Quality of life during acute and intermittent treatment of gastro-oesophageal reflux disease with omeprazole compared with ranitidine. Results from a multicentre clinical trial. The European Study Group.
Wiklund I. Bardhan KD. Muller-Lissner S. Bigard MA. Bianchi Porro G. Ponce J. Hosie J. Scott M. Weir D. Fulton C. Gillon K. Peacock R.
Astra Hassle AB, Molndal, Sweden.
AIMS: To investigate quality of life in patients with gastro-oesophageal reflux disease. PATIENTS: A series of 704 patients were randomised to treatment with ranitidine 150 mg bd, omeprazole 10 mg om or omeprazole 20 mg om for 2 weeks. Asymptomatic/mildly symptomatic patients were followed for 12 months. METHODS: The Psychological General Well-Being index and the Gastrointestinal Symptom Rating Scale were completed before and during short-term and intermittent treatment. RESULTS: The quality of life response rate was > 80%. The majority of the patients receiving omeprazole 20 mg om (55%) had symptom relief after 2 weeks despite the fact that more patients on ranitidine required 4 weeks' treatment and an increased dose. There was no difference in the reflux dimension of Gastrointestinal Symptom Rating Scale between treatments in the initial treatment phase, but the total Gastrointestinal Symptom Rating Scale score improved significantly more on omeprazole 10 mg om than on ranitidine 150 mg bd (p = 0.006). Both doses of omeprazole improved the total Psychological General Well-Being score more than ranitidine (omeprazole 10 mg om versus ranitidine 150 mg bd, p = 0.005, omeprazole 20 mg om versus ranitidine 150 mg bd, p = 0.031). During follow-up, relapsing patients returned to pre-treatment symptom and well-being scores, but these dimensions were restored after treatment. CONCLUSION: The quality of life is impaired in patients presenting with reflux symptoms. Irrespective of whether the patients presented with endoscopy positive or endoscopy negative reflux disease, treatment on demand improved the quality of life.
Increased risk for Helicobacter pylori recurrence by continuous acid suppression: a randomized controlled study.
Manes G. Dominguez-Munoz JE. Uomo G. Labenz J. Hackelsberger A. Malfertheiner P.
Dipartimento di Gastroenterologia, Ospedale Cardarelli, Napoli, Italy.
BACKGROUND AND AIMS: Acid hyposecretion may enhance Helicobacter pylori colonization. We tested the hypothesis that maintenance therapy with ranitidine after cure of Helicobacter pylori infection increases the risk of recurrence of infection. PATIENTS AND METHODS: Sixty-six patients with duodenal ulcer and cured Helicobacter pylori infection were randomly assigned to 12 months maintenance treatment with ranitidine 150 mg daily (group A) or no treatment (group B). Follow-up consisted of clinical and endoscopic controls with biopsies for histology and rapid urease test every 4 months. RESULTS: Six patients, 3 in each group, were lost to follow up. Helicobacter pylori recurrence occurred in 9 patients in group A and in 2 patients in group B (30% versus 7%; p < 0.05). Duodenal ulcer recurred in one patient in group A and in 2 in group B, all three patients were reinfected with Helicobacter pylori. A corpus-predominant gastritis was observed in all reinfected patients in group A but in none in group B. CONCLUSIONS: Long-term inhibition of gastric acid secretion after eradication of Helicobacter pylori increases the risk of recurrence of infection. Our data imply that gastric acid not only influences the pattern of Helicobacter pylori localization in gastric mucosa, but also plays a key role in preventing recurrence of infection with Helicobacter pylori.
Mucosal and systemic antibody levels against Helicobacter pylori do not parallel gastric inflammatory changes.
Luzza F. Maletta M. Imeneo M. Marcheggiano A. Biancone L. Pallone F.
Department of Clinical and Experimental Medicine, University of Catanzaro, Italy.
BACKGROUND AND AIMS: Mucosal and systemic antibodies against Helicobacter pylori have been detected but their role in the natural history of Helicobacter pylori-related diseases is unclear. In this study, the levels of Helicobacter pylori IgG and IgA were related to the grade of gastritis. PATIENTS AND METHODS: A series of 152 dyspeptic patients underwent gastroscopy with biopsies. Helicobacter pylori was detected in 131 (86%) patients. Samples of serum and unstimulated saliva were collected. Helicobacter pylori IgG and IgA were measured in homogenised gastric biopsies, saliva and serum by an in-house enzyme linked immunosorbent assay. RESULTS: Levels of gastric mucosa, salivary and serum Helicobacter pylori IgG were higher (p < or = 0.01) in Helicobacter pylori positive than negative patients. Likewise, levels of gastric mucosa and serum Helicobacter pylori IgA were higher (p < 0.01) in Helicobacter pylori positive patients. Gastric mucosa, saliva and serum Helicobacter pylori antibody levels did not differ between superficial and atrophic, active and inactive Helicobacter pylori positive gastritis. CONCLUSIONS: These data indicate that gastric inflammatory changes may not necessarily be related to the antibody response against Helicobacter pylori.
