Liverpool Heart and Chest Hospital NHS Trust

The American Society of Anesthesiologists (ASA) physical status is a tool commonly used to classify a patient's physical fitness before surgery. Since its introduction in 1941 it has undergone very few modifications to improve its reliability and to eliminate subjectivity, despite vast changes in both surgical and anaesthetic technique. We present the history of the ASA physical status and review the literature on its applicability to contemporary anaesthetic practice.

AIM: The neural cardiac therapy for heart failure (NECTAR-HF) was a randomized sham-controlled trial designed to evaluate whether a single dose of vagal nerve stimulation (VNS) would attenuate cardiac remodelling, improve cardiac function and increase exercise capacity in symptomatic heart failure patients with severe left ventricular (LV) systolic dysfunction despite guideline recommended medical therapy. METHODS: Patients were randomized in a 2 : 1 ratio to receive therapy (VNS ON) or control (VNS OFF) for a 6-month period. The primary endpoint was the change in LV end systolic diameter (LVESD) at 6 months for control vs. therapy, with secondary endpoints of other echocardiography measurements, exercise capacity, quality-of-life assessments, 24-h Holter, and circulating biomarkers. RESULTS: Of the 96 implanted patients, 87 had paired datasets for the primary endpoint. Change in LVESD from baseline to 6 months was -0.04 ± 0.25 cm in the therapy group compared with -0.08 ± 0.32 cm in the control group (P = 0.60). Additional echocardiographic parameters of LV end diastolic dimension, LV end systolic volume, left ventricular end diastolic volume, LV ejection fraction, peak V02, and N-terminal pro-hormone brain natriuretic peptide failed to show superiority compared to the control group. However, there were statistically significant improvements in quality of life for the Minnesota Living with Heart Failure Questionnaire (P = 0.049), New York Heart Association class (P = 0.032), and the SF-36 Physical Component (P = 0.016) in the therapy group. CONCLUSION: Vagal nerve stimulation as delivered in the NECTAR-HF trial failed to demonstrate a significant effect on primary and secondary endpoint measures of cardiac remodelling and functional capacity in symptomatic heart failure patients, but quality-of-life measures showed significant improvement.

BACKGROUND: Hand eczema is a common inflammatory skin disorder. Health care providers need continuously updated information about the management of hand eczema to ensure best treatment for their patients. OBJECTIVES: To update the European Society of Contact Dermatitis guideline on the diagnosis, prevention, and treatment on of hand eczema. METHOD: The Guideline Development Group (GDG) was established on behalf of the ESCD. A call for interest was launched via the ESCD website and via the ESCD members' mailing list. Appraisal of the evidence for therapeutic and preventive interventions was applied and a structured method of developing consensus was used and moderated by an external methodologist. The final guideline was approved by the ESCD executive committee and was in external review on the ESCD webpage for 1 month. RESULTS: Consensus was achieved for several statements and management strategies. CONCLUSION: The updated guideline should improve management of hand eczema.

BACKGROUND: This study aimed to show that SHOX2 DNA methylation is a tumor marker in patients with suspected lung cancer by using bronchial fluid aspirated during bronchoscopy. Such a biomarker would be clinically valuable, especially when, following the first bronchoscopy, a final diagnosis cannot be established by histology or cytology. A test with a low false positive rate can reduce the need for further invasive and costly procedures and ensure early treatment. METHODS: Marker discovery was carried out by differential methylation hybridization (DMH) and real-time PCR. The real-time PCR based HeavyMethyl technology was used for quantitative analysis of DNA methylation of SHOX2 using bronchial aspirates from two clinical centres in a case-control study. Fresh-frozen and Saccomanno-fixed samples were used to show the tumor marker performance in different sample types of clinical relevance. RESULTS: Valid measurements were obtained from a total of 523 patient samples (242 controls, 281 cases). DNA methylation of SHOX2 allowed to distinguish between malignant and benign lung disease, i.e. abscesses, infections, obstructive lung diseases, sarcoidosis, scleroderma, stenoses, at high specificity (68% sensitivity [95% CI 62-73%], 95% specificity [95% CI 91-97%]). CONCLUSIONS: Hypermethylation of SHOX2 in bronchial aspirates appears to be a clinically useful tumor marker for identifying subjects with lung carcinoma, especially if histological and cytological findings after bronchoscopy are ambiguous.

