Just wondering

[Tictak]

Hi everyone,

(My first post, hope I get it right!) I have PA and regular B12 injections, my stomach has lost the intrinsic thing of absorbing it. I found out / diagnosed a few years ago (6 - 7 ish years ago) then a few years after I became celiac. Anyway, my question is.... I've found out that people with PA are at a higher risk of stomach cancer, my grandad on my dads side died from stomach cancer and I recently found out my grandmother on my mums side also died of stomach, could this possibly mean I am at an even higher risk of getting stomach cancer (sort of like 3-fold rather than just due to the PA) ? and should there be anything specific to look out for?

Thanks all

[Rexz]

Hi Tictak

OK, here's my feeble attempt at answering your questions...

Pernicious Anemia is a late-stage manifestation of Autoimmune Gastritis (AIG), a chronic inflammatory condition – also called Autoimmune Metaplastic Atrophic Gastritis (AMAG). With AMAG, as your immune system is destroying your Parietal Cells, in an attempt to heal, your immune system replaces destroyed Parietal Cells with cells that look like they belong in the walls of the small intestine. These are called Gastric Intestinal Metaplasia (GIM). I call them my imposter cells.

I will say before we get into risk discussion that not everyone with AIG/PA will get cancer. It is but a small percentage of which I happen to have drawn that lucky lottery ticket. The etiology (causation) of why some people with AIG/PA progress to cancer and others do not is not clearly understood by the health care industry and the data to support any conclusion is very scant. So, the following is not to scare but rather to bring awareness as an early diagnosis of gastric cancer is perfectly curable through endoscopic or gastroscopic mucosal resection.

Increased Risk: Patients with autoimmune atrophic gastritis have a markedly increased risk of developing gastric adenocarcinoma. The relative risk is estimated to be approximately 3-fold to 13-fold increased risk than that of the general population. I have seen studies on this anywhere from 3 to 7-fold to 6.8 to 11-fold, and as high as 13-fold increased risk. The real data for this is very scant indeed.

Just for clarification the formulae to convert fold to percentage is [percentage increase = (n-fold -1) * 100]. So an 11 fold increase is 1,000% increase from the general population.

GIM are considered precancerous lesions that can progress to dysplasia and carcinoma. These need to be monitored periodically anywhere between 1 to 3 years for those with PA and high risk extensive GIM. A baseline endoscopy/gastroscopy should be requested and performed with Gastric Mapping in accordance with what’s called the Sydney Protocol. This is a protocol where they will take 6 to 8 random biopsies to assess the extent of GIM and plan a surveillance interval for you. For progression according to the Correa Scale see the graphic at the bottom herein. Again, this happens for some small subset of all of us.

The different Gastro guidelines are here for your reference but all, US, British, and European Guidelines recommends an initial cancer screening and Gastric mapping endoscopy/gastroscopy.

British Society of Gastroenterology (BSG) Guidelines: The BSG recommends endoscopic surveillance for patients with autoimmune gastritis due to their elevated risk of gastric cancer. A baseline endoscopy is advised to assess the extent of gastric mucosal atrophy and dysplasia, which can inform future surveillance strategies (BSG Guidelines on the Management of Gastric Cancer, 2020).

BSG Recommendations:

4. We recommend that patients at higher risk for gastric adenocarcinoma, including GA and GIM, should undergo a full systematic endoscopy protocol of the stomach with clear photographic documentation of gastric regions and pathology. We suggest a minimum examination time of 7 min (evidence level: moderate quality; grade of recommendation: strong; level of agreement: 100%). [3]

12. We suggest that a baseline endoscopy with biopsies should be considered in individuals aged ≥50 years, with laboratory evidence of pernicious anaemia, defined by vitamin B12 deficiency and either positive gastric parietal cell or intrinsic factor antibodies. As GA affects the corpus in pernicious anaemia, biopsies should be taken from the greater and lesser curves (evidence level: low quality; grade of recommendation: weak; level of agreement: 93%). [3]

13. We recommend endoscopic surveillance every 3 years should be offered to patients diagnosed with extensive GA or GIM, defined as that affecting the antrum and body (evidence level: low quality; grade of recommendation: strong; level of agreement: 100%). [3]

The European Society of Gastrointestinal Endoscopy (ESGE) Guidelines (ESGE) guidelines emphasize the importance of early endoscopic evaluation for patients with autoimmune gastritis, particularly those presenting with symptoms or additional risk factors such as pernicious anemia. This early assessment aids in stratifying patients into appropriate surveillance categories based on their risk (ESGE Guidelines on Endoscopic Surveillance in Patients with Gastric Cancer Risk Factors, 2021).

