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.

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.

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.

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.

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.

Chromosome 5q loss in colorectal flat adenomas.

PURPOSE: Flat adenomas are a subgroup of colorectal adenomas that have been associated with a more aggressive clinical behavior compared with their polypoid counterparts. Here, we aimed to compare one of the molecular changes most explicitly associated with adenoma to carcinoma progression, that is, chromosomal instability, between flat and polypoid colorectal adenomas. EXPERIMENTAL DESIGN: Consecutive series of 83 flat and 35 polypoid adenomas were analyzed for DNA copy number changes using a high-resolution array comparative genomic hybridization platform, microsatellite instability (MSI) status, and for mutations in the adenomatous polyposis coli (APC) gene. Immunohistochemical stainings for CD3, CD8, and FoxP3 expression were carried out. RESULTS: Patterns of DNA copy number changes differed between the two phenotypes, with significantly more frequent loss of 5q14.3 and 5q15-q31.1 in flat adenomas, whereas losses of 1p36.32-p35.3, 10q25.3, 17p12, and chromosome 18 were more frequent in polypoid adenomas (false discovery rate < 0.2). MSI was observed in one flat adenoma. As the 5q15-q31.1 region harbors the APC locus, APC mutation status was investigated, showing significantly less mutations in flat adenomas (P = 0.04). An initial exploration of a possible association of 5q loss with inflammation indicated that tumor-infiltrating lymphocytes were more abundant in the stroma of flat adenomas compared with that of polypoid adenomas. CONCLUSION: Flat and polypoid adenomas have partially distinct chromosomal profiles, consistent with differences in the biology underlying these phenotypes. Alterations more specific to flat adenomas, in particular 5q loss, may be associated with inflammation.

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.

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.

Inflammatory bowel disease and the eye.

Inflammatory bowel disease includes Crohn's disease and ulcerative colitis, and is characterized by chronic inflammation of the intestines. The advances in understanding of the inflammatory process have resulted in improved treatment of inflammatory bowel disease. The systemic complications of inflammatory bowel disease involve many organs, eyes included. The ophthalmic complications are usually of inflammatory origin. Some of these complications, like scleritis, may reflect overall disease activity. Treatment of intestinal inflammation-either medical or surgical-usually helps resolution of ophthalmic complications. This review describes recent developments in the diagnosis and management of the inflammatory bowel disease and its ophthalmic complications.