Richard Berrisford

Health-related quality of life after minimally invasive oesophagectomy

Open oesophagectomy has a detrimental impact on health‐related quality of life (HRQL), with recovery taking up to a year. Minimally invasive oesophagectomy (MIO) may enable a more rapid recovery of HRQL.

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

BackgroundThere 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/DesignA 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.DiscussionThe ROMIO study aims to establish efficient methods to undertake a main trial of minimally invasive surgery versus open surgery for esophageal cancer.Trial registrationThe 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.

The implementation and effectiveness of an enhanced recovery programme after oesophago-gastrectomy: A prospective cohort study

BACKGROUNDnOesophageal resection is notoriously complicated and produces a cohort of patients prone to postoperative complications. Maintaining quality care demands a systematic approach to patient management yet postoperative recovery after oesophagectomy is often needlessly inefficient, heterogeneous and governed by the idiosyncrasies of the operating surgeon. Enhanced recovery after surgery (ERAS) programmes are now well established in colorectal surgery and here we describe the implementation and effectiveness of an ERAS programme for the postoperative management of Ivor Lewis oesophago-gastrectomy (ILOG).nnnMETHODSnAn ERAS programme was devised and implemented with the support of a dedicated in-hospital task-force. Three consultant surgeons allocated consecutive patients to the programme (ERAS) and outcomes were compared to consecutive patients not on the ERAS programme (non-ERAS) and a pre-ERAS cohort (pre-ERAS). Principal outcome measures were total length of stay (TLOS), Accordion postoperative complication grade and 30-day readmission rate.nnnRESULTSn75 patients were enrolled on the ERAS programme, 41 continued as a non-ERAS cohort and 80 consecutive pre-ERAS patients were identified. A significant improvement in median TLOS was observed in the ERAS group (10 days r.7-58) compared to pre-ERAS (13 days r. 8-57) (p = <0.001) and non-ERAS patients (13 days r.8-42) (p = <0.001). No significant difference in Accordion scores for postoperative complications or 30-day readmission rates were observed.nnnDISCUSSIONnThe introduction of an ERAS programme after ILOG can significantly reduce TLOS without jeopardising patient safety or clinical outcomes. The successful introduction of an ERAS programme requires full motivation and support from all team members including the patient.

Positron Emission Tomography–Computed Tomography in Oesophageal Cancer Staging: A Tailored Approach

BackgroundPositron emission tomography–computed tomography (PET–CT) scanning is used routinely in the staging of oesophageal cancer to identify occult metastases not apparent on CT and changes the management in typically 3–18xa0% patients. The authors aim to re-evaluate its role in the management of oesophageal cancer, investigating whether it is possible to identify a group of patients that will not benefit and can safely be spared from this investigation.MethodsConsecutive patients with oesophageal cancer undergoing PET–CT staging between 2010 and 2013 were identified from a specialist modern multidisciplinary team database. Without knowledge of the PET–CT result, patients were stratified into low-risk or high-risk groups according to the likelihood of identifying metastatic disease on PET–CT based on specified criteria routinely available from endoscopy and CT reports. Clinical outcomes in the two groups were investigated.ResultsIn 383 undergoing PET–CT, metastatic disease was identified in 52 (13.6xa0%) patients. Eighty-three patients were stratified as low risk and 300 as high risk. None of the low-risk patients went on to have metastatic disease identified on PET–CT. Of the high-risk patients, 17xa0% had metastatic disease identified on PET–CT.ConclusionsIn one of the largest studies to date investigating the influence of staging PET–CT on management of patients with oesophageal cancer, the authors report a classification based on endoscopy/CT criteria is able to accurately stratify patients according to the risk of having metastatic disease. This could be used to avoid unnecessary PET–CT 22xa0% of patients, saving cost, inconvenience and reducing potential delay to definitive treatment in this group.

A randomised trial of post-discharge enteral feeding following surgical resection of an upper gastrointestinal malignancy

