Owen Epstein

A prospective study of colonoscopy practice in the UK today: are we adequately prepared for national colorectal cancer screening tomorrow?

Aim: To study the availability and quality of adult and paediatric colonoscopy in three National Health Service (NHS) regions. Method: A prospective four month study of colonoscopies in North East Thames, West Midlands, and East Anglia. Patients: Subjects undergoing colonoscopy in 68 endoscopy units. Results: A total of 9223 colonoscopies were studied. The mean number of colonoscopies performed over the four month period was 142 in district general hospitals and 213 in teaching hospitals. Intravenous sedation was administered in 94.6% of procedures, but 2.2% and 11.4% of “at risk” patients did not have continuous venous access or did not receive supplemental oxygen, respectively. Caecal intubation was recorded in 76.9% of procedures but the adjusted caecal intubation rate was only 56.9%. Reasons for failing to reach the caecum included patient discomfort (34.7%), looping (29.7%), and poor bowel preparation (19.6%). A normal colonoscopy was reported in 42.1%. The most common diagnosis was polyps (22.5%) followed by diverticular disease (14.9%). Inflammatory bowel disease was recorded in 13.9% and carcinoma in 3.8%. Only half of the patients remembered being told of possible adverse events prior to the procedure. Rectal bleeding requiring admission following colonoscopy was reported in six patients. The overall perforation rate was 1:769 and colonoscopy was considered a possible factor in six deaths occurring within 30 days of the procedure. Only 17.0% of colonoscopists had received supervised training for their first 100 colonoscopies and only 39.3% had attended a training course. Conclusion: There is serious under provision of colonoscopy service in most NHS hospitals. Endoscopy sedation guidelines are not always adhered to and there is a wide variation in practice between units. Colonoscopy is often incomplete and does not achieve the target 90% caecal intubation rate. Serious complications of colonoscopy were comparable with previous studies. Training in colonoscopy is often inadequate and improved practice should result from better training.

EFFECTS OF CYCLOSPORIN A ON SUPPRESSOR AND INDUCER T LYMPHOCYTES IN PRIMARY BILIARY CIRRHOSIS

There is a significant decrease in the ratio of inducer (helper) to suppressor T lymphocytes in the peripheral blood of patients with primary biliary cirrhosis (PBC). These changes are not seen in other forms of cholestatic liver disease, but are similar to those described in chronic graft-versus-host disease. Cyclosporin A treatment increased the proportion of suppressor A lymphocytes and improved liver function in 6 patients with PBC. This indicates that cyclosporin A is an immunoregulatory drug. Unfortunately nephrotoxicity precluded long-term use.

Colon capsule endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless ingestible capsule technique that allows exploration of the colon without the need for sedation and gas insufflation. Although it is already available in European and other countries, the clinical indications for CCE as well as the reporting and work-up of detected findings have not yet been standardized. The aim of this evidence-based and consensus-based guideline, commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare providers with a comprehensive framework for potential implementation of this technique in a clinical setting.

Abnormalities of the electrogastrogram in functional gastrointestinal disorders

OBJECTIVE:Cutaneous electrogastrography records gastric electrical activity and detects gastric arrhythmias. Abnormalities of the electrogastrogram have been described in a variety of disorders, but their specificity and their prevalence in patients with functional gastrointestinal disorders has not been reported. The aim of this study was to assess the specificity of electrogastrography as well as the prevalence and pattern of abnormalities in functional dyspepsia and irritable bowel syndrome.METHODS:Electrogastrography was performed in 170 patients with functional dyspepsia, 70 patients with irritable bowel syndrome, 20 patients with gastroesophageal reflux disease, and 30 asymptomatic controls. The abnormal electrogastrogram was defined as <70% normal electrical activity either before or after a test meal.RESULTS:The electrogastrogram was abnormal in 36% of patients with functional dyspepsia and in 25% with irritable bowel syndrome who complained of concurrent dyspepsia. The electrogastrogram was normal in 93% of asymptomatic controls, 90% of patients with gastroesophageal reflux, and 92% of patients with irritable bowel syndrome who did not complain of dyspepsia. As a group, functional dyspepsia patients had a greater degree of tachygastrias both before (p < 0.02) and after (p < 0.01) a test meal. The electrical frequency after the test meal was also more unstable (p < 0.003).CONCLUSIONS:The electrogastrogram is abnormal in approximately 36% of functional dyspepsia patients and has a specificity of approximately 93%. Electrogastrography defines a subgroup of patients with functional dyspepsia and electrical rhythm disturbance. In irritable bowel syndrome, the electrogastrogram is usually abnormal only if concurrent dyspepsia is present.

