Main content

Ovarian cancer, PBC, Treating severe head injury

Margaret McCartney looks at the evidence linking talc use and ovarian cancer, which has hit the headlines. Plus PBC, an often-missed condition, and severe head injury.

The use of talc and its potential connection with ovarian cancer has hit the headlines after a court ruling in America. Given that nearly half the UK population uses talc to some degree GP Dr Margaret McCartney looks at the evidence and puts any link in perspective. PBC is an often missed condition that causes severe itching and fatigue with the resulting liver damage mistakenly associated with drinking too much. Laura Gilmore lived with the symptoms for many years - scratching herself raw and falling asleep during the day but still not waking refreshed - before getting a diagnosis. Professor James Neuberger explains the science behind PBC.

Plus treating severe head injury and why a commonly used intervention used in intensive care units across the country is being questioned. Professor Peter Andrews is the man behind a new trial looking at the evidence for hypothermia, or cooling people with head trauma to prevent damage. The trial was stopped because early evidence suggested harms from this commonly used practice. Dr Mark Porter discusses the implications for critical care medicine across the world with Peter Andrews and Professor John Myburgh who is at the University of New South Wales in Sydney.

Available now

28 minutes

Programme Transcript - Inside Health

Downloaded from www.bbc.co.uk/radio4 

THE ATTACHED TRANSCRIPT WAS TYPED FROM A RECORDING AND NOT COPIED FROM AN ORIGINAL SCRIPT.  BECAUSE OF THE RISK OF MISHEARING AND THE DIFFICULTY IN SOME CASES OF IDENTIFYING INDIVIDUAL SPEAKERS, THE BBC CANNOT VOUCH FOR ITS COMPLETE ACCURACY.

 

 

INSIDE HEALTH

 

Programme 8. – Ovarian cancer, PBC, Treating severe head injury

 

TX:  01.03.16  2100-2130

 

PRESENTER:  MARK PORTER

 

PRODUCER:  ERIKA WRIGHT

 

 

Porter

Hello, coming up in today’s programme:

 

PBC – an often missed liver complaint that causes fatigue and itching, and one that is all too easily confused with the effects of drinking too much, particularly in middle-aged women.

 

Skiing – and why it may be worse for your knees than you might imagine.

 

And hypothermia – why the standard practice of cooling people who have had serious head injuries may be doing be more harm than good. I meet the man behind the research that has had intensive care units questioning their protocols.

 

Clip

Andrews

Basically the bottom line is there’s an absence of evidence for the commonly used interventions that we practise on a daily basis.

 

Porter

And when you say common interventions, these are the sort of treatments that are being offered to people with serious head injury in units across the world right now?

 

Andrews

Correct.

 

Porter

More from Professor Peter Andrews later. 

 

But first talc and recent media headlines linking it to ovarian cancer. The coverage in the media follows a ruling in America against Johnson and Johnson, sued by the family of a woman who died of ovarian cancer after using its products. So given that nearly half the female population here in the UK use talc to some degree, how concerned should they be?

 

Paul Pharoah is, Professor of Cancer Epidemiology at the University of Cambridge and joins us on the line from his office.  Paul, could you put that link in perspective?

 

Pharoah

Studies have fairly consistently shown a weak link, in that women who have regularly used talcum powder have been shown to be at slight increased risk of epithelial ovarian cancer in the future.  So a young woman in the United Kingdom will have about an 18 – that’s one eight – chance in a 1,000 of getting ovarian cancer during her lifetime.  A regular talcum powder user, using talcum powder in the genital area, that risk might increase to 21 or 22 in a 1,000.  So it’s a small risk that is increased ever so slightly.  It’s really of no real importance or significance.

 

Porter

Do we understand the mechanism, what is it about talc that might be doing the harm?

 

Pharoah

We don’t really know for sure.  The association between talc and cancer is biologically plausible because we know that talcum powder can be an irritant on some tissues and irritation can cause inflammation and inflammation can be associated with cancer.  There’s been no research that really shows that this is an actual mechanism that really is occurring.

