The Endometriosis Roller Coaster: Understanding Recurrence and How to Prevent It

The Endometriosis Roller Coaster: Understanding Recurrence and How to Prevent It

Surgery is a cornerstone for initial diagnosis of endometriosis and is an effective treatment option. But, it is not a guaranteed cure, because endometriosis can recur after surgery.  What? Why? 

The reasons for endo recurrence are complex and multifactorial and involve a combination of factors.  These include incomplete removal of the endometriosis tissue, hormonal imbalances, immune influences, toxin influences, molecular influences and probably even more we still do not fully understand. So, while thorough and meticulous initial excision is key, a poor excision is not the only reason for recurrence and progression.  Let’s look at these factors in more detail, and, more importantly, explore what you might be able to proactively do to help reduce the recurrence risk.   

Incomplete Excision

Incomplete removal of endometriosis lesions is probably the most common cause of recurrence after surgery.  Endo can be difficult to remove completely, especially if it has grown deep into the pelvic tissues and organs, and if an affected uterus and/or ovaries are being preserved. Of course, expert surgeons are trained to optimize excision and minimize recurrence.  But in some cases, the remaining lesions can be obscured by inflammation or microscopic and not visible to the surgeon, making it difficult or impossible to remove no matter what level skillset the surgeon has.  If even a small amount of endometriosis is left behind after surgery, it can and probably will grow back over time.  The more that is left behind, potentially the faster it may grow back.  However, this is not a linear growth relationship because of the factors we explore below.  Some lesions simply grow slower than others for various reasons, and some might not grow at all to a symptom-producing level.   

So, what can be done to improve the chances of initially optimal surgery?  We’ll explore the pros and cons of available tools below.  But first, what about the surgeon?  Depending on your situation and resources available to you, some combination of advanced surgeons will be key to your treatment in most cases. The details about your options are as follows.   

Published research generally favors excision (removal) over fulguration (burning) of endometriosis implants, especially in deep infiltrating endo and for endometriomas. While there is some debate over this, fulguration near delicate structures like the ureters or bowel can be very unsafe and fulguration generally causes more scarring or fibrosis.  Fibrosis itself may increase pain as your body heals, even if all the endo itself was destroyed.  

So, the first step is to make sure that your potential surgeon is trained and capable of excision surgery and not just fulguration.  There are a number of pathways to this.  General gynecologists that are trained to perform thorough excisions are very far and few between.  So the trail leads to gynecologists that have had additional training in excision and minimally invasive surgery.  Who are they?  

Most advanced endo excision surgeons have trained in a one to three year minimally invasive surgery or “MIGS” fellowship. These are not regulated or accredited by any boards but are usually sponsored by the AAGL (American Association of Gynecologic Laparoscopists). This means the training is usually quite good, but not all mentors are created equal and there is no board required standardization.  Hence, some surgeons graduate being far better at excision than others.  So, you should still do your due diligence about the surgeon you select, based on as much information as possible, including their background, their results, what patients say, and so on.  

The other consideration is that this MIGS training, at least in the United States, may not include bowel and urologic surgery and usually does not provide  the credentials to obtain hospital privileges in these procedures.  So, an excision surgeon will often work with general surgeons, urologists and others as a team to cover the bowel and urinary tract aspects of surgery.  This can be very effective, but in some centers, logistic coordination of multiple surgeons works better than in others.   Unless this coordination is well worked out, it might be better to seek someone that is trained to do all or most excision without requiring a large team of supporting surgeons.

The other main way that gynecologic surgeons get advanced complex surgical training is through a three to four year gynecologic oncology fellowship accredited by the American Board of Obstetrics and Gynecology (ABOG) and American Council for Graduate Medical Education (ACME). This training includes the ability to operate on any organ in the abdomen and pelvis, including the diaphragm.  However, the training focus is on cancer and not much, if anything, on the pathophysiology of endometriosis.  So, while this surgical training leads to the absolute pinnacle of gynecologic surgeon expertise, not many of them understand and/or know how to treat endometriosis beyond what they learned in residency.  So, in some cases, an excisionist works with a gynecologic oncologist instead of a general surgeon or urologist.  On the other hand, a relative handful of gynecologic oncologists do focus on advanced endometriosis. 

If chest endo is strongly suspected on imaging, a thoracic surgeon is required as part of the team for formal lung surgery.  Similarly, if large nerves such as the sciatic nerve to the leg is likely to be involved on imaging, a neurosurgeon may also be part of a team or backup.   

