Strategies for Prevention of Gastric Cancer: Progress from Mass Eradication Trials

2016 ◽  
Vol 34 (5) ◽  
pp. 500-504 ◽  
Author(s):  
Kentaro Sugano

Background:Helicobacter pylori infection is the cause of the majority of gastric cancer. Meta-analyses on several interventional trials, irrespective of the target population, unanimously demonstrated the benefit of eradication therapy in reducing the occurrence of gastric cancer. Based on the evidence for the preventive effects on gastric cancer by eradication therapy in the general population, the International Agency for Research on Cancer advocated eradication of H. pylori as the primary preventive strategy for gastric cancer. Consensus reports on H. pylori gastritis by experts also recommended eradication of H. pylori as the strategy for prevention of gastric cancer. Key Messages:H. pylori is responsible for the majority of gastric cancer. As the eradication of the infection has been shown to reduce subsequent development of gastric cancer, a number of large-scale controlled trials involving a large number of subjects are currently underway in various countries to further verify the feasibility and effects of H. pylori eradication on gastric cancer prevention. However, such studies might be considered unethical as we already knew that the criminal role of H. pylori in gastric carcinogenesis. In Japan, rather than conducting clinical trials, the government adopted insurance coverage for H. pylori gastritis irrespective of symptoms. This policy brought about a massive surge in eradication therapy, which will ensue in a drastic reduction in the prevalence of H. pylori by 2030 as well as gastric cancer. Conclusions: Primary prevention of gastric cancer is now moving into implementation phase in Japan and will be spreading in other counties where long-term clinical trials have started.

2018 ◽  
Vol 01 (1) ◽  
Author(s):  
Takalkar U Vidyadhar

Gastric cancer is a multifactorial disease with complex interplay of environmental and genetic factors. Helicobacter pylori (H. pylori) infestation has been identified as the most important etiological agent in the pathogenesis of gastric cancer. Also, the role of dietary factors that is low consumption of fruits and vegetables have been found to be associated with gastric cancer. Among the dietary factors, antioxidants especially vitamin C has been found to confer the strongest protection against gastric cancer. Its anti-proliferative and pro-apoptotic action has been suggested in vitro. Because of its antioxidant activity, it protects cells against oxidative DNA damage caused by toxic effects of reactive oxygen species. It also inhibits production of carcinogenic N-nitroso compound in the stomach. The person with H. pylori infection has low levels of vitamin C in their gastric juice and levels of vitamin C normalizes on eradication of H. pylori. Vitamin C levels are high in gastric mucosa and gastric juice, sometimes more than that of in plasma. But gastric pathological conditions cause lowered secretion of vitamin C into gastric juice. Effect of H. pylori on vitamin C in gastric juice is reversible and on eradication of H. pylori, it returns to normal level. Hence, eradication of H. pylori and chemoprevention with antioxidant supplementation will be an effective preventive strategy to reduce the incidence of gastric cancer and related mortality. Vitamin C and gastric cancer is an area of potential interest for researchers as a preventive measure. Keywords: Vitamin C, H. pylori, gastric cancer.


2017 ◽  
Vol 55 (07) ◽  
pp. 653-656 ◽  
Author(s):  
Caspar Franck ◽  
Armin Hoffmann ◽  
Alexander Link ◽  
Christian Schulz ◽  
Kerstin Wuttig ◽  
...  

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.


2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
De-Min Cao ◽  
Qun-Feng Lu ◽  
Song-Bo Li ◽  
Ju-Ping Wang ◽  
Yu-Li Chen ◽  
...  

The genusHelicobacteris a group of Gram-negative, helical-shaped pathogens consisting of at least 36 bacterial species.Helicobacter pylori(H. pylori), infecting more than 50% of the human population, is considered as the major cause of gastritis, peptic ulcer, and gastric cancer. However, the genetic underpinnings ofH. pylorithat are responsible for its large scale epidemic and gastrointestinal environment adaption within human beings remain unclear. Core-pan genome analysis was performed among 75 representativeH. pyloriand 24 non-pylori Helicobactergenomes. There were 1173 conserved protein families ofH. pyloriand 673 of all 99Helicobactergenus strains. We found 79 genome unique regions, a total of 202,359bp, shared by at least 80% of theH. pyloribut lacked in non-pylori Helicobacterspecies. The operons, genes, and sRNAs within theH. pyloriunique regions were considered as potential ones associated with its pathogenicity and adaptability, and the relativity among them has been partially confirmed by functional annotation analysis. However, functions of at least 54 genes and 10 sRNAs were still unclear. Our analysis of protein-protein interaction showed that 30 genes within them may have the cooperation relationship.


