus TEA after liver resection.METHODS:A randomized unblinded clinical trial of patients undergoing open liver resection was commenced in December 2012, with follow-up to August 2014. Patients were randomized to receive either wound catheter and nerve block (CWI group) or TEA for 48 h after surgery. The primary outcome measure was functional recovery time. Secondary outcomes were pain scores, complication rates, inflammatory response and central venous pressure (CVP) during transection.RESULTS:Of 50 patients randomized initially to each group, 44 received TEA and 49 CWI. Median (i.q.r.) recovery time was 6·5 (5-9·75) and 5·75 (4-7) days in the TEA and CWI groups respectively (P = 0·036). Pain scores were not significantly different between the two groups, and there were no differences in morbidity, inflammatory response or CVP during transection.CONCLUSION:Wound infiltration is associated with a reduced time to recovery after open liver resection compared with epidural analgesia. TEA does not offer an advantage over CWI in terms of attenuation of the inflammatory response or pain scores.REGISTRATION NUMBER:NCT01747122 ( http://www.clinicaltrials.gov).

Background: Enhanced recovery after surgery (ERAS) is a well-established pathway of perioperative care in surgery in an increasing number of specialties. To implement protocols and maintain high levels of compliance, continued support from care providers and patients is vital. This survey aimed to assess the perceptions of care providers and patients of the relevance and importance of the ERAS targets and strategies.Materials and methods: Pre- and post-operative surveys were completed by patients who underwent major hepatic, colorectal, or oesophagogastric surgery in three major centers in Scotland, Norway, and The Netherlands. Anonymous web-based and article surveys were also sent to surgeons, anesthetists, and nurses experienced in delivering enhanced recovery protocols. Each questionnaire asked the responder to rate a selection of enhanced recovery targets and strategies in terms of perceived importance.Results: One hundred nine patients and 57 care providers completed the preoperative survey. Overall, both patients and care providers rated the majority of items as important and supported ERAS principles. Freedom from nausea (median, 10; interquartile range [IQR], 8-10) and pain at rest (median, 10; IQR, 8-10) were the care components rated the highest by both patients and care providers. Early return of bowel function (median, 7; IQR, 5-8) and avoiding preanesthetic sedation (median, 6; IQR, 3.75-8) were scored the lowest by care providers.Conclusions: ERAS principles are supported by both patients and care providers. This is important when attempting to implement and maintain an ERAS program. Controversies still remain regarding the relative importance of individual ERAS components. (C) 2015 Elsevier Inc. All rights reserved.

IMPORTANCE The optimal analgesic technique following open abdominal surgery within an enhanced recovery protocol remains controversial. Thoracic epidural is often recommended; however, its role is increasingly being challenged and alternative techniques are being suggested as suitable replacements. OBJECTIVE To determine by meta-analysis whether epidurals are superior to alternative analgesic techniques following open abdominal surgery within an enhanced recovery setting in terms of postoperative morbidity and other markers of recovery. DATA SOURCES A literature search was performed of EMBASE, Medline, PubMed, and the Cochrane databases from 1966 through May 2013. STUDY SELECTION All randomized clinical trials comparing epidurals with an alternative analgesic technique following open abdominal surgery within an enhanced recovery protocol were included. DATA EXTRACTION AND SYNTHESIS All studies were assessed by 2 independent reviewers. Study quality was assessed using the Cochrane bias assessment tool and the Jadad and Chalmers modified bias risk assessment tools. Dichotomous data were analyzed by random or fixed-effects odds ratios. Qualitative analysis was performed where appropriate. RESULTS Seven trials with a total of 378 patients were identified. No significant difference in complication rate was detected between epidurals and alternative analgesic methods (odds ratio, 1.14; 95% CI, 0.49-2.64; P = .76). Subgroup analysis showed fewer complications in the patient-controlled analgesia group compared with epidural analgesia (odds ratio, 1.97; 95% CI, 1.10-3.53; P = .02). Following qualitative assessment, epidural analgesia was associated with faster return of gut function and reduced pain scores; however, no difference was observed in length of stay. CONCLUSIONS AND RELEVANCE Epidurals may be associated with superior pain control but this does not translate into improved recovery or reduced morbidity when compared with alternative analgesic techniques when used within an enhanced recovery protocol.