Does helicobacter pylori eradication prevent gastric cancer?
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Biomedical subjects
Publications and source records attributed to A N Barkun.
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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.
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.
BACKGROUND: Pancreatic intraductal papillary mucinous neoplasms (IPMN), morphologically resembling colonic adenomas, often have an indefinable malignant potential. We used a monoclonal antibody (MAb) raised against colonic adenomas, Adnab-9, to identify patients with a better prognosis. METHODS: We assessed Adnab-9-labeled sections of these neoplasms from 50 patients, 13 pancreatic adenocarcinomas, and 32 colonic adenomas using standard immunohistochemical techniques. RESULTS: 26% of the IPMNs labeled with Adnab-9 as compared to 0% of pancreatic ductal cancers or surrounding benign tissues, (p < 0.001) and 53% of adenomas (p < 0.025). Labeling in IPMNs was usually seen in the noninvasive epithelium suggesting that Adnab-9 is a premalignant marker in these lesions. Labeling of invasive IPMN's identified a group of patients with a superior overall survival (p = 0.027). CONCLUSION: Adnab-9 labeling-characteristics appear similar for both IPMNs and adenomatous polyps, suggesting that they are analogous lesions. Adnab-9 labeling may also be a useful prognostic marker for invasive intraductal papillary mucinous neoplasms.
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Helicobacter pylori has an unusual pattern of genetic variation, which complicates research on this organism. To gain a better understanding of the forces behind this phenomenon, the extent to which recombination and single point mutations affect genetic variability in H. pylori was quantified and the influence of both geographical distance and clinical background were assessed. Site-directed restriction-endonuclease digestion of 2 gene fragments was performed on 168 isolates from Montreal and Berlin. Allelic diversity was found to be much higher for H. pylori than for other bacterial species. This finding is consistent with those of previous studies on H. pylori that were conducted using other techniques. However, nucleotide diversity was within the range reported for other bacterial species. Phylogenetic analysis found no grouping of strains with clinical background or geographical origin. Recombination at a rate that resulted in linkage equilibrium within genes can explain these observations.
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OBJECTIVES: A recent report has suggested an association between Helicobacter pylori eradication and the development of gastroesophageal reflux disease (GERD). We therefore assessed the incidence of GERD among comparable patients having undergone successful versus failed H. pylori eradication in a controlled trial. We also compared the H. pylori strains in the subjects that developed GERD to those that did not. METHODS: Patients with a history of proven duodenal ulcer and H. pylori infection were randomised into a H. pylori eradication study. Patients subsequently underwent gastroscopy with gastric biopsies every 3 months for 1 yr. At each visit, the presence of GERD symptoms and endoscopic esophagitis were noted, and the incidence of these variables among patients in whom H. pylori eradication was successful was compared to those in whom it was not. In a subgroup, the presence of the cagA, cagE, and vacA genotypes and of cagA antibodies were determined. RESULTS: Of 98 patients randomized into this study, 11 dropped out before determination of H. pylori eradication, leaving 87 patients with analyzable results. H. pylori eradication was successful in 63 (72%). By the end of the follow-up period, patients with GERD symptoms or endoscopic esophagitis were more prevalent in the successful than in the failed eradication group (37% [95% CI: 25-50%] vs 13% [95% CI: 3-32%], p = 0.04, 95% CI for the difference: 6-42%), as were patients with GERD symptoms alone (29% [95% CI: 18-41%] vs 8% [95% CI: 1-27%], p = 0.04, 95% CI for the difference: 4-36%) or esophagitis alone (21% [95% CI: 12-33%] vs 4% [95% CI: 0-21%], p = 0.10, 95% CI for the difference: 4-29%, respectively). Multivariate analysis revealed no significant association between the incidence of symptoms or esophagitis and age, gender, Quetelet index, caffeine or alcohol intake, smoking, weight change, or the presence of a hiatus hernia. There were also no differences in the prevalence of H. pylori genotypes from patients who developed GERD as compared to those who did not. CONCLUSIONS: In this patient population, the incidence of new GERD-type symptoms or endoscopic esophagitis was greater in patients in whom successful eradication was achieved. This difference does not appear to be attributable to weight gain, habits, or specific H. pylori strains.
