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Background and Aims: Recent guidelines dictate that all Helicobacter pylori (H. pylori) infected subjects should receive curative therapy. The efficacy of empirical regimens for H. pylori eradication might decline with bacterial, drug, and host factors. The necessity of a tailored therapy still remains controversial. Here we provide a meta-analysis of the current status of susceptibility-based (tailored) therapy in which susceptibility-based therapies were compared to the currently accepted choice of empiric therapy. In this rapidly closing era, neither the susceptibility nor empiric therapies were routinely optimized, such that we report the outcome of comparisons on the efficacy of unoptimized tailored vs. locally preferred empiric treatments., Methods: PubMed, Medline, and Embase databases were searched using suitable keywords. Individual and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the fixed- or random-effects model as appropriate. Heterogeneity was calculated employing the Cochrane Q test and I 2 values, whereas the possibility of publication bias was examined by constructing funnel plots. Additionally, subgroup and sensitivity analyses were performed., Results: Thirty-four studies were included with a total of 9613 patients. Tailored therapy proved superior to empiric treatment [OR 2.07 (95% CI 1.53-2.79)]. However, tailored therapy achieved eradication rates >90% in only 15 (44%) studies and >95% in only 6 (17.6%)., Conclusions: Although tailored therapy performed better than empiric treatment, the lack of optimization of therapies failed to reliably achieve high cure rates (>90%). These results emphasize that H. pylori infection, like other infectious diseases, should utilize the principles of antimicrobial stewardship in relation to treatment guidance., (© 2022 John Wiley & Sons Ltd.)

Gastric cancer (GC) is still the fifth most frequently diagnosed cancer and the third leading cause of cancer deaths in both sexes worldwide. Although the incidence of GC is predicted to continue declining in a growing number of countries in the future, on a global scale the number of newly diagnosed GC cases will remain high, or increase even further, due to changes in population size and increasing risks observed in younger generations. In a retrospective cohort study, collecting data from the Veterans Health Administration, treatment of Helicobacter pylori infection decreased GC risk only if eradication was successful. In a German case-control study, among GC patients with autoimmune gastritis, pernicious anemia was associated with earlier detection of GC, which translated into a significantly better 5-year survival. In an updated meta-analysis, H. pylori eradication therapy in healthy individuals significantly reduced both GC incidence and mortality from GC with a number needed to treat of 72 and 135, respectively. In Korea, successful H. pylori eradication substantially reduced GC incidence in first-degree relatives of GC patients as well. A meta-analysis of four trials including 1,556 patients with resectable GC reported that the patient subgroup tumors with high microsatellite instability undergoing surgery did not benefit from perioperative or adjuvant chemotherapy., (© 2020 John Wiley & Sons Ltd.)

Background: Experience in Helicobacter pylori eradication treatment of patients allergic to penicillin is very scarce. A triple combination with a PPI, clarithromycin (C), and metronidazole (M) is often prescribed as the first option, although more recently the use of a quadruple therapy with PPI, bismuth (B), tetracycline (T), and M has been recommended., Aim: To evaluate the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin in the "European Registry of H pylori management" (Hp-EuReg)., Methods: A systematic prospective registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H pylori infection. An e-CRF was created on AEG-REDCap. Patients with penicillin allergy were analyzed until June 2019., Results: One-thousand eighty-four patients allergic to penicillin were analyzed. The most frequently prescribed first-line treatments were as follows: PPI + C + M (n = 285) and PPI + B + T + M (classic or Pylera ® ; n = 250). In first line, the efficacy of PPI + C + M was 69%, while PPI + B + T + M reached 91% (P < .001). In second line, after the failure of PPI + C + M, two rescue options showed similar efficacy: PPI + B + T + M (78%) and PPI + C + levofloxacin (L) (71%) (P > .05). In third line, after the failure of PPI + C + M and PPI + C + L, PPI + B + T + M was successful in 75% of cases., Conclusion: In patients allergic to penicillin, a triple combination with PPI + C + M should not be generally recommended as a first-line treatment, while a quadruple regimen with PPI + B + T + M seems to be a better option. As a rescue treatment, this quadruple regimen (if not previously prescribed) or a triple regimen with PPI + C + L could be used but achieved suboptimal (<80%) results., (© 2020 John Wiley & Sons Ltd.)