D-PENICILLAMINE TREATMENT IMPROVES SURVIVAL IN PRIMARY BILIARY CIRRHOSIS

The copper-chelating, immunological, and antifibrotic effects of D-penicillamine indicated that it might be suitable for the treatment of primary biliary cirrhosis (PBC). In a randomised clinical trail, 55 PBC patients received penicillamine (600 mg daily), and 32 received a placebo. Drug reactions developed in 16 patients on penicillamine. All deaths occurred in patients with stage 3 or 4 (late stage) liver histology on entry to the study. 5 (14%) of 37 penicillamine-treated patients and 10 (43%) of 23 placebo patients have died (p less than 0.01). Improvement in survival only became evident after 18 months. Survivors in the penicillamine group demonstrated a significant fall in serum aspartate transaminase, serum immunoglobulins, and liver copper concentrations. On follow-up liver biopsy 12-72 months (median 33) after joining the study, 21% of penicillamine-treated patients had less pronounced inflammation and piecemeal necrosis, whereas there had been no improvement in patients on placebo (p less than 0.02). Penicillamine did not retard the histological evolution of the liver disease from the early prefibrotic stages to the late fibrotic or cirrhotic stages. Both the copper-chelating and immunological effects of penicillamine are probably important in improving survival. The excellent prognosis of patients with PBC in its early histological stages, and the failure of penicillamine to prevent histological progression from early to late stages, suggests that penicillamine treatment should not be given to patients with PBC in the early (stage 1 or 2) histological phase of the disease. Penicillamine treatment is recommended in patients once liver biopsy has demonstrated histological results typical of late stage 3 or 4 PBC.

Reduction of Immune Complexes and Immunoglobulins Induced by D-Penicillamine in Primary Biliary Cirrhosis

Penicillamine has an effect on immune complexes and immunoglobulins both in vivo and in vitro. We therefore studied the effect of penicillamine on immune complexes and immunoglobulins in primary biliary cirrhosis. Twenty-eight patients were randomly allocated into a treatment group receiving 600 to 900 mg of penicillamine, or a control group, and followed for a maximum of 24 months. After 12 and 24 months, serum immune complexes had fallen significantly in treated patients as compared to controls (P less than 0.05, P less than 0.01). Treatment reduced IgA, IgG and IgM concentrations, with IgM being significantly different from controls at six, 12 and 24 months (P less than 0.01). Over 24 months, serum aspartate transaminase levels fell in treated patients but rose in controls (P less than 0.01). Bilirubin concentrations increased at a slower rate in treated patients. Penicillamine may favorably influence the course of primary biliary cirrhosis by its immunologic action in addition to its copper-chelating action.

Granulomas in Primary Biliary Cirrhosis: A Prognostic Feature

To evaluate the significance of granulomas in primary biliary cirrhosis, 295 liver biopsy specimens from 100 patients with primary biliary cirrhosis were reviewed. Granulomas were found in specimens from 54 patients and were less frequent as histologic stage increased. They often persisted in multiple specimens from individual patients. Granulomas did not correlate with clinical presentation or biochemical values, but were associated with better survival since of the 18 patients who died, only 2 showed granulomas on biopsy. To test this finding in patients at a uniform stage of progression, patients with late primary biliary cirrhosis were evaluated separately. Patients with and without granulomas were closely matched in clinical, laboratory, and histologic features. Although 23 of these 57 patients showed granulomas, they were present in only 1 of 14 patients who died. Thus, the presence of granulomas in primary biliary cirrhosis seems to be of prognostic significance, independent of previously reported prognostic indicators.