Prevention of gastroduodenal damage with omeprazole in patients receiving continuous NSAIDs treatment. A double blind placebo controlled study.
Bianchi Porro G. Lazzaroni M. Petrillo M. Manzionna G. Montrone F. Caruso I.
Gastro-intestinal Unit, L. Sacco University Hospital, Milano, Italy.
AIM: The aim of this study was to compare omeprazole (20 mg once daily) with placebo in the long-term prevention of gastroduodenal lesions induced by indomethacin, diclofenac and ketoprofen. PATIENTS AND METHODS: 114 patients with arthritic disorders and requiring indomethacin, diclofenac or ketoprofen were randomized in a double blind manner to receive omeprazole-20 mg once daily- or identical placebo for three weeks. The gastroduodenal mucosa damage was scored according to a 0-4 point endoscopic scale. RESULTS: Of the 114 patients, 103 (50 in the omeprazole group, 53 in the placebo group) were submitted to endoscopy, while 11 patients dropped out for non-medical reasons. At the final endoscopy, 26/57 (46%) of omeprazole group, and 20/57 (35%) of the placebo group had normal gastroduodenal mucosa (score = 0) (p ns; 95% IC -0.073 + 0.284). A gastric ulcer was observed in 7/57 (12%) patients, all in the placebo group (p < 0.01 vs omeprazole); 2 patients (1 in the omeprazole group and 1 in the placebo group) developed a duodenal ulcer. Dyspeptic symptoms developed in 10% of the patients treated with omeprazole and 29% of those receiving placebo (p ns). CONCLUSIONS: Omeprazole, 20 mg once daily, provides effective prophylactic therapy in patients at risk of developing NSAID-associated gastric and duodenal ulcer.
A capture-recapture estimate of inflammatory bowel disease prevalence: the Florence population-based study.
Palli D. Masala G. Trallori G. Bardazzi G. Saieva C.
Analytical Epidemiology Section, CSPO, Firenze, Italy. email@example.com
BACKGROUND: A recent population-based epidemiological study identified the patients with a diagnosis of ulcerative colitis or Crohn's disease resident in the metropolitan Florence area in the period 1978-1992 and defined their vital status on 31 December, 1992. AIMS: To estimate the completeness of Inflammatory Bowel Disease prevalent case ascertainment in the study area. SUBJECTS AND METHODS: In a Registry, specifically developed during the study, 767 patients fulfilled the criteria for the definition of prevalent cases as of 31 December, 1992. At the same time, we had access to an independent source of potential patients: the Regional Health Department kept a list of all Inflammatory Bowel Disease patients allowed free access to specific health care provided only to selected diagnostic categories. We then compared the two different sources and used a capture recapture analysis to estimate the number of cases missed by both sources. RESULTS: A total of 331 patients were reported by both sources, 436 were found only in the Registry while a large group of potential cases not present in our Registry was found only in the List. After careful confirmation of the diagnosis for each individual patient and contact with his/her physician, we identified an additional 102 cases that were included in the final population series of 869 prevalent cases. This capture-recapture analysis led to a revised estimate of 1,003 prevalent cases, suggesting that 134 patients had been missed by both sources, resulting in an Inflammatory Bowel Disease prevalence rate of 186 per 100,000. CONCLUSIONS: According to this method our previous study underestimated the true prevalence of 13.4% (95% confidence interval: 9.8-16.6%). On account of some degree of negative dependence between the two sources the loss was probably in the lower range of this interval. Completeness of case ascertainment should be evaluated and discussed in all studies designed to provide population-based estimates for health care planning.
HLA antigens and pANCA define ulcerative colitis as a genetically heterogeneous disorder.
Perri F. Annese V. Piepoli A. Napolitano G. Lombardi G. Ciavarella G. Di Giorgio G. Andriulli A.
Division of Gastroenterologiy, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, FG, Italy.
