EnROL: A multicentre randomised trial of conventional versus laparoscopic surgery for colorectal cancer within an enhanced recovery programme
© Kennedy et al.; licensee BioMed Central Ltd. 2012
Received: 2 May 2012
Accepted: 3 May 2012
Published: 16 May 2012
During the last two decades the use of laparoscopic resection and a multimodal approach known as an enhanced recovery programme, have been major changes in colorectal perioperative care. Clinical outcome improves using laparoscopic surgery to resect colorectal cancer but until recently no multicentre trial evidence had been reported regarding whether the benefits of laparoscopy still exist when open surgery is optimized within an enhanced recovery programme. The EnROL trial (Enhanced Recovery Open versus Laparoscopic) examines the hypothesis that laparoscopic surgery within an enhanced recovery programme will provide superior postoperative outcomes when compared to conventional open resection of colorectal cancer within the same programme.
EnROL is a phase III, multicentre, randomised trial of laparoscopic versus open resection of colon and rectal cancer with blinding of patients and outcome observers to the treatment allocation for the first 7 days post-operatively, or until discharge if earlier. 202 patients will be recruited at approximately 12 UK hospitals and randomised using minimization at a central computer system in a 1:1 ratio. Recruiting surgeons will previously have performed >100 laparoscopic colorectal resections and >50 open total mesorectal excisions to minimize conversion. Eligible patients are those suitable for elective resection using either technique. Excluded patients include: those with acute intestinal obstruction and patients in whom conversion from laparoscopic to open procedure is likely. The primary outcome is physical fatigue as measured by the physical fatigue domain of the multidimensional fatigue inventory 20 (MFI-20) with secondary outcomes including postoperative hospital stay; complications; reoperation and readmission; quality of life indicators; cosmetic assessments; standardized performance indicators; health economic analysis; the other four domains of the MFI-20. Pathological assessment of surgical quality will also be undertaken and compliance with the enhanced recovery programme will be recorded for all patients.
Should this trial demonstrate that laparoscopic surgery confers a significant clinical and/or health economic benefit this will further support the transition to this type of surgery, with implications for the training of surgeons and resource allocation.
KeywordsLaparoscopy Colon cancer Rectal cancer Enhanced recovery programme Fast track surgery Health economics Cosmetic assessment Fatigue Randomised controlled trial EnROL
During the last 20 years laparoscopic colorectal cancer resection has developed, improving short term clinical outcomes [1–3] while providing equivalent oncological results [4–8]. Some authors [9–11] have reported 3–4 day median postoperative hospital stays after laparoscopic surgery, whereas previously it would have been >10 days [12, 13] . Systematic reviews [1, 2] document improvements in short term outcomes after laparoscopy, particularly reduction in complications, postoperative pain and hospital stay. However despite these reports the proportion of elective colorectal resections performed laparoscopically in England during 2011 was still only estimated to be 33% (personal communication, MG Coleman)
The last 12 years have also seen the appearance of Enhanced Recovery care or Fast Track Surgery. This applies a multimodal approach to improving care using evidence based interventions and has even resulted in mean and median postoperative hospital stays of 3 days [9, 14, 15]. Enhanced Recovery care involves preconditioning of patient expectation, modification of surgical technique with smaller incisions, improved anaesthetic and fluid replacement practices, better postoperative pain control, omission of opiates where possible, avoidance of drains and nasogastric tubes, early removal of urinary catheters, mobilization and feeding immediately after surgery, early discharge, and expedited review when necessary. As a result of these developments trials on enhanced recovery care report reductions in postoperative complications and hospital stay [16–18]. There has understandably been great interest in the introduction of enhanced recovery care but it is unclear what proportion of hospitals have introduced it. We estimate that it will not have been introduced effectively in more than 50% of UK hospitals to date.
Given the significant shortening of hospital stay and decrease in complications resulting from the use of an Enhanced Recovery Programme (ERP), can laparoscopic surgery further improve recovery? Two small single centre studies from Denmark and England [10, 19] provided conflicting results. The Danish study reported 3 day median postoperative hospital stays in both arms, whereas the English trial showed a significant reduction in median hospital stay and readmission rate for the laparoscopic group. It is, therefore, unclear whether optimal results following elective colorectal resection are achieved by laparoscopy or by using open surgery which has been optimized within an Enhanced Recovery Programme. To answer this question the EnROL trial has been designed to examine outcomes in a multicentre setting. This study examines the hypothesis that laparoscopic surgery within an ERP will provide superior postoperative outcomes when compared to conventional open resection of colorectal cancer within the same programme.