Introduction: Helicobacter pylori infection (H pylori-I) affects more than half of the global population and consists an important burden to public health and healthcare expenditures, by contributing to many diseases' pathogenesis., Aim: This study aimed to evaluate the current nonbismuth quadruple eradication regimens in a high antibiotic resistance area, such as Greece, concerning their cost-effectiveness, especially during financial crisis period., Materials and Methods: Eight hundred and nine patients who received eradication treatment against H pylori-I were included to evaluate five different regimens, using amoxicillin, clarithromycin, and metronidazole as antibiotics and one proton-pump inhibitor, based on their current eradication rates. Regimes compared 10-day concomitant use of (a) pantoprazole or (b) esomeprazole; 10-day sequential use of (c) pantoprazole or (d) esomeprazole; and 14-day hybrid using esomeprazole. Cost-effectiveness analysis ratio (CEAR) and incremental cost-effectiveness ratios were calculated taking into account all direct costs and cases who needed second-line treatment. Additionally, sensitivity analysis was performed to predict all potential combinations., Results: Ten-day concomitant regimen with esomeprazole was characterized by the lowest CEAR (179.17€) followed by the same regimen using pantoprazole (183.27€). Hybrid regimen, although equivalent in eradication rates, was found to have higher CEAR (187.42€), whereas sequential regimens were not cost-effective (CEAR: 204.12€ and 216.02€ respectively)., Discussion: This is the first study evaluating the cost-effectiveness of H pylori-I treatment regimens in a high clarithromycin-resistance (≈26.5%) European area, suggesting the 10-day concomitant regimen with generics using esomeprazole 40 mg as the most appropriate one. National and regional guidelines should include cost-effectiveness in their statements, and further studies are required to clarify the necessity of a wide "test and treat" policy for H pylori-I., (© 2019 John Wiley & Sons Ltd.)

Gastric cancer (GC) was responsible for over 1 000 000 new cases in 2018 and an estimated 783 000 deaths, making it still the fifth most frequently diagnosed cancer and the third leading cause of cancer deaths in both sexes worldwide. Divergent trends for GC incidence were observed in the USA. Incidence rates, particularly for non-cardia GC, were stable or increasing among persons aged <50 years. In an analysis of data from a public hospital database in Hong Kong, treatment of Helicobacter pylori infection was associated with a lower risk of GC, particularly in older subjects who received treatment ≥10 years before. Based on the results of a 16-year endoscopy-based follow-up eradication trial, patients with incomplete-type intestinal metaplasia (IM) should receive endoscopic surveillance upon H. pylori eradication therapy. Updated guidelines on the endoscopic surveillance of preneoplastic conditions of the stomach (MAPS II) have been published. In the RAINFALL trial, the addition of ramucirumab to a backbone chemotherapy as a first-line regimen failed to improve overall survival (OS) of patients with metastatic disease. Also, pembrolizumab did not prolong OS when compared to paclitaxel in the second-line treatment of patients with advanced GC or esophagogastric junction (EGJ) cancer. Trifluridine/tipiracil improved OS by 2.1 months in the third or further treatment line of patients with advanced GC. In a systematic investigation conducted on Chinese patients with GC, CLDN18-ARHGAP26/6 fusion was associated with signet-ring cell content and was prognostic for a worse outcome and predictive for no benefit from oxaliplatin/fluoropyrimidine-based chemotherapy. Organoid cultures represent an appealing model that may be applied for therapy response testing in the near future., (© 2019 John Wiley & Sons Ltd.)

