Thursday, 1 December 2011

Endometriosis in an 18 month old infant

This month appears to be the month for rarities, a few days ago I was reporting on the case of endometriosis in a man and just today a case report from Hong Kong was published on something even rarer, ovarian endometriosis in an 18 month old girl. This alone would be enough to raise an eyebrow, but what made both my eyebrows almost fly off my forehead was that this girl also had an endometriosis-associated ovarian tumour.

It has been known for ovarian endometriosis to be associated with an increase risk of developing tumours of the ovary, but this in itself is a rare event and to find this occurring in an infant means the odds of this occurring must be astronomical.

This isn’t the first case of endometriosis in a pre-pubertal girl I’ve heard of; there have been documented occurrences of endometriosis in girls aged as young as 8 years old and I’ve wrote about several publications from Italy concerning the discovery of endometriotic tissue in unborn human foetuses. But ovarian endometriosis associated with ovarian tumours is something which is more often reported in older women with advanced stage endometriosis.

So it concerns me greatly how this could have occurred in an 18 month old infant. The authors of the case report state that the girl’s hormone levels were normal for someone he age and there was no evidence of precocious puberty or genital abnormality. Perhaps this girl had a particularly disproportionate genetic or epigenetic susceptibility to endometriosis, in which case further investigation along this line may answer some of our most long standing questions about which genes (or gene variants) make someone more at risk of developing endometriosis.

It could be hat this girl had been exposed to high concentrations of some environmental pollutant, either whilst still in the womb or during early development which triggered onset of the disease. Hong Kong is a heavily industrialised urban area with a serious pollution problem, so exposure to pollutants could be a contributor to this rare occurrence; it really is very hard to draw any definite conclusions though.

Whatever the cause of this particularly peculiar event, it highlights how little we know for certain about endometriosis. With the growing body of research on the disease, scientists involved in endometriosis need to take a step back and have a long hard look at the current state of our understanding because, personally, I think a radical shift in our thinking is needed.

Tuesday, 29 November 2011

The Art of Endometriosis

They say that suffering inspires creativity, after all some of the most notable artists from any time period you care to mention have drawn on their own personal tragedy when composing some of the greatest works to grace the halls of our museums and galleries. Of course, if it were true that suffering is indeed the well from which creative genius is drawn, then women with endometriosis would have contributed more to the cultural development of humanity than all the other artists, philosophers, musicians and playwrights combined.

Nevertheless, endometriosis can be a source of inspiration for people of all walks of life; for instance, I can say that personally the disease has inspired me to research and understand it in as greater depth as possible (because the first rule of war is “know your enemy”).

Some have used their experience with endometriosis to generate creative works; for example, poetry like that by Belle Browne and Roberta Speyer, paintings such as those by Adelaide Damoah and even organising events based around art to raise money for endometriosis research and awareness, like the ‘Art for Endometriosis’ event in 2009.

Some have even suggested that art therapy may be of use to women with endometriosis. Mostly as a means of expressing how you feel about the disease or even helping to work through anxiety, fear and even grief associated with the disease. Whatever your feelings may be I would still encourage you to embrace your inner artist, be it through writing down how you feel or expressing it with a pencil, paintbrush or digital media. Even if, like me, you’re not going to be invited to repaint the ceiling of the Sistine Chapel anytime soon, you still might surprise yourself (in a good way!).

So in the spirit of joining in I fired up my newly acquired version of Photoshop and did a few bits of official Endometriosis Update artwork. (Click on the thumbnails below for the full version)

Happy creating! And if you do decide to make some endo art (or any other art for that matter) and want to share it, feel free to post a link to it in the comments.

Thursday, 24 November 2011

There’s something you don’t see everyday

Endometriosis in a man. Yep, thats right, it is an incredibly rare occurrence but it has been known to happen. This, particularly detailed, report comes from Japan and concerns a 69 year old man who had been undergoing estrogen therapy for 9 years to treat prostate cancer. In the abstract no account of the symptoms are given, but it does state that the man was found to have a series of endometriotic cysts measuring approximately 5x3cm in the left paratestis (the region just above the testicle).

The authors state that this may have occurred due to, what is known as, endometriotic metaplasia or stromal hyperplasia. Basically, what both of these terms mean is that, under the influence of increased estrogen levels, the normal tissue has undergone a change into a different tissue type.

This case report isn’t the first to observe endometriosis in a man; it’s not even the first report of it occurring in this area of the body.