OBJECTIVE: Helicobacter pylori (H. pylori) is a recognized pathogen, but it may also have a protective effect for gastroesophageal reflux disease (GERD). We compared the prevalence of potential virulence factors (cagA, cagE, vacA genotypes) in GERD to other upper gastrointestinal diseases and controls. METHODS: A total of 405 patients underwent gastroscopy with H. pylori isolation and serum testing. Patient diagnostic subgroups were prospectively defined. Genotypes were determined by amplification using polymerase chain reaction. CagA antibodies were determined by western blot, enzyme-linked immunosorbent, and flow microsphere immunofluorescent assays. RESULTS: Patients were grouped as follows: nonulcer dyspepsia (26%), GERD (20%), gastric ulcer (17%), duodenal ulcer (12%), gastric cancer (6%), or controls (19%). The cagA gene was present in 94-97% of subjects in all categories, but the cagA antibody was less prevalent in nonulcer dyspepsia (69%, 95% CI: 48-86%, p = 0.02) and GERD (69%, CI: 39-91%, p < 0.05) than in those with gastroduodenal pathology including gastric ulcer, duodenal ulcer, and gastric cancer (92%, CI: 81-98%). The cagE gene and vacA S1 genotype were more frequent in patients with gastroduodenal pathology (p < 0.01). GERD was associated with a significantly lower rate of vacA S1 genotype than controls (29% (CI: 10-56%) versus 80% (CI: 59-93%), p < 0.01). The vacA S1 genotype was associated with the presence of cagA antibodies. CONCLUSIONS: The cagE and vacA S1 genotypes are more prevalent in patients with peptic ulcer or gastric cancer, suggesting a potential function in virulence for these genes. However, the vacA S1 genotype was also more prevalent in controls than GERD, suggesting a potential protective effect against GERD.
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BACKGROUND: Current recommendations for the use of standard catheters or sphincterotomes for the initial attempt at selective common bile duct cannulation have been made in the absence of prospective comparative data. METHODS: A prospective study was carried out in which patients were randomized to undergo cannulation with a standard catheter or a sphincterotome (standard or wire-guided). Multivariate models were constructed to determine significant independent predictors of the success rates of initial and selective cannulation and the number of attempts and time needed to achieve selective cannulation. RESULTS: Eighty-three successive patients were evaluated; 36 were excluded because they had undergone previous therapeutic endoscopic retrograde cholangiopancreatography (ERCP) or a Billroth II operation. Of the 47 patients (28 women, mean age 60.6 +/- 14.5 years), indications for ERCP included suspected bile duct stones in 41 patients, pancreatico-biliary malignancies in 4, and biliary leaks in 2. Eighteen patients were randomized to undergo selective common bile duct cannulation with standard catheter and 29 to standard/wire-guided sphincterotome. Initial common bile duct cannulation for the standard catheter and standard/wire-guided sphincterotome groups was successful in 12 (67% [95% CI: 41%, 87%]) and 28 (97% [95% CI: 82%, 100%]) patients, respectively (95% CI for the difference: -0.57 to -0.03, p = 0.009). Using intention to treat analysis, selective common bile duct cannulation was successful for standard catheter and standard/wire-guided sphincterotome patients in 17 (94% [95% CI: 73%, 99%]) and 28 (97% [95% CI: 82%, 100%]) cases, respectively (95% CI for the difference: -0.15 to +0.10, p > 0.05). The mean number of attempts required to achieve selective common bile duct cannulation were 12.4 +/- 6.0 and 2.8 +/- 3.1 (p = 0.0001). The mean time taken to achieve selective common bile duct cannulation was 13.5 +/- 6.14 and 3.1 +/- 5.1 minutes (p = 0.0001). Multivariate modeling revealed that the initial choice of catheter was the only significant independent predictor of the time taken and the number of attempts performed to achieve selective common bile duct cannulation (p = 0. 0001 for each model). CONCLUSION: The use of standard/wire-guided sphincterotome was superior to that of standard catheter for the initial attempt at cannulation of the common bile duct. The number of attempts required may bear clinical significance with regard to the development of post-ERCP pancreatitis and warrants further study.
Despite a decreased incidence of ulcer disease and improvements in the management of acute upper gastrointestinal (GI) bleeding, mortality remains at about 6-7%. Although endoscopic haemostatic therapy has been demonstrated to be the mainstay of management, the search continues for less invasive medical modalities that might also improve patient outcome. In vitro data have indicated the important role of acid in impairing haemostasis and causing clot digestion. Therefore, theoretically, maintenance of a high intragastric pH (above 6.0) during management of upper GI bleeding is warranted. Until recently, available agents did not permit such a sustained elevation in gastric pH. Early studies with H2-receptor antagonists have not demonstrated significant improvements in important patient outcomes, such as rebleeding, surgery or mortality. With the availability of intravenous formulations of proton pump inhibitors, it is now possible to aim at maintaining gastric pH above 6.0 for 24 h per day. Recent clinical trial data would appear to support the use of proton pump inhibitors to decrease the rate of rebleeding and the need for surgery. This paper provides a review of non-variceal acute GI bleeding, with special reference to the role of proton pump inhibitors in this clinical setting.
Greater than one-half of the world's population harbors Helicobacter pylori. The majority of infected individuals, however, remain asymptomatic, with only 10% to 20% developing diseases, including peptic ulcer disease, gastric cancer, and gastric mucosa-associated lymphoid tissue lymphoma. This article reviews host factors that may predispose an individual to both the acquisition of H. pylori infection and subsequent clinical outcome. Individuals with specific blood group antigens and human leukocyte antigen genotypes may be more susceptible to H. pylori infection. Additional factors, such as the age of acquisition, the host immune response, the site of infection, acid secretion, and interactions with nonhost factors (including bacterial virulence factors and environmental influences) may play a role in determining clinical outcome. Further investigation is required to clarify the mechanisms by which these interactions occur and, more critically, to determine their relative importance. This knowledge will enable the identification of individuals at risk of developing clinical disease with H. pylori infection.