The primary endpoint is patient reported physical fatigue measured by the physical fatigue domain of the multidimensional fatigue inventory 20 (MFI-20)  at 4 weeks after surgery. The secondary endpoints include postoperative hospital stay; 30 day and in-hospital complications; 30 day re-admission and re-operation rates; the other four domains of the MFI-20; a generic and cosmetic health related quality of life assessments [21–23]; observer measures of performance [10, 24] and measures of resource use.
The study population is patients of age 18 and above who require elective resection of colonic or rectal cancer and are suitable for laparoscopic surgery. Exclusions to trial entry are acute intestinal obstruction, previous complex laparotomies, emergency admission and pregnancy. Patients are also ineligible when, in the opinion of the treating surgeon, conversion to open surgery is likely (such as in rectal cancer when preoperative imaging suggests tumour is present at the resection margin – ‘threatened margin’). Preoperative identification of the inability to insert an epidural catheter is also an exclusion criterion, as it would prevent patients who require it receiving postoperative epidural analgesia.
The EnROL trial has been approved by the National Research Ethics Service Committee South Central - Oxford B (REC reference: 07/H0605/150). The trial is co-ordinated by the Oncology Clinical Trials Office (OCTO) at the University of Oxford, with statistical support from the Centre for Statistics in Medicine, which together form Oxford Clinical Trials Research Unit (OCTRU). OCTRU is a UKCRN Registered Clinical Trials Unit. The trial is sponsored by the University of Oxford and North West London Hospitals NHS Trust. The Data Safety and Monitoring Committee and Trial Steering Committee, which includes a patient representative, will meet regularly in order to oversee the trial appropriately. Funding has come principally from the Bobby Moore Fund, Cancer Research UK (CR-UK) (Ref number: CRUK/07/019). Ethicon Endo-surgery have provided additional funding to facilitate provision of wound dressings and collection of pathology material.
Following consent, eligible patients will be randomised in a 1:1 ratio to open or laparoscopic resection using a central computer system at the Oncology Clinical Trials Office. Simple randomisation will be used for the first 50 patients then minimization with a random element (0.8) . The stratification factors used in the minimization are hospital, cancer site (colon/rectum) and age (<66 years, 66–75 years, >75 years). To facilitate blinding of outcome observers the randomisation allocation will be sent directly to the patient’s surgeon via email and will not be made available to the site staff member completing the randomisation process.
Surgery is to be carried out by one of the centre’s trial-accredited surgeons no later than 6 weeks after randomisation.
Surgery should be performed in a standard fashion by the trial surgeon(s) at each site, the only difference being the method of access. Rectal tumours within 10 cm of the anal verge should be treated by total mesorectal excision accompanied, whenever possible, by preservation of the hypogastric nerves. Tumours are defined as being rectal when at or within 15 cm of the anal verge on rigid sigmoidoscopy, performed with the patient awake on their left side. Conversion is defined as the inability to complete the dissection fully laparoscopically, including the vascular division, and it usually but not always, requires the use of a larger incision than that needed to remove the specimen.
Patients and outcome observers are to be blinded to the randomisation allocation until 7 days after surgery or the day of discharge if earlier. To facilitate this large Allevyn™ adhesive dressings will be provided for all trial patients. In addition, centres should ensure that all patient records which detail the randomisation allocation are stored in a sealed envelope within the patient’s notes until after the patient is unblinded.
Blinding is an important design feature of randomised controlled trials, reducing the risk of several forms of bias including reporting bias and observer bias. A successfully implemented blinding protocol improves the validity of trial results, however the success of blinding is infrequently tested or reported in randomised controlled trials. To investigate the role and success of blinding in surgical randomised controlled trials, and its impact on patient experience, the trial protocol was amended to include collection of quantitative data about the success of blinding using the Bang Blinding Index . This statistical measure calculates the proportion of un-blinded patients (and research staff) in the trial by asking them to state to which arm of the study they believe they (their patient) have been allocated.
Enhanced recovery care
Standardised Enhanced Recovery Programme for the EnROL Trial
Conditioning of expectations of patient and carer by receipt of oral and written information at a dedicated preadmission visit, or by telephone counselling, with provision of a dedicated booklet or video sent by post.
Meeting with stoma nurse if stoma anticipated.
Identification of factors that might delay discharge and consideration of solutions e.g. provision of support when discharged if living alone.
Co-morbid risk assessment: optimised pre-morbid health status.
Day before surgery
Avoidance of oral bowel preparation except in patients undergoing total mesorectal excision (TME) and reconstruction.
