The drugs don't work: evaluation of educational theatre to gauge and influence public opinion on antimicrobial resistance.

Increased public awareness of antimicrobial resistance (AMR) is a key component of effective antimicrobial stewardship strategies. Educational theatre combined with an expert panel was used to engage the public about AMR through delivery of a play entitled 'The drugs don't work'. Audience knowledge and understanding of AMR were measured by pre- and post-play questionnaires. Performance of the play and discussion with the expert panel significantly improved audience knowledge and understanding of AMR, including antibiotic misuse and prescribing. Educational theatre provides a positive learning experience and is an innovative method of public engagement to disseminate important public health messages.

The antimicrobial efficacy of zinc doped phosphate-based glass for treating catheter associated urinary tract infections.

In this study, a series of phosphate-based glasses; (P2O5)50(Na2O)20(CaO)30-x (ZnO)x were prepared with increasing concentration of zinc oxide to determine the antimicrobial effect against clinically relevant microorganisms. The addition of 1 and 3 mol% zinc oxide decreased glass degradation however a higher dissolution rate was observed for 5 and 10 mol% ZnO. The antimicrobial results showed a concentration dependent effect on the viability of microorganisms. When in direct contact zinc doped glasses showed a complete kill, within 24 h, against Escherichia coli and a significant (p < 0.01) kill was observed against Staphylococcus aureus however the effect of dissolution products was not seen until 48 h. Furthermore, the cytotoxic studies showed no toxic effects on the viability of uroepithelial cells. This study has shown that zinc doped phosphate-based glasses can potentially be used to prevent/treat catheter associated urinary tract infections.

The Antimicrobial Efficacy of Hypoxia Mimicking Cobalt Oxide Doped Phosphate-Based Glasses against Clinically Relevant Gram Positive, Gram Negative Bacteria and a Fungal Strain.

Bioactive phosphate glasses are of considerable interest for a range of soft and hard tissue engineering applications. The glasses are degradable and can release biologically important ions in a controlled manner. The glasses can also potentially be used as an antimicrobial delivery system. In the given study, novel cobalt-doped phosphate-based glasses, (P2O5)50(Na2O)20(CaO)30-x(CoO)x where 0 ≤ x (mol %) ≤ 10, were manufactured and characterized. As the cobalt oxide concentration increased, the rate of dissolution was observed to decrease. The antimicrobial potential of the glasses was studied using direct and indirect contact methods against both Escherichia coli (NCTC 10538) Staphylococcus aureus (ATCC 6538) and Candida albicans (ATCC 76615). The results showed strong, time dependent, and strain specific antimicrobial activity of the glasses against microorganisms when in direct contact. Antimicrobial activity (R) ≥ 2 was observed within 2 h against Escherichia coli, whereas a similar effect was achieved in 6 h against Staphylococcus aureus and Candida albicans. However, when in indirect contact, the dissolution products from the bioactive glasses failed to show an antimicrobial effect. Following direct exposure to the glasses for 7 days, osteoblast-like SAOS-2 cells showed a 5-fold increase in VEGF mRNA while THP-1 monocytic cells showed a 4-fold increase in VEGF mRNA expression when exposed to 10% CoO-doped glass compared with the cobalt free control glass. Endothelial cells stimulated with conditioned medium taken from cell cultures of THP-1 monocytes exposed to 10% CoO doped glass showed clear tubelike structure (blood vessel) formation after 4 h.

Centralisation for resection of the pancreatic head: A comparison of operative factors and early outcomes during the evolving unit and tertiary unit phases at a UK institution.

