That Recurring Feeling

It’s that time of year again! Endometriosis awareness month is upon us and I’m a little bit late to the party with this first blog post, but I’ll be trying to get a few posts done this month to help raise awareness of the research most relevant to women with endo.

One of the major issues surrounding endometriosis therapy is surgical treatment for the disease. We all know that complete surgical removal of endometriosis offers the best hope of symptomatic relief (provided endometriosis is the only culprit contributing to symptoms, there are often other conditions associated with endo, like adenomyosis and interstitial cystitis, which can contribute to pelvic pain symptoms, that require differing treatment approaches). However, we don’t really have a lot of studies and empirical evidence in the area of surgical success for endometriosis surgery. Mostly it is down to self-reported numbers from surgeons themselves, which is fine, but it narrows the scope somewhat of how we can assess the success of surgery. The subject of this blog post will be looking at some recent publications concerning how endometriosis surgery is investigated and what we can learn about its effectiveness.

To begin with we have a study from China looking at the outcomes of laparoscopic surgery for endometriosis and how medical treatment after surgery affected the recovery. This study followed 199 with ovarian endometriosis for 3 years after laparoscopic surgery to remove all visible endometriosis and adhesions. These women were then divided into 3 groups depending on what treatment they had after surgery.

Group A were 43 women who only had surgical treatment

Group B were 47 women who had surgery and a GnRH drug afterward

Group C were 109 women who had surgery and mifepristone afterward.

So after the patients had been followed up after three years they were assessed to see whether their disease had returned (recurrence) or showed no signs of return (remission).

Group A – 58% were in remission, 28% had recurrence

Group B – 70% were in remission, 13% had recurrence

Group C – 61% were in remission, 25% had recurrence

You may notice that those percentages don’t really add up, that’s because there was another category of ‘improvement’ which was defined as symptoms remaining, but improving. However the numbers for this category weren’t reported in the paper. What this tells us is that there wasn’t a great deal of difference between women who had surgery alone and women who took mifepristone after surgery. There seemed to be a decrease in risk of recurrence with post-operative GnRH agonist therapy. This effect has also been seen in studies looking at surgery for endometriotic ovarian cysts. Unfortunately this therapy also comes with a long and unpleasant list of side-effects and is not suitable for long term therapy.

The next part was to look at the recurrence rate in women of different ages and different stages of endometriosis.

For the different age groups:

Women aged 25 or under, the recurrence rate was 0%

Women aged 25-29, the recurrence rate was 19%

Women aged 30-34, the recurrence rate was 25%

Women aged 34-38, the recurrence rate was 25%

When you look at these numbers you have to take into consideration  how many were in each age bracket. For example, there were only fourteen women in the 25 years old and under category, but there were one hundred and one in the 30-34 category. So although it looks as if there is more recurrence with age, it could be that there wasn’t a large enough number of patients in each group to give an accurate representation.

In terms of disease stage:

11% of women with stage II disease had recurrence

28% of women with stage III disease had recurrence

43% of women with stage IV disease had recurrence

So it seems as if there is a clear trend of increasing chance of recurring symptoms and disease at higher stages of endo. This could make sense as with advanced stages of endometriosis the pelvis can be congested with adhesions or obliteration of the cul-de-sac, making it difficult to see and excise all the endometriosis, leading to further operations.

The next is another study from China looking at deeply infiltrating endometriosis (DIE) and what are the outcomes for patients undergoing complete or incomplete removal of the disease. You may be wondering what the point of incomplete excision is. Surely you should always strive for complete removal of the disease? Because deeply infiltrating endometriosis, infiltrates deep (the clue’s in the name), this can mean that removing it all could cause damage the affected organs. This can be particularly dangerous where DIE affects the bowel and could lead to severe complications. So, incomplete removal of DIE is only performed where safety is an issue.

For this study there were 51 patients who underwent complete excision and 34 who underwent incomplete excision of their disease.  

