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.

The value of inflammation based prognostic scores in patients undergoing surgical resection for oesophageal and gastric carcinoma.

BACKGROUND AND OBJECTIVES: Surgical interventions for oesophagogastric cancer carry a significant burden of morbidity and mortality. A range of inflammation based prognostic scores have been proposed in an attempt to predict outcome. This study evaluated five such prognostic scores in oesophageal and gastric carcinoma patients. METHODS: The modified Glasgow Prognostic Score (mGPS), Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI), and Prognostic Nutrition Index (PNI) were calculated for 723 consecutive patients undergoing oesophagectomy or gastrectomy at a single center. The predictive accuracy of each score was assessed using ROC curves and survival analyses. RESULTS: Overall, only PLR and PNI were significantly predictive of patient survival (both P < 0.001), with no significant association detected for mGPS (P = 0.480), NLR (P = 0.210), or PI (P = 0.808). Subgroup analysis found the predictive accuracy of PNI to be significantly greater in oesophagectomy than gastrectomy patients (hazard ratio 2.75 vs 1.39, P = 0.016) and mGPS to be predictive of patient survival only in oesophagectomies (P < 0.001). CONCLUSIONS: Inflammation based prognostic scores may have a role in patients undergoing resection for oesophageal and gastric cancer. These scores are easily calculable from routinely collected data and could be used as an adjunct to existing staging modalities.

A potential role for hepcidin in obesity-driven colorectal tumourigenesis.

The obesity epidemic is associated with increases in the incidence of several types of cancer, including colorectal cancer, and is associated with poor outcomes for patients. Adipose tissue is considered biologically active and represents a plausible link between cancer and obesity due to the many factors that it secretes. In the present study, human adipose tissue was cultured in vitro and predifferentiated adipocyte secretome [preadipocyte (PAS)] and differentiated adipocyte secretome (DAS) were collected. Quantification of interleukin-6 (IL-6), leptin and hepcidin in the DAS medium was compared to the PAS medium. Fold change levels of hepcidin, leptin and IL-6 in DAS (2.88±0.28, 12.34±0.95 and 31.29±1.89 fold increases) were significantly higher compared to these in PAS (p=0.05). The SW480 colorectal cancer cells were co-cultured with DAS in the presence or absence of leptin, IL-6 or hepcidin inhibitors and cellular viability and proliferation assays were performed. The culture of SW480 with DAS increased the cell proliferation and viability by 30 and 15% (p=0.02 and p=0.03) respectively, which was reversed in the presence of inhibitors. Challenging the SW480 cells with IL-6 or hepcidin significantly elevated colonocyte­secreted leptin (p=0.05). Challenging the SW480 cells with leptin or hepcidin resulted in elevated levels of colonocyte-secreted IL-6 (p=0.05). Similarly, challenging cells with either IL-6 or leptin markedly elevated the level of secreted hepcidin (p=0.05) and this was associated with an induction in colonocyte iron levels in both cases. Collectively, these data revealed that adipocyte-secreted factors can ultimately modulate colonocyte iron levels and phenotype.

BRAF mutations are associated with increased iron regulatory protein-2 expression in colorectal tumorigenesis.

A role for iron in carcinogenesis is supported by evidence that iron metabolism proteins are modulated in cancer progression. To date, however, the expression of iron regulatory protein-2 (IRP2), which is known to regulate several iron metabolism proteins, has not been assessed in colorectal cancer. Expression of IRP2 was assessed by quantitative RT-PCR and immunohistochemistry in human colorectal cancer tissue. By interrogating The Cancer Genome Atlas (TCGA) database, expression of IRP2 and transferrin receptor-1 (TfR1) was assessed relative to common mutations that are known to occur in cancer. The impact of suppressing IRP2 on cellular iron metabolism was also determined by using siRNA and by using the MEK inhibitor trametinib. IRP2 was overexpressed in colorectal cancer compared to normal colonic mucosa and its expression was positively correlated with TfR1 expression. In addition, IRP2 expression was associated with mutations in BRAF. The MEK inhibitor trametinib suppressed IRP2 and this was associated with a suppression in TfR1 and the labile iron pool (LIP). Moreover, epidermal growth factor stimulation resulted in decreased ferritin expression and an increase in the LIP which were independent of IRP2. Results presented here suggest that ablating IRP2 provides a therapeutic platform for intervening in colorectal tumorigenesis.

Organometallic nucleoside analogues with ferrocenyl linker groups: synthesis and cancer cell line studies.

Examples of organometallic compounds as nucleoside analogues are rare within the field of medicinal bioorganometallic chemistry. We report on the synthesis and properties of two chiral ferrocene derivatives containing a nucleobase and a hydroxyalkyl group. These so-called ferronucleosides show promising anticancer activity, with cytostatic studies on five different cancer cell lines indicating that both functional groups are required for optimal activity.

Iron chelation in the treatment of cancer: a new role for deferasirox?

Iron plays a crucial role in a number of metabolic pathways including oxygen transport, DNA synthesis, and ATP generation. Although insufficient systemic iron can result in physical impairment, excess iron has also been implicated in a number of diseases including ischemic heart disease, diabetes, and cancer. Iron chelators are agents which bind iron and facilitate its excretion. Experimental iron chelators have demonstrated potent anti-neoplastic properties in a number of cancers in vitro. These agents have yet to be translated into clinical practice, however, largely due to the significant side effects encountered in pre-clinical models. A number of licensed chelators, however, are currently in clinical use for the treatment of iron overload associated with certain non-neoplastic diseases. Deferasirox is one such agent and the drug has shown significant anti-tumor effects in a number of in vitro and in vivo studies. Deferasirox is orally administered and has demonstrated a good side effect profile in clinical practice to date. It represents an attractive agent to take forward into clinical trials of iron chelators as anti-cancer agents.

Administration of hyoscine- n-butylbromide during colonoscopy: a survey of current UK practice.

OBJECTIVE: Current British Society of Gastroenterology (BSG) guidelines suggest that hyoscine-n-butylbromide (Buscopan) should be avoided during colonoscopy in patients with a history of angle-closure glaucoma. Angle-closure glaucoma, however, is not very common, is asymptomatic before onset and is treated definitively by a single laser treatment (if spotted early). Open-angle glaucoma is not affected by hyoscine. The aim of this study was to assess the use of hyoscine among colonoscopists, with particular reference to glaucoma. DESIGN AND SETTING: Following BSG endoscopy subcommittee approval, a short questionnaire was electronically administered to members of the BSG and the Association of Coloproctology of Great Britain and Ireland. MAIN OUTCOME MEASURES: Hyoscine use among colonoscopists, and effect of glaucoma history upon prescribing practice. RESULTS: 188 colonoscopists responded to some or all of the questions. 123/183 (67.2%) of respondents claimed they were aware of the BSG guidelines. 160/187 (85.6%) sometimes or always use hyoscine, while 27/187 (14.4%) never do. 137/177 (77.4%) always enquire about glaucoma history prior to administration, although 147/176 (83.0%) make no differentiation between open-angle or angle-closure forms. 126/178 (70.8%) would (incorrectly) withhold hyoscine if the patient declares a history of any form of glaucoma. 140/179 (78.2%) do not substitute glucagon as an antispasmodic. 4/180 (2.2%) had encountered ophthalmic complications post-administration. CONCLUSIONS: Current BSG guidelines pertaining to hyoscine use and glaucoma are inappropriate; the authors recommend revision. Patients undergoing colonoscopy who have received hyoscine should, instead, be advised to seek urgent medical advice if they develop ophthalmic symptoms.