AIMS: To assess impact of centralisation on patients undergoing pancreatic head resections at a tertiary hepatobiliary (HPB) centre in the UK. METHODS: Data were analysed from a prospectively maintained database from 1998 to 2014 on all patients undergoing pancreatic head resections. Two specific time periods were defined; these were the evolving unit phase (EU) from 1998 to 2009 and finally the established tertiary unit phase (TU) from 2010 to 2014. Peri-operative factors and post-operative outcomes were analysed. RESULTS: 395 resections were undertaken during the study period. Following establishment of our tertiary HPB unit, the volume of resections undertaken increased greater than three-fold with an associated increase in case-complexity (p = 0.004). Operating time was found to increase in the TU phase compared with EU phase (p=>0.0005) whilst there was no significant difference in the rate of peri-operative transfusion, or in post-operative morbidity rates. There was a significant reduction in the post-operative length of stay in the TU phase (p = 0.003) with a significantly higher proportion of patients being discharged within 9 days of their procedure (p=<0.0005). There was also a significant reduction in 30-day post-operative mortality in the TU phase (0.5%) compared with the EU phase (3%) (p = 0.029). CONCLUSIONS: Data from our series of 395 cases suggests that centralisation of pancreatic cancer services to a tertiary centre does result in improved patient outcomes. The benefits of a multi-disciplinary and specialist HPB service results in a high volume, high quality unit with improved patient outcomes.

Enhanced chlorhexidine skin penetration with 1,8-cineole.

BACKGROUND: Chlorhexidine (CHG) penetrates poorly into skin. The purpose of this study was to compare the depth of CHG skin permeation from solutions containing either 2% (w/v) CHG and 70% (v/v) isopropyl alcohol (IPA) or 2% (w/v) CHG, 70% (v/v) IPA and 2% (v/v) 1,8-cineole. METHODS: An ex-vivo study using Franz diffusion cells was carried out. Full thickness human skin was mounted onto the cells and a CHG solution, with or without 2% (v/v) 1,8-cineole was applied to the skin surface. After twenty-four hours the skin was sectioned horizontally in 100 µm slices to a depth of 2000 µm and the concentration of CHG in each section quantified using high performance liquid chromatography (HPLC). The data were analysed with repeated measures analysis of variance. RESULTS: The concentration of CHG in the skin on average was significantly higher (33.3% [95%, CI 1.5% - 74.9%]) when a CHG solution which contained 1,8-cineole was applied to the skin compared to a CHG solution which did not contain this terpene (P = 0.042). CONCLUSIONS: Enhanced delivery of CHG can be achieved in the presence of 1,8-cineole, which is the major component of eucalyptus oil. This may reduce the numbers of microorganisms located in the deeper layers of the skin which potentially could decrease the risk of surgical site infection.

Acute afferent loop syndrome in the early postoperative period following pancreaticoduodenectomy.

INTRODUCTION: Afferent loop syndrome (ALS) is a recognised complication of foregut surgery caused by mechanical obstruction at the gastrojejunostomy anastomosis itself or at a point nearby. Acute ALS has only been reported following pancreaticoduodenectomy (PD) after several years due to recurrence of malignancy at the anastomotic site. We report five cases of acute ALS in the first postoperative week. METHODS: The presentation, clinical findings and successful management of the 5 patients with ALS were obtained from a prospectively collected database of 300 PDs. All five patients with early acute ALS presented with signs and symptoms of a bile leak. Since the fifth patient, the surgical technique has been modified with the creation of a larger window in the transverse mesocolon and a Braun enteroenterostomy. RESULTS: There have been no further incidents of ALS since the adoption of these modifications to the standard technique of PD and there has also been a reduction in postoperative bile leaks (6.4% vs 3.6%, p=0.416). CONCLUSIONS: Acute ALS is a rare but important complication in the immediate postoperative period following PD and causes disruption to adjacent anastomoses, resulting in a bile leak. A prophylactic Braun anastomosis and wide mesocolic window may prevent this complication and subsequent deterioration.

The two-port laparoscopic retroperitoneal approach for minimal access pancreatic necrosectomy.

INTRODUCTION: Despite advances in surgery and critical care, severe pancreatitis continues to be associated with a high rate of mortality, which is increased significantly in the presence of infected pancreatic necrosis. Controversy persists around the optimal treatment for such cases, with specialist units variously advocating open necrosectomy, simple percutaneous drainage or one of several minimal access approaches. We describe our technique and outcomes with a two-port laparoscopic retroperitoneal necrosectomy (2P-LRN). METHODS: Thirteen consecutive patients with proven infected pancreatic necrosis were treated by 2P-LRN over a three-year period in the setting of a specialist hepatopancreatobiliary unit. The median patient age was 46 years (range: 28-87 years) and 10 of the patients were male. RESULTS: The median number of procedures required to clear the necrosis was 2 (range: 1-5), with a median time to discharge following the procedure of 44 days (range: 10-135 days). There was no 90-day mortality and the morbidity rate was 38%, consisting of pancreatic fistula (31%) and bleeding (23%). CONCLUSIONS: Two-port laparoscopic retroperitoneal necrosectomy has been demonstrated to confer similar or better outcomes to other techniques for necrosectomy. It carries the additional advantages of better visualisation, leading to fewer procedures and the opportunity to deploy simple laparoscopic instruments such as diathermy or haemostatic clips.

