Helicobacter pylori resistance rates for levofloxacin, tetracycline and rifabutin among Irish isolates at a reference centre.

INTRODUCTION: Helicobacter pylori eradication rates using conventional triple therapies are falling, making viable second-line and rescue regimens necessary. Levofloxacin, tetracycline and rifabutin are three efficacious antibiotics for rescue therapy. AIM: We aimed to assess the resistance rates for H. pylori against these antibiotics in an Irish cohort. METHODS: Gastric biopsies were collected from 85 patients infected with H. pylori (mean age 46 years) in the Adelaide and Meath Hospital, Dublin in 2008 and 2009. Susceptibility to antibiotics was tested using the Etest. Clinical information was obtained from endoscopy reports and chart review. RESULTS: 50.6 % of patients were females. Mean age was 47 years. Ten had prior attempts at eradication therapy with amoxicillin-clarithromycin-PPI, two had levofloxacin-based second-line therapy. 11.7 % [95 % CI (6.5-20.3 %)] (N = 10) had strains resistant to levofloxacin. There were no strains resistant to rifabutin or tetracycline. Levofloxacin resistance in the under 45 age group was 2.6 % (1/38) compared to 19.1 % (9/47) of above 45 age group (p = 0.02). DISCUSSION: The levofloxacin rates illustrated in this study are relatively low by European standards and in line with other studies from the United Kingdom and Germany, with younger patients having very low levels of resistance. Levofloxacin, tetracycline and rifabutin are all valid options for H. pylori eradication in Irish patients but the importance of compliance cannot be underestimated.

Inappropriate colonoscopic surveillance of hyperplastic polyps.

Colonoscopic surveillance of hyperplastic polyps alone is controversial and may be inappropriate. The colonoscopy surveillance register at a university teaching hospital was audited to determine the extent of such hyperplastic polyp surveillance. The surveillance endoscopy records were reviewed, those patients with hyperplastic polyps were identified, their clinical records were examined and contact was made with each patient. Of the 483 patients undergoing surveillance for colonic polyps 113 (23%) had hyperplastic polyps alone on last colonoscopy. 104 patients remained after exclusion of those under appropriate surveillance. 87 of the 104 patients (84%) were successfully contacted. 37 patients (8%) were under appropriate colonoscopic surveillance for a significant family history of colorectal carcinoma. 50 (10%) patients with hyperplastic polyps alone and no other clinical indication for colonoscopic surveillance were booked for follow up colonoscopy. This represents not only a budgetary but more importantly a clinical opportunity cost the removal of which could liberate valuable colonoscopy time for more appropriate indications.

A changing trend in the management of patients with newly diagnosed Crohn's disease.

BACKGROUND: Epidemiologic shift with rising incidence of Crohn's disease (CD) has been reported in recent studies. AIMS: To determine disease behaviour and therapeutic interventions undertaken in newly diagnosed patients with CD. METHODS: Patients diagnosed with CD between January 2006 and June 2008 were included. Disease type, location, degree of involvement and type of therapeutic interventions were recorded. RESULTS: A total of 78 patients were included. Colonic, ileo-colonic, terminal ileal and isolated small bowel disease were present in 37, 27, 9 and 5 patients, respectively. Disease phenotype was inflammatory, stenosing and fistulising in 42, 30 and 6 patients, respectively. Surgery was required in 22 patients, including right hemicolectomy (n = 8), subtotal colectomy (n = 4), segmental colonic resection (n = 2), segmental small bowel resection (n = 2), appendectomy (n = 2) and perianal surgery (n = 4). Fourteen patients underwent surgery at the time of diagnosis. Laparoscopic surgery was performed in 14 patients. CONCLUSIONS: A significant proportion of newly diagnosed patients with CD underwent surgical intervention on their first admission to hospital. This may signify a changing trend in the management approach.

A comparative study of faecal occult blood kits in a colorectal cancer screening program in a cohort of healthy construction workers.