BACKGROUND: Several genetic and subclinical markers have been associated with ulcerative colitis. AIM: To determine whether a significant association with HLA class I and II antigens was present in Italian ulcerative colitis patients considered as a whole population or stratified according to their anti-neutrophil cytoplasmatic antibodies. METHODS: HLA class I and II antigens were studied by serological typing techniques and related to the presence of anti-neutrophil cytoplasmatic antibodies detected by means of indirect immunofluorescence. RESULTS: Patients with ulcerative colitis (n = 45) had a significantly increased frequency of DQ6 (p = 0.04) and DQ7 (p = 0.003) and a decreased frequency of DQ5 (p = 0.03) and DQ8 (p = 0.02) when compared with ethnically matched healthy controls (n = 252 for HLA class I and 173 for HLA class II). No significant difference in HLA I- and DR-antigens was observed. Anti-neutrophil cytoplasmatic antibodies were found in 27/45 (60%) ulcerative colitis patients and in 0/252 controls (p < 0.001). After stratifying ulcerative colitis patients according to their anti-neutrophil cytoplasmatic antibodies status, anti-neutrophil cytoplasmatic antibodies +ve patients had an increased frequency of A19 (p = 0.007), DR2 (p = 0.03), and DR15 (p = 0.006), and a decreased frequency of A1 (p = 0.004) compared with anti-neutrophil cytoplasmatic antibodies -ve ones. CONCLUSIONS: We suggest that specific HLA-class II loci play an important role in the susceptibility to ulcerative colitis in Italy. A subset of ulcerative colitis patients is characterised by the presence of a specific subclinical marker (anti-neutrophil cytoplasmatic antibodies) which seems to be genetically determined as shown by the increased frequencies of HLA-A19 and DR2 observed in anti-neutrophil cytoplasmatic antibodies +ve ulcerative colitis.
Substance P and vasoactive intestinal polypeptide but not calcitonin gene-related peptide concentrations are reduced in patients with moderate and severe ulcerative colitis.
Renzi D. Mantellini P. Calabro A. Panerai C. Amorosi A. Paladini I. Salvadori G. Garcea MR. Surrenti C.
Department of Clinical Pathophysiology, University of Florence, Italy.
BACKGROUND AND AIMS: Ulcerative colitis is a chronic inflammatory condition characterized by an altered intestinal immunoinflammatory response. Since increasing evidence indicates that neuropeptides play a key role in the regulation of gastrointestinal immune function, the aims of this study were: a) to determine tissue and plasma levels of Vasoactive Intestinal Polypeptide, Substance P, and Calcitonin Gene-Related Peptide in patients with ulcerative colitis, and b) to ascertain whether a relationship exists between tissue concentrations of neuropeptides and the histological grading of mucosal inflammation. METHODS: A total of 29 patients with active and 39 with inactive ulcerative colitis, and 16 control subjects took part in the study. Biopsy specimens of colonic mucosa and blood samples were obtained from each subject, and neuropeptide concentrations were measured by sensitive and specific radioimmunoassays. RESULTS: Both Vasoactive Intestinal Polypeptide and Substance P concentrations were found to be significantly reduced in endoscopic biopsy specimens of patients with ulcerative colitis compared to controls (p < 0.01 and p = 0.05, respectively), and the reduction appeared to be related to the degree of mucosal inflammation; in contrast, Calcitonin Gene-Related Peptide tissue levels were unchanged. In addition, there was no significant difference in the neuropeptide plasma levels between ulcerative colitis patients and control subjects. CONCLUSIONS: Taken together, our results suggest that the reduction of Vasoactive Intestinal Polypeptide and Substance P is probably a secondary phenomenon, correlated with the degree of mucosal inflammation; whatever the mechanism, the decreased availability of these neuropeptides in the local microenvironment may play an important role in the pathogenesis of ulcerative colitis, by affecting many components of the normal immune response. Moreover, based on our data, the measurement of neuropeptide plasma concentrations does not appear to be a useful tool to monitor disease activity.
Organ-specific autoimmunity and genetic predisposition in interferon-treated HCV-related chronic hepatitis patients.
Floreani A. Chiaramonte M. Greggio NA. Fabris P. De Lazzari F. Naccarato R. Betterle C.
Dept. of Gastroenterology, University of Padova, Italy.
