Pharmacological prophylaxis versus pancreatic duct stenting plus pharmacological prophylaxis for prevention of post-ERCP pancreatitis in high risk patients: a randomized trial.

BACKGROUND: Acute pancreatitis is a serious complication of endoscopic retrograde cholangiopancreatography (ERCP). The aim of this noninferiority study was to evaluate the effectiveness of pancreatic duct (PD) stenting plus pharmacological prophylaxis vs. pharmacological prophylaxis alone in the prevention of post-ERCP pancreatitis (PEP) in high risk patients. METHODS: In this randomized, controlled, double-blind, noninferiority trial, patients at high risk of developing PEP were randomly allocated to pharmacological prophylaxis (rectal indomethacin, sublingual isosorbide dinitrate, and intravenous hydration with Ringer's lactate) plus PD stenting (group A) or pharmacological prophylaxis alone (group B). The rate and severity of PEP, serum amylase levels, and length of hospital stay after ERCP were assessed. RESULTS: During 21 months, a total of 414 patients (mean age 55.5 ±â€Š17.0 years; 60.2 % female) were enrolled (207 in each group). PEP occurred in 59 patients (14.3 %, 95 % confidence interval [CI] 11.1 % - 17.9 %: 26 patients [12.6 %, 95 %CI 8.6 % - 17.6 %] in group A and 33 [15.9 %, 95 %CI 11.4 % - 21.4 %] in group B). There was no significant difference between the two groups in PEP severity (P = 0.59), amylase levels after 2 hours (P = 0.31) or 24 hours (P = 0.08), and length of hospital stay (P = 0.07). CONCLUSIONS: The study failed to demonstrate noninferiority or inferiority of pharmacological prophylaxis alone compared with PD stenting plus pharmacological prophylaxis in the prevention of PEP in high risk patients.

A randomized trial of rectal indomethacin and sublingual nitrates to prevent post-ERCP pancreatitis.

OBJECTIVES: Acute pancreatitis is the most common adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Recent data suggest that indomethacin can reduce the risk of post-ERCP pancreatitis (PEP) in high-risk individuals. However, whether the combination of indomethacin and sublingual nitrates is superior to indomethacin alone is unknown. Therefore, we aimed to evaluate the efficacy of rectally administered indomethacin plus sublingual nitrate compared with indomethacin alone to prevent PEP. METHODS: During a 17-month period, all eligible patients who underwent ERCP were enrolled in this study. We excluded patients who had undergone a prior endoscopic sphincterotomy. In a double-blind controlled randomized trial, patients received a suppository containing 100 mg of indomethacin, plus 5 mg of sublingual nitrate (group A), or a suppository containing 100 mg of indomethacin, plus sublingual placebo (group B), before ERCP. Serum amylase levels and clinically pertinent evaluations were measured in all patients after ERCP. RESULTS: Of the 300 enrolled patients, 150 received indomethacin plus nitrate. Thirty-three patients developed pancreatitis: 10 (6.7%) in group A and 23 (15.3%) in group B (P=0.016, risk ratio=0.39, 95% confidence intervals (CI): 0.18-0.86). More than 80% of the patients were at high risk of developing pancreatitis after ERCP. Absolute risk reduction, relative risk reduction, and number needed to treat for the prevention of PEP were 8.6% (95% CI: 4.7-14.5), 56.2% (95% CI: 50.6-60.8), and 12 (95% CI: 7-22), respectively. CONCLUSIONS: Combination of rectal indomethacin and sublingual nitrate given before ERCP was significantly more likely to reduce the incidence of PEP than indomethacin suppository alone. Multicenter trials to confirm these promising findings are needed.

Sequential metronidazole-furazolidone or clarithromycin-furazolidone compared to clarithromycin-based quadruple regimens for the eradication of Helicobacter pylori in peptic ulcer disease: a double-blind randomized controlled trial.

