Thursday, 15 January 2015

Seeing the Light



Welcome to 2015! Firstly apologies are in order for not posting for ages, although it’s not a great excuse the first year of my PhD has been very busy (in a good way) and my research is finally taking shape (more on that to come). Nevertheless, one of my new year’s resolutions was to post here more often so I’ll be endeavouring to pull my various fingers out and get writing.

To jump right in, we’ll begin this year with a piece about seeing the light, or rather seeing a part of it. Narrow band imaging (NBI) is a technique that can be used with video laparoscopy (or other endoscopy technique) whereby certain colours of light are shined onto an area of interest to enhance the image. In this case red light is filtered out to make the image appear in shades of green and blue. This is useful because the main component of blood absorbs blue and green light, making blood vessels or blood containing lesions, appear darker and therefore, easier to see.

Here is an example of the technique used to enhance an image of bladder cancer.

Image source http://www.medgadget.com/2014/12/olympus-narrow-band-imaging-for-cystoscopy-cleared-by-fda.html

On the left is an unaltered image of bladder cancer as the surgeon would normally see through the endoscope. On the right is the same image but with the red light filtered out using the narrow band imaging. The difference is quite striking; the blood vessels and even the diseased areas become much more clearly discernible. Whilst this approach has been predominantly used for the identification of potentially cancerous tissue, it has led some to investigate whether narrow band imaging could be useful in enhancing subtle areas of endometriosis that could otherwise be easily missed.

A study published this month has shown that narrow band imaging can indeed be useful for enhancing the appearance of endometriosis. In particular it was found that this method made clear vesicular lesions of endo easier to identify. Under normal circumstances clear vesicular lesions look like tiny see-through bubbles, making them particularly difficult to spot. Below is an example of a vesicular lesion, it’s made slightly easier to see in this image by the light reflecting off its surface.

Image source: http://www.gynsurgery.org/topics/endometriosis-overview/types-of-endometriosis/

Complete removal of all endometriosis is the best chance anyone stands at gaining relief from the associated symptoms. Therefore utilising new technologies such as this to improve the visualisation of the disease can only mean more thorough excisions and better outcomes for the patient.

Wednesday, 23 July 2014

Endo Seeking Missile



Just a quick update about a potentially interesting piece of research I noticed today.

Researchers have identified a protein (called z13) that selectively binds to and is absorbed by, endometriotic cells. In a way, finding this protein has been like the child’s toy where you have a box with different shaped holes in it and you have to find the right shaped peg to fit in the hole, except imagine you have a box with tens of thousands of different holes and tens of thousands of accompanying pegs, not an easy task. Now that this protein has been discovered it means we have a way to target endometriosis specifically and ignore all other tissue and organs in the body.  

What the researchers then did was attach other proteins to z13 which would induce cells to die. Effectively, what they now had was an endo seeking missile. So far the researchers have tested this on peritoneal endometriosis in baboons and found that the targeted proteins caused the endometriotic cells to die whilst leaving the surrounding tissue unharmed.

One of the best things about this approach, from a patient perspective, is that this is completely non-hormonal; no messing around with the ovaries, no pumping the whole body with hormones, just targeting the disease itself.

Cautious optimism aside, it may be a while before we see this approach translated into humans and there are still many more tests to be done to make sure it is safe. Nevertheless this shows that research is not continuously bogged down in the old ‘hormone therapy’ mindset and people are exploring new and exciting possibilities and, whilst this may not be a cure, it is a step in the right direction.

Monday, 9 June 2014

Highlights from WCE 2014 - Part 3



Carrying on with our WCE 2014 highlights, let’s have a look at some of the research into fertility issues and endometriosis. Reduced fertility is one of the major problems faced by women with endometriosis, yet there are still many mysteries surrounding how endometriosis affects fertility.

In order to shed at least some light on the issue an Italian research team investigated how ovarian endometriosis (endometrioma) can affect the viability of ovarian follicles in women undergoing IVF. What they found was that follicles closer to endometrioma showed higher levels of iron. Iron, of course, is important for your body but in endometriomas iron accumulates in high amounts, probably due to blood filling the inside of the cyst. These high levels of iron can be toxic to anything close by, in this case, ovarian follicles. This leads to impaired development of the follicle and perhaps partly explains why so many women with endometrioma/s find it hard to conceive.