Nutrition: three high protein/high calorie drinks if receiving oral bowel preparation.
Day of surgery
Preoperative oral carbohydrate loading to be given 2-4 hours prior to anaesthesia, using 200ml of fluid containing 12.5g/100ml CHO with a proven safety profile.
Avoidance of long acting sedative medication from midnight prior to surgery.
Activation of thoracic epidural (T6-11) prior to skin incision.
Avoidance of abdominal drains at primary operation.
Avoidance of nasogastric drainage in the immediate postoperative period.
Total volume of IV fluid < 3000ml.
The use of upper body forced air heating intraoperatively.
Local anaesthetic infiltration to the largest wound in minimal access surgery.
Open surgery: small transverse or curved incisions when possible.
Oral intake of ≥ 800ml fluid (including oral nutritional supplements) postoperatively on the day of surgery, before midnight.
≥ 200ml oral nutritional supplement postoperatively on the day of surgery, before midnight.
Mobilisation by walking or sitting in a chair.
First Postoperative day from midnight – midnight (Day 1)
≥ 2 units of oral nutritional supplement taken.
Termination of IV fluid infusion.
Intake and tolerance of solid food.
Intake of lactulose or a magnesium preparation to enhance bowel movements.
Use of thoracic epidural analgesia.
Mobilisation (out of bed) for at least 6 hours.
Provided patient mobile, termination of urinary drainage on day 1, except after TME when it may be preferable to leave it until day 3
Assisted mobilisation – 4 × 60m walks.
Second Postoperative day from midnight – midnight (Day 2)
Pain relief: termination of the thoracic epidural analgesia.
Use of a multi-modal analgesic regime at, or before, discontinuation of thoracic epidural analgesia e.g. paracetamol and non steroidal anti-inflammatory or equivalent.
Termination of urinary drainage on day 2 or earlier, except after TME when it may be preferable to leave it until day 3.
Aim for discharge day 2-3 for colonic and proximal rectal resection; day 5 when a stoma fashioned.
Discharge Criteria: patients must be tolerating normal food, mobilising independently and be managed on oral analgesics to fulfil discharge criteria.
Follow up: provision of hospital contact numbers to allow discussion of problems; expedited review on ward if problems within 2 weeks of surgery.
Review in out patient clinic at two weeks post operation.
Measurement of outcomes
The primary endpoint is physical fatigue 4 weeks after surgery as measured using the physical fatigue domain of the multidimensional fatigue inventory 20 (MFI-20). The MFI-20 is a 20-item self-report instrument designed to measure fatigue. It covers the following dimensions: general fatigue, physical fatigue, reduced activity, reduced motivation and mental fatigue.
Postoperative hospital stay
Postoperative hospital stay will be reported, counting the day of operation as day zero.
Complications, re-admission, re-operation and mortality rates
Standard definitions of complications for assessing morbidity of trial patients
Respiratory failure - requiring mechanical ventilation
Cardiac failure: cardiac index < 2 litres per m2 (treated first by fluid resuscitation and if no response by inotropic or vasoconstrictive medication)
Pulmonary oedema - radiological diagnosis
Arrhythmia - ECG changes requiring medical treatment and/or electroconversion
Pleural fluid - radiographic diagnosis
Acute myocardial infarction - electrocardiographic diagnosis
Acute renal failure - requiring haemofiltration
Stroke with neurological symptoms
Deep vein thrombosis - requiring duplex, radiological or other confirmation
Unexpected blood loss >0.5 litres during operation
Wound dehiscence involving separation of deep abdominal wall closure
Postoperative bleeding - overt blood loss requiring > 2 litre transfusion with a normal clotting profile.
Delayed oral intake - intravenous fluids > 1 week owing to postoperative ileus
Bowel obstruction requiring reoperation
Anastomotic leakage defined within 30 days of surgery radiologically (demonstration on abdominal CT with oral contrast, MRI or by contrast enema), surgically (visual evidence of faecal leakage at reoperation) or at autopsy (presence of a disrupted anastomosis).
