Incidence of metachronous visible lesions in patients referred for radiofrequency ablation (RFA) therapy for early Barrett's neoplasia: a single-centre experience.

OBJECTIVE: Evaluate the incidence of metachronous visible lesions (VLs) in patients referred for radiofrequency ablation (RFA) for early Barrett's neoplasia. DESIGN: This study was conducted as part of the service evaluation audit. SETTING: Tertiary referral centre. PATIENTS: All patients with dysplastic Barrett's oesophagus referred for RFA were included for analysis. White light high-resolution endoscopy (HRE), autofluorescence imaging and narrow band imaging were sequentially performed. Endoscopic mucosal resection (EMR) was performed for all VL. Three to six months after EMR, all patients underwent initial RFA and then repeat RFA procedures at three monthly intervals. INTERVENTIONS: All endoscopy reports and final staging by EMR/surgery were evaluated and included for analysis. RESULTS: Fifty patients were analysed; median age 73 years, 84% men. 38/50 patients (76%) had a previous EMR due to the presence of VL before referred for ablation; twelve patients had no previous treatment. In total, 151 ablation procedures were performed, median per patient 2.68. Twenty metachronous VL were identified in 14 patients before the first ablation or during the RFA protocol; incidence was 28%. All metachronous lesions were successfully resected by EMR. Upstaging after rescue EMR compared with the initial histology was observed in four patients (28%). CONCLUSIONS: In total, 28% of patients enrolled in the RFA programme were diagnosed to have metachronous lesions. This high-incidence rate highlights the importance of a meticulous examination to identify and resect any VL before every ablation session. RFA treatment for early Barrett's neoplasia should be performed in tertiary referral centres with HRE and EMR facilities and expertise.

British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus

These guidelines provide a practical and evidence-based resource for the management of patients with Barrett's oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was followed to provide a methodological strategy for the guideline development. A systematic review of the literature was performed for English language articles published up until December 2012 in order to address controversial issues in Barrett's oesophagus including definition, screening and diagnosis, surveillance, pathological grading for dysplasia, management of dysplasia, and early cancer including training requirements. The rigour and quality of the studies was evaluated using the SIGN checklist system. Recommendations on each topic were scored by each author using a five-tier system (A+, strong agreement, to D+, strongly disagree). Statements that failed to reach substantial agreement among authors, defined as >80% agreement (A or A+), were revisited and modified until substantial agreement (>80%) was reached. In formulating these guidelines, we took into consideration benefits and risks for the population and national health system, as well as patient perspectives. For the first time, we have suggested stratification of patients according to their estimated cancer risk based on clinical and histopathological criteria. In order to improve communication between clinicians, we recommend the use of minimum datasets for reporting endoscopic and pathological findings. We advocate endoscopic therapy for high-grade dysplasia and early cancer, which should be performed in high-volume centres. We hope that these guidelines will standardise and improve management for patients with Barrett's oesophagus and related neoplasia.

Clinical trial: chest pain caused by presumed gastro-oesophageal reflux in coronary artery disease - controlled study of lansoprazole vs. placebo.

BACKGROUND: Gastro-oesophageal reflux (GER) and coronary artery disease commonly co-exist. Coronary artery disease patients may mistake GER-induced pain for cardiac pain or GER might provoke angina. AIM: To investigate if GER might contribute to nocturnal/rest chest pain among coronary artery disease patients. METHODS: Double-blind placebo-controlled crossover study investigating effect of lansoprazole on chest pain; 125 patients with angiographically proven coronary artery disease enrolled with at least one weekly episode of nocturnal/rest pain, randomized to lansoprazole 30 mg daily or placebo with crossover after 4 weeks. Symptoms recorded and QOL assessed by Nottingham Health Profile Questionnaire; ST segment depression episodes counted from 24 h electrocardiographic monitoring in final week of both periods. STATISTICAL ANALYSIS: ANCOVA with period and carryover analysis. RESULTS: In all, 108 patients completed the study. There was a modest increase in pain-free days on lansoprazole vs. placebo (P < 0.02), with fewer days with pain at rest (P < 0.05) and at night (P < 0.009) on lansoprazole vs. placebo, but no significant differences in ST segment depression episodes (P = 0.64). There was a trend for reduction in the 'physical pain' QOL domain. CONCLUSIONS: Among coronary artery disease patients, lansoprazole modestly increases pain-free days and reduces rest/nocturnal pain. As lansoprazole did not affect ST segments, this may be by suppression of GER-provoked pain misinterpreted as angina, rather than acid-provoked ischaemia.

Prevalence of inflammatory bowel disease in patients with airways disease.