Liver metastases from esophageal carcinoma: is there a role for surgical resection?

Esophageal cancer recurrence rates after esophagectomy are high, and locally recurrent or distant metastatic disease has poor prognosis. Management is limited to palliative chemotherapy and symptomatic interventions. We report our experience of four patients who have undergone successful liver resection for metastases from esophageal cancer. All underwent esophagectomy and were referred to our unit with metastatic recurrent liver disease, two with solitary metastases and two with multi-focal disease. The patients underwent multidisciplinary assessment and proceeded to a course of neoadjuvant chemotherapy followed by open or laparoscopic liver resection. Three patients were male, and the mean age was 57.5 (range 44-71) years. Response to chemotherapy ranged from partial to complete response. Following liver resection, two patients developed recurrent disease at 5 and 15 months, and both had disease-specific mortality at 10 and 21 months, respectively. The other two patients remain disease free at 22 and 92 months. Recurrent metastatic esophageal cancer continues to have a poor prognosis, and the majority of patients with liver involvement will not be candidates for hepatic resection. However, this series suggests that in selected patients, liver resection of metastases from esophageal cancer combined with neoadjuvant and adjuvant chemotherapy is feasible, but further research is required to determine whether this can offer a survival advantage.

Randomized clinical trial on enhanced recovery versus standard care following open liver resection.

BACKGROUND: Enhanced recovery programmes (ERPs) have been shown to reduce length of hospital stay (LOS) and complications in colorectal surgery. Whether ERPs have the same benefits in open liver resection surgery is unclear, and randomized clinical trials are lacking. METHODS: Consecutive patients scheduled for open liver resection were randomized to an ERP group or standard care. Primary endpoints were time until medically fit for discharge (MFD) and LOS. Secondary endpoints were postoperative morbidity, pain scores, readmission rate, mortality, quality of life (QoL) and patient satisfaction. ERP elements included greater preoperative education, preoperative oral carbohydrate loading, postoperative goal-directed fluid therapy, early mobilization and physiotherapy. Both groups received standardized anaesthesia with epidural analgesia. RESULTS: The analysis included 46 patients in the ERP group and 45 in the standard care group. Median MFD time was reduced in the ERP group (3 days versus 6 days with standard care; P < 0·001), as was LOS (4 days versus 7 days; P < 0·001). The ERP significantly reduced the rate of medical complications (7 versus 27 per cent; P = 0·020), but not surgical complications (15 versus 11 per cent; P = 0·612), readmissions (4 versus 0 per cent; P = 0·153) or mortality (both 2 per cent; P = 0·987). QoL over 28 days was significantly better in the ERP group (P = 0·002). There was no difference in patient satisfaction. CONCLUSION: ERPs for open liver resection surgery are safe and effective. Patients treated in the ERP recovered faster, were discharged sooner, and had fewer medical-related complications and improved QoL. REGISTRATION NUMBER: ISRCTN03274575 (http://www.controlled-trials.com).

Routine on-table cholangiography during cholecystectomy: a systematic review.

