British Society of Gastroenterology position statement on serrated polyps in the colon and rectum

Serrated polyps have been recognised in the last decade as important premalignant lesions accounting for between 15% and 30% of colorectal cancers. There is therefore a clinical need for guidance on how to manage these lesions; however, the evidence base is limited. A working group was commission by the British Society of Gastroenterology (BSG) Endoscopy section to review the available evidence and develop a position statement to provide clinical guidance until the evidence becomes available to support a formal guideline. The scope of the position statement was wide-ranging and included: evidence that serrated lesions have premalignant potential; detection and resection of serrated lesions; surveillance strategies after detection of serrated lesions; special situations-serrated polyposis syndrome (including surgery) and serrated lesions in colitis; education, audit and benchmarks and research questions. Statements on these issues were proposed where the evidence was deemed sufficient, and re-evaluated modified via a Delphi process until >80% agreement was reached. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool was used to assess the strength of evidence and strength of recommendation for finalised statements. Key recommendation: we suggest that until further evidence on the efficacy or otherwise of surveillance are published, patients with sessile serrated lesions (SSLs) that appear associated with a higher risk of future neoplasia or colorectal cancer (SSLs ≥10 mm or serrated lesions harbouring dysplasia including traditional serrated adenomas) should be offered a one-off colonoscopic surveillance examination at 3 years (weak recommendation, low quality evidence, 90% agreement).

Tumour expression of leptin is associated with chemotherapy resistance and therapy-independent prognosis in gastro-oesophageal adenocarcinomas.

BACKGROUND: Cytotoxic chemotherapy remains the main systemic therapy for gastro-oesophageal adenocarcinoma, but resistance to chemotherapy is common, resulting in ineffective and often toxic treatment for patients. Predictive biomarkers for chemotherapy response would increase the probability of successful therapy, but none are currently recommended for clinical use. We used global gene expression profiling of tumour biopsies to identify novel predictive biomarkers for cytotoxic chemotherapy. METHODS: Tumour biopsies from patients (n=14) with TNM stage IB-IV gastro-oesophageal adenocarcinomas receiving platinum-based combination chemotherapy were used as a discovery cohort and profiled with Affymetrix ST1.0 Exon Genechips. An independent cohort of patients (n=154) treated with surgery with or without neoadjuvant platinum combination chemotherapy and gastric adenocarcinoma cell lines (n=22) were used for qualification of gene expression profiling results by immunohistochemistry. A cisplatin-resistant gastric cancer cell line, AGS Cis5, and the oesophageal adenocarcinoma cell line, OE33, were used for in vitro validation investigations. RESULTS: We identified 520 genes with differential expression (Mann-Whitney U, P<0.020) between radiological responding and nonresponding patients. Gene enrichment analysis (DAVID v6.7) was used on this list of 520 genes to identify pathways associated with response and identified the adipocytokine signalling pathway, with higher leptin mRNA associated with lack of radiological response (P=0.011). Similarly, in the independent cohort (n=154), higher leptin protein expression by immunohistochemistry in the tumour cells was associated with lack of histopathological response (P=0.007). Higher leptin protein expression by immunohistochemistry was also associated with improved survival in the absence of neoadjuvant chemotherapy, and patients with low leptin protein-expressing tumours had improved survival when treated by neoadjuvant chemotherapy (P for interaction=0.038). In the gastric adenocarcinoma cell lines, higher leptin protein expression was associated with resistance to cisplatin (P=0.008), but not to oxaliplatin (P=0.988) or 5fluorouracil (P=0.636). The leptin receptor antagonist SHLA increased the sensitivity of AGS Cis5 and OE33 cell lines to cisplatin. CONCLUSIONS: In gastro-oesophageal adenocarcinomas, tumour leptin expression is associated with chemoresistance but a better therapy-independent prognosis. Tumour leptin expression determined by immunohistochemistry has potential utility as a predictive marker of resistance to cytotoxic chemotherapy, and a prognostic marker independent of therapy in gastro-oesophageal adenocarcinoma. Leptin antagonists have been developed for clinical use and leptin and its associated pathways may also provide much needed novel therapeutic targets for gastro-oesophageal adenocarcinoma.

Validation of the Global Rating Scale for endoscopy.