 

Porter

Well listening to that in our Glasgow studio is Dr Margaret McCartney.  Margaret, what’s your take on the evidence that’s out there, because there’s quite a lot isn’t there?

 

McCartney

There is heaps of evidence out there and the problem is that some is more reliable than others and none are the gold standard randomised control trial.  So we have to try and make do with what we know so far.  So there are some studies that have asked women did you use talcum powder 10, 20, 30 years ago, well I can’t remember what I had for breakfast, so I’m not sure that these studies are hugely reliable.  Then we have other studies that have followed women over many years.  One study looked at women over 12 years, another over 20 years, asking women what did you use, have you used these products and then looking to see who developed ovarian cancer.  It’s true to say that in most of these studies the results are equivocal, they haven’t shown a big relationship.  One study has shown a small increase in risk, another similar study didn’t show an increase in risk.  So it’s difficult to know really what best to believe and I think we have to be cautious but I’m not sure that there’s been a convincing link demonstrated by the data, looking at it overall.

 

Porter

Well let’s use Paul’s figures and assume that there is a small increase in risk amongst talc users.  I mean it is tiny though isn’t it, it’s going back to Margaret McCartney’s twice not very much isn’t very much.

 

McCartney

Yes I do agree.  However, I think if when we’re talking about ovarian cancer it’s not a cancer that you would wish to have, it can often be difficult to treat, it can be difficult to diagnose effectively early, so I think it’s really important that we think about what the causes are and what the avoidable causes are and if the avoidable cause is something like talcum powder being used on the genitals that would be something really easy to exclude, I mean why are we using these products anyway, is what I ask myself.  So I would be really keen to know what simple measures we can do to reduce our risk and if that’s one of them, great, I’m just not hugely convinced that it is.

 

Porter

Historically talcum powder was made up slightly differently, that might have been a factor in the mechanism mightn’t it?

 

McCartney

Yes, now originally I understand that talcum powder was created with small amounts of asbestos in it and we’re talking many, many, many decades ago here and because of that the international agency for research in cancer, who are part of the World Health Organisation, they had classified talcum that contained asbestos as carcinogenic cancer causing to humans, obviously we know enough about asbestos now.  And what they have done is they’ve said that in humans they believe that the limited evidence we have so far we should classify talcum that’s not got asbestos in it as possible carcinogenic to humans.  So there’s a bit of a red flagging up there or an amber flag – just go careful, think carefully, do you really need this stuff or not, sounds quite reasonable to me.

 

Porter

So as a pragmatic GP what sort of advice are you giving to your concerned women in your consulting room?

 

McCartney

Well you know Mark I am just sick of these companies that manufacture products that women don’t need and then tell women somehow that they need to smell different, look different, that their natural state is somehow not acceptable and these products are somehow essential to our wellbeing, which is just nonsense.  And if it’s not talcum powder it’s other lotions and potions that are meant to make your vagina or your genitals look different from what they should. And I really ask myself are these good for women, I think not.  Unless you’re treating a medical condition and there’s a reason to be using it really normal is good.

 

Porter

Margaret McCartney and Professor Paul Pharoah, than you both very much.

 

Now, as William Shakespeare famously once asked: What’s in a name?

 

Well quite a lot in medicine where it often pays to choose your words carefully. PBC – a liver condition that affects around 20,000 people in the UK – being a case in point.

 

PBC is an auto-immune condition that mainly affects the livers of middle-aged women. It is an easy one to miss and the classic symptoms of lack of energy and itching often get wrongly attributed to other problems. But it is the all too common assumption that alcohol is to blame that upsets many of those affected – a misunderstanding that is exacerbated by the original name.

 

PBC traditionally stood for primary biliary cirrhosis and although cirrhosis simply means liver scarring from any cause, it is synonymous with alcohol related damage in most people’s minds.

 

So to avoid that confusion cirrhosis has become cholangitis. Still PBC but a simple tweak that reflects the real underlying problem – cholangitis, inflammation of the channels draining the liver.