BACKGROUNDnPatients undergoing upper gastrointestinal surgery often eat poorly post-operatively, despite dietetic input. A pilot study was conducted to examine the benefit of a 6 week nutritional supplementation via a feeding jejunostomy on fatigue, quality of life and independent living.nnnMETHODSnA feeding jejunostomy was placed routinely at oesophagectomy or total gastrectomy for cancer. At discharge, patients were randomised to nutritional supplementation (600xa0kcal/day) via their feeding jejunostomies or no jejunal supplement. Patients were assessed at discharge and 3, 6, 12 and 24 weeks following discharge for fatigue (MFI-20), quality of life (QLQ-OES18), health economic analysis (EQ5D) as well as completing a two-day dietary diary.nnnRESULTSn44 patients (M:F, 29:15) were randomised, 23 received jejunal supplements. There were no differences between the groups. Percentage of calculated energy requirement received was greater in the supplemented group at weeks 3 and 6 (pxa0<xa00.0001). Oral energy intake was not different between the groups at any time period. After hospital discharge, there were no differences in MFI-20, EQ5D and QLQ-OES18 scores at any time point. From hospital discharge fatigue improved and plateaued at 6 weeks (pxa0<xa00.05 for both groups), independence at 12 weeks (pxa0<xa00.05 for both groups). No improvement was seen in quality of life until 24 weeks in the active group alone (pxa0<xa00.02) and not at all in the control group.nnnCONCLUSIONSnAddition of jejunal feeding is effective in providing patients with an adequate energy intake. Increased energy intake however, produced no obvious improvement in measures of fatigue, quality of life or health economics.

Induction Therapy for Resectable Esophageal Cancer

A number of factors need to be considered when attempting to analyze the potential utility of induction therapy in patients with clinically resectable esophageal cancer. Many factors reflect problems with older staging and therapeutic concepts. In addition, prior publications frequently fail to adequately isolate patients by stage and cell type in reporting outcomes of induction therapy. These features lead to difficulties in identifying appropriate therapeutic options based on outdated reports, and will be discussed in detail below.

Minimally-invasive subtotal oesophagectomy: three-stage thoracoscopic, laparoscopic subtotal oesophagectomy with cervical anastomosis

This contribution describes a minimally-invasive approach to subtotal oesophagectomy. Indications, pre-emptive ischaemic conditioning and feeding jejunostomy are discussed. In the lateral position, the oesophagus is mobilized thoracoscopically in a specific order, formally identifying at risk structures. A radical en bloc dissection is performed with formal lymphadenectomy. Slings are placed around proximal and distal oesophagus and a paravertebral catheter is inserted for postoperative analgesia. In the supine position, the stomach is mobilized laparoscopically, preserving the gastroepiploic arcade and the right gastric artery. Kochers manoeuvre is undertaken. Lymphadenectomy is performed around the coeliac axis, common hepatic, left gastric and splenic arteries. The proximal oesophagus is delivered through a cervical approach and transected, suturing the distal end to a delivery system to facilitate passage of the conduit through the mediastinum. The mobilized stomach is delivered through a 6-cm right paramedian minilaparotomy and a wide gastric conduit formed, preserving collateral supply and venous drainage from the distal lesser curve. The conduit is passed to the neck using a vacuum/camera sleeve technique and anastomosed to the transected cervical oesophagus with a semi-mechanical technique. The paramedian minilaparotomy is closed with a local anaesthetic catheter in the posterior sheath and the conduit brought back into an anatomical position laparoscopically. Postoperative care is described.

Prospective cohort study of neoadjuvant therapy toxicity in the treatment of oesophageal adenocarcinoma

BACKGROUNDnEarly studies investigating the benefits of neoadjuvant therapy in oesophageal cancer showed conflicting results, taking many years before a survival advantage was demonstrated in randomised trials. Gains are modest, limited by progressive disease and toxicity. This study aimed to investigate the relationship between neoadjuvant therapy-associated toxicity and clinical outcomes including survival in patients with potentially curable oesophageal adenocarcinoma.nnnMATERIALS AND METHODSnA cohort of 286 patients undergoing neoadjuvant therapy followed by surgical resection at a single institution was identified from a prospective database. Adverse events from neoadjuvant therapy were recorded and graded. Patients were divided into two groups according to whether they suffered toxicity or not. Clinical outcomes including whether patients completed the neoadjuvant course, whether they proceeded to resection and overall survival, were compared between the groups.nnnRESULTSnNeoadjuvant therapy-related toxicity was identified in 67/286 patients. 46 patients suffered severe, life-threatening or fatal adverse events. In patients with toxicity, 47% did not complete the chemotherapy course compared to 17% without toxicity, RR 2.7 (95%CI 1.7-4.4), (Pu202f<u202f0.001). In patients suffering toxicity, 17.9% failed to proceed to resection compared with 7.8% in those without toxicity, RR 2.3 (95%CI 1.2-4.6) Pu202f=u202f0.02. Median overall survival was shorter in patients suffering toxicity (20.7 months) compared to those without toxicity (37.8 months), Pu202f=u202f0.008. When patients failing to proceed to resection were excluded, median overall survival was shorter in patients suffering toxicity (26.2 months) compared with those without toxicity (47.8), Pu202f=u202f0.039.nnnCONCLUSIONnNeoadjuvant therapy-related toxicity is common and can have serious consequences including failure to complete chemotherapy cycles, a higher risk of not proceeding to surgical resection and poorer overall survival. Efforts should be made to reduce toxicity and research should aim to identify responders and factors predictive of toxicity.