BACKGROUND: The incidence of colorectal cancer (CRC) has been increasing. We evaluated uptake rates and outcomes of faecal immunochemical test (FIT) and Guaiac test (gFOBT) kits as part of a two-step CRC screening. METHODS: A 3-year CRC screening program for a defined population of construction workers was conducted. Those satisfying the inclusion criteria were provided with gFOBT or FIT kits. Individuals testing positive were invited for a colonoscopy. RESULTS: A total of 909 faecal testing kits were distributed. Age range was 53-60 years. Compliance rate was higher for FIT (58.3%) as compared to gFOBT (46.7%) (p = 0.0006). FIT detected adenomatous polyps and CRC in 37.5 and 25%, respectively, whereas; gFOBT detected 23.5 and 18%. Colonoscopies were normal in 53 and 25% tested positive by gFOBT and FIT, respectively (p = 0.016). CONCLUSION: The FIT was more cost-effective when compared with gFOBT with higher return rate, sensitivity and specificity. A comparative study of faecal occult blood kits in a CRC screening program in a healthy cohort of construction workers.

Endoscopic ultrasound with fine needle aspiration and biopsy in lung cancer and isolated mediastinal lymphadenopathy.

Endoscopic ultrasound with fine-needle aspiration and biopsy (EUS-FNAB) is well established in diagnosing and staging lung cancer in patients with mediastinal adenopathy. EUS-FNAB is highly sensitive, less invasive and has lower complication rates when compared to surgical staging of mediastinal nodes. In this study we describe our experience of EUS-FNAB in lung cancer and other causes of mediastinal lymphadenopathy. EUS-FNAB was performed for assessment of PET positive mediastinal lymph nodes between January 2007 and March 2009 in AMNCH. The endpoints of our study were sensitivity and specificity of EUS-FNAB, morbidity and length of hospital stay. Thirty four patients underwent EUS-FNAB during the study period for both diagnosis and staging. Thirty patients had positive lymph node invasion and 4 had no evidence of malignant invasion. In these 4 patients negative cytology was confirmed on mediastinoscopy giving EUS-FNAB a sensitivity and specificity of 100%. EUS-FNAB upstaged the disease in 12 patients. EUS-FNAB is a reliable tool for mediastinal staging in lung cancer, significantly reducing the need for surgical staging procedures in patients with suspected mediastinal involvement.

Feasibility study of preemptive withdrawal of immunosuppression based on chimerism testing in children undergoing myeloablative allogeneic transplantation for hematologic malignancies.

An increasing percentage of autologous cells (increasing chimerism) in the whole blood (WB) chimerism test following allogeneic transplant is related to a very high risk of relapse. Preemptive immunotherapy may decrease the risk of relapse in some patients. Our prospective multi-institutional study evaluated the feasibility of longitudinal chimerism testing in a central laboratory, compared WB, CD3+ and leukemia-specific lineage chimerism in patients with a variety of hematologic malignancies, and evaluated the feasibility of fast withdrawal of immunosuppression based on WB chimerism results. Centralized chimerism testing was feasible and showed low interassay variability. Increasing mixed chimerism (MC) in WB was not useful as a predictor of relapse in our study. The presence of full donor chimerism in WB, CD3+ and leukemia-specific lineages on all measurements was related to a significantly lower risk of relapse than the presence of MC in either subset (11 vs 71%, respectively; P=0.03). Increasing host chimerism in leukemia-specific lineage heralds relapse, but it was not detected early enough to allow immunotherapy. Further studies correlating lineage-specific chimerism and minimal residual disease are required. The goal of preemptive immunotherapy should be to achieve full donor chimerism in WB in CD3+ and leukemia-specific lineages.

Intestinal permeability is increased in a proportion of spouses of patients with Crohn's disease.

