Study protocol for a multicenter prospective cohort study on esophagogastric anastomoses and anastomotic leak (the Oesophago-Gastric Anastomosis Audit/OGAA).

Esophagectomy is a mainstay in curative treatment for esophageal cancer; however, the reported techniques and outcomes can vary greatly. Thirty-day mortality of patients with an intact anastomosis is 2-3% as compared to 17-35% in patients who have an anastomotic leak. The subsequent management of leaks postesophagectomy has great global variability with little consensus on a gold standard of practice. The aim of this multicentre prospective audit is to analyze current techniques of esophagogastric anastomosis to determine the effect on the anastomotic leak rate. Leak rates and leak management will be assessed to determine their impact on patient outcomes. A 12-month international multicentre prospective audit started in April 2018 and is coordinated by a team from the West Midlands Research Collaborative. This will include patients undergoing esophagectomy over 9 months and encompassing a 90-day follow-up period. A pilot data collection period occurred at four UK centers in 2017 to trial the data collection form. The audit standards will include anastomotic leak and the conduit necrosis rate should be less than 13% and major postoperative morbidity (Clavien-Dindo Grade III or more) should be less than 35%. The 30-day mortality rate should be less than 5% and the 90-day mortality rate should be less than 8%. This will be a trainee-led international audit of esophagectomy practice. Key support will be given by consultant colleagues and anesthetists. Individualized unit data will be distributed to the respective contributing sites. An overall anonymized report will be made available to contributing units. Results of the audit will be published in peer-reviewed journals with all collaborators fully acknowledged. The key information and results from the audit will be disseminated at relevant scientific meetings.

Cost-effectiveness of emergency versus delayed laparoscopic cholecystectomy for acute gallbladder pathology.

BACKGROUND: The optimal timing of cholecystectomy for patients admitted with acute gallbladder pathology is unclear. Some studies have shown that emergency cholecystectomy during the index admission can reduce length of hospital stay with similar rates of conversion to open surgery, complications and mortality compared with a 'delayed' operation following discharge. Others have reported that cholecystectomy during the index acute admission results in higher morbidity, extended length of stay and increased costs. This study examined the cost-effectiveness of emergency versus delayed cholecystectomy for acute benign gallbladder disease. METHODS: Using data from a prospective population-based cohort study examining the outcomes of cholecystectomy in the UK and Ireland, a model-based cost-utility analysis was conducted from the perspective of the UK National Health Service, with a 1-year time horizon for costs and outcomes. Probabilistic sensitivity analysis was used to investigate the impact of parameter uncertainty on the results obtained from the model. RESULTS: Emergency cholecystectomy was found to be less costly (£4570 versus £4720; €5484 versus €5664) and more effective (0·8868 versus 0·8662 QALYs) than delayed cholecystectomy. Probabilistic sensitivity analysis showed that the emergency strategy is more than 60 per cent likely to be cost-effective across willingness-to-pay values for the QALY from £0 to £100 000 (€0-120 000). CONCLUSION: Emergency cholecystectomy is less costly and more effective than delayed cholecystectomy. This approach is likely to be beneficial to patients in terms of improved health outcomes and to the healthcare provider owing to the reduced costs.

A national audit of colonic interposition for esophageal replacement.

Esophageal replacement by colonic interposition is an uncommon procedure. This study sought to identify the frequency of this operation in England, identify techniques and associated problems, and also assess health-related quality of life (HR QOL) from the two largest centers performing this procedure. Hospital Episode Statistics were used to identify patients and centers undertaking colon interposition between March 2001 and March 2015. An online survey of UK consultants discussed methods and experience. HR QOL was assessed using the Short Form 36(SF-36v2) with additional gastrointestinal questions. Hospital Episode Statistics identified 328 interpositions (22 in pediatric hospitals). The two highest volume units did 42 and 45 operations, respectively. Thirty-four surgeons (79% response rate) replied to the survey. Fifty-two percent preferred to use the left colon with 81% preferring a substernal placement. The HR QOL survey was performed on 24 patients with a median of 3 years after surgery (ranging from 9 months to 10 years) from the two largest centers and a 56% response rate. Five patients had physical QOL scores above population average and 10 had mental scores above population average. All patients had early satiety, 20 described dysphagia, and 18 regularly took antireflux medication. There was an estimated mean loss of 13.1% body weight (10.6 kg) postoperatively and three patients still relied on a feeding tube for nutrition after an average of 3 years. Colon interposition results in an acceptable long-term QOL. Few centers regularly perform this operation, and centralizing to high-volume centers may lead to better outcomes.

