Resection margin involvement after endoscopic excision of malignant colorectal polyps: definition of margin involvement and its impact upon tumour recurrence.

AIMS: Malignant polyps are examined to assess histological features which predict residual tumour in the unresected bowel and guide surgical decision-making. One of the most important of these features is resection margin involvement, although the best definition of margin involvement is unknown. In this study we aimed to investigate three different definitions and determine their impact on clinical outcomes. METHODS AND RESULTS: One hundred and sixty-five malignant polyps removed endoscopically were identified and histological features correlated with either residual tumour in subsequent surgical resections or tumour recurrence following a period of clinical follow-up. Involvement of the polyp margin by cancer was defined in three different ways and outcomes compared. Tumour recurrence was associated with tumour grade, mucinous histology and resection margin involvement. All three definitions of margin involvement separated polyps into clinically significant categories; however, a margin ≤ 1 mm identified 73% of polyps as 'high-risk' compared with 59.1% when involvement was defined as tumour within the zone of coagulation artefact at the polyp base or 50% when tumour was present at the margin. All three 'low-risk' groups had a locoregional recurrence rate < 6.5%. CONCLUSIONS: Definitions of margin involvement for endoscopically removed malignant polyps in the colon and rectum vary between health-care systems, but a 1-mm clearance is widely used in Europe and North America. Our results suggest that a 1-mm margin is unnecessary and should be replaced by a definition based on tumour at the margin or within coagulation artefact at the polyp base.

Multimodality endoscopic eradication for neoplastic Barrett oesophagus: results of an European multicentre study (EURO-II).

OBJECTIVE: Focal endoscopic resection (ER) followed by radiofrequency ablation (RFA) safely and effectively eradicates Barrett's oesophagus (BO) containing high-grade dysplasia (HGD) and/or early cancer (EC) in smaller studies with limited follow-up. Herein, we report long-term outcomes of combined ER and RFA for BO (HGD and/or EC) from a single-arm multicentre interventional study. DESIGN: In 13 European centres, patients with BO ≤ 12 cm with HGD and/or EC on 2 separate endoscopies were eligible for inclusion. Visible lesions (<2 cm length; <50% circumference) were removed with ER, followed by serial RFA every 3 months (max 5 sessions). Follow-up endoscopy was scheduled at 6 months after the first negative post-treatment endoscopic control and annually thereafter. OUTCOMES: complete eradication of neoplasia (CE-neo) and intestinal metaplasia (CE-IM); durability of CE-neo and CE-IM (once achieved) during follow-up. Biopsy and resection specimens underwent centralised pathology review. RESULTS: 132 patients with median BO length C3M6 were included. After entry-ER in 119 patients (90%) and a median of 3 RFA (IQR 3-4) treatments, CE-neo was achieved in 121/132 (92%) and CE-IM in 115/132 patients (87%), per intention-to-treat analysis. Per-protocol analysis, CE-neo and CE-IM were achieved in 98% and 93%, respectively. After a median of 27 months following the first negative post-treatment endoscopic control, neoplasia and IM recurred in 4% and 8%, respectively. Mild-to-moderate adverse events occurred in 25 patients (19%); all managed conservatively or endoscopically. CONCLUSIONS: In patients with early Barrett's neoplasia, intensive multimodality endotherapy consisting of ER combined with RFA is safe and highly effective, and the treatment effect appears to be durable during mid-term follow-up. TRIAL REGISTRATION NUMBER: NTR 1211, http://www.trialregister.nl.

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.

British Society of Gastroenterology/Association of Coloproctologists of Great Britain and Ireland guidelines for the management of large non-pedunculated colorectal polyps.

These guidelines provide an evidence-based framework for the management of patients with large non-pedunculated colorectal polyps (LNPCPs), in addition to identifying key performance indicators (KPIs) that permit the audit of quality outcomes. These are areas not previously covered by British Society of Gastroenterology (BSG) Guidelines.A National Institute of Health and Care Excellence (NICE) compliant BSG guideline development process was used throughout and the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to structure the guideline development process. A systematic review of literature was conducted for English language articles up to May 2014 concerning the assessment and management of LNPCPs. Quality of evaluated studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) Methodology Checklist System. Proposed recommendation statements were evaluated by each member of the Guideline Development Group (GDG) on a scale from 1 (strongly agree) to 5 (strongly disagree) with >80% agreement required for consensus to be reached. Where consensus was not reached a modified Delphi process was used to re-evaluate and modify proposed statements until consensus was reached or the statement discarded. A round table meeting was subsequently held to finalise recommendations and to evaluate the strength of evidence discussed. The GRADE tool was used to assess the strength of evidence and strength of recommendation for finalised statements.KPIs, a training framework and potential research questions for the management of LNPCPs were also developed. It is hoped that these guidelines will improve the assessment and management of LNPCPs.