Gastric cancer (GC) is still the third leading cause of cancer death in both sexes worldwide. Helicobacter pylori infection is the most important risk factor for GC and, in spite of the consistent trend of a decreasing incidence, in 2015 approximately 4.4 billion individuals-more than half the world's population-were infected with H. pylori. The birth cohort pattern of decreased H. pylori infection reported in a systematic review contributes to explain the declining GC mortality in Japan. Current trends in estimated annual percentage change of GC incidence foreshadow expected reversals in both falling incidence and male predominance among US non-Hispanic whites. Combining serum pepsinogen 1 and H. pylori serology was shown to be useful for GC risk stratification in a Finnish population. Gastritis staging by operative link on gastritis assessment was confirmed to be reliable in predicting GC risk in a large prospective study. In a randomized trial from South Korea, H. pylori eradication therapy significantly reduced the rates of metachronous GC in patients who received curative endoscopic resection for early GC. A study based on a territory-wide health care database of the Hong Kong Hospital Authority showed that aspirin use is associated with a reduced GC risk. Another study based on the same database showed that proton pump inhibitors increase GC risk, but methodological biases have most likely acted as confounders. Confirmatory data on the role of endoscopic submucosal dissection in patients with early GC have been published. The phase III FLOT4 trial has shown that the FLOT triplet regimen (docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil) improves the outcome of patients with GC and locoregional disease as compared to the ECF triplet (epirubicin, cisplatin, and 5-fluorouracil). In the phase III ATTRACTION-2 trial, nivolumab was shown to be an effective treatment option with a relative safe profile for heavily pretreated patients with advanced GC., (© 2018 John Wiley & Sons Ltd.)

In a retrospective study performed in California, U.S.A., ca. 3% of patients with gastric intestinal metaplasia (GIM) developed gastric cancer (GC) within a median time period of 4.6 years after diagnosis of GIM. This observation stresses the importance of targeted surveillance even in regions with a low GC prevalence. Patients with alcoholic liver disease as well as survivors of colorectal and lobular breast cancer were found to be at increased risk of secondary GC. A population-based Chinese study confirmed "serologic biopsy" as a useful screening tool for stratifying the individual risk of developing GC. Concerning GC therapy, a post hoc analysis of the MAGIC trial reported that regression of lymph node metastases, but not the tumor regression itself, predicts overall survival. Furthermore, in patients with high microsatellite instable tumors, perioperative chemotherapy leads to an increased risk of mortality. Two studies confirmed that eradication therapy is worthwhile as an initial treatment for gastric mucosa-associated lymphoid tissue (MALT) lymphoma irrespective of the H. pylori infection status and stage. An increased risk of a second primary malignancy including GC was observed in these patients treated with immuno/chemotherapy but not in patients treated solely with an H. pylori eradication treatment. With respect to gastrointestinal malignancies other than GC, discrepant data have been published regarding the association of H. pylori with pancreatic cancer whereas no association has been reported with esophageal squamous cell carcinoma. The majority of published studies still support an association of H. pylori with colon neoplasms., (© 2017 John Wiley & Sons Ltd.)

Gastric cancer (GC) ranks fifth for cancer incidence and second for cancer deaths. Epidemiological data showed that survivors of Hodgkin's lymphoma and patients with pernicious anemia etiologically linked to autoimmune gastritis are at increased risk of GC. Screening of patients with autoimmune thyroid disease by means of pepsinogen (PG) I and PG I/II detected autoimmune gastritis with oxyntic gastric atrophy in one of four patients and may be recommended for GC prevention purposes. The International Agency for Research on Cancer reported a positive association between consumption of processed meet and increased GC risk. A new GC risk prediction model based on biological markers, age, gender, smoking status, family history of GC, and consumption of highly salted food showed good predictive performance, and might prompt individuals to modify their lifestyle habits, attend regular check-up visits or participate in screening programs. A novel GC classification based on gene expression of primary resected cancers correlated with clinicopathological features. Noncoding RNA for GC screening remains the focus of multiple studies. Patients with early GC undergoing endoscopic resection are more likely to develop metachronous lesions than patients undergoing surgery and endoscopic surveillance is warranted in this special cohort. The addition of gastrectomy to chemotherapy did not improve survival of patients with advanced GC and a single noncurable factor. Apatinib, a novel oral vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, improved the median overall survival of patients with advanced GC and progressive disease after two or more lines of prior chemotherapy of nearly 3 months., (© 2016 John Wiley & Sons Ltd.)

