Ursodeoxycholic acid in the management of symptomatic gallstone disease: systematic review and clinician survey.

BACKGROUND: Symptomatic gallstones are common. Ursodeoxycholic acid (UDCA) is a bile acid that dissolves gallstones. There is increasing interest in UDCA for symptomatic gallstones, particularly in those unfit for surgery. METHOD: A UK clinician survey of use and opinions about UDCA in symptomatic gallstones was performed, assessing clinicians' beliefs and perceptions of UDCA effectiveness. A systematic review was performed in accordance with the PRISMA guidelines. PubMed, MEDLINE, and Embase databases were searched for studies of UDCA for symptomatic gallstones (key terms included 'ursodeoxycholic acid'; 'UDCA'; 'biliary pain'; and 'biliary colic'). Information was assessed by two authors, including bias assessment, with independent review of conflicts. RESULTS: Overall, 102 clinicians completed the survey, and 42 per cent had previous experience of using UDCA. Survey responses demonstrated clinical equipoise surrounding the benefit of UDCA for the management of symptomatic gallstones, with no clear consensus for benefit or non-benefit; however, 95 per cent would start using UDCA if there was a randomized clinical trial (RCT) demonstrating a benefit. Eight studies were included in the review: four RCTs, three prospective studies, and one retrospective study. Seven of eight studies were favourable of UDCA for biliary pain. Outcomes and follow-up times were heterogenous, as well as comparator type, with only four of eight studies comparing with placebo. CONCLUSION: Evidence for UDCA in symptomatic gallstones is scarce and heterogenous. Clinicians currently managing symptomatic gallstone disease are largely unaware of the benefit of UDCA, and there is clinical equipoise surrounding the benefit of UDCA. Level 1 evidence is required by clinicians to support UDCA use in the future.

Single-centre review of the management of intra-thoracic oesophageal perforation in a tertiary oesophageal unit: paradigm shift, short- and long-term outcomes over 15 years.

BACKGROUND: Oesophageal perforation is an uncommon surgical emergency associated with high morbidity and mortality. The timing and type of intervention is crucial and there has been a major paradigm shift towards minimal invasive management over the last 15 years. Herein, we review our management of spontaneous and iatrogenic oesophageal perforations and assess the short- and long-term outcomes. METHODS: We performed a retrospective review of consecutive patients presenting with intra-thoracic oesophageal perforation between January 2004 and Dec 2020 in a single tertiary hospital. RESULTS: Seventy-four patients were identified with oesophageal perforations: 58.1% were male; mean age of 68.28 ± 13.67 years. Aetiology was spontaneous in 42 (56.76%), iatrogenic in 29 (39.2%) and foreign body ingestion/related to trauma in 3 (4.1%). The diagnosis was delayed in 29 (39.2%) cases for longer than 24 h. There was change in the primary diagnostic modality over the period of this study with CT being used for diagnosis for 19 of 20 patients (95%). Initial management of the oesophageal perforation included a surgical intervention in 34 [45.9%; primary closure in 28 (37.8%), resection in 6 (8.1%)], endoscopic stenting in 18 (24.3%) and conservative management in 22 (29.7%) patients. On multivariate analysis, there was an effect of pathology (malignant vs. benign; p = 0.003) and surgical treatment as first line (p = 0.048) on 90-day mortality. However, at 1-year and overall follow-up, time to presentation (≤ 24 h vs. > 24 h) remained the only significant variable (p = 0.017 & p = 0.02, respectively). CONCLUSION: Oesophageal perforation remains a condition with high mortality. The paradigm shift in our tertiary unit suggests the more liberal use of CT to establish an earlier diagnosis and a higher rate of oesophageal stenting as a primary management option for iatrogenic perforations. Time to diagnosis and management continues to be the most critical variable in the overall outcome.

Surgical implementation gap: an interrupted time series analysis with interviews examining the impact of surgical trials on surgical practice in England.