AIMS: Interferon alpha has been reported to enhance autoantibody production and to increase the risk of autoimmunity particularly against thyroid tissue. We designed a study with the following aims: 1) to assess the incidence of organ- and non-organ-specific autoantibodies during Interferon treatment; 2) to evaluate whether these autoantibodies have any clinical relevance; 3) to establish whether the development of autoimmune disorders can be related to a genetic predisposition. METHODS: A panel of 5 non-organ-specific and 6 organ-specific autoantibodies was evaluated in serum samples collected before treatment and then at 3 and 12 months in 47 patients enrolled in a treatment protocol with a 2b-recombinant Interferon (3 MU, 3 times a week for 12 months). In the second part of the study we explored genetic predisposition for autoimmune disorders in 31 patients by DNA-HLA class II typing using Restriction Fragment Length Polymorphism (RFPL). RESULTS: Non-organ-specific autoantibodies were absent in all patients before and after Interferon. During follow-up 6 patients showed an increment in thyroid microsomal antibody titres; 3 of these also developed thyroglobulin autoantibodies; 3 of the 6 patients developed persistent hypothyroidism; a fourth had a transient subclinical hypothyroidism and a fifth had a transient subclinical hyperthyroidism. Two patients with initial positivity for ICA and PCA maintained their reactivity during treatment without impairment of the respective target organs. Eight out of 39 initially negative patients developed one or more organ-specific autoantibodies during follow-up. One of these developed a persistent hypothyroidism, and another developed insulin-dependent diabetes. HLA-typing did not reveal any particular allele frequency in patients with thyroid antibody positivity as compared with those without autoantibodies and controls. Moreover, four of the 6 patients positive for islet-cell antibodies were carrying the non-Asp 57 allele which is considered a marker of a genetic predisposition for insulin-dependent diabetes. CONCLUSIONS: These findings suggest that, besides the thyroid gland, pancreatic beta-cells could be a target of autoimmunity during Interferon-treatment for chronic HCV hepatitis. A genetic predisposition may be important, though insufficient alone, in the development of Interferon-induced autoimmune phenomena.
Recurrence of hepatitis B in liver transplants treated with antiviral therapy.
Marzano A. Debernardi-Venon W. Smedile A. Brunetto MR. Torrani Cerenzia MR. Actis GC. Zamboni F. Ghisetti V. Piantino P. David E. Salizzoni M. Rizzetto M.
Department of Gastroenterology, Molinette Hospital, Turin, Italy.
BACKGROUND AND AIMS: In patients with terminal Hepatitis B Virus-related liver diseases, liver transplantation carries a consistent risk of Hepatitis B Virus recrudescence in the graft. In the attempt to reduce the reinfection rate with antiviral therapy, we studied a total of 16 viraemic patients. PATIENTS AND METHODS: Twelve patients received Ganciclovir, starting 4-67 days (mean 25 days) before transplantation and prolonged for 10 days after transplantation; four patients were treated with Lactosaminated Arabinoside-Monophosphate 6 hours before surgery and prolonged for 28 days after surgery. All received hepatitis B immunoglobulins. RESULTS: At transplantation, HBV-DNA had decreased to about 10(4) virus/ml (as assessed by the polymerase chain reaction assay) in 10 of the 12 patients treated with Ganciclovir. Of these patients, 4 died perioperatively from causes unrelated to Hepatitis B Virus reinfection. Of the eight survivors, only the patient who maintained a titre of 10(6) virus/ml at the time of transplantation developed viral recurrence 4 months after surgery. Before transplantation, 2 of the patients treated with Lactosaminated Arabinoside-Monophosphate had a viraemic load of 10(6) and 2 of 10(4) virus/ml. In all cases, viraemia became undetectable at the end of therapy. None died and Hepatitis B Virus recurred 2 months after transplantation in one. The overall rate of Hepatitis B Virus recurrence was 16.6%. The recurrence rate decreased to 9% in patients in whom the viraemic load decreased to around 10(4) virus/ml following treatment, compared to an overall recurrence rate of 50% in our historical series of patients transplanted for Hepatitis B Virus-related cirrhosis. CONCLUSION: Antiviral therapy was effective in decreasing the risk of Hepatitis B Virus reinfection of the liver graft by decreasing the viral load before surgery.
Endoscopy in the treatment of benign biliary strictures.
De Masi E. Fiori E. Lamazza A. Ansali A. Monardo F. Lutzu SE. Recchioni G.
I Department of Surgery Pietro Valdoni, University of Rome, La Sapienza, Italy.
