Clarithromycin is a macrolide antibiotic widely used for eradication of Helicobacter pylori infection, and thus resistance to this antibiotic is a major cause of treatment failure. Here, we present ...the results of a retrospective observational study of clarithromycin resistance (Cla-res) in 4744 H. pylori-infected patients from Central Hungary. We use immunohistochemistry and fluorescence in situ hybridization on fixed gastric tissue samples to determine H. pylori infection and to infer Cla-res status, respectively. We correlate this information with macrolide dispensing data for the same patients (available through a prescription database) and develop a mathematical model of the population dynamics of Cla-res H. pylori infections. Cla-res is found in 5.5% of macrolide-naive patients (primary Cla-res), with no significant sex difference. The model predicts that this primary Cla-res originates from transmission of resistant bacteria in 98.7% of cases, and derives from spontaneous mutations in the other 1.3%. We find an age-dependent preponderance of female patients among secondary (macrolide-exposed) clarithromycin-resistant infections, predominantly associated with prior use of macrolides for non-eradication purposes. Our results shed light into the sources of primary resistant cases, and indicate that the growth rate of Cla-res prevalence would likely decrease if macrolides were no longer used for purposes other than H. pylori eradication.
Autoimmune gastritis is a chronic progressive inflammatory condition that results in the replacement of the parietal cell mass by atrophic and metaplastic mucosa. A complex interaction of ...autoantibodies against the parietal cell proton pump and sensitized T cells progressively destroy the parietal cells, inducing hypochlorhydria and then achlorhydria, while autoantibodies against the intrinsic factor impair the absorption of vitamin B₁₂. The resulting cobalamin deficiency manifests with megaloblastic anaemia and neurological and systemic signs and symptoms collectively known as pernicious anaemia. Previously believed to be predominantly a disease of elderly women of Northern European ancestry, autoimmune gastritis has now been recognized in all populations and ethnic groups, but because of the complexity of the diagnosis no reliable prevalence data are available. For similar reasons, as well as the frequent and often unknown overlap with Helicobacter pylori infection, the risk of gastric cancer has not been adequately assessed in these patients. This Review summarizes the epidemiology, pathogenesis and pathological aspects of autoimmune metaplastic atrophic gastritis. We also provide practical advice for the diagnosis and management of patients with this disease.
Operative link on gastritis assessment (OLGA) staging for gastritis ranks the risk for gastric cancer (GC) in progressive stages (0-IV). This prospective study aimed at quantifying the cancer risk ...associated with each gastritis stage.
A cohort of 1755 consecutive patients with dyspepsia underwent initial (T-0) oesophagogastroduodenoscopy with mapped gastric biopsies, OLGA staging and assessment of
infection. Patients were followed for 55 months (median); patients with stages II III and IV underwent a second endoscopy/restaging (T-1), and those with stages 0 and I were followed clinically and through in-depth clinical and record checking. Endpoints were OLGA stage at T-1 and development of gastric epithelial neoplasia.
At T-0, 77.6% of patients had stage 0, 14.4% stage I, 5.1% stage II, 2.1% stage III and 0.85% stage IV.
infection was detected in 603 patients at T-0 and successfully eradicated in 602 of them; 220 had a documented history of
eradication; and 932 were
naïve-negative. Incident neoplastic lesions (prevalence=0.4%; low-grade intraepithelial neoplasia (IEN)=4; high-grade IEN=1; GC=2) developed exclusively in patients with stages III-IV. The risk for epithelial neoplasia was null in patients at stages 0, I and II (95% CI 0 to 0.4), 36.5 per 1000 person-years in patients at stage III (95% CI 13.7 to 97.4) and 63.1 per 1000 person-years in patients at stage IV (95% CI 20.3 to 195.6).
This prospective study confirms that OLGA staging reliably predicts the risk for development of gastric epithelial neoplasia. Although no neoplastic lesions arose in
naïve patients, the
eradication in subjects with advanced stages (III-IV) did not abolish the risk for neoplastic progression.
As Helicobacter pylori is a first-class carcinogen, eradication of the infection would be expected to be a beneficial measure for the (primary) prevention of gastric cancer. Given the natural history ...of gastric cancer, it is plausible that eradication before gastric atrophy sets in offers the best chance for cancer risk reduction. The beneficial effects of eradication may, nevertheless, still be achievable in more advanced disease. The reversibility of inflammatory lesions has been supported by undeniable evidence; the regression of mucosal atrophy/metaplasia has also been confirmed by several recent histologic studies.
Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This ...latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic(and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and(intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integratingendoscopy, serology, histology and molecular profiling.
Autoimmune gastritis (AIG) is an increasingly prevalent, organ-specific, immune-mediated disorder characterized by the destruction of gastric parietal cells, leading to the loss of intrinsic factor ...and reduced acid output. These alterations result in malabsorption of iron, vitamin B
(pernicious anaemia) and potentially other micronutrients. For several years, most studies have focused on pernicious anaemia only, generating confusion between the two entities. In AIG, the gastric proton pump, H
/K
ATPase, is the major autoantigen recognized by autoreactive T cells. The T cell-dependent activation of B cells stimulates the production of anti-parietal cell antibodies, the serological hallmark of AIG. The role of Helicobacter pylori infection in activating or favouring the autoimmune process is still uncertain. Early histopathological alterations allowing a more precise and prompt recognition have recently been described. AIG is burdened by a substantial diagnostic delay as it can present with varied clinical signs including, among others, gastrointestinal symptoms and neuropsychiatric manifestations. In advanced stages, AIG might progress to neuroendocrine tumours and gastric adenocarcinoma. Management includes early detection through a proactive case-finding strategy, micronutrient supplementation and endoscopic surveillance. This Primer comprehensively describes the most important insights regarding the epidemiology, pathophysiology, diagnosis and management of AIG, focusing on the most controversial, outstanding issues and future directions.
Summary Worldwide, colorectal cancer (CRC) screening programs have significantly increased the detection of sub-mucosal (pT1) adenocarcinoma. Completion surgery may be indicated after endoscopic ...excision of these potentially metastasizing early cancers. However, the post-surgical prevalence of nodal implants does not exceed 15%, leading to questions concerning the clinical appropriateness of any post-endoscopy surgery. Eastern scientific societies (Japanese Society for Cancer of the Colon-Rectum, in particular) include tumor budding (TB), defined as the presence of isolated single cancer cells or clusters of fewer than five cancer cells at the tumor invasive front, among the variables that must be included in histological reports. In Western countries, however, no authoritative endorsements recommend the inclusion of TB in the histology report due to the heterogeneity of definitions and measurement methods as well as its apparent poor reproducibility. To assess the prognostic value of TB in pT1-CRCs, this meta-analysis evaluated 41 studies involving a total of 10,137 patients. We observed a strong association between the presence of TB and risk of nodal metastasis in pT1-CRC. In comparing TB-positive (684/2,401; 28.5%) versus TB-negative (557/7,736; 7.2%) patients, the prevalence of nodal disease resulted in an OR value of 6.44 (95%CI: 5.26–7.87; p<0.0001; I2=30%). This increased risk of regional nodal metastasis was further confirmed after accounting for potential confounders. These results support the priority of histologically reporting TB in any endoscopically removed pT1-CRC to direct more appropriate patient management.
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