 

Gilmour

My name is Laura Gilmour, I’m 59 now but ever since I was at high school I had severe bouts of real tiredness – come home from school, go straight to sleep, wake up at midnight because I was just so, so tired.  But the sleep didn’t make me feel refreshed and I had trouble with itch, particularly in my legs.  People were always saying – stop scratching – I was having to change bed sheets every day because they were covered in blood because I was even scratching in my sleep.  I have been like raw meat, clawing and clawing, just scratching, can’t get rid of it.  There were nights when I was up in the middle of the night scratching, covered in blood, thinking what is this, is it in my head.  And my mother started off with the itch and the extreme tiredness, we frequently came home from school and found my mother sound asleep on the floor, she’d just to stop and lie down and sleep.  Nobody knew why.  She attended our GP and he thought that my mother had scabies because she was scratching so hard.  My mother was appalled at the thought that she might have something like that, she classed that as something dirty.  And eventually my parents made an appointment with a private doctor in Glasgow, this was ’77.  He did various blood tests and suchlike and he got back to my mother with PBC diagnosis and he said he had never come across anybody with it but he had read about it.  She died in 1985.  In 2005 my sister was diagnosed with PBC, which made me go to the doctor and make enquiries and I was diagnosed too.

 

Neuberger

My name is James Neuberger, I’m a consultant physician at the Queen Elizabeth Hospital, Birmingham, in the liver unit and I also work for NHS Blood and Transport.  A typical case that I might see in clinic now is a middle aged woman who has for many years often been complaining of lethargy – it’s not the sort of tiredness like you’ve had a good night out the night before, it’s a sort of draining, a switching off of the batteries if you will – maybe with some itching.  I’ve seen patients who’ve been referred to psychiatrists because they’ve had itching and no cause was found and it was thought to be a psychiatric cause, I’ve seen people with pictures of scrubbing brushes on various pieces of wood so that they can get to the parts of the body that even lager can’t get to, scratching themselves, sitting at home with no clothes on because the itching’s so bad.  They’ve often gone to their GP – tiredness is very common, itching is common and there’re many causes, there may be some delay.

 

Porter

They’re fairly vague symptoms aren’t they but actually some of – one of the things we might do as a GP, part of the routine investigation of that sort of symptom, would be a blood test to check the liver.

 

Neuberger

Patients will often have slightly abnormal liver tests and it’s certainly not uncommon for people with PBC to be considered as having liver damage from alcohol.

 

Porter

That’s the first thing that most – you know you look at somebody and you see a slightly deranged liver and there’s no obvious reason then we think alcohol.

 

Neuberger

And statistically of course you’re absolutely right.  But a lot of the patients they do get very much stigmatised as being alcoholics and when they deny alcohol the response is well of course they would say that anyway.  So they’re in a no win situation.

 

Gilmour

As soon as you mention cirrhosis immediately people think – drink.  I’ve never been a heavy drinker and I have been told specifically that it is nothing to do with alcohol and that, I think, is one of the reasons why the name has now been changed, it’s still PBC but it’s Primary Biliary Cholangitis and that alone makes a difference to how people react to you, even medical people – nurses in clinics – I’ve never heard of that, are you alcoholic?

 

Neuberger

That is part of the importance I think of making a diagnosis, you understand your symptoms, knowing that it’s not psychology, they’re not going mad as a cause of their symptoms at least, they may go bad as a result if we can’t control them.   The itching we can treat and people know what they’re living with.

 

Porter

Of course the other thing that we see a lot of increasingly in general practice that can lead to deranged liver function tests and fatigue and things is obesity.  Is there a way that you can tell, looking at liver function tests, whether this is likely to be something else more sinister?

 

Neuberger

The shorter answer is there’s no robust way looking at the standard liver tests.  They’re abnormal and they will indicate something maybe wrong with their liver but although we call them liver function tests it’s really a misnomer because they’re neither specific for the liver, nor do they measure liver function.  The key diagnostic test is looking for what’s called an antibody, which is a protein that the body makes normally in response to an infection.  But there’s a group of these antibodies, called auto-antibodies, which react against the normal body and the key auto-antibody in Primary Biliary Cirrhosis or Cholangitis is called the anti-mitochondrial antibody.  And this is present in over 95%, 19 out of 20 patients with PBC and in the context of a woman with abnormal liver tests and the symptoms it’s virtually diagnostic.