Early rectal cancer: the European Association for Endoscopic Surgery (EAES) clinical consensus conference.

BACKGROUND: The last 30 years have witnessed a significant increase in the diagnosis of early-stage rectal cancer and the development of new strategies to reduce the treatment-related morbidity. Currently, there is no consensus on the definition of early rectal cancer (ERC), and the best management of ERC has not been yet defined. The European Association for Endoscopic Surgery in collaboration with the European Society of Coloproctology developed this consensus conference to provide recommendations on ERC diagnosis, staging and treatment based on the available evidence. METHODS: A multidisciplinary group of experts selected on their clinical and scientific expertise was invited to critically review the literature and to formulate evidence-based recommendations by the Delphi method. Recommendations were discussed at the plenary session of the 14th World Congress of Endoscopic Surgery, Paris, 26 June 2014, and then posted on the EAES website for open discussion. RESULTS: Tumour biopsy has a low accuracy. Digital rectal examination plays a key role in the pre-operative work-up. Magnification chromoendoscopy, endoscopic ultrasound and magnetic resonance imaging are complementary staging modalities. Endoscopic submucosal dissection and transanal endoscopic microsurgery are the two established approaches for local excision (LE) of selected ERC. The role of all organ-sparing approaches including neoadjuvant therapies followed by LE should be formally assessed by randomized controlled trials. Rectal resection and total mesorectal excision is indicated in the presence of unfavourable features at the pathological evaluation of the LE specimen. The laparoscopic approach has better short-term outcomes and similar oncologic results when compared with open surgery. CONCLUSIONS: The management of ERC should always be based on a multidisciplinary approach, aiming to increase the rate of organ-preserving procedures without jeopardizing survival.

Standardized endoscopic reporting.

The need for standardized language is increasingly obvious, also within gastrointestinal endoscopy. A systematic approach to the description of endoscopic findings is vital for the development of a universal language, but systematic also means structured, and structure is inherently a challenge when presented as an alternative to the normal spoken word. The efforts leading to the "Minimal Standard Terminology" (MST) of gastrointestinal endoscopy offer a standardized model for description of endoscopic findings. With a combination of lesion descriptors and descriptor attributes, this system gives guidance to appropriate descriptions of lesions and also has a normative effect on endoscopists in training. The endoscopic report includes a number of items not related to findings per se, but to other aspects of the procedure, formal, technical, and medical. While the MST sought to formulate minimal lists for some of these aspects (e.g. indications), they are not all well suited for the inherent structure of the MST, and many are missing. Thus, the present paper offers a recommended standardization also of the administrative, technical, and other "peri-endoscopic" elements of the endoscopic report; important also are the numerous quality assurance initiatives presently emerging. Finally, the image documentation of endoscopic findings is becoming more obvious-and accessible. Thus, recommendations for normal procedures as well as for focal and diffuse pathology are presented. The recommendations are "minimal," meaning that expansions and subcategories will likely be needed in most centers. Still, with a stronger common grounds, communication within endoscopy will still benefit.

Promoter methylation of Wnt-antagonists in polypoid and nonpolypoid colorectal adenomas.

BACKGROUND: Nonpolypoid adenomas are a subgroup of colorectal adenomas that have been associated with a more aggressive clinical behaviour compared to their polypoid counterparts. A substantial proportion of nonpolypoid and polypoid adenomas lack APC mutations, APC methylation or chromosomal loss of the APC locus on chromosome 5q, suggesting the involvement of other Wnt-pathway genes. The present study investigated promoter methylation of several Wnt-pathway antagonists in both nonpolypoid and polypoid adenomas. METHODS: Quantitative methylation-specific PCR (qMSP) was used to evaluate methylation of four Wnt-antagonists, SFRP2, WIF-1, DKK3 and SOX17 in 18 normal colorectal mucosa samples, 9 colorectal cancer cell lines, 18 carcinomas, 44 nonpolypoid and 44 polypoid adenomas. Results were integrated with previously obtained data on APC mutation, methylation and chromosome 5q status from the same samples. RESULTS: Increased methylation of all genes was found in the majority of cell lines, adenomas and carcinomas compared to normal controls. WIF-1 and DKK3 showed a significantly lower level of methylation in nonpolypoid compared to polypoid adenomas (p < 0.01). Combining both adenoma types, a positive trend between APC mutation and both WIF-1 and DKK3 methylation was observed (p < 0.05). CONCLUSIONS: Methylation of Wnt-pathway antagonists represents an additional mechanism of constitutive Wnt-pathway activation in colorectal adenomas. Current results further substantiate the existence of partially alternative Wnt-pathway disruption mechanisms in nonpolypoid compared to polypoid adenomas, in line with previous observations.