Loco-regional staging accuracy in oesophageal cancer—How good are we in the modern era?

INTRODUCTIONnAccuracy of locoregional staging in patients with oesophageal cancer is critical in determining operability and the need for neoadjuvant treatment. Imaging technology has advanced significantly in recent years but it is not known whether this translates to improved staging accuracy. This study investigates staging accuracy in relation to CT, EUS, PET-CT and final pre-operative stage. It specifically addresses the accuracy of staging with respect to the threshold for administering neoadjuvant therapies.nnnMATERIALS AND METHODSnPre-operative staging according to CT, EUS, PET-CT and final pre-operative stage were compared to the postoperative histological staging in 133 patients undergoing potentially curative surgery (without neoadjuvant therapy) for oesophageal cancer between January 2010 and January 2015. T and N stage accuracies were reported separately for each imaging modality. Patients were also divided into two groups depending on whether the final pre-operative stage was below (≤T2, N0, early tumours) or above (≥T3 and/or ≥N1, locally advanced tumours) the threshold for offering neoadjuvant therapy. Accuracy of pre-operative staging was then analysed with respect to identification of patients below/above this threshold. The additional benefit offered by EUS for this purpose was investigated.nnnRESULTSnT stage accuracies were 72.6%, 76.7% and 79.3% for CT, EUS and final pre-operative stage respectively. N stage accuracies were 75.6%, 77.2%, 74.5% and 78.6% for CT, EUS, PET-CT and final pre-operative stage respectively. Staging accuracy with respect to threshold for neoadjuvant treatment showed 62.0% early tumours were correctly staged and 80.5% advanced tumours were correctly staged. Whether or not patients underwent EUS did not affect the staging accuracy with respect to neoadjuvant treatment threshold.nnnCONCLUSIONSnStaging accuracy with respect to the threshold for treatment with neoadjuvant therapy is poor, leading to potential over/under treatment. Predicting individual response to neoadjuvant therapy would provide a better way to determine which patients should receive this additional treatment.

OC-078 Evaluating innovative surgery: a nested ideal phase 2 study within an external randomised pilot (the romio trial)

Introduction There is a need for well designed and conducted pragmatic randomised controlled trials (RCTs) of open and minimally invasive approaches for oesophageal cancer, but totally minimally invasive techniques are still evolving. The NIHR ROMIO pilot RCT was designed to inform a definitive trial. This paper describes how the ROMIO Study informed the main trial design and incorporated a nested IDEAL (Idea, Development, Evaluation, Assessment and Long-term evaluation of innovative surgery) Phase 2a evaluation of totally minimally invasive oesophagectomy (TMIO). Method The pilot ROMIO trial was conducted in two centres. In one centre (with a team of 3 surgeons) patients were randomised to open gastric mobilisation and right thoracotomy (open surgery) or laparoscopic gastric mobilisation and right thoractomy (hybrid surgery) and in the other centre (team of 6 surgeons) patients were randomised into three groups, also including totally TMIO. The surgical protocol for open and hybrid surgery was agreed and monitored during the trial, where as the protocol for TMIO was deliberately flexible to monitor development of the technique and to document changes in the procedure and collect prospective data. Results During 20 months of recruitment, 256 patients were assessed for eligibility, 132 (52%) were found to be eligible and 101 (76.5%) agreed to participate. A high proportion of patients received their randomised allocation (87%). Dressing patients with large bandages, covering all possible incisions, was successful in keeping patients blind whilst pain was assessed during the first week post-surgery (patients were unable to guess the type of surgery they had received). In the TMIO group three-phase surgery was undertaken by three of the six surgeons in one centre. This evolved to two-phase TMIO surgery with continuing modifications to the anastomotic technique. During the study period the national audit data showed that only 14% of oesophagectomies are TMIO. Conclusion Rapid recruitment to the pilot ROMIO trial and the successful refinement of methodology indicated that a definitive two group trial comparing open and hybrid surgery is feasible. Techniques for TMIO are however still evolving and the procedure is not widely undertaken. The main ROMIO trial, therefore, is designed within a continuing IDEAL Phase 2b study to monitor when this complex technique has stabilised and ready for full evaluation within a pragmatic trial design. Disclosure of interest None Declared.