If you have an endometrioma, chances are you’ll want surgery to remove it, but you’ll also want to know what the risk of recurrence is and what factors influence that risk. A team from Brazil looked at the records from 202 women undergoing laparoscopic excision of endometrioma between and 2003-2012 and analysed those records to see what influenced endometrioma recurrence. They found that the overall rate of endometrioma recurrence was 16.4% and that factors such as age, race, symptoms, exercise, number of children and type of surgical procedure had no effect on recurrence rates. However, they found that having a cyst larger than 6cm (which is pretty large) and stopping medical therapy after surgery significantly increased the chance of endometrioma recurrence (although the abstract didn’t specify which medical therapy was used). Because of the side effects associated with some of the medical treatments for endometriosis, it is unsurprising some women need to stop treatment. However, if stopping treatment means an increased risk of disease recurrence, then more work needs to be put into ensuring other, more tolerable medical options are made available.

Speaking of IVF, some women who suffer with fertility issues may consider IVF as a means of conception. It is therefore important for women with endo to know if their condition may affect their IVF outcome. A group from France compared 291 women with endo to 1316 women without to see what the effects, if any, endo made to the delivery rates after undergoing IVF. What the researchers found was that, in the women who had good ovarian stimulation response and high quality embryos, the total cumulative successful delivery rate for fresh and frozen embryos was 52.3% for women with endo and 45.8% for women without. Although women with endo had lower rates of good ovarian stimulation, the overall outcome was no different between women with and without endo. This suggests that having endo (regardless of stage) may not impact the success of IVF.

Although it appears that endo doesn’t affect the success of IVF, it would still be good to have some way of improving IVF outcomes. A group from New Zealand has been conducting a randomised, controlled trial to see if a drug called Lipiodol has any benefit on IVF outcomes, as their initial tests showed this treatment improved the fertility of women with endo much more than women who couldn’t conceive but didn’t have endo. Lipiodol can normally be used for hysterosalpingography (a procedure used to determine the shape of the uterus and fallopian tubes) and is injected into the uterine cavity so comes into contact with the endometrium. The authors of this study think that Lipiodol ‘bathes’ the endometrium, making it more receptive to a fertilized egg. Their results are still very preliminary so should be met with cautious optimism, but are still encouraging. The women who received IVF alone achieved a live delivery in 22.7% of cases, but the women who had Lipiodol treatment plus IVF achieved a live delivery 43.8%. These results are encouraging, but we’ll have to wait until the clinical trials have been completed and the results properly analyzed before drawing any firm conclusions.

Thursday, 5 June 2014

Highlights from WCE 2014 - Part 2



Let’s continue our exploration through the World Congress on Endometriosis 2014 and we’re going to delve into some of the research about what makes women with endo different from those without and how this could give us clues as to what causes endo in the first place.

A team from Australia made an interesting discovery regarding stem cells and endometriosis. You have probably heard about stem cells before, but why would they be of interest in endometriosis? Stem cells are the precursors to the different types of cells in your body and are mostly of use during the very early part of your development when you were a foetus growing new organs. But they still have some use as an adult, for example, inside the uterus there are a population of stem cells that your body uses to regrow the endometrium after each menstruation, which are unsurprisingly referred to as endometrial stem cells. If these cells can grow endometrium and endometriosis is endometrium-like tissue, it becomes clear how these stem cells could play a role in endometriosis. Some researchers believe that genetic changes associated with endometriosis result in some endometrial stem cells becoming displaced during embryo development, which go on to produce endometriotic lesions as a girl approaches adolescence. Others believe these stem cells are shed into the pelvic cavity by retrograde menstruation (where the menstrual blood goes into the pelvic cavity) and implant around the pelvis and then develop into endometriotic lesions.

This investigation by the Australian team looked at the number of endometrial stem cells in the blood, menstrual blood and peritoneal fluid of women with and without endometriosis. What they found was that, although the amount of peritoneal fluid was similar between the two groups, the number of viable endometrial stem cells in the peritoneal fluid was massively higher in women with endo. So how did those cells get there? Retrograde menstruation is a likely explanation, but they found no difference in the amount of stem cells in the menstrual blood between women with and without endo.  It could be that the immune system of women with endo doesn’t clear the refluxed stem cells and they just accumulate or maybe there is some other way these cells are getting into the pelvic cavity, at this moment nobody knows for sure.