Unlike the previous study this one included the location of the DIE as well. The most common sites of DIE in these patients were the uterosacral ligaments (one of the sets of ligaments that hold the uterus in place) and the posterior vaginal fornix (basically the ‘back of the vagina), which you can see labelled as ‘fornix’ in this diagram. Interestingly these two sites are pretty close to one another and as you move away from this area the incidence of DIE becomes less. For example, the number of cases of bladder DIE in this study was 4.3%, but the number of cases of uterosacral ligament DIE was 41.9%, so it would appear there is something about this region of the pelvis that is particularly prone to deeply infiltrating endometriosis. What exactly it is that causes the predisposition isn’t fully understood.  

After the women who underwent surgery were followed-up it was found that there was a substantial decrease in pain scores for women in both surgery groups. What will come as no surprise though is that the women who had complete excision had a much more dramatic decrease in pain scores compared to those who had incomplete excision. You will be similarly unsurprised to learn that the recurrence of disease was 3.9% in the complete excision group, compared to 35.3% in the incomplete excision group. In addition, the time it took for disease recurrence was almost 4 times longer in the complete excision group.

Leading on from this, the quality of life measurements showed that there were notable improvements in all aspects of quality of life (physical, psychological, social etc) in both surgery groups. The only significant difference though, was that women who had complete excision had a greater improvement in the ‘psychological’ component of the quality of life.  

Amongst all the women in this study who wished to conceive, no difference in the fertility outcomes between women who had incomplete or complete excision.

Like the previous study, this one also looked at how post-operative medical therapy can affect the outcome of surgery. This was, again, using GnRH therapy as the standard preoperative therapy, but only in the complete excision group who kept their ovaries. The authors divided patients into four groups depending on what and when they received their treatment:

Group 1) Did not receive GnRH before or after surgery (10 patients)

Group 2) Only received GnRH after surgery (30 patients)

Group 3) Only received GnRH before surgery (1 patient)

Group 4) Received GnRH both before and after surgery ((10 patients)

The authors then compared things like quality of life scores, pain scores and recurrence of disease between the groups to see if there was any effect the treatment regimens had on these outcomes. And the conclusion? There was no significant difference between any of these groups. The only difference they did observe was that those women who received GnRH therapy for 6 months (as opposed to 3 months) were less likely to need further surgery, but were more likely to develop osteoporosis. What is quite telling when you look at the numbers in the four groups is what preference doctors have for post-operative treatment. There are far more women who were given GnRH therapy after surgery who had not taken it before (group 2). It is fairly common practice to offer this type of therapy to women after surgery, yet this study seems to suggest (even though it is a fairly small study) that post-operative therapy makes very little, or no, difference to patient outcomes, but complete  excision of disease does benefit patients the most. Which I think is the take home message from this paper.          

Endometriosis Awareness Month: Part1

Well we are now fully into the swing of endometriosis awareness month so let’s kick things off with some posts.

First off there is study from China looking at how the type and position of endometriosis can determine the symptoms. This study took 177 women with deeply infiltrating endometriosis (DIE) and 177 women with non-DIE and compared their symptoms and what their disease looked like. This is a summary of they found:

• Women with DIE had been suffering with their symptoms for an average of 13.8 years compared to 5.2 years for women with non-DIE

• The infertility rate for both DIE and non-DIE sufferers was about the same (36% and 35% respectively)

• Women with DIE were more likely to have a higher stage of the endometriosis (58.8% of women with DIE were stage IV; the majority of the non-DIE women were stage III, 43.5%)

• Severe dysmenorrhoea, chronic pelvic pain, deep dyspareunia, dyschezia and dysuria were all more common in women with DIE. It’s interesting that dysuria (painful urination) was only found in the DIE patients (although, this study only looked at a relatively small number of women).

• Women with non-DIE were more likely to have endometriotic lesions on the surface of the uterus, bladder peritoneum and the broad ligament. Women with DIE were more likely to have lesions on the uterosacral ligaments, fallopian tubes, ureter and the rectum. Women with DIE were also much more likely to have obliteration of the cul-de-sac (44.6% compared to 22% for non-DIE), which may explain the higher frequency of dyspareunia.