BACKGROUND: Furazolidone is a much cheaper drug with a very low resistance against Helicobacter pylori compared to clarithromycin. We aim to evaluate safety and efficacy of a sequential furazolidone-based regimen versus clarithromycin-based therapy in H. pylori eradication for ulcer disease. MATERIALS: Patients with proven peptic ulcer or duodenitis were randomized into three groups: OAB-M-F; metronidazole (M) (500 mg bid) for the first 5 days, followed by furazolidone (F) (200 mg bid) for the second 5 days; OAC-P; clarithromycin (C) (500 mg bid) for 10 days; and OAB-C-F; clarithromycin (500 mg bid) for the first 5 days and furazolidone (200 mg bid) for the second 5 days. All groups received omeprazole (O) (20 mg bid) and amoxicillin (A) (1 g bid). Groups OAB-M-F and OAB-C-F were also given bismuth subcitrate (B) (240 mg bid), whereas a placebo (P) was given to group OAC-P. Adverse events were scored and recorded. Two months after treatment, a C(13) -urea breath test was performed. RESULTS: Three hundred and ten patients were enrolled and 92 (OAB-M-F), 95 (OAC-P), and 98 (OAB-C-F) completed the study. The intention-to-treat eradication rates were 78.5% (95% CI = 69-85), 81.1% (95% CI = 73-88), and 82% (95% CI = 74-89), and per-protocol eradication rates were 91.3% (95% CI = 83-96), 90.4% (95% CI = 82-95), and 88.7% (95% CI = 81-94), for group OAB-M-F, OAC-P, and OAB-C-F, respectively. Eradication rate differences did not reach statistical significance. The most common adverse event, bad taste, occurred in all groups, but more frequently in groups OAC-P (34%) and OAB-C-F (32%), than OAB-M-F (14%) (p < .05). Adverse symptoms score were 0.88 ± 2.05 in group OAB-M-F, 1.15 ± 1.40 in group OAC-P, and 1.87 ± 1.62 in group OAB-C-F. CONCLUSION: Furazolidone can replace clarithromycin in H. pylori eradication regimens because of lack of development of resistance and very low cost.

Needle-knife fistulotomy versus standard method for cannulation of common bile duct: a randomized controlled trial.

BACKGROUND: Endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy has become widely available for the treatment of pancreatobiliary diseases; however, it has mortality and complications. The aim of this study was to compare the success rates and complications of two different methods of common bile duct cannulation. METHODS: From June 2003 though February 2004, patients who were candidates for endoscopic retrograde cholangiopancreatography and/or endoscopic sphincterotomy were randomly divided into two groups: standard cannulation (group A) and suprapapillary needle-knife fistulotomy (group B). Postendoscopic retrograde cholangiopancreatography pancreatitis, cholangitis, bleeding, and perforation were evaluated. RESULTS: Two hundred and eighteen cases (86 males and 132 females with a mean+/-SD age of 56.2+/-17.5 years) were enrolled in this study. Group A, contained 112 patients and group B included 106 patients. In group A, the final cannulation success was achieved in 100 patients (89.3%). Cannulation was successful in 88 patients (83.0%) in group B. Difficulty in cannulation occurred more frequently in group A (25.5% vs. 2.6%, P=0.002). There were two patients in group B and three patients in group A who developed pancreatitis after endoscopic retrograde cholangiopancreatography. Perforation occurred in one patient in group B, which was improved with medical support. Bleeding and cholangitis were not occurred in any of the groups. The overall complication rate was 3/112 in group A and 3/106 in group B. CONCLUSION: Needle-knife fistulotomy is safe and can be applied as an effective alternative to standard technique for common bile duct cannulation in expert hands.

Furazolidone-based, metronidazole-based, or a combination regimen for eradication of Helicobacter pylori in peptic ulcer disease.