Meta-analysis of perioperative antibiotics in patients undergoing laparoscopic cholecystectomy.

BACKGROUND: The effectiveness of perioperative antibiotics in reducing surgical-site infection (SSI) and overall nosocomial infections in patients undergoing laparoscopic cholecystectomy for biliary colic and low- and moderate-risk cholecystitis (Tokyo classification) is unclear. A systematic review and meta-analysis was performed to assess this. METHODS: Searches were conducted of the MEDLINE, Embase and Cochrane databases. Only randomized clinical trials (RCTs) were included. The analysis was performed using the random-effects method, and the risk ratio (RR) with 95 per cent c.i. was employed. RESULTS: Nineteen RCTs, published between 1997 and 2015, with a total of 5259 participants, of whom 2709 (51·5 per cent) were treated with antibiotics, were included. SSI and overall nosocomial infections were detected in 2·4 and 4·2 per cent respectively of patients given perioperative antibiotics, and in 3·2 and 7·2 per cent of those who received no antibiotics. Antibiotics did not significantly reduce the risk of SSI (RR 0·81, 95 per cent c.i. 0·58 to 1·13; P = 0·21) or overall nosocomial infections (RR 0·64, 0·36 to 1·14; P = 0·13). There was no significant between-study heterogeneity for SSI, but significant between-study heterogeneity in the eight studies that reported nosocomial infections. Analysis of studies considered to be high quality, grouped according to the timing of antibiotics (preoperative only or perioperative) and reporting intention-to-treat analyses, again failed to show a significant reduction in SSI. CONCLUSION: Antibiotics should not be administered before laparoscopic cholecystectomy in patients with biliary colic and/or low- and moderate-risk cholecystitis.

Metabolism of aceclofenac in cattle to vulture-killing diclofenac.

The nonsteroidal anti-inflammatory drug (NSAID) diclofenac is highly toxic to Gyps vultures, and its recent widespread use in South Asia caused catastrophic declines in at least 3 scavenging raptors. The manufacture of veterinary formulations of diclofenac has since been banned across the region with mixed success. However, at least 12 other NSAIDs are available for veterinary use in South Asia. Aceclofenac is one of these compounds, and it is known to metabolize into diclofenac in some mammal species. The metabolic pathway of aceclofenac in cattle, the primary food of vultures in South Asia, is unknown. We gave 6 cattle the recommended dose of aceclofenac (2 mg/kg), collected blood thereafter at intervals for up to 12 h, and used liquid chromatography with mass spectrometry in a pharmacokinetic analysis of aceclofenac and diclofenac in the plasma. Nearly all the aceclofenac administered to the cattle was very rapidly metabolized into diclofenac. At 2 h, half the aceclofenac had been converted into diclofenac, and at 12 h four-fifths of the aceclofenac had been converted into diclofenac. Therefore, administering aceclofenac to livestock poses the same risk to vultures as administering diclofenac to livestock. This, coupled with the risk that aceclofenac may replace diclofenac in the veterinary market, points to the need for an immediate ban on all aceclofenac formulations that can be used to treat livestock. Without such a ban, the recovery of vultures across South Asia will not be successful.

Influence of day of surgery on mortality following elective colorectal resections.