2019 ◽  
Vol 41 (1) ◽  
pp. 97-108 ◽  
Author(s):  
Fujiao Duan ◽  
Chunhua Song ◽  
Jintao Zhang ◽  
Peng Wang ◽  
Hua Ye ◽  
...  

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.


2018 ◽  
Vol 06 (11) ◽  
pp. E1289-E1295 ◽  
Author(s):  
Kazuyoshi Yagi ◽  
Itsuo Nagayama ◽  
Takahiro Hoshi ◽  
Satoshi Abe ◽  
Shin-ichi Morita ◽  
...  

Abstract Background and study aims Assessment of the extent of gastric cancer detected by endoscopy after successful eradication of H. pylori is often difficult even with narrow-band imaging (NBI)-magnifying endoscopy. Using the latter modality, it has often been noted that the cancerous area has a brownish color surrounded by green epithelium (GE). If the histological origin of this GE could be clarified, it could be of practical use for endoscopic assessment of the extent of cancer. Materials and methods The endoscopic appearance of gastric cancer after eradication therapy was classified into four types: (A) cancer brownish, surrounding mucosa green; (B) cancer brownish, surrounding mucosa brownish; (C) cancer green, surrounding mucosa brownish; and (D) cancer green, surrounding mucosa green. A histological series of sections taken from tissues in each endoscopic view was stained with HE, and also for CDX2, MUC2, CD10 and MUC5AC. Staining intensity was evaluated by microscopy using a visual analog scale ranging from 0 to 3+: intensities of 0 and 1+ were rated as negative, and those of 2+ and 3+ as positive. Positive or negative immunostaining was examined for each type of endoscopic appearance A – D. Results Among 42 lesions examined, 16 were type A, 18 type B, 6 type C and 2 type D. MUC2 was positive in the surrounding mucosa in 100 % of type A and D cases, but in only 28 % and 17 % of type B and C cases, respectively. Conclusions GE observed by NBI-endoscopy corresponds to MUC2-positive mucosa and is thought to be a feature for practical assessment of the extent of cancer.


PLoS ONE ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. e0239434
Author(s):  
Natsuda Aumpan ◽  
Ratha-Korn Vilaichone ◽  
Pongjarat Nunanan ◽  
Soonthorn Chonprasertsuk ◽  
Sith Siramolpiwat ◽  
...  

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 431-431
Author(s):  
Hiroki Hara ◽  
Atsushi Takeno ◽  
Hisateru Yasui ◽  
Hiroshi Imamura ◽  
Hiroki Akamatsu ◽  
...  

431 Background: FGFR2 and HER2 proteins are well-known molecular targets for cancer therapy, and there are emerging attractive protein-targeted agents such as second generation antibody-drug conjugates. However, there are still limited information about the expression status of FGFR2 and HER2 in gastrointestinal cancer and their relationship to patient background with cancer. In this study, expression status of FGFR2 and HER2 in advanced/metastatic gastric cancer (GC) and colorectal cancer (CRC) were prospectively analyzed in clinical setting. Moreover, eligible patients for the clinical trials of DS-1123 or DS-8201, which are FGFR2- or HER2-targeting anti-cancer agent respectively, were screened. Methods: Patients with advanced/metastatic GC, gastroesophageal junctional cancer (GEJ), and CRC were enrolled. Expression status of FGFR2 and HER2 were prospectively analyzed by IHC and/or FISH. Results: A total of 565 patients (GC; 160, GEJ; 16, CRC; 389) have been enrolled in this study from November 2016 to June 2018. FGFR2 expression (IHC 1+~3+) was observed in 24%, 44%, and 3% of GC, GEJ, and CRC respectively. HER2 expression (IHC 2+, 3+) was observed in 24%, 44%, and 17% of GC, GEJ, and CRC respectively. Expression levels of FGFR2 and HER2 seemed to be not correlated with each other in all 3 types of cancer. Distributions of expression level of FGFR2 or HER2 were slightly different among the histological types in GC. In CRC, distribution of HER2 expression level was also slightly different among the histological types and HER2 expression level was higher in KRAS/NRAS wild type compared to KRAS/NRAS mutant. There was no association between HER2 expression level and primary tumor sites in patients with CRC. Slight concordance of HER2 expression was observed between IHC and FISH in CRC. A total of 7 patients have been enrolled in clinical trials of DS-1123 or DS-8201 through this study based on the analysis findings. Conclusions: This study showed insights into the expression status of FGFR2 and HER2 in GC and CRC as a large-scale prospective analysis. Seven patients who had no standard therapy could access exploratory new drug based on targetable agents through this study. Clinical trial information: 163380.


