Patients with a corpus predominant or pangastritis have a much higher stomach cancer risk than those with an antral predominant gastritis

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Differences in the nature and severity of gastritis in the antrum and corpus of those patients with consensus gastritis in the two populations were further explored by comparing the cumulative scores for each of the parameters of the updated Sydney system (chronic inflammation, polymorph activity, atrophy, and IM) given by both pathologists for biopsies 1 and 2 (antrum) and biopsies 4 and 5 (corpus). The results are shown in fig 44.. Comparisons for each decennial are shown with patients grouped into <50 and >50 for statistical comparison. Chronic inflammation and activity scores were comparable in the antrum but markedly lower in the corpus of the UK patients. This largely explains the greater prevalence of antrum predominant gastritis in UK subjects; Japanese subjects had the same, or even higher, scores for chronic inflammation in the antrum but in general had far more corpus chronic inflammation. The degree of corpus atrophy was more marked in the Japanese patients, especially in the older age groups.

 

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H pylori associated gastritis​

Gastritis patients were assessed for H pylori infection (table 55).). Forty six of 59 (78%) UK patients had histological or microbiological (culture) evidence of H pylori infection compared with 54 of 76 (71%) Japanese patients (χ2 test, p = 0.6). However, these values do not include those in whom H pylorimay have originally caused inflammation but had subsequently disappeared. If serological evidence is taken into account, 53 of 59 (90%) UK patients and 67 of 76 (88%) of Japanese patients may have been infected at some time (χ2 test, p = 1). Alternatively, if the diagnosis of H pylori infection is taken to require two positive tests, there were 51 (85%) UK and 56 (74%) (χ2 test, p = 0.5) Japanese positives (table 55).

 

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H pylori associated gastritis​

Gastritis patients were assessed for H pylori infection (table 55).). Forty six of 59 (78%) UK patients had histological or microbiological (culture) evidence of H pylori infection compared with 54 of 76 (71%) Japanese patients (χ2 test, p = 0.6). However, these values do not include those in whom H pylorimay have originally caused inflammation but had subsequently disappeared. If serological evidence is taken into account, 53 of 59 (90%) UK patients and 67 of 76 (88%) of Japanese patients may have been infected at some time (χ2 test, p = 1). Alternatively, if the diagnosis of H pylori infection is taken to require two positive tests, there were 51 (85%) UK and 56 (74%) (χ2 test, p = 0.5) Japanese positives (table 55).

So both uk and Japan have similar h pylori and yet only Japan has high incidence of stomach cancer. Conclusion Angmoh the best genes!

 

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H pylori pathogenicity​

CagA status was assessed using an immunoblot assay. Forty seven (37%, mean age 54 years) UK and 72 (57%, mean age 56 years; χ2test, p = 0.003) Japanese samples were positive for the 116 kDa protein that corresponds to the presence of the CagA antibody. Histology of the CagA positive patients was compared. There were similar antral activity and chronic inflammation scores in the two populations but greater corpus atrophy, chronic inflammation, and polymorph activity in the Japanese population (fig 55,, table 88).). The proportions of corpus predominant/pangastritis and antral predominant in CagA positive cases were similar to those found in all cases of gastritis (antral predominant 49% Japan, 67% UK; p = 0.06).

 

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We were able to culture and subtype 53/56 (94%) Japanese H pylori positive patients and 29/51 (57%) UK patients. All 53 Japanese patients were VacA subtype s1m1. Fifty two of 53 Japanese patients were CagA positive although one patient had CagA positive antral and CagA negative body cultures. Eleven of 29 UK patients had VacA s1m1 subtype, 13 were s1m2, and five were s2m2. Overall 26/29 were CagA positive.

Histological differences remained when 52 Japanese and 10 UK patients who were CagA positive and VacA s1m1 on antral biopsy culture were compared. It is apparent that the differences seen for all H pylori gastritis patients are maintained when like is compared with like. Cag and Vac pathogenicity of H pylori does not appear to be the decisive factor explaining the differences in gastritis between the two populations.

 

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Gastric cancer risk scores for H pylori positive patients​

In order to further explore the histological data, we used a previously validated gastric cancer risk score, as described by Meining and colleagues.15 They compared gastritis in patients with small early gastric cancers with histologically proven H pylori infection with a control group of H pylori positive duodenal ulcer patients who had a low risk of gastric cancer. Their scoring system was calculated as follows:

1. Infiltration with chronic inflammatory cells is more pronounced in the corpus mucosa than in the antrum, or is equally distributed = 1 point.
2. Infiltration with neutrophils ( = “activity” in the Sydney system) is more pronounced in the corpus mucosa than in the antrum, or is equally distributed = 1 point.
3. Presence of IM in the antrum or corpus = 1 point.

In Meining's study, the predictive value for the presence of gastric carcinoma was 0.166 for 0 points, 0.464 for 1 point, 0.791 for 2 points, and 0.943 for 3 points.

Histology results of the 45 UK patients and 54 Japanese patients who had histological evidence of H pylori infection were analysed (in keeping with the original study).

