Randomised clinical trial: MRCP-first vs. ERCP-first approach in patients with suspected biliary obstruction due to bile duct stones.

BACKGROUND: The preferred initial investigation with either magnetic resonance (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) in patients with suspected biliary obstruction remains controversial in many clinical settings. AIM: To assess the effectiveness of an initial MRCP vs. ERCP in the work-up of patients at moderate likelihood of a suspected biliary obstruction. METHODS: Patients with an unconfirmed benign biliary obstruction, based on laboratory and ultrasound findings, were randomised to an ERCP-first or MRCP-first strategy, stratified by level of obstruction. The primary outcome was the occurrence of a disease or procedure-related bilio-pancreatic adverse events within the next 12 months. Secondary outcomes were the number of subsequent bilio-pancreatic procedures, duration of hospitalisation, days away from activities of daily living (ADL), quality of life (SF-36) and mortality. RESULTS: We randomised 126 patients to ERCP-first and 131 to MRCP-first (age 54 ± 18 years, 62% female, 39% post-cholecystectomy). In follow-up, 18/126 (14.3%) ERCP-first and 25/131 (19.1%) MRCP-first patients experienced a procedure- or disease-related complication (P = 0.30) (disease-related in 13 and 18 patients, and procedure-related in 5 and 7 patients respectively). A cause of biliary obstruction was found in 39.7% vs. 49.6% of patients (P = 0.11). Sixty-six (50%) patients in the MRCP-first group ended up avoiding an ERCP in follow-up. ERCP-first and MRCP-first patients were away from usual activities for 3.4 ± 7.7 days and 2.0 ± 4.8 days respectively (P < 0.001). CONCLUSION: A strategy of MRCP-first decreased the need for subsequent MRCPs, but not complications. Further study is required to define factors influencing the eventual use of MRCP vs. ERCP in appropriately selected patients (ClinicalTrial.gov: NCT01424657).

Use and perceived effectiveness of non-analgesic medical therapies for chronic pancreatitis in the United States.

BACKGROUND: Effectiveness of medical therapies in chronic pancreatitis has been described in small studies of selected patients. AIM: To describe frequency and perceived effectiveness of non-analgesic medical therapies in chronic pancreatitis patients evaluated at US referral centres. METHODS: Using data on 516 chronic pancreatitis patients enrolled prospectively in the NAPS2 Study, we evaluated how often medical therapies [pancreatic enzyme replacement therapy (PERT), vitamins/antioxidants (AO), octreotide, coeliac plexus block (CPB)] were utilized and considered useful by physicians. RESULTS: Oral PERT was commonly used (70%), more frequently in the presence of exocrine insufficiency (EI) (88% vs. 61%, P < 0.001) and pain (74% vs. 59%, P < 0.002). On multivariable analyses, predictors of PERT usage were EI (OR 5.14, 95% CI 2.87-9.18), constant (OR 3.42, 95% CI 1.93-6.04) or intermittent pain (OR 1.98, 95% CI 1.14-3.45). Efficacy of PERT was predicted only by EI (OR 2.16, 95% CI 1.36-3.42). AO were tried less often (14%) and were more effective in idiopathic and obstructive vs. alcoholic chronic pancreatitis (25% vs. 4%, P = 0.03). Other therapies were infrequently used (CPB - 5%, octreotide - 7%) with efficacy generally <50%. CONCLUSIONS: Pancreatic enzyme replacement therapy is commonly utilized, but is considered useful in only subsets of chronic pancreatitis patients. Other medical therapies are used infrequently and have limited efficacy.

Endoscopic management of gastric varices: efficacy and outcomes of gluing with N-butyl-2-cyanoacrylate in a North American patient population.

BACKGROUND: Gastric variceal bleeding is associated with significant morbidity and mortality in patients with portal hypertension. Outside of North America, gastric variceal injection of N-butyl-2-cyanoacrylate has been shown to be safe and effective. The majority of studies on this mode of therapy are in Asian populations in which the etiology of portal hypertension differs from North America. AIM: To assess the safety and efficacy of gastric variceal glue injection in a North American population. METHODS: Consecutive patients that underwent glue injection of gastric varices in the Calgary Health Region from 2001 to 2006 were assessed. RESULTS: Thirty-four patients (19 men, 15 women) underwent a total of 47 separate gluing procedures. Of those presenting with active bleeding at endoscopy, immediate hemostasis was achieved in 93.8% of patients. Rebleeding within 48 h of gluing was observed after four procedures. Gastric varices were eradicated in 84.0% of cases. Complications included superior mesenteric vein thrombosis in one patient. Twenty-eight (82.4%) patients were alive at the end of follow-up. The treatment failure-related mortality rate was 2.1%. CONCLUSIONS: The present study is one of the few to assess the role of gastric variceal gluing in a North American population. Glue injection with cyanoacrylate is safe and effective in the treatment of bleeding gastric varices.