Necrosis of stoma - requiring surgery
Aspiration Pneumonia - radiological diagnosis with appropriate history
Sepsis - pyrexia > 38 oC, septic focus or positive blood culture
Postoperative peritonitis - clinical diagnosis
Abdominal abscess - ultrasonograpy, computed tomography or operative diagnosis
Wound infection - defined as any one of the following: (modified from reference 26)
1. Purulent discharge or the aspiration of pus
2. Erythema or localised swelling requiring antibiotics or surgical drainage, unless the drainage is clear and negative on culture i.e. a seroma
3. A diagnosis of a wound infection made by a doctor.
4. Report of wound discharge by the patient unless it is proven to be uninfected
Chest infection - radiological diagnosis or empyema
Urinary tract infection
Disseminated intravascular coagulation
Other infective complication
Patient reported and functional outcomes
Time points for the collection of patient reported and functional outcome data
Data Collection Time Point
An observer assessment of physical function will be measured using standardized, objective performance indicators (SPIs)  which comprise a test of lower limb strength, balance and endurance. SPIs will be measured prior to surgery and then at 4 weeks, 3 and 6 months postoperatively. The tests differs from those described by Guralnik et al., in that patients will be measured for walking speed along a 10 metre, instead of 8 foot course, with a 61.5 cm (2 foot) clear zone at each end as originally described.
Health economics outcomes
Health Economics questionnaires and EQ-5D will be completed by all patients providing information about the use of healthcare post-operatively for 6 months. Data collected will include GP surgery visits, GP home visits, in- patient stays, out-patients visits, District Nurse visits, physiotherapy and stoma nurse usage. Data will also be collected from the trial records to calculate the relative cost of the operative and peri- operative periods. Costs to be calculated include in-patient hotel costs, in-patient treatments costs (including re-admission and re-operation within 30 days and convalescent care), operating theatre costs and drug costs .
Other domains of the MFI
The other four domains general fatigue, reduced activity, reduced motivation and mental fatigue will be analysed.
Follow up & data collection
Patients will be seen at 2 and 4 weeks and then at 3 and 6 months post operatively. Follow up data will also be collected at 12 months after surgery. Research staff at the centres will collect the data and submit it to the Trial Office via the EnROL electronic data capture website.
Resection specimens will be photographed to judge the quality of surgery of the mesorectum , anal sphincters, [31, 32] and the mesocolon . Dissection will be carried out according to the trial protocol using cross sectional slicing, careful inspection for distance of extramural spread, lymph nodes, extramural vascular invasion and peritoneal involvement. TNM version 5 and modified Dukes grading including C2 and stage D will be used and regression grading and data collected by protocol. The distance to the high tie from the tumour will be recorded. Quality will be assessed locally and centrally with the addition of measurements of the specimens’ physical characteristics performed centrally. The quality of laparoscopic and open surgery will be compared to previous studies to facilitate assessment of the results of the trial.
Sample size: The original sample size calculation required 266 patients (133 per treatment arm) to allow 90% power to detect a difference in the primary outcome of fatigue (as measured by physical fatigue domain of the MFI-20) of 0.45 standard deviations at p = 0.05 (two-sided). This includes a loss to follow up of 15% and a conversion rate of 8% from laparoscopic to open surgery. Following slower than expected recruitment the power was lowered to 80% in order to complete the study in a timely manner. With all other variables remaining the same the subsequent sample size of 202 (101 per treatment arm) is required. Additionally the study is powered to detect a 3 day difference in hospital stay at 80% power and p = 0.05 (two-sided).
All analyses will be on an intention-to-treat basis.
The primary outcome will be physical fatigue as measured by the physical fatigue domain of the MFI-20 at four weeks post operatively. If the primary outcome is normally distributed it will be compared using a t-test, ANCOVA adjusting for the minimization factors (primary analysis) and ANCOVA with further adjustment for prognostic factors.
Physical fatigue will also be compared at three and six months, the remaining quality of life variables at 4 weeks, 3 and 6 months, and the cosmetic outcome at 6 and 12 months, using the same analyses as for the primary outcome. Physical fatigue will be adjusted for the level of physical fatigue prior to surgery. The other measures of fatigue will also be reported.
For all continuous outcome variables, if there is severe departure from Normality the first approach will be transformation. If the data cannot be transformed to Normality, a Mann–Whitney test will be used. In the latter case no adjustment will be made for the minimization or prognostic factors.
Hospital stay will be compared using Kaplan Meier plots and log rank tests. The complications, re-operation and re-admission data will be binary and will hence be compared between the randomisation groups using a chi square test (or Fisher exact test if the data is sparse).
Quality of Life assessments at 4 weeks as measured by the SF-36 will be analysed as suggested in the SF-36 manual, comparison between treatments will use t-test and ANCOVA to adjust for prognostic factors. Mixed-effects models of repeated measures will be used to evaluate longitudinal comparisons (4 weeks, 3 months and 6 months).
The other four domains of the MFI will be analysed in the same way as the physical fatigue domain specified in the primary analysis.