Regarding fertility issues, an ABOG/ACGME board-accredited fellowship leading to specialization in Reproductive Endocrinology also exists and such physicians may be involved in your care with advanced technologies such as in vitro fertilization (IVF).  This was historically a more surgically focused specialty in the United States.  Today it is not, but some REI specialists have retained an interest in things surgical and may be trained in excision surgery.    

Determining the surgical strategy in your specific case can influence the outcome as well.  Related potential contributors to endometriosis recurrence after surgery include age, disease severity, and the type of planned surgical procedure performed. Older patients and those with more severe endometriosis are at higher risk of recurrence after surgery, unless perhaps the uterus and both ovaries are removed.  Patients who undergo conservative surgery, which aims to preserve fertility by removing as little normal tissue as possible, may also be at higher risk of recurrence compared to those who undergo more aggressive surgery.  This depends on the disease locations and the skill of the surgeon.  Conservative surgery can still result in removal of all visible endometriosis in many cases, with the right surgeon and right equipment.  So, discussion of your ranked, and possibly competing, priorities with your surgeon is essential for the best outcome.   For example, is the main goal pain relief or is it fertility preservation?  Or is it both? What is most important to you?  Being on the same page with your main surgeon, especially if there is a team involved with potential multiple opinions, is crucial to get the results you want. 

Hormonal Influences

Hormonal imbalances play a crucial role in the development and recurrence of endometriosis. Endometriosis is believed to be strongly influenced by an excess of estrogen in the body, which can cause the endometrial-like tissue to grow outside the uterus. Hormonal therapies such as hormonal contraceptives, progestins, and gonadotropin-releasing hormone (GnRH) agonists and antagonists can be used to manage these hormonal imbalances.  The problem is that Mother Nature is infinitely smarter than the best doctor(s) and some of these therapies are worse than the disease, in terms of symptoms and side effects.  It really depends on the individual situation. 

Even after menopause, whether natural or by surgical excision of the ovaries, estrogen does not completely disappear.  Endo affected tissues can produce estrogen locally, other hormones and toxins you take in can convert to estrogen in your fat cells and, of course, hormonal replacement are all additional sources which can contribute to endometriosis recurrence. 

So, if the hormonal imbalances are not addressed, the endometriosis tissue can grow back after surgery.  But what does that really mean and what can you do to favorably influence this risk factor?   

One thing is for sure, doing something beyond surgery is better than nothing.  Anything you can do to reduce your estrogen load is first priority and use of progestins to balance this overload may also be recommended.  Whether or not to go for complete ovarian shutdown of estrogen production (GnRH analogs) is situation specific but usually not ideal due to the significant health effects of basically being in menopause.  The newer variations which provide some estrogen giveback are better but still have their limitations.  More often the pharmaceutical solution is oral contraceptives, which is far easier to handle in terms of potential side effects.   

One of the easiest things you can do yourself to reduce excess estrogen fairly quickly is to make sure your gut microbiome is functioning optimally.  This requires a close look at your diet, avoiding toxic junk food, and using probiotics and prebiotics.  When your gut bacteria are working well they metabolize the excess estrogen in your body and this leaves your body through bowel movements.  If not, excess estrogen is reabsorbed, recirculated and contributes to estrogen load.  

Another natural strategy is to lose weight.  Your fat cells store xenoestrogens from the toxins we all take in daily and slowly release this estrogen back into the bloodstream.  Also, the more fat cells you have the more other hormones are converted to estrogens which are also released into your blood stream. Weight loss is not a rapid proposition, but the best time to get started is yesterday.   

Reducing stress through mind-body techniques can also reduce estrogen levels.  Reducing alcohol intake improves your liver’s ability to break down estrogen.  Finally, some supplements, notably seaweed, can reduce estrogen in your body.  Others that top the list are Vitamin D, Magnesium, Milk Thistle, Omega 3 fatty acids (fish oil), Vitamin B6 and DIM (diindolylmethane).  DIM is found in cruciferous veggies, so you can up that intake easily through diet.  

Only after doing some of these things should you get radical on altering your hormones through medical pharmaceuticals.  There is a whole range of hormonal strategies including more natural compounded preparations.  Having said that, work with your doctor for the best strategy for your specific situation.   This is not something you should do on your own beyond diet and lifestyle modification.  The main take home message is that there is plenty of data which supports doing something to balance your estrogen and progesterone after surgery to reduce recurrence.   