OBJECTIVES: Landmark studies published near the turn of the 21st century found an implementation gap concerning the effect of evidenced-based findings on clinical practice. The current study examines the uptake of six trials that produced actionable findings to describe the effects of evidence on practice and the reasons for those effects. DESIGN: A sequential, explanatory mixed methods study was conducted. First, a quantitative study assessed whether actionable findings from large, publicly funded elective surgical trials influenced practice. Subsequently, qualitative interviews were conducted to explain the quantitative findings. SETTING: Changes in NHS-funded practice were tracked across hospitals in England. Interviews were conducted online. DATA AND PARTICIPANTS: The six surgical trials were funded and published by England's National Institute for Health Research's Health Technology Assessment programme between 2006 and 2015. Quantitative time series analyses used data about the frequencies or proportions of relevant surgical procedures conducted in England between 2001 and 2020. Subsequently, qualitative interviews were conducted with 25 participants including study authors, surgeons and other healthcare staff in the supply chain. Transcripts were coded to identify major temporal events and Consolidated Framework for Implementation Research (CFIR) domains/constructs that could influence implementation. Findings were synthesised by clinical area. RESULTS: The quantitative analyses reveal that practice changed in accordance with findings for three trials. In one trial (percutaneous vs nasogastric tube feed after stroke), the change took a decade to occur. In another (patella resurfacing), change anticipated the trial findings. In the third (abdominal aortic aneurysm repair), changes tracked the evolving evidence base. In the remaining trials (two about varicose veins and one about gastric reflux), practice did not change in line with findings. For varicose veins, the results were superseded by a further trial. For gastric reflux, surgical referrals declined as medical treatment increased. The exploratory qualitative analysis informed by CFIR found that evidence from sources apart from the trial in question was mentioned as a reason for non-adoption in the three trials where evidence did not affect practice and in the trial where uptake was delayed. There were no other consistent patterns in the qualitative data. CONCLUSION: While practice does not always change in the direction indicated by clinical trials, our results suggest that individuals, official committees and professional societies do assimilate trial evidence. Decision-makers seem to respond to the totality of evidence such that there are often plausible reasons for not adopting the evidence of any one trial in isolation.

The Perioperative Quality Improvement Programme (PQIP patient study): protocol for a UK multicentre, prospective cohort study to measure quality of care and outcomes after major surgery.

INTRODUCTION: Major surgery accounts for a substantial proportion of health service activity, due not only to the primary procedure, but the longer-term health implications of poor short-term outcome. Data from small studies or from outside the UK indicate that rates of complications and failure to rescue vary between hospitals, as does compliance with best practice processes. Within the UK, there is currently no system for monitoring postoperative complications (other than short-term mortality) in major non-cardiac surgery. Further, there is variation between national audit programmes, in the emphasis placed on quality assurance versus quality improvement, and therefore the principles of measurement and reporting which are used to design such programmes. METHODS AND ANALYSIS: The PQIP patient study is a multi-centre prospective cohort study which recruits patients undergoing major surgery. Patient provide informed consent and contribute baseline and outcome data from their perspective using a suite of patient-reported outcome tools. Research and clinical staff complete data on patient risk factors and outcomes in-hospital, including two measures of complications. Longer-term outcome data are collected through patient feedback and linkage to national administrative datasets (mortality and readmissions). As well as providing a uniquely granular dataset for research, PQIP provides feedback to participating sites on their compliance with evidence-based processes and their patients' outcomes, with the aim of supporting local quality improvement. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Health Research Authority in the UK. Dissemination of interim findings (non-inferential) will form a part of the improvement methodology and will be provided to participating centres at regular intervals, including near-real time feedback of key process measures. Inferential analyses will be published in the peer-reviewed literature, supported by a comprehensive multi-modal communications strategy including to patients, policy makers and academic audiences as well as clinicians.

Delivery of drinking, eating and mobilising (DrEaMing) and its association with length of hospital stay after major noncardiac surgery: observational cohort study.