• Women with DIE were also more likely to also have adenomyosis than those with non-DIE (15.8% compared to 4.7%, respectively)

• If the patient also had ovarian endometriotic cysts, women with DIE were more likely to have them on both ovaries (35.2%), whereas women with non-DIE were more likely to have them just on one side (31.6% on the left, 22.6% on the right side).

These types of studies are potentially very useful and much larger studies like this are needed. This is because, if a certain type/location of endometriotic lesions are associated with certain symptoms, this should give surgeons a better idea of where to look for the disease, thus increasing the accuracy of diagnosis. More posts coming soon!

Surgical treatment for Deeply Infiltrating Endometriosis (DIE)

If you suffer from endometriosis then you may be offered surgical treatment to remove the disease. I say you may be offered surgical intervention because there are several factors that determine how likely this option will be given to you, such as; the severity of your symptoms, your fertility, your age, your response to drug treatment, what country you live in and how wealthy you are (sad, but true). If you are offered a surgical treatment, one of your main concerns is going to be, how successful will the surgery be? After all, you are placing a great deal of faith in the hands of the surgeon and you don’t want that faith to be misplaced. No surgery is to be taken lightly, so you want to know the investment you’re making with your health is going to be worth the payoff.

There are several different types of surgery for women with endometriosis, with varying degrees of success, which broadly fall into the two categories of conservative (e.g. excision or ablation) and radical (e.g. partial or complete remove of affected organs). I’ve spoken about the success rates of different surgeries before, but I’ve yet to discuss the success of surgery in the context of what type of endometriosis is being operated on. So, first off, a basic reminder of the different types of endometriosis. There are superficial endometriotic implants, which appear on the surface of organs like the ones in the picture below. These implants come in a variety of colours such a red, blue or black and generally the colour denotes how active the implant is.

In this picture you can see some blue implants as well as reddish-brown ones.

Picture courtesy of endometriosiszone.org

Then there are endometriotic cysts (endometrioma) which usually occur on the ovary and can range from as small as a pea to as large as a melon.

The endometrioma is the dark reddish-purple patch in the middle of the picture.

Picture courtesy of endometriosiszone.org

And there is also deeply infiltrating endometriosis (DIE) which can be one of the most difficult types to visualise and hence, operate on. The reason this type of endometriosis is so difficult to see is that the implants can be very small, up the point of being microscopic and so, invisible to the naked eye. The reason it is known as deeply infiltrating is that, unlike superficial endometriosis, DIE can ‘burrow into’ organs at depths ranging from 2mm to over 15mm and this is thought to be a significant cause of the very painful symptoms associated with endometriosis.

I’m going to focus on DIE for the rest of this post because the article I’ve come across recently is about the success of surgery for this type of endometriosis. The article in question followed 193 women with and without DIE, undergoing excisional surgery in the Päijät-Häme Central Hospital, Lahti, Finland. Women undergoing surgery for DIE were found to have significantly higher rASRM scores than those with other forms of the disease.

rASRM, to clarify, stands for the revised scoring system of the American Society of Reproductive Medicine, who devised this scheme to classify the severity of different kinds of endometriosis. It is based on several features found inside the pelvis during surgery such as type, size and location of endometriosis, as well as the presence and severity of adhesions. The scoring system then classifies the endometriosis into one of four stages; minimal, mild, moderate or severe (although it is worth noting that severity of endometriosis appears to have little bearing on severity of symptoms). In this Finnish study, women with DIE had average rASRM scores that were very close to classing them with severe endometriosis. Women without DIE had average rASRM scores that would classify them as having moderate disease.

This study also found that women with DIE had significantly more previous surgeries for endometriosis and more were indicated for surgery because of pain. With respect to the surgical procedures performed; 60% of women with DIE had surgical excision of peritoneal lesions compared to 82% of those without DIE. This could be reflecting the difficulty of removing lesions in women with DIE, or it may be that women with DIE do not have as many peritoneal lesions.