The comparison between treatment groups of standardised performance indicators will use t-tests and ANCOVA adjusting for prognostic factors and baseline.
The tumour stage, quality of surgery grade, the physical measurements and the frequency of Dukes’ C2 cases will be compared between groups.
Analysis of the health economic data will be undertaken separately by those involved in the health economic analysis. Costs will be estimated from the perspective of the UK NHS and health benefits expressed in terms of quality-adjusted life-years (QALYs). The cases where laparoscopic surgery may be considered cost effective will be pre-defined and the mean differential costs and QALYs will be calculated in order to assess whether any of these conditions are satisfied. The relative costs of the operative and peri-operative period will be derived for all trial patients including the cost of consumables that are likely to differ between the two surgical procedures.
QALYs will be calculated for each patient in the trial, on the basis of their responses to the EQ-5D pre-operatively, at one month, three months and six months. Given that the time horizon of the analysis will be less than one year, total costs and QALYs remain undiscounted. To account for the skewed nature of the data, 95% CIs for the differential costs and QALYs will be estimated using bootstrapping methods. Missing data will be imputed using a multivariate multiple imputation procedure (Solas 3.0).
Statistical analysis will be undertaken using Stata (StataCorp LP).
The EnROL trial has been set up to examine the hypothesis that laparoscopic surgery improves outcome when compared to open surgery for colorectal cancer resection, even when both methods are optimized within an ERP. Prior to 2011 there had only been two small studies examining this issue [10, 19] and they reported conflicting results. Other trials reporting an improvement in clinical outcome following laparoscopic surgery did not use an enhanced recovery programme to optimize the open group [1, 2, 4].
In 2011 the LAFA trial  published outcomes comparing the two approaches to surgery +/− an ERP. In this study of patients having segmental colectomy, total hospital stay was reduced following laparoscopic surgery when compared to open surgery. There are significant differences between the EnROL and LAFA trials that warrant continuation of EnROL. The EnROL trial only involves very experienced laparoscopic surgeons; it will include patients with rectal carcinoma; it will not include patients with benign diagnoses; and there will be no attempt to randomise between ER care and non ER care, as happened in the LAFA trial.
The involvement in this trial of surgeons experienced in laparoscopy is important as it minimises the % conversion rate to open surgery, thus providing a more homogeneous laparoscopic group of patients (given the intention to treat analysis) and increasing the potential to demonstrate differences in outcome. The choice of 100 prior laparoscopic resections to enable surgeons to contribute to EnROL is both intuitive and based on data from studies examining the acquisition of surgical competence with this approach . Rectal carcinoma has been included in the EnROL trial as rectal resection is often more difficult than colonic surgery and also more demanding laparoscopically. As a result only one large randomised trial has been reported to date examining outcomes following resection of both high and low rectal cancers . Generally hospital stay following rectal surgery is longer than after colonic surgery and therefore the potential to improve outcome after rectal surgery is greater, assuming laparoscopy decreases complications.
Patients with benign diagnoses have not been included in this study as in general they are younger and therefore fitter. By restricting the study to the treatment of cancer, and therefore an older age group who are generally less fit, it is likely surgery will have a greater impact on the patients - manifesting itself as a higher incidence of postoperative complications. The use of laparoscopic surgery has been shown to decrease postoperative complications [1, 2] and the choice of only malignancy in the treatment group should highlight the potential benefits of this approach.
The primary endpoint of physical fatigue as measured by the Multidimensional Fatigue Inventory 20 (MFI-20) was chosen in order to provide a more global assessment of recovery than the normally used measure of postoperative hospital stay. In the past multicentre randomised trials looking at laparoscopic surgery have rarely found a difference in outcome when using a quality of life indicator. One exception was a trial of laparoscopic versus open donor nephrectomy that demonstrated a benefit to laparoscopy using both the MFI-20 and the SF-36 questionnaires . The EnROL trial differs to many in that the surgeons are more experienced laparoscopic practitioners and thus we expect to see a lower conversion rate to open surgery and a more homogeneous ‘laparoscopic’ group of patients. The potential to detect a significant difference in outcomes will therefore be more likely than in some previous studies.
Currently laparoscopic colorectal resection costs more than open surgery because of the disposable equipment that is required. Many surgeons who practise conventional open colorectal surgery do not have the skills that would allow them to take on the minimal access technique and they will need extensive retraining in laparoscopy if they are to provide this new approach, which again has cost implications. In addition the procedure can take longer to perform than equivalent open operations, at least in the early stages of a surgeon’s laparoscopic experience. For all these reasons and also the potential for laparoscopic surgery to improve clinical outcomes when compared to open surgery, it is important that the EnROL trial examines this question within a multicentre setting.
