Early clinical and pathophysiological manifestations of gastric cancer at the outpatient clinic stage (The “RADIUS” study)

Objective. To study the early clinical and pathophysiological manifestations of gastric cancer in the outpatient phasefor early diagnosis disease.Methods. A total of 300 outpatient cards of patients treated in Smolensk Oncology Hospital with gastric cancer were analyzed during 2016-2019. Data collection included filling out a questionnaire consisting of 32 questions aimed at clarifying demographic data, diagnosing the symptoms of the disease and their duration, identifying the warning signs, precancerous lesion of the gastric mucosa, previous diagnosis and treatment of H. pylori. The study included patients with gastric cancer aged 31 to 88 years. The mean age of patients was 65.12±9.92 years, the median age was 65.5 years. Among 300 patients, 153 (51%) were male and 147 (49%) were female.Results. 2.7% (n=8) of diagnosed patients account for young people. 32.7% (n=98) of patients were diagnosed with the stage II cancer, 32.3% (n=97) — with the stage III cancer. The most common symptoms of the disease were epigastric pain — 57% (n=171), dysphagia — 19.3% (n=58), nausea — 15% (n=45), unmotivated weight loss — 12% (n=36) and epigastric burning — 7% (n=21). These symptoms bothered patients up to 6 months in 32.7% (n=98) of cases. Biochemical blood tests (80%, n=192/240), accelerated ESR (76%, n=183/241), decreased hemoglobin (69%, n=178/258), and leukocytosis (48%, n=120/248) were identified as the most common “warning” signs. 24.7% (n=74) of patients had atrophic gastritis preceded the development of gastric cancer, 24% (n=72) — gastric ulcer, 12% (n=36) — polyps of the stomach. The previous diagnostics of H. pylori was carried out only in 1.3% (n=4) of patients.Conclusions. If a patient, including a young patient, has epigastric pain, primary care physicians should recommend esophagogastroduodenoscopy with biopsies to determine precancerous changes in the gastric mucosa and the presence of H. pylori, followed by eradication therapy.

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The Presence of Periodontal Pathogens in Gastric Cancer

10.1101/2020.03.23.003426 ◽

2020 ◽

Author(s):

Marcel A. de Leeuw ◽

Manuel X. Duval

Keyword(s):

Gastric Cancer ◽

Gastric Mucosa ◽

Eradication Therapy ◽

Downstream Processing ◽

Data Sets ◽

Periodontal Pathogens ◽

Public Data ◽

H Pylori ◽

Pathogen Spectrum

BackgroundThe microbiome is thought to play a role in the development of gastric cancer (GC). Several studies have put forward putatively carcinogenic species in addition to Helicobacter pylori, but are not in perfect alignment, possibly due to variable parameters in the experiments, including downstream processing. Meta-analyses have not been published so far, so there is lack in clinical guidance beyond H. pylori eradication therapy.MethodsHere, we analysed gastric mucosa samples from nine public data sets, including GC samples. Using both unsupervised and supervised learning, we defined fine grain bacterial networks of gastric mucosa and identified species associated with tumor status of samples.ResultsWe found anatomic locations and cohort regions among the possible factors leading to the observation of study specific gastric microbiomes. Despite this variability, the periodontal species Fusobacterium nucleatum, Parvimonas micra and Peptostreptococcus stomatis were found in association with tumor status in several datasets. The three species were predicted to be in interaction by ecological network analysis and also formed the intersection of tumor associated species between four GC data sets and five colorectal cancer (CRC) data sets we reanalyzed. We formulated a probiotic composition putatively competing with the GC pathogen spectrum, from correlation analysis in a large superset of gut samples (n=17,800) from clinical- and crowd-sourced studies.ImplicationsThe overlapping bacterial pathogen spectrum between two gastrointestinal tumor types, GC and CRC, has implications for etiology, treatment and prevention. In vitro testing results reported in literature suggest H. pylori eradication treatment should be efficient against the GC pathogen spectrum, yet the existence of an upstream periodontal reservoir is of concern. To address this, we propose longer term use of the formulated probiotics composition.