The sum of the chronic inflammatory scores for both pathologists for biopsies 1 and 2 (antrum) were compared with the scores for biopsy 4 and 5 (corpus). The same approach was used for activity in the corpus and antrum. Finally, IM in the antrum or corpus reported by either pathologist was noted. Again the results for both pathologists were added together and this value used to establish the cancer risk score.

Comparing the cumulative scores (table 99),), there were significantly more Japanese patients with a score of 3, and conversely more UK patients with a score of 0. The proportion of patients with intermediate scores of 1 and 2 were similar in both patient groups.

 

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Discussion​

We believe this to be the first study to prospectively compare the histology of two matched populations from countries with substantially different gastric cancer rates. The selection process excluded patients with macroscopic pathology such as cancer, peptic ulcer, and reflux oesophagitis. Only those with symptoms of “functional” dyspepsia were assessed and the protocol ensured similar age cohorts.

The major weakness of the study is that dyspeptic symptoms were not identical because of differences in culture, language, and health seeking behaviour in the two countries. However, strict adherence to inclusion and exclusion criteria should have minimised this effect; in particular we ensured that the National Cancer Centre patients were attending for investigation of simple dyspepsia and not for possible malignancy. It also proved impossible to “blind” the two pathologists with respect to the source of the material they were examining. The kappa statistics were generally good with the sole exception of antral atrophy in young patients; however, antral atrophy has previously been recognised as a difficult feature to assess.16 A further weakness of the study was that we were unable directly to compare social class between the two countries because a system of social assessment does not exist in Japan. Nor was it considered possible to obtain an accurate dietary history from the Japanese patients.

The cause of the gastritis was predominantly H pylori infection. Other aetiologies are unlikely because of the histological findings, and patients on recent non‐steroidal anti‐inflammatory drugs were excluded. No patient had the characteristic histological appearance of autoimmune gastritis (a condition that is very rare in Japan anyway) but parietal cell antibodies were not checked.

As this was a cross sectional analysis we must remember that the age of infection with H pylori (assumed to be in childhood) is not known. The rate at which patients were infected and at what age would be important factors in determining the future histological changes.

The difference in prevalence (12.5%) of gastritis between the two groups was lower than anticipated and this reflected the unexpected similarity in H pylori infection rates. This finding is commensurate with the falling rate of infection in the Japanese population. Our results show that gastritis in Japan is histologically more severe, is present at an earlier age, and is more likely to be corpus predominant or pangastritis. Three possible explanations may account for the differences between the two populations: the genetic constitution of the host, the genotype of the infecting organism, and the environment.

 

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Severity of inflammation​

Cytokine production is largely responsible for the host's inflammatory response to H pylori infection and is genetically determined. Interleukin (IL) 1β and tumour necrosis factor α (TNF‐α) are proinflammatory cytokines that also inhibit acid production. Polymorphisms of the genes controlling production of these cytokines have been linked to different levels of IL‐1β and TNF‐α production and have been associated with an increased risk of gastric cancer, chronic atrophic gastritis, IM, and gastric ulcer.5,17,18,19
Bacterial factors are also important. Possession of the Cag associated pathogenicity island leads to production of the CagA protein20 and is associated with an increased severity of gastritis and incidence of peptic ulcer disease and gastric cancer.21,22,23,24 Production of the vacuolating toxin VacA, and the genotype of the VacA gene, are also associated with increased pathogenicity.25
Another environmental factor likely to play a role in the severity of gastritis is diet. Diet has long been postulated as an aetiological factor for non‐cardia gastric cancer, with nitrate and salt intake both being implicated,1,2,26 while antioxidants such as vitamins A, C, and E may be protective.27 The Japanese diet is higher in salt than a standard Western diet and animal models show that a high salt diet causes an acute gastritis.28

 

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Severity of inflammation​

Cytokine production is largely responsible for the host's inflammatory response to H pylori infection and is genetically determined. Interleukin (IL) 1β and tumour necrosis factor α (TNF‐α) are proinflammatory cytokines that also inhibit acid production. Polymorphisms of the genes controlling production of these cytokines have been linked to different levels of IL‐1β and TNF‐α production and have been associated with an increased risk of gastric cancer, chronic atrophic gastritis, IM, and gastric ulcer.5,17,18,19
Bacterial factors are also important. Possession of the Cag associated pathogenicity island leads to production of the CagA protein20 and is associated with an increased severity of gastritis and incidence of peptic ulcer disease and gastric cancer.21,22,23,24 Production of the vacuolating toxin VacA, and the genotype of the VacA gene, are also associated with increased pathogenicity.25
Another environmental factor likely to play a role in the severity of gastritis is diet. Diet has long been postulated as an aetiological factor for non‐cardia gastric cancer, with nitrate and salt intake both being implicated,1,2,26 while antioxidants such as vitamins A, C, and E may be protective.27 The Japanese diet is higher in salt than a standard Western diet and animal models show that a high salt diet causes an acute gastritis.28

So diet or high salt diet is only one factor. The rest are genes and bacteria aka LUCK indeed.

 

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Cytokine production is largely responsible for the host's inflammatory response to H pylori infection and is genetically determined.

 

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Interleukin (IL) 1β and tumour necrosis factor α (TNF‐α) are proinflammatory cytokines that also inhibit acid production.

 

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tumour necrosis factor α (TNF‐α)