The Global Rating Scale for endoscopy is a web-based tool that can be used to assess and improve the quality of an endoscopy service. It was developed by asking endoscopy health professionals what they would want from the service for themselves or their relatives if they were undergoing an endoscopic procedure. To date, the Global Rating Scale has not been validated by patients themselves. We used focus groups in order to access the views and opinions of patients who had recently had experience of endoscopy services. Six focus groups were undertaken in five different Health Board areas across Scotland; in total 26 people participated. The results indicated that from the patients' perspective the 12 items of the GRS covered all areas of the endoscopy experience. There were no specific concerns identified that were not already covered within the Global Rating Scale. We conclude that the Global Rating Scale does address quality issues that matter to patients undergoing endoscopy, and validates the use of the GRS as a quality assessment tool for endoscopy services.

Systematic review and meta-analysis of the evidence for flexible sigmoidoscopy as a screening method for the prevention of colorectal cancer.

BACKGROUND: Colorectal cancer is a significant cause of death. Removal of precancerous adenomas, and early detection and treatment of cancer, has been shown to reduce the risk of death. The aim of this review and meta-analysis was to determine whether flexible sigmoidoscopy (FS) is an effective population screening method for reducing mortality from colorectal cancer. METHODS: MEDLINE (1946 to December 2012) and Embase (1980-2012, week 15) were searched for randomized clinical trials in which FS was used to screen non-symptomatic adults from a general population, and FS was compared with either no screening or any other alternative screening methods. Meta-analysis was carried out using a random-effects Mantel-Haenzsel model. RESULTS: Twenty-four papers met the inclusion criteria, reporting results from 14 trials. Uptake of FS was usually lower than that for stool-based tests, although FS was more effective at detecting advanced adenoma and carcinoma. FS reduced the incidence of colorectal cancer after screening, and long-term mortality from colorectal cancer, compared with no screening in a selected population. Compared with stool-based tests in a general population, FS was associated with fewer interval cancers. CONCLUSION: FS is efficacious at reducing colorectal cancer mortality compared with no screening. It is more effective at detecting advanced adenoma and carcinoma than stool-based tests. FS may be compromised by poorer uptake. Introduction of FS as a screening method should be done on a pilot basis in populations in which it is not currently used, and close attention should be paid to maximizing uptake. The relative risk of adverse events with FS compared with stool-based tests should be quantified, and its real-world effectiveness evaluated against the most effective stool-based tests.

MR colonography without bowel cleansing or water enema: a pilot study.

OBJECTIVES: The value of screening for colorectal cancer has been well demonstrated, and national programmes are being implemented. At present the primary imaging modality is colonoscopy, which has an associated morbidity and mortality. CT colonography (CTC) has been proposed as an alternative, but this is associated with radiation exposure and generally requires bowel preparation. The aim of this pilot study was to assess the feasibility of MR colonography (MRC) without bowel preparation or water enema for the detection of colorectal neoplasia. METHODS: Patients scheduled for colonoscopy were invited to participate in the study; informed consent was obtained. MRC (with oral barium faecal tagging and colonic air distension) was performed 1-2 weeks before the colonoscopy. Axial T(2) weighted single-shot fast spin-echo (prone and supine) and axial T(1) weighted fast spoiled gradient-recalled (pre- and post-iv gadolinium) supine MRI sequences were performed. The examinations were reported by two gastrointestinal radiologists by consensus. Colonoscopy following standard bowel preparation was performed by a single endoscopist blinded to the MRC results. Significant lesions were defined as polyps or masses >10 mm in diameter. RESULTS: 29 patients were studied. Colonoscopy revealed 25 mass lesions in 13 patients. MRC correctly identified four of the nine lesions >10 mm in diameter (sensitivity 44%; specificity 100%). Although specificity remained high for smaller lesions, sensitivity was poor. CONCLUSION: This pilot study has demonstrated the feasibility of performing MRC without bowel preparation or water enema. This would seem to be a promising modality for colorectal cancer screening. Larger studies are required to determine the accuracy of this modality for the detection of colorectal neoplasia.

Audit of bowel preparation with Picolax (sodium picosulfate plus magnesium citrate) for colonoscopy.