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Helicobacter pylori Eradication Therapy - Recent Trend in Research

The Korean Journal of Helicobacter and Upper Gastrointestinal Research ◽

10.7704/kjhugr.2019.0051 ◽

2020 ◽

Vol 20 (3) ◽

pp. 210-217

Author(s):

Heung Up Kim

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Antibiotic Resistance ◽

Gastric Mucosa ◽

Drug Exposure ◽

Eradication Therapy ◽

Dual Therapy ◽

Resistance Rate ◽

H Pylori ◽

Selection Of

It is well known that Helicobacter pylori (H. pylori) can cause peptic ulcer, mucosa-associated lymphoid tissue lymphoma, atrophic gastritis, intestinal metaplasia, and ultimately, gastric cancer. Various studies have proven that H. pylori, which attaches to the gastric mucosa, is the cause of gastric cancer and can be eradicated using appropriate antibiotics. Since 2013, Japan has been carrying out national-led eradication treatment of H. pylori for the whole population. However, as drug exposure increases, the resistance rate to some antibiotics increases, and the pattern of antibiotic resistance varies from region to region. Therefore, the development of individualized antimicrobial therapies has become important since antibiotic resistance to H. pylori eradication is a problem worldwide. To help overcome this, remedies such as selection of antibiotics through susceptibility testing, selection of empirical treatment combinations appropriate for the region, dual therapy with high doses of amoxicillin, and the use of rifabutin or sitafloxacin with low antibiotic resistance have been studied. Potassium-competitive acid blocker has been reported to be more potent in inhibiting acid secretion than proton pump inhibitor, and its role in H. pylori eradication is expected. Drug formulations and regimens that are easy to take are being developed to increase compliance. New treatments such as spraying antibiotics directly to the gastric mucosa are being developed and studied.

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Amoxicillin secretion by gastric mucosa in Chernobyl nuclear power plant accident recovery workers with atrophic and nonatrophic gastritis undergoing eradication therapy

Medico-Biological and Socio-Psychological Problems of Safety in Emergency Situations ◽

10.25016/2541-7487-2020-0-3-36-42 ◽

2020 ◽

pp. 36-42

Author(s):

A. O. Sablina ◽

O. A. Sablin ◽

S. S. Aleksanin ◽

G. G. Rodionov ◽

I. I. Shantyr' ◽

...

Keyword(s):

