Can Antibiotics Prevent Deaths From Stomach Cancer?

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A new report finds that taking antibiotics for a common bacteria, Helicobacter pylori, reduces the occurrence of gastric cancer. For decades, doctors have understood that H. pylori infection plays a role in malignancy of the stomach. In infected adults, a brief course of antibiotics lessens cancer risk. But the analysis, published by the Cochrane Library, did not show that this pre-emptive strategy lowers deaths from gastric cancer. The paper raises interesting and hard questions about the benefit of screening for h. pylori and treating with antibiotics as a means of cancer prevention.

Since the early 1900s, gastric cancer rates have declined in Europe and North America. Yet this form of malignancy remains one of the world’s most common and fatal tumors, particularly in developing regions. In 2014, the International Agency for Research on Cancer (IARC) deemed gastric malignancy a neglected cancer.

The IARC estimates that stomach cancer diagnoses approach one million, and deaths at 723,000, per year. As recently as 1975, stomach cancer was the most common neoplasm around the world. Now it ranks fifth among malignancies, and third as a cause of cancer-related deaths worldwide. More than half of known cases occur in Eastern Asia. If affects men more than women. Treatment options are limited; most people affected die from this disease.

H. pylori, the organism implicated in gastric cancer, infects a high proportion of the world’s population. How these bacteria spread may involve water, animals and contaminated food. Most people affected do not develop gastric cancer; peptic ulcer disease is a more frequent associated condition. Ways of testing for H. pylori include checking blood for evidence of infection, a breath test, examining material taken from the stomach taken by endoscopy (by various methods including culture, enzyme assays, PCR and looking under the microscope), and checking stool.

“We wanted to see if we could prevent gastric cancer” said Dr. Paul Moayyedi, senior author of the Cochrane paper, in a telephone interview. He is a professor at McMaster University in Ontario, Canada, where he hold the Richard Hunt-AstraZeneca Chair in Gastroenterology. In recent years, he has received fees for speaking from AstraZeneca and Shire Pharmaceuticals.

“For many years people have known that there’s an association between H. pylori and gastric cancer.” Moayyedi said. “So it made sense to ask this question.” We did show that the intervention decreased gastric cancer, but not mortality.

“It’s exciting but perhaps not as dramatic as one would have hoped.” The randomized studies included in the analysis were underpowered to show a treatment effect, Moayyedi said. “It takes years to develop gastric cancer. With longer follow-up, we might have seen a survival benefit.”

“Everyone realizes that if you reduce the incidence of gastric cancers, you’ll reduce deaths from it,” Moayyedi said. That’s because gastric cancer is usually fatal. “The one exception is in South Korea, where everyone is screened and it’s usually found early.” Even in North America and the U.K. and most of Europe, where good surgery is generally available, most people with a gastric cancer diagnosis will die from the disease, he indicated.

In the United States, stomach cancer is far less common than in years past. The rate has been declining since the 1930s for reasons that aren’t entirely known. Refrigeration and dietary changes may play a role. The diagnosis is most common in men between the ages of 65 and 74 years. Gastric cancer disproportionately affects Asians, Pacific Islanders, Alaskans and Native Americans. Known risk factors, besides infection with H. pylori, include smoking, a high-salt diet, and a family history. Effective treatment, apart from surgery in early-stage cases, is rarely helpful in this disease; 5-year survival remains at 29 percent.

It’s been 30 years since researchers postulated that H. pylori, formerly known as Campylobacter pyloridis, causes stomach cancer. Earlier on, scientists considered that chronic irritation of the stomach, such as occurs in gastritis, disposes to cancer formation. In the 1980s, this species of bacteria was linked to peptic ulcers and, by 1991, connected with stomach cancer. Since 1994, the IARC lists H. pylori as a human carcinogen. Yet the specific mechanisms by which the bacteria cause malignancy – and other possible cofactors – remain elusive.

“H. pylori infection is the single most common risk factor for developing gastric cancer,” said Dr. Dimitrios Iliopoulos, an Associate Professor of Medicine at UCLA’s David Geffen School of Medicine. His laboratory studies the role of inflammation in gastrointestinal malignancies, including gastric cancer. He was not involved in the Cochrane study.

