Eoin Lalor

Cholestatic hepatocellular injury with azathioprine: A case report and review of the mechanisms of hepatotoxicity

Azathioprine is a drug commonly used for the treatment of inflammatory bowel disease, organ transplantation and various autoimmune diseases. Hepatotoxicity is a rare, but important complication of this drug. The cases reported to date can be grouped into three syndromes: hypersensitivity; idiosyncratic cholestatic reaction; and presumed endothelial cell injury with resultant raised portal pressures, venoocclusive disease or peliosis hepatis. The components of azathioprine, 6-mercaptopurine and the imidazole group, may play different roles in the pathogenesis of hepatotoxicity. The strong association with male sex, and perhaps with human leukocyte antigen type, suggests a genetic predisposition of unknown type. Many of the symptoms of hepatotoxicity, such as nausea, abdominal pain and diarrhea, can be nonspecific and can be confused with a flare-up of inflammatory bowel disease. As well, the subtype resulting in portal hypertension can occur without biochemical abnormalities. A 63-year-old man with Crohns disease who is presented developed the rare idiosyncratic form of azathioprine hepatotoxicity, but also had a severe disabling steroid myopathy, peripheral neuropathy, resultant deep venous thrombosis and pulmonary embolism related to immobility, and a nosocomial pneumonia. His jaundice and liver enzyme levels improved markedly on withdrawal of the drug, returning to almost normal in five weeks. Treating inflammatory bowel disease effectively while trying to limit iatrogenic disease is a continuous struggle. Understanding the risks of treatment is the first important step. There must be a low threshold for obtaining liver function tests, especially in men, and alertness to the need to discontinue the drug or perform a liver biopsy should patients on azathioprine develop liver biochemical abnormalities, unexplained hepatomegaly or signs of portal hypertension.

Endoscopic perforation rates at a Canadian university teaching hospital.

BACKGROUND Despite advances in training, operative techniques and endoscopic technology, upper and lower endoscopic procedures continue to have potential for intestinal perforation. Perforation rates provided to patients at the time of consent have frequently been derived from historical cohorts and survey datasets. OBJECTIVE This study examined the perforation rates of upper and lower endoscopic procedures at a major Canadian tertiary care centre. METHODS Inpatient and outpatient gastroscopies and colonoscopies performed during a three year period were evaluated. Endoscopies with perforations occurring within 14 days of procedure were retrospectively isolated using the International Classification of Diseases - 9th Revision code descriptions, then retrieved and hand searched to confirm a procedure-related perforation. Data were extracted to identify risk factors and patient outcomes. RESULTS A total of 21,217 endoscopies (13,792 gastroscopies and 7425 colonoscopies) were reviewed. Of these, 359 were identified, isolated and hand searched for confirmation of a perforation event. Eighteen were found to have an endoscopy-associated perforation. Ten perforations occurred with colonoscopy (0.13%) (incidence, 1.3/1000 procedures), resulting in one death (0.013%) (incidence, 0.13/1000 procedures). Eight perforations occurred with gastroscopy (0.06%) (incidence, 0.6/1000 procedures), resulting in zero mortality. Of colonoscopy procedures the rate of perforation with diagnostic colonoscopy was 0.13% (incidence, 1.3/1000 procedures) and with therapeutic colonoscopy was 0.14% (incidence, 1.4/1000 procedures). Of gastroscopy procedures the rate with therapeutic gastroscopy was 0.15% (incidence, 1.5/1000 procedures). No perforations occurred with diagnostic gastroscopy. CONCLUSION Gastroscopy and colonoscopy procedures, especially those with therapeutic maneuvers, continue to carry morbidity and mortality risks associated with perforation.