Speaking of peritoneal fluid, a group from the US and Brazil analysed the peritoneal fluid looking for inflammatory factors that are related to endometriosis associated pain. What they found was that dyspareunia (painful sex), non-cyclic pain and infertility were not related to the inflammatory factors they were studying. What they did find though was that certain inflammatory factors were associated with dysmenorrhea (excessively painful periods). This has some potentially very interesting implications, particularly as dysmenorrhea is the most common symptom of endometriosis. This suggests that dysmenorrhea is caused by areas of chronic inflammation around the sites of endometriosis regardless of stage or location. If it were possible to find out how these inflammatory factors are being produced and find a way to reduce the level of these factors, in the future this could be a new way of treating the pain associated with endo. 

More highlights on the way soon...

Tuesday, 3 June 2014

Highlights from the World Congress on Endometriosis 2014



It’s that time again, that time when the best and brightest in the field of endometriosis gather together in one place to share their collective experience and figure out where the future of endometriosis research and treatment is going; all whilst enjoying a caipirinha on the sunny beaches of Sao Paulo (us science types know how to multitask). Although I managed to go to the previous WCE in France, unfortunately I couldn’t make it this year, so instead of enjoying the glorious heat of the Brazilian south I was enjoying the drizzly rain of the English northwest, oh well. However, thanks to a friend, I did manage to get the book of abstracts (which is basically a summary of all the talks, presentations and posters at the conference) so I can give you a rundown of what’s been going on in the field of endometriosis research now and in the future.

Before I continue I must mention that the information I’ll be presenting here is taken only from the abstracts, which as basic summaries of the research and not in depth discussions and may or may not be taken from completed or peer-reviewed research. Also because these are conference papers I can’t provide links to source material as I normally would.

To start with, just looking at the book is encouraging, over 400 pages of research into all the many and varied aspects of endometriosis, which is broken down into different subject matters, so I’ll start with genetics and endometriosis.

Genetics is an important factor in endometriosis, mainly because we don’t really fully understand how genetic changes contribute to endometriosis risk. A team from Sweden aimed to examine indirectly the role genetics play, by looking at the rate of endometriosis in twins. There are two different types of twins: monozygotic (where both twins come from the same egg and are essentially genetically identical) and dizygotic twins (where each embryo comes from a different egg and can so each twin can be very different from the other). Of all the female twins this research looked at they found that there was a much higher risk of endometriosis if your monozygotic twin also had endometriosis. That certainly seems to suggest that genetics plays a role in the origin of the disease. Of course there are other factors at play too in determining endometriosis risk. This team, after doing some calculations, found that in the women they studied, genetics accounted for around half of the risk associated with endometriosis and environmental factors accounted for the other half. Finding out what the specific genetic and environmental factors are and how they increase or decrease the risk of endometriosis, is an ongoing challenge for the future.

Several other studies presented at the conference aimed to find out what these genetic factors are. Our genetic material (our DNA) is a funny thing, it can change in many different ways, some bits can swap, duplicate or be deleted all together and sometimes specific changes can be associated with specific diseases. Other research identified some of these specific changes associated with endometriosis which may, in the future, might allow us to identify women at risk of the disease with greater ease and hopefully give us to better understand the way in which the disease works.

Of course there are problems to consider, for example, are the genetic changes we see the same across all women? One of the presentations from an international team found that the genetic changes we know of so far are very similar between women of European and Japanese ancestry, but we still have no information on women of African, Chinese, Indian etc ancestry to compare them to. These types of studies though require a great deal of time and money invested in them, so it may be a while before we see a complete picture of the genetic risk associated with endometriosis for women across the world.

Another point to consider is the difference between types of endometriosis. One piece of research from a Danish team found genetic alterations specific to deeply infiltrating endometriosis. Therefore it could be that peritoneal, deeply infiltrating and ovarian endo all have different genetic alterations (and different genetic risks) associated with them. It’s good to know though there are people actually looking into this and one day, maybe soon, we’ll have that complete picture.

More to follow soon.