Immune Influences

The immune system plays a critical role in the development and progression of endometriosis. Endometriosis implants produce inflammatory factors that attract immune cells to the site, which can cause inflammation and pain. However, immune cells can also help to fight recurrence.  

Surgery may temporarily disrupt the balance between pro-inflammatory and anti-inflammatory immune cells, but acute inflammation helps with healing and this is self-limited in almost all cases.  This type of inflammation you do not want to interfere with in the short term.  On the other hand, inflammation can contribute to recurrence if it is allowed to become chronic.   Research suggests that immune-modulating therapies such as immunosuppressive agents and immunomodulatory cytokines could be effective in preventing the recurrence of endometriosis after surgery.  However, there are no reliable pharmaceutical treatments along this line yet.  On the other hand, research suggests that natural killer cells (NK) are deficient in endo patients.  An integrative nutritional approach to enhancing NK number and function is mushroom consumption.  Work with an integrative specialist on this.  

A recent sub-theory for endo development and recurrence is the “bacterial contamination hypothesis”.  This is based on the role of bacterial endotoxin (lipopolysaccharide, LPS) stimulating the pelvic inflammatory immune response.  Since patients with a history of pelvic infection, chronic endometritis and SIBO are known to have higher incidence of endometriosis, the commonality is a bacterial endotoxin (LPS).  So, regardless of whether the bacterial LPS got there via intestinal translocation (micro-leaking) or retrograde menstruation, its presence is potentially key in stimulating endo growth and regrowth.  Along these lines, treatment with either natural or pharmaceutical antibiotics may help attenuate chronic low level infection related inflammation. 

This is certainly not mainstream thought but plausible and based on at least animal model evidence with some human study support as well.  Attention to keeping your microbiome healthy and minimizing leaky gut as well as vigilance for any gynecologic infections may be prudent and is low risk. 

Toxin Influences

Exposure to toxins and pollutants can also contribute to the development and recurrence of endometriosis. Certain toxins, such as dioxins and polychlorinated biphenyls (PCBs), have been shown to disrupt hormone levels, acting mainly as xenoestrogens, and increase the risk of endometriosis growth.  Therefore, lifestyle modifications such as avoiding environmental toxins and adopting a healthy diet may be beneficial in preventing the recurrence of endometriosis after surgery.  

Molecular Influences

Recent research has shown that molecular changes in endometriosis implants may also contribute to the development and recurrence of endometriosis. Mutations in certain genes involved in regulating inflammation and hormone levels are examples.  Environmental and inflammatory influences can also upregulate hormone receptors, which means less estrogen is required to stimulate regrowth from micro-foci of endometriosis.   All these changes can be genetic mutations or epigenetic influences which turn normal and abnormal genes on and off. 

There is a lot of molecular crosstalk that regulates hormonal, inflammatory, immune, neurologic and other processes.  This is the glue that interconnects all of these factors that affect progression of endo and symptom causation.   

If your endo recurrence seems to be too rapid after a good excision surgery, or you have multiple recurrences and especially if you are older and/or have a family history of cancer or endo, please consider the following.  While rare, endo can degenerate into cancer or increase ovarian cancer risk and, even before that might happen, some gene mutations (e.g. ARID1A, KRAS, PIK3CA) can contribute to a more aggressive variant of endometriosis.  To determine if this is a contributor to your disease, genetic counseling and testing may be a good idea. 

Surgical Equipment Influences

Minimally invasive surgery is the gold standard of endometriosis surgery these days, not surgery though a big incision called a laparotomy.  Having said that, after multiple prior surgeries, a surgeon may try to convince you that a laparotomy is what you need because you probably have too many scars or fibrosis and, therefore, minimally invasive surgery may be too risky.  While this may be true in very rare cases, it is not true in the vast majority of cases and you should probably seek other opinions.  Laparotomy surgery often leaves behind much more scarring than minimally invasive surgery.  There is always a possibility you may need yet another surgery, so find an expert to minimize all risks for this surgery and possibly subsequent ones. 

Minimally invasive surgery may mean laparoscopy or it may mean robotically assisted laparoscopy, depending on the surgeon you choose.  While laparoscopy has been around much longer, there are major technologic differences.  For simple to moderate cases, either is fine. However, for more complex cases and recurrence, you should understand the technical differences and what they mean.  Imaging may suggest but it is often not possible to accurately predict how much disease is present, or how much anatomic distortion there is, until the actual surgery starts.  But you can bet that if you are facing a repeat surgery, the anatomy may be more distorted than the first time.   

