Gynaecologist & Endoscopic Surgeon

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Controversies in the management of endometriosis: should we expand the definition?

Endometriosis is currently defined as the presence of endometrial glands and stroma outside the uterus. Unfortunately this definition, whilst widely utilised, is also widely recognised as only a part of the underlying disease process. At this point in time the underlying etiology of endometriosis is unknown despite large bodies of research. The simplistic use of the current definition creates major problems for patients, healthcare workers and society. It has been known for some time that there are multiple other abnormalities present in individuals with endometriosis and these abnormalities have the potential for clinical effects. There is therefore an expectation mismatch in the way the disease is represented. If endometriosis is only ectopic endometrium, then removal of this tissue is all that is required to deal with it. Whilst often treatment is suggested as either medical or surgical it is becoming increasingly apparent that surgery alone is insufficient and that ideally progestogenic support ideally via pregnancy or via some other form such as Mirena results in better long term outcomes. Surgery, when indicated, should involve excision of all the disease. Possibly the current definition should be expanded to incorporate some of the myriad other abnormalities these patients have such that we can begin to address some of their other concerns.

There are multiple abnormalities not covered in the definition but which have been noted in research. The following paragraphs gives a very brief outline of some of the issues in an attempt to illustrate that the simple current definition is inadequate.

The eutopic endometrium in patients with endometriosis is known to be abnormal. One feature is the presence of small unmyelinated nerve fibres identified by a specific nerve marker, PGP 9.5 1. These are not found to any great extent in a control group without endometriosis. It is postulated that these nerve fibres may contribute to the pain of endometriosis and may also be present adjacent to endometriotic lesions.

There is substantial evidence to support alterations in both cell-mediated and humoral immunity which could contribute to the pathogenesis of endometriosis. The disease has been considered to be autoimmune and has been linked with the presence of autoantibodies, other autoimmune disease and possibly with recurrent immune-mediated abortion2.

A genetic association has been identified3. Genome-wide association studies have also identified loci associated with endometriosis and also other traits such as fat distribution 4. The latter may help to explain the often seen relationship between the presence of endometriosis and low BMI5.

Advances in the field of epigenetics adds further information to the underlying disease process with endocrine disruptors such as dioxin and Bisphenol A implicated in the development of endometriosis 6,7. These findings further demonstrate that surgery alone is unlikely to be the key to complete treatment.

Epidemiological studies of large populations provide further evidence of the myriad of associations with other clinical diseases and endometriosis. Cancer associations include breast, ovary and melanoma. Other chronic disease associations include cardiovascular disease and autoimmune diseases such as asthma, atopy, lupus and rheumatoid arthritis8-10. Endometriosis sufferers often note irritable type bowel symptoms and it may be the underlying pathology in many patients who have been diagnosed with irritable bowel syndrome11.

In future is possible that endometriosis may be considered an obstetric disorder. One recent large scale linkage study has revealed increased rates of miscarriage, ectopic pregnancies, prematurity, placenta praevia, antepartum and postpartum haemorrhage12. It was postulated that these outcomes may relate to endometriosis induced inflammation in the pelvis and structural and functional changes within the uterus. A further hypothesis along this line has indicated that endometriosis may be associated with a decreased risk of pre-clampsia13. It has been postulated that menstruation preconditions the uterus for successful pregnancy and that endometriosis via its effect on the eutopic endometrium assists this process14. It may thus be that endometriosis assists pregnancies for younger patients particularly in the teenage years but may be problematic for older patients.

It has been known for some years that laparoscopic surgery for minimal or mild endometriosis improves pregnancy rates15 and meta-analysis reveals that endometriosis decreases IVF success rates for patients with endometriosis16. More recently data have emerged confirming the same if not more pronounced effect for patients with more advanced disease. It is probable that surgical treatment particularly of severe endometriosis significantly increases the chance of both natural and assisted pregnancy post operatively. This also includes patients with bowel involvement17,18.

More recent concern has surrounded the issue of ovarian reserve in patients with endometriomas. Several studies have suggested that cystectomy may result in an up to 50% reduction. There has been a change in thinking in several units to be more conservative with the ovary with the possibility of staged procedures encompassing oocyte or embryo vitrification and then definitive surgery prior to embryo transfer19.

In relation to assisted conception cycles evidence is emerging around the world that frozen transfers may be more successful than fresh transfers as a consequence of the adverse effect of ovarian stimulation on the underlying endometrium. Studies have revealed improved maternal and perinatal outcomes in the frozen cycles as compared to the fresh transfers20. In the knowledge the underlying eutopic endometrium is abnormal in patients with endometriosis it would not be unreasonable to consider these differences more marked in the setting of endometriosis and possibly this sub group would benefit even more from frozen transfers.

Clearly further data are required but the evolving nature of the wider implications of a diagnosis of endometriosis should be considered when discussing these issues with patients so that expectations are being managed accordingly.