AIM: Lung metastases from colorectal cancer are resected in selected patients in the belief that this confers a significant survival advantage. It is generally assumed that the 5-year survival of these patients would be near zero without metastasectomy. We tested the clinical effectiveness of this practice in Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC), a randomized, controlled noninferiority trial. METHOD: Multidisciplinary teams in 14 hospitals recruited patients with resectable lung metastases into a two-arm trial. Randomization was remote and stratified according to site, with minimization for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, number of metastases and carcinoembryonic antigen level. The trial management group was blind to patient allocation until after intention-to-treat analysis. RESULTS: From 2010 to 2016, 93 participants were randomized. These patients were 35-86 years of age and had between one and six lung metastases at a median of 2.7 years after colorectal cancer resection; 29% had prior liver metastasectomy. The patient groups were well matched and the characteristics of these groups were similar to those of observational studies. The median survival after metastasectomy was 3.5 (95% CI: 3.1-6.6) years compared with 3.8 (95% CI: 3.1-4.6) years for controls. The estimated unadjusted hazard ratio for death within 5 years, comparing the metastasectomy group with the control group, was 0.93 (95% CI: 0.56-1.56). Use of chemotherapy or local ablation was infrequent and similar in each group. CONCLUSION: Patients in the control group (who did not undergo lung metastasectomy) have better survival than is assumed. Survival in the metastasectomy group is comparable with the many single-arm follow-up studies. The groups were well matched with features similar to those reported in case series.

Importance: Microvascular obstruction commonly affects patients with acute ST-segment elevation myocardial infarction (STEMI) and is associated with adverse outcomes. Objective: To determine whether a therapeutic strategy involving low-dose intracoronary fibrinolytic therapy with alteplase infused early after coronary reperfusion will reduce microvascular obstruction. Design, Setting, and Participants: Between March 17, 2016, and December 21, 2017, 440 patients presenting at 11 hospitals in the United Kingdom within 6 hours of STEMI due to a proximal-mid-vessel occlusion of a major coronary artery were randomized in a 1:1:1 dose-ranging trial design. Patient follow-up to 3 months was completed on April 12, 2018. Interventions: Participants were randomly assigned to treatment with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145) by manual infusion over 5 to 10 minutes. The intervention was scheduled to occur early during the primary PCI procedure, after reperfusion of the infarct-related coronary artery and before stent implant. Main Outcomes and Measures: The primary outcome was the amount of microvascular obstruction (% left ventricular mass) demonstrated by contrast-enhanced cardiac magnetic resonance imaging (MRI) conducted from days 2 through 7 after enrollment. The primary comparison was the alteplase 20-mg group vs the placebo group; if not significant, the alteplase 10-mg group vs the placebo group was considered a secondary analysis. Results: Recruitment stopped on December 21, 2017, because conditional power for the primary outcome based on a prespecified analysis of the first 267 randomized participants was less than 30% in both treatment groups (futility criterion). Among the 440 patients randomized (mean age, 60.5 years; 15% women), the primary end point was achieved in 396 patients (90%), 17 (3.9%) withdrew, and all others were followed up to 3 months. In the primary analysis, the mean microvascular obstruction did not differ between the 20-mg alteplase and placebo groups (3.5% vs 2.3%; estimated difference, 1.16%; 95% CI, -0.08% to 2.41%; P = .32) nor in the analysis of 10-mg alteplase vs placebo groups (2.6% vs 2.3%; estimated difference, 0.29%; 95% CI, -0.76% to 1.35%; P = .74). Major adverse cardiac events (cardiac death, nonfatal MI, unplanned hospitalization for heart failure) occurred in 15 patients (10.1%) in the placebo group, 18 (12.9%) in the 10-mg alteplase group, and 12 (8.2%) in the 20-mg alteplase group. Conclusions and Relevance: Among patients with acute STEMI presenting within 6 hours of symptoms, adjunctive low-dose intracoronary alteplase given during the primary percutaneous intervention did not reduce microvascular obstruction. The study findings do not support this treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT02257294.

Guidelines have been compiled by the Joint Tuberculosis Committee of the British Thoracic Society for the prevention and management of Mycobacterium tuberculosis infection and disease in patients with all grades of renal impairment.