OBJECTIVE: Increased small intestinal permeability has been found in patients with Crohn's disease and in a proportion of their healthy relatives. This may reflect a shared environment or shared genes. The finding of abnormal permeability in the healthy spouses of patients would favor an environmental cause for this observation. METHODS: The healthy spouses of patients with Crohn's disease attending three gastroenterology clinics were invited to participate. Eligible subjects consumed a 350-ml solution containing lactulose, mannitol, and sucrose before bedtime. All overnight urine was collected, assayed by high performance liquid chromatography, and the ratio of fractional excretion of lactulose to mannitol was calculated as an index of permeability. The results were compared with those of a previously determined control group. RESULTS: Sixty spouses completed the study. Increased permeability was present in eight (13.3%, 95% CI = 6.0-24.6%). The presence of increased permeability was not related to age, gender, duration of cohabitation, alcohol use, nonsteroidal anti-inflammatory drug use or to disease activity in the patient with Crohn's disease. There was a nonsignificant trend for abnormal permeability to occur in those spouses cohabiting with the patient with Crohn's disease at the time of disease diagnosis (p = 0.128). CONCLUSIONS: Small intestinal permeability is increased in a proportion of healthy spouses of patients with Crohn's disease. The presence of abnormal permeability studies in patients with Crohn's disease and a proportion of their healthy close contacts suggests that this phenomenon is caused by environmental factors.

Increased mast cells in the irritable bowel syndrome.

Mast cells (MC) release potent mediators which alter enteric nerve and smooth muscle function and may play a role in the pathogenesis of the irritable bowel syndrome (IBS). The aim of this study was to determine if MC were increased in the colon of IBS patients compared to controls. Biopsy specimens were obtained from the caecum, ascending colon, descending colon and rectum of 28 patients: 14 IBS (Rome criteria); seven normal; and seven inflammatory controls. Tissue was stained immunohistochemically using a monoclonal mouse antibody for human mast cell tryptase (AA1). Tissue area occupied by tryptase-positive MC (volume density of mast cells) was quantified by image analysis. The number of plasma cells, lymphocytes, eosinophils, neutrophils and macrophages were each graded semiquantitatively (0-4) in haematoxylin and eosin stained sections. Mast cell volume density was significantly (P < 0.05) higher in IBS (0.91 +/- 0.18; CI 0.79; 1.0) than normal controls (0.55 +/- 0.14; CI 0.40; 0.69) in the caecum but not at other sites. Apart from MC, there was no evidence of increased cellular infiltrate in the IBS group. MC were significantly increased in the caecum of IBS patients compared to controls. The multiple effects of the intestinal mast cell alone, or as a participant of a persistent inflammatory response, may be fundamental to the pathogenesis of IBS.

The effects of blood on rapid urease testing for Helicobacter pylori in mucosal biopsies from the gastric antrum.

BACKGROUND: While the eradication of Helicobacter pylori in patients with bleeding peptic ulcer disease (PUD) decreases the rate of ulcer re-bleeding, the sensitivity of the rapid urease test (RUT) for H. pylori diagnosis is lower in this setting. The aim of this study was therefore to determine if exposing a gastric biopsy specimen to blood before its use in the RUT (CLOtest) could account for these findings. METHODS: In patients undergoing endoscopy for the evaluation of dyspepsia gastric mucosal biopsies were obtained for H. pylori diagnosis (RUT, microbiology, and histology). Mucosal biopsies from each patient were also exposed to blood for 15, 30 and 45 minutes before use in the RUT. RESULTS: Using a combination of diagnostic tests (histology, microbiology and routine CLOtest) as the 'gold standard', the sensitivity, specificity, positive predictive value and negative predictive value of the CLOtest remained above 90% despite prior exposure of the gastric biopsy specimen to blood, and these values were not significantly different from the performance characteristics of the CLOtest processed in a routine manner. CONCLUSION: The exposure of gastric mucosal biopsy specimens to blood alone is not the explanation for the reduced sensitivity of the RUT in patients with bleeding peptic ulcers.

Rapid urease tests lack sensitivity in Helicobacter pylori diagnosis when peptic ulcer disease presents with bleeding.