Enhanced Recovery Open versus Laparoscopic
Magnetic Resonance Imaging
LAparoscopy and/or FAst track multimodal management versus standard care trial
Enhanced Recovery Programme
Cancer Research United Kingdom
Clinical Trials Awards and Advisory Committee
Multidimensional Fatigue Inventory 20
Oncology Clinical Trials Office
Short Form 36
Euroqol 5 Dimensions
Standardised Performance Indicators
Oxford Clinical Trials Research Unit.
We gratefully acknowledge The Bobby Moore Fund, CR-UK, as principle funder. Additional funding from Ethicon Endo-surgery facilitated supply of dressings and collection of pathology material. We would like to thank former OCTO staff who were involved with set up of the study; the NCRI Colorectal CSG surgical subgroup for their support and Sue Bulley for the advice on practical aspects of the protocol and trial management. PQ is supported by a Yorkshire Cancer Research programme grant. The EnROL Trial is a UKCRN portfolio study (UKCRN ID: 3830).
The Bobby Moore Fund, Cancer Research UK (study number: CRUK/07/019), with additional funding from Ethicon Endo-surgery (Europe) GmbH.
- Abraham NS, Young JM, Solomon MJ: Meta-analysis of short-term outcomes after laparoscopic resection for colorectal cancer. Br J Surg. 2004, 91 (9): 1111-1124. 10.1002/bjs.4640.View ArticlePubMedGoogle Scholar
- Veldkamp R, Gholghesaei M, Bonjer HJ, Meijer DW, Buunen M, Jeekel J, Anderberg B, Cuesta MA, Cuschierl A, Fingerhut A, et al: Laparoscopic resection of colon Cancer: consensus of the European Association of Endoscopic Surgery (EAES). Surg Endosc. 2004, 18 (8): 1163-1185. 10.1007/s00464-003-8253-3.View ArticlePubMedGoogle Scholar
- Leung KL, Kwok SP, Lam SC, Lee JF, Yiu RY, Ng SS, Lai PB, Lau WY: Laparoscopic resection of rectosigmoid carcinoma: prospective randomised trial. Lancet. 2004, 363 (9416): 1187-1192. 10.1016/S0140-6736(04)15947-3.View ArticlePubMedGoogle Scholar
- Lacy AM, Garcia-Valdecasas JC, Delgado S, Castells A, Taura P, Pique JM, Visa J: Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial. Lancet. 2002, 359 (9325): 2224-2229. 10.1016/S0140-6736(02)09290-5.View ArticlePubMedGoogle Scholar
- Weeks JC, Nelson H, Gelber S, Sargent D, Schroeder G: Short-term quality-of-life outcomes following laparoscopic-assisted colectomy vs open colectomy for colon cancer: a randomized trial. Jama. 2002, 287 (3): 321-328. 10.1001/jama.287.3.321.View ArticlePubMedGoogle Scholar
- Guillou PJ, Quirke P, Thorpe H, Walker J, Jayne DG, Smith AM, Heath RM, Brown JM: Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial. Lancet. 2005, 365 (9472): 1718-1726. 10.1016/S0140-6736(05)66545-2.View ArticlePubMedGoogle Scholar
- Veldkamp R, Kuhry E, Hop WC, Jeekel J, Kazemier G, Bonjer HJ, Haglind E, Pahlman L, Cuesta MA, Msika S, et al: Laparoscopic surgery versus open surgery for colon cancer: short-term outcomes of a randomised trial. Lancet Oncol. 2005, 6 (7): 477-484.View ArticlePubMedGoogle Scholar
- The Clinical Outcomes of Surgical Therapy Study Group: A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med. 2004, 350 (20): 2050-2059.View ArticleGoogle Scholar
- Bardram L, Funch-Jensen P, Kehlet H: Rapid rehabilitation in elderly patients after laparoscopic colonic resection. Br J Surg. 2000, 87 (11): 1540-1545. 10.1046/j.1365-2168.2000.01559.x.View ArticlePubMedGoogle Scholar
- King PM, Blazeby JM, Ewings P, Franks PJ, Longman RJ, Kendrick AH, Kipling RM, Kennedy RH: Randomized clinical trial comparing laparoscopic and open surgery for colorectal cancer within an enhanced recovery programme. Br J Surg. 2006, 93 (3): 300-308. 10.1002/bjs.5216.View ArticlePubMedGoogle Scholar