Atrial fibrillation (AF) and stroke remain a major cause of morbidity and mortality. The two conditions shared common co-morbidities and risk factors. AF-related strokes are associated with worse clinical outcomes and higher mortality compared to non-AF-related. Early detection of AF is vital for prevention. While various scores have been developed to predict AF in such a high-risk group, they are yet to incorporated into clinical guidelines. Novel markers and predictors of AF including coronary and intracranial arterial calcification have also been studied. There are also ongoing debates on the management of acute stroke in patients with AF, and those who experienced breakthrough stroke while on oral anticoagulants. We provided an overview of the complex interplay between AF and stroke, as well as the treatment and secondary prevention of stroke in AF. We also comprehensively discussed the current evidence and the ongoing conundrums, and highlighted the future directions on the topic.

Journal Article Guidelines for the Management of Drug-Resistant Tuberculosis. J. Crofton, P. Chaulet & D. Maher (contributions from J. Grosset, W. Harris, N. Horne, M. Iseman & B. Watt). Geneva: World Health Organization, 1997. 48pp. Price not stated. WHO/TB/96.210 (Rev. 1) Get access Guidelines for the Management of Drug-Resistant Tuberculosis. Crofton J., Chaulet P. & Maher D. (contributions from J. Grosset, W. Harris, N. Horne, M. Iseman & B. Watt). Geneva: World Health Organization, 1997. 48pp. Price not stated. WHO/TB/96.210 (Rev. 1). P.D.O. Davies P.D.O. Davies The Cardiothoracic Centre-Liverpool NHS Trust Thomas Drive Liverpool, L14 3PE, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 92, Issue 2, March-April 1998, Pages 238–239, https://doi.org/10.1016/S0035-9203(98)90767-2 Published: 01 April 1998

The incidence of heart failure (HF) increases with age. This study sought to determine whether aging exacerbates structural and functional remodeling of the myocardium in HF. HF was induced in young (~18 months) and aged sheep (>8 years) by right ventricular tachypacing. In non-paced animals, aging was associated with increased left ventricular (LV) end diastolic internal dimensions (EDID, P<0.001), reduced fractional shortening (P<0.01) and an increase in myocardial collagen content (P<0.01). HF increased EDID and reduced fractional shortening in both young and aged animals, although these changes were more pronounced in the aged (P<0.05). Age-associated differences in cardiac extracellular matrix (ECM) remodeling occurred in HF with collagen accumulation in young HF (P<0.001) and depletion in aged HF (P<0.05). MMP-2 activity increased in the aged control and young HF groups (P<0.05). Reduced tissue inhibitor of metalloproteinase (TIMP) expression (TIMPs 3 and 4, P<0.05) was present only in the aged HF group. Secreted protein acidic and rich in cysteine (SPARC) was increased in aged hearts compared to young controls (P<0.05) while serum procollagen type I C-pro peptide (PICP) was increased in both young failing (P<0.05) and aged failing (P<0.01) animals. In conclusion, collagen content of the cardiac ECM changes in both aging and HF although; whether collagen accumulation or depletion occurs depends on age. Changes in TIMP expression in aged failing hearts alongside augmented collagen synthesis in HF provide a potential mechanism for the age-dependent ECM remodeling. Aging should therefore be considered an important factor when elucidating cardiac disease mechanisms.

OBJECTIVE: To test the hypothesis that selective decontamination of the digestive tract improves outcome in cardiac surgical patients. DESIGN: Prospective, consecutive, controlled trial over two 4-month periods. SETTING: Eight-bed, open-plan postcardiac surgery ICU. PATIENTS: All patients undergoing cardiac bypass surgery were eligible. Patients requiring endotracheal intubation for greater than 4 days were included in the analysis. In the initial 4 months, 12 (8.5%) of 141 patients required greater than 4 days of intubation. These 12 patients were not treated with selective decontamination of the digestive tract. We therefore used these patients as the control group. In the second 4-month period, 12 (6.6%) of 180 patients were treated with selective decontamination of the digestive tract and formed the study group. MAIN OUTCOME MEASURES: The primary measure was mortality. Secondary measures included oropharyngeal decontamination and the presence of lower airway infection. INTERVENTIONS: Cephradine prophylaxis. The study group received every 6 hrs 4 mL orally and 20 mL intragastrically a suspension of antimicrobial agents (tobramycin 80 mg, polymyxin E 100 mg, amphotericin B 500 mg), starting on postoperative day 1. The control group did not receive any oral antimicrobial agents. RESULTS: Mortality rate was significantly (p less than .05) reduced from eight (66%) of 12 patients in the control group to two (16.7%) of 12 patients in the selective decontamination of the digestive tract group. No differences in oropharyngeal decontamination or lower airway infection rates between the two groups were found. CONCLUSIONS: There is a reduced mortality rate in patients receiving selective decontamination of the digestive tract. However, the reader should recognize the small sample size studied. A simple suspension of the antimicrobial agents failed to rid the oropharynx of bacteria.