“A lot of studies have shown that eradication of H. pylori results in reduced risk of developing gastric cancer.” Infections cause an inflammatory state, Iliopoulos said. “Over time, that can promote cancer,” he considered. It could be that H. pylori infection is an early step in gastric cancer formation. Tumor growth, and death, are late events, he considered. “So it could be that other factors play a role, in between.”

“We don’t know exactly why gastric cancer rates have gone down in the United States. One leading theory to explain this change is the advent of refrigeration” Iliopoulos said. Factors that may enhance gastric cancer risk include consumption of nitrates, alcohol, and highly salted, pickled, fermented, or smoked foods, he added by email. “Other environmental factors which may promote gastric cancer could be inappropriate food storage, metal and cement dust exposure, and cigarette smoking. On the other hand, high intakes of fruits and vegetables or of antioxidants, such as beta-carotene, vitamin E, and vitamin C may decrease the risk.”

The Cochrane investigators examined published trials from around the world, including conference proceedings, to identify randomized, controlled trials to address the role of treating H. pylori to reduce deaths from gastric cancer. They winnowed the results to six trials involving nearly 6500 enrollees. One of the studies was performed in Columbia; four in China; and one in Japan. The duration of follow-up ranged from 4 years to over 14 years.

Among the 6,497 participants in the six trials with h. pylori infection, taking a course of antibiotics led to a clear reduction in gastric malignancies: Of those adults given treatment in a randomized trial, only 1.6 percent (51 of 3294) developed stomach cancer; of those who received no treatment or a placebo, (2.4 percent 76 of 3203) developed stomach cancer. The numbers of deaths from cancer, among those 127 who received a gastric cancer diagnosis in any of these trials, was too small to draw conclusions. The authors concluded that there was insufficient evidence to discern if eradication of the bacterial infection improved survival.

Screening for h. pylori, the bacteria that causes gastric cancer, is “certainly worthwhile in high-risk countries such as China and Japan,” Moayyedi said. “There is little argument there, because it’s a significant cause of death in those populations. In countries with a lower risk of gastric cancer, such as in North America, the benefit is less clear,” he said.

“We’ve previously shown that you also prevent peptic ulcers by screening and treating for h. pylori” Prophylactic treatment can save money, he suggested. “So even in western populations, it might be cost-effective.” But screening will be most beneficial in countries where gastric cancer is very common, such as China and other Asian regions, he indicated.

It’s not clear why only some people with h. pylori infection develop gastric cancer, Moayyedi considered. “It’s multifactorial. Also, people have to live long enough to get this kind of cancer.” A high salt diet, and low Vitamin C may play a role. “The virulence of the organism is much greater in Asian countries,” he said. “It causes higher rates of inflammation there, which underlies greater risk.”

“I would encourage all countries where gastric cancer is common to introduce a screening program,” Moayyedi said. But screening for h. pylori and giving antibiotics to those infected needs be done carefully, he emphasized. “We need to assess what happens if we give antibiotics in each population,” he said. “There could be unexpected effects,” he cautioned.

The cost of treating the bacteria shouldn’t be prohibitive, Moayyedi considered. “The price is getting lower all the time,” he said. “If you’re buying it to give to many people, I can’t imagine it would cost over $20,” he stated

While the numbers from the Cochrane report are clear, and in some ways dramatic – demonstrating a risk reduction of 34 percent in people treated for H. pylori – the low proportion of the nearly 6500 study participants who developed gastric cancer in these combined studies was low: only 2.4 percent in the untreated group. This means that number needed to treat in a population, or NNT, would be large relative to the number of gastric cancers prevented and deaths (if any) reduced.

Yet the potential for cutting the incidence of this malignancy by a third or half, and lessening other illness caused by h. pylori, is not trivial. As many as 1 in 6 cancers are thought to be caused by infection and, therefore, might be prevented. The IARC considers the potential of preventing gastric cancer, with antibiotics, as a significant area of possibility for improving public health.

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Source: Forbes