Friday, 29 April 2016

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.          


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  2. These are very interesting data, AND I am more interested in how we can improve long term, post-surgical outcomes for women using targeted nutritional, supplementation, and lifestyle modifications, because we know that the hormonal treatments are only somewhat effective, and that they, as you said, come with a long list of unpleasant side effects. Side effects indicate to me that collateral damage is happening, which shouldn't be supported. I want to see treatments that do no harm, and support the underlying mechanisms of healing in the face of this disease.