The utility of endoscopy in the management of patients with gastroesophageal reflux symptoms

Objective:The utility of endoscopy in the management of patients with symptoms of gastroesophageal reflux disease (GERD) is unclear. The purpose of this prospective study was to assess the impact of endoscopy on the subsequent management of patients with uncomplicated reflux symptoms.Methods:A total of 742 patients underwent endoscopy for symptoms of GERD. Endoscopists recorded the therapy before endoscopy, the findings of endoscopy, and the treatment recommendations after endoscopy.Results:There was no difference in pre-endoscopy therapy or grade of esophagitis in subjects undergoing endoscopy for failed therapy versus GERD symptoms alone. After endoscopy, the most common strategy for patients taking omeprazole was to maintain or increase the dose. For those taking an H2 blocker before endoscopy, the most common outcome was to switch the patient to omeprazole, independent of the grade of esophagitis.Conclusion:Most patients undergoing endoscopy for symptoms of GERD were switched to omeprazole regardless of the endoscopic findings. No esophageal cancer was identified and the incidence of Barretts esophagus was low. It appears that endoscopy itself did not change the management of patients receiving H2-blocker therapy. A trial of a proton pump inhibitor before endoscopy should be considered.

Clinical experience with infliximab for Crohn's disease: the first 100 patients in Edmonton, Alberta.

OBJECTIVE To determine whether the clinical efficacy and safety of infliximab in diverse clinical referral practices was similar to that seen in the randomized, controlled clinical trials. METHODS Data were gathered from a review of charts of 109 consecutive patients with inflammatory and/or fistulizing Crohns disease who received infliximab infusions. Responses were recorded based on the physicians global clinical assessment and classified as complete, partial or nonresponse. RESULTS One hundred nine patients were treated with one to nine infusions of infliximab at a dose of 5 mg/kg and followed up for a median of 24 weeks (range one to 40 weeks). Fifty-four patients were treated for inflammatory disease, 38 for fistulizing disease and 17 for both. Clinical response occurred in 73% (17% complete response, 55% partial response). The clinical response rate did not vary relative to patient demographics, disease distribution, indication for infliximab, or the concomitant use of corticosteroids or immune modifiers. For those taking concomitant immune modifiers, the response rate was 75%. The median time to response was two weeks (range one to six weeks). The median duration of response was 12 weeks (range six to 88 weeks). Reduction or cessation of steroids was possible in 17 of 32 patients. Adverse events related to infliximab occurred in 7% of patients. These events were characterized as mild and did not require stoppage of infliximab therapy, except in one patient who had a treatable anaphylactic-like infusion reaction. CONCLUSIONS The patient group in the present study realized significant clinical benefit, with minimal adverse effects, following treatment with infliximab. Clinical response rates paralleled those previously described in placebo controlled trials and retrospective clinical practice reviews. Nevertheless, the complete response rate (ie, remission) in this patient group was lower than that previously described.

Defining the role of fiberoptic sigmoidoscopy in the investigation of patients presenting with bright red rectal bleeding

OBJECTIVE:This study was done to determine whether sigmoidoscopy could theoretically constitute sufficient investigation for some patients with bright red rectal bleeding.METHODS:One hundred and forty-three patients undergoing investigative colonoscopy for bright red rectal bleeding and whose source of bleeding was identified were studied. The investigation took place in a large urban hospital over an 11-month period. Data obtained included changes in stool pattern, characteristics of the bleeding, lesions identified, and the distance of the lesion from the anus.RESULTS:In patients younger than 55 yr, all serious lesions except for one malignancy in a patient with massive bleeding lay within 60 cm of the anus and theoretically within reach of the fiberoptic sigmoidoscope. The mixing of red blood with stool was commonly due to distal lesions, especially hemorrhoids.CONCLUSIONS:In young persons with bright red rectal bleeding, fiberoptic sigmoidoscopy may prove to constitute appropriate initial investigation.

A prospective audit of patient experiences in colonoscopy using the Global Rating Scale: A cohort of 1187 patients

