Enhanced recovery after surgery

Enhanced Recovery or Fast Track Recovery after Surgery protocols (ERAS) have significantly changed perioperative care following colorectal surgery and are promoted as reducing the stress response to surgery. The present systematic review aimed to examine the impact on the magnitude of the systemic inflammatory response (SIR) for each ERAS component following colorectal surgery using objective markers such as C-reactive protein (CRP) and interleukin-6 (IL-6). A literature search was performed of the US National Library of Medicine (MEDLINE), EMBASE, PubMed, and the Cochrane Database of Systematic Reviews using appropriate keywords and subject headings to February 2015. Included studies had to assess the impact of the selected ERAS component on the SIR using either CRP or IL-6. Nineteen studies, including 1898 patients, were included. Fourteen studies (1246 patients) examined the impact of laparoscopic surgery on the postoperative markers of SIR. Ten of these studies (1040 patients) reported that laparoscopic surgery reduced postoperative CRP. One study (53 patients) reported reduced postoperative CRP using opioid-minimising analgesia. One study (142 patients) reported no change in postoperative CRP following preoperative carbohydrate loading. Two studies (108 patients) reported conflicting results with respect to the impact of goal-directed fluid therapy on postoperative IL-6. No studies examined the effect of other ERAS components, including mechanical bowel preparation, antibiotic prophylaxis, thromboprophylaxis, and avoidance of nasogastric tubes and peritoneal drains on markers of the postoperative SIR following colorectal surgery. The present systematic review shows that, with the exception of laparoscopic surgery, objective evidence of the effect of individual components of ERAS protocols in reducing the stress response following colorectal surgery is limited

Long-term follow-up of patients undergoing resection of tnm stage i colorectal cancer: an analysis of tumour and host determinants of outcome

Background Screening for colorectal cancer improves cancer-specific survival (CSS) through the detection of early-stage disease; however, its impact on overall survival (OS) is unclear. The present study examined tumour and host determinants of outcome in TNM Stage I disease. Methods All patients with pathologically confirmed TNM Stage I disease across 4 hospitals in the North of Glasgow between 2000 and 2008 were included. The preoperative modified Glasgow Prognostic Score (mGPS) was used as a marker of the host systemic inflammatory response (SIR). Results There were 191 patients identified, 105 (55 %) were males, 91 (48 %) were over the age of 75 years and 7 (4 %) patients underwent an emergency operation. In those with a preoperative CRP result (n = 150), 35 (24 %) patients had evidence of an elevated mGPS. Median follow-up of survivors was 116 months (minimum 72 months) during which 88 (46 %) patients died; 7 (8 %) had postoperative deaths, 15 (17 %) had cancer-related deaths and 66 (75 %) had non-cancer-related deaths. 5-year CSS was 95 % and OS was 76 %. On univariate analysis, advancing age (p < 0.001), emergency presentation (p = 0.008), and an elevated mGPS (p = 0.012) were associated with reduced OS. On multivariate analysis, only age (HR = 3.611, 95 % CI 2.049–6.365, p < 0.001) and the presence of an elevated mGPS (HR = 2.173, 95 % CI 1.204–3.921, p = 0.010) retained significance. Conclusions In patients undergoing resection for TNM Stage I colorectal cancer, an elevated mGPS was an objective independent marker of poorer OS. These patients may benefit from a targeted intervention

Validation of a modified clinical risk score to predict cancer-specific survival for stage II colon cancer

Many patients with stage II colon cancer will die of their disease despite curative surgery. Therefore, identification of patients at high risk of poor outcome after surgery for stage II colon cancer is desirable. This study aims to validate a clinical risk score to predict cancer-specific survival in patients undergoing surgery for stage II colon cancer. Patients undergoing surgery for stage II colon cancer in 16 hospitals in the West of Scotland between 2001 and 2004 were identified from a prospectively maintained regional clinical audit database. Overall and cancer-specific survival rates up to 5 years were calculated. A total of 871 patients were included. At 5 years, cancer-specific survival was 81.9% and overall survival was 65.6%. On multivariate analysis, age ≥75 years (hazard ratio (HR) 2.11, 95% confidence intervals (CI) 1.57–2.85; P<0.001) and emergency presentation (HR 1.97, 95% CI 1.43–2.70; P<0.001) were independently associated with cancer-specific survival. Age and mode of presentation HRs were added to form a clinical risk score of 0–2. The cancer-specific survival at 5 years for patients with a cumulative score 0 was 88.7%, 1 was 78.2% and 2 was 65.9%. These results validate a modified simple clinical risk score for patients undergoing surgery for stage II colon cancer. The combination of these two universally documented clinical factors provides a solid foundation for the examination of the impact of additional clinicopathological and treatment factors on overall and cancer-specific survival

Factors associated with the efficacy of polyp detection during routine flexible sigmoidoscopy