BACKGROUND: Furazolidone has been effective against Helicobacter pylori in Iran, with no resistance, but with intolerable side effects in the second week. One-week regimens have not been useful here. We compared the efficacy and side effect profiles of three anti-H. pylori regimens. METHODS: Patients with peptic ulcer disease and positive H. pylori infection were randomly allocated into three groups. The patients in group A received omeprazole 20 mg + amoxicillin 1g + metronidazole 500 mg, and bismuth subcitrate 240 mg twice daily each, for two weeks; the patients in group B received the same regimen but metronidazole was replaced by furazolidone 200 mg twice daily; and the patients in group C received regimen B for the first week and regimen A for the second week. H. pylori eradication was verified with 13C-urea breath test at the tenth week. RESULTS: Three hundred and fourteen patients were enrolled; 107, 104, and 103 patients in groups A-C, respectively but 278 patients completed the study. Seven, three, and six patients discontinued their medication in groups A-C, respectively. Fever, dizziness, and weakness were more common in group B than group C (P < 0.05). Vomiting, pruritus, and rash were more common in group C than group A (P < 0.05). Per-protocol eradication rates were 83.1%, 95.2%, and 95.3% in groups A-C, respectively (P = 0.005, groups A and C). Intention to treat eradication rates were 74.5%, 87.0%, and 86.6% in groups A-C, respectively (P = 0.02, groups A and C). CONCLUSION: One-week furazolidone followed by one-week metronidazole regimen is as efficient as two-week furazolidone regimen but with fewer side effects. Furazolidone-based regimens are superior to metronidazole-based ones for H. pylori eradication in Iran.

Peptic ulcer bleeding: is Helicobacter pylori a risk factor in an endemic area?

BACKGROUND/OBJECTIVE: A high prevalence of Helicobacter pylori infection has been reported in Iran. Although the importance of H. pylori in the induction of peptic ulcer disease is clearly defined, only few studies have addressed its role in bleeding from peptic ulcers. We evaluated the role of H. pylori in peptic ulcer bleeding. METHODS: Patients with acute peptic ulcer bleeding (PUB) and those with peptic ulcer disease without bleeding ('controls') were enrolled. Upper GI endoscopy and rapid urease test were performed in both groups. Histological study for detection of H. pylori was performed in patients with active bleeding, if RUT was negative. Other variables evaluated included sex, age, smoking, previous history of bleeding, non-steroidal anti-inflammatory drugs use, ulcer size, ulcer location, and duration of acid-peptic disease. Multivariate logistic regression analysis was performed to identify independent risk factors. RESULTS: 161 patients with PUB and 287 control patients were enrolled. H. pylori infection was seen more frequently in patients with duodenal ulcer than gastric ulcer (88.9% vs. 60.5%, p< 0.001). Univariate analysis showed that patients with PUB were more often male, older in age, used NSAID, had history of PUB in the past, had ulcer located in the stomach and not in the duodenum, and more often had large ulcer (>1 cm). Logistic regression analysis showed that H. pylori infection was protective in PUB after controlling for confounders (OR 0.41, 95% CI 0.21-0.79), when ulcer location was not entered in the model. A second model including ulcer location (to test for a residual effect) showed that H. pylori infection was not a significant risk factor in PUB (OR 0.61, 95% CI 0.30-1.24). CONCLUSIONS: H. pylori may not be an independent factor in bleeding from peptic ulcers. The lower frequency of this infection in these patients can be described by the higher frequency of bleeding from gastric ulcers, which are less H. pylori related compared with duodenal ulcer.

The effect of adding gentamicin to contrast media for prevention of cholangitis after biliary stenting for non-calculous biliary obstruction, a randomized controlled trial.

AIM: Cholangitis is the most common infectious complication of ERCP. In vitro studies showed that addition of aminoglycosides to contrast medium was effective in reducing cholangitis but the results of clinical trials are conflicting. We studied the effect of adding gentamicin to contrast medium in reducing the rate of post-ERCP cholangitis in patients with non-calculous obstructive jaundice. METHODS: All patients with non-calculous obstructive jaundice who underwent endoscopic biliary stenting at the Shariati Hospital, Tehran, between December 2009 and October 2010 were enrolled in the study. Gentamicin (10 mg) or distilled water was added to each 10 cc contrast medium during ERCP. Intravenous antibiotics were administered before and after the procedure in all patients. After ERCP and stent deployment, patients were followed for 72 h for symptoms and signs of cholangitis. RESULTS: A total of 114 patients were eligible for the study. Of these, 57 patients were included in each group. Cholangiocarcinoma was the most prevalent diagnosis. The obstruction was relieved in all patients by stenting. Five patients in each group (8.8 %) developed cholangitis. There was no significant difference in the incidence of cholangitis between the two groups (p = 1.000). CONCLUSIONS: With adequate drainage of the obstructed biliary tract by proper stenting, adding gentamicin to contrast media had no significant effect on incidence of post-ERCP cholangitis.