OBJECTIVE: The eradication of Helicobacter pylori (H. pylori) in patients with bleeding peptic ulcer disease (PUD) decreases the rate of ulcer rebleeding. Although all methods for H. pylori diagnosis have been extensively evaluated in uncomplicated PUD the efficacy of the commonly used rapid urease test (RUT) has not been established in patients with bleeding peptic ulcer disease. The aim of this study was to evaluate the efficacy of the RUT (CLOtest) in patients with bleeding duodenal ulcers (DUs). METHODS: Consecutive patients with symptoms of upper GI tract hemorrhage and a DU at the time of endoscopy were evaluated. The presence of H. pylori infection was determined by RUT, microbiology, and histology. Consecutive patients with uncomplicated DUs were similarly evaluated. The prevalence of H. pylori as determined by the RUT alone was compared to that determined by a combination of all tests in both patient groups. RESULTS: Fifty-five patients with bleeding DUs and 69 with nonbleeding DUs were evaluated. The prevalence of H. pylori in patients presenting with bleeding was 72.7% (95% confidence interval [CI] 61.0-84.5%) and lower than the prevalence rate of 92.8% (95% CI 86.6-98.8%) in patients with uncomplicated PUD (p < 0.05). The prevalence of H. pylori in the bleeding DU group as determined by RUT alone (54.5%) was less than that determined by a combination of all tests (73%) with a false-negative rate of 10 of 40 (25%; 95% CI 11.6-38.4%) (p < 0.05). This false-negative rate was significantly greater than that observed in the group presenting with dyspepsia (1 of 64 [1.6%; 95% CI 0-4.6%]) (p < 0.01). CONCLUSIONS: The prevalence of H. pylori is lower in patients with bleeding DUs when compared to patients with uncomplicated DUs. In addition, the sensitivity and negative predictive value of the RUT is lower in patients presenting with bleeding, and other methods of H. pylori diagnosis should be used in this patient group.

Gastric cancer and other endoscopic diagnoses in patients with benign dyspepsia.

BACKGROUND: It has been suggested that endoscopy could be replaced with non-invasive assessment of helicobacter status in the initial work up of young dyspeptic patients without sinister symptoms. AIMS: To determine the incidence of gastro-oesophageal malignancy in young dyspeptic patients. METHODS: The Alberta Endoscopy Project captured clinical and demographic data on all endoscopies performed from April 1993 to February 1996 at four major adult hospitals in Alberta. The endoscopic and histological diagnosis in a subgroup of patients under 45 years of age without alarm symptoms that had undergone gastroscopy was reviewed. In addition, a random list of 200 patients was generated and their medical records reviewed in order to assess the proportion with symptoms suitable for a non-invasive management strategy. RESULTS: Gastroscopy was performed in 7004 patients under 45 years. In 3634 patients (56% female) alarm type symptoms were absent; 78.9% of patients had symptoms amenable to a non-invasive initial approach, giving a corrected sample size of 2867 patients (correction factor 0.789). Three gastric cancers, one case of moderate dysplasia, 10 biopsy proved cases of Barrett's oesophagus, and 19 oesophageal strictures/rings were detected within this sample. The corrected prevalence of gastric cancer in this select population was 1.05 per thousand patients. DISCUSSION: Endoscopy yielded three gastric cancers in this sample of under 45 year old dyspeptic patients without sinister symptoms. While initial non-invasive screening with one-week triple therapy for helicobacter positive individuals is unlikely to have a detrimental outcome the physician is advised to consider endoscopy in patients with persisting, recurrent, or sinister symptoms.

Mucosa-associated lymphoid tissue (MALT) lymphoma manifesting as multiple lymphomatosis polyposis of the gastrointestinal tract.

There have been a number of previous case reports of lymphomas in the form of multiple mucosal polyps affecting variable lengths of colonic and intestinal mucosa. Invariably these have been classified histologically as mantle cell lymphomas. We report a case of this rare syndrome that illustrates many of its typical features but which demonstrates significant histological and immunophenotypic differences. A 67-yr-old man was referred with a 3-month history of altered bowel habit and a barium enema suggestive of extensive ulcerative colitis. At colonoscopy, diffuse umbilicated mucosal polyps were seen throughout the colon and a larger circumferential mass lesion at the ileocecal valve. Biopsies demonstrated a diffuse B-cell lymphoma consistent with "multiple lymphomatous polyposis" of the colon. Flow cytometry revealed CD25 positive/CD5 negative lymphoid cells confirming marginal B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. Upper gastrointestinal investigations confirmed similar involvement of the stomach, duodenum, and small bowel. Helicobacter pylori was absent. Flow cytometry abnormalities consistent with marrow involvement were present. These features led to a diagnosis of stage IV marginal zone B-cell lymphoma of MALT type, presenting as multiple lymphomatous polyposis of the gastrointestinal tract. Three months of combination chemotherapy resulted in an excellent symptomatic and endoscopic response.