Gastric Cancer ◽

Power Plant ◽

Nuclear Power Plant ◽

Gastric Mucosa ◽

Gastric Secretion ◽

Nuclear Power ◽

Eradication Therapy ◽

Chernobyl Nuclear Power Plant ◽

Normal Gastric Mucosa ◽

H Pylori

Relevance. Today gastric cancer is still one of the oncologic diseases most often leading to death. H. pylori eradication reduces risk of gastric cancer, but its efficacy depends on gastric mucosa state. Atrophy of gastric mucosa is more common in Chernobyl nuclear power plant (CNPP) accident recovery workers than in patients who have not been involved in CNPP accident recovery works. It seems especially important to investigate the features of antibiotics transport to H. pylori colonization area in this contingent.Intention – to determine the features of amoxicillin secretion by gastric mucosa in CNPP accident recovery workers with atrophic and nonatrophic gastritis undergoing H. pylori eradication.Methodology. 65 CNPP accident recovery workers were divided into groups depending on state of gastric mucosa according to endoscopic and histological examination, immunosorbent assay of pepsinogens I and II and gastrin-17 basal serum levels. On the first day of eradication therapy, gastric secretion samples were obtained via nasogastric probe 30, 60, 120, 180 and 240 minutes after oral amoxicillin administration. Drug concentrations in gastric secretion were assessed via liquid chromatography-mass spectrometry.Results and discussion. Amoxicillin concentrations in gastric secretion samples were lower (р < 0.01) in patients with atrophic antral gastritis than in patients with normal gastric mucosa and atrophic fundal gastritis. Patients with fundal atrophy were characterized by lower amoxicillin concentrations 30 and 60 (p = 0.02) minutes after drug intake than in patients with normal gastric mucosa, and higher concentration in the 120th (p < 0.01) and 180th (p = 0.02) minute than in patients with antral atrophy. Amoxicillin concentrations in patients with antral atrophy were lower (p < 0.01) than in non-atrophy group in the 30th, 60th and 120th minute. In the 240th minute, amoxicillin concentrations in patients with fundal atrophy exceeded concentrations in both other groups (p < 0.01). Amoxicillin concentration peak was registered in patients with fundal and antral atrophy in the 180th minute, in patients without atrophy – from the 30th to 120th minute.Conclusion. Atrophy of gastric mucosa is characterized by decreased transport of orally administered amoxicillin from bloodstream to gastric lumen. Depending on gastric mucosa state, amoxicillin concentrations in gastric secretion should be evaluated at different time points after drug administration: in patients with atrophic gastritis – in the 180th minute, in patients without atrophy – in the 120th minute. While predicting the efficacy and choosing H. pylori eradication regimen, morphological and functional state of gastric mucosa should be taken into account.

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Potential Association of EEF1A Dimethylation at Lysine 55 in the Basal Area of Helicobacter Pylori-Eradicated Gastric Mucosa with the Risk of Gastric Cancer: A Retrospective Observational Study

10.21203/rs.3.rs-1072695/v1 ◽

2021 ◽

Author(s):

Yuka Hirashita ◽

Masahide Fukuda ◽

Masaaki Kodama ◽

Yoshiyuki Tsukamoto ◽

Tadayoshi Okimoto ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Gastric Mucosa ◽

Eradication Therapy ◽

Basal Area ◽

Immunofluorescent Staining ◽

Upper Gastrointestinal Endoscopy ◽

H Pylori ◽

The Relationship

Abstract Background Although eradication therapy for chronic Helicobacter pylori reduces the risk of gastric cancer (GC), its effectiveness is incomplete. Therefore, it is critically important to identify those patients who remain at high risk after H. pylori eradication therapy. Accumulation of protein methylation is strongly implicated in cancer, and a recent study showed that dimethylation of eEF1A lysine 55 (eEF1AK55me2) promotes carcinogenesis in vivo. We aimed to investigate the relationship between eEF1A dimethylation and H. pylori status in gastric mucosa and to reveal potential downstream molecules of eEF1A dimethylation in H. pylori-eradicated mucosa. Methods Records of 115 patients (11 H. pylori-negative, 29 H. pylori-positive, 75 post-eradication patients) who underwent upper gastrointestinal endoscopy were retrospectively reviewed. The eEF1A dimethyl level was evaluated in each functional cell type of gastric mucosa by immunofluorescent staining. We also investigated the relationship between eEF1AK55me2 downregulation by CRISPR/Cas9-mediated deletion of Mettl13, which is known as a dimethyltransferase of eEF1AK55me2. Results The level of eEF1A dimethylation significantly increased in the surface and basal areas of H. pylori-positive mucosa compared with -negative mucosa (surface, p=0.0031; basal, p<0.0001). The eEF1A dimethyl levels in the surface area were significantly reduced by eradication therapy (p=0.005), but those in the basal area were maintained even after eradication therapy. Multivariate analysis revealed that high dimethylation of eEF1A in the basal area of the mucosa was the independent factor related to GC incidence (odds ratio=3.6611, 95% confidence interval=1.0350–12.949, p=0.0441). We also showed the relationship between eEF1A dimethylation and expressions of reprogramming factors Oct4 and Nanog by immunohistochemistry and in vitro genome editing experiments. Conclusions The results indicated that H. pylori infection potently induced eEF1A dimethylation in gastric mucosa. The accumulation of dimethyl-eEF1A in the basal area of the mucosa might contribute to GC risk via regulation of reprograming factors in H. pylori-eradicated gastric mucosa.

