Laparoscopically assisted versus open oesophagectomy for patients with oesophageal cancer-the Randomised Oesophagectomy: Minimally Invasive or Open (ROMIO) study: protocol for a randomised controlled trial (RCT).

INTRODUCTION: Surgery (oesophagectomy), with neoadjuvant chemo(radio)therapy, is the main curative treatment for patients with oesophageal cancer. Several surgical approaches can be used to remove an oesophageal tumour. The Ivor Lewis (two-phase procedure) is usually used in the UK. This can be performed as an open oesophagectomy (OO), a laparoscopically assisted oesophagectomy (LAO) or a totally minimally invasive oesophagectomy (TMIO). All three are performed in the National Health Service, with LAO and OO the most common. However, there is limited evidence about which surgical approach is best for patients in terms of survival and postoperative health-related quality of life. METHODS AND ANALYSIS: We will undertake a UK multicentre randomised controlled trial to compare LAO with OO in adult patients with oesophageal cancer. The primary outcome is patient-reported physical function at 3 and 6 weeks postoperatively and 3 months after randomisation. Secondary outcomes include: postoperative complications, survival, disease recurrence, other measures of quality of life, spirometry, success of patient blinding and quality assurance measures. A cost-effectiveness analysis will be performed comparing LAO with OO. We will embed a randomised substudy to evaluate the safety and evolution of the TMIO procedure and a qualitative recruitment intervention to optimise patient recruitment. We will analyse the primary outcome using a multi-level regression model. Patients will be monitored for up to 3 years after their surgery. ETHICS AND DISSEMINATION: This study received ethical approval from the South-West Franchay Research Ethics Committee. We will submit the results for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN10386621.

Protocol for developing quality assurance measures to use in surgical trials: an example from the ROMIO study.

INTRODUCTION: Randomised controlled trials (RCTs) in surgery are frequently criticised because surgeon expertise and standards of surgery are not considered or accounted for during study design. This is particularly true in pragmatic trials (which typically involve multiple centres and surgeons and are based in 'real world' settings), compared with explanatory trials (which are smaller and more tightly controlled). OBJECTIVE: This protocol describes a process to develop and test quality assurance (QA) measures for use within a predominantly pragmatic surgical RCT comparing minimally invasive and open techniques for oesophageal cancer (the NIHR ROMIO study). It builds on methods initiated in the ROMIO pilot RCT. METHODS AND ANALYSIS: We have identified three distinct types of QA measure: (i) entry criteria for surgeons, through assessment of operative videos, (ii) standardisation of operative techniques (by establishing minimum key procedural phases) and (iii) monitoring of surgeons during the trial, using intraoperative photography to document key procedural phases and standardising the pathological assessment of specimens. The QA measures will be adapted from the pilot study and tested iteratively, and the video and photo assessment tools will be tested for reliability and validity. ETHICS AND DISSEMINATION: Ethics approval was obtained (NRES Committee South West-Frenchay, 25 April 2016, ref: 16/SW/0098). Results of the QA development study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN59036820, ISRCTN10386621.

Using real-time, anonymous staff feedback to improve staff experience and engagement.

Improving staff engagement has become a priority for NHS leaders, although efforts in this area vary between organisations. University Hospital Bristol NHS Foundation Trust (UH Bristol) is a tertiary teaching hospital where concerns about staff satisfaction and communication were reflected in the 2014 staff survey. To improve staff engagement, a real-time feedback mechanism to capture staff experience and to facilitate feedback from local leaders, was developed and piloted using the Model for Improvement. Initially piloted in two areas in January 2015, the Staff Participation Engagement and Communication application (SPEaC-app) was gradually rolled out to 23 areas within the trust by November 2016. The 2015 staff survey revealed significant improvements in staff motivation, satisfaction with level of responsibility and involvement, and perceived support from managers. These improvements cannot be attributed to this new mechanism in their entirety, but local surveys indicated satisfaction with SPEaC-app, the majority reporting that giving feedback about their shift was valuable while fewer staff had noticed changes in their work area as a result of the comments made via SPEaC-app. Between March 2015 and November 2016, 9259 entries were recorded, with an average of 15 entries per day across all areas. Of the entries, 45.7% were positive and nearly 40% were negative, and 'team working' was the most frequent theme. The project has identified the key factors associated with usability of the SPEaC-app, including, access, location, reliability and perceived privacy of the SPEaC-app. The SPEaC-app is valued and used most by staff in areas where feedback from local leaders is regular, rapid and comprehensive, and where staff comments are acted upon, leading to tangible change. This suggests that strong, consistent local management is required in order to embed it in new areas. SPEaC-app has the potential to support local engagement between managers and their service delivery teams, stimulate tangible improvements in service delivery and support the process of change. Longer term data are needed to determine whether SPEaC-app can influence other factors including staff turnover, recruitment and retention.

