John Green

Controlled trial of antituberculous chemotherapy in Crohn’s disease: a five year follow up study

Background—It has been suggested thatMycobacterium paratuberculosis is the cause of Crohn’s disease. In a previous report the immediate effect of two years treatment with antituberculous chemotherapy showed no clinical benefit. Aims—To assess both the immediate and longer term effect of treatment on the disease. Methods—Patients were followed for five years from their date of entry to the study. One hundred and thirty patients entered the initial study, and of these 111 (81%) were followed regularly. Results—Overall, there was no evidence of consistent benefit or disadvantage from antituberculous chemotherapy in any of the assessments made, including the number of acute relapses, surgical episodes, hospital admissions, disease activity, blood tests, or medication required for Crohn’s disease during the follow up period. Conclusion—The absence of any benefit at the end of the initial two year trial period, and during the three year subsequent follow up, fails to support the hypothesis that mycobacteria play an important part in the pathogenesis of Crohn’s disease, or that antituberculous chemotherapy may be of benefit.

Role of smoking in inflammatory bowel disease: implications for therapy

The relationship between smoking and inflammatory bowel disease is now firmly established but remains a source of confusion among both patients and doctors. It is negatively associated with ulcerative colitis but positively associated with Crohns disease. In addition, it has opposite influences on the clinical course of the two conditions with benefit in ulcerative colitis but a detrimental effect in Crohns disease. These differences have been the subject of much interest and scrutiny with the hope that they may offer some insight into the pathogenesis of the two conditions and possibly lead to alternative therapeutic options. Nicotine is probably the principal active ingredient in smoking responsible for the association; trials have shown it to be of some benefit in ulcerative colitis, but further research is required to establish its therapeutic role, and the relevant mechanisms responsible for its action. In this article, we review the role of smoking in inflammatory bowel disease and its implication for therapy.

A Randomized Trial of Nicotine Enemas for Active Ulcerative Colitis

BACKGROUND & AIMSnUlcerative colitis (UC) is largely a disease of nonsmokers in which transdermal nicotine improves the symptoms but often causes adverse events (AEs). Nicotine enemas cause fewer AEs and were used as supplemental treatment for active UC.nnnMETHODSnWe treated 104 patients with active UC with either 6-mg nicotine enemas or placebo enemas for 6 weeks in a randomized double-blind study. Patients continued their oral therapy, if any, for UC: 68 patients were taking mesalamine, 15 patients were taking prednisolone, and 12 patients were taking thiopurines during the study. Clinical, sigmoidoscopic, and histologic assessments were made at baseline and at the end of the study and symptoms were recorded daily on a diary card. The primary end point was induction of clinical remission and clinical improvement also was measured by the UC disease activity index. After the study, patients then used nicotine enemas daily for 4 weeks and sigmoidoscopy with a biopsy examination was repeated. AEs and salivary cotinine levels were monitored throughout the study.nnnRESULTSnClinical remission was achieved in 14 of 52 (27%) patients on active treatment and 14 of 43 (33%) patients on placebo (P = .55). The UC disease activity index improved by 1.45 points in the active group and by 1.65 points for those on placebo (P = .88). Only 1 patient discontinued treatment because of an AE (abdominal pain). In the 47 patients taking mesalamine only, active treatment conferred benefit that was not statistically significant; disease remission occurred in 9 of 25 patients on active therapy and 4 of 21 patients on placebo (P = .20).nnnCONCLUSIONSnSix-milligram nicotine enemas were well tolerated but were not found to be efficacious for active UC.

Pharmacokinetics of nicotine carbomer enemas: A new treatment modality for ulcerative colitis

Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic value in the active disease. Because side effects are common, we developed a topical enema formulation of nicotine.

Intra-luminal nicotine reduces smooth muscle tone and contractile activity in the distal large bowel

BACKGROUNDnNicotine may be of therapeutic value in ulcerative colitis (UC), although its mechanism of action has not been established.nnnOBJECTIVEnTo examine the effect of a solution of nicotine on sustained resting pressure (tone) and contractile activity in the human colon.nnnMETHODSnTen healthy volunteers, and seven with UC in symptomatic remission took part; all were non-smokers. All 17 subjects were given nicotine or placebo solution on two separate occasions in a randomized sequence. A water-perfused manometry catheter, with openings at 5, 10 and 15 cm from the tip, was placed by rigid sigmoidoscopy in the recto-sigmoid region. Baseline tone and activity were measured for 15 min prior to instillation of 20 ml of saline alone or with nicotine, 1.2 mg, at pH 4.5. Observations were made over the subsequent 15-20 min.nnnRESULTSnBaseline spontaneous activity in all subjects showed both high- and low-frequency components; in three patients with UC, the low-frequency activity was of high amplitude. The nicotine reduced both tone and activity in all subjects, with reduction or abolition of the large contractions in UC. Tone in all 17 subjects was reduced significantly at 3 min after nicotine (P = 0.000015, sign test); the rate of recovery varied in individuals. Results from normals and UC did not differ significantly from each other. No significant change in tone or activity was observed with the saline solution.nnnCONCLUSIONnIntra-luminal nicotine significantly reduces both smooth muscle tone and contractile activity in the recto-sigmoid colon in both normal subjects and patients with UC.