The American Gastroenterological Association (AGA) Guidelines recommend baseline endoscopic screening for patients with autoimmune gastritis and pernicious anemia due to the heightened risk of gastric cancer. This recommendation includes a comprehensive evaluation to guide the need for subsequent surveillance intervals (AGA Clinical Practice Update on Surveillance for Gastric Cancer, 2022).

Having a previous instance of Gastric Adenocarcinoma and extensive GIM I have an endoscopy every 9 months.

Risk Factors for Gastric Cancer:

1. Having AIG/PA

2. Family history of Gastric Cancer

3. Extensive versus limited GIM (this they will check during initial endoscopy)

4. Incomplete versus complete GIM

5. Type A blood type

6. Men doubly higher than women

7. Achlorhydria (an advanced condition of AIG)

Hereditary nature of AIG/PA:

It is well known that AIG/PA runs in families and has a genetic component. Many studies show a higher incidence rate amongst those with Scandinavian or Northern European descent. The exact genetic etiology of AIG/PA is not yet known but they are making some progress and have identified several possible Genetic Loci.

If your mother has been diagnosed with Pernicious Anemia, then you or any of your siblings should be closely monitored for AIG/PA. One test I have my kids do annually is a Parietal Cell Antibody (PCAB) test starting at 40 yrs. Although Parietal Cell Antibodies by themselves are not diagnostic of AIG/PA I consider them more like “the Canary in The Coal Mine” so to speak, as 90% of those with AIG/PA will be positive for PCAB.

Bottom line is to emphasize the importance of a proper diagnosis of AIG/PA and getting the proper cancer screening and endoscopic surveillance.

Hope this is helpful, Rexz

Progression of GIM to Adenocarcinoma

[Tictak in reply to Rexz]

Thank you Rexz. I shall read through this a few times and for a better understanding. Thanks once again, you've been very helpful x

[wedgewood in reply to Rexz]

Enormous thanks to you Rexz for this important information, which we would never get anywhere else,( especially not from our GPs !)

[Artemisfowl]

Having Autoimmune Metaplastic Gastric Atrophy means you’re more likely to get Gastric Neuroendocrine Tumours (NETs).

While this is a form of cancer the tumours are indolent. Standard treatment is an annual gastroscopy to check they’re still doing nothing.

[Rexz in reply to Artemisfowl]

Yes, enterochromaffin cells at the base of the stomach can change to neuroendocrine tumors due to overstimulation of Gastrin (hypergastrinemia). High levels of Gastrin is caused by very low levels of stomach acid (hypochlorhydria) or zero stomach acid (achlorhydria). This occurs once enough of Parietal Cells are destroyed as they also are your acid producing cells. Neuroendocrine tumors are very slow growing and usually benign as opposed to adenocarcinoma.

Rexz

[Bacca in reply to Rexz]

In order to slow (prevent?) that conversion and prevent high gastrin, does increasing stomach acid help? Using apple cider vinegar or others?

Thanks for your explanations Rexz, as you say knowledge in this area is very scant.

[Rexz in reply to Bacca]

That's a good question Bacca

No increasing stomach acidity through anything other than natural gastric acid does not seem to work. I take 3 grams of Betaine HCL before each meal for three years now and it has not reduced at all my serum Gastrin. Continuous high levels of Gastrin are what is causing the e-cells to be continuously overexcited. Gastrin being part of the feedback control that turns parietal cell proton pumps on to produce acid. I've researched and talked to the GI heads of most University Hospitals in SoCal but there is no way currently to stop excess Gastrin production.

[Bacca in reply to Rexz]

Oh wow. Hats off for your resilience, and research efforts. What would we do without you!

Thanks for your response and hope you’re having a ‘good day’! X

[Rexz in reply to Bacca]

What would you do without me? Probably have a happy blissful day! 😂🤗

[wedgewood in reply to Rexz]

But ignorance is NOT bliss when it comes to the subject of P.A. / B12D . ! Thanks again Rexz

[Rexz in reply to wedgewood]

You're so correct wedgewood so very correct. Such a great reminder. We all know the "Pernicious" in Pernicious Anemia is alive and well. Although treatable, It can kill you, even today, if not treated properly!