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last updated: Sun, 17 Dec 2017 03:14:03 GMT

 Fri, 03 Nov 2017 17:00:00 GMT Cancer treatment response may be affected by gut bacteria

"Gut bacteria 'boost' cancer therapy," BBC News reports.

The news comes from research into whether people with cancer might respond differently to cancer treatment depending on the bacteria in their gut.

Researchers specifically looked at a type of cancer treatment called immunotherapy.

This involves stimulating the immune system to attack cancerous cells – in this case, by using specially engineered antibodies known as monoclonal antibodies.

Some people respond better to this treatment than others. The researchers wanted to see if the make-up of gut bacteria influenced the outcome of treatment.

The study involved looking at the gut bacteria of 249 people who'd received immunotherapy for different types of cancer, some of whom had also taken antibiotics.

Researchers found gut bacteria differed between people who responded well to immunotherapy and those who didn't.

People who had a positive response tended to have more of a bacteria called Akkermansia muciniphilia.

Transplanting gut bacteria from these people into mice with tumours seemed to improve cancer outcomes in the mice.

The researchers also observed that both people and mice with cancer who'd been given antibiotics tended to have poorer cancer outcomes.

But this research is in its very early stages and the reasons behind these observations are unknown.

We're a long way from being able to say categorically that our gut bacteria directly affect how we respond to treatments, or whether altering the gut bacteria could boost people's responses to immunotherapy.

 

Where did the story come from?

The study was carried out by researchers from a number of research institutions in France, including Gustave Roussy Cancer Campus, Nationale contre le Cancer, Université Paris-Sud and Université Paris-Saclay, as well as the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College in the US, and Karolinska University Hospital in Sweden.

The researchers were funded by grants from a range of organisations.

The study was published in the peer-reviewed journal Science.

The story was covered well by BBC News, with accurate reporting of the details of the research and appropriate cautions from experts about how we interpret the results.

 

What kind of research was this?

The research involved several studies, including laboratory experiments, that aimed to see whether bacteria present in the gut may affect how people respond to certain types of cancer treatment.

Treatments that target aspects of the immune system, such as specially engineered antibodies know as monoclonal antibodies, can be effective for certain types of cancer, including advanced malignant melanoma or lung cancer.

But the cancers are resistant to these treatments in around two-thirds of people.

Recent animal studies suggest gut bacteria may influence how tumours respond to immunotherapy treatment.

The researchers wanted to see whether gut imbalance as a result of cancer or antibiotic use could affect how people respond to treatment.

They looked at mice with tumours and whether giving antibiotics to people with cancer affected their response to cancer treatment.

These are only very early-stage studies, so there aren't any definitive answers at this stage.

 

What did the research involve?

The researchers first tested how effective 2 types of immunotherapy were in mice with either sarcoma (cancers of bone, muscle and connective tissue) or melanoma (aggressive skin cancer). Some of the mice were also given antibiotics.

They then looked at 249 people with an advanced form of the most common type of lung cancer (non-small cell), cancer of the kidney (renal cell), or cancer of the bladder or ureters (urothelial carcinoma).

The researchers noted whether people had received antibiotics (for example, for a dental infection) either 2 months before or 1 month after starting immunotherapy, and whether this affected their response to immunotherapy.

The researchers then looked at the specific microbes found in the guts of 100 of the people in the study using DNA sequencing.

They also looked at whether mice treated with antibiotics could have an improved response to immunotherapy if they received a stool transplant from people in the study.

 

What were the basic results?

The results of the different studies were as follows:

  • Mice with melanoma or sarcoma that were treated with antibiotics were less likely to survive after immunotherapy compared with those who weren't treated with antibiotics.
  • People who took antibiotics around the time they started immunotherapy had less positive outcomes from their cancer treatment than those who didn't take antibiotics (lower rates of overall survival and lower rates of survival without cancer progression).
  • People who responded well to treatment were more likely to have a particular bacteria called Akkermansia muciniphila in their gut.
  • Mice given stool transplants from people who responded well to immunotherapy had slower-growing tumours than those who had transplants from people who had a poor response.

 

How did the researchers interpret the results?

The researchers concluded the study showed that gut microbes impacted the response people had to cancer treatment.

They acknowledged, however, it wasn't clear exactly how the microbes influenced people's responses to treatment with immunotherapy with monoclonal antibodies.