The aim of this study was to assess the quality of bowel preparation for colonoscopy with standard dose Picolax (two sachets administered on the day prior to the procedure, as per the manufacturer's instructions) in a large cohort of patients. A retrospective audit was performed of colonoscopies performed at our institution over a 1-year period. Patients were excluded if standard dose Picolax was not used, if the quality of the bowel preparation was not recorded or if completion of the procedure was not recorded. Of the 619 fully evaluable cases, the quality of the bowel preparation was assessed by the colonoscopist performing the procedure as good in 263 (42.5%), satisfactory in 242 (39.1%) and poor in 114 (18.4%) of the cases. In only 28 (4.5%) cases, poor bowel preparation was the reason cited for an incomplete colonoscopy. There was no difference in the quality of bowel preparation between inpatients and outpatients. In clinical practice, Picolax is an effective bowel preparation for colonoscopy in the vast majority of cases.

Endoscopic findings in the upper gastrointestinal tract of faecal occult blood-positive, colonoscopy-negative patients.

BACKGROUND: Detection of faecal occult blood is recommended for colorectal cancer screening in average risk populations. However, many subjects do not have any cause found in the colon to account for the occult blood loss. AIMS: To determine the prevalence of upper gastrointestinal tract disease in faecal occult blood-positive, colonoscopy-negative patients. PATIENTS AND METHODS: Retrospective audit of 99 patients (56 females; mean age 60 years, range 18-83) who underwent same-day colonoscopy and upper gastrointestinal endoscopy over a 2-year period. RESULTS: Fifty-two of the 99 patients had a normal colonoscopy, 16 had diverticulosis and 2 had hyperplastic polyps; these 70 patients comprised the colonoscopy-negative group. Significant upper gastrointestinal tract disease was noted in 25 (36%) of the colonoscopy-negative group compared with 10 (34%) of the 29 colonoscopy-positive group (p=ns). Most of the upper gastrointestinal tract lesions identified were benign. Within the colonoscopy-negative group, patients with anaemia or upper gastrointestinal tract symptoms had a higher prevalence of positive findings in the upper gastrointestinal tract, but this association was not statistically significant. CONCLUSIONS: Endoscopic examination of the upper gastrointestinal tract in faecal occult blood-positive individuals reveals mostly benign disease, with an equal prevalence in colonoscopy-negative and colonoscopy-positive patients. Routine performance of upper gastrointestinal endoscopy in faecal occult blood-positive individuals is not indicated and should be undertaken only for appropriate symptoms.

Age threshold for endoscopy and risk of missing upper gastrointestinal malignancy--data from the Scottish audit of gastric and oesophageal cancer.

BACKGROUND: Urgent endoscopy is indicated for suspected upper gastrointestinal malignancy. However, there is limited evidence on the age threshold for performing urgent endoscopy in uncomplicated dyspepsia (that is, without alarm features). AIM: To quantify the risk of missing upper gastrointestinal malignancy within Scotland, if the age threshold for urgent endoscopy in uncomplicated dyspepsia was increased from 45 to 55 years. METHODS: Analysis of data collected prospectively by the Scottish Audit of Gastric and Oesophageal Cancer. 'Alarm' features at presentation were defined as dysphagia, weight loss, gastrointestinal bleeding, anaemia, vomiting, history of gastric surgery and history of peptic ulcer disease. RESULTS: Of the 3293 patients diagnosed with upper gastrointestinal malignancy, 290 (8.8%) patients were <55 years of age. Twenty-one of the patients aged <55 years had no alarm features (0.64% of all patients); 12 were aged 45-55 years and nine were aged <45 years. Only two patients (one aged <45 years) underwent potentially curative surgery. CONCLUSION: Upper gastrointestinal malignancy is uncommon under 55 years of age and most of the patients present with alarm features. Raising the age threshold for endoscopy for new-onset uncomplicated dyspepsia from 45 to 55 years would not impact adversely on the diagnosis or outcome of upper gastrointestinal malignancy.

Gastroduodenal mucosal vitamin-C levels in Helicobacter pylori infection.

BACKGROUND: Vitamin C is an important endogenous antioxidant, and epidemiologic evidence suggests that it may protect against the development of gastric cancer. We therefore determined mucosal vitamin-C levels in the stomach and duodenum of subjects with and without Helicobacter pylori infection. METHODS: The patients were 30 subjects undergoing routine gastroscopy for investigation of dyspepsia. High-performance liquid chromatography with electrochemical detection was used to determine mucosal ascorbic acid and total vitamin-C levels. RESULTS: In H. pylori-negative subjects with normal gastroduodenal histology the antrum contained significantly higher levels of ascorbic acid and total vitamin C than the corpus or duodenum (P < 0.05). No significant changes were seen in gastric mucosal ascorbic acid or total vitamin-C levels in the presence of H. pylori infection and related inflammation. The presence of gastric atrophy did not affect mucosal ascorbic acid or total vitamin C levels. Duodenal ascorbic acid and total vitamin-C levels did not change significantly in the presence of gastric H. pylori or duodenal inflammation. CONCLUSIONS: Although high levels of vitamin C are present in the gastroduodenal mucosa, these are not altered in the presence of H. pylori infection and inflammation. These observations suggest that the mucosal antioxidant potential of vitamin C is not impaired by H. pylori infection.