Helicobacter pylori infection is the principal trigger of gastric carcinogenesis and gastric cancer (GC) and remains the third leading cause of cancer-related death in both sexes worldwide. In a big Japanese study, the risk of developing GC in patients with peptic ulcer disease who received H. pylori eradication therapy and annual endoscopic surveillance for a mean of 9.9 years was significantly lower after successful eradication therapy compared to the group with persistent infection (0.21%/year and 0.45%/year, respectively, p = .049). According to a recent meta-analysis, H. pylori eradication is insufficient in GC risk reduction in subjects with advanced precancerous conditions (i.e., intestinal metaplasia and dysplasia). A microsimulation model suggested screening smokers over the age of 50 in the U.S. for serum pepsinogens. This would allow to detect advanced gastric atrophy with endoscopic follow-up of subjects testing positive as a cost-effective strategy to reduce GC mortality. In a Taiwanese study, the anti-H. pylori IgG-based test-and-treat program had lower incremental cost-effectiveness ratios than that with (13)C-urea breath test in both sexes to prevent GC whereas expected years of life lost for GC were higher and the incremental cost-effectiveness ratios of test-and-treat programs were more cost-effective in young adults (30-69 years old) than in elders (>70 years old). With respect to gastrointestinal malignancies other than GC, a meta-analysis confirmed the inverse association between H. pylori infection and esophageal adenocarcinoma. In a Finnish study, H. pylori seropositivity was associated with an increased risk of biliary tract cancers (multivariate adjusted OR 2.63; 95% CI: 1.08-6.37), another meta-analysis showed a slightly increased rate of pancreatic cancer in patients with CagA-negative strains (OR: 1.30; 95% CI: 1.02-1.65), whereas current data suggest that the association between H. pylori and colorectal neoplasms may be population dependent., (© 2015 John Wiley & Sons Ltd.)

Gastric cancer (GC) continues to be an important health threat as the third leading cause of cancer related death in both sexes worldwide. In a recent analysis, the mortality trends for the time period from 1980 till 2011 were significantly downward in all countries, but the declines in the USA, EU and several other major countries were of low magnitude when compared with the past. Furthermore, the relative contribution of cardia cancers compared with noncardia cancers increased among countries with higher GC rates. With respect to preneoplastic changes of the gastric mucosa, a large population-based study suggests that Helicobacter pylori infection and antigastric parietal cell antibodies-mediated autoimmune response might, for the most part, be independent and follow distinct pathways rather than causally related pathways leading to chronic atrophic gastritis. A large prospective, randomized, open-label Korean trial questioned the role of H. pylori eradication for the prevention of metachronous lesions after endoscopic resection of early GC. A review of 1258 Japanese cases undergoing curative endoscopic submucosa dissection for early GC showed that scheduled follow-up endoscopy is mandatory for detecting metachronous lesions at an early stage, where they can be treated by endoscopic resection. Ramucirumab, a vascular endothelial growth factor receptor-2 antagonist, is the first biological treatment that provides survival benefits to patients with advanced GC in progress after first-line chemotherapy. The target agent rilotumumab is currently being evaluated in patients with advanced GC overexpressing the HGF/c-MET signaling pathway. In the near future, ipilimumab and nivolumab, two immunostimulatory monoclonal antibodies with antineoplastic effects, might offer new therapeutic options for patients with advanced GC., (© 2014 John Wiley & Sons Ltd.)

A multifactorial and multistep model of gastric cancer (GC) is currently accepted, according to which different environmental and genetic factors are involved at different stages in the cancer process. The aim of this article is to review the most relevant information published on the relative contribution of genetic and environmental factors. Large meta-analyses confirmed the association between IL8, IL10, TNF-b, TP53 and PSCA, while genetic variation at different genes such as XPG, PLCE1, HFE, ERCC5, EZH2, DOC2, CYP19A1, ALDH2, and CDH1 have been reported to be associated with GC risk. Several microRNAs have also been associated with GC and their prognosis. Cohort studies have shown the association between GC and fruit, flavonoid, total antioxidant capacity, and green tea intake. Obesity was associated with cardia GC, heme iron intake from meat with GC risk. Several large meta-analyses have confirmed the positive association of GC with salt intake and pickled foods and the negative association with aspirin use., (© 2013 John Wiley & Sons Ltd.)