Comparing open and minimally invasive surgical procedures for oesophagectomy in the treatment of cancer: the ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) feasibility study and pilot trial.

BACKGROUND: Localised oesophageal cancer can be curatively treated with surgery (oesophagectomy) but the procedure is complex with a risk of complications, negative effects on quality of life and a recovery period of 6-9 months. Minimal-access surgery may accelerate recovery. OBJECTIVES: The ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) study aimed to establish the feasibility of, and methodology for, a definitive trial comparing minimally invasive and open surgery for oesophagectomy. Objectives were to quantify the number of eligible patients in a pilot trial; develop surgical manuals as the basis for quality assurance; standardise pathological processing; establish a method to blind patients to their allocation in the first week post surgery; identify measures of postsurgical outcome of importance to patients and clinicians; and establish the main cost differences between the surgical approaches. DESIGN: Pilot parallel three-arm randomised controlled trial nested within feasibility work. SETTING: Two UK NHS departments of upper gastrointestinal surgery. PARTICIPANTS: Patients aged ≥ 18 years with histopathological evidence of oesophageal or oesophagogastric junctional adenocarcinoma, squamous cell cancer or high-grade dysplasia, referred for oesophagectomy or oesophagectomy following neoadjuvant chemo(radio)therapy. INTERVENTIONS: Oesophagectomy, with patients randomised to open surgery, a hybrid open chest and minimally invasive abdomen or totally minimally invasive access. MAIN OUTCOME MEASURE: The primary outcome measure for the pilot trial was the number of patients recruited per month, with the main trial considered feasible if at least 2.5 patients per month were recruited. RESULTS: During 21 months of recruitment, 263 patients were assessed for eligibility; of these, 135 (51%) were found to be eligible and 104 (77%) agreed to participate, an average of five patients per month. In total, 41 patients were allocated to open surgery, 43 to the hybrid procedure and 20 to totally minimally invasive surgery. Recruitment is continuing, allowing a seamless transition into the definitive trial. Consequently, the database is unlocked at the time of writing and data presented here are for patients recruited by 31 August 2014. Random allocation achieved a good balance between the arms of the study, which, as a high proportion of patients underwent their allocated surgery (69/79, 87%), ensured a fair comparison between the interventions. Dressing patients with large bandages, covering all possible incisions, was successful in keeping patients blind while pain was assessed during the first week post surgery. Postsurgical length of stay and risk of adverse events were within the typical range for this group of patients, with one death occurring within 30 days among 76 patients. There were good completion rates for the assessment of pain at 6 days post surgery (88%) and of the patient-reported outcomes at 6 weeks post randomisation (74%). CONCLUSIONS: Rapid recruitment to the pilot trial and the successful refinement of methodology indicated the feasibility of a definitive trial comparing different approaches to oesophagectomy. Although we have shown a full trial of open compared with minimally invasive oesophagectomy to be feasible, this is necessarily based on our findings from the two clinical centres that we could include in this small preliminary study. TRIAL REGISTRATION: Current Controlled Trials ISRCTN59036820. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 48. See the NIHR Journals Library website for further project information.

A comparative study of survival after minimally invasive and open oesophagectomy.