Diagnostic accuracy of endoscopic ultrasonography in patients with inconclusive magnetic resonance imaging diagnosis of biliopancreatic abnormalities.

AIM: To determine the sensitivity and specificity of endoscopic ultrasonography (EUS) in patients with inconclusive magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP) in pancreatobiliary abnormalities. METHODS: During 10 months, patients with pancreatobiliary diseases referred to endoscopic retrograde cholangiopancreatography (ERCP) because of inconclusive MRI/MRCP diagnosis were scheduled to undergo endoscopic ultrasonography. Patients were divided into four major groups: patients with (i) resectable periampullary neoplasms who were referred to a surgeon, (ii) unresectable periampullary cancer who underwent ERCP for biliary stenting, (iii) bile duct stone who were referred to ERCP for stone extraction, and (iv) normal pancreatobiliary tract. Reference standards for comparison were ERCP, surgery, a biopsy confirming malignancy, or the clinical course during follow up (at least 12 months) in cases without evidences of malignancy. RESULTS: One hundred and seven patients (51 men; mean [SD] age 60.0 [15.5]) were included in the study. Final diagnoses were common bile duct (CBD) stone (n = 24), periampullary neoplasms (n = 46), others (n = 23) and no pathologic findings (n = 14). EUS determined the staging for clinical decision-making in 47 patients with neoplasms which showed that tumors in 34 patients (79.1%) were unresectable (advanced stage). After EUS, 47 patients (43.9%) did not require ERCP. The accuracy of EUS for the diagnosis of CBD stone and periampullary neoplasms were 96.3% and 99.1%, respectively. CONCLUSIONS: EUS is a useful modality in cases of inconclusive MRI/MRCP indicating pancreatobiliary disorders.

Coeliac disease in autoimmune liver disease: a cross-sectional study and a systematic review.

BACKGROUND: Several studies have reported an association between coeliac disease and autoimmune liver disease, but there is little information on the prevalence of coeliac disease in certain autoimmune liver diseases, particularly from non-European, non-American countries. AIMS: To investigate prevalence of coeliac disease in autoimmune liver disease in Iran and to summarize previous literature. METHODS: We investigated prevalence of coeliac disease among 100 autoimmune liver disease patients and compared it with the prevalence in healthy individuals. We also performed an extensive search of the English literature in PubMed Database. RESULTS: We found substantially elevated prevalence of coeliac disease in patients with overlap syndrome (10-15%) compared to the general population (0.1-1%). To a lesser extent, the prevalence was high in patients with autoimmune hepatitis (2-4%). In our systematic review, prevalence of coeliac disease in autoimmune hepatitis in the majority of studies was 4% or more; several studies also reported such prevalence in primary biliary cirrhosis. CONCLUSIONS: Since coeliac disease is common among patients with autoimmune liver disease, screening autoimmune liver disease patients for coeliac disease is indicated. Although the magnitude of benefit from a gluten-free diet in reversing autoimmune liver disease in patients with coeliac disease is controversial, it may reduce the risk of further complications of coeliac disease.

Long-term follow-up of common bile duct diameter after endoscopic sphincterotomy in patients with common bile duct stones.

BACKGROUND AND AIMS: To determine the time to normalization of common bile duct (CBD) diameter after endoscopic sphincterotomy and stone extraction in patients with choledocholithiasis. METHODS: Patients with CBD dilation due to choledocholithiasis were enrolled. CBD diameter was measured by transabdominal ultrasonography before, and repeated after one, three, six and twelve months after endoscopic sphincterotomy and stone extraction, until normalization of CBD diameter. RESULTS: Of 115 cases enrolled over a 36-month period, CBD diameter reversed to normal in 71 (61.7%) patients after one month. Of the remaining 44 patients, CBD diameter reversed to normal in 36 patients (including 3 in whom repeat ERCP revealed choledocholithiasis) at the end of three months. CBD diameter had not reversed to normal diameter in 8 (18.2%) patients; none of these patients had symptoms. Two of them had asymptomatic dilated CBD after 6 months with no abnormal liver function tests (LFT); the duct reversed to normal at the last follow-up (month 12). CONCLUSIONS: Asymptomatic CBD dilation may persist in a minority of patients (18% at the end of 3 months) after removal of CBD stones. A dilated CBD can be attributed to retained choledocholithiasis within the first month, if it is associated with symptoms and abnormal LFT.