The greatest challenge in Helicobacter pylori-related diseases continues to remain prevention of gastric cancer. New evidence supports the beneficial effect of H. pylori eradication not only on prevention of gastric cancer but also on the regression of preneoplastic conditions of the gastric mucosa. Concerning early detection of gastric cancer there are still no adequate means and there is urgent need to define appropriate markers, for example, by genome-wide research approaches. Currently, the best available method is the "serologic" biopsy based on pepsinogen I and the pepsinogen I/II ratio for identification of patients with severe gastric atrophy at increased risk for gastric cancer development. The treatment of early gastric cancer by endoscopic techniques can be performed safely and efficiently, but patients need meticulous follow-up for detection of metachronous lesions. In case of advanced disease, laparoscopically assisted surgical procedures are safe and favorable compared to open surgery. Two phase III trials support the role of adjuvant systemic treatment with different regimens. Unfortunately, there is still only slow progress in the development of palliative treatment regimens or modification of the existing therapy protocols. There is accumulating evidence for a role of H. pylori infection also in colorectal carcinogenesis. Seropositive individuals are at higher risk for the development of colorectal adenomas and consequently adenocarcinomas of this anatomical region. This phenomenon can partly be attributed to the increase of serum gastrin as response to atrophic changes of the gastric mucosa., (© 2012 Blackwell Publishing Ltd.)

The validity and usefulness of the 7th edition of the UICC tumor node metastasis classification in the context of clinical management of gastric cancer are discussed. The most relevant new agent in gastric cancer therapy is trastuzumab for HER2-positive gastric carcinomas. This marks the success of continuous effort of translational research. Trastuzumab, initially applied in palliative settings, is currently being evaluated also in neoadjuvant treatment regimens. Several new meta-analyses support the carcinogenic effect of high salt intake and smoking in the context of Helicobacter pylori infection. Further data have become available on the efficacy of protective agents, acetyl salicylic acid/nonsteroidal anti-inflammatory drugs, and antioxidants. In search for a successful prevention strategy, the focus is on the identification of individuals at high risk who demand screening (testing) and surveillance. Serological assessment of gastric mucosal abnormalities with increased risk for gastric cancer development is extensively studied, and new data are presented from Asia as well as from Europe. New high-throughput techniques combined with bioinformatic vector analysis open the gate to the identification of new potential diagnostic and therapeutic targets. Furthermore, these approaches allow us to elucidate the interplay of bacterial virulence factors and the host's immune response as well as H. pylori-associated alterations of mucosal gene expression., (© 2011 Blackwell Publishing Ltd.)

Gastric cancer still represents a global health care burden, and in the absence of strategies implemented for early detection, the disease continues to have a dismal prognosis. Patients presenting with clinical manifestations of gastric cancer have limited options for cure. Thus, early detection and prevention play a key role in the fight against gastric cancer. Serologic-based test methods have the potential to detect a subset of patients at high risk of gastric cancer that require a close clinical and endoscopic follow-up. More data have been produced to support Helicobacter pylori eradication as an efficient strategy to prevent gastric cancer. Treatment options for patients with an advanced disease are still limited, but the introduction of new agents opens a more optimistic perspective for the future., (© 2010 Blackwell Publishing Ltd.)

In spite of important new insights into the basic mechanisms of gastric carcinogenesis, progress in the management of gastric cancer has been modest. Some modifications in the chemotherapies used for palliation and strategies for downstaging of the disease prior to surgical intervention are noteworthy. The positive experience with endoscopic mucosal resection (EMR) and submucosal dissection (ESD) for treatment of early gastric cancer has been confirmed and extended. The procedure-related morbidity and post-interventional quality of life is clearly favorable compared to open surgical resection in well-selected patients. New data on Helicobacter pylori revealed that eradication after endoscopic resection of early gastric cancer significantly reduces the incidence of recurrent and metachronous gastric neoplasias. It can further improve healing rates of treatment induced gastric ulcers. Eradication therapy therefore remains the best target for prevention of the disease. Critical is the "point of no return" when mucosal alterations (i.e. intestinal metaplasia, glandular atrophy) are no longer reversible. A population-based screen-and-eradicate strategy for H. pylori infection can at present only be recommended in high incidence regions.