- Delaney CP, Kiran RP, Senagore AJ, Brady K, Fazio VW: Case-matched comparison of clinical and financial outcome after laparoscopic or open colorectal surgery. Ann Surg. 2003, 238 (1): 67-72.PubMedPubMed CentralGoogle Scholar
- Kehlet H, Buchler MW, Beart RW, Billingham RP, Williamson R: Care after colonic operation - Is it evidence-based? Results from a multinational survey in Europe and the United States. J Am Coll Surgeons. 2006, 202 (1): 45-54. 10.1016/j.jamcollsurg.2005.08.006.View ArticleGoogle Scholar
- Faiz O, Warusavitarne J, Bottle A, Tekkis PP, Darzi AW, Kennedy RH: Laparoscopically Assisted vs. Open Elective Colonic and Rectal Resection: A Comparison of Outcomes in English National Health Service Trusts Between 1996 and 2006. Dis Colon Rectum. 2009, 52 (10): 1695-1704. 10.1007/DCR.0b013e3181b55254.View ArticlePubMedGoogle Scholar
- Basse L, Hjort Jakobsen D, Billesbolle P, Werner M, Kehlet H: A clinical pathway to accelerate recovery after colonic resection. Ann Surg. 2000, 232 (1): 51-57. 10.1097/00000658-200007000-00008.View ArticlePubMedPubMed CentralGoogle Scholar
- Fearon KC, Ljungqvist O, Von Meyenfeldt M, Revhaug A, Dejong CH, Lassen K, Nygren J, Hausel J, Soop M, Andersen J, et al: Enhanced recovery after surgery: a consensus review of clinical care for patients undergoing colonic resection. Clin Nutr. 2005, 24 (3): 466-477. 10.1016/j.clnu.2005.02.002.View ArticlePubMedGoogle Scholar
- Anderson AD, McNaught CE, MacFie J, Tring I, Barker P, Mitchell CJ: Randomized clinical trial of multimodal optimization and standard perioperative surgical care. Br J Surg. 2003, 90 (12): 1497-1504. 10.1002/bjs.4371.View ArticlePubMedGoogle Scholar
- Delaney CP, Zutshi M, Senagore AJ, Remzi FH, Hammel J, Fazio VW: Prospective, randomized, controlled trial between a pathway of controlled rehabilitation with early ambulation and diet and traditional postoperative care after laparotomy and intestinal resection. Dis Colon Rectum. 2003, 46 (7): 851-859. 10.1007/s10350-004-6672-4.View ArticlePubMedGoogle Scholar
- Varadhan KK, Neal KR, Dejong CH, Fearon KC, Ljungqvist O, Lobo DN: The enhanced recovery after surgery (ERAS) pathway for patients undergoing major elective open colorectal surgery: a meta-analysis of randomized controlled trials. Clin Nutr. 2010, 29 (4): 434-440. 10.1016/j.clnu.2010.01.004.View ArticlePubMedGoogle Scholar
- Basse L, Jakobsen DH, Bardram L, Billesbolle P, Lund C, Mogensen T, Rosenberg J, Kehlet H: Functional recovery after open versus laparoscopic colonic resection: a randomized, blinded study. Ann Surg. 2005, 241 (3): 416-423. 10.1097/01.sla.0000154149.85506.36.View ArticlePubMedPubMed CentralGoogle Scholar
- Smets EM, Garssen B, Cull A, de Haes JC: Application of the multidimensional fatigue inventory (MFI-20) in cancer patients receiving radiotherapy. Br J Cancer. 1996, 73 (2): 241-245. 10.1038/bjc.1996.42.View ArticlePubMedPubMed CentralGoogle Scholar
- Ware JE, Snow KK, Kosinski M, Gandek B: SF-36 Health Survey: Manual and Interpretation Guide. 1993, The Health Institute, New England Medical Centre, BostonGoogle Scholar
- The EuroQol Group: EuroQol--a new facility for the measurement of health-related quality of life. The EuroQol Group. Health Policy. 1990, 16 (3): 199-208.View ArticleGoogle Scholar
- Whistance RN, Gilbert R, Fayers P, Longman RJ, Pullyblank A, Thomas M, Blazeby JM: Assessment of body image in patients undergoing surgery for colorectal cancer. Int J Colorectal Dis. 2010, 25 (3): 369-374. 10.1007/s00384-009-0851-7.View ArticlePubMedGoogle Scholar
- Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, Scherr PA, Wallace RB: A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994, 49 (2): M85-94.View ArticlePubMedGoogle Scholar