BACKGROUND: Case reports and case series have suggested an association between inflammatory bowel disease (IBD) and airways disease, but there are no data demonstrating a higher prevalence of IBD among patients with airways disease. Furthermore, no consistent radiological, pulmonary or pathological abnormalities have been demonstrated in patients with both conditions. AIMS: To determine the prevalence of IBD among patients with airways disease and to evaluate clinical and pathophysiological features. METHODS: A retrospective analysis of outpatients with airways disease over a 10-year period. RESULTS: IBD was four times more prevalent among patients with airways disease compared with published local IBD prevalence [Odds Ratio 4.26, 95% CI 1.48, 11.71, p=0.006; Crohn's disease OR 5.96, 95% CI 1.94, 18.31, p=0.002 and ulcerative colitis OR 4.21, 95% CI 1.71, 10.41, p=0.001]. IBD was more frequent in all types of airways disease except asthma; the association was particularly strong for conditions associated with productive cough. All except 1 patient had established IBD before the onset of respiratory symptoms. There were no obvious radiological differences between ulcerative colitis and Crohn's disease cases. There was a trend for a higher lymphocyte count (despite a tendency to lower blood lymphocyte count) but lower sputum neutrophil count in patients with Crohn's disease compared with ulcerative colitis. There were no significant differences in physiological measurements of pulmonary function between the two types of IBD. CONCLUSION: Our findings support an association between airways disease and inflammatory bowel disease, particularly non-asthmatic airways disease with productive cough.

Meta analysis: Cancer risk in Barrett's oesophagus.

BACKGROUND: Risk of cancer in Barrett's oesophagus is reported to vary between studies and also between countries, where the studies were conducted as per several systematic reviews. Cancer incidence has implications on surveillance strategies. AIM: To perform a meta-analysis to determine the incidence of oesophageal cancer in Barrett's oesophagus. METHODS: Articles retrieved by MEDLINE search (English language, 1966-2004). Studies had to necessarily include verified Barrett's oesophagus surveillance patients, documented follow-up and cancer identified as the outcome measure. A random effects model of meta-analysis was chosen and results were expressed as mean (95% CI). RESULTS: Forty-one articles selected for conventional Barrett's oesophagus (length >3 cm); eight included short segment Barrett's oesophagus (one additional article including only short segment Barrett's oesophagus). Cancer incidence was 7/1000 (6-9) person-years duration of follow-up (pyd), with no detectable geographical variation [UK 7/1000 (4-12) pyd, USA 7/1000 (5-9) pyd and Europe 8/1000 (5-12) pyd]. Cancer incidence in the UK was 10/1000 (7-14), when two large studies were excluded. Cancer incidence in SSBO was 6/1000 (3-12) pyd. When short segment Barrett's oesophagus compared to conventional Barrett's oesophagus, there was a trend towards reduced cancer risk [OR 0.55, (95% CI: 0.19-1.6), P = 0.25]. CONCLUSION: We found no geographical variations in Barrett's oesophagus cancer risk, but observed a trend towards reduced cancer risk in short segment Barrett's oesophagus. There is a time trend of decreasing cancer incidence.

Normalization of oesophageal pH does not guarantee control of duodenogastro-oesophageal reflux in Barrett's oesophagus.

BACKGROUND: Proton-pump inhibitors are effective at preventing the acid component of gastro-oesophageal refluxate from entering the oesophagus. It is not clear whether proton-pump inhibitors prevent duodenogastro-oesophageal reflux. AIM: To measure oesophageal exposure to duodenogastro-oesophageal refluxate while on proton-pump inhibitors in patients with Barrett's oesophagus. METHODS: Twenty-five patients (23 male) with Barrett's oesophagus underwent 24 h oesophageal pH and Bilitec 2000 monitoring while on omeprazole 40 mg/day (n = 19) or omeprazole 60 mg/day (n = 6). All patients were undergoing argon plasma ablation of their Barrett's epithelium as part of a clinical trial and the Bilitec measurements were only carried out after the ablation had been completed. RESULTS: 20 of 25 (80%) patients had a normal oesophageal pH profile. Fifteen of the 25 (60%) had abnormal oesophageal exposure to bile as measured by Bilitec 2000. Of the 20 patients who had a normal 24 h oesophageal pH profile, 11 (55%) had pathological exposure to bile in their oesophagus. CONCLUSION: Complete acid suppression does not guarantee elimination of duodenogastro-oesophageal reflux.

High-grade dysplasia in Barrett's oesophagus: natural history and review of clinical practice.