INTRODUCTION: The aim of this review was to systemically analyse trials evaluating the efficacy of routine on-table cholangiography (R-OTC) versus no on-table cholangiography (N-OTC) in patients undergoing cholecystectomy. METHODS: Randomised trials evaluating R-OTC versus N-OTC in patients undergoing cholecystectomy were selected and analysed. RESULTS: Four trials (1 randomised controlled trial on open cholecystectomy and 3 on laparoscopic cholecystectomy) encompassing 860 patients undergoing cholecystectomy with and without R-OTC were retrieved. There were 427 patients in the R-OTC group and 433 patients in the N-OTC group. There was no significant heterogeneity among trials. Therefore, in the fixed effects model, N-OTC did not increase the risk (p=0.53) of common bile duct (CBD) injury, and it was associated with shorter operative time (p<0.00001) and fewer peri-operative complications (p<0.04). R-OTC was superior in terms of peri-operative CBD stone detection (p<0.006) and it reduced readmission (p<0.03) for retained CBD stones. CONCLUSIONS: N-OTC is associated with shorter operative time and fewer peri-operative complications, and it is comparable to R-OTC in terms of CBD injury risk during cholecystectomy. R-OTC is helpful for peri-operative CBD stone detection and there is therefore reduced readmission for retained CBD stones. The N-OTC approach may be adopted routinely for patients undergoing laparoscopic cholecystectomy providing there are no clinical, biochemical or radiological features suggestive of CBD stones. However, a major multicentre randomised controlled trial is required to validate this conclusion.

Liver resection for colorectal cancer metastases involving the caudate lobe.

BACKGROUND: Up to 5 per cent of liver resections for colorectal cancer metastases involve the caudate lobe, with cancer-involved resection margins of over 50 per cent being reported following caudate lobe resection. METHODS: Outcomes of consecutive liver resections for colorectal metastases involving the caudate lobe between 1996 and 2009 were reviewed retrospectively, and compared with those after liver surgery without caudate resection. RESULTS: Twenty-five patients underwent caudate and 432 non-caudate liver resection. Caudate resection was commonly performed as part of extended resection. There were no differences in operative complications (24 versus 21·1 per cent; P = 0·727) or blood loss (median 300 versus 250 ml; P = 0·234). The operating time was longer for caudate resection (median 283 versus 227 min; P = 0·024). Tumour size was larger in the caudate group (median 40 versus 27 mm; P = 0·018). Resection margins were smaller when the caudate lobe was involved by tumour, than in resections including tumour-free caudate or non-caudate resection; however, there was no difference in the proportion of completely excised tumours between caudate and non-caudate resections (96 versus 96·1 per cent; P = 0·990). One-year overall survival rates were 90 and 89·3 per cent respectively (P = 0·960), with 1-year recurrence-free survival rates of 62 and 71·2 per cent (P = 0·340). CONCLUSION: Caudate lobe surgery for colorectal cancer liver metastases does not increase the incidence of resection margin involvement, although when the caudate lobe contains metastases the margins are significantly closer than in other resections.

Histidine acts as a co-germinant with glycine and taurocholate for Clostridium difficile spores.

AIMS: It is well established that the bile salt sodium taurocholate acts as a germinant for Clostridium difficile spores and the amino acid glycine acts as a co-germinant. The aim of this study was to determine whether any other amino acids act as co-germinants. METHODS AND RESULTS: Clostridium difficile spore suspensions were exposed to different germinant solutions comprising taurocholate, glycine and an additional amino acid for 1 h before heating shocking (to kill germinating cells) or chilling on ice. Samples were then re-germinated and cultured to recover remaining viable cells. Only five amino acids out of the 19 common amino acids tested (valine, aspartic acid, arginine, histidine and serine) demonstrated co-germination activity with taurocholate and glycine. Of these, only histidine produced high levels of germination (97·9-99·9%) consistently in four strains of Cl. difficile spores. Some variation in the level of germination produced was observed between different PCR ribotypes, and the optimum concentration of amino acids with taurocholate for the germination of Cl. difficile NCTC 11204 spores was 10-100 mmol l-1. CONCLUSIONS: Histidine was found to be a co-germinant for Cl. difficile spores when combined with glycine and taurocholate.

Serum procalcitonin, interleukin-6, soluble intercellular adhesin molecule-1 and IgG to short-chain exocellular lipoteichoic acid as predictors of infection in total joint prosthesis revision.