Objectives To obtain more powerful assessment of the prognostic value of fractional flow reserve CT testing we performed a systematic literature review and collaborative meta-analysis of studies that assessed clinical outcomes of CT-derived calculation of FFR (FFR CT ) (HeartFlow) analysis in patients with stable coronary artery disease (CAD). Methods We searched PubMed and Web of Science electronic databases for published studies that evaluated clinical outcomes following fractional flow reserve CT testing between 1 January 2010 and 31 December 2020. The primary endpoint was defined as ‘all-cause mortality (ACM) or myocardial infarction (MI)’ at 12-month follow-up. Exploratory analyses were performed using major adverse cardiovascular events (MACEs, ACM+MI+unplanned revascularisation), ACM, MI, spontaneous MI or unplanned (&gt;3 months) revascularisation as the endpoint. Results Five studies were identified including a total of 5460 patients eligible for meta-analyses. The primary endpoint occurred in 60 (1.1%) patients, 0.6% (13/2126) with FFR CT &gt;0.80% and 1.4% (47/3334) with FFR CT ≤0.80 (relative risk (RR) 2.31 (95% CI 1.29 to 4.13), p=0.005). Likewise, MACE, MI, spontaneous MI or unplanned revascularisation occurred more frequently in patients with FFR CT ≤0.80 versus patients with FFR CT &gt;0.80. Each 0.10-unit FFR CT reduction was associated with a greater risk of the primary endpoint (RR 1.67 (95% CI 1.47 to 1.87), p&lt;0.001). Conclusions The 12-month outcomes in patients with stable CAD show low rates of events in those with a negative FFR CT result, and lower risk of an unfavourable outcome in patients with a negative test result compared with patients with a positive test result. Moreover, the FFR CT numerical value was inversely associated with outcomes.

BACKGROUND: Surgeons provide patients with information before surgery, although standards of information are lacking and practice varies. The development and use of a 'core information set' as baseline information before surgery may improve understanding. A core set is a minimum set of information to use in all consultations before a specific procedure. This study developed a core information set for oesophageal cancer surgery. METHODS: Information was identified from the literature, observations of clinical consultations and patient interviews. This was integrated to create a questionnaire survey. Stakeholders (patients and professionals) were surveyed twice to assess views on importance of information from 'not essential' to 'absolutely essential' using Delphi methods. Items not meeting predefined criteria were discarded after each survey and the final retained items were voted on, in separate patient and professional stakeholder meetings, to agree the core set. RESULTS: Some 67 information items were identified initially from multiple sources. Survey response rates were 76·5 per cent (185 of 242) and 54·8 per cent (126 of 230) for patients and professionals respectively (first round), and over 83 per cent in both groups thereafter. Health professionals rated short-term clinical outcomes most highly (technical complications), whereas patients prioritized information related to long-term benefits. The consensus meetings agreed the final set, which consisted of: in-hospital milestones to recovery, rates of open-and-close surgery, in-hospital mortality, major complications (reoperation), milestones in recovery after discharge, longer-term eating and drinking and overall quality of life, and chances of survival. CONCLUSION: This study has established a core information set for surgery for oesophageal cancer.

