Simple biliary cysts of the liver can be lined by mucinous epithelium.

AIMS & METHODS: Simple biliary cysts of the liver are described to be lined by biliary epithelium and may be managed nonsurgically or by deroofing only. By contrast, its important differential diagnosis-mucinous cystic neoplasm (MCN)-is at least focally lined by mucinous epithelium, has malignant potential, and therefore should be resected. Following anecdotal observations in routine diagnostic practice, the following case series was assembled to confirm whether simple biliary cysts of the liver can be lined by mucinous epithelium. Detailed clinicoradiological review, including postoperative follow-up, was also completed to assess whether the presence of mucinous epithelium had any associations, including a risk of hepatobiliary neoplasia. RESULTS: Histological review of 21 simple biliary cysts received as surgical specimens over a 3- year period confirmed an absence of ovarian-like stroma in all cases. The lining epithelium of seven cysts showed focal supranuclear/apical mucin, as confirmed histochemically. Cysts with mucinous epithelium were generally larger and more often showed histological evidence of previous haemorrhage than cysts without this epithelium. There were no other statistically-significant differences in clinicoradiological features between cysts with and without mucinous epithelium, including at postoperative radiological follow-up. CONCLUSIONS: Focal mucinous epithelium can be present in at least one-third of surgically-managed, simple biliary cysts of the liver. Such epithelium may be metaplastic and should not be misinterpreted to indicate a diagnosis of MCN but, apart from this, appears to have no clinical significance. Ovarian-like stroma may therefore be the only histological feature that reliably distinguishes MCN from simple biliary cyst.

A Systematic Review of Minimally Invasive Trans-thoracic Liver Resection to Examine Intervention Description, Governance, and Outcome Reporting of an Innovative Technique.

INTRODUCTION: The 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 trans-thoracic 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. METHODS: A 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 components of MITTLR were identified and summarized to understand technique development over time. Governance arrangements (eg, Institutional Review Board approval) and steps taken to mitigate harm were recorded. Finally, specific outcomes reported across studies were documented. RESULTS: Of 2067 screened articles, 16 were included reporting data from 145 patients and 6 countries. Selection criteria for patients was explicitly stated in 2 papers. No studies fully described the technique. Five papers reported ethical approval and 3 gave details of patient consent. No study reported on steps taken to mitigate harm.Technical outcomes were commonly reported, for example, blood loss (15/16 studies), operative time (15/16), and margin status (11/16). Information on patient-reported outcomes and costs were lacking. CONCLUSIONS: Technical 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.

Microscopic resection margins adversely influence survival rates after surgery for colorectal liver metastases: An open ambidirectional Cohort Study.

BACKGROUND: Liver resection is the most effective treatment for patients with colorectal liver metastases (CRLMs). Patients with tumour at the resection margin (R1) are reported to have worse survival compared to those with an uninvolved resection margin (R0). Recent data has questioned this finding. This study investigates whether R1 resections adversely influence survival when compared to R0 resections. MATERIAL AND METHODS: Patients undergoing surgery for CRLM, identified from a prospectively maintained database, from January 2007 to January 2017, were included. Univariate and multivariate survival analyses were performed. p < 0.05 was significant. RESULTS: 282 patients were included. Median age 72 (32-90) years. 236 patients (83.7%) had chemotherapy and surgery, whilst 46 (16.3%) had surgery alone. 149 patients (52.8%) were alive at the end of the study period. R1 resection on univariate survival analysis was associated with better survival (HR 2.12, 95%CI 1.60-4.61, p = 0.0002). Multivariate analysis controlling for age and gender, identified presence of extrahepatic disease (HR 2.03, 95%CI 1.17-3.52, p < 0.001), R0 resection (HR 0.33, 95%CI 0.19-0.59, p = 0.003), primary tumour stage (HR 1.57, 95%CI 1.04-2.40, p = 0.034) and primary tumour differentiation (HR 2.56, 95%CI 1.01-6.46, p = 0.047), as prognostic factors for poorer survival. Five-year and 10-year survival were 54.3% and 41.7% respectively in patients with an R0 resection and, 25.8% and 17.2% in those with an R1 resection. CONCLUSION: The presence of extrahepatic disease, an R1 resection margin, advanced T-stage and poorer tumour differentiation were associated with worse survival in CRLM surgery and R0 resection is recommended.

Effectiveness, cost-effectiveness and safety of gabapentin versus placebo as an adjunct to multimodal pain regimens in surgical patients: protocol of a placebo controlled randomised controlled trial with blinding (GAP study).

INTRODUCTION: Gabapentin 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 ANALYSIS: The 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 DISSEMINATION: This 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 NUMBER: ISRCTN63614165.

Outcomes following liver trauma in equestrian accidents.

BACKGROUND: Equestrian 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. METHODS: We 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. RESULTS: 20 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. CONCLUSIONS: The 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.

Improved long-term survival after resection of colorectal liver metastases following staging with FDG positron emission tomography.

BACKGROUND AND OBJECTIVES: Actual long-term survival of patients with colorectal liver metastases staged by PET CT has not been reported. Objectives were to investigate whether PET CT staging results in actual improved long-term survival, to examine outcome in patients with 'equivocal' PET CT scans, and those excluded from hepatectomy by PET CT. METHODS: A retrospective analysis of patients undergoing hepatectomy for colorectal liver metastases between March 1998 and September 2008. RESULTS: Overall 5- and 10-year survival was 44.8% and 23.9%. PET CT staging resulted in management changes in 23% of patients. PET CT staged patients showed significantly better survival than those staged by CT alone at 3 years (79.8% vs. 54.1%) and at 5 years (54.1% vs. 37.3%) with median survivals of 6.4 years versus 3.9 years (log rank P = 0.018). Patients with equivocal PET CT scans showed worse median survival than those with favourable PET CT (log rank P = 0.002), but may include a subpopulation whose prognosis trends towards a more favourable outcome than those excluded from liver resection by PET CT, whose median survival remains limited to 21 months. CONCLUSIONS: 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.

The influence of folate supplementation on global gene expression in normal colonic mucosa of subjects with colorectal adenoma.

SCOPE: We determined whether short-term supplementation with a physiological dose of folate alters global gene expression in the normal colonic mucosa of subjects with colorectal adenoma. METHODS AND RESULTS: Fourteen subjects with adenoma, randomised to receive folic acid (400µg/day, n = 6) or placebo (n = 8) for 10 weeks, had blood samples and colonic tissue biopsies collected before and after the intervention. RNA extracted from colonic tissue samples was used to determine global gene expression in the colon using Affymetrix® Microarray GeneChips and real-time RT-PCR. Following intervention, 67 genes were upregulated and 13 genes were downregulated in the folic acid group, while 21 genes were upregulated and none were downregulated in the placebo group (p < 0.05, adjusted for multiple testing). Thirty-six genes were upregulated and 18 genes were downregulated in the folic acid group when compared with placebo, but none of these were statistically significant after adjustment for multiple testing. These genes are involved in multiple pathways, including cell cycle, signal transduction, cell differentiation, transport, cell division, cell motility, protein transport, and immune response. CONCLUSION: 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.

Short-term folate supplementation in physiological doses has no effect on ESR1 and MLH1 methylation in colonic mucosa of individuals with adenoma.

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.