Upper gastrointestinal cancer in its early stages is predominantly asymptomatic

Background Current guidelines for urgent endoscopic investigation of dyspepsia are based on alarm features and age criteria. However, there is concern that this type of guideline may delay the diagnosis of upper gastrointestinal (GI) cancer. Objective To evaluate the timescale of symptoms in upper GI cancer, determining whether patients experience dyspepsia before developing alarm features, and hence whether the current guidelines may delay diagnosis. Method A prospective study of patients diagnosed with upper GI cancer between May 2004 and January 2007. A structured interview was performed directly after endoscopic diagnosis regarding the nature and duration of symptoms. Results Alarm features were present in 56 of the 60 patients interviewed. Only eight patients reported dyspepsia before developing their alarm feature; three of these had complained of dyspepsia for >10 years, one reported dyspepsia preceding the alarm feature by 18 months and in four patients dyspepsia preceded the alarm feature by ≤8 weeks. Preceding dyspepsia did not cause significant delay in referral for endoscopy (p=0.670), or affect tumour stage at diagnosis (p=0.436) or length of survival (p=0.325). Conclusion It is rare for patients with upper GI cancer to experience significant dyspepsia before the onset of their alarm symptoms, therefore limiting the prospect of an earlier diagnosis. Early upper GI cancer is largely asymptomatic, and guidelines should limit the availability of open-access gastroscopy in simple dyspepsia. Increased awareness of the need to urgently investigate patients with concurrent anaemia or weight loss is required.

PTH-044 Improving safety and reducing error in endoscopy (ISREE) – a jag initiative

Introduction JAG is committed to providing universal high quality and safe endoscopy as embedded in the Global Rating Scale. This requires acknowledgement that error is common, may not result in harm or complications, but that addressing latent risk can prevent patient safety incidents. Many errors relate to failures in human factors, ENTS and teamwork, which require training and assessment. Medical error is more prevalent in situations of complexity. Though generally safe, endoscopy is a complex task, performed in teams. As population demographics evolve, straight-to-test pathways become embedded and complex therapeutic options extended; endoscopists need to develop a proactive culture towards safety and learning from error. Aims JAG aims to develop a work stream to Improve Safety and Reduce Error in Endoscopy (ISREE). A 1u2009day workshop was designed to develop an implementation plan to achieve this goal. Methods 35 multi-disciplinary clinicians and a patient with specific expertise in this area were invited to ISREE workshop. Participants were asked to recall as many endoscopy adverse events or errors as possible. Key presentations highlighted the background to medical error, how to investigate it, development of non-technical skills frameworks (anaesthetics and endoscopy), safe sedation, human factors training and implementation science. A patient recounted her experiences of endoscopy. Facilitated group sessions focused on 5 key areas – improving training in ENTS and human factors, error prevention, reporting error, learning from error and managing underperformance (endoscopists, teams or units). Wider discussion synthesised a list of feasible actions that JAG could prioritise for staged implementation. Results Multiple errors were reported by all delegates and recurrent themes were common. Examples related to wrong patient for procedure (n=4), histology mislabelling (n=5), drug errors (n=3) and failure to follow MDT advice (n=1). 23 key priorities were agreed and formulate an implementation strategy for JAG (table 1): Table. No title available. Summary JAG plans to develop a 5 y ISREE Implementation Strategy reflecting the identified priorities to 1) improve endoscopists training in effective error reporting and learning and 2) implement system level approaches to safety and performance improvement. JAG also aims to improve its communication to disseminate learning and support endoscopy services in the UK.