BACKGROUND: Although insulin treatment confers short-term benefit in cystic fibrosis-related diabetes (CFRD), few studies have compared its long-term effect on the clinical outcome. OBJECTIVES: In this study, we aimed to investigate the long-term impact of insulin treatment on pulmonary function, nutritional status and hospital admissions in patients with CFRD. METHODS: We reviewed pulmonary function, body mass index (BMI) and hospital admissions 5 years before and 3 years after insulin therapy in 42 adult CFRD patients. RESULTS: Prior to treatment, over a period of 5 years, the annual rate of change in forced expiratory volume in 1 s (FEV(1)) was -3.2%, forced vital capacity (FVC) -2.5%, and BMI -0.07%. At treatment of CFRD (baseline), the mean FEV(1) was 51.6% predicted (range 24-96), FVC 66.4% (range 29-103) and BMI 19.5 (range 15.3-29.5). At 3 months following insulin treatment, there was a significant improvement in all parameters, which was maintained at 1 year for FEV(1) (55.1%; p < 0.002), 2 years for FVC (72.1%; p < 0.01) and at 3 years for BMI (20.4%; p < 0.002). After 3 months, FEV(1) declined at a rate similar to that before treatment (-3.2 vs. -3.1% per year; p = 0.77), such that the mean FEV(1) after treatment returned to pretreatment baseline values at 34 months. There was no difference in the number of hospital admissions with insulin treatment. CONCLUSIONS: Insulin enhances the nutritional state and temporarily improves pulmonary function in CFRD patients, on average delaying the decline in FEV(1) by 34 months.

OBJECTIVE: The implantable cardioverter defibrillator (ICD) has become the treatment of choice for ventricular arrhythmia (VA; abnormal heart rhythms) and the prevention of sudden cardiac death (SCD). Recent clinical trials have shown the ICD to be superior to anti-arrhythmic medication in reducing mortality; however, research has suggested that ICD recipients experience poor psychosocial adjustment following implantation of the device. This aim of this study was to identify the key psychological characteristics associated with ICD implantation and to establish whether poor psychosocial outcome can be attributed directly to the device and its therapy. METHOD: Studies which reported valid and reliable measures of psychological functioning in ICD patients and appropriate comparison groups were considered for inclusion in a meta-analytic review. A systematic search of electronic databases and reference lists identified 20 studies which fulfilled the inclusion criteria. RESULTS: There were no significant differences in psychosocial outcome between ICD patients and drug-maintained VA patients or between pre- and post-implant ICD patients. However, ICD patients reported significantly worse psychological functioning and physical functioning than other cardiac controls. CONCLUSION: These findings suggest that poor psychosocial outcome in ICD patients may occur as a result of variables associated with the underlying VA condition, rather than as a direct response to implantation of the device and its therapy. This holds important implications for the development and implementation of psychological interventions for patients experiencing VA, in preference to ICD-specific programmes.

OBJECTIVE: To assess the cost-effectiveness of radiofrequency catheter ablation (RFCA) compared with anti-arrhythmic drug (AAD) therapy for the treatment of atrial fibrillation (AF) from the perspective of the UK NHS. DESIGN: Bayesian evidence synthesis and decision analytical model. METHODS: A systematic review and meta-analysis was conducted and Bayesian statistical methods used to synthesise the effectiveness evidence from randomised control trials. A decision analytical model was developed to assess the costs and consequences associated with the primary outcome of the trials over a lifetime time horizon. MAIN OUTCOME MEASURE: Costs from a health service perspective and outcomes measured as quality-adjusted life years (QALYs). RESULTS: The incremental cost-effectiveness ratio of RFCA varied between pound7763 and pound7910 for each additional QALY according to baseline risk of stroke, with a probability of being cost-effective from 0.98 to 0.99 for a cost-effectiveness threshold of pound20 000. Results were sensitive to the duration of quality of life benefits from treatment. CONCLUSIONS: RFCA is potentially cost-effective for the treatment of paroxysmal AF in patients' predominantly refractory to AAD therapy provided the quality-of-life benefits from treatment are maintained for more than 5 years. These findings remain subject to limitations in the existing evidence regarding the nature of life benefits and the prognostic importance of restoring normal sinus rhythm conferred using RFCA.