BACKGROUND/AIMS: Operative endoscopy is now the method of choice for treating numerous biliary tree diseases. In the treatment of benign strictures of the biliary tree, endoscopy serves as an alternative to surgical interventions. We evaluated the efficacy of endoscopic biliary stents in the treatment of benign biliary strictures. PATIENTS: Fifty-three consecutive patients with benign strictures of the biliary tree underwent endoscopic placement of one or more 10-12 Fr endoprostheses. Thirty-nine patients (73.6%) had iatrogenic strictures and 14 had inflammatory strictures (in 8 patients due to gallstones and in 6, chronic pancreatitis). Of the 53 patients, 20 (37.7%) had strictures classified as Bismuth type I, 23 (43.3%) Bismuth type II, 7 (13.2%) Bismuth type III and 3 (5.7%) Bismuth type IV. RESULTS: None of the patients died during the study period; three patients (5.6%) had immediate endoscopy-related complications treated conservatively. Late complications developed in 47.1% of the patients: 11.3% had cholangitis amenable to medical therapy, 5.6% had dislodged endoprostheses and 30.2% had obstructed endoprostheses. The reason why blocked stents accounted for most of the long-term complications in this series was that endoprostheses were not changed electively: they were changed only when clinical and laboratory signs indicated obstruction. Follow-up (6-84 months) in 42 of the 56 patients. 20 after stent removal, showed that 71.4% had an excellent outcome, 14.3% good results and 14.3% needed surgery. CONCLUSION: In benign biliary stricture endoscopic stenting is the first approach, providing definitive treatment or preparing patients for surgery.
Main issues in push enteroscopy.
Pennazio M. Rossini FP.
Department of Oncology, S. Giovanni AS Hospital, Turin, Italy.
Endoscopic evaluation of the small bowel has rapidly evolved over the last ten years, marking an important milestone in the diagnosis and treatment of small bowel diseases. Gradual progress in endoscopic techniques and development of new instruments with full therapeutic options have aided and spread the use of enteroscopy. However, some basic issues concerning its appropriate use in clinical practice remain to be solved. This article stresses the importance of lesions missed at oesophagogastroduodenoscopy in patients with obscure gastrointestinal bleeding who undergo push enteroscopy, focuses on the limits of outcome studies related to therapeutic enteroscopy, and critically reviews the clinically relevant indications to push enteroscopy.
Helicobacter pylori and the liver: any relationship?
Farinati F. De Bona M. Floreani A. Foschia F. Rugge M.
Chair of Gastroenterology, University of Padova, Italy.
Helicobacter pylori infection is being correlated to a number of human diseases, among which also those of the liver. From a clinical point of view, 4 "areas of interest" for the suggested correlation can be identified: 1. Helicobacter pylori and portal hypertension-related congestive gastropathy in cirrhotics. There are, in the literature, at least 7 studies confirming that the microorganism has no role in causing or worsening the disease. 2. Helicobacter pylori and duodenal ulcer in cirrhotic patients. Apparently, in the cirrhotic patient, the microorganism has no role in causing duodenal ulcer. 3. Helicobacter pylori, ammonia production and hepatic encephalopathy. In this case, there are at least three studies showing that Helicobacter pylori infection increases the risk of developing encephalopathy in the cirrhotic patient, this being a somewhat expected finding. 4. Helicobacter pylori infection in chronic liver disease and its diagnosis. Evidence in the literature suggests: a) that hypertensive gastropathy might not represent a favourable environment for Helicobacter pylori thus making the diagnostic sensitivity of the biopsy lower than expected, and b) that even serological diagnosis might provide data of difficult interpretation, as shown in non alcoholic cirrhosis and, by our own group, in primary biliary cirrhosis. More intriguing are the data generated with respect to the potential capacity of Helicobacter pylori and Helicobacter pylori-like bacteria such as, in particular, Helicobacter hepaticus to damage the liver by producing toxins with a granulating effect on liver cell lines which, in vivo, through the portal tract, might reach the liver, thus causing hepatocellular damage. The point has been addressed by a number of investigators and autoimmune mechanisms have also been suggested. In summary, from the clinical point of view, some evidence suggests that Helicobacter pylori infection might be relevant in the pathogenesis of hepatic encephalopathy in cirrhosis. The data being generated with respect to a direct hepatotoxicity are, at present, stimulating but only speculative.
Does Helicobacter pylori play a role in inflammatory bowel disease?
Nardone G. Rocco A. Budillon G.
Chair of Gastroenterology, University of Naples, Italy.
The cause of inflammatory bowel disease is still unknown although several bacterial and viral agents have been implicated in their aetiologies. Helicobacter pylori infection, the main cause of gastroduodenal diseases, could, theoretically, be involved in the pathogenesis of inflammatory bowel disease. In fact, it induces permeability alterations and immunological derangements in the stomach similar to those detected in the colon of inflammatory bowel disease patients. However, epidemiological data do not support this hypothesis and recent evidence even points to a low prevalence of Helicobacter pylori in inflammatory bowel disease. These data are discussed in the light of possible confounding factors.