Endoscopy in 2017: a national survey of practice in the UK

Introduction The Joint Advisory Group on Gastrointestinal Endoscopy (JAG), hosted by the Royal College of Physicians, London, oversees the quality assurance of endoscopy services across the UK. Additional questions focusing on the pressures faced by endoscopy units to meet targets were added to the 2017 annual Global Rating Scale (GRS) return. This provides a unique insight into endoscopy services across all nations of the UK involving the acute and non-acute Nation Health Service sector as well as the independent sector. Methods All 508 services who are registered with JAG were asked to complete every field of the survey online in order to submit their completed April 2017 GRS return. Results A number of services reported difficulty in meeting national waiting time targets with a national average of only 55% of units meeting urgent cancer wait targets. Many services were insourcing or outsourcing patients to external providers to improve waiting times. Services are striving hard to increase capacity by backfilling lists and working weekends. Data collection was done in most units to reflect productivity but not to look at demand and capacity. Some of the units did not have an agreed capacity plan. The Did Not Attend rates for patients in the bowel cancer screening programme were much lower compared with standard lists. Conclusion This review highlights the increased pressure endoscopy services are under and the ‘just about coping’ situation. This is the first published overview of different aspects of UK-wide endoscopy services and the future challenges.

Late gastrointestinal effects of pelvic radiation: a nurse-led service

There are currently at least 2 million people in the UK living with and following a cancer diagnosis. Typically four out of every ten people with cancer will receive radiotherapy, but a large proportion of people who have pelvic radiotherapy may go on to develop gastrointestinal (GI) symptoms. This includes rectal bleeding and faecal incontinence, which can have a huge impact on quality of life. These problems often go under-reported by patients and are also under-recognised or under-treated by health professionals. Cancer survivorship is a growing topic that is likely to have a major impact on the NHS, with increasing numbers of patients presenting. A late GI effects of pelvic radiotherapy clinic was set up to address these growing needs of patients with GI symptoms following radiotherapy. This article also shares insights from a doctoral study that is underway looking at peoples experiences of living with symptoms following their treatment, in order to improve awareness of the major impact that this can have.

PWE-031 How many Colorectal Cancers (CRC) Have Been Missed in the 36 Months after ‘Normal’ Lower Gi Endoscopy (Colonoscopy/Flexible Sigmoidscopy)

Introduction Colonoscopy and flexible sigmoidscopy are the primary tools for diagnosis of CRC, although they have false negative rates of 2–6%.¹ The aim of this study was to estimate how frequently lower GI endoscopy might have failed to detect cancer within 36 months preceding a confirmed diagnosis of CRC. Methods We identified 253 patients diagnosed with CRC between Sep 2010 – Aug 2012 from the database of cellular pathology in Cardiff and Vale University Health Board. Medical records were reviewed for the results of colonoscopy, flexible sigmoidscopy, histology and CT imaging. Patients with missed cancer were those who had had a ‘normal’ (if no cancer discovered) lower GI endoscopy procedure 1–36 months before diagnosis. We examined the characteristics that might be risk factors for missed CRC. Results Among the 253 patients included in the study, cancer was located in the rectosigmoid colon (78.5%), descending colon (2.7%), splenic flexure (1.9%), transverse colon (4.3%), hepatic flexure (1.1%) and right colon (9.4%). We identified 10 (5 females, 5 males, mean age 80 years, range 42–92) patients (3.9%) who had had colonoscopy and/or flexible sigmoidscopy that had not shown CRC 1–36 months prior to the final diagnosis. In the missed cancer group only one flexible sigmoidscopy was incomplete due to suboptimal bowel preparation and difficult sigmoid bend. Nine patients had false negative lower GI endoscopy. The median diagnostic delay was 13.6 months (1–36). Two of the missed cancers were diagnosed with Dukes’ C colon cancer, one with Dukes’ D colon cancer and one presented with emergency complications due perforation. Of the ten missed cancers, eight were in rectosigmoid colon, one in the transverse colon and one in the ascending colon. Conclusion Bressler et al reported 2–6% missed CRC at colonoscopy performed 6–36 months prior to a final diagnosis of cancer.¹ Our miss rates are in line with previous studies. However, the available literature suggests that lesion miss rate is higher for proximal colonic tumours. In our study, the missed cancers were predominantly in the rectosigmoid colon (3.1%) and were minimal in the right colon (0.4%). The reasons for missed cancers in our study are likely related to incomplete procedure, suboptimal bowel preparation, inadequate technique, failure to recognise flat lesions and diverticulosis. Optimal withdrawal technique, good luminal view, frequent position change, high quality bowel prep and adequate time for inspection are of utmost importance to minimise the rate of missed CRC. Disclosure of Interest None Declared. Reference Bressler B, et al. Rates of new or missed colorectal cancer after colonoscopy and their risk factors: a population–based study. Gastroenterology 2007; 132(1):96–102