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Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

Cells ◽

10.3390/cells10010027 ◽

2020 ◽

Vol 10 (1) ◽

pp. 27

Author(s):

Jacek Baj ◽

Alicja Forma ◽

Monika Sitarz ◽

Piero Portincasa ◽

Gabriella Garruti ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Gastric Mucosa ◽

Virulence Factors ◽

Premalignant Lesions ◽

Bacterial Pathogenicity ◽

Current State ◽

Genetic And Environmental Factors ◽

H Pylori ◽

Stimulation Of

Gastric cancer constitutes one of the most prevalent malignancies in both sexes; it is currently the fourth major cause of cancer-related deaths worldwide. The pathogenesis of gastric cancer is associated with the interaction between genetic and environmental factors, among which infection by Helicobacter pylori (H. pylori) is of major importance. The invasion, survival, colonization, and stimulation of further inflammation within the gastric mucosa are possible due to several evasive mechanisms induced by the virulence factors that are expressed by the bacterium. The knowledge concerning the mechanisms of H. pylori pathogenicity is crucial to ameliorate eradication strategies preventing the possible induction of carcinogenesis. This review highlights the current state of knowledge and the most recent findings regarding H. pylori virulence factors and their relationship with gastric premalignant lesions and further carcinogenesis.

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Prevalence of Helicobacter pylori infection among blood donors in Saxony-Anhalt, Germany – a region at intermediate risk for gastric cancer

Zeitschrift für Gastroenterologie ◽

10.1055/s-0043-106311 ◽

2017 ◽

Vol 55 (07) ◽

pp. 653-656 ◽

Cited By ~ 8

Author(s):

Caspar Franck ◽

Armin Hoffmann ◽

Alexander Link ◽

Christian Schulz ◽

Kerstin Wuttig ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Blood Donors ◽

Eradication Therapy ◽

Surrogate Marker ◽

University Hospital ◽

Study Cohort ◽

Emergency Ward ◽

Age Related ◽

H Pylori

Abstract Background In the federal state of Saxony-Anhalt, gastric cancer (GC) incidence ranks among the highest in Germany. Helicobacter pylori prevalence is a surrogate marker for GC risk in a given population. In 2010 we reported an H. pylori seroprevalence of 44.4 % in patients at the emergency ward of the University Hospital of Magdeburg, the capital of Saxony-Anhalt. Our aim is to update these findings in a cohort of healthy blood donors from the same region. Materials and methods The sera of 516 consecutive blood donors (40.1 ± 14.1 years; 286 males and 230 females) were tested for antibodies against H. pylori and CagA. Data on demographics and previous H. pylori eradication therapy were obtained by means of a structured questionnaire. Blood donors with positive serology for H. pylori or CagA and/or history of eradication therapy were classified as H. pylori-positive. Results Overall, 28.9 % of the study cohort were H. pylori-positive. The prevalence was higher in older generations (9 % in 18 – 20 years up to 47 % in 61 – 70 years). In 44.4 % of H. pylori IgG-positive donors, CagA serology was also positive. This proportion was not age-dependent. Study participants with siblings were by trend more often H. pylori-positive (p = 0.066). Conclusion Compared to our previous study in patients at the emergency ward, we found by trend lower age-related H. pylori prevalence rates. In our cohort of healthy blood donors, we confirmed a lower H. pylori prevalence in younger generations.