Comparison of colonic transit time between patients with constipation-predominant irritable bowel syndrome and functional constipation.

BACKGROUND/AIM: Functional constipation (FC) and constipation-predominant IBS (C-IBS) are two main subtypes of constipation. Using radio-opaque markers is an easy and cost effective method to measure colonic transit time (CTT). We designed this study to compare the CTT between these two groups of constipated patients. METHODS: Patients with chronic constipation of no organic etiology were classified as having FC or C-IBS according to the Rome II criteria. All patients ingested 10 radio opaque markers daily for six days. A plain abdominal X-ray was taken on the seventh day. To calculate the total and segmental colonic transit time in hours, number of markers in right and left colonic and rectosigmoid area were counted and multiplied by 2.4. The mean total and segmental colonic transit time were compared between the two groups. RESULTS: A total of 100 patients (50 FC and 50 C-IBS) were enrolled. The mean (SD) total CTT was not significantly different between FC patients (52.2 [35.5] h) and C-IBS patients (41.2 [31.6] h; p = 0.10). The mean rectosigmoid transit time was significantly slower in FC patients (19.9 [15.5] h) compared to C-IBS patients (11.9 [10.6] h; p = 0.003). CONCLUSION: Rectosigmoid transit time in FC patients is slower than in C-IBS patients.

Indomethacin may reduce the incidence and severity of acute pancreatitis after ERCP.

OBJECTIVES: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Many medications have been used to prevent this complication. We aimed to evaluate the efficacy of rectally administered indomethacin for the prevention of post-ERCP pancreatitis. METHODS: During 18 months, all eligible patients who underwent ERCP were enrolled in this study. In a double-blind randomized trial, patients received a suppository containing indomethacin, 100 mg, or an inert placebo immediately before ERCP. Serum amylase levels and clinically pertinent evaluations were measured in all patients after ERCP. RESULTS: A total of 490 patients entered the trial, of which half received indomethacin. Twenty-two patients developed pancreatitis; seven cases in the indomethacin group and 15 in the placebo group (P=0.06). Pancreatic duct injection (OR=3.0, 95% CI: 1.3-7.4), pancreatic duct cannulation more than once (OR=4.2, 95% CI: 1.7-10.0), and age less than 60 yr (OR=2.7, 95% CI: 1.0-7.1) were shown to be significant risk factors for developing post-ERCP pancreatitis. In patients who underwent pancreatography with or without cholangiography, the risk of pancreatitis was significantly lower in the indomethacin group compared with the control group (P=0.01, RRR=88%, ARR=0.16, NNT=6). Moderate to severe pancreatitis was significantly higher in the placebo group (P= 0.03). CONCLUSIONS: This trial shows that rectal indomethacin given immediately before ERCP can reduce the incidence and severity of post-ERCP pancreatitis.

Probucol in the treatment of nonalcoholic steatohepatitis: an open-labeled study.

GOALS: To evaluate the effects of probucol, an agent with strong antioxidant properties, in reversing biochemical changes in nonalcoholic steatohepatitis (NASH). BACKGROUND: There is currently no well-established medical treatment of NASH. It is believed that oxidative stress plays a major role in hepatic damage in these patients. STUDY: Cases of biopsy-proven NASH referring to a referral center in Tehran during a 12-month period were included in the study. Viral, autoimmune and other hepatic diseases were excluded. Alcohol ingestion was excluded by repeated questioning of the patient and at least two family members. Patients were given 500mg of probucol daily for 6 months. Serum levels of liver enzymes, the serum lipid profile, and weight was recorded monthly. RESULTS: A total of 17 patients completed the study. The mean age was 37.2 years, 13 patients were male and 4 female. The mean pretreatment value of ALT and AST was 93.5 and 80.4 U/L, and the mean posttreatment value was 41.8 and 35.9 U/L respectively ( = 0.001 and 0.006). CONCLUSION: Probucol, even in the low dose of 500 mg/d, appears to be significantly effective in decreasing the ALT and AST levels in patients with NASH.