 

Porter

So what’s the underlying mechanism, what’s responsible for this inflammation of the liver?

 

Neuberger

The short answer is we don’t know.  It’s considered to be a combination of genetic factors and probably an environmental trigger, whether that’s a virus, bacteria, something in the atmosphere, we don’t know but something we believe triggers in susceptible individuals.

 

Porter

You suggest that a lot of these people there’s quite a long delay before they’re diagnosed, does that matter – if I’m on the ball, the patient comes and sees me early and I refer to a unit like yours, the diagnosis is confirmed – does early intervention affect the outcome?

 

Neuberger

Probably is the answer.  We don’t have a cure for PBC as yet, there is a drug called Irsodeoxycholic acid which slows down progression, it doesn’t cure the disease, it doesn’t stop it but it slows it down.  So we believe earlier diagnosis will help.  The majority of people with PBC die with the condition and not from it but there’s a small proportion of people who develop end stage liver disease or such severe itching that we can’t control, that their life is intolerable, and for these patients we offer liver transplantation.  The itching will go overnight and I see people who are scratching themselves, they get transplanted, they wake up the next morning from the operation and the itching has gone, it’s miraculous.  The lethargy, in contrast, does not go away and why that is we don’t know.  We also know that the PBC can come back in the new liver and we see it maybe in a third to a half by five years.  But liver transplantation is a superb treatment for the right person at the right time, it revolutionises their lives, maybe in Birmingham we perhaps transplant two or three patients a year who have such severe itching that we can’t treat them in any other way.

 

Gilmour

I’ve had all sorts of treatments – drugs that did work, various drugs that didn’t – I still have bad days when I can’t even get out of bed, I have better days when I do too much and then I suffer for it later.  I don’t have much of a social life because I can’t arrange today to go out tomorrow night because I might not be able to go, might be too tired, might be sleeping.  But on the positive side my mother required a transplant but she became too ill and a liver didn’t become available, so she died on Valentine’s Day 1985 and she was 56, so I look on every day as a bonus.

 

Porter

Laura Gilmour.  And you will find links to more information on PBC on our website. Where you will also find details of how you can in touch.

 

Nick listened to our item on the first e-cig to get a medical licence – manufactured by tobacco giant BAT – and – well he wasn’t impressed by the idea:

 

Nick

We don’t need e-cigarettes on the NHS. This new licensed version will be next to useless for many smokers as the nicotine levels are too low, and it doesn’t produce enough vapour. The manufacturers must be laughing at the thought of selling loads of these e-cigs only for users to go back to tobacco because they find them inadequate.

 

Porter

And our item on rugby associated injuries – which are more common than most people think – prompted this response from Catherine Barker.

 

Barker

I really appreciated the item on rugby injuries but it didn’t mention what has generally been cited as the greatest cause of dangerous injuries in school rugby which is that teams play by age not size.  I speak from bitter experience.  My son’s school started a rugby club, therefore allowing them to play the contact sport, he had his shoulder dislocated in training because the boy who tackled him simply didn’t realise how light he was.  Certain schools are now looking at school boy games played by weight, which they do, for example, in New Zealand.

 

Porter

While this listener was keen to move the debate to another sport, popular at this time of year.

 

Bollen

My name is Steve Bollen, I’m an orthopaedic consultant surgeon with a special interest in sports injuries and in particular knee injuries and I was intrigued by your recent piece on rugby injuries and I thought you might be interested in talking a bit about skiing injuries which at this time of year is particularly relevant.  I was skiing in the first week in January and on our return trip the departure lounge at Salzburg airport looked rather like a war zone – there were crutches and wheelchairs and people in plaster and slings.  And we’ve done some work in the past looking at this, we looked at the figures across Europe a few years ago, and came to the conclusion that your risk of suffering a significant injury if you go for a week skiing is about one in 70 and compared with most sports that’s very high.  And a colleague of mine told me that he saw six people last week with a ruptured anterior cruciate ligament in their knee from their holiday skiing.