OBJECTIVES: To determine the safety, clinical effectiveness and cost-effectiveness of radio frequency catheter ablation (RCFA) for the curative treatment of atrial fibrillation (AF) and typical atrial flutter. DATA SOURCES: For the systematic reviews of clinical studies 25 bibliographic databases and internet sources were searched in July 2006, with subsequent update searches for controlled trials conducted in April 2007. For the review of cost-effectiveness a broad range of studies was considered, including economic evaluations conducted alongside trials, modelling studies and analyses of administrative databases. REVIEW METHODS: Systematic reviews of clinical studies and economic evaluations of catheter ablation for AF and typical atrial flutter were conducted. The quality of the included studies was assessed using standard methods. A decision model was developed to evaluate a strategy of RFCA compared with long-term antiarrhythmic drug (AAD) treatment alone in adults with paroxysmal AF. This was used to estimate the cost-effectiveness of RFCA in terms of cost per quality-adjusted life-year (QALY) under a range of assumptions. Decision uncertainty associated with this analysis was presented and used to inform future research priorities using the value of information analysis. RESULTS: A total of 4858 studies were retrieved for the review of clinical effectiveness. Of these, eight controlled studies and 53 case series of AF were included. Two controlled studies and 23 case series of typical atrial flutter were included. For atrial fibrillation, freedom from arrhythmia at 12 months in case series ranged from 28% to 85.3% with a weighted mean of 76%. Three RCTs suggested that RFCA is more effective than long-term AAD therapy in patients with drug-refractory paroxysmal AF. Single RCTs also suggested superiority of RFCA over electrical cardioversion followed by long-term AAD therapy and of RFCA plus AAD therapy over AAD maintenance therapy alone in drug-refractory patients. The available RCTs provided insufficient evidence to determine the effectiveness of RFCA beyond 12 months or in patients with persistent or permanent AF. Adverse events and complications were generally rare. Mortality rates were low in both RCTs and case series. Cardiac tamponade and pulmonary vein stenosis were the most frequently recorded complications. For atrial flutter, freedom from arrhythmia at 12 months in case series ranged from 85% to 92% with a weighted mean of 88%. Neither of the atrial flutter RCTs reported freedom from arrhythmia at 12 months. One RCT found a statistically significant benefit favouring ablation over AADs in terms of freedom from arrhythmia at a mean follow-up of 22 months. A second RCT reported a more modest effect favouring ablation in terms of freedom from atrial flutter at follow-up in older patients (mean age 78 years) after their first episode of flutter. In the atrial flutter case series, mortality was rare and the most frequent complications were atrioventricular block and haematomas. Complications in the RCTs were similar, except for those events likely to have been caused by AAD therapy (e.g. thyroid dysfunction). The review of cost-effectiveness evidence found one relevant study, which from a UK NHS perspective had a number of important limitations. The base-case analysis in the decision model demonstrated that if the quality of life benefits of RFCA are maintained over the remaining lifetime of the patient then the cost-effectiveness of RFCA appears clear. These findings were robust over a wide range of alternative assumptions, being between 7763 and 7910 pounds per additional QALY with very little uncertainty. If the quality of life benefits of RFCA are assumed to be maintained for no more than 5 years, cost-effectiveness of RFCA is dependent on a number of factors. Estimates of cost-effectiveness that explored the influence of these factors ranged from 23,000 to 38,000 pounds per QALY. CONCLUSIONS: RFCA is a relatively safe and efficacious procedure for the therapeutic treatment of AF and typical atrial flutter. There is some randomised evidence to suggest that RFCA is superior to AADs in patients with drug-refractory paroxysmal AF in terms of freedom from arrhythmia at 12 months. RFCA appears to be cost-effective if the observed quality of life benefits are assumed to continue over a patient's lifetime. However, there remain uncertainties around longer-term effects of the intervention and the extent to which published effectiveness findings can be generalised to 'typical' UK practice. All catheter ablation procedures for the treatment of AF or atrial flutter undertaken in the UK should be recorded prospectively and centrally and measures to increase compliance in recording RFCA procedures may be needed. This would be of particular value in establishing the long-term benefits of RFCA and the true incidence and impact of any complications. Collection of appropriate quality of life data within any such registry would also be of value to future clinical and cost-effectiveness research in this area. Any planned multicentre RCTs comparing RFCA against best medical therapy for the treatment of AF and/or atrial flutter should be conducted among 'non-pioneering' centres using the techniques and equipment typically employed in UK practice and should measure relevant outcomes.