BACKGROUND The Global Rating Scale (GRS) comprehensively evaluates the quality of an endoscopy department, providing a patient-centred framework for service improvement. OBJECTIVE To assess patient experiences during colonoscopy and identify areas that need service improvement using the GRS. METHODS Consecutive outpatients undergoing colonoscopy were asked to complete a pre- and postprocedure questionnaire. Questions were based on GRS items and a literature review. The preprocedure questionnaire addressed items such as patient characteristics and information provision. The postprocedure questionnaire contained questions regarding comfort, sedation, the attitude of endoscopy staff and aftercare. RESULTS The preprocedure questionnaire was completed by 1,187 patients, whereas the postprocedure part of the questionnaire was completed by 851 patients (71.9%). Fifty-four per cent of patients were first seen in the outpatient clinic. The indication for colonoscopy was explained to 85% of the patients. Sixty-five per cent of the patients stated that information about the risks of colonoscopy was provided. Sedation was used in 94% of the patients; however, 23% judged the colonoscopy to be more uncomfortable than expected. Ten per cent of patients rated the colonoscopy as (very) uncomfortable. Preliminary results of the colonoscopy were discussed with 87% of patients after the procedure. Twenty-one per cent of the patients left the hospital without knowing how to obtain their final results. Being comfortable while waiting for the procedure (OR 9.93) and a less uncomfortable procedure than expected (OR 2.99) were important determinants of the willingness to return for colonoscopy. CONCLUSIONS The present study provided evidence supporting the GRS in identifying service gaps in the quality of patient experiences for colonoscopy in a North American setting. Assessing experiences is useful in identifying areas that need improvement such as the provision of pre- and postprocedure information.

Recognizing immunoglobulin G4 related overlap syndromes in patients with pancreatic and hepatobiliary diseases.

The first description of autoimmune pancreatitis and elevated serum immunoglobulin-G4 (IgG4) in 2001 heralded further reports of several related autoimmune diseases with raised IgG4 levels. It is now recognized that a spectrum of overlap syndromes associated with increased IgG4 and biopsy evidence of IgG4-producing plasma cells, which has now been convincingly linked with cholangitis, autoimmune hepatitis, Sjögrens syndrome, nephritis and retroperitoneal fibrosis. Collectively, this disease cluster is referred to as IgG4-related systemic disease. The importance of making the correct diagnosis is underscored by the management of individuals with IgG4-related systemic disease. In the first instance, patients generally have a dramatic response to immunosuppressive therapy, whereas patients with other forms of cholangitis and pancreatitis do not. Also, surgical management of pancreatic malignancy can be avoided once the correct diagnosis of IgG4-related disease has been made. In the present review, an overview of the current information regarding the role of IgG4 and IgG4-positive cells affecting the biliary system, pancreas and liver is provided.

The clinical impact and cost implications of endoscopic ultrasound on the use of endoscopic retrograde cholangiopancreatography in a Canadian university hospital

BACKGROUND Endoscopic ultrasound (EUS) is a safe alternative to endoscopic retrograde cholangiopancreatography (ERCP) for diagnostic biliary imaging in choledocholithiasis. Evidence linking a decline in diagnostic ERCP with the introduction of EUS in clinical practice is limited. OBJECTIVE To assess the clinical impact and cost implications of a new EUS program on diagnostic ERCP at a tertiary referral centre. PATIENTS AND METHODS A retrospective review was performed of data collected during the first year of EUS at the University of Alberta Hospital (Edmonton, Alberta). Patients were referred for ERCP because of suspicion of choledocholithiasis based on clinical, biochemical and/or radiological parameters. If they were assessed to have an intermediate probability of choledocholithiasis, EUS was performed first. ERCP was performed if EUS suggested choledocholithiasis, whereas patients were clinically followed for six months if their EUS was normal. Cost data were assessed from a third-party payer perspective, and cost savings were expressed in terms of ERCP procedures avoided. RESULTS Over 12 months, 90 patients (63 female, mean age 58 years) underwent EUS for suspected biliary tract abnormalities. EUS suggested choledocholithiasis in 20 patients (22%), and this was confirmed by ERCP in 17 of the 20 patients. EUS was normal in 69 patients, and none underwent a subsequent ERCP during a six-month follow-up period. One patient had pancreatic cancer and did not undergo ERCP. The sensitivity and specificity of EUS for choledocholithiasis were 100% and 96%, respectively. A total of 440 ERCP procedures were performed over the same 12-month period, suggesting that EUS resulted in a 14% reduction in ERCP procedures (70 of 510). There were no complications of EUS. The cost of 90 EUS procedures was

Endoscopists' opinions of indications for upper gastrointestinal endoscopy.

42,840, compared with

Alberta Gastroenterologists Symposium: A Debate of the Proposal that Patients with Duodenal Ulcer in 1992 Should be Treated with Antibiotics

108,854 for 70 ERCP procedures. The cost savings for the first year were