Survey of current practices among members of CAG in the follow-up of patients diagnosed with gastric ulcer.

INTRODUCTION: Guidelines recommend a policy of endoscopic follow-up of all gastric ulcers until healing. Analysis of data from the Alberta Endoscopy Project indicates that fewer than 50% of patients diagnosed with benign gastric ulcer had undergone a repeat procedure. The practice and attitudes of physician members of the Canadian Association of Gastroenterology (CAG) on the follow-up of such patients were assessed. METHODS: A self-administered questionnaire was mailed to members of CAG. Respondents were asked to indicate their practice setting and to estimate the proportion of gastric ulcer patients in whom they perform follow-up endoscopy. They were also asked to indicate factors influencing this choice, including the role of Helicobacter pylori. RESULTS: Fifty-seven per cent of 220 respondents indicated that they perform repeat endoscopy in 95% to 100% of individuals with benign gastric ulcer. The most common reasons influencing this choice were to ensure healing (86.3%) and to confirm the benign nature of the lesion (79.5%). Nonsteroidal anti-inflammatory drug (NSAID) use (83.2%) and patient ill health (62.9%) were the most common reasons for not repeating the endoscopy. Twenty per cent of individuals indicated that H pylori had influenced a change in their practice. DISCUSSION: Physicians vary widely in their follow-up of benign gastric ulcer. Studies on the occurrence of gastric cancer in this setting are not unanimous in their conclusions. Subgroups of patients with NSAID exposure and successfully eradicated H pylori infection may have a lower risk of malignancy. Studies to confirm this are warranted, and modified guidelines may be appropriate.

Screening for Helicobacter pylori in young dyspeptic patients referred for investigation--endoscopy for those who test negative.

BACKGROUND: Studies in young dyspeptic patients have suggested that screening strategies based on non-invasive H. pylori testing can reduce endoscopy workload by 25-40%. Such strategies usually propose that only H. pylori-positive individuals should undergo endoscopy. This approach may fail to diagnose idiopathic ulcers, ulcers in patients whose screening test is falsely negative and reflux disease. AIM: To investigate a hypothetical screening strategy in which endoscopy is initially performed only in H. pylori-negative dyspeptics. METHODS: Seventy-two consecutive patients under 45 years of age undergoing investigation for 'ulcer-like' dyspepsia had invasive and non-invasive determination of H. pylori status. Individuals found to be H. pylori-positive at endoscopy received 1 week of proton pump inhibitor-based triple therapy. H. pylori-negative individuals received therapy tailored to their diagnosis. Endoscopy was repeated in the positive group to confirm successful eradication. Results were analysed according to our strategy, i.e. serologically-positive patients would have received eradication therapy without endoscopy, but patients found to be negative would have been referred for endoscopy. RESULTS: According to the serology test there were 39 positive and 33 negative results. Symptoms failed to resolve during follow-up in nine of the serological positives despite successful eradication. There were also five false positives who were deemed likely treatment failures. Thus according to our strategy, these 14 serologically-positive patients would ultimately have required an endoscopy and the other 25 serologically-positive patients would have avoided an endoscopy, resulting in a 35% reduction in endoscopy usage in this population. In the serologically-negative group there were three cases of peptic ulcer disease where the test was falsely negative, but they were detected by the strategy. No cases of gastric malignancy were detected at endoscopy. Thus our strategy would have reduced initial endoscopy referrals by 35% in this selected population. CONCLUSION: A strategy of empirical H. pylori eradication therapy can safely reduce the requirement for endoscopy in young dyspeptic patients without sinister symptoms.

The case against routine post-operative therapy for prevention of recurrence in Crohn's disease.