 

Porter

I suppose the difference Steve is with our item on rugby is that rugby’s a compulsory sport for many whereas you elect to go skiing and I think most skiers know that they are risking a tweaked knee or a broken leg or a broken arm, don’t they?

 

Bollen

I think the possibly do but I don’t think they quite realise how risky it is.  And if you think about it when you fly out in your plane of about 200 people, when you fly back a week later there’s almost invariably three or four people who are either on crutches, in a knee brace, with their arm in plaster.  And most people will have an insurance policy that actually covers them for treatment while they’re abroad but the problem with it is that most of them stop as soon as you cross the UK border and you’re then thrown back on to the NHS system.  So far this year I’ve seen 13 people with a ruptured anterior cruciate in their knee from skiing and one poor lady who had had essentially a knee dislocation, rupturing three of the four ligaments in her knee, which in a 52 year old lady is a very serious injury.

 

Porter

Looking at the sorts of injuries that you’re likely to sustain skiing is the knee the predominant joint at risk?

 

Bollen

Yes, if you were designing a piece of apparatus to rupture an anterior cruciate ligament in the knee, you would fix the lower leg in a rigid boat, put a six foot lever on the end of it and then give it a good twist, which is essentially what skiing does.  Part of the problem with skiing is that a lot of people see it as a holiday, as opposed to a sport, and don’t do any other sport at all and so they go for a week skiing once a year, which is a crazy way of approaching any sport in which there’s a potential risk.  And the risks of skiing do include death.  An awful lot of them are from head injuries in collisions because it’s often a very high speed, high impact injury and if you haven’t got a helmet on and you smash heads with someone else then you are in real trouble.

 

Porter

Orthopaedic surgeon Steve Bollen talking to me on the line from his office.

 

And now from a cause of head injury to a therapy used to treat it. Cooling is a standard method used by intensive care units to lower intracranial pressure – the pressure inside the skull - of people with serious head injuries. The theory is straightforward. Swollen damaged brains have nowhere to expand – the skull is a rigid box – so injury can increase intracranial pressure, which in turn can further damage delicate brain tissue.

 

Reducing pressure by cooling the patient – effectively inducing hypothermia - should help then, but the recent Eurotherm study has led doctors to question that approach, and has rocked one of the pillars of modern head injury management.

 

Professor Peter Andrews from the Department of Anaesthesia, Critical Care and Pain Medicine at the University of Edinburgh led Eurotherm.

 

Andrews

My clinical trial was stopped early by an independent data monitoring committee because of a trend towards harm.  I was very surprised because during the whole work up and design of the trial all the evidence suggests that it should be a magic treatment.  There is already some evidence suggesting that cooling would reduce brain pressure and there are evidence showing that cooling beneficially changes some of the injury processes that are ongoing after the brain trauma.  So there were many positive reasons that we would think that hypothermia would have a beneficial effect.

 

Porter

And how widely is this technique currently used?

 

Andrews

It’s really very widely used, in Europe and within the UK, to the extent that there were at least four centres in England who couldn’t participate in the trial because they already believed that it worked.

 

Porter

So what did you find?

 

Andrews

Well what we found was that cooling reduced brain pressure.  Unfortunately at six months the mortality was higher with cooling and most surprising I guess of all was that the functional recoveries were worse with cooling.

 

Porter

So although the parameter that you were interested in – the intracranial pressure – reduced, it actually killed more patients…

 

Andrews

Sadly yes.

 

Porter

… and those who survived didn’t do as well as expected?

 

Andrews

Correct.

 

Porter

So we shouldn’t be using it.

 

Andrews

We should not be using it.  On reflection the human body, the mammal, has evolved over millions of years to regulate its body temperature over one or two degrees and we thought it was a good idea to decrease it by maybe seven or eight degrees.  So it’s 50 years of not very good science against millions of years of evolutionary biology.

 

Porter

And in retrospect does that feel a little naïve?

 

Andrews

Well it does now.