BACKGROUND: Enhanced recovery pathways are associated with improved postoperative outcomes. However, as enhanced recovery pathways have become more complex and varied, compliance has reduced. The 'DrEaMing' bundle re-prioritises early postoperative delivery of drinking, eating, and mobilising. We investigated relationships between DrEaMing compliance, postoperative hospital length of stay (LOS), and complications in a prospective multicentre major surgical cohort. METHODS: We interrogated the UK Perioperative Quality Improvement Programme dataset. Analyses were conducted in four stages. In an exploratory cohort, we identified independent predictors of DrEaMing. We quantified the association between delivery of DrEaMing (and its component variables) and prolonged LOS in a homogenous colorectal subgroup and assessed generalisability in multispecialty patients. Finally, LOS and complications were compared across hospitals, stratified by DrEaMing compliance. RESULTS: The exploratory cohort comprised 22 218 records, the colorectal subgroup 7230, and the multispecialty subgroup 5713. DrEaMing compliance was 59% (13 112 patients), 60% (4341 patients), and 60% (3421), respectively, but varied substantially between hospitals. Delivery of DrEaMing predicted reduced odds of prolonged LOS in colorectal (odds ratio 0.51 [0.43-0.59], P<0.001) and multispecialty cohorts (odds ratio 0.47 [0.41-0.53], P<0.001). At the hospital level, complications were not the primary determinant of LOS after colorectal surgery, but consistent delivery of DrEaMing was associated with significantly shorter LOS. CONCLUSIONS: Delivery of bundled and unbundled DrEaMing was associated with substantial reductions in postoperative LOS, independent of the effects of confounder variables. Consistency of process delivery, and not complications, predicted shorter hospital-level length of stay. DrEaMing may be adopted by perioperative health systems as a quality metric to support improved patient outcomes and reduced hospital length of stay.

A 16-year Longitudinal Cohort Study of Incidence and Bacteriology of Necrotising Fasciitis in England.

BACKGROUND: Necrotising fasciitis (NF) is a rapidly progressive, destructive soft tissue infection with high mortality. The primary aim of this study was to evaluate the incidence and mortality of NF amongst patients admitted to English National Health Service (NHS) hospitals. The secondary aims included the identification of risk factors for mortality and causative pathogens. METHODS: The Hospital Episodes Statistics database identified patients with NF admitted to English NHS Trusts from 1/1/2002 to 31/12/2017. Information on patient demographics, co-morbid conditions, microbiology specimens, surgical intervention and in-hospital mortality was collected. Uni- and multivariable analyses were performed to investigate factors related to in-hospital mortality. RESULTS: A total of 11,042 patients were diagnosed with NF. Age-standardised incidence rose from 9 per million in 2002 to 21 per million in 2017 (annual percentage change = 6.9%). Incidence increased with age and was higher in men. Age-standardised mortality rate remained at 16% over the study period, while in-hospital mortality declined. On multivariable analysis, the following factors were associated with increased risk of in-hospital mortality: emergency admission, female sex, history of congestive heart failure, peripheral vascular disease, chronic kidney disease and cancer. Admission year and diabetes, which was significantly prevalent at 27%, were not associated with increased risk of mortality. Gram-positive pathogens, particularly Staphylococci, decreased over the study period with a corresponding increase in Gram-negative pathogens, predominantly E. coli. CONCLUSION: The incidence of NF increased markedly from 2002 to 2017 although in-hospital mortality did not change. There was a gradual shift in the causative organisms from Gram-positive to Gram-negative.

Distribution of lymph node metastases in esophageal carcinoma [TIGER study]: study protocol of a multinational observational study.

BACKGROUND: An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. METHODS: The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. DISCUSSION: The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics. TRIAL REGISTRATION: NCT03222895 , date of registration: July 19th, 2017.

Dysregulated alveolar function and complications in smokers following oesophagectomy.

Acute respiratory distress syndrome (ARDS) has a significant impact on post-operative morbidity and mortality following oesophagectomy. Smoking is a risk factor for the development of ARDS, although the mechanism is unclear. We examined the effect of smoking on alveolar and systemic inflammation, in addition to alveolar-capillary permeability, leading to ARDS in patients undergoing oesophagectomy. We compared clinical, biomarker and PiCCO system data between current smokers (n=14) and ex-smokers (n=36) enrolled into a translational substudy of the BALTI-P (Beta Agonist Lung Injury Trial Prevention) trial. Current smokers compared with ex-smokers had significantly higher numbers of circulating neutrophils, elevated bronchoalveolar lavage (BAL) interleukin (IL)-1 receptor antagonist (IL-1ra), soluble tumour necrosis factor receptor-1 and pre-operative plasma soluble intercellular adhesion molecule-1, and lower BAL vascular endothelial growth factor and post-operative plasma IL-17 (p<0.05). On post-operative day 1, current smokers had higher extravascular lung water index (9.80 versus 7.90; p=0.026) and pulmonary vascular permeability index (2.09 versus 1.70; p=0.013). Current smokers were more likely to develop ARDS (57% versus 25%; p=0.031) and had a significantly reduced post-operative median survival (421 versus 771 days; p=0.023). Smoking prior to oesophagectomy is associated with dysregulated inflammation, with higher concentrations of inflammatory mediators and lower concentrations of protective mediators. This translates into a higher post-operative inflammatory alveolar oedema, greater risk of ARDS and poorer long-term survival.