Objective: Flexible sigmoidoscopy reduces the incidence of colonic cancer through the detection and removal of premalignant adenomas. However, the efficacy of the procedure is variable. The aim of the present study was to examine factors associated with the efficacy of detecting polyps during flexible sigmoidoscopy. Design and patients: Retrospective observational cohort study of all individuals undergoing routine flexible sigmoidoscopy in NHS Greater Glasgow and Clyde from January 2013 to January 2016. Results: A total of 7713 patients were included. Median age was 52 years and 50% were male. Polyps were detected in 1172 (13%) patients. On multivariate analysis, increasing age (OR 1.020 (1.016–1.023) p<0.001), male sex (OR 1.23 (1.10–1.38) p<0.001) and the use of any bowel preparation (OR 3.55 (1.47–8.57) p<0.001) were associated with increasing numbers of polyps being detected. There was no significant difference in the number of polyps found in patients who had received an oral laxative preparation compared with an enema (OR 3.81 (1.57–9.22) vs 3.45 (1.43–8.34)), or in those who received sedation versus those who had not (OR 1.00 vs 1.04 (0.91–1.17) p=0.591). Furthermore, the highest number of polyps was found when the sigmoidoscope was inserted to the descending colon (OR 1.30 (1.04–1.63)). Conclusions: Increasing age, male sex and the utilisation of any bowel preparation were associated with an increased polyp detection rate. However, the use of sedation or oral laxative preparation appears to confer no additional benefit. In addition, the results indicate that insertion to the descending colon optimises the efficacy of flexible sigmoidoscopy polyp detection

Application of Cryopreserved Human Hepatocytes in Trichloroethylene Risk Assessment: Relative Disposition of Chloral Hydrate to Trichloroacetate and Trichloroethanol

BACKGROUND: Trichloroethylene (TCE) is a suspected human carcinogen and a common ground-water contaminant. Chloral hydrate (CH) is the major metabolite of TCE formed in the liver by cytochrome P450 2E1. CH is metabolized to the hepatocarcinogen trichloroacetate (TCA) by aldehyde dehydrogenase (ALDH) and to the noncarcinogenic metabolite trichloroethanol (TCOH) by alcohol dehydrogenase (ADH). ALDH and ADH are polymorphic in humans, and these polymorphisms are known to affect the elimination of ethanol. It is therefore possible that polymorphisms in CH metabolism will yield subpopulations with greater than expected TCA formation with associated enhanced risk of liver tumors after TCE exposure. METHODS: The present studies were undertaken to determine the feasibility of using commercially available, cryogenically preserved human hepatocytes to determine simultaneously the kinetics of CH metabolism and ALDH/ADH genotype. Thirteen human hepatocyte samples were examined. Linear reciprocal plots were obtained for 11 ADH and 12 ALDH determinations. RESULTS: There was large interindividual variation in the V(max) values for both TCOH and TCA formation. Within this limited sample size, no correlation with ADH/ALDH genotype was apparent. Despite the large variation in V(max) values among individuals, disposition of CH into the two competing pathways was relatively constant. CONCLUSIONS: These data support the use of cryopreserved human hepatocytes as an experimental system to generate metabolic and genomic information for incorporation into TCE cancer risk assessment models. The data are discussed with regard to cellular factors, other than genotype, that may contribute to the observed variability in metabolism of CH in human liver

Systemic inflammation predicts all-cause mortality: a Glasgow Inflammation Outcome Study

Introduction: Markers of the systemic inflammatory response, including C-reactive protein and albumin (combined to form the modified Glasgow Prognostic Score), as well as neutrophil, lymphocyte and platelet counts have been shown to be prognostic of survival in patients with cancer. The aim of the present study was to examine the prognostic relationship between these markers of the systemic inflammatory response and all-cause, cancer, cardiovascular and cerebrovascular mortality in a large incidentally sampled cohort.<p></p> Methods: Patients (n = 160 481) who had an incidental blood sample taken between 2000 and 2008 were studied for the prognostic value of C-reactive protein (>10mg/l, albumin (>35mg/l), neutrophil (>7.5×109/l) lymphocyte and platelet counts. Also, patients (n = 52 091) sampled following the introduction of high sensitivity C-reactive protein (>3mg/l) measurements were studied. A combination of these markers, to make cumulative inflammation-based scores, were investigated.<p></p> Results: In all patients (n = 160 481) C-reactive protein (>10mg/l) (HR 2.71, p<0.001), albumin (>35mg/l) (HR 3.68, p<0.001) and neutrophil counts (HR 2.18, p<0.001) were independently predictive of all-cause mortality. These associations were also observed in cancer, cardiovascular and cerebrovascular mortality before and after the introduction of high sensitivity C-reactive protein measurements (>3mg/l) (n = 52 091). A combination of high sensitivity C-reactive protein (>3mg/l), albumin and neutrophil count predicted all-cause (HR 7.37, p<0.001, AUC 0.723), cancer (HR 9.32, p<0.001, AUC 0.731), cardiovascular (HR 4.03, p<0.001, AUC 0.650) and cerebrovascular (HR 3.10, p<0.001, AUC 0.623) mortality. Conclusion The results of the present study showed that an inflammation-based prognostic score, combining high sensitivity C-reactive protein, albumin and neutrophil count is prognostic of all-cause mortality