BACKGROUND: Oesophageal cancer is increasing in incidence worldwide. Minimally invasive techniques have been used to perform oesophagectomy, but concerns regarding these techniques remain. Since its description by Cuschieri in 1992, the use of minimally invasive oesophagectomy (MIO) has increased, but still only used in a minority of resections in the UK in 2009. In particular, there has been reluctance to use minimally invasive (thoracoscopic and laparoscopic) techniques in more advanced cancers for fears regarding the adequacy of the oncological resection. In order to identify any factors that could affect survival, we undertook a retrospective analysis on all patients who underwent surgery in our department over an 8-year period. METHODS: A retrospective data analysis was undertaken on all patients who underwent oesophagectomy in a tertiary upper gastrointestinal surgery unit, from 2005 to 2012 inclusive. Data were collected from the departmental database and case note review, with follow-up and survival data to time of data collection. The survival data were analysed using univariate and multivariate Cox proportional hazard regression models to determine which variables affected survival. Variables examined included age, tumour position, tumour stage (T0, 1, 2 vs T3, 4), nodal stage (N0 vs N1), tumour histology, completeness of resection (R0 vs R1), use of neoadjuvant chemotherapy and operative technique (thoracoscopic/laparoscopic (MIO) vs laparoscopic abdomen/open chest (Lap assisted) vs Open. RESULTS: 334 patients underwent oesophagectomy between 2005 and 2012. Male to female ratio was 3.75:1, with a mean age of 64 years (range 36-87). There were 83 open oesophagectomies, 187 laparoscopically assisted oesophagectomies and 64 minimally invasive oesophagectomies. Following univariate regression analysis the following factors were found to be correlated to survival: use of neoadjuvant chemotherapy (Hazard Ratio 2.889, 95 % CI 1.737-4.806), T stage 3 or 4 (3.749, 2.475-5.72), Node positive (5.225, 3.561-7.665), R1 resection (2.182, 1.425-3.341), type of operation (MIO compared to open oesophagectomy) (0.293, 0.158-0.541). There was no significant relationship between age, tumour position or tumour histology and length of survival. When these factors were entered into a multivariate model, the independently significant factors correlated to survival were found to be T stage 3 or 4 (HR 1.969, 1.248-3.105), Node positive (3.833, 2.548-5.766) and type of operation (MIO compared to open) (0.5186, 0.277-0.972). CONCLUSION: Multiple small studies have found reduced pulmonary complication rates and duration of hospital stay when using a minimally invasive approach compared to open. Concerns in the literature over long-term outcomes, however, have led to limited utilisation of this method, especially in advanced disease. The data from this large study show significantly better survival following operations performed using minimally invasive techniques compared to open, however, we have not adjusted for some known or unknown confounding factors. International and national RCTs, however, will provide more information in due course.

The feasibility of a randomized controlled trial of esophagectomy for esophageal cancer--the ROMIO (Randomized Oesophagectomy: Minimally Invasive or Open) study: protocol for a randomized controlled trial.

BACKGROUND: There is a need for evidence of the clinical effectiveness of minimally invasive surgery for the treatment of esophageal cancer, but randomized controlled trials in surgery are often difficult to conduct. The ROMIO (Randomized Open or Minimally Invasive Oesophagectomy) study will establish the feasibility of a main trial which will examine the clinical and cost-effectiveness of minimally invasive and open surgical procedures for the treatment of esophageal cancer. METHODS/DESIGN: A pilot randomized controlled trial (RCT), in two centers (University Hospitals Bristol NHS Foundation Trust and Plymouth Hospitals NHS Trust) will examine numbers of incident and eligible patients who consent to participate in the ROMIO study. Interventions will include esophagectomy by: (1) open gastric mobilization and right thoracotomy, (2) laparoscopic gastric mobilization and right thoracotomy, and (3) totally minimally invasive surgery (in the Bristol center only). The primary outcomes of the feasibility study will be measures of recruitment, successful development of methods to monitor quality of surgery and fidelity to a surgical protocol, and development of a core outcome set to evaluate esophageal cancer surgery. The study will test patient-reported outcomes measures to assess recovery, methods to blind participants, assessments of surgical morbidity, and methods to capture cost and resource use. ROMIO will integrate methods to monitor and improve recruitment using audio recordings of consultations between recruiting surgeons, nurses, and patients to provide feedback for recruiting staff. DISCUSSION: The ROMIO study aims to establish efficient methods to undertake a main trial of minimally invasive surgery versus open surgery for esophageal cancer. TRIAL REGISTRATION: The pilot trial has Current Controlled Trials registration number ISRCTN59036820(25/02/2013) at http://www.controlled-trials.com; the ROMIO trial record at that site gives a link to the original version of the study protocol.

Surgical ward rounds in England: a trainee-led multi-centre study of current practice.

