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Summary Background Radical surgery via total mesorectal excision might not be the optimal first-line treatment for early-stage rectal cancer. An organ-preserving strategy with selective total mesorectal excision could reduce the adverse effects of treatment without substantially compromising oncological outcomes. We investigated the feasibility of recruiting patients to a randomised trial comparing an organ-preserving strategy with total mesorectal excision. Methods TREC was a randomised, open-label feasibility study done at 21 tertiary referral centres in the UK. Eligible participants were aged 18 years or older with rectal adenocarcinoma, staged T2 or lower, with a maximum diameter of 30 mm or less; patients with lymph node involvement or metastases were excluded. Patients were randomly allocated (1:1) by use of a computer-based randomisation service to undergo organ preservation with short-course radiotherapy followed by transanal endoscopic microsurgery after 8–10 weeks, or total mesorectal excision. Where the transanal endoscopic microsurgery specimen showed histopathological features associated with an increased risk of local recurrence, patients were considered for planned early conversion to total mesorectal excision. A non-randomised prospective registry captured patients for whom randomisation was considered inappropriate, because of a strong clinical indication for one treatment group. The primary endpoint was cumulative randomisation at 12, 18, and 24 months. Secondary outcomes evaluated safety, efficacy, and health-related quality of life assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and CR29 in the intention-to-treat population. This trial is registered with the ISRCTN Registry, ISRCTN14422743. Findings Between Feb 22, 2012, and Dec 19, 2014, 55 patients were randomly assigned at 15 sites; 27 to organ preservation and 28 to radical surgery. Cumulatively, 18 patients had been randomly assigned at 12 months, 31 at 18 months, and 39 at 24 months. No patients died within 30 days of initial treatment, but one patient randomly assigned to organ preservation died within 6 months following conversion to total mesorectal excision with anastomotic leakage. Eight (30%) of 27 patients randomly assigned to organ preservation were converted to total mesorectal excision. Serious adverse events were reported in four (15%) of 27 patients randomly assigned to organ preservation versus 11 (39%) of 28 randomly assigned to total mesorectal excision (p=0·04, χ2 test). Serious adverse events associated with organ preservation were most commonly due to rectal bleeding or pain following transanal endoscopic microsurgery (reported in three cases). Radical total mesorectal excision was associated with medical and surgical complications including anastomotic leakage (two patients), kidney injury (two patients), cardiac arrest (one patient), and pneumonia (two patients). Histopathological features that would be considered to be associated with increased risk of tumour recurrence if observed after transanal endoscopic microsurgery alone were present in 16 (59%) of 27 patients randomly assigned to organ preservation, versus 24 (86%) of 28 randomly assigned to total mesorectal excision (p=0·03, χ2 test). Eight (30%) of 27 patients assigned to organ preservation achieved a complete response to radiotherapy. Patients who were randomly assigned to organ preservation showed improvements in patient-reported bowel toxicities and quality of life and function scores in multiple items compared to those who were randomly assigned to total mesorectal excision, which were sustained over 36 months’ follow-up. The non-randomised registry comprised 61 patients who underwent organ preservation and seven who underwent radical surgery. Non-randomised patients who underwent organ preservation were older than randomised patients and more likely to have life-limiting comorbidities. Serious adverse events occurred in ten (16%) of 61 non-randomised patients who underwent organ preservation versus one (14%) of seven who underwent total mesorectal excision. 24 (39%) of 61 non-randomised patients who underwent organ preservation had high-risk histopathological features, while 25 (41%) of 61 achieved a complete response. Overall, organ preservation was achieved in 19 (70%) of 27 randomised patients and 56 (92%) of 61 non-randomised patients. Interpretation Short-course radiotherapy followed by transanal endoscopic microsurgery achieves high levels of organ preservation, with relatively low morbidity and indications of improved quality of life. These data support the use of organ preservation for patients considered unsuitable for primary total mesorectal excision due to the short-term risks associated with this surgery, and support further evaluation of short-course radiotherapy to achieve organ preservation in patients considered fit for total mesorectal excision. Larger randomised studies, such as the ongoing STAR-TREC study, are needed to more precisely determine oncological outcomes following different organ preservation treatment schedules. Funding Cancer Research UK.

Background and study aims: The resolution of endoscopes has increased in recent years. Modern Fujinon colonoscopes have a charge-coupled device (CCD) pixel density of 650000 pixels compared with the 410000 pixel CCD in standard-definition scopes. Acquiring high-definition scopes represents a significant capital investment and their clinical value remains uncertain. The aim of the current study was to investigate the impact of high-definition endoscopes on the in vivo histology prediction of colonic polyps. Patients and methods: Colonoscopy procedures were performed using Fujinon colonoscopes and EPX-4400 processor. Procedures were randomized to be performed using either a standard-definition EC-530 colonoscope or high-definition EC-530 and EC-590 colonoscopes. Polyps of Results: A total of 293 polyps of Conclusions: There was no difference between high- and standard-definition colonoscopes when white light was used, but FICE significantly improved the in vivo diagnosis of small polyps when high-definition scopes were used compared with standard definition.