Whole Genome Methylation Analysis of Nondysplastic Barrett Esophagus that Progresses to Invasive Cancer.

OBJECTIVE: To investigate differences in methylation between patients with nondysplastic Barrett esophagus who progress to invasive adenocarcinoma and those who do not. BACKGROUND: Identifying patients with nondysplastic Barrett esophagus who progress to invasive adenocarcinoma remains a challenge. Previous studies have demonstrated the potential utility of epigenetic markers for identifying this group. METHODS: A whole genome methylation interrogation using the Illumina HumanMethylation 450 array of patients with nondysplastic Barrett esophagus who either develop adenocarcinoma or remain static, with validation of findings by bisulfite pyrosequencing. RESULTS: In all, 12 patients with "progressive" versus 12 with "nonprogressive" nondysplastic Barrett esophagus were analyzed via methylation array. Forty-four methylation markers were identified that may be able to discriminate between nondysplastic Barrett esophagus that either progress to adenocarcinoma or remain static. Hypomethylation of the recently identified tumor suppressor OR3A4 (probe cg09890332) validated in a separate cohort of samples (median methylation in progressors 67.8% vs 96.7% in nonprogressors; P = 0.0001, z = 3.85, Wilcoxon rank-sum test) and was associated with the progression to adenocarcinoma. There were no differences in copy number between the 2 groups, but a global trend towards hypomethylation in the progressor group was observed. CONCLUSION: Hypomethylation of OR3A4 has the ability to risk stratify the patient with nondysplastic Barrett esophagus and may form the basis of a future surveillance program.

Enhanced recovery after surgery decreases intestinal recovery time and pain intensity in patients undergoing curative gastrectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) reduces postoperative stress, increases patient satisfaction, and reduces postoperative stay and cost. In this study, we evaluated the feasibility and effectiveness of ERAS protocols compared with conventional perioperative care group and their effect in gastric cancer patients undergoing gastrectomy. METHODS: A cohort of 366 patients were analyzed from a prospectively maintained database. The patients' characteristics, tumor profile, surgical information data and postoperative complications were evaluated. RESULTS: Patients in the ERAS had a faster gastrointestinal function recovery and first flatus (3.26±0.64; P<0.001). Pain intensity of patients in the ERAS group was significantly lower than that of patients in the conventional care group on postoperative days 1 (2.33±0.98; P<0.001) and 3 (1.06±0.63; P<0.001). Postoperative hospital stays were significantly shorter in patients receiving ERAS program (6.66±3.36; P<0.001), than in those patients who received conventional perioperative care (9.02±2.61). CONCLUSION: ERAS can reduce postoperative stress, enhance the recovery of the gut, reduce the pain intensity, and increase satisfaction in gastric cancer patient undergoing curative gastrectomy.

Vitamin D to Prevent Lung Injury Following Esophagectomy-A Randomized, Placebo-Controlled Trial.

OBJECTIVES: Observational studies suggest an association between vitamin D deficiency and adverse outcomes of critical illness and identify it as a potential risk factor for the development of lung injury. To determine whether preoperative administration of oral high-dose cholecalciferol ameliorates early acute lung injury postoperatively in adults undergoing elective esophagectomy. DESIGN: A double-blind, randomized, placebo-controlled trial. SETTING: Three large U.K. university hospitals. PATIENTS: Seventy-nine adult patients undergoing elective esophagectomy were randomized. INTERVENTIONS: A single oral preoperative (3-14 d) dose of 7.5 mg (300,000 IU; 15 mL) cholecalciferol or matched placebo. MEASUREMENTS AND MAIN RESULTS: Primary outcome was change in extravascular lung water index at the end of esophagectomy. Secondary outcomes included PaO2:FIO2 ratio, development of lung injury, ventilator and organ-failure free days, 28 and 90 day survival, safety of cholecalciferol supplementation, plasma vitamin D status (25(OH)D, 1,25(OH)2D, and vitamin D-binding protein), pulmonary vascular permeability index, and extravascular lung water index day 1 postoperatively. An exploratory study measured biomarkers of alveolar-capillary inflammation and injury. Forty patients were randomized to cholecalciferol and 39 to placebo. There was no significant change in extravascular lung water index at the end of the operation between treatment groups (placebo median 1.0 [interquartile range, 0.4-1.8] vs cholecalciferol median 0.4 mL/kg [interquartile range, 0.4-1.2 mL/kg]; p = 0.059). Median pulmonary vascular permeability index values were significantly lower in the cholecalciferol treatment group (placebo 0.4 [interquartile range, 0-0.7] vs cholecalciferol 0.1 [interquartile range, -0.15 to -0.35]; p = 0.027). Cholecalciferol treatment effectively increased 25(OH)D concentrations, but surgery resulted in a decrease in 25(OH)D concentrations at day 3 in both arms. There was no difference in clinical outcomes. CONCLUSIONS: High-dose preoperative treatment with oral cholecalciferol was effective at increasing 25(OH)D concentrations and reduced changes in postoperative pulmonary vascular permeability index, but not extravascular lung water index.