The diagnosis of prosthetic joint infection and its differentiation from aseptic loosening remains problematic. The definitive laboratory diagnostic test is the recovery of identical infectious agents from multiple intraoperative tissue samples; however, interpretation of positive cultures is often complex as infection is frequently associated with low numbers of commensal microorganisms, in particular the coagulase-negative staphylococci (CNS). In this investigation, the value of serum procalcitonin (PCT), interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1) as predictors of infection in revision hip replacement surgery is assessed. Furthermore, the diagnostic value of serum IgG to short-chain exocellular lipoteichoic acid (sce-LTA) is assessed in patients with infection due to CNS. Presurgical levels of conventional serum markers of infection including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell count (WBC) is also established. Forty-six patients undergoing revision hip surgery were recruited with a presumptive clinical diagnosis of either septic (16 patients) or aseptic loosening (30 patients). The diagnosis was confirmed microbiologically and levels of serum markers were determined. Serum levels of IL-6 and sICAM-1 were significantly raised in patients with septic loosening (P = 0.001 and P = 0.0002, respectively). Serum IgG to sce-LTA was elevated in three out of four patients with infection due to CNS. In contrast, PCT was not found to be of value in differentiating septic and aseptic loosening. Furthermore, CRP, ESR and WBC were significantly higher (P = 0.0001, P = 0.0001 and P = 0.003, respectively) in patients with septic loosening. Serum levels of IL-6, sICAM-1 and IgG to sce-LTA may provide additional information to facilitate the diagnosis of prosthetic joint infection.

Antimicrobial efficacy of eucalyptus oil and 1,8-cineole alone and in combination with chlorhexidine digluconate against microorganisms grown in planktonic and biofilm cultures.

OBJECTIVES: Effective disinfection and antisepsis is pivotal in preventing infections within the healthcare setting. Chlorhexidine digluconate (CHG) is a widely used disinfectant/antiseptic possessing broad-spectrum antimicrobial activity; however, its penetration into bacterial biofilms and human skin is poor. The aim of this study was to investigate the antimicrobial efficacy of crude eucalyptus oil (EO) and its main component 1,8-cineole (a recognized permeation enhancer), alone and in combination with CHG, against a panel of clinically relevant microorganisms grown in planktonic and biofilm cultures. METHODS: MICs and minimum bactericidal/fungicidal concentrations were determined for each microorganism grown in suspension and biofilm using microbroth dilution and ATP bioluminescence, respectively. Chequerboard assays were used to determine synergistic, indifferent or antagonistic interactions between CHG and EO or 1,8-cineole. RESULTS: Antimicrobial activity was demonstrated by CHG, EO and 1,8-cineole; however, CHG was significantly more active against microorganisms in both planktonic and biofilm modes of growth (P < 0.05). Crude EO was significantly more efficacious against microorganisms grown in suspension compared with 1,8-cineole (P < 0.05). Synergistic activity was demonstrated between CHG and both EO and 1,8-cineole against suspensions of Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Escherichia coli and Candida albicans, and biofilm cultures of MRSA and Pseudomonas aeruginosa. CONCLUSIONS: In conclusion, CHG may be combined with either crude EO or its major component 1,8-cineole for enhanced, synergistic antimicrobial activity against a wide range of microorganisms in planktonic and biofilm modes of growth; however, the superior antimicrobial efficacy associated with crude EO alone, compared with 1,8-cineole, favours its combination with CHG.

Survival and recurrence after neo-adjuvant chemotherapy and liver resection for colorectal metastases: a ten year study.

BACKGROUND: Currently liver resection offers the only potential cure for colorectal liver metastases (CRLM). We prospectively audited the outcome of CRLM treated by a combination of neo-adjuvant chemotherapy and surgery. METHODS: 283 consecutive patients underwent liver resection for CRLM over 10 years with curative intent. Patients received chemotherapy preoperatively for synchronous and early (< 2 years) metachronous metastases. Univariate and multivariate analyses were used to identify mortality risk factors. RESULTS: Overall survival at 1, 3 and 5 years was 90%, 59.2% and 46.1%, respectively. Disease free survival at 1, 3 and 5 years was 68.1%, 34.8% and 27.9%, respectively. Operative mortality was 2.1% and morbidity was 23.7%. Patients with macroscopic diaphragm invasion by tumour, CEA > 100 ng/ml, tumour size > 5 cm or cancer involved resection margins (CIRM) had a significantly worse overall survival. Incidence of CIRM and re-resection was 4.9% and 4.5%, respectively. CONCLUSIONS: Neo-adjuvant chemotherapy followed by liver surgery is associated with improved survival and low CIRM and re-resection rates.

A 10-year study of outcome following hepatic resection for colorectal liver metastases - The effect of evaluation in a multidisciplinary team setting.