Other than that there have only been six other cases of male endometriosis reported in locations such as the bladder, prostate and lower abdominal wall. However, if we look at all of these cases, most of them have one thing in common; they have been undergoing long term estrogen therapy for the treatment of prostate cancer. This is quite important, as unusual presentations of a disease can often give us clues as to how it arises in women.

One of the reports of male endometriosis was from a young man aged 27 who was otherwise completely healthy, very different to the other reports which are mostly much older men with prostate cancer. So not only was this an unusual presentation of endometriosis, it was an unusual, unusual presentation, if that makes sense. So what can this tell us about the disease as a whole?

The authors of this report looked to the very beginning of the development of the reproductive organs. Whilst still only a developing embryo, there are different structures that will form the male and female reproductive systems (there’s a nice illustration here). The female organs develop from the müllerian duct which in male embryos regresses because the embryo produces the imaginatively named müllerian inhibiting substance (MIS). The authors of this report suggest that exposure to certain environmental toxicants (such as diethylstilbestrol or other hormone disrupters) whilst the embryo is still developing, may lead to abnormal production of MIS which in turn stops the müllerian duct regressing properly, leaving small remnant patches of tissue that could, given the right stimulus, develop into endometrial like tissue, which would appear as endometriosis.

Could something similar explain endometriosis in women? Well there could be if this ties in with the theory of mullerian rest. This theory states that during normal foetal development, tiny parts of the mullerian duct, perhaps only a few cells, get displaced and deposited on other organs. Once there, the displaced deposits do nothing until stimulated to transform into endometriotic tissue later in life. What these exact stimuli are, or why some women experience this displacement are mysteries, as yet, unsolved, but answering these questions may be a defining moment in the history of endometriosis.

Monday, 21 November 2011

Thinking outside the box

When you look back at the history of science, you'll notice that it is heavily punctuated by radical ideas to solve complex problems. Some of these radical ideas have lead to changes that shaped and changed the world, others not so much. For example, American doctor Jonas Salk saved the lives of millions and practically eradicated the disease polio in the 1950s by injecting people (including himself and his own family) with ‘inactive’ versions of the polio virus; a hefty risk that paid off. Other medical cures haven’t proved quite so successful. For example, there is the sad case of Alan Turing, a brilliant British scientist without whom you would not have the computer you are reading this on now. Around the same time Salk was developing his polio vaccine Turing was convicted of being a homosexual (a custodial offence in the UK at the time) and rather than face prison he was forced to undergo estrogen injections to ‘cure’ his homosexual urges. The side effects were, of course, horrific and not long after he committed suicide by taking a bite from an apple laced with deadly cyanide (some people speculate the logo for Apple computers pays homage to Turing).

Obviously those are two very extreme examples, but they set the scene for the topic of this post, which is radical thinking in science, especially in relation to endometriosis.

Endometriosis is complicated, no matter what your views on the origin, treatment or mechanism of the disease; we can all agree it is complicated. In order to solve a complex problem, no matter what it is, people have come up with many different possible solutions and endometriosis is a shining example of that. There are so very many different types of treatment for the disease, from established treatments like the multitude of hormonal therapies and surgeries, through alternative medicine all the way to cutting edge technology like gene therapy.

But the field is always progressing, as scientists we are always researching and doing experiments to try and solve complex problems and sometimes the ideas that are borne of these experiments can seem a little different or unusual at first.

Take, for example, this piece of research by a group from Turkey. This group induced endometriosis in rats and then divided them into two groups. One group of rats were left to get on with their business without any interventions (a control group), whilst the other group was placed in hyperbaric oxygen therapy (HBO) for two hours a day over 6 weeks. So what is hyperbaric oxygen therapy? Basically it involves the subject being placed in a chamber which contains pure oxygen which they breathe for a period of time. This isn’t a new treatment either; it’s been used for a long time to treat all sorts of conditions, from sports injuries to carbon monoxide poisoning and even alleviate the side effects of radiotherapy, but never as a possible treatment for endometriosis (for more on HBO follow this link). Below is a picture of a HBO system used for humans.


Anyway, back to our original study. The results of this study showed that endometriotic implants of rats receiving HBO had decreased in size compared to the implants from the control group. There was also a marked decrease in markers of inflammation in the HBO rats. Essentially endometriosis in the HBO rats had gone into remission. So why might his be the case and where do we go from here? Well, HBO is used for the purposes I mentioned above because it encourages wound healing and also helps boost the immune system, so it could be that the HBO therapy is helping the body destroy the endometriotic implants. Despite this being an animal based study (which means it may not work the same in humans) this is still an encouraging result as HBO therapy has no serious side effects and is overall very safe. Because of this, in the future it would be easy to test HBO therapy on human subjects with endometriosis to see if it could help recovery from surgery or reduce symptoms.