Pilot comparison of adhesion formation following colonic perforation and repair in a pig model using a transgastric, laparoscopic, or open surgical technique.

BACKGROUND AND STUDY AIM: Postoperative adhesions create significant morbidity and mortality. Natural orifice transluminal endoscopic surgery (NOTES) procedures may reduce or eliminate adhesions by avoiding disruption of the parietal peritoneum. The primary aim of this pilot study was to compare adhesion formation after performance and subsequent repair of colonic perforation via transgastric, laparoscopic, or open surgical techniques. The secondary aim was to test the feasibility and outcome of transgastric management of bowel perforation in a prepared model. MATERIAL AND METHODS: 15 Yorkshire pigs were divided into three groups of five: transgastric (needle-knife entry with balloon dilation over a wire), laparoscopic, and open surgical. Aspects of adhesion formation (density/vascularity, width of bands, and number of organ pairs involved) were compared after perforation and repair during the same procedure. Intra- and postoperative complications were documented during the 21-day survival period. RESULTS: All 15 pigs recovered fully with no immediate procedural complications. After 21 days, there was a trend towards a lower adhesion burden regarding density/vascularity and number of organ pairs involved, and a significant reduction in the width of the adhesive bands, when the transgastric group was compared with the surgical groups. Additionally, there was a trend towards decreased adhesions to the peritoneum in the transgastric group. CONCLUSIONS: Repair of colonic perforation during transgastric (NOTES) procedures appear feasible and safe in a porcine model. There appears to be a trend towards a lower rate of adhesion formation with the transgastric approach compared with laparoscopic or open surgery.

Small prophylactic pancreatic duct stents: an assessment of spontaneous passage and stent-induced ductal abnormalities.

BACKGROUND AND STUDY AIMS: Placing small stents in the pancreatic duct at endoscopic retrograde cholangiopancreatography reduces the risk of pancreatitis. However, this practice means that a second procedure might be required to remove the stent, and stents can also damage the duct. The aims of this study were to determine the frequency of spontaneous dislodgment and to assess the incidence of stent-induced ductal irregularities. PATIENTS AND METHODS: We performed a retrospective analysis of consecutive patients seen over a 3-year period (2001 - 2004) who had undergone placement of a 3-Fr pancreatic duct stent and in whom the fate of the stent had been documented. Radiographs were reviewed to determine stent passage at 30 days. If applicable, follow-up pancreatograms were reviewed to assess for stent-induced ductal abnormalities. Statistical analysis was performed using chi-squared and Fisher's exact tests for proportions, and 95 % binomial confidence intervals (CI) were calculated. RESULTS: Records for 125 consecutive patients who had had 3-Fr pancreatic stents placed were reviewed. The stents had passed spontaneously within 30 days in 110/125 patients (88 %). In the remaining 15 patients (12 %, 95 % CI 6.9 % - 19 %), the stents were still present on follow-up radiographs after a median time of 36 days, (range 31 - 116 days). Stent length, pancreatic sphincterotomy, and pancreas divisum had no effect on the likelihood of spontaneous passage. No stent-induced ductal irregularities were observed. CONCLUSIONS: Nearly 90 % of prophylactic 3-Fr pancreatic duct stents pass spontaneously within 30 days, and these stents were not observed to induce changes in the pancreatic duct.

Predicting the liver histology in chronic hepatitis C: how good is the clinician?

OBJECTIVE: Liver biopsy is believed to be necessary before antiviral treatment in hepatitis C. Studies have found symptoms and biochemistry poorly predictive of grade and stage. In practice, a combination of factors is used to anticipate histology. The aim of this study is to evaluate the ability of global clinical assessment to predict histology in hepatitis C. METHODS: Fifty-four consecutive patients referred to a university center for consideration of antiviral therapy were enrolled. Clinical and laboratory data were recorded as was a prediction of the inflammatory grade (0-3) and fibrotic stage (0-3), with fibrotic stage 3 referring to cirrhosis. Liver biopsies were read by a blinded pathologist. The predictive value of the clinical assessment and individual parameters was assessed. RESULTS: All predictions were < or = 1 point off the actual grade and stage. Thirty-six (66.7%) patients' grades and 41 (75.9%) patients' stages were exactly predicted. All four cirrhotic patients (sensitivity 100%, specificity 94%) and one case of hemochromatosis were correctly predicted. Spider nevi, organomegaly, white blood cell count < or = 4 x 10(9)/L, ALT > 120 U/L, bilirubin > 20 micromol/L, albumin < or = 35 g/L, and ferritin > 200 microg/L predicted grade > or =2. Stage > or =2 was associated with age > 40 yr, previous decompensation, spider nevi, organomegaly, white blood cell count < or = 4 x 10(9)/L, albumin < or = 35 g/L, platelets < or = 150 x 10(9)/L, and international normalized ratio > 1.2. Grade correlated with stage (Spearman coefficient = 0.54, p < 0.001). By multivariate analysis, ferritin plus spider nevi or hypoalbuminemia was independently predictive of inflammation. Spider nevi and thrombocytopenia, with either splenomegaly or hypoalbuminemia, were useful three-variable models for predicting fibrosis. The corresponding scoring systems produced useful likelihood ratios. CONCLUSIONS: Global clinical assessment mirroring clinical practice in a tertiary liver transplant center is moderately accurate in predicting grade and stage in hepatitis C. Liver biopsy is the current gold standard; however, the amount of new information gleaned is less than was perceived. The need for routine biopsy before antiviral treatment in hepatitis C should be reevaluated in a multicenter study.

