Background/Aims: Low folate intake may increase risk of colorectal cancer by altering gene-specific methylation in the colon. We determined whether supplementation with physiological doses of folate could alter methylation in the oestrogen receptor 1 (ESR1) and mutL homolog 1 (MLH1) genes in colonic mucosa of subjects with colorectal adenoma. Methods: This was a randomised, double-blind, placebo-controlled trial. Subjects received either 400 µg/day folic acid (n = 15) or placebo (n = 14) for 10 weeks. Blood and colonic tissue samples were collected at baseline and after intervention to determine biomarkers of folate and vitamin B₁₂ status, MTHFR C677T and MS A2756G genotypes, and ESR1 and MLH1 methylation. Results: Although serum and red cell folate increased (p < 0.001 vs. placebo) and plasma homocysteine decreased (p = 0018 vs. placebo) in the folic acid group, there were no significant changes in ESR1 (p = 0.649 vs. placebo) or MLH1 (p = 0.211 vs. placebo) methylation. There was a significant effect of gender on ESR1 methylation (p = 0.004) and significant gender and genotype (MTHFR C677T and MS A2756G) interactions (p = 0.04 and p = 0.014, respectively) that were independent of treatment group allocation. Conclusions: Short-term folate supplementation in physiological doses decreases plasma homocysteine but has no effect on ESR1 and MLH1 methylation in colonic mucosa of individuals with adenoma. Further studies to investigate the interactions between gender, genotype and DNA methylation suggested in this study are warranted.

These results indicate that while folic acid can modify gene expression, it is difficult to separate its effects from the natural variability in gene expression in the colon.

IntroductionThe number of laparoscopic liver resections undertaken has increased. However, lesions located postero-superiorly are difficult to access. This may be overcome by the novel use of transthoracic port(s). Methods for the safe and transparent introduction of new and modified surgical procedures are limited and a summary of these issues, for minimally invasive trans thoracic liver resections (MITTLR), is lacking.This study aims to understand and summarize technique description, governance procedures and reporting of outcomes for MITTLR. MethodsA systematic literature search to identify primary studies of all designs describing MITTLR was undertaken. How patients were selected for the new technique was examined. The technical Technical outcomes were commonly reported e.g. blood loss (15/16 studies), operative time (15/16) and margin status (11/16). Information on patient reported outcomes and costs were lacking. ConclusionsTechnical details and governance procedures were poorly described. Outcomes focussed on short term details alone. Transparency is needed for reporting the introduction of new surgical techniques to allow their safe dissemination.

IntroductionGabapentin is an antiepileptic drug currently licensed to treat epilepsy and neuropathic pain but has been used off-label to treat acute postoperative pain. The GAP study will compare the effectiveness, cost-effectiveness and safety of gabapentin as an adjunct to standard multimodal analgesia versus placebo for the management of pain after major surgery.Methods and analysisThe GAP study is a multicentre, double-blind, randomised controlled trial in patients aged 18 years and over, undergoing different types of major surgery (cardiac, thoracic or abdominal). Patients will be randomised in a 1:1 ratio to receive either gabapentin (600 mg just before surgery and 600 mg/day for 2 days after surgery) or placebo in addition to usual pain management for each type of surgery. Patients will be followed up daily until hospital discharge and then at 4 weeks and 4 months after surgery. The primary outcome is length of hospital stay following surgery. Secondary outcomes include pain, total opioid use, adverse health events, health related quality of life and costs.Ethics and disseminationThis study has been approved by the Research Ethics Committee . Findings will be shared with participating hospitals and disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Patients will be informed of the results through patient organisations and participant newsletters.Trial registration numberISRCTN63614165.

BackgroundEquestrian sports are common outdoor activities that may carry a risk of liver injury. Due to the relative infrequency of equestrian accidents the injury patterns and outcomes associated with liver trauma in these patients have not been well characterized.MethodsWe examined our experience of the management of equestrian liver trauma in our regional hepatopancreaticobiliary unit at a tertiary referral center. The medical records of patients who sustained liver trauma secondary to equestrian activities were analysed for parameters such as demographic data, liver function tests, patterns of injury, radiological findings, the need for intervention and outcomes.Results20 patients sustained liver trauma after falling from or being kicked by a horse. The majority of patients were haemodynamically stable on admission. Alanine transaminase (ALT) levels were elevated in all patients and right-sided rib fractures were a frequently associated finding. CT demonstrated laceration of the liver in 12 patients, contusion in 3 and subcapsular haematoma in 2. The right lobe of the liver was most commonly affected. Only two patients required laparotomy and liver resection; the remaining 18 were successfully managed conservatively.ConclusionsThe risk of liver injury following a horse kick or falling off a horse should not be overlooked. Early CT imaging is advised in these patients, particularly in the presence of high ALT levels and concomitant chest injuries such as rib fractures. Despite significant liver trauma, conservative management in the form of close observation, ideally in a high-dependency setting, is often sufficient. Laparotomy is only rarely warranted and associated with a significantly higher risk of post-operative bile leaks.

Staging of patients with colorectal liver metastases by PET CT is associated with significantly improved actual long-term survival, and provides valuable prognostic information which guides surgical and oncological treatments.

Introduction CONTACT is a national multidisciplinary study assessing the impact of the COVID-19 pandemic upon diagnostic and treatment pathways among patients with pancreatic ductal adenocarcinoma (PDAC). Methods The treatment of consecutive patients with newly diagnosed PDAC from a pre-COVID-19 pandemic cohort (07/01/2019-03/03/2019) were compared to a cohort diagnosed during the first wave of the UK pandemic (‘COVID’ cohort, 16/03/2020-10/05/2020), with 12-month follow-up. Results Among 984 patients (pre-COVID: n = 483, COVID: n = 501), the COVID cohort was less likely to receive staging investigations other than CT scanning (29.5% vs. 37.2%, p = 0.010). Among patients treated with curative intent, there was a reduction in the proportion of patients recommended surgery (54.5% vs. 76.6%, p = 0.001) and increase in the proportion recommended upfront chemotherapy (45.5% vs. 23.4%, p = 0.002). Among patients on a non-curative pathway, fewer patients were recommended (47.4% vs. 57.3%, p = 0.004) or received palliative anti-cancer therapy (20.5% vs. 26.5%, p = 0.045). Ultimately, fewer patients in the COVID cohort underwent surgical resection (6.4% vs. 9.3%, p = 0.036), whilst more patients received no anti-cancer treatment (69.3% vs. 59.2% p = 0.009). Despite these differences, there was no difference in median overall survival between the COVID and pre-COVID cohorts, (3.5 (IQR 2.8–4.1) vs. 4.4 (IQR 3.6–5.2) months, p = 0.093). Conclusion Pathways for patients with PDAC were significantly disrupted during the first wave of the COVID-19 pandemic, with fewer patients receiving standard treatments. However, no significant impact on survival was discerned.

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