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Incidence of gastric cancer, its subtypes, and correlation with Helicobacter Pylori

Journal of Pathology of Nepal ◽

10.3126/jpn.v3i5.7869 ◽

2013 ◽

Vol 3 (5) ◽

pp. 403-407

Author(s):

Shiva Raj KC ◽

GL Amatya ◽

A Lakhey ◽

S Basnet ◽

G Aryal

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Demographic Data ◽

College Teaching ◽

Study Data ◽

Upper Gastrointestinal Endoscopy ◽

Tubular Adenocarcinoma ◽

Common Cause ◽

Medical College ◽

H Pylori

Background: Gastric cancer is the fourth most commonly diagnosed cancer and the second most common cause of cancer related death worldwide. It is the common cause of cancer related death in Nepal. Helicobacter Pylori has been classified as a definite carcinogen along with other factors. The aim of this study was to fi nd the incidence of gastric cancer among the patients undergoing upper gastroscopy, its various subtypes and association with Helicobacter Pylori. Materials and Methods: This is a retrospective and prospective study carried out at GRP Polyclinic and Kist Medical College Teaching Hospital. All the patients undergoing upper gastrointestinal endoscopy were included in this study. Data of all the gastric endoscopic biopsies done from June 2011 to January 2013 were collected and analyzed. All the biopsy specimens were processed routinely in histopathology laboratory. Specimens showing carcinoma were enrolled in this study and all the relevant demographic data were collected. Results: Out of 3395 biopsy cases; 49 cases (1.44%) were diagnosed as adenocarcinoma stomach. The overall mean age for carcinoma was 47.6 years with a mild male preponderance. Thirty cases (61.2%) were of intestinal type, (n=11; 22.4%) were of diffuse type and (n=8; 16.3%) were mixed type of adenocarcinoma. According to WHO classifi cation the most common subtype was tubular adenocarcinoma (n=35; 71.5%) followed by signet ring type (11 cases; 22.4%). Out of 49 cases of adenocarcinoma stomach 39 cases (79.5%) were Helicobacter Pylori positive. Conclusion: This study shows that gastric carcinoma is a male predominant neoplasm usually of old age but can occur at younger ages. It predominantly occurs in Helicobacter Pylori infected patients and H. Pylori eradication will help to decrease the incidence rate and mortality of stomach cancer. Journal of Pathology of Nepal (2013) Vol. 3, No.1, Issue 5, 403-407 DOI: http://dx.doi.org/10.3126/jpn.v3i5.7869

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Prognostic Nomogram on Clinicopathologic Features and Serum Uric Acid for Precancerous Lesions and Gastric Cancer

10.21203/rs.3.rs-748722/v1 ◽

2021 ◽

Author(s):

Shanshan Tang ◽

Ying Chen ◽

Chenhong Fu ◽

Xin Xie ◽

Ziyu Song ◽

...

Keyword(s):

Gastric Cancer ◽

Uric Acid ◽

Serum Uric Acid ◽

Precancerous Lesions ◽

Multiple Logistic Regression Analysis ◽

Precancerous Lesion ◽

Multiple Logistic Regression ◽

Diagnosis Rate ◽

H Pylori ◽

The Relationship

Abstract The relationship between Uric acid (UA) and malignant tumor are still confusing. Gastric cancer(GC) is recognized to be closely related to Helicobacter pylori (H. pylori) infection, early diagnosis rate is very low. In this study, we aimed to investigate the relationship between H. pylori and hyperuricemia (HUA), and evaluate the predictive value of serum uric acid (SUA) in gastric precancerous lesion (GPL) and gastric cancer (GC). This retrospective study included 486 patients who underwent gastroscopy (155 controls, 272 GPL, 59 GC patients). The risk factors for GPL and GC were identified by multiple logistic regression analysis and nomogram was constructed to evaluate the ability of SUA to predict the risk of these diseases based on SUA score. We found that in healthy controls, HUA is positively correlated with H. Pylori (+). SUA was an independent risk factor for GPL and GC. Verification shows that the nomogram was better fitted for GC than for GPL. In conclusion, our study established nomogram based on SUA to predict the risk of GPL and GC, suggested that the incidence of GPL and GC is higher in H. pylori (+) HUA patients, so early intervention and vigilance should be raised.