Post-polypectomy colonoscopy surveillance: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

MAIN RECOMMENDATIONS: The following recommendations for post-polypectomy endoscopic surveillance should be applied only after a high quality baseline colonoscopy with complete removal of all detected neoplastic lesions.1 In the low risk group (patients with 1 - 2 tubular adenomas < 10 mm with low grade dysplasia), the ESGE recommends participation in existing national screening programmes 10 years after the index colonoscopy. If no screening programme is available, repetition of colonoscopy 10 years after the index colonoscopy is recommended (strong recommendation, moderate quality evidence). 2 In the high risk group (patients with adenomas with villous histology or high grade dysplasia or ≥10 mm in size, or ≥ 3 adenomas), the ESGE recommends surveillance colonoscopy 3 years after the index colonoscopy (strong recommendation, moderate quality evidence). Patients with 10 or more adenomas should be referred for genetic counselling (strong recommendation, moderate quality evidence). 3 In the high risk group, if no high risk adenomas are detected at the first surveillance examination, the ESGE suggests a 5-year interval before a second surveillance colonoscopy (weak recommendation, low quality evidence). If high risk adenomas are detected at first or subsequent surveillance examinations, a 3-year repetition of surveillance colonoscopy is recommended (strong recommendation, low quality evidence).4 The ESGE recommends that patients with serrated polyps < 10 mm in size with no dysplasia should be classified as low risk (weak recommendation, low quality evidence). The ESGE suggests that patients with large serrated polyps (≥ 10 mm) or those with dysplasia should be classified as high risk (weak recommendation, low quality evidence).5 The ESGE recommends that the endoscopist is responsible for providing a written recommendation for the post-polypectomy surveillance schedule (strong recommendation, low quality evidence).

Development and validation of a novel method for assessing competency in polypectomy: direct observation of polypectomy skills.

BACKGROUND: Despite its ubiquitous use over the past 4 decades, there is no structured, formal method with which to assess polypectomy. OBJECTIVE: To develop and validate a new method with which to assess competency in polypectomy. DESIGN: Polypectomy underwent task deconstruction, and a structured checklist and global assessment scale were developed (direct observation of polypectomy skills [DOPyS]). Sixty bowel cancer screening polypectomy videos were randomly chosen for analysis and were scored independently by 7 expert assessors by using DOPyS. Each parameter and the global rating were scored from 1 to 4 (scores ≥3 = competency). The scores were analyzed by using generalizability theory (G theory). SETTING: Multicenter. RESULTS: Fifty-nine of the 60 videos were assessable and scored. The majority of the assessors agreed across the pass/fail divide for the global assessment scale in 58 of 59 (98%) polyps. For G-theory analysis, 47 of the 60 videos were analyzed. G-theory analysis suggested that DOPyS is a reliable assessment tool, provided that it is used by 2 assessors to score 5 polypectomy videos all performed by 1 endoscopist. DOPyS scores obtained in this format would reflect the endoscopist's competence. LIMITATIONS: Small sample and polyp size. CONCLUSIONS: This study is the first attempt to develop and validate a tool designed specifically for the assessment of technical skills in performing polypectomy. G-theory analysis suggests that DOPyS could reliably reflect an endoscopist's competence in performing polypectomy provided a requisite number of assessors and cases were used.

Colonoscopy for colonic wall thickening at computed tomography: a worthwhile pursuit?