Crohn's disease is inevitably characterized by episodes of relapse followed by remission. The majority of patients will require at least one resection, unfortunately many will have, at some time in the future, further recurrences requiring additional surgery. Faced with this clinical situation, the physician or surgeon may respond to the therapeutic imperative, i.e., it is better to do something rather than to do nothing at all (i.e., treat the patient). Because of these factors, various authors have suggested that the aminosalicylates or, in certain cases, azathioprine, should be prescribed following resection. From a health system point of view, the case for maintenance therapy must be reviewed against several criteria. First, the therapy to be prescribed must be safe for patients over the long term. For the most part, the safety profile of mesalamine has been well established. There is also increasing evidence for the safety of azathioprine when used in chronic inflammatory diseases such as rheumatoid arthritis. Second, there must be objective evidence of efficacy as assessed by randomized controlled, double-blind trials. To date, several trials have been performed, unfortunately, the most recent have only been reported in abstract form. The results of the trials have been contradictory with a mixture of positive and negative findings. There is a lack of consistency for both the dose response and preferred disease site, the use of placebos, the evaluation of outcome and the statistical analysis. Third, the cost-benefit ratio must favour the therapy. Calculation of the number to reat (NNT) to prevent one recurrence is often helpful. Finally, compliance in a group of patients who often decide on surgery so that they can stop taking medication must be considered. A variety of criteria have been developed to assist in making choices regarding prophylaxis. The first relates to the ease of treating the patient with recurrence. Some patients will respond promptly to conventional therapy and enter remission. Unfortunately, this is not the case for the majority of patients. We lack predictors of response. The second concerns the issue as to whether or not the condition to be prevented, recurrence, is a "serious" event. There would be little discussion of that issue at an IBD meeting! The third considers the possibility of adverse events related to the prophylaxis. Again, there does not appear to be concern related to safety. It is the final criterion regarding effectiveness that balances the argument against a routine recommendation for post-operative maintenance therapy.

Monozygotic twins with Crohn's disease and ulcerative colitis: a unique case report.

BACKGROUND: A large number of monozygotic and dizygotic twin pairs with inflammatory bowel disease have been reported. To date no twin pair has developed phenotypically discordant inflammatory bowel disease. This case report is the first documented occurrence of discordant inflammatory bowel disease occurring in monozygotic twins. CASE REPORT: Twenty two year old identical male twins presented within three months of each other with inflammatory bowel disease that proved to be discordant in overall disease type, disease distribution, clinical course, and histopathological findings. Twin 1 developed a severe pancolitis necessitating total colectomy while twin 2 developed a predominantly distal patchy colitis with frequent granulomas, controlled by aminosalicylates. Twin 1 was antineutrophil cytoplasmic antibody (ANCA) negative at the time of testing while twin 2 (Crohn's disease) was ANCA positive. Significantly, the twins possessed the HLA type DR3-DR52-DQ2 previously associated with extensive colitis. CONCLUSION: This case report confirms the important role played by genetic factors in the development of inflammatory bowel disease. It also highlights the crucial role of undetermined environmental agents in dictating disease expression and phenotype.

Surgical and smoking history in inflammatory bowel disease: a case-control study.

: An inverse relation between appendectomy and ulcerative colitis and smoking and ulcerative colitis has been proposed. Our study examined the frequency of common surgical interventions and of smoking in 500 patients with inflammatory bowel disease. They comprised 177 patients with ulcerative colitis, 134 patients with Crohn's disease, and 189 controls matched for age, sex, and socioeconomic group. Subjects were questioned on all previous surgery and on smoking history. The appendectomy rate among controls was 17.5% (33 of 189), which was significantly greater than that of patients with ulcerative colitis: 8.5% (15 of 177; p < 0.05). However, after using multiple variable logistic regression analysis, this was no longer statistically significant. There was no significant difference in appendectomy rate between patients with Crohn's disease and controls. The three groups had comparable rates of tonsillectomy and cholecystectomy. Of patients with ulcerative colitis, 84.2% were nonsmokers at the time of diagnosis in contrast to 50.4% among the patients with Crohn's disease (p < 0.01). In this case-control study, by using multivariate logistic regression analysis, appendectomy offers no significant protection from developing ulcerative colitis or Crohn's disease. Smoking appears to be deleterious in Crohn's disease, whereas a cessation of smoking precedes the onset of ulcerative colitis in a significant number of cases.