BACKGROUND: Management of high-grade dysplasia in Barrett's oesophagus is controversial: surgery carries an appreciable morbidity/mortality, high-grade dysplasia may not progress to cancer and endoscopic ablation is an emerging option. AIM: To review Barrett's oesophagus-related high-grade dysplasia management and outcome over a 10-year period. METHODS: This was a retrospective case note review of 36 patients identified from a pathology database. RESULTS: There were 31 men of mean age 67 years. Endoscopic surveillance identified nine. Median follow-up was 21 months. Seven patients had no further intervention because of age/comorbidity. The other 29 had repeat endoscopic biopsies, nine showing cancer (six oesophagectomized). Of the 20 remaining patients with persisting high-grade dysplasia, eight had surgery (histology showed cancer in six), seven continued endoscopic surveillance (high-grade dysplasia regressed in four) and five had 'curative' argon ablation. An intensive biopsy protocol was not followed in 55% of endoscopies. Prevalent cancers occurred in 44% with an annual incidence of 5% over 5 years. All cause mortality was 39% (14 of 36, eight of 14 from cancer). CONCLUSIONS: Management of high-grade dysplasia was not uniform. Unsuspected cancer was common in high-grade dysplasia patients undergoing surgery but 13% regressed under surveillance. High-grade dysplasia patients have a high mortality but 43% did not die from cancer.

Audit of a Barrett's epithelium surveillance database.

BACKGROUND: Barrett's epithelium is a premalignant condition in which endoscopic surveillance is recommended but remains contentious. AIM: To audit our Barrett's epithelium surveillance database and to calculate the incidence and natural history of dysplasia and cancer in this cohort. METHODS: A retrospective analysis of a computerised database of patients with columnar lined oesophagus containing specialised intestinal metaplasia was undertaken over a 5-year period. The surveillance protocol was annual endoscopy with 2-cm interval quadrantic biopsies with patients on continuous acid-suppression therapy. RESULTS: A total of 138 (102 men) patients underwent active surveillance. The mean age was 62.1 years and the mean Barrett's epithelium length was 5.9 cm. Ten patients had low-grade dysplasia, with a mean age of 73.5 years, a mean Barrett's epithelium length of 7.8 cm, a prevalence of 7.2% over 5 years and an incidence of 1.4% per annum. Low-grade dysplasia regressed in five patients, persisted in four patients, and was associated with a concurrent squamous carcinoma in one patient. Three patients had high-grade dysplasia at index endoscopy, with no incident cases. One progressed to adenocarcinoma after 2 years. A cancer incidence of one per 202 patient-years of surveillance was found, equivalent to 0.5% per year. CONCLUSION: Short-interval (1-year) endoscopic surveillance of Barrett's epithelium offers little reward. Low-grade dysplasia is uncommon, and no progression to adenocarcinoma was seen in this cohort. No incident high-grade dysplasia was observed. Prospective evaluation of a longer endoscopic surveillance interval in controlled clinical studies is warranted.

Efficacy and one year follow up of argon plasma coagulation therapy for ablation of Barrett's oesophagus: factors determining persistence and recurrence of Barrett's epithelium.

INTRODUCTION: Barrett's epithelium (BE) has malignant potential. Neither acid suppression nor antireflux surgery produce consistent or complete regression of the metaplastic epithelium. Endoscopic thermoablation with argon plasma coagulation (APC) offers a different approach but factors influencing its outcome have not been systematically examined. AIM: To assess the efficacy of APC and factors influencing initial and one year outcome. METHODS: Fifty patients, mean age 61.4 years, mean BE length 5.9 cm (range 3-19), underwent APC therapy at four weekly intervals while receiving proton pump inhibitor (PPI) therapy. BE margins were marked by India ink tattooing and extent was documented by grid drawings, photography, and 2 cm interval quadrantic jumbo biopsies. Twenty four hour ambulatory oesophageal pH studies were done while on PPIs before and after APC therapy, and Bilitec bilirubin monitoring after APC completion. RESULTS: A total of 68% of patients achieved >90% BE ablation after a median of four APC sessions. Persistent BE (>10% original BE area) was associated with longer initial BE length despite more APC sessions. Persistent acid and bile reflux on PPIs, although commoner in this group, were not significantly different from those successfully ablated. Fifteen of 34 patients (44%) with successful macroscopic clearance had buried glands, present in 8.3% of a total of 338 biopsies. At the one year follow up, only 32% of those with initial successful ablation showed no recurrence. BE recurred or increased in most with mean segment length increases of 1.1 cm and 1.6 cm, respectively, in patients with previous full ablation and those with persistent BE. The presence of buried glands did not predict BE recurrence. Patients who reduced their PPI dose had significantly greater BE recurrence. CONCLUSIONS: APC is most effective for shorter segment BE ablation but "buried" glands do occur. Recurrence of BE is common at one year, especially in those with initial persistent and/or long segment BE and those who reduce their PPI dose.

Surveillance in Barrett's oesophagus: a personal view.

