Stomach Cancer

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Stomach Cancer
The Helicobacter Foundation

Stomach cancers (gastric adenocarcinomas) are often associated with H.pylori (70-90%). In an extensive review of gastric cancer and H.pylori the Eurogast Study Group determined that presence of H.pylori confers an approxi-mately six fold risk of gastric cancer, accounting for about half of all gastric cancers. Supposedly, chronic gastritis leads to intestinal metaplasia (atrophic gastritis) which then undergoes malignant change. In the final stage H.pylori may no longer be detected on biopsy but immunologic studies may show evidence of past infection.

Mucosa associated lymphoid tissue (MALT) may undergo malignant change causing a low-grade lymphoma of the stomach. Retrospective biopsy studies show that 90% of such MALT lymphomas are asso-ciated with H.pylori. Early reports indicate about 50% cure for localized MALT after cure of H.pylori.

This document reports observations made by Dr. Marshall at Helicobacter pylori conferences in Bologna Italy and San Marino between 9/30/95 and 10/7/95.

Background
This article was posted after Dr. Marshall returned from the San Marino symposium on gastric cancer in October 1995.

Italy has a high prevalence of HP, affecting about 50% of the "normal" population. It also has a moderately high incidence of gastric cancer, in the range of 30 cases per 100,000 persons per year. In comparison, USA incidence is <10 (the world's lowest) and Japan's rate is about 60 (competing with Korea as the world's highest).

San Marino faces the Adriatic sea, occupying the top of a mountain. The views are spectacular and of course it is a major tourist attraction. It is known for quite a high incidence of gastric cancer (50-100)

Gastric Cancer Histology and Etiology
Gastric cancer can be at the top of the stomach (esophageal junction also called the cardia), in the middle (corpus or body of the stomach) or at the bottom (pyloric area). Probably the middle and lower parts of the stomach are most susceptible to cancer caused by HP.

There are several classifications of gastric cancer, the most recent by the WHO was defined in a lecture by Dr. Sipponen. In the past the main groups have been called intestinal type (well differentiated adenocarcinoma) and diffuse (cygnet ring or poorly differentiated type). Intestinal might be more likely to form lumpy tumors but diffuse type might be more likely to diffusely infiltrate the stomach wall.

In countries where gastric cancer is common (and in the United States before 1940), intestinal type cancer is the most common. In Japan for example, intestinal type is the most common type and can be cured (by surgery) if it is detected by endoscopy while the tumor is still very small and localized to the stomach. Cure is usually impossible once the cancer has spread beyond the stomach.

It is well known that most gastric cancers occur on a background of changes in the stomach called variously "atrophic gastritis" or "intestinal metaplasia". The latter means that intestinal brush border and goblet cell mucosa replaces the normal mucus secreting gastric mucosa. This abnormal "metaplasia" is the type which is the most susceptible to the malignant change.

Dr Sipponen from Finland described studies carried out in that country and in Estonia over the past 50 years which almost certainly proved that gastritis (as caused by H.P.) was the underlying cause of intestinal metaplasia. It should follow then that if gastritis is cured or prevented, then gastric cancer should be prevented. There are other data from several other countries showing that in normal persons without HP, gastritis and intestinal metaplasia are very rare, as is gastric cancer.

In the San Marinese population, about 75% of persons are infected with HP and half of these have already developed intestinal metaplasia ( and are therefore at risk of developing cancer).

What is the Actual Cancer Risk ?
Following on from the discussion above, the incidence of 100 cases per 100,000 persons per annum translates into a risk of 1 in 1000 per year or a chance of dying from gastric cancer of 1 in 20. In the USA the risk is much less, about 1 in 200. It may be higher (in the USA) for persons with HP infection. Probably the cancer risk depends on the age at which HP is contracted. If you catch HP from your older brothers and sisters when you are aged 2-5 years, you may have a higher risk than if you contract HP at age 5-10 years. Also, diet and ethnic group may confer protection. Fresh fruit and vegetables, use of refrigerators and improved standard of living in the United States have been associated with an, 80% drop in gastric cancer incidence since 1930.