Patient satisfaction after MRCP and ERCP.

OBJECTIVE: Magnetic resonance cholangiopancreatography (MRCP) is an accurate diagnostic test for detecting abnormalities of the pancreaticobiliary system. Because it is noninvasive, MRCP appears to be more tolerable than ERCP, although this has not been studied. The purpose of this study is to compare patient satisfaction after MRCP and ERCP performed sequentially. METHODS: We prospectively recruited 34 patients undergoing ERCP, for whom an MRCP was able to be performed before ERCP. Patient satisfaction was assessed by validated questionnaires using seven-point Likhert scales (individual ratings and direct comparisons). The following dimensions were explored: anxiety, pain, discomfort, tolerability (relative to expectations), willingness to repeat the procedure, and overall preference. Chi2 and Student's t tests (paired and unpaired) were performed, and 95% CIs were provided. RESULTS: Two patients (5.9%) were unable to undergo MRCP because of claustrophobia. The remaining 32 completed both tests (94% same day) and all questionnaires. Average age was 56+/-18 yr, and 66% were women. In 23 patients, some degree of biliary obstruction was suspected; nine patients had pancreatitis. Patients reported a lower degree of pain (p < 0.001) and discomfort (p = 0.047) with MRCP, but MRCP was more difficult than they expected (p = 0.0 12). Patients were marginally more willing to repeat MRCP (ns, p = 0.09). On direct comparisons, patients were more satisfied with MRCP regarding anxiety (p = 0.04) and pain (p = 0.001). Patients displayed a higher overall preference for MRCP compared with ERCP (p = 0.01); however, only 59% clearly preferred MRCP over ERCP. The most common problem with MRCP was claustrophobia or noise (n = 15), and the differences were more striking in the subgroup without this problem. The subgroup undergoing purely diagnostic ERCPs showed clear preferences for MRCP. CONCLUSIONS: In many respects, MRCP is well tolerated, and certain subgroups, especially those undergoing diagnostic ERCPs, prefer MRCP over ERCP. As an endoscopist, one needs to be aware of the limitations of MRCP and relay these to the patient, as it seems that patients find MRCP more difficult than anticipated, and a significant number still prefer ERCP over MRCP. Patient satisfaction may be further improved by reducing noise and claustrophobia with selective premedication, earplugs, and the use of the new quieter fenestrated magnetic resonance imaging scanners.

Hyperhomocysteinemia and inflammatory bowel disease: prevalence and predictors in a cross-sectional study.

OBJECTIVE: Homocysteine is a sulfur-containing amino acid formed during the demethylation of methionine. Vitamin B12 and folate deficiency and therapy with antifolate drugs may predispose patients with inflammatory bowel disease (IBD) to hyperhomocysteinemia. The known associations between hyperhomocysteinemia and smoking, osteoporosis, and thrombosis make it an interesting candidate as a pathogenetic link in IBD. The aim of this study was to identify the prevalence and risk factors of hyperhomocysteinemia in patients with IBD. METHODS: Sixty-five consecutive IBD patients were recruited from a tertiary outpatient gastroenterology practice. Fasting plasma homocysteine levels were measured, along with vitamin B12 and folate. Data regarding medication use, multivitamin use, disease location and severity, and extraintestinal manifestations of IBD were gathered. Homocysteine levels in 138 healthy control subjects were compared with the IBD cohort, and adjustments for age and sex were made using logistic regression. Multivariate analysis was performed to seek predictors of homocysteine levels. RESULTS: The mean age in the IBD cohort was 42+/-13.4 yr (+/-SD), and 43% were male. The mean disease duration was 13.8+/-9.4 yr, and 32% had used steroids within the last 3 months. Immunomodulator therapy had been used in 32%, and 75% had had an intestinal resection. Osteoporosis was present in 33% of patients. Five patients had experienced venous thrombosis or stroke, but only one of these had hyperhomocysteinemia. Of the 10 IBD patients (15.4%) with hyperhomocysteinemia, only two had vitamin B12 deficiency. The homocysteine levels in the IBD cohort cases and controls were 8.7 and 6.6 micromol/L, respectively (p < 0.05). IBD significantly increased the risk of hyperhomocysteinemia (adjusted odds ratio = 5.9 [95% CI: 1.5-24]). Advanced age, male sex, vitamin B12 deficiency or lower vitamin B12 serum levels, and multivitamin therapy were independently associated with higher homocysteine levels in the multivariate analysis (R2 = 0.55; p = 0.001). CONCLUSIONS: Hyperhomocysteinemia is significantly more common in patients with IBD compared with healthy controls, and is associated with lower (but not necessarily deficient) vitamin B12 levels.