Barrett's oesophagus is defined as columnar-lined oesophagus of any length containing specialised intestinal metaplasia. Diagnosis depends on close corroboration between the endoscopist and histopathologist. It occurs in 10% of patients presenting endoscopically with reflux symptoms and has an adenocarcinoma incidence of 0.4% to 2%. Surveillance is performed to detect precancerous change (dysplasia) and early stage disease has a good surgical prognosis. Computer models suggest cost efficacy comparable to other health measures. However most patients with Barrett's do not die of oesophageal cancer and elective oesophagectomy has an appreciable mortality. Endoscopic ablation techniques and improved definition of high risk subgroups will help shape future surveillance programmes.

Clinical value of [(18)F]fluoro-deoxyglucose positron emission tomography for patients with fever of unknown origin.

We describe the diagnostic contribution of [(18)F]fluoro-deoxyglucose (FDG) positron emission tomography (PET) scan in 58 consecutive cases of fever of unknown origin (FUO) and compare this new approach with gallium scintigraphy. This investigation was performed from March 1996 through October 1998 at Gasthuisberg University Hospital in Leuven, Belgium. A final diagnosis was established for 38 patients (64%). Forty-six FDG-PET scans (79%) were abnormal; 24 of these abnormal scans (41% of the total number of scans) were considered helpful in diagnosis, and 22 (38% of the total number) were considered noncontributory to the diagnosis. In a subgroup of 40 patients (69%), both FDG-PET and gallium scintigraphy were performed. FDG-PET scan and gallium scintigraphy were normal in 23% and 33% of these cases, respectively; helpful in diagnosis in 35% and 25%, respectively; and noncontributory in 42% each. All foci of abnormal gallium accumulation were also detected by use of an FDG-PET scan. We conclude that FDG-PET is a valuable second-step technique in patients with FUO because it yielded diagnostic information in 41% of the patients in whom the probability of a definite diagnosis was only 64%. FDG-PET scan compares favorably with gallium scintigraphy for this indication. Because of the quick results (within hours instead of days), FDG-PET scan may replace gallium scintigraphy as a radiopharmaceutical for the evaluation of patients with FUO.

Production and evaluation of guidelines for the management of inflammatory bowel disease: the Leicester experience.

Consensus guidelines for the management of patients with inflammatory bowel disease were produced by gastroenterologists, gastrointestinal surgeons and a cross-section of general practitioners (GPs) from Leicestershire in order to develop a seamless pattern of care with a common approach to diagnosis and treatment. It was hoped that the guidelines would encourage a movement towards care in the community for many patients with stable disease and so speed up new consultation rates. The study then assessed the impact of these guidelines on the referral letters of GPs to hospital consultants, the prediction of disease and adherence to them on re-referring patients after discharge. The guidelines were distributed to all 487 GPs in the Leicester Health Authority area and the gastroenterology teams within the hospitals. The value of the guidelines was assessed by an audit of referral letters, the length of time from referral letter to out-patient appointment, both before and after the launch of the guidelines, adherence to the guidelines on re-referral, and monitoring the outcome of the discharged patients. Whilst the guidelines may have helped GPs to manage stable patients in the community, the content of referral letters and the diagnostic abilities of GPs were not seen to improve since the launch of the guidelines. However, only 5% of stable patients who were discharged from one clinic were re-referred for inflammatory bowel disease.

Bile acid therapy and markers of immune-mediated damage in primary biliary cirrhosis.

In primary biliary cirrhosis (PBC), liver damage results from both immune- and bile acid-mediated mechanisms. Therapies directed against the former have been either ineffective or toxic, while bile salt therapy is well tolerated but of uncertain long-term benefit. Because of slow disease progression, there is a need for surrogate markers of long-term efficacy. Candidates include markers of immune activation, such as soluble intercellular adhesion molecule-1 (sICAM-1) which shows promise in this respect. Using this marker, evidence has been presented to suggest an additive effect of the combination of ursodeoxycholic acid (UDCA) with azathioprine and prednisone in a short-term trial in PBC.

Measuring duodenogastro-oesophageal reflux (DGOR)

The importance of duodenogastro-oesophageal reflux (DGOR) in gastro-oesophageal reflux disease (GORD) is controversial. Most evidence points to a possible synergistic effect between refluxed acid and bile, which may be more frequent in patients with Barrett's oesophagus, particularly those with complications. Techniques for long-term measurement of DGOR include continuous aspiration, which is cumbersome and laborious, ambulatory spectrophotometric bilirubin measurement as a proxy for bile acids and sodium ion measurement using a sodium electrode. The two latter are the most promising techniques which are improving understanding of DGOR in clinical situations. Both have advantages and drawbacks. The Bilitec system for measuring bilirubin has been most studied and has been well validated. The sodium electrode has so far only been used for short-term monitoring but may be capable of development into a practical tool for longer-term monitoring of DGOR.