The management of young dyspeptic patients in the era of Helicobacter pylori.

The management of young dyspeptic patients remains controversial in the modern Helicobacter pylori era. The use of non-invasive screening for H. pylori in one proposed strategy has demonstrated a substantial reduction in the endoscopy workload by excluding H. pylori negative patients under the age of 45 years with uncomplicated dyspepsia. An alternative screening strategy proposes a 'test and treat' approach, with H. pylori positive patients proceeding directly to an empirical course of eradication therapy. Ednoscopy would be reserved for patients who failed to respond symptomatically or who were H. pylori negative on intial screening. At present there are few data available from clinical studies of putting the 'test and treat' policy into practice. Although there is likely to be a role for screening young dyspeptic patients for H. pylori in primary care, subsequent management requires well-planned studies in order to assess the benefits of any particular strategy.

Plasma free radical activity and antioxidant vitamin levels in dyspeptic patients: correlation with smoking and Helicobacter pylori infection.

BACKGROUND: The pathological processes by which Helicobacter pylori infection leads to the development of gastroduodenal disease are still incompletely understood. Oxygen-derived free radicals are important mediators of inflammation and potential carcinogens. Furthermore, dietary studies have suggested that antioxidant vitamins may protect against gastric cancer. OBJECTIVE: To determine plasma free radical activity and antioxidant vitamin levels in dyspeptic patients and to correlate the results with H. pylori infection and tobacco smoking. SUBJECTS: Forty-three patients undergoing routine endoscopy for investigation of dyspepsia. METHODS: Plasma free radical activity was determined by measurement of thiobarbituric acid-reactive substances (TBARS). Plasma samples were also assayed for the antioxidant vitamins A, C and E. Gastroduodenal biopsies were obtained from all patients for histological examination. RESULTS: Plasma TBARS levels were significantly higher in H. pylori positive versus negative subjects (P < 0.03), smokers versus non-smokers (P < 0.04) and males versus females (P < 0.01). Multiple regression analysis revealed that after correcting for male sex and smoking there was no significant association between plasma free radical activity and H. pylori infection. Smokers had significantly lower levels of plasma vitamin C than non-smokers (P< 0.05); no differences were seen in vitamin A and E levels. Gender and H. pylori infection did not significantly affect plasma antioxidant vitamin levels. Gastroduodenal disease was present in all of the smokers compared with 67% of the non-smokers (P < 0.05); 69% of the smokers were H. pylori positive versus 53% of the non-smokers. CONCLUSIONS: Tobacco smoking and male sex, both recognized risk factors for gastroduodenal disease, appear to be the major determinants of increased plasma free radical activity in dyspeptic subjects, rather than H. pylori infection. The reason for the higher prevalence of H. pylori infection and gastroduodenal disease in dyspeptic smokers is unclear but may relate to weakened antioxidant defences.

Recurrence of duodenal ulcer after Helicobacter pylori eradication is related to high acid output.

BACKGROUND: Helicobacter pylori eradication reduces the recurrence of duodenal ulcers. It is unclear why duodenal ulcers rarely recur in the absence of reinfection with H. pylori or NSAID treatment. METHODS: Basal, gastrin-releasing peptide- and pentagastrin-stimulated peak acid outputs in patients with ulcer relapse after H. pylori eradication were measured, and compared with patients without ulcer relapse after H. pylori eradication. RESULTS: Pentagastrin-stimulated peak acid output was significantly higher in H. pylori-positive patients with duodenal ulcers than in H. pylori-negative controls, and fell significantly after H. pylori eradication. In H. pylori-negative patients with recurrent duodenal ulcers, pentagastrin-stimulated peak acid output was significantly higher than in controls and similar to H. pylori-positive patients with duodenal ulcers. CONCLUSIONS: These findings suggest that duodenal ulcer relapse after eradication of H. pylori may be related to high pentagastrin-stimulated peak acid output. In this subset of patients with duodenal ulcers, maintenance anti-secretory treatment may be necessary to prevent relapse.