A systematic review of epigenetic biomarkers in progression from non-dysplastic Barrett's oesophagus to oesophageal adenocarcinoma.

OBJECTIVES: The objective of this systematic review is to identify and summarise studies which examine epigenetic biomarkers in patients with Barrett's oesophagus (BO) and their association with progression to oesophageal adenocarcinoma (OADC). BO is a precursor lesion for OADC. There is no clinical test to predict patients who are likely to progress to OADC. An epigenetic biomarker could predict patients who are at high risk of progression from BO to OADC which could facilitate earlier diagnosis and spare those unlikely to develop cancer from regular invasive surveillance endoscopy. SETTING: A systematic search was conducted of the following databases: MEDLINE, MEDLINE in Process, EMBASE, Cochrane Central, ISI Conference Proceedings Citation Index and the British Library's ZETOC. Studies were conducted in secondary and tertiary care settings. PARTICIPANTS: All studies measuring epigenetic change in patients over 18 years old who progressed from non-dysplastic BO to OADC were included. Genetic, in vitro and studies which did not measure progression in the same patient cohort were excluded. Study inclusion and risk of bias of individual eligible studies were assessed in duplicate by two reviewers using a modified Quality in Prognostic Studies tool. RESULTS: 14 studies met the inclusion criteria. 42 epigenetic markers were identified, and 5 studies developed models aiming to predict progression to OADC. CONCLUSIONS: The evidence from this systematic review is suggestive of a role for p16 as an epigenetic biomarker for the progression of BO to OADC. PROSPERO NUMBER: CRD42016038654.

Potential cost savings by minimisation of blood sample delays on care decision making in urgent care services.

BACKGROUND: Timely availability of blood sample results for interpretation affects planning and delivery of patient care from initial assessment in Accident and Emergency (A&E) departments. MATERIALS AND METHODS: Rates of, and reasons for, rejected blood samples submitted from all clinical areas over one month were evaluated. Haemoglobin (Hb) represented haematology and potassium (K+), biochemistry. A prospective observational study evaluated the methodology of sample collection and impact on utility. RESULTS: 16,061 haematology and 16,209 biochemistry samples were evaluated; 1.4% (n = 229, range 0.5-7.3%) and 4.7% (n = 762, range 0.9-14%) respectively were rejected, with 14% (n = 248/1808) K+ rejection rate in A&E. Patients with rejected K+ and Hb had a longer median in-hospital stay of 9 and 76 h respectively and additional stay fixed costs of £26,824.74 excluding treatment. The rejection rate with Vacutainer and butterfly (4.0%) was lower than Vacutainer and cannula (28%). CONCLUSION: Sample rejection rate is high and is associated with increased in-hospital stay and cost. Blood sampling technique impacts on rejection rates. Reduction in sample rejection rates in emergency care areas in acute hospitals has the potential to impact on patient flow and reduce cost.

ARDS following oesophagectomy: a comparison of two trials.