BACKGROUND: The aim of this study was to investigate whether the increased mortality previously identified for surgery performed on Fridays was apparent following major elective colorectal resections and how this might be affected by case mix. METHODS: Patients undergoing elective colorectal resections in England from 2001 to 2011 were identified using Hospital Episode Statistics. Propensity scores were used to match patients having operations on a Friday in a 1 : 1 ratio with those undergoing surgery on other weekdays. Multivariable analyses were used to investigate overall deaths within 1 year of operation. RESULTS: A total of 204,669 records were extracted for patients undergoing major elective colorectal resections. Patients who had surgery on Fridays were more deprived (4780 (17.1 per cent) of 27,920 versus 28,317 (16.0 per cent) of 176,749; P < 0.001), a greater proportion had had an emergency admission in the 3 previous months (7870 (28.2 per cent) of 27,920 versus 48,623 (27.5 per cent) of 176,749; P = 0.019), underwent minimal access surgery (4565 (16.4 per cent) of 27,920 versus 23,783 (13.5 per cent) of 176,749; P < 0.001) and had surgery for benign diagnoses (6502 (23.3 per cent) of 27,920 versus 38,725 (21.9 per cent) of 176,749; P < 0.001) than those who had surgery on Mondays to Thursdays. In a matched analysis the odds ratio for 30-day mortality after colorectal resections performed on Fridays compared with other weekdays was 1.25 (95 per cent c.i. 1.13 to 1.37); odds ratios for 90-day and 1-year mortality were 1.16 (1.07 to 1.25) and 1.10 (1.04 to 1.16) respectively. CONCLUSION: Patients selected for colorectal resections on Fridays had a higher mortality rate than patients operated on from Monday to Thursday and had different characteristics, suggesting that increased mortality may reflect patient factors rather than hospital variables alone.

A prospective study of patient reported outcomes in pancreatic and peri-ampullary malignancy.

BACKGROUND: The purpose of the present study was to describe the impact of treatment of pancreatic and peri-ampullary malignancy on patient reported outcomes (PRO). However, limited data are available describing the impact of curative or palliative therapy on pancreatic/peri-ampullary malignancy and quality of life. METHODS: Patients selected for pancreaticoduodenectomy (PD) completed the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire pre-surgery and 6 weeks, 3, 6, 12, 18, and 24 months postoperatively. Patients selected for palliative treatments completed the same questionnaire before treatment and monthly thereafter. Mean scores and 95 % confidence intervals (CI) were calculated for functional scales. Symptom scales and single items were categorized as either minimal or severe, and they were reported as proportions of patients experiencing severe symptoms with 95 % CI. RESULTS: A total of 100 patients (53 planned PD, 47 palliative) were enrolled. Of the 53 patients planned for surgery, 12 had tumors that were unresectable and 41 underwent pancreatoduodenectomy (PD). Seven patients were excluded because of benign histology or concurrent malignancy. Baseline questionnaire compliance was 70 %. For those undergoing PD, there were 53 complications, 7 deaths at 1 year, and 14 deaths at 2 years. Post-surgery most functions and symptoms deteriorated. Recovery in global health and most symptoms occurred by 3 months, and functional scales recovered by 6 months. Recovery of PRO was maintained in the survivors at 2 years. Palliative patients had poorer function and more symptoms at baseline; however, poor follow-up questionnaire compliance prevented further analysis of this group. CONCLUSIONS: Pancreaticoduodenectomy has a short-term negative impact on PRO that recovers within 6 months and is maintained at 2 years in survivors. Further work evaluating palliative and curative treatment in larger patient groups with disease-specific questionnaires is necessary.

Integrative analysis of array-comparative genomic hybridisation and matched gene expression profiling data reveals novel genes with prognostic significance in oesophageal adenocarcinoma.

