Selenium Deficiency and Chronic Pancreatitis: Disease Mechanism and Potential for Therapy

Background: It has been suggested that antioxidant deficiency may play a role in the pathogenesis of chronic pancreatitis. The aim of this review was to analyse the evidence for this relationship and to consider the role of antioxidant supplementation in the treatment of chronic pancreatitis

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Neutrophil priming by cytokines in patients with obstructive jaundice.

Patients with obstructive jaundice frequently suffer postoperative complications. We have investigated the relationship of obstructive jaundice to the neutrophil oxidase response and the “priming” of the response by the cytokines TNFα, interleukin-1 (IL-1), IL-6, and IL-8. On stimulation with f-met-leuphe (fmlp), the respiratory burst in neutrophils from jaundiced patients was greatly increased compared with controls (p < 0.01), jaundiced patients having the highest respiratory burst levels were those with the poorest prognosis. Neutrophils from controls were primed by all the cytokines tested, whereas “jaundiced” cells were primed only by IL-1, and not by TNFα, IL-6, or IL-8, which in fact produced slight inhibition. We conclude that neutrophils from obstructive jaundiced patients have raised oxidative responses which may be due to “pre-priming” in vivo by cytokines, such as IL-6, IL-8, or TNFα. This exaggeration of the oxidative response in circulating neutrophils may contribute to the peri-operate complications of patients with obstructive jaundice

Expression of the HGF/SF Receptor, c-met, and its ligand in human colorectal cancers

The c-met proto-oncogene product is a receptor tyrosine kinase that mediates the effects of the multifunctional cytokine hepatocyte growth factor/scatter factor (HGF/SF). We have studied the expression of both the c-met receptor and HGF/SF at both the protein and message level in colorectal cancer tissues of varying disease stage. All of the tumors displayed an overexpression of the c-met mRNA compared to their normal tissue counterparts while 16 of 21 tissues (75%) displayed up-regulation of c-met protein. No HGF/SF mRNA or protein could be detected in either tissue type. Viable tumor cells extracted from cancer tissue exhibited increased motility in response to HGF/SF stimulation demonstrating that c-met was functionally active. No correlation between expression of c-met and tumor stage or degree of differentiation was observed. HGF/SF is known to be a potent stimulator of tumor cell motility and invasion, two cellular properties essential for the metastatic development of cancers. The overexpression of the HGF/SF receptor in colorectal cancers may result in an increased sensitivity to HGF/SF, which may confer an enhanced metastatic potential to the cancer cells within the tumor body

Prospective multicentre randomised controlled trial of early enteral nutrition for patients undergoing major upper gastrointestinal surgical resection

Background & aims The evidence in support of Early Enteral Nutrition (EEN) after upper gastrointestinal surgery is inconclusive. The aim of this study was to determine if EEN improved clinical outcomes and shortened length of hospital stay. Methods Open, prospective multicentre randomised controlled trial within a regional UK Cancer Network. One hundred and twenty-one patients with suspected operable upper gastrointestinal cancer (54 oesophageal, 38 gastric, 29 pancreatic) were studied. Patients were randomised to receive EEN (n = 64) or Control management postoperatively (nil by mouth and IV fluid, n = 57). Analysis was based on intention-to-treat and the primary outcome measure was length of hospital stay. Results Operative morbidity was less common after EEN (32.8%) than Control management (50.9%, p = 0.044), due to fewer wound infections (p = 0.017), chest infections (p = 0.036) and anastomotic leaks (p = 0.055). Median length of hospital stay was 16 days (IQ = 9) after EEN compared with 19 (IQ = 11) days after Control management (p = 0.023). Conclusions EEN was associated with significantly shortened length of hospital stay and improved clinical outcomes. These findings reinforce the potential benefit of early oral nutrition in principle and as championed within enhanced recovery after surgery programmes, and such strategies deserve further research in the arena of upper GI surgery

Regulation of desmosomal cell adhesion in human tumour cells by polyunsaturated fatty acids

Desmosomes are key structures in cell-cell adhesion. In this study we examined the effect of n-6 essential fatty acids on the expression of desmoglein (Dsg), desmosomal cadherin and the formation of desmosomes in E-cadherin negative human breast, colon and lung cancer cells and melanoma cells. Electron microscopy revealed that cells cultured with gamma linolenic acid (GLA) showed increased cell-cell adhesion together with an increase in the formation of desmoglein-containing desmosomes. Western blotting studies of cellular proteins demonstrated that, following culture with fatty acids, Dsg expression was modified, with the greatest increase seen after GLA treatment. Other fatty acids increased Dsg expression, but to a lesser extent. It is concluded that GLA regulates desmosome-mediated cell-cell adhesion in human cancer cells, particularly in cells without E-cadherin