The following represents the opinion of this author surgeon who has used both laparoscopy and robotics over the past three decades, but, due to the reasons noted, has converted almost exclusively to robotics.  Having said that, it is important to understand that at the end of the day the skill of the surgeon trumps the equipment in most cases.  However, at some point, better technology does offer some clear advantages for most surgeons, should they choose to avail themselves of it.  Herein lies the problem.  Many have chosen to only dabble in robotics or ignore it altogether as an option.  So, beware of any surgeon who says that robotics is just a fad or training wheels for laparoscopy.  This is likely a surgeon who never took the time to master the superior technology offered by robotics to appreciate the difference.  The final major argument against robotics is that it costs too much or takes a little longer.  This does not affect the patient whatsoever because the costs to you are exactly the same.  In terms of surgery length, that is measurable in minutes.  So, wouldn’t you rather have a difficult surgery done properly or simply be the first one in the post-anesthesia recovery area?

Benefits of Robotic Surgery over Laparoscopy

Robotic surgery is a minimally invasive surgical technique that uses robotic arms to help perform the surgery with more precision. This offers several benefits over traditional laparoscopy that may help to reduce the risk of endometriosis recurrence. These benefits include more precise removal of endometriosis implants, less damage to surrounding tissue, reduced risk of complications, and possibly a shorter recovery time. 

Precise Instrumentation

Robotic surgery allows for more precise surgical movements, especially in delicate and anatomically distorted areas, reducing the risk of incomplete excision. The robotic arms move with reliably greater precision, dexterity and control than laparoscopic instruments.  During laparoscopy the surgeon is directly controlling the straight inflexible instruments with graspers and scissors at the tip.  This means that any undue exaggerated movements or tremors are amplified by the time they get to the tips, located twelve to seventeen inches away.  That is a long distance.  Try writing with a pen that long.  This does not happen with robotics which is micro-controlled.  In addition, the instruments at the tips of the robotic apparatus are wristed, meaning they are flexible and move like tiny human hands.  This also allows for more precision in difficult anatomical areas and in the presence of scar or fibrosis.   

Traditional laparoscopic instruments are limited by the possible motions at the surgical tips.  These motions are cutting, pushing, pulling and tearing, can be awkwardly unreliable and are reminiscent of eating with chopsticks.  One can certainly get good at it, but there are limitations. No question, the better the surgeon and the more that anatomy is normal, the smoother the surgery. However, at the end of the day, this can never match the smooth reliability of robotics. 

Due to the more precise control of instruments, robotic surgery can help reduce the risk of damage to surrounding tissues and organs. This helps reduce complications (e.g inadvertent damage to bowel, ureters or blood vessels) and, in this manner, enhances and accelerates the healing process. 

Superior 3-Dimensional Optics

Robotics offers a 3-D magnified camera, which means there is depth perception as compared to laparoscopy.  In other words, you can see minute differences in how far one object is compared to one right next to it. There are laparoscopic simulated 3-D options available (3-D glasses as opposed to real binocular lenses as found in robotics), but most surgeons use a 2–D camera.  Using this, the surgeon cannot appreciate the distances accurately.  So, without depth perception, the surgeon can’t precisely tell the separation between tissues in a highly distorted anatomical situation. For example, there may be a section of bowel stuck to an endometrioma, or the blood vessels to the ovary may be obscured in inflammation. Dissecting this all safely is facilitated by a 3-D view. You can prove to yourself why 3-D is better. Put an eye patch on and try to (very carefully) try to do things around the house with only one eye to help you navigate. You will find that you underestimate or overestimate the distance between objects when you try to pick them up and might even bump into things too often. Hence you should not try this experiment without someone to help keep you steady. Humans are created with and are best equipped to function with 3-D vision, powered by two eyeballs. We can accommodate to 2-D but it is not natural or optimal.  This means with traditional laparoscopy your surgeon is operating with a handicap and, regardless of skill, that may make all the difference in some cases. 

Conclusion

In conclusion, endometriosis recurrence after surgery is a complex issue. Incomplete excision due to surgeon experience or technology differences, hormonal imbalances, immune influences, toxin influences, and molecular influences can all contribute to endometriosis recurrence after surgery.  Take time to digest all of this information and seek the best endometriosis specialist and surgeon available to you for your specific needs.  

Get in touch with Dr. Steve Vasilev

More articles from Dr. Steve Vasilev:

Endometriosis And Menopause; Everything You Need To Know

How to tell the difference between endometriosis and ovarian cancer

What would happen to the signs and symptoms of endometriosis after menopause?

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