INTRODUCTION: The Beta Agonist Lung Injury Trial-Prevention (BALTI-P) translational substudy and Vitamin D to Prevent Acute Lung Injury Following Oesophagectomy (VINDALOO) trials recruited patients undergoing oesophagectomy, 4 years apart. The acute respiratory distress syndrome (ARDS) rates were lower in the VINDALOO trial. We sought to identify changes between these two trials and identify risk factors for ARDS in oesophagectomy. METHODS: There were data available from 61 patients in the BALTI-P substudy and 68 from VINDALOO. Databases were available for both trials; additional data were collected. Multivariate logistic regression was used to analyse risk factors for ARDS and postoperative complications in the cohorts combined. RESULTS: Logistic regression analysis showed active smoking was associated with an increase in ARDS (OR 3.91; 95% CI 1.33 to 11.5) and dihydropyridine use (OR 5.34;95% CI 1.56 to 18.3). Hospital length of stay was longer for those who took dihydropyridines (median 29 days (IQR 17-42) vs 13 days (IQR 10-18), P=0.0007) or were diabetic (median 25 days (IQR 14-39) vs 13 (IQR 10-19), P=0.023) but not for current smokers (median in never/ex-smokers 13 (IQR 10-23) vs current smokers 15 (IQR 11-20), P=0.73). CONCLUSIONS: Smoking cessation trials should be promoted. Dihydropyridine effects perioperatively require further clinical and mechanistic evaluation. Patients undergoing oesophagectomy are a useful model for studying perioperative ARDS.

A systematic review and meta-analysis of perioperative oral decontamination in patients undergoing major elective surgery.

BACKGROUND: Oral antiseptics reduce nosocomial infections and ventilator-associated pneumonia in critically ill medical and surgical patients intubated for prolonged periods. However, the role of oral antiseptics given before and after planned surgery is not clear. The aim of this systematic review and meta-analysis is to determine the effect of oral antiseptics (chlorhexidine or povidone-iodine) when administered before and after major elective surgery. METHODS: Searches were conducted of the MEDLINE, EMBASE and Cochrane databases. The analysis was performed using the random-effects method and the risk ratio (RR) with 95 % confidence interval (CI). RESULTS: Of 1114 unique identified articles, perioperative chlorhexidine was administered to patients undergoing elective surgery in four studies. This identified 2265 patients undergoing elective cardiac surgery, of whom 1093 (48.3 %) received perioperative chlorhexidine. Postoperative pneumonia and nosocomial infections were observed in 5.3 and 20.2 % who received chlorhexidine compared to 10.4 and 31.3 % who received a control preparation, respectively. Oral perioperative chlorhexidine significantly reduced the risk of postoperative pneumonia (RR = 0.52; 95 % CI 0.39-0.71; p < 0.01) and overall nosocomial infections (RR = 0.65; 95 % CI 0.52-0.81; p < 0.01), with no effect on in-hospital mortality (RR = 1.01; 95 % CI 0.49-2.09; p = 0.98). CONCLUSIONS: Perioperative oral chlorhexidine significantly decreases the incidence of nosocomial infection and postoperative pneumonia in patients undergoing elective cardiac surgery. There are no randomised controlled studies of this simple and cheap intervention in patients undergoing elective non-cardiac surgery. TRIAL REGISTRATION: This systematic review was registered with the International prospective register of systematic reviews (PROSPERO). The registration number is CRD42015016063.

The incremental benefit of two quadrant lavage for peritoneal cytology at staging laparoscopy for oesophagogastric adenocarcinoma.

BACKGROUND: Patients with positive peritoneal cytology from oesophagogastric cancer have a poor prognosis. The purpose of this study was to compare lavage cytology from the pelvis alone with the pelvis and subphrenic areas at staging laparoscopy in patients with potentially resectable oesophagogastric adenocarcinoma. METHODS: Between November 2006 and November 2010, all patients with operable oesophagogastric adenocarcinoma on spiral CT considered fit for surgical resection underwent staging laparoscopy. Subphrenic and pelvic peritoneal lavage for cytology was performed followed by laparoscopic biopsy of any visible peritoneal disease. Patients were divided into groups: macroscopic peritoneal metastases (P+), no macroscopic peritoneal disease with negative cytology (P-C-), no macroscopic peritoneal disease with positive pelvic cytology (P-PC+), no macroscopic peritoneal disease with positive subphrenic cytology (P-SC+), or both (P-PSC+). RESULTS: A total of 316 staging laparoscopy procedures were performed; 245 patients (78 %) were P-C-, 28 (9 %) were P+, and 43 (14 %) were P-C+, of whom 29 (9 %) were P-PSC+, 10 (3 %) were P-SC+, and 4 (1 %) were P-PC+. Pelvic cytology alone had 76.7 % sensitivity for peritoneal disease, and subphrenic cytology alone had 90.7 % sensitivity. CONCLUSIONS: Peritoneal lavage for cytology at staging laparoscopy has an incremental benefit for staging oesophagogastric adenocarcinoma in the absence of macroscopic metastatic disease. Subphrenic washings have the highest yield of positive results. Performing isolated pelvic washings for cytology will understage 23.3 % of patients with microscopic peritoneal disease. The routine use of subphrenic in combination with pelvic lavage for cytology at staging laparoscopy in patients with oesophagogastric adenocarcinoma has an incremental benefit in detecting cytology-positive disease over either pelvic or subphrenic cytology alone.