Whilst I’m not anticipating hyperbaric oxygen therapy will be a cure for endometriosis, the type of thinking that the authors of this study were doing will eventually lead to a cure. By that I mean in science it is important to step out of one’s comfort zone occasionally, take risks, think of the radical ideas no-one has thought of before but be prepared to be proved wrong and always be held accountable. It is only by embracing what is new and being fearless in our approach that means we will, one day, find a cure for endometriosis.

Tuesday, 8 November 2011

A Recurring Problem

One of the problems with a disease like endometriosis is that, because our understanding of the disease changes over time, the things that we hold as true today may turn out to be inaccurate, misunderstood, or just plain wrong in the future. For example, it used to be thought that endometriosis was a problem reserved almost exclusively for women in their 30’s, ‘career women’ as they used to say. There never seemed to be any rationale for this, no reason as to why women of this age appeared to be more at risk, it was just accepted, most likely because the shared experience of many people in the field led them to that conclusion.

However, this perception seems to be radically shifting, especially over the last five years or so. Nowadays it is becoming increasingly recognised that cases of endometriosis are rising higher and higher in younger and younger women, particularly girls in adolescence (case in point, there was a recent report of an 11 year old girl diagnosed with an endometrioma). If we look at the literature we can see that in the last 10 years there have been 526 articles published containing the keywords ‘endometriosis’ and ‘adolescent’. Compare that to the previous decade there were only 278 articles published.

So why might this be the case? Is there some evidence to suggest young women are becoming more susceptible to the disease? Or is it that increased awareness, both in the medical and public environment, leads to women getting their symptoms investigated seriously at a younger age? I know that the average time until diagnosis stands at a completed unacceptable 7-9 years (depending on who you talk to) and I also know that many, many women have to struggle to get their symptoms taking seriously in the first place, so the age at which a woman is diagnosed cannot be used as an indicator for when the disease first appeared. This is probably where the whole idea of endometriosis being a disease of women in their 30’s came from; because that was the age they were being diagnosed, not the age at which the disease/symptoms appeared.

Have you ever watched a horror film where the protagonist goes into a room, expecting to find a nasty surprise, only to find the room is empty? They feel a huge sense of relief, turn around to walk away and then a monster jumps out of the shadows, in the process lifting you several feet off your chair, well endometriosis is kind of like that monster. Because even if endometriosis is removed surgically, and we all breathe a collective sigh of relief, it can still be waiting in the shadows. This study from Italy exemplifies the recurrent potential of endometriosis with its finding that approximately 1 in 5 women undergoing laparoscopic surgery for endometriosis experienced recurrence of the disease. Further studies looking at a wide range of literature found that recurrence of endometriosis after surgery can be as high as 21.5% after 2 years and 40-50% after 5 years. At the moment we don’t have a good idea why recurrence should be this high. Certainly the skill of the surgeon and the quality of equipment used play a big part, but whether there are other factors that could influence the recurrence of endometriosis, such as lifestyle factors, medication or genetics, remains to be shown.

The reason I’ve been talking about endometriosis in younger women and the recurrence problem is that there has been a paper published recently combining those very subjects. This study, also from Italy, took 57 girls under 21 who had been diagnosed with endometriosis and followed their medical history over the next 5 years. Out of the 57 girls that enrolled in this study, 32 (56%) had a recurrent diagnosis of endometriosis. Of these 32 girls with a recurrence, 11 had further laparoscopic surgery to treat the disease. The authors of this study found that factors such as: symptoms, stage/site of disease, type of surgery, medical treatment did not influence who got a recurrence and who didn’t.

The recurrence rate of endometriosis in these young girls is very high, well over half of the girls treated experienced either a recurrence of the disease, or of their symptoms. But the million dollar question still remains, why?

I have no definitive answer, but I know that endometriosis can be an insidious disease. Tiny patches of endometriosis can evade the eye of even the most skilled surgeon and from these seeds, the vicious thorns of the disease can flourish. In the future better methods for visualising the disease may vastly increase the ability of a surgeon to remove all of the disease. Until that time though, for some people, endometriosis will be a recurring problem.