BACKGROUND AND AIMS: The incidence of oesophageal adenocarcinoma (OAC) has been increasing rapidly with a dismal survival rate of less than 20%. Understanding the genomic aberrations and biology of this cancer may enhance disease interventions. This study aimed to use genome-wide genomic and expression data to enhance the understanding of OAC pathogenesis and identify groups with differential outcomes. METHODS: Array-comparative genomic hybridisation (aCGH) analysis was carried out on 56 fresh frozen OAC resection samples with long-term clinical follow-up data. Samples with aberrations were further analysed with whole-genome single-nucleotide polymorphism arrays to confirm aCGH findings. Matched gene expression microarray data were used to identify genes with high copy number-expression correlations. Nested-multiplex PCR on DNA from microdissected specimens and fluorescence in situ hybridisation assays were used for target validation. Immunohistochemistry on the same cohort and independent samples (n=371) was used for subsequent validation. Kaplan-Meier survival analyses were performed based on aCGH data after unsupervised K-means clustering (K=5, 50 iterations) and immunohistochemistry data. RESULTS: aCGH identified 17 common regions (>5% samples) of gains and 11 common regions of losses, including novel regions in OAC (loci 11p13 and 21q21.2). Integration of aCGH data with matched gene expression microarray data highlighted genes with high copy number-expression correlations: two deletions (p16/CDKN2A, MBNL1) and four gains (EGFR, WT1, NEIL2, MTMR9). Immunohistochemistry demonstrated protein over-expression of targets with gains: EGFR (10%), WT1 (20%), NEIL2 (14%) and MTMR9 (25%). These targets individually (p<0.060) and in combination had prognostic significance (p=0.008). On the genomic level, K-means clustering identified a cluster (32% of cohort) with differential log(2) ratios of 16 CGH probes (p<4×10(-7)) and a worse prognosis (median survival=1.37 years; p=0.015). CONCLUSIONS: Integration of aCGH and gene expression data identified copy number aberrations and novel genes with prognostic potential in OAC.

Systematic review of intraperitoneal chemotherapy for gastric cancer.

BACKGROUND: Gastric cancer with peritoneal carcinomatosis has a poor prognosis. Intraperitoneal chemotherapy has been proposed as a treatment option. This systematic review examined recent literature to determine the role of intraperitoneal chemotherapy in gastric cancer. METHODS: Four electronic databases were searched between January 2004 and January 2010 for relevant studies. Defined outcomes of interest were treatment-related morbidity and mortality, long-term survival and sites of recurrence. RESULTS: Fourteen studies were identified involving 914 patients with gastric cancer, of whom 819 (89·6 per cent) received intraperitoneal chemotherapy. There were two randomized controlled trials, two case-control studies and ten observational studies. Methodological quality was rated as poor in 12 studies, with selection and observer bias apparent in most non-randomized cohorts. Studies were often small and varied in terms of intraperitoneal timing of chemotherapy, chemotherapeutic agents, treatment temperature, and the use of adjuvant therapies. In the better conducted studies, survival was longer in patients receiving intraperitoneal chemotherapy and surgery than in those having surgery alone. CONCLUSION: There is limited good-quality evidence to determine the role of intraperitoneal chemotherapy in gastric cancer. Intraperitoneal chemotherapy in gastric cancer is worthy of further appraisal. However, the quality of trials must be improved, and studies must be conducted more uniformly to minimize bias and aid comparison between centres.

The effect of surgical complications on ENT trainees.

BACKGROUND: The 'second victim phenomenon' is a term attributed to the traumatic effect a medical error can have on healthcare professionals. Patient safety incidents have been shown to occur in as many as one in seven patients in hospital. These incidents cause significant, potentially devastating, trauma to patients and their relatives, and can have deep and long-lasting effects on the health professionals involved. These incidents can have a negative impact on doctors' emotional wellbeing; their professional practice in relation to this impact has not been extensively investigated in surgical trainees. METHOD: A survey of UK otolaryngology trainees was conducted to investigate the effects of complications and medical errors on trainees, and examine how these are discussed within departments. RESULTS AND CONCLUSION: The findings suggest that further training is required and would be warmly received by otolaryngology trainees as part of higher surgical training.