 

Conclusion

This early-stage study gives us some insights into factors that might influence people's responses to a specific type of cancer treatment (immunotherapy with monoclonal antibodies).

The findings are of interest, but don't have any immediate implications for cancer treatment.

  • We don't know what the conditions that required antibiotic treatment were and whether these could have affected the response to immunotherapy.
  • We don't know whether the antibiotics themselves influenced how well the immunotherapy worked, or whether it was their effect on gut bacteria.
  • We also don't know whether having high levels of particular bacteria improves people's responses to immunotherapy, or whether the immunotherapy somehow influences the levels of specific bacteria.
  • It's unclear whether the findings are more relevant to certain cancers or specific immunotherapies or antibiotic types, or if they're influenced by other patient characteristics.

Further research first needs to clarify whether the gut bacteria directly influences people's responses to immunotherapy, and exactly how this happens.

The next step would be to investigate whether treatment to change the gut bacteria could improve people's responses to cancer treatment.

Overall, it's likely to be some time before we see whether this early study eventually leads to any changes in the way immunotherapy is given.

These findings shouldn't cause any concern for people with cancer who need to take antibiotics.

The risk of not taking the antibiotics you need to treat an infection is likely to be far greater than any potential effect the medicines may have on the cancer or how you respond to treatment.

Links To The Headlines

Gut bacteria 'boost' cancer therapy. BBC News, November 3 2017

Links To Science

Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science. Published online November 2 2017

 Thu, 02 Nov 2017 17:00:00 GMT Could a blood test in middle age predict dementia risk?

"Tissue inflammation blood test points to dementia risk," is the headline in The Times.

Researchers in the US say people who have higher measures of inflammation in middle age are likely to have less brain tissue in some parts of their brain in older age.

The differences in brain volume, seen on MRI scans, were also accompanied by small differences in performance on memory tests.

But the study didn't find that people with raised inflammatory measures in middle age were more likely to get dementia, as it wasn't set up to directly measure dementia risk.

Previous research found people with dementia and a smaller brain volume are likely to have higher measures of substances linked to inflammation in their blood.

But it wasn't clear whether the inflammation happened before the dementia, or afterwards.

The association is further complicated by the fact it's normal for people's brains to experience some shrinkage as they get older. And, obviously, not everyone gets dementia as they get older.

While the study is certainly interesting, it doesn't provide any concrete answers.

For example, we don't know how people's inflammatory measures changed over time, or what role factors other than inflammation may have had.

There are steps you can take to reduce your risk of dementia, although these aren't guarantees.

This includes eating a healthy diet, maintaining a healthy weight, exercising regularly, moderating how much alcohol you drink, and quitting smoking if you smoke.

Where did the story come from?

The researchers came from the Johns Hopkins School of Medicine, the Baylor College of Medicine, the University of Minnesota, the Mayo Clinic, and the University of Mississippi Medical Centre, all in the US.

The study was funded by the US National Heart, Lung and Blood Institute, and was published in the peer-reviewed journal Neurology.

The Times and the Mail Online covered the study in reasonably balanced and accurate stories.

Both made it clear in the article (although not in The Times' headline) that the study didn't show a cause and effect relationship between inflammation and dementia.

What kind of research was this?

This was a prospective cohort study.

These types of observational study are good for spotting links between factors – in this case, inflammation and brain volume – but can't prove that one factor causes another.

What did the research involve?

Researchers recruited more than 15,000 people aged 45 to 65 for an ongoing study principally intended to look at heart disease risk.

As part of the study, they measured 5 substances linked to inflammation in the participants' blood when they were aged 53 on average.

Twenty-four years later, they selected 1,978 participants to have their brain volume measured by MRI scan and take a word recall memory test.

They then looked at whether higher inflammatory measures were linked to brain volume and memory test performance.

The researchers specifically sought to find out whether age, sex or race might have affected the results, as these have already been linked to dementia risk.

The 5 substances chosen as markers of inflammation were:

  • fibrinogen
  • albumin
  • von Willebrand factor
  • factor VIII
  • white blood cell count

Most of these are linked to blood clotting or the body's response to infection.

The researchers combined people's scores to give an overall inflammatory marker score.

The memory test involved listening to a list of 10 words and recalling as many as possible after a short delay.

The MRI scans looked at total brain volume, as well as analysing specific areas of the brain known to be affected by Alzheimer's disease (AD), such as the hippocampus.