BACKGROUND: Recent guidance advocates daily consultant-led ward rounds, conducted in the morning with the presence of senior nursing staff and minimising patients on outlying wards. These recommendations aim to improve patient management through timely investigations, treatment and discharge. This study sought to evaluate the current surgical ward round practices in England. METHODS: Information regarding timing and staffing levels of surgical ward rounds was collected prospectively over a one-week period. The location of each patient was also documented. Two surgical trainee research collaboratives coordinated data collection from 19 hospitals and 13 surgical subspecialties. RESULTS: Data from 471 ward rounds involving 5622 patient encounters was obtained. 367 (77.9%) ward rounds commenced before 9am. Of 422 weekday rounds, 190 (45%) were consultant-led compared with 33 of the 49 (67%) weekend rounds. 2474 (44%) patients were seen with a nurse present. 1518 patients (27%) were classified as outliers, with 361 ward rounds (67%) reporting at least one outlying patient. CONCLUSION: Recommendations for daily consultant-led multi disciplinary ward rounds are poorly implemented in surgical practice, and patients continue to be managed on outlying wards. Although strategies may be employed to improve nursing attendance on ward rounds, substantial changes to workforce planning would be required to deliver daily consultant-led care. An increasing political focus on patient outcomes at weekends may prompt changes in these areas.

Surgical training: the impact of changes in curriculum and experience.

INTRODUCTION: Craft specialties, such as surgery, rely on practice to acquire skill. Yet recent changes in training in the United Kingdom have decreased experience and altered the balance of curriculum content. Most recently, the European Working Time Directive has led to a reduction in working hours and expansion in the number of trainees. The impact that these changes have had on operative experience, patient management, communication, and teaching skills is unclear. This study aims to assess the effects of the changing curriculum and work patterns on the experience of trainees at senior house officer (SHO, equivalent to junior resident) level in general surgery. METHODS: A structured questionnaire was sent to general surgery trainees at the SHO (n = 52) and specialist registrar (SpR, n = 69) levels (equivalent to senior resident) in the Severn Deanery, United Kingdom. RESULTS: In all, 70% of both SHOs and SpRs responded. SpRs had spent a mean of 50 months (21 months in general surgery) at the SHO level, compared with 24 months (9 months in general surgery) for current SHOs. A total of 90% of SpRs could perform an open appendectomy unsupervised by the end of their SHO training, compared with 28% of current SHOs. In all, 63% of SpRs and 8% of SHOs could undertake inguinal hernia repair unsupervised at SHO level. In addition, 90% of SpRs and 84% of SHOs felt operative skills have declined, whereas communication and teaching skills were deemed the same or better. Of the respondents, 88% of SpRs and 76% of SHOs thought surgical training was getting worse. DISCUSSION: Trainees are spending less time in surgery at the SHO level, and this is reflected in reported operative ability. The introduction of communication and teaching skills into the curriculum has had a perceived benefit. The reduction in working hours must be offset by implementing measures to maximize limited training opportunities. The potential implications of these changes in training and experience on patient outcomes remain to be determined.

A comparison study of gastric cancer risk in patients with duodenal and gastric ulcer: roles of gastric mucosal histology and p53 codon 72 polymorphism.

Gastric ulcer is positively, and duodenal ulcer negatively, associated with the risk of gastric cancer. The relationship between a common p53 polymorphism at codon 72 and gastric cancer risk in patients with gastric and duodenal ulcer was examined in 397 Caucasian patients using PCR-RFLP. Noncardiac cancer patients had a distribution pattern of codon 72 genotypes similar to that of other non-cancer patient groups, though the frequency of the Pro/Pro genotype looks higher in duodenal ulcer. However, patients with cancer of the cardiac region had a significantly higher frequency of the Arg/Arg genotype than patients with chronic gastritis, duodenal ulcer, and noncardiac cancer. There was no significant difference in the distribution patterns between gastric ulcer and noncardiac or cardiac cancer or between gastric and duodenal ulcer. These findings may be a reflection of differences in the interaction between p53 codon 72 polymorphism and local factors in the stomach.

Insulin-like growth factor binding protein-3: relationship to the development of gastric pre-malignancy and gastric adenocarcinoma (United Kingdom).