BMJ Open ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. e016999 ◽  
Author(s):  
Marcis Leja ◽  
Jin Young Park ◽  
Raul Murillo ◽  
Inta Liepniece-Karele ◽  
Sergejs Isajevs ◽  
...  

IntroductionPopulation-based eradication ofHelicobacter pylorihas been suggested to be cost-effective and is recommended by international guidelines. However, the potential adverse effects of widespread antibiotic use that this would entail have not been sufficiently studied. An alternative way to decrease gastric cancer mortality is by non-invasive search for precancerous lesions, in particular gastric atrophy; pepsinogen tests are the best currently available alternative. The primary objective of GISTAR is to determine whetherH pylorieradication combined with pepsinogen testing reduces mortality from gastric cancer among 40–64-year-old individuals. The secondary objectives include evaluation ofH pylorieradication effectiveness in gastric cancer prevention in patients with precancerous lesions and evaluation of the potential adverse events, including effects on microbiome.Methods and analysisIndividuals are recruited from general population (50% men) in areas with high gastric cancer risk in Europe and undergo detailed lifestyle and medical history questionnaire before being randomly allocated to intervention or control groups. The intervention group undergoesH pyloritesting and is offered eradication therapy if positive; in addition, pepsinogen levels are detected in plasma and those with decreased levels are referred for upper endoscopy. All participants are offered faecal occult blood testing as an incentive for study participation. Effectiveness of eradication and the spectrum of adverse events are evaluated in study subpopulations. A 35% difference in gastric cancer mortality between the groups is expected to be detectable at 90% power after 15 years if 30 000 individuals are recruited. Biological materials are biobanked for the main and ancillary studies. The study procedure and assumptions will be tested during the pilot phase.Ethics and disseminationThe study was approved by the respective ethics committees. An independent Data Safety and Monitoring Board has been established. The findings will be published in peer-reviewed journals and presented at scientific meetings.Trial registration numberNCT02047994


2018 ◽  
Author(s):  
Takalkar U Vidyadhar

Gastric cancer is a multifactorial disease with complex interplay of environmental and genetic factors. Helicobacter pylori (H. pylori) infestation has been identified as the most important etiological agent in the pathogenesis of gastric cancer. Also, the role of dietary factors that is low consumption of fruits and vegetables have been found to be associated with gastric cancer. Among the dietary factors, antioxidants especially vitamin C has been found to confer the strongest protection against gastric cancer. Its anti-proliferative and pro-apoptotic action has been suggested in vitro. Because of its antioxidant activity, it protects cells against oxidative DNA damage caused by toxic effects of reactive oxygen species. It also inhibits production of carcinogenic N-nitroso compound in the stomach. The person with H. pylori infection has low levels of vitamin C in their gastric juice and levels of vitamin C normalizes on eradication of H. pylori. Vitamin C levels are high in gastric mucosa and gastric juice, sometimes more than that of in plasma. But gastric pathological conditions cause lowered secretion of vitamin C into gastric juice. Effect of H. pylori on vitamin C in gastric juice is reversible and on eradication of H. pylori, it returns to normal level. Hence, eradication of H. pylori and chemoprevention with antioxidant supplementation will be an effective preventive strategy to reduce the incidence of gastric cancer and related mortality. Vitamin C and gastric cancer is an area of potential interest for researchers as a preventive measure. Keywords: Vitamin C, H. pylori, gastric cancer.


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