BACKGROUND: In the absence of official guidance for the management of colonic wall thickening identified by computed tomography (CT), a common clinical dilemma surrounds the volume of colonoscopies subsequently performed. METHODS: To identify whether colonic wall thickening identified at CT consistently warrants colonoscopy, consecutive colonoscopies performed at Leeds Teaching Hospitals Trust in 2008 and recorded as "possible colonic lesion on cross-sectional abdominal CT" in an endoscopic database were retrospectively analyzed. Clinical, radiologic, colonoscopic, and histologic data were obtained from medical records. RESULTS: Of 4,702 colonoscopies, 94 (2%) had a full data set meeting the inclusion criteria. The primary diagnoses were normal condition (n = 11, 11.7%), adenocarcinoma (n = 25, 26.6%), adenoma (n = 23, 24.5%), diverticular disease (n = 12, 12.8%), nonspecific colitis (n = 6, 6.4%), Crohn's disease (n = 4, 4.3%), and hyperplastic polyp (n = 3, 3.2%). Computed tomography and colonoscopy were concordant for specific pathology in 79.8% of the cases (n = 75). Compared with diagnosis after histology, colonoscopy alone correctly identified specific pathology in 18.1% of the cases (n = 17), and CT alone was correct in 4.3% of the cases (n = 4)), whereas both were incorrect in 3.2% of the cases (n = 3). Computed tomography had a sensitivity of 72.3% (95% confidence interval [95% CI], 61.9-80.8%), a specificity of 96.5% (95% CI, 94.9-97.6%), a positive predictive value of 72.3%, and a negative predictive value of 96.5%. In 63.8% of the cases (n = 60), CT identified pathology necessitating further intervention at the time of colonoscopy or afterward, and in 28.7% of the cases (n = 27), CT identified pathology requiring no additional intervention. In the remaining 7.4% of the cases (n = 7), CT detected no new pathology. CONCLUSION: Computed tomography is highly predictive of colonic pathology compared with final outcome after colonoscopy and biopsy. For patients without a pre-existing diagnosis, colonic wall thickening demonstrated at CT warrants further investigation with colonoscopy.

Minimal standard terminology for gastrointestinal endoscopy - MST 3.0.

Standardization of the language of gastrointestinal endoscopy is becoming increasingly important on account of international collaboration, standardized documentation requirements, and computer-based reporting. Version 1 of the Minimal Standard Terminology (MST) was devised to facilitate this development, and, through broad international collaboration, the document was developed and tested further to produce version 2.0, published in 2000. The document forms the basis for computer software by offering standard minimal lists of terms to be used in the structured documentation of endoscopic findings. The ownership of the MST has been transferred to the World Organisation of Digestive Endoscopy (OMED) and in this context, a new revision of the MST document is now in place. Version 3.0 of the terminology includes terms for endoscopic ultrasound (EUS) and enteroscopy, as well as for adverse event reporting. In addition, acknowledged scoring systems have been included for specific findings, and some structural enhancements have been implemented. The entire document is freely available for noncommercial use from www.omed.org.

Standard "inject and cut" endoscopic mucosal resection technique is practical and effective in the management of superficial colorectal neoplasms.

BACKGROUND: Standard polypectomy techniques may be contributing to ineffective eradication of colonic superficial neoplasia, an increasing number of which are nonpolypoid. We aimed to demonstrate the practicality and efficacy of the "inject and cut" endoscopic mucosal resection (EMR) technique in routine clinical practice. METHODS: Colonic EMRs performed for polypoid and nonpolypoid lesions at a tertiary institution were prospectively collected and analyzed for efficacy, and short and long-term complications. RESULTS: 224 colonic neoplasms (143 flat, 65 sessile and 16 subpedunculated) were excised by the standard inject-and-cut method, with standard accessories. The median size of all lesions was 10 mm (range 2-50 mm) and 110 (49.2%) lesions were located in the proximal colon. Histological completeness of resection was achieved in 87% of cases. Of the lesions 77.2% were dysplastic, with 5 cases of carcinoma in situ and 18 severely dysplastic adenomas. Complications included bleeding in five cases (2.2 %) and a single case of perforation (0.4%). All complications were managed endoscopically. Median follow up at 24 +/- 16 months (range 12-84 months) revealed a 7.2% local recurrence rate, all of which were subsequently eradicated by repeat EMR. CONCLUSIONS: Standard inject-and-cut colonic EMR is practical and effective in the eradication of superficial colonic neoplasia.

First UK experience of endoscopic vacuum therapy for the management of oesophageal perforations and postoperative leaks.

Oesophageal perforations and anastomotic leaks are associated with high morbidity and mortality. Endoscopic vacuum therapy (EVT) is a promising novel treatment that promotes healing and avoids sepsis. There are no data reporting its use in the UK. We report the first British experience of EVT in two elderly frail patients. Two patients were treated in our institution with EVT using Eso-SPONGE®. One patient had spontaneous oesophageal perforation and the other had anastomotic leakage post-Merendino oesophageal reconstruction (oesophagogastric continuity with jejunal interposition anastomosis). Both patients were over 65 years of age. One patient had 13 endoscopic Eso-SPONGE® exchanges over 8 weeks, while the other one had 6 exchanges over 4 weeks. Complete resolution of oesophageal leakage was achieved in both cases. EVT should be considered in the management of patients with oesophageal perforations and postoperative leaks. This novel therapeutic intervention has the potential to significantly reduce morbidity and mortality in these patients.