Why do we think HP causes Cancer?
As well as the link between HP and precursor lesions described above, HP has been found to be common in nearly all countries where gastric cancer is a problem. The best example is Japan which has the highest stomach cancer risk (closely followed by Korea). Japanese investigators have noted that more than 65% of Japanese above the age of 50 years are infected with HP. In recent years HP has been declining in Japan so that persons under the age of 20 years only have about a 20% infection rate. In parallel, the gastric cancer rate has declined. When persons with early gastric cancer are carefully examined, about 90% appear to have HP, regardless of age.

What is the Risk of Cancer if I have HP?
Various studies find that persons with HP have 3-6 times the normal stomach cancer risk. As an example, if the background lifetime risk in the USA is 0.5%, then persons with HP have about a 1.5-3% chance of developing gastric cancer in their lifetime. HP is classified as a grade 1 carcinogen, the same classification given to cigarette smoking.

Should I worry about cancer if I have HP?
No. Remember that about 30% of persons in the USA have HP and usually feel fine. In any one year, your risk of developing cancer is only about one in 5,000. Your risk of developing peptic ulcer is higher, about 1% per annum.

My recommendation is that you do get treated for the infection because it is quite easy to do these days. It would be reasonable to discuss the situation with your doctor before making up your mind. If treatment would be difficult (for example if you have allergies to the usual antibiotics), then you could postpone treatment and review the options on a yearly basis. Ultimately however you would be wise to get treatment somewhere. Some doctors refuse to treat patients who they know have HP. In most cases the patients choose a different doctor because there are plenty around these days who like to treat HP. Even in the UK, patients can ask to be sent to a different family doctor if their own doctor will not treat them.

Does Everyone believe HP causes Stomach Cancer
Yes and No!! The theory seems to fit well in countries like Japan and the USA but in quite a few areas with high HP infection rates, cancer is rare. For example, many parts of Africa and India have HP infection in more than 80% of the population but they have stomach cancer rates not much more than the USA. Probably there is some under-reporting in these areas because stomach cancer is tricky to diagnose and many patients who die from it would be called liver cancer instead (if stomach cancer is undiagnosed, it usually spreads to the liver). But there are probably many factors which are important. In the United States, the decline in stomach cancer probably occurred because of improved diet with more fruit and vegetables. These contain anti-oxidants and vitamin C which protect the stomach lining from cancer forming agents, and probably also from HP effects.

Another possibility is that diet affects stomach acid levels and distribution of HP in the stomach. When HP localizes to the lower end of the stomach, the middle (corpus) is still able to secrete plenty of acid and may even secrete excess acid (in duodenal ulcer cases). Whereas high acid predisposes to ulcer problems, it keeps the stomach sterile (except for HP), less area of the stomach is involved in the gastritis and less cancer risk is seen.

If the whole stomach is involved with the gastritis, then acid levels are lower, other bacteria may colonize the stomach, greater areas of the stomach are exposed to the gastritis and there is a greater chance of the stomach developing a cancer.

In summary then, it is fact that HP predisposes to changes in the stomach which are thought to be the cause of stomach cancer. It is fact also that other factors are important as well and that some countries have low stomach cancer rates but very high HP infection rates. it is therefore fact that even the top scientists argue quite a lot about what this all means and what we should do about it.

Options for the Future
The questions we ask are:

How risky is it to have HP?
The risk is not great but is in the region where health authorities would like to reduce it.

Is it worth treating the HP to prevent cancer?
The cost of various treatment strategies has been worked out by Dr. Parsonnett and colleagues at Stanford University using computer models. In the average North American, the cost of screening for HP at age 50 years and treating persons who are positive is about $25,000 per year of life saved. Since the data is imprecise then the value of this strategy would be arguable and probably will not be implemented.