What were the basic results?

People who had higher total inflammatory marker scores in middle age (the average age was 53 at the start of the study) were more likely to have a smaller brain volume in certain areas at the end of the study.

These were:

  • hippocampal volume – the hippocampus is an area of the brain that helps regulate memory
  • occipital volume – the occipital lobe is an area of the brain responsible for visual processing
  • AD signature region volume – an area of the brain previously thought to be smaller in people with Alzheimer's disease; it consists mainly of the cerebrum, which is responsible for higher brain functions

But the people involved in the study did have larger volumes in ventricular parts of the brain (these are cavities in the brain filled with fluid).

Compared with people who didn't have raised levels of any inflammatory markers at the start of the study, those with raised levels on 3 or more markers had smaller hippocampal (4.6% smaller), occipital lobe (5.7% smaller) and AD signature region (5.3% smaller) volumes.

They also did very slightly worse on the memory test, remembering on average 5 words out of 10, compared with 5.5 words for those without inflammatory markers.

The researchers didn't see any link between total brain volume and inflammatory markers.

The association between inflammatory markers and brain volume was stronger in people who had higher markers of inflammation at a younger age, and was weaker in African American participants. There were no differences between the sexes.

How did the researchers interpret the results?

The researchers said their findings "provide support" for an early role for inflammation "in the development of neurodegenerative brain changes associated with late-life cognitive decline, AD [Alzheimer's disease] and other forms of dementia".

Conclusion

Inflammation in the body is a response to injury or disease. But if the body is constantly in an inflammatory state, it can harm blood vessels and lead to heart disease.

This study suggests high levels of inflammation over the long term might also damage the brain.

That's not surprising – what's good for the heart is usually good for the brain, and we already know exercising, avoiding high blood pressure and eating healthily may help protect the brain.

Studies like this will help researchers work out more precisely what's happening in the brain when people experience memory loss or dementia.

But this study has some limitations.

The first and most important is that researchers didn't measure people's brain volume at the start of the study.

This means we don't know whether the results at the end of the study end represent brain shrinkage, or whether some people had always had smaller brain volume in certain areas.

This makes it harder to be sure that differences in inflammatory markers predated the differences in brain volume. This type of study design can't prove cause and effect – and in this case, it can't prove that one situation predated another.

Also, the substances measured may not be very precise measures of inflammation – they're also involved in other physiological processes.

And the study didn't look at whether people with higher inflammatory markers were more likely to get dementia, only at their brain volume and performance in one type of memory test.

We don't know the effect of the smaller brain volume in some areas on those people. The different performance on the memory test was also pretty small.

All in all, it's far too early to say we could ever have a blood test that accurately predicts dementia risk.

Links To The Headlines

Tissue inflammation blood test points to dementia risk. The Times (subscription required), November 2 2017

Inflammation in midlife linked to brain shrinkage later. Mail Online, November 1 2017

Links To Science

Walker KA, Hoogeveen RC, Folsom AR, et al. Midlife systemic inflammatory markers are associated with late-life brain volume. Neurology. Published online November 1 2017

 Wed, 01 Nov 2017 17:00:00 GMT Acid reflux drugs linked to increased stomach cancer risk

"A drug commonly used to treat acid reflux is linked to a more than doubled risk of developing stomach cancer," reports The Guardian.

Researchers wanted to investigate whether there's a link between medicines known as proton pump inhibitors (PPIs) and stomach cancer. Widely used PPIs include esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole.

PPIs are used to treat acid reflux and protect the stomach lining, have been linked to stomach cancer before.

But they're also used to treat H. pylori, a bacterial infection that can also cause reflux-like symptoms and is known to raise the risk of stomach cancer. This somewhat complicates the picture.

Researchers from Hong Kong studied 63,397 people who'd been treated for stomach infection with H. pylori bacteria.

Even after the bacteria had been killed, those who took PPIs on a long-term basis were more likely to be diagnosed with stomach cancer in the following 7 to 8 years of follow-up.

Because of the study design, we can't tell if PPIs were the cause of the increased stomach cancer risk. It could also have been down to other factors.

It's important to keep the results in proportion. Long-term use of PPIs was linked to around 4 additional stomach cancers cases per 10,000 people per year.

PPIs are one of the most widely prescribed types of drug. But people who use them shouldn't be particularly concerned by this study: an increase in a very small risk is still a very small risk.

Where did the story come from?