Risk stratification of colorectal polyps for predicting residual or recurring adenoma using the Size/Morphology/Site/Access score.

BACKGROUND AND AIMS: Endoscopic mucosal resection is an effective and safe procedure to manage large non-pedunculated colonic polyps for which residual/recurrent adenoma is the main drawback. Size/Morphology/Site/Access score determines polypectomy difficulty. We aimed to describe residual/recurrent adenoma rate according to Size/Morphology/Site/Access and to select the ize/Morphology/Site/Access cut-off to predict low residual/recurrent adenoma. METHODS: This was a retrospective cohort study of endoscopic mucosal resection for large non-pedunculated colonic polyps performed in a tertiary centre. RESULTS: Three hundred and sixteen procedures were included. The mean size of lesions was 34.5 ± 17.1 mm, 59.5% were sessile, 60.4% were in the right colon and in 17.7% (n = 56) the access was difficult. Of the lesions, 83.6% were Size/Morphology/Site/Access 3-4. Residual/recurrent adenoma at first and second follow-up was significantly lower in Size/Morphology/Site/Access 2 (1.9% and 0.0%, respectively) when compared to Size/Morphology/Site/Access 3 (18.2%, p = 0.004 and 6.7%, p = 0.049) and Size/Morphology/Site/Access 4 (30.8%, p < 0.001 and 22.7%, p = 0.030). The negative predictive value of Size/Morphology/Site/Access 2 for residual/recurrent adenoma at second follow-up was 86.1%. On multivariate analyses, Size/Morphology/Site/Access 3-4 predicted residual/recurrent adenoma at first (odds ratio 11.96, 95% confidence interval 1.57-91.13) and second follow-up (odds ratio 2.47, 95% confidence interval 1.51-4.22) and had higher cumulative incidence of residual/recurrent adenoma compared to Size/Morphology/Site/Access 2 (p ≤ 0.003). CONCLUSION: Use of the Size/Morphology/Site/Access score allows cases to be identified with a low risk of residual/recurrent adenoma.

Giant gastric ulcers: Malignancy yield and predictors from a 10-year retrospective single centre cohort.

BACKGROUND AND STUDY AIMS: Gastric cancer is known to reside in some gastric ulcers but what predicts this association is still unclear. Historically it has been thought that the increasing size of gastric ulcers may be a predictor for harbouring malignancy. Giant gastric ulcers are arbitrarily defined as ≥3 cm. The aim of this retrospective study was to examine patients with giant gastric ulcers within a single tertiary centre over a 10-year period. Our primary outcomes included the malignancy yield in giant gastric ulcers and to determine if any demographic, clinical or endoscopic predictors for malignancy exist. Secondary outcomes included the 30-day and 12-month mortality. METHOD: Patients with giant gastric ulcers ≥3 cm presenting from September 2005 to December 2015 were included in the study. Malignancy yield was obtained by looking at histology reports. Predictors for malignancy were tested using binary logistic regression, after demographic, clinical and endoscopic variables were tested using univariate analysis and for collinearity. RESULTS: A cohort of 111 patients was included for the final analysis. Forty-two giant gastric ulcers were malignant, equating to a yield of 37.8% (95% CI 28.8-46.8). Binary logistic regression revealed predictors for malignancy included: ulcer location being within the fundus, cardia or incisura (odds ratio (OR) 4.417; 95% CI 1.10-17.76; P = 0.036); younger age of patient (OR 0.202; 95% CI 0.06-0.71; P = 0.013); and endoscopic 'non-suspicion' (OR 0.138; 95% CI 0.049-0.39; P < 0.001). Patient's 12-month mortality for giant gastric ulcer was 61.9% (26/42) for malignant and 21.9% (11/73) for benign histology. CONCLUSION: We have shown a high malignancy yield of 37.8% (95% CI 28.8-46.8) and a 12-month mortality of 61.9% for malignant giant gastric ulcers and 21.9% for benign giant gastric ulcers. Predictors for malignancy in patients with giant gastric ulcers include ulcer location, patient's age and endoscopist's 'suspicion' during endoscopy.