OBJECTIVE: In light of evidence that Helicobacter pylori treatment fails 5% to 20% of the time, the objective of this study was to determine predictors of unsuccessful H. pylori eradication and of duodenal ulcer recurrence. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Gastroenterology services of 2 general hospitals in Montreal, Que. PATIENTS: All patients (aged 16 to 90) with an endoscopically proven duodenal ulcer within the previous year and H. pylori infection detected on antral biopsy were asked to participate; 85 were included. INTERVENTIONS: Patients were randomized in double-blind fashion to 1 of 2 eradication therapies, consisting of metronidazole, bismuth subcitrate and either amoxicillin or placebo. Endoscopy was performed at follow-up every 3 months for 12 months. OUTCOME MEASURES: Demographic data, characteristics of patients and disease, previous history and family history of ulcer disease, compliance at day 10 and day 28 of therapy; in vitro metronidazole resistance of H. pylori; eradication of H. pylori (determined by endoscopic biopsy 3 months after therapy); and ulcer recurrence within 12 months after therapy. RESULTS: Metronidazole resistance (odds ratio [OR] 0.11, 95% confidence interval [CI] 0.017 to 0.69) was the only independent predictor of eradication. Compliance (as defined in the study), density of organisms on culture, as well as several other factors examined, were not significant predictors. Treatment group, although a significant factor on univariate analysis, was not an independent predictor on multivariate analysis, as there were relatively good eradication rates (82% and 97% among compliant patients) in both groups. With regard to ulcer recurrence, 3 independent predictors were identified: failed H. pylori eradication (OR 86.5, 95% CI 4.2 to 1769), unemployment (OR 13.2, 95% CI 1.8 to 95) and a family history of ulcer disease (OR 12.2, 95% CI 1.2 to 128). CONCLUSIONS: The best predictor of ulcer recurrence is failure of H. pylori eradication, which, in turn, depends on metronidazole resistance. Hence, treatments containing metronidazole should be avoided in populations with high rates of metronidazole resistance. A family history of ulcer disease and unemployment were also predictors of ulcer recurrence, which suggests a potential role for treatment of contacts.
BACKGROUND AND STUDY AIMS: Determinants of complications after endoscopic retrograde cholangiopancreatography (ERCP) have not yet been completely characterized. PATIENTS AND METHODS: Data were collected from an endoscopic database. Univariate analysis and multivariate logistic regression analysis were used to generate the best model of independent predictors of post-ERCP pancreatitis. RESULTS: The database included 1239 ERCP examinations carried out to investigate suspected choledocholithiasis over a five-year period. From these, 45 patients who developed post-ERCP complications were compared to a random sample of 486 patients who had undergone an uncomplicated ERCP for suspected choledocholithiasis. Univariate analysis demonstrated significant differences between the two patient groups for the following factors: age, using a cut-off point of 59 years (27% vs. 51%, P = 0.002), pancreatic channel opacification (73% vs. 58%, P = 0.05), and absence of common bile duct stones (41% vs. 24%, P = 0.03). Using multivariate logistic regression, the best model for predicting post-ERCP pancreatitis in patients undergoing sphincterotomy included age under 59 years (P = 0.04), and absence of a common bile duct stone (P = 0.004). The model yielded probabilities of developing post-sphincterotomy pancreatitis that ranged from 2.8% if no predictor was present, to 27% when both predictors were present. Among patients in whom a sphincterotomy was not performed, the only significant independent predictor found was pancreatic channel opacification (P = 0.05). CONCLUSION: Age under 59 years, pancreatic channel opacification, and an absence of common bile duct stones at ERCP are all independent predictors of post-ERCP pancreatitis.
PURPOSE: To evaluate the test performance of magnetic resonance (MR) cholangiography for help in diagnosing choledocholithiasis. MATERIALS AND METHODS: Fast spin-echo MR cholangiography was performed by using a torso multicoil array in 110 patients suspected of having bile duct obstruction. Axial and coronal images were reviewed by two observers who were blinded to results of direct cholangiography and final diagnoses. The final diagnosis was established by using direct cholangiographic (n = 103) or surgical (n = 7) findings. RESULTS: Of the 110 patients, 30 (27%) had choledocholithiasis, and 80 (73%) did not. Reviewer 1 used MR cholangiograms to achieve a sensitivity of 90%, specificity of 100%, positive predictive value of 100%, negative predictive value of 96%, and overall accuracy of 97%. Reviewer 2 achieved a sensitivity of 90%, specificity of 93%, positive predictive value of 82%, negative predictive value of 96%, and overall accuracy of 92%. Interobserver agreement for MR cholangiograms was 93% (kappa = 0.82). CONCLUSION: MR cholangiography exhibited excellent test performance and resulted in excellent interobserver agreement for the diagnosis of choledocholithiasis.