Lansoprazole plus clarithromycin: evaluation of a new dual therapy for Helicobacter pylori eradication.

The aim of this pilot study was to evaluate the efficacy and safety of lansoprazole plus clarithromycin for eradication of Helicobacter pylori. A total of 26 patients with H. pylori infection were randomised to receive clarithromycin, 500 mg t.i.d. for 14 days, plus either lansoprazole, 30 mg o.m., (group L30, n = 13) or lansoprazole, 30 mg b.i.d., (group L60, n = 13). H. pylori status was determined pre-treatment and four to six weeks after completion of the study medication by histology and 13C-urea breath test. Two patients were unable to complete the course of medication. Of the remaining 24 patients, 14 (58%) successfully eradicated H. pylori--8/12 (67%) patients in group L30 and 6/12 (50%) in group L60. Side-effects were experienced by 17/26 (65%) of patients, most commonly a taste disturbance. The results from this pilot study suggest that dual therapy with lansoprazole plus clarithromycin is only a moderately effective regimen for eradicating H. pylori.

Vitamin E concentrations in the human stomach and duodenum--correlation with Helicobacter pylori infection.

BACKGROUND: Vitamin E (alpha-tocopherol) is an important endogenous antioxidant and may also act as an anticarcinogen. AIM: To determine the vitamin E status of subjects with, and without, gastroduodenal inflammation and Helicobacter pylori infection. SUBJECTS: 36 patients undergoing routine gastroscopy for investigation of dyspepsia. METHODS: High performance liquid chromatography with fluorometric detection was used to determine alpha-tocopherol values. RESULTS: In H pylori negative subjects with normal gastroduodenal histology (n = 11) median alpha-tocopherol values (ng/mg tissue weight) were significantly higher in the corpus (16.4, interquartile range (IQR) 8.9-22.6) than in the antrum (3.0, IQR 2.6-6.7, p = 0.001) or duodenum (6.7, IQR 2.5-8.4, p = 0.001). H pylori infection (n = 19) was associated with a reduction in the corpus alpha-tocopherol values (median 8.3, IQR 4.9-13.7, p < 0.05) but there was no significant change in the antral concentrations although this was the main site of inflammation and neutrophil activity. Duodenal alpha-tocopherol values were not significantly changed in the presence of duodenitis or gastric H pylori infection. alpha-Tocopherol was not detected in the gastric juice of any of the subjects. Plasma alpha-tocopherol concentrations in the H pylori negative subjects (median 10.4 mg/l, IQR 7.2-11.9) were not significantly different to the values in the H pylori positive subjects (median 11.1 mg/l, IQR 7.6-12.7). CONCLUSIONS: Concentrations of alpha-tocopherol in H pylori negative subjects are higher in the corpus than in the antrum or duodenum. In the presence of predominantly antral H pylori infection and neutrophil activity the major change seen is a reduction in corpus alpha-tocopherol values while antral concentrations are maintained. These findings may reflect a mobilisation of antioxidant defences to the sites of maximal inflammation in the stomach.

Histology of chronic gastritis with and without duodenitis in patients with Helicobacter pylori infection.

AIM: To compare the histological characteristics of Helicobacter pylori positive chronic gastritis in patients with and without associated duodenitis. METHODS: Gastric mucosal biopsy specimens were obtained from patients undergoing endoscopy for dyspepsia. Severity of gastritis and density of H pylori infection were graded according to the Sydney system. RESULTS: Of the 69 patients studied, 15 had normal histology, 22 had chronic gastritis only (77.3% H pylori positive), 21 had duodenitis (90.5% H pylori positive), and 11 had other diagnoses. In the H pylori positive patients, the median gastritis score was higher in the duodenitis group (6, range 3-9) than in the chronic gastritis only group (5, range 2-8), because of greater neutrophil activity scores in patients with duodenitis (median score 2 v 1). There were no differences in the density of H pylori infection, inflammation, atrophy, or intestinal metaplasia between patients with chronic gastritis only and those with duodenitis. CONCLUSIONS: These results suggest that H pylori positive patients with duodenitis have a more severe form of gastritis than those without associated duodenal inflammation. This is because of increased neutrophil activity, which seems to be independent of the density of H pylori infection.