 

Porter

What sort of response did you get from your colleagues, given how widespread it is used?

 

Andrews

A bit of disbelief, many of my colleagues who work in intensive care will not see these patients at six months and their practice is therefore dominated by physiological measurements, such as intracranial pressure.  They could see that this intervention was helpful at manipulating this numeric value but unfortunately – it always takes time for these results to sort of sink in.  We like to adopt new things into clinical practice, we’re a bit less quick at getting rid of things that don’t work.

 

Myburgh

This is a question that’s been round for many years and I think this trial will have quite a large impact in avoiding giving unnecessary treatments to patients.

 

Porter

John Myburgh is Professor of Intensive Care Medicine at the University of New South Wales in Sydney.

 

Myburgh

A number of early studies have suggested that there was a benefit.  But of course the actual benefit, as tested in high quality trials, remained unknown.  So when the results were presented I was neither surprised, nor was I disappointed.  I think the trial was done very well and the study showed, without much doubt, that in fact the use of hypothermia was harmful.

 

Porter

So will that change practice though in a unit like yours?

 

Myburgh

Well I think it will and I think the use of hypothermia as a rescue therapy to lower/raise intracranial pressure will be done with much more caution.  It was used often blindly and often with much enthusiasm and I think what we have seen in brain injury over the last few years, and the Eurotherm trial is a good example of this, is in fact that many of the therapies that we held dear to our hearts, in terms of clinical practice and experience, may in fact be harmful.

 

Porter

Why is it so difficult in the head injury arena to collect the sort of evidence that you need to form guidance that’s founded on solid foundations?

 

Myburgh

The first thing is that you’ve got to have a trial that can recruit a large enough population of patients.

 

Andrews

There are a number of challenges to running any large scale clinical trial and to get robust evidence you have to do a large trial.  And usually when we meet the families of the head injured patient, when they’re admitted to an intensive care unit, we’re explaining that there’s that 25% chance of them not surviving and very likely that they will be brain damaged afterwards.  So taking in further information and then randomising them in a clinical trial and explaining we don’t really have strong evidence for many of the things we’re doing is challenging all round.

 

Myburgh

The trial that Pete Andrews did in fact was not a particularly large trial, it was only 387 patients, but it was done in 47 centres across 18 countries, which for a brain injury trial is a big trial.  But more importantly I think is what do you measure in terms of the outcomes.  Many of the earlier trials looked primarily at mortality, at death, death is a very easy outcome to measure, people are alive or dead.  But in fact what is probably more important for brain injury research is whether or not the treatment results in a higher population of functional survivors.  In other words patients who survive their injury but are left in a good functional state.  And this trial that Peter Andrews did looked at that metric as their primary outcome measure.  And many other recent trials have done this too.  And what it has shown in fact is that whilst mortality rates may in fact not be much different the proportion of patients who are left with higher levels of disability in fact are higher.  And in many ways having an intervention which results in a higher population of more disabled survivors is a much worse result than death.  What this means of course is that maybe the parameters that we’ve been treating aren’t necessarily the right ones.

 

Porter

So where are we now in terms of the latest guidance for you and your colleagues?

 

Myburgh

Well unfortunately I can’t give you a positive answer, that’s the truth.  The Brain Trauma Foundation guidelines has been a very good body which has set up evidence based guidelines to look at interventions in brain injury for the last decade plus.  The committee that sat around the table and worked through a treatment plan to work out what was the best algorithm to treat raised intracranial pressure came to a bunch of conclusions, based on evidence, based on [indistinct word], based on opinion but today that hasn’t been published.  And I think that’s not a reflection of tardy behaviour, it’s a reflection of the difficulty in getting together an evidence based protocol that can inform clinicians.

 

Porter

Professor John Myburgh talking to me online from Australia. And there is a link to Peter Andrew’s Eurotherm study on our website.

 

Just time to tell you about the next Inside Health when I will be investigating antidepressants – not the usual debate about whether or not someone should be started on them, but when people should stop them and how once they have recovered. Join me next week to find out.

ENDS

Broadcasts

Podcast