Meta-analysis: the relative efficacy of oral bowel preparations for colonoscopy 1985-2010

Aliment Pharmacol Ther 2012; 35: 222–237

Primary Biliary Cirrhosis

Primary biliary cirrhosis is a disease with progressive granulomatous destruction of small intrahepatic bile ducts. It is of unknown etiology. The disease is associated with a profound immunological disturbance, and this has been related to the bile duct destruction (TABLE 1). The final event seems to be an attack by cytotoxic lymphocytes on biliary epithelium. The antigen might be the individual’s own human leukocyte antigens (HLA’s), antigens also known as avidin-biotin complex (ABC), which are present in high concentrations on biliary epithelium. It is unclear why the reaction should be to normal rather than foreign proteins. Perhaps the patient’s own lymphoid system is at fault so that self and self antigens are not recognized. This could be due to failure of schooling by cytotoxic T cells in the thymus. These cells are regulated by suppressor cells which have been shown to be diminished both in number and function in primary biliary cirrhosis.’ Alternatively, and perhaps more likely, the HLA proteins may have become foreign due to an extrinsic environmental factor. The identification of such a factor is an ongoing challenge to all those investigating primary biliary cirrhosis. In many respects, primary biliary cirrhosis is analogous to the graft-versus-host syndrome as seen, for instance, after bone marrow transplants and where the immune system has become sensitized to foreign HLA proteins? Structural changes in the bile ducts are similar. Other ducts, such as the lacrimal and pancreatic ducts,) with high concentrations of HLA’s on their epithelia are involved. The condition can be viewed as a dry gland syndrome.’ Ultrastructural changes in the bile ducts are similar. The granulomas might be related to immune complexes. Indeed, complement has been identified within them. They predominantly consist of cytotoxic T cells, monocytes, and macrophages, however, and such compositions are indicative of cell-mediated tissue injury. Patients with many granulomas are usually seen early in the disease where bile duct destruction is not prominent and the prognosis better. Such patients have normal or only slightly decreased concentrations of suppressor cells in the peripheral blood. This might be related to the rarity of diffuse bile duct destruction and the good progno~is.~ Copper is retained in the liver, but in a nonhepatotoxic form?

Hypertrophic hepatic osteoarthropathy: Clinical, roentgenologic, biochemical, hormonal and cardiorespiratory studies, and review of the literature

Twenty patients with biopsy proved liver disease, and roentgenologic features of hypertrophic osteoarthropathy have been studied, and the literature has been reviewed. The syndrome is a rare association of many chronic liver diseases, including primary biliary cirrhosis, bile duct carcinoma, benign bile duct stricture, chronic active hepatitis, posthepatitic cirrhosis and alcoholic cirrhosis. Patients may be asymptomatic, although bone pain, arthralgia or arthritis may be presenting symptoms. Ninety per cent of the patients are clinical jaundiced at the time of diagnosis, and 95 per cent have digital clubbing. The distal tibia and fibula are the first bones to become involved, although wrist, foot bones, femurs, hand bones and humeri may be affected in order of frequency. There is no correlation between the presence of esophageal varices or surgical portacaval shunts and the extent of the syndrome, neither is there a correlation with the degree of liver function impairment. Serum calcium and phosphate levels are normal, as is urinary hydroxyproline and estrogen excretion. There was no evidence to implicate elevated levels of growth hormone or overdosage of vitamin A. Although the majority of patients tested had mild arterial hypoxemia, increased cardiac output and evidence of right to left shunting, these were also present in disease-matched control subjects without osteoarthropathy. For screening purposes, patients with chronic liver disease and clubbing should have roentgenologic studies of the lower tibias and fibulas, to select those patients suitable for a more extensive skeletal survey.