AIMS: Tumour budding and host inflammatory response are parameters easily assessed histologically that have prognostic significance in many cancers. There have been few studies examining these parameters in oesophageal or gastro-oesophageal cancers. This study aims to address that deficiency. METHODS AND RESULTS: A two-centre, retrospective study was carried out on 356 patients. Tumour budding and host inflammatory response at the invasive front were assessed histologically. Statistical analysis was performed to determine the prognostic significance of these factors. The median number of tumour buds was four (range 0-50) with 172 of 356 cases having five or more buds at the invasive front. The presence of five or more buds was associated with a poor prognosis on univariate analysis (P = 0.0001), as was a sparse or moderate host inflammatory response (P = 0.001). Tumour budding retained prognostic significance when tumours were separated into adenocarcinomas (n = 287) and squamous cell carcinomas (n = 69), but host inflammatory response was a significant prognostic factor only for adenocarcinomas. On multivariate analysis the presence of five or more buds retained significance (P = 0.002). CONCLUSIONS: Tumour budding and host inflammatory response are important prognostic factors in patients with oesophageal/gastro-oesophageal cancer and can be used to identify high-risk patients who would benefit from closer follow-up and adjuvant therapies.

UNLABELLED: Despite receiving thoracic epidural analgesia, severe ipsilateral shoulder pain is common in patients after thoracotomy. We recruited 44 patients into a double-blinded randomized placebo-controlled study to investigate whether suprascapular nerve block would treat postthoracotomy shoulder pain effectively. All patients received a standard anesthetic with a midthoracic epidural. Thirty patients who experienced shoulder pain within 2 h of surgery were randomly assigned to receive a suprascapular nerve block with either 10 mL of 0.5% bupivacaine or 10 mL of 0.9% saline. Shoulder pain was assessed before nerve blockade, at 30 min, and then hourly for 6 h after the block using a visual analog scale (VAS) and a 5-point verbal ranking score (VRS). The incidence of shoulder pain before nerve block was 78%. There was no significant decrease in either VAS or VRS in the Bupivacaine group. These results suggest that this pain is unlikely to originate in the shoulder and lead us to question the role of a somatic afferent in referred visceral pain. We conclude that suprascapular nerve block does not treat ipsilateral shoulder pain after thoracotomy in patients with an effective thoracic epidural. IMPLICATIONS: This randomized, double-blinded, placebo-controlled trial showed that suprascapular nerve block does not treat the severe ipsilateral shoulder pain that patients experience after thoracotomy. This has implications for established theories of referred pain and indicates that this pain is unlikely to originate in the shoulder.

OBJECTIVE: To assess the cost effectiveness of drug eluting stents (DES) compared with conventional stents for treatment of symptomatic coronary artery disease in the UK. DESIGN: Cost-utility analysis of audit based patient subgroups by means of a simple economic model. SETTING: Tertiary care. PARTICIPANTS: 12 month audit data for 2884 patients receiving percutaneous coronary intervention with stenting at the Cardiothoracic Centre Liverpool between January 2000 and December 2002. MAIN OUTCOME MEASURES: Risk of repeat revascularisation within 12 months of index procedure and reduction in risk from use of DES. Economic modelling was used to estimate the cost-utility ratio and threshold price premium. RESULTS: Four factors were identified for patients undergoing elective surgery (n = 1951) and two for non-elective surgery (n = 933) to predict risk of repeat revascularisation within 12 months. Most patients fell within the subgroup with lowest risk (57% of the elective surgery group with 5.6% risk and 91% of the non-elective surgery group with 9.9% risk). Modelled cost-utility ratios were acceptable for only one group of high risk patients undergoing non-elective surgery (only one patient in audit data). Restricting the number of DES for each patient improved results marginally: 4% of stents could then be drug eluting on economic grounds. The threshold price premium justifying 90% substitution of conventional stents was estimated to be 112 pound sterling (212 USD, 162 pound sterling) (sirolimus stents) or 89 pound sterling (167 USD, 130 pound sterling) (paclitaxel stents). CONCLUSIONS: At current UK prices, DES are not cost effective compared with conventional stents except for a small minority of patients. Although the technology is clearly effective, general substitution is not justified unless the price premium falls substantially.