Background: Helicobacter pylori infection is a crucial factor in the multistep carcinogenic process of gastric cancer. In this process the gastric mucosa evolves through the stages of acute gastritis, chronic gastritis, gastric atrophy (GA), and intestinal metaplasia (IM) before developing gastric adenocarcinoma., Aims: The main aim of this study was to systematically review the long-term effects of H. pylori eradication on gastric histology (i.e. effects on GA and IM for both antrum and corpus) by meta-analyzing all relevant studies., Methods: Extensive English-language medical literature searches for human studies were performed through October 2006, using suitable key words. Pooled estimates [odds ratio (OR) with 95% confidence intervals (CI)] were obtained using random-effects model., Results: For antrum GA the pooled OR with 95% CI was 0.554 (0.372-0.825), p=0.004. For corpus GA the pooled OR was 0.209 (0.081-0.538), p<0.001. For antrum IM the pooled OR was 0.795 (0.587-1.078), p=0.14. For corpus IM the pooled OR was 0.891 (0.663-1.253), p=0.506., Conclusion: The results showed significant improvement of GA, whereas improvement was not shown for IM.

In recent years, the focus of Helicobacter pylori clinical research has been mainly on gastric malignancy. However, the role of H. pylori in non-malignant diseases, such as peptic ulcer, gastroesophageal reflux disease (GERD) and non-ulcer dyspepsia, as well as non-steroidal anti-inflammatory drug consumption, is still of great interest. A 1- to 2-week course of H. pylori eradication therapy is an effective treatment for H. pylori-positive peptic ulcer disease and a positive CagA status is a predictor for successful eradication of H. pylori. Antral prostaglandin-E2-basal levels appear to be critical for the development of aspirin-induced gastric damage in subjects without H. pylori infection. In clinical practice, among patients treated with proton-pump inhibitors, H. pylori status has no effect on the speed or degree of GERD symptom relief. For the management of dyspepsia in primary care, antisecretory therapy confers a small insignificant benefit compared to strategies based on H. pylori testing while these latter strategies may be cost-effective. H. pylori eradication therapy has a small but statistically significant effect on H. pylori-positive non-ulcer dyspepsia. An economic model suggests that this modest benefit may still be cost-effective but more research is needed.

Background: A high incidence of Helicobacter pylori among family members of children with H. pylori gastritis has previously been documented on biopsy material. The main objective of this study was the genetic clarification of H. pylori strains involved in intrafamilial dispersion., Materials and Methods: Formalin-fixed, paraffin-embedded material of antral mucosa from 32 members of 11 families was studied for the presence of genetic homogeneity. To achieve this goal, the entire genome of H. pylori was studied by the polymerase chain reaction (PCR)-based random amplified polymorphic DNA (RAPD) fingerprinting method. Furthermore, the Urease A gene was analyzed using a multiplex PCR-assay and an alternative mutation detection method based on the Hydrolink trade mark analysis., Results: RAPD fingerprinting confirmed that closely related H. pylori strains were involved in the intrafamilial dispersion. Mutations and small deletions in Urease A gene were found in 22 out of 32 individuals., Conclusions: The homology of the H. pylori genome in members of the same family strongly supports the hypothesis of transmission of H. pylori from person-to-person or from a common source.

For the therapeutic management of Helicobacter pylori infection, the Maastricht 2-2000 Consensus Report have introduced the concept of the 'treatment package' that considers first- and second-line eradication therapies together. According to this consensus statement, the first-line therapy for H. pylori eradication is a combination of the proton pump inhibitors (PPI) or ranitidine bismuth citrate (RBC) and claritromycin plus either amoxicillin or metronidazole. The second-line treatment is suggested to be PPI-quadruple therapy for a minimum of 7 days. If bismuth compounds are not available, PPI-based triple therapy will have to be used as a second-line treatment only after susceptibility testing. Since no considerable progress has been made during the past year in treatment regimens, there is still a need for new compounds that are specific for H. pylori, which could constitute future therapies.