The study, published in the peer-reviewed journal Gut, was done by researchers from the University of Hong Kong and University College London. No information about funding was included.

Most of the UK media reports seized on the higher risk figures reported in the study, which applied only to people taking PPIs daily for at least 3 years.

The headlines should have made it clear that while the results suggested a statistically significant increase in risk, this doesn't always translate into a clinically significant increase.

But most articles also included expert comments stating that the absolute risk of cancer was low and the study doesn't prove PPIs are the cause of the risk.

What kind of research was this?

This population-based cohort study is a good type of study for looking for links between factors (such as PPIs and stomach cancer), but can't prove that one factor causes the other.

What did the research involve?

Researchers identified everyone who'd had successful treatment for H. pylori infection in a Hong Kong database, and followed them for an average of 7 years.

Successful treatment (eradication) is often known as triple therapy, as it involves taking 3 different antibiotics in combination.

The researchers looked at who used PPIs after H. pylori treatment, and who got stomach cancer.

After adjusting their figures to take account of possible confounding factors, they looked at whether people taking PPIs were more likely to get stomach cancer.

The researchers also identified a cohort of 142,460 people taking PPIs who didn't receive triple therapy treatment for H. pylori.
PPIs are used to treat stomach discomfort caused by acid reflux, which could mean that people start taking them because they already have symptoms of stomach cancer.

To avoid overestimating the effect of PPIs, researchers excluded people who'd been prescribed PPIs in the 6 months before a diagnosis of stomach cancer.

Researchers adjusted for age, sex and other illnesses, but were unable to adjust for diet, family history of cancer, and socio-economic status – or adjust properly for alcohol or tobacco use and obesity – because these factors weren't routinely recorded in the database.

What were the basic results?

In total, 153 of the 63,397 people in the study got stomach cancer (0.24% of the total):

  • Those who had a history of successful treatment for H. pylori and used PPIs at least weekly were more likely to be diagnosed with stomach cancer. This group of people had a more than twofold, or 244%, increase in chances of stomach cancer (adjusted hazard ratio [aHR] 2.44, 95% confidence interval [CI] 1.42 to 4.20).
  • There was no increase in risk for those taking H2RAs (a different type of reflux medication).
  • The increased risk with PPIs amounted to 4.29 additional cancers per 10,000 people per year (95% CI 1.25 to 9.54).
  • The risk was higher for people taking them long term and daily – an eightfold, or 834%, increase in risk (HR 8.34, 95% CI 2.02 to 34.1).

When comparing rates of stomach cancer between people using PPIs who did and didn't have a history of H. pylori treatment:

  • The incidence of stomach cancer was 1.0 per 10,000 in people without previous treatment, compared with 8.1 per 10,000 in people who had been treated.

How did the researchers interpret the results?

The researchers said: "To our knowledge this is the first study to demonstrate that long-term PPI use, even after H. pylori eradication therapy, is still associated with an increased risk of gastric cancer."

They added: "Physicians should therefore exercise caution when prescribing long-term PPIs to these patients."

Conclusion

PPIs are commonly used medicines for acid reflux. This may seem like alarming news for the many people in the UK who take them, but it's important to remember that the overall risk of stomach cancer is still very low.

This study has several limitations that mean we should be cautious about the results:

  • This type of study can't prove PPIs caused the increased risk of cancer. The increased risk could be down to other factors.
  • Researchers were unable to adjust their figures to take account of some relevant confounding factors, such as alcohol and tobacco use, as these weren't routinely recorded.
  • Almost all the patients in the study were Chinese. Asians are known to have a higher risk of developing stomach cancer than other populations, so the results may not be applicable to the general UK population.

But PPIs, like most drugs, do have side effects. They're not usually intended to be taken long term.

If you're taking them regularly, it may be worth discussing with your doctor whether you still need to. There could be alternative treatments that would be of more benefit.

Links To The Headlines

Acid reflux drug linked to more than doubled risk of stomach cancer – study. The Guardian, October 31 2017

Heartburn pills raise chance of developing stomach cancer by eight times. The Sun, November 1 2017

Over-the-counter and prescription acid reflux pills taken by millions 'raise the risk of stomach cancer by up to eight-fold' if they are used regularly. Mail Online, October 31 2017

Links To Science

Cheung KS. Chan EW, Wong AYS, et al. Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study. Gut. Published online October 31 2017


 

 
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