IGF family proteins play a pivotal role in regulating cell growth and apoptosis in normal and tumour tissues. IGFBP-3 is the major binding protein of IGFs and modulates the bioactivity of IGFs. To examine the role of IGFBP-3 in gastric cancer, an IGFBP3 promoter polymorphism, and serum and gastric mucosal levels of IGFBP-3 were assessed in two independent groups of patients (396 and 117 patients, respectively) with gastroduodenal diseases. There was no significant association between IGFBP-3 polymorphism and different gastroduodenal diseases ( p = 0.6), but a significantly higher frequency of CC, a genotype related to lower levels of serum IGFBP-3 previously, were observed in patients with antral intestinal metaplasia when compared with those without this pre-malignancy ( p = 0.04). Similarly, data from another independent group of patients further showed that patients with antral or corpus intestinal metaplasia had significantly lower serum levels of IGFBP-3 than those without these changes ( p = 0.03 and 0.04, respectively). Furthermore, the percentage of positive IGFBP-3 staining in tumour tissue was significantly higher in patients with well or moderately differentiated tumours than those with poorly differentiated tumours ( p = 0.04), indicating that IGFBP-3 may be associated with a better prognosis. In conclusion, our study suggests that IGFBP-3 may be protective against the development of gastric adenocarcinoma by preventing the formation of intestinal metaplasia and improve the prognosis of gastric cancer.

Prognostic value of TP53 codon 72 polymorphism in advanced gastric adenocarcinoma.

PURPOSE: A common polymorphism of the tumor suppressor gene TP53 at codon 72 has been associated with human cancer susceptibility. The prognostic role of the polymorphism was assessed in 102 patients with advanced gastric adenocarcinoma. EXPERIMENTAL DESIGN: We followed up 102 consecutive Caucasian patients with advanced gastric adenocarcinoma for >5 years and determined the status of the TP53 codon 72 polymorphism in DNA samples extracted from archived gastric tissues. RESULTS: The frequency of the arginine homozygous allele was positively correlated to patient age at baseline (P = 0.002). However, the age-related increase in the percentage of codon 72 arginine p53 was not correlated to the prognosis for gastric cancer patients. Multivariable analysis in patients who had surgery showed that baseline age may be inversely associated with patient survival (odds ratio, 1.1; 95% confidence interval, 1.0-1.2; P = 0.02). Furthermore, alcohol consumption may be associated with reduced survival (P = 0.06). CONCLUSIONS: These findings indicate that codon 72 arginine p53 may not be associated with a prolonged survival in patients with advanced gastric adenocarcinoma, but further study is needed to assess whether this polymorphism is associated with a late onset or slow progress of early gastric adenocarcinoma.

Age-associated increase of codon 72 Arginine p53 frequency in gastric cardia and non-cardia adenocarcinoma.

PURPOSE: A common polymorphism of the tumor suppressor gene TP53 at codon 72 has been associated with human cancer susceptibility and prognosis. To examine the role of the polymorphism in the gastric adenocarcinoma, we examined 397 patients with or without the cancer. EXPERIMENTAL DESIGN: DNA samples were extracted from archived gastric tumor tissues and/or normal tissues of gastric adenocarcinoma and noncancer patients. The TP53 codon 72 genotypes were determined by PCR-RFLP. RESULTS: The overall genotype frequencies for Pro/Pro, Arg/Pro, and Arg/Arg were 7.3, 45.1, and 47.6%, respectively. A significant stepwise increased frequency of codon 72 Arg p53 with age was observed in patients with gastric cancer, but not in noncancer patients (P = 0.01). Patients with gastric cardia cancer had a significantly higher frequency of homozygous Arg allele than those with non-cardia tumors (P = 0.03) or than noncancer patients. After adjustment for age and gender, a logistic regression analysis suggested that the risk for a p53 Arg homozygous patient to develop cardia cancer is 3.1 95% confidence interval, 1.4-7.3) times greater than for p53 Pro homozygous and p53 Arg/Pro heterozygous patients. No close relationship was observed among patient gender, tumor histological type, p53 protein expression, and codon 72 genotype distribution. CONCLUSIONS: These findings indicate that codon 72 Arg p53 may be associated with a prolonged survival for patients who have had gastric adenocarcinoma, especially non-cardia adenocarcinoma. It may confer, however, a different role on patients who suffer cardia gastric adenocarcinoma.