Expandable metal biliary stenting in patients with recurrent premature polyethylene stent occlusion.

OBJECTIVES: Expandable metal stents are currently used to treat biliary tract obstruction. Few data exist on the role of metal stents in patients with recurrent premature plastic biliary stent occlusion. We report our preliminary results using an expandable metal biliary stent with enhanced stent flexibility in this group of patients. Our aim was to assess the efficacy of the Diamond biliary stent in the treatment of recurrent premature biliary plastic stent blockage. METHODS: From September 1997 to June 1998, six patients with inoperable biliary obstruction and at least one prior episode of plastic stent occlusion were treated with an expandable metal biliary prosthesis. There were four women and six men, with a mean age of 73+/-11 yr. Five patients had malignant biliary obstruction, and one inoperable patient had a biliary stricture secondary to chronic pancreatitis. Patients were followed-up prospectively until either stent occlusion or death. The patency duration of the metal stents was compared to that of the most recently placed plastic stents. RESULTS: All stents were successfully inserted endoscopically with visualized biliary drainage. No significant immediate postprocedural complications were noted. Median time from initial diagnosis of biliary obstruction to metal stent insertion was 35 wk (range 7-142), during which time patients had occluded a median of 4.5 plastic stents (range 2-5). Median patient survival was 117 days (15-312) and median time to blockage of the last plastic stent was 25.5 days (range 10-90 days). Three cases of metal stent occlusion occurred. One patient had early stent occlusion at 9 days because of debris and sludge clogging the metal stent. Two other patients developed stent occlusion at 120 and 157 days. Two stents remained patent until the patients' deaths at 15 and 87 days. Overall median stent patency was 139 days. The three patients who developed stent occlusion were treated with successful insertion of one or more plastic stents through the existing metal stent. Duration of metal stent patency was significantly longer than that of the last plastic stent (58.8 days longer; 95% CI [6.4, 111]; p = 0.03). CONCLUSIONS: Metal biliary prostheses represent an effective management strategy for recurrent plastic biliary stent obstruction. Patients in this subgroup may have a shorter duration of metal stent patency than the reported duration of stent patency in patients receiving initial metal stent placement. However the duration of patency still seems to be significantly longer than that of the most recently placed plastic stent.

Graft-versus-host disease after liver transplantation complicated by systemic aspergillosis with pancarditis.

Graft-versus-host disease after liver transplantation complicated by systemic aspergillosis with pancarditis. Can J Gastroenterol 2000;14(7):637-640. Acute graft-versus-host disease (GVHD) is a common complication after bone marrow transplantation, with characteristic rash and diarrhea being the most common features. After liver transplantation, however, this phenomenon is very rare. Most transplant patients are on a variety of medications, including immunosuppressants; therefore, the differential diagnosis of skin rash or diarrhea is broad. A 37-year-old man who underwent liver transplantation for primary biliary cirrhosis, and developed a rash and watery diarrhea, is presented. Skin and colonic biopsies confirmed acute GVHD. A pulse of intravenous steroids was given. The skin rash improved, but he developed pancytopenia. His course was complicated by central line infection, jugular and subclavian vein thrombosis, pseudomembranous colitis, recurrent bacteremia, cholestasis on total parenteral nutrition and cytomegalovirus infection. After the onset of pleuritic chest pain and clinical sepsis, spiral computed tomography scan of his chest and abdomen revealed septic infarcts in multiple organs. Despite empirical treatment with amphotericin B, he died of multiorgan dysfunction syndrome within 72 h. Autopsy revealed systemic aspergillosis with pancarditis, endocardial vegetations, and septic pulmonary, splenic, hepatic and renal infarcts. The pathogenesis and experience with this rare, but often fatal, complication of liver transplantation are reviewed. In contrast to GVHD after bone marrow transplantation, pancytopenia is common and liver dysfunction is rare. One should have a high level of suspicion in the liver transplant recipient presenting with rash and/or diarrhea.

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 Crohn's 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.