- Brown S, Thorpe H, Hawkins K, Brown J: Minimization–reducing predictability for multi-centre trials whilst retaining balance within centre. Stat Med. 2005, 24 (24): 3715-3727. 10.1002/sim.2391.View ArticlePubMedGoogle Scholar
- Bang H, Ni L, Davis CE: Assessment of blinding in clinical trials. Control Clin Trials. 2004, 25 (2): 143-156. 10.1016/j.cct.2003.10.016.View ArticlePubMedGoogle Scholar
- Lang M, Niskanen M, Miettinen P, Alhava E, Takala J: Outcome and resource utilization in gastroenterological surgery. Br J Surg. 2001, 88 (7): 1006-1014. 10.1046/j.0007-1323.2001.01812.x.View ArticlePubMedGoogle Scholar
- Hopwood P, Fletcher I, Lee A, Al Ghazal S: A body image scale for use with cancer patients. Eur J Cancer. 2001, 37 (2): 189-197. 10.1016/S0959-8049(00)00353-1.View ArticlePubMedGoogle Scholar
- Franks PJ, Bosanquet N, Thorpe H, Brown JM, Copeland J, Smith AM, Quirke P, Guillou PJ: Short-term costs of conventional vs laparoscopic assisted surgery in patients with colorectal cancer (MRC CLASICC trial). Br J Cancer. 2006, 95 (1): 6-12. 10.1038/sj.bjc.6603203.View ArticlePubMedPubMed CentralGoogle Scholar
- Quirke P, Steele R, Monson J, Grieve R, Khanna S, Couture J, O'Callaghan C, Myint AS, Bessell E, Thompson LC, et al: Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial. Lancet. 2009, 373 (9666): 821-828. 10.1016/S0140-6736(09)60485-2.View ArticlePubMedPubMed CentralGoogle Scholar
- Nagtegaal ID, van de Velde CJ, Marijnen CA, van Krieken JH, Quirke P: Low rectal cancer: a call for a change of approach in abdominoperineal resection. J Clin Oncol. 2005, 23 (36): 9257-9264. 10.1200/JCO.2005.02.9231.View ArticlePubMedGoogle Scholar
- West NP, Finan PJ, Anderin C, Lindholm J, Holm T, Quirke P: Evidence of the oncologic superiority of cylindrical abdominoperineal excision for low rectal cancer. J Clin Oncol. 2008, 26 (21): 3517-3522. 10.1200/JCO.2007.14.5961.View ArticlePubMedGoogle Scholar
- West NP, Morris EJ, Rotimi O, Cairns A, Finan PJ, Quirke P: Pathology grading of colon cancer surgical resection and its association with survival: a retrospective observational study. Lancet Oncol. 2008, 9 (9): 857-865. 10.1016/S1470-2045(08)70181-5.View ArticlePubMedGoogle Scholar
- West NP, Sutton KM, Ingeholm P, Hagemann-Madsen RH, Hohenberger W, Quirke P: Improving the quality of colon cancer surgery through a surgical education program. Dis Colon Rectum. 2010, 53 (12): 1594-1603. 10.1007/DCR.0b013e3181f433e3.View ArticlePubMedGoogle Scholar
- Vlug MS, Wind J, Hollmann MW, Ubbink DT, Cense HA, Engel AF, Gerhards MF, van Wagensveld BA, van der Zaag ES, van Geloven AA, et al: Laparoscopy in combination with fast track multimodal management is the best perioperative strategy in patients undergoing colonic surgery: a randomized clinical trial (LAFA-study). Ann Surg. 2011, 254 (6): 868-875. 10.1097/SLA.0b013e31821fd1ce.View ArticlePubMedGoogle Scholar
- Tekkis PP, Fazio VW, Lavery IC, Remzi FH, Senagore AJ, Wu JS, Strong SA, Poloneicki JD, Hull TL, Church JM: Evaluation of the learning curve in ileal pouch-anal anastomosis surgery. Ann Surg. 2005, 241 (2): 262-268. 10.1097/01.sla.0000152018.99541.f1.View ArticlePubMedPubMed CentralGoogle Scholar
- Kok NF, Lind MY, Hansson BM, Pilzecker D, Borg IR Mertens zur, Knipscheer BC, Hazebroek EJ, Dooper IM, Weimar W, Hop WC, et al: Comparison of laparoscopic and mini incision open donor nephrectomy: single blind, randomised controlled clinical trial. Bmj. 2006, 333 (7561): 221-10.1136/bmj.38886.618947.7C.View ArticlePubMedPubMed CentralGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/12/181/prepub
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.