Peritoneal lavage cytology in patients with oesophagogastric adenocarcinoma.

BACKGROUND: The aim of the study was to determine the value of performing peritoneal lavage cytology during laparoscopy in the management of oesophagogastric adenocarcinoma. METHODS: Laparoscopy combined with peritoneal cytology was performed in patients with potentially resectable oesophagogastric adenocarcinoma. Macroscopic peritoneal findings at laparoscopy and the presence of free peritoneal tumour cells were recorded. All patients were followed to death or the census point. Patients with overt peritoneal disease or positive cytology were offered palliative chemotherapy, subject to performance status. RESULTS: Forty-eight (18.8 per cent) of 255 patients had overt peritoneal metastases at staging laparoscopy. Fifteen (7.2 per cent) of the remaining 207 patients had positive cytology; these patients had a median (95 per cent confidence interval) survival of 13 (3.1 to 22.9) months, versus 9 (7.4 to 10.6) months for those with overt peritoneal metastases (P = 0.517). Of patients receiving chemotherapy, those without overt metastases had a slight survival advantage over patients with metastases (median 15 (10.8 to 19.2) versus 9 (7.4 to 10.7) months; P = 0.045). CONCLUSION: Positive peritoneal cytology in the absence of overt peritoneal metastases is not uncommon in oesophagogastric adenocarcinoma. It is a marker of poor prognosis even in the absence of overt peritoneal metastases.

Health-related quality of life among patients with adenocarcinoma of the gastro-oesophageal junction treated by gastrectomy or oesophagectomy.

BACKGROUND: Tumours of the gastro-oesophageal junction may be resected by total gastrectomy (TG) or transthoracic oesophagectomy (TTO). This study compared health-related quality of life (HRQL) following these procedures. METHODS: Prospective clinical and HRQL data (European Organization for Research and Treatment of Cancer QLQ-C30) were collected from 63 consecutive patients (20 TG and 43 TTO) before and 6 months after surgery for Siewert type I-III gastro-oesophageal tumours. RESULTS: Questionnaire response rates exceeded 90 per cent. Patients were similar with respect to disease stage, treatment-related mortality and survival, but those selected for TTO were younger with less co-morbidity than those undergoing TG. These differences were reflected in baseline HRQL scores, which were better in patients selected for TTO. Six months after surgery, however, HRQL showed a greater deterioration after TTO than after TG in terms of role and social function, global quality of life and fatigue. Symptom scores for pain and diarrhoea increased in both groups. CONCLUSION: TTO had a greater negative impact on HRQL than TG for tumours of the gastro-oesophageal junction.

Quality of life during potentially curative treatment for locally advanced oesophageal cancer.

BACKGROUND: Combination chemoradiotherapy with or without surgery are internationally applied alternative strategies for potential cure of oesophageal cancer. This study compared health-related quality of life (HRQL) between patients selected for chemoradiation and those who had combination treatment including oesophagectomy. METHODS: Patients with stage II or III oesophageal cancer completed HRQL assessments at baseline, at the worst expected HRQL time point and at expected recovery. HRQL was compared between groups using linear regression, adjusting for age, sex, performance status, tumour stage and type, and baseline HRQL. RESULTS: Some 132 patients began treatment, of whom 51 had chemoradiotherapy and 81 combination treatment including surgery. Patients selected for chemoradiotherapy were older, more likely to have squamous cell cancer and reported poorer HRQL than those selected for surgery. At the worst expected time point after treatment, both groups reported multiple symptoms and poor function, but surgery was associated with a greater reduction in HRQL from baseline than chemoradiotherapy. Recovery of HRQL was achieved within 6 months after chemoradiotherapy, but complete recovery had not occurred 6 months after surgery and there was persistent significant deterioration in some aspects. CONCLUSION: The negative treatment-related impact of chemoradiation on short-term HRQL is less than that experienced with combination treatment including surgery. Patients preferring early recovery should consider definitive chemoradiation.