Vitamin D to prevent acute lung injury following oesophagectomy (VINDALOO): study protocol for a randomised placebo controlled trial.

BACKGROUND: Acute lung injury occurs in approximately 25% to 30% of subjects undergoing oesophagectomy. Experimental studies suggest that treatment with vitamin D may prevent the development of acute lung injury by decreasing inflammatory cytokine release, enhancing lung epithelial repair and protecting alveolar capillary barrier function. METHODS/DESIGN: The 'Vitamin D to prevent lung injury following oesophagectomy trial' is a multi-centre, randomised, double-blind, placebo-controlled trial. The aim of the trial is to determine in patients undergoing elective transthoracic oesophagectomy, if pre-treatment with a single oral dose of vitamin D3 (300,000 IU (7.5 mg) cholecalciferol in oily solution administered seven days pre-operatively) compared to placebo affects biomarkers of early acute lung injury and other clinical outcomes. The primary outcome will be change in extravascular lung water index measured by PiCCO® transpulmonary thermodilution catheter at the end of the oesophagectomy. The trial secondary outcomes are clinical markers indicative of lung injury: PaO2:FiO2 ratio, oxygenation index; development of acute lung injury to day 28; duration of ventilation and organ failure; survival; safety and tolerability of vitamin D supplementation; plasma indices of endothelial and alveolar epithelial function/injury, plasma inflammatory response and plasma vitamin D status. The study aims to recruit 80 patients from three UK centres. DISCUSSION: This study will ascertain whether vitamin D replacement alters biomarkers of lung damage following oesophagectomy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27673620.

MALDI profiles of proteins and lipids for the rapid characterisation of upper GI-tract cancers.

AIM: To identify a reliable MALDI 'cancer fingerprint' to aid in the rapid detection and characterisation of malignant upper GI-tract disease from endoscopic biopsies. METHODS: A total of 183 tissue biopsies were collected from 126 patients with or without oesophago-gastric malignancy and proteins and lipids separated by methanol/chloroform extraction. Peak intensities in the lipid and protein MALDI spectra from five types of samples (normal oesophageal mucosa from controls, normal oesophageal mucosa from patients with oesophageal adenocarcinoma, nondysplastic Barrett's oesophagus, oesophageal adenocarcinoma, normal gastric mucosa and gastric adenocarcinoma) were compared using non-parametric statistical tests and ROC analyses. RESULTS: Normal oesophageal and gastric tissue generated distinct MALDI spectra characterised by higher levels of calgranulins in oesophageal tissue. MALDI spectra of polypeptides and lipids discriminated between oesophageal adenocarcinoma and Barrett's and normal oesophagus, and between gastric cancer and normal stomach. Many down-regulations were unique to each cancer type whilst some up-regulations, most notably increased HNPs 1-3, were common. CONCLUSIONS: MALDI spectra of small tissue biopsies generated with this straightforward method can be used to rapidly detect numerous cancer-associated biochemical changes. These can be used to identify upper GI-tract cancers regardless of tumour location.

An alternative option in the management of blunt splenic injury.

Splenic injury is a preventable cause of mortality following blunt trauma. The majority of splenic injuries can be managed conservatively. Laparotomy is indicated in the haemodynamically unstable patient, or those with other intra-abdominal injuries requiring surgery. Angio-embolization can be used to achieve haemostasis and preserve splenic parenchyma. The expertise and experience of the multidisciplinary trauma team and resources of the receiving facility are critical in determining the optimal management approach. We present a patient with a successful outcome following selective angio-embolization for ongoing bleeding from a Grade 4 splenic injury.