92% of women with DIE had to have adhesions cut away compared to 69% of women without DIE. This might be reflective of the fact that women with DIE have had more previous surgeries, which would increase the chances of adhesions forming. Interestingly, 32% of women with DIE had a hysterectomy of some variety, compared to only 8% of women without DIE. The reason for this could be that, because deeply infiltrating lesions can be very challenging and time consuming to remove individually (hence, increasing the likelihood of serious complications arising), surgeons may opt for complete removal of the uterus as a quicker and safer procedure.

This study also looked at the completeness of excision of endometriosis during a single operation. Women with DIE compared favourably to those without in this aspect as complete excision was reported in 95% and 97% of cases respectively. However, excision during a laparoscopic surgery for DIE was only complete in 79% in of cases compared to 95% complete removal of endometriosis in women without DIE.

The final important finding of this study was that deep lesions are frequently found outside of the ‘typical’ locations i.e. the uterus, ovaries etc. This is significant because gynaecological surgeons may be unfamiliar with operating in atypical locations, therefore a multidisciplinary approach may be required involving additional specialist surgeons.

Then there is the issue of should patients have preoperative medical therapy? On the one hand some studies suggest that medical therapy before surgery may reduce the risk of complications arising during surgery. However some eminent specialists in endometriosis surgery forgo the use of drugs that may suppress endometriosis due to the fact that they may make the endometriotic implants harder to see whilst operating. If you are due to have surgical treatment for endometriosis anytime soon, these are issues you should raise with your surgeon. It is also important to remember that, if you do have deeply infiltrating endometriosis and are due for surgical excision, it is in your best interest to have a surgeon who is well experienced in this type of procedure and familiar with the problems this type of endometriosis can present.

Whilst we must always remember that one, relatively small, study such as this does not set the standard for all surgeries for DIE, it does give us a good example of what can be expected, the problems faced by patients and surgeons, and perhaps ways in which we can improve the surgical treatment of endometriosis.

The kids aren't alright

If you have endometriosis, when did your symptoms start? That can be a difficult question to answer as it probably wasn’t something that appeared overnight. A lot of the women I speak to found that their symptoms started when they were in their teens and gradually got worse. With endometriosis it’s never simple though, onset of symptoms is usually just the start of the journey. Often is it the case that symptoms, whilst clearly abnormal, are dismissed as trivial and the suffering continues; and it isn’t just the suffering, but the uncertainty. Despite being told otherwise, you know if there is something wrong with your body but no-one can tell you what it is. Diagnosis is one of the biggest hurdles to overcome for a great deal of women with endometriosis. Most of the sources of information on the subject put the average time to diagnosis at 7 to 9 years (although I met a woman once who told me it took her over 20 years to get diagnosed). You have to ask yourself, would people stand for this sort of delay for cancer diagnosis? Doubtful.

There are several factors at play to create these diagnostic delays; the symptoms of endometriosis can be varied and non-specific, endometriosis is hardly ever considered as the first explanation for the symptoms, and sadly a lot of women find it hard to get taken seriously (“some period pain is normal” being the mantra of the more obtuse members of the medical profession).

The good news is some research is being done to help reduce the diagnostic delay, particularly for young women. A recent study from France found that there were significant differences in the adolescent history of women with Deep Infiltrating Endometriosis (DIE). The study took 229 women who were being operated on for endometriosis and gave questionnaires to the 98 who were found to have DIE. These are the highlights of their findings, women with DIE during their adolescence had:
- Greater family history of endometriosis
- More absenteeism from school during menstruation
- Higher frequency and longer duration of oral contraceptive use before the age of 18
This information can therefore offer markers for DIE in young women. Training medical professionals to recognise these markers could therefore drastically reduce the diagnostic delay for DIE and increased the chances of successful treatment.

DIE is a particularly important type of endometriosis as it is one of, if not the most, painful form of the disease. Studies have shown that DIE has an increased number of nerve fibres present in the lesions which may explain their propensity for generating pain. Additionally, the different pain symptoms associated with DIE can often be explained by the location of the lesion (see the results section of this study http://www.ncbi.nlm.nih.gov/pubmed/12372446 ).

Oh, and I apologise for the lateness but I hope you all had a good holiday season and that 2011 is an excellent year for us all.