A copula model of wind turbine performance

The conventional means of assessing the performance of a wind turbine is through consideration of its power curve which provides the relationship between power output and measured wind speed. In this paper it is shown how the joint probability distribution of power and wind speed can be learned from data, rather than from examination of the implied function of the two variables. Such an approach incorporates measures of uncertainty into performance estimates, allows inter-plant performance comparison, and could be used to simulate plant operation via sampling. A preliminary model is formulated and fitted to operational data as an illustration

Clinicopathological determinants of an elevated systemic inflammatory response following elective potentially curative resection for colorectal cancer

Introduction: The postoperative systemic inflammatory response (SIR) is related to both long- and short-term outcomes following surgery for colorectal cancer. However, it is not clear which clinicopathological factors are associated with the magnitude of the postoperative SIR. The present study was designed to determine the clinicopathological determinants of the postoperative systemic inflammatory response following colorectal cancer resection. Methods: Patients with a histologically proven diagnosis of colorectal cancer who underwent elective, potentially curative resection during a period from 1999 to 2013 were included in the study (n = 752). Clinicopathological data and the postoperative SIR, as evidenced by postoperative Glasgow Prognostic Score (poGPS), were recorded in a prospectively maintained database. Results: The majority of patients were aged 65 years or older, male, were overweight or obese, and had an open resection. After adjustment for year of operation, a high day 3 poGPS was independently associated with American Society of Anesthesiologists (ASA) grade (hazard ratio [HR] 1.96; confidence interval [CI] 1.25–3.09; p = 0.003), body mass index (BMI) (HR 1.60; CI 1.07–2.38; p = 0.001), mGPS (HR 2.03; CI 1.35–3.03; p = 0.001), and tumour site (HR 2.99; CI 1.56–5.71; p < 0.001). After adjustment for year of operation, a high day 4 poGPS was independently associated with ASA grade (HR 1.65; CI 1.06–2.57; p = 0.028), mGPS (HR 1.81; CI 1.22–2.68; p = 0.003), NLR (HR 0.50; CI 0.26–0.95; p = 0.034), and tumour site (HR 2.90; CI 1.49–5.65; p = 0.002). Conclusions: ASA grade, BMI, mGPS, and tumour site were consistently associated with the magnitude of the postoperative systemic inflammatory response, evidenced by a high poGPS on days 3 and 4, in patients undergoing elective potentially curative resection for colorectal cancer

Simple and objective prediction of survival in patients with lung cancer: staging the host systemic inflammatory response

Background. Prediction of survival in patients diagnosed with lung cancer remains problematical. The aim of the present study was to examine the clinical utility of an established objective marker of the systemic inflammatory response, the Glasgow Prognostic Score, as the basis of risk stratification in patients with lung cancer. Methods. Between 2005 and 2008 all newly diagnosed lung cancer patients coming through the multidisciplinary meetings (MDTs) of four Scottish centres were included in the study. The details of 882 patients with a confirmed new diagnosis of any subtype or stage of lung cancer were collected prospectively. Results. The median survival was 5.6 months (IQR 4.8–6.5). Survival analysis was undertaken in three separate groups based on mGPS score. In the mGPS 0 group the most highly predictive factors were performance status, weight loss, stage of NSCLC, and palliative treatment offered. In the mGPS 1 group performance status, stage of NSCLC, and radical treatment offered were significant. In the mGPS 2 group only performance status and weight loss were statistically significant. Discussion. This present study confirms previous work supporting the use of mGPS in predicting cancer survival; however, it goes further by showing how it might be used to provide more objective risk stratification in patients diagnosed with lung cancer

A functional description of CymA, an electron-transfer hub supporting anaerobic respiratory flexibility in Shewanella

CymA (tetrahaem cytochrome c) is a member of the NapC/NirT family of quinol dehydrogenases. Essential for the anaerobic respiratory flexibility of shewanellae, CymA transfers electrons from menaquinol to various dedicated systems for the reduction of terminal electron acceptors including fumarate and insoluble minerals of Fe(III). Spectroscopic characterization of CymA from Shewanella oneidensis strain MR-1 identifies three low-spin His/His co-ordinated c-haems and a single high-spin c-haem with His/H2O co-ordination lying adjacent to the quinol-binding site. At pH 7, binding of the menaquinol analogue, 2-heptyl-4-hydroxyquinoline-N-oxide, does not alter the mid-point potentials of the high-spin (approximately −240 mV) and low-spin (approximately −110, −190 and −265 mV) haems that appear biased to transfer electrons from the high- to low-spin centres following quinol oxidation. CymA is reduced with menadiol (Em=−80 mV) in the presence of NADH (Em=−320 mV) and an NADH–menadione (2-methyl-1,4-naphthoquinone) oxidoreductase, but not by menadiol alone. In cytoplasmic membranes reduction of CymA may then require the thermodynamic driving force from NADH, formate or H2 oxidation as the redox poise of the menaquinol pool in isolation is insufficient. Spectroscopic studies suggest that CymA requires a non-haem co-factor for quinol oxidation and that the reduced enzyme forms a 1:1 complex with its redox partner Fcc3 (flavocytochrome c3 fumarate reductase). The implications for CymA supporting the respiratory flexibility of shewanellae are discussed.</jats:p