To examine the efficacy and potential cost implications of acetic acid (AA) chromoendoscopy in the assessment of Barrett's neoplasia. Our prospective database of patients referred between 2005 and 2010 with suspected early neoplasia was reviewed. High-resolution Fujinon gastroscopes and EPX-4400 processor were used. Inspection of Barrett's neoplasia was carried out using white light followed by AA. Neoplastic areas were noted, and targeted biopsy was carried out. This was followed by quadrantic biopsies of the remaining Barrett's neoplasia. The cost of protocol-guided biopsies was compared with AA-guided biopsy protocols. Two hundred sixty-three procedures on 197 patients were examined. High-risk neoplasia was found during 143 procedures. In 96% of cases it was identified with AA. The cost of histological evaluation by Cleveland protocol would be £139,416.30. The cost by AA-targeted biopsy followed by random biopsies in one pot would be £25,032.50. For AA-targeted biopsies alone the cost would be £9,541.8 but results in a 4% miss rate. AA localizes neoplastic lesions in the majority of patients and could potentially represent a significant cost saving in patients with suspected neoplasia.

Aim The purpose of this survey was to ascertain reporting habits of pathologists towards sessile serrated adenomas/polyps (SSA/P). Methods A questionnaire designed to highlight diagnostic criteria, approach and clinical implications of SSA/P was circulated electronically to 45 pathologists in the UK and North America. Results Forty-three of 45 pathologists agreed to participate. The vast majority (88%) had a special interest in gastrointestinal (GI) pathology, had great exposure to GI polyps in general with 40% diagnosing SSA/P at least once a week if not more, abnormal architecture was thought by all participants to be histologically diagnostic, and 11% would make the diagnosis if a single diagnostic histological feature was present in one crypt only, while a further 19% would diagnose SSA/P in one crypt if more than one diagnostic feature was present. The vast majority agreed that deeper sections were useful and 88% did not feel proliferation markers were useful. More than one-third did not know whether, or did not feel that, their clinicians were aware of the implications of SSA/P. Conclusions 98% of pathologists surveyed are aware that SSA/P is a precursor lesion to colorectal cancer, the majority agree on diagnostic criteria, and a significant number feel that there needs to be greater communication and awareness among pathologists and gastroenterologists about SSA/P.

Background and study aims: Acetic acid reacts with Barrett’s mucosa to produce acetowhitening which disappears with time. The clinical significance of this is unknown. We aimed to quantify the acetowhitening time, developing an objective tool for diagnosis of neoplasia in Barrett’s esophagus. Patients and methods: Prospective cohort study in a tertiary referral center, enrolling patients undergoing surveillance of Barrett’s metaplasia or referred with suspected neoplasia. Acetic acid 2.5 % was applied to the mucosa via a spray catheter. Acetowhitening was observed and time to disappearance recorded. Targeted biopsies of any neoplasia and quadrantic 2-cm biopsies of residual Barrett’s area were then taken. Histological findings were investigated in relation to duration of acetowhitening. Results: 132 patients were examined. A receiver operating characteristic (ROC) curve was produced for identifying high risk neoplasia according to acetowhitening duration. The area under the curve (AUC) was 0.93 (0.89 – 0.97). Using a threshold of 142 seconds yielded a sensitivity for neoplasia of 98 % (95 % confidence interval [95 %CI] 89 % – 100 %) and specificity of 84 % (74 % – 91 %). The ROC curve for mucosal neoplasia (high grade dysplasia or intramucosal carcinoma) versus deep invasive cancer showed an AUC of 0.786 (0.61 – 0.96); a cutoff of 20 seconds yielded a sensitivity and specificity for invasive cancer of 67 % (35 % – 90 %) and 85 % (69 % – 95 %), respectively. Conclusion: The time to disappearance of acetowhitening can serve as a simple but very sensitive tool for the diagnosis of high risk neoplasia in Barrett’s esophagus. It can be used to distinguish mucosal neoplasia from deep invasive cancer.

Background: There is growing evidence that indigo carmine chromoendoscopy is effective for the in vivo diagnosis of colonic polyps. However, the impact of colonoscope resolution on diagnostic accuracy has not been investigated. Objective: We aimed to compare the effectiveness of in vivo diagnosis of small colonic polyps using indigo carmine dye spray with standard-definition and high-definition colonoscopes. Methods: Procedures were performed using Fujinon colonoscopes and EPX 4400 processor. Fujinon standard-definition (SD) and high-definition (HD) colonoscopes were used, with the endoscopist blinded to colonoscope definition. Polyps