AIMS: Colorectal carcinoma is the second most common cause of cancer death in the western world and nearly 50% of patients develop liver metastases. Many cancers are managed via a multidisciplinary team process. This study compares the long term outcome of patients with metastatic colorectal cancer referred via a multidisciplinary team including a liver surgeon (MDT) with those referred directly to a specialist hepatobiliary unit. PATIENTS AND METHOD: This is a prospective study of 331 consecutive referrals made to a specialist hepatobiliary unit over ten years out of which 108 patients were referred via a colorectal MDT which included a liver surgeon and 223 were directly referred via colorectal MDTs without a liver surgeon. Pre-operative assessment and management were standardised and short and long term data were recorded. RESULTS: Patients referred via the MDT had 1-, 3- and 5-year survival rates of 89.6%, 67.5% and 49.9% respectively and 1-, 3- and 5-year disease-free survival of 65.4%, 31% and 27.2% respectively. Patients referred directly had 1-, 3- and 5-year survival rates of 90.3%, 54.1% and 43.3% respectively and 1-, 3- and 5-year disease-free survival rates of 70.3%, 37.6% and 27.9% respectively. The difference in overall survival was significant (P=0.0001), although the difference in disease-free survival was not (P=0.21). CONCLUSION: Assessing, managing and referring patients with metastatic colorectal cancer via a multidisciplinary team including a liver surgeon is associated with improved overall survival.

A comparison of right and extended right hepatectomy with all other hepatic resections for colorectal liver metastases: a ten-year study.

AIMS: Colorectal liver metastases are treated by a combination of adjuvant chemotherapy followed by liver resection. In this study we compared all major right-sided resections with left or parenchymal sparing resections. METHODS: Consecutive patients (n=283) who had successful hepatic resections for colorectal metastases from September 1996 to November 2006 were prospectively studied. Early and late outcomes of those who had right and extended right hepatectomies (RH) were compared with those who had all other types of liver resection (AOLR). Adjuvant therapy and pre-operative assessment were standardised for all. RESULTS: The 1-, 3- and 5-year overall survival rates in the RH group were 84.1%, 54.3% and 38.9%, respectively. The 1-, 3- and 5-year overall survival rates in the AOLR group were 95.4%, 65.9% and 53.3%, respectively. The difference was statistically significant (p=0.03). The 1-, 3- and 5-year disease-free survival rates in the RH group were 69.5%, 34.4% and 25.5%, respectively and 68.4%, 34.91% and 34.91%, respectively in the AOLR group (p=0.46). Operative mortality was 3.9% in the RH group and 0.7% in the AOLR group (p=0.04). Morbidity was 31.3% in the RH group and 18% in the AOLR group. CONCLUSION: Patients undergoing right and extended right hepatectomies for colorectal metastases have a greater operative morbidity and mortality and have a significantly worse overall survival compared to all other liver resections for the same disease.

Epidemiology of community-acquired meticillin-resistant Staphylococcus aureus obtained from the UK West Midlands region.

SUMMARY: Between January 2005 and December 2005, 199 meticillin-resistant Staphylococcus aureus (MRSA) isolates were obtained from non-hospitalised patients presenting skin and soft tissue infections to local general practitioners. The study area incorporated 57 surgeries from three Primary Care Trusts in the Lichfield, Tamworth, Burntwood, North and East Birmingham regions of Central England, UK. Following antibiotic susceptibility testing, pulsed-field gel electrophoresis, Panton-Valentine leukocidin gene detection and SCCmec element assignment, 95% of the isolates were shown to be related to hospital epidemic strains EMRSA-15 and EMRSA-16. In total 87% of the isolate population harboured SCCmec IV, 9% had SCCmec II and 4% were identified as carrying novel SCCmec IIIa(-mecI). When mapped to patient home postcode, a diverse distribution of isolates harbouring SCCmec II and SCCmec IV was observed; however, the majority of isolates harbouring SCCmec IIIa(-mecI) were from patients residing in the north-west of the study region, highlighting a possible localised clonal group. Transmission of MRSA from the hospital setting into the surrounding community population, as demonstrated by this study, warrants the need for targeted patient screening and decolonisation in both the clinical and community environments.