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Lower LINE-1 methylation is associated with promoter hypermethylation and distinct molecular features in gastric cancer

Epigenomics ◽

10.2217/epi-2019-0091 ◽

2019 ◽

Vol 11 (15) ◽

pp. 1651-1659

Author(s):

Sayumi Tahara ◽

Tomomitsu Tahara ◽

Noriyuki Horiguchi ◽

Masaaki Okubo ◽

Tsuyoshi Terada ◽

...

Keyword(s):

Gastric Cancer ◽

Gastric Mucosa ◽

Cpg Island ◽

Methylation Status ◽

Promoter Hypermethylation ◽

Cpg Island Methylator Phenotype ◽

Line1 Methylation ◽

Methylator Phenotype ◽

H Pylori ◽

Mlh1 Methylation

Aim: To investigate the associations between LINE1 methylation, an indicator for genome-wide hypomethylation, molecular and clinicopathological characteristics of gastric cancer (GC) patients. Patients & methods: LINE1 methylation statuses were examined in paired cancerous, non-neoplastic mucosa from 217 GC and gastric mucosa from separate group of 224 noncancer patients. CpG island methylator phenotype, TP53 and KRAS mutation, MLH1 methylation status and promoter hypermethylation of GC related and H. pylori-related genes were examined. Results: Lower LINE1 methylation was observed in primary GC compared with non-neoplastic gastric mucosa and associated with CpG island methylator phenotype, TP53 mutation, MLH1 methylation and promoter hypermethylation of GC related and H. pylori-related genes. Conclusion: Lower LINE1 methylation correlates specific molecular subtypes and promoter hypermethylation in GC.

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Evaluation of the Epidemiologic Efficacy of Eradicating Helicobacter pylori on Development of Gastric Cancer

Epidemiologic Reviews ◽

10.1093/epirev/mxz006 ◽

2019 ◽

Vol 41 (1) ◽

pp. 97-108 ◽

Cited By ~ 2

Author(s):

Fujiao Duan ◽

Chunhua Song ◽

Jintao Zhang ◽

Peng Wang ◽

Hua Ye ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Population Attributable Risk ◽

Eradication Therapy ◽

Attributable Risk ◽

Chinese Patients ◽

Controlled Trials ◽

Mixed Effect ◽

H Pylori ◽

Development Of Gastric Cancer

Abstract Eradication of Helicobacter pylori colonization has been reported to affect the progression of gastric cancer. A comprehensive literature search was performed from 1997 to 2017 using electronic databases. All randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCT) evaluated the effect of H. pylori eradication on development of gastric cancer. Four RCTs and 9 non-RCTs were included (n = 40,740 participants; 321,269 person-years). Overall, H. pylori eradication therapy was associated with a significantly reduced risk of gastric cancer (incidence rate ratio (IRR) = 0.52, 95% confidence interval (CI): 0.41, 0.65). Results of mixed-effect Poisson regression meta-analysis were similar to those of traditional meta-analyses. In stratified analyses, the IRRs were 0.59 (95% CI: 0.41, 0.86) in RCTs and 0.48 (95% CI: 0.36, 0.64) in non-RCTs. The IRRs were 0.45 (95% CI: 0.34, 0.61) in patients and 0.63 (95% CI: 0.44, 0.90) in the general population. Moreover, the relative risk reduction was approximately 77% on the development of noncardiac gastric cancer with H. pylori eradication therapy in China. Attributable risk percentage and population attributable risk percentage for Chinese patients were 77.08% and 75.33%, respectively, and for Japanese patients were 57.80% and 45.99%, respectively. H. pylori eradication therapy reduces the risk of noncardiac gastric cancer development. The findings indicate the importance of early intervention with H. pylori eradication therapy from the perspective of epidemiology.

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