How much would it cost?
In high risk groups, the cost of each year of life saved would be much less than $25,000 per year of life saved and would be easily affordable in the United States. If treatment of HP prevents 25% of stomach cancers then the cost of treating infected Japanese Americans is only $5,000. Therefore, everyone in a high risk group should be treated if they have it.

Dr. Marshall's Opinion
In ethnic groups who have a high gastric cancer risk, screen for HP (with a blood or breath test) and treat it if present . Examples of suitable ethnic groups would be: Japanese, Chinese, Koreans, Russians, Colombians.

In persons who have a family history of stomach cancer, screen for HP and treat it.

In persons who are discovered to have HP, regardless of presence of symptoms or gastric disease, treat the HP.

Don't screen the whole USA population for HP yet!

Current Research
World Health Orgnization (IARRC) is considering large intervention studies in high cancer risk areas to see what effect treatment of HP has. For example, 10,000 Japanese citizens with asymptomatic HP might be treated and then followed up for 5-10 years and compared to 10,000 others who were not treated. However, these studies are not undertaken lightly. They would cost millions of dollars and when completed their data might no longer be relevant.

An alternative strategy would be to select very high risk patients and study them very intensively in lesser numbers.

In order to identify the protective factor,studies will also be done in areas with high HP but low cancer rates .

Some groups are working with animal models of HP infection in cats rats and mice. These studies will help identify dietary and other factors which might worsen or lessen cancer risk for persons with HP infection. When these are known, much simpler and more precise studies could be planned in humans.

Several groups are working on a vaccine for HP. If the HP infection could be treated by boosting gastric immunity, then it would be easy to treat whole populations and wipe out HP.

It appears that by cleaning up the water supply and improving general hygiene we can also greatly reduce HP so in developing countries the least expensive route (vaccine or other general measures) would be chosen.

What Treatment is There for People Who Already have Stomach Cancer?
Sorry, but we do not have a cure.

In brief, once you have developed stomach cancer, treatment of HP will not cure it. Often the HP goes away anyhow. It might be worthwhile to treat the HP because it could aggravate stomach symptoms but treatment of HP might not really make a big difference to the cancer.

The cancer would need to be biopsied (at endoscopy) and a decision made whether or not it is resectable. A detailed CT scan of the abdomen should be done and any suggestion of spread of the cancer should be followed up by needle biopsy, aspiration or other studies to obtain diagnostic tissue. If the tumor is localized to the stomach then surgery is the best choice. If the tumor has spread then surgery is only palliative and might only need to be done to relieve or prevent blockage or hemorrhage.

Chemotherapy has progressed modestly in the past 20 years such that about 50% of gastric cancers respond to chemotherapy. These are usually partial responses rather than complete remissions. The survival of inoperable stomach cancer is usually only a few months if untreated. With chemotherapy the average survival is about 12 months. In my experience, good quality of life can be achieved in these 12 months, even with the chemotherapy side effects. Patients with gastric cancer should see an oncologist (cancer specialist) for expert advice.

I Heard That Cancer Can Be Cured By Treating H.pylori; Is it True?
Sorry, but no. However....

In very rare tumors called Gastric MALT cell Lymphomas, about 50% of patients are cured when HP is treated. The theory is that the MALT lymphoma is a malignancy caused by the B lymphocytes in the gastritis. Treating the HP removes the stimulus and the tumor goes away. The longest survivor was a child in the USA who remains well 7 years after treatment of the HP.

The rule is that any lymphoma of the stomach should be checked for HP and the HP should be treated. I recommend biopsy and serology in all cases. If the lymphoma is localized and not aggressive, (i.e. typical MALT type), then wait a few months to see if it regresses before moving on to chemotherapy. Common sense must rule however and every case needs to be carefully and completely assessed and discussed with the oncologist. Dr Peter Isaacson in the UK has a special molecular technique which can evaluate biopsy specimens and help decide the correct course. If you contact any world experts via this page, please be sure to offer fair remuneration for their time ($150 US per hour plus laboratory costs). If you can't pay don't worry about it, but we appreciate a nice card or thank-you note.

© Helicobacter Foundation 2006