References

1. Al-Jefout M, Dezarnaulds G, Cooper M, et al. Diagnosis of endometriosis by detection of nerve fibres in an endometrial biopsy: a double blind study. Hum Reprod 2009; 24(12): 3019-24.
2. Olovsson M. Immunological Aspects of Endometriosis: An Update. American Journal of Reproductive Immunology 2011; 66: 101-4.
3. Painter JN, Anderson CA, Nyholt DR, et al. Genome-Wide Association Study Identifies a Locus at 7p15.2 Associated With Endometriosis. Obstetrical & Gynecological Survey 2011; 66(4): 214-6.
4. Rahmioglu N, Macgregor S, Drong AW, et al. Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci. Human Molecular Genetics 2015; 24(4): 1185-99.
5. Ferrero S, Anserini P, Remorgida V, Ragni N. Body mass index in endometriosis. European Journal of Obstetrics Gynecology and Reproductive Biology 2005; 121(1): 94-8.
6. Zhang J, Huang FY. Epigenetics: an emerging research field of infertility associated with endometriosis. International Journal of Clinical and Experimental Medicine 2016; 9(10): 18883-9.
7. Borghese B, Zondervan KT, Abrao MS, Chapron C, Vaiman D. Recent insights on the genetics and epigenetics of endometriosis. Clinical Genetics 2017; 91(2): 254-64.
8. Harris HR, Costenbader KH, Mu F, et al. Endometriosis and the risks of systemic lupus erythematosus and rheumatoid arthritis in the Nurses’ Health Study II. Annals of the Rheumatic Diseases 2016; 75(7): 1279-84.
9. Kvaskoff M, Mu F, Terry KL, et al. Endometriosis: a high-risk population for major chronic diseases? Human Reproduction Update 2015; 21(4): 500-16.
10. Poole EM, Lin WT, Kvaskoff M, De Vivo I, Terry KL, Missmer SA. Endometriosis and risk of ovarian and endometrial cancers in a large prospective cohort of US nurses. Cancer Causes & Control 2017; 28(5): 437-45.
11. Maroun P, Cooper MJ, Reid GD, Keirse MJ. Relevance of gastrointestinal symptoms in endometriosis. AustNZJObstetGynaecol 2009; 49(4): 411-4.
12. Saraswat L, Ayansina DT, Cooper KG, Bhattacharya S, Miligkos D, Horne AW. Pregnancy outcomes in women with endometriosis: a national record linkage study. Bjog-an International Journal of Obstetrics and Gynaecology 2017; 124(3): 444-52.
13. Brosens IA, De Sutter P, Hamerlynck T, et al. Endometriosis is associated with a decreased risk of pre-eclampsia. Hum Reprod 2007; 22(6): 1725-9.
14. Brosens JJ, Parker MG, McIndoe A, Pijnenborg R, Brosens IA. A role for menstruation in preconditioning the uterus for successful pregnancy. American Journal of Obstetrics and Gynecology 2009; 200(6).
15. Marcoux S, Maheux R, Berube S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis [see comments]. New England Journal of Medicine 1997; 337(4): 217-22.
16. Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. FertilSteril 2002; 77(6): 1148-55.
17. Wills HJ, Reid GD, Cooper MJW, Morgan M. Fertility and pain outcomes following laparoscopic segmental bowel resection for colorectal endometriosis: A review. Australian & New Zealand Journal of Obstetrics & Gynaecology 2008; 48(3): 292-5.
18. Nesbitt-Hawes EM, Campbell N, Maley PE, et al. The Surgical Treatment of Severe Endometriosis Positively Affects the Chance of Natural or Assisted Pregnancy Postoperatively. BioMed research international 2015; 2015: 438790.
19. Psaroudakis D, Hirsch M, Davis C. Review of the management of ovarian endometriosis: paradigm shift towards conservative approaches. Current opinion in obstetrics & gynecology 2014; 26(4): 266-74.
20. Bhattacharya S. Maternal and perinatal outcomes after fresh versus frozen embryo transfer-what is the risk-benefit ratio? Fertility and Sterility 2016; 106(2): 241-3.

Commentary on Procedures and Complications to end of May 2017.

The tables display all procedures and major complications to the end of May 2017. It should be noted that considerable care should be taken when interpreting these numbers. Associate Professor Cooper operates on a large number of patients with significant endometriosis and the risk profile of this group of patients for complications is higher than the general population. Secondly he may not be aware of some complications and as such these figures may under represent the true numbers.

Since commencing practice as a specialist gynaecologist in 1995 Associate Professor Cooper has undertaken over 10,000 operative procedures. He has performed over 5,500 laparoscopies most being of an operative rather than a diagnostic nature. Over the last 10-15 years his practice has predominantly moved towards endometriosis and he has performed over 1,500 interventions for the excision of endometriosis. Of these at the time of writing 388 have had bowel resections of various forms of being performed. These procedures represent the most difficult and complex of gynaecological surgery including cancer. The significant complications and issues are listed in the table.

There were 3 significant vascular complications all of which were treated by immediate laparotomy and oversewing of various vessels.

Fourteen patients required laparotomy to deal with some form of issue involving the bowel. There was an overall colostomy rate of 12 with a rate of 0.2% of all laparoscopies. Ten of the stomas related to patients with endometriosis and 6 of these were planned intra-operatively with a rate of 0.36% per endometriosis patient. Four unplanned stomas were performed in the post operative period at a rate of 0.24% Two patients who had procedures unrelated to endometriosis required stomas with an overall rate of 0.04%. An additional patient with endometriosis had a recto-vaginal fistula which healed spontaneously (0.02%).

Three patients required laparotomy for bladder injuries (0.05%) and of these 1 patient had endometriosis (0.06%).

Twelve patients required some form of intervention in relation to the ureter. All of these patients had endometriosis as an underlying condition. Delayed recognition of the injury occurred in 2 patients (0.12%) and 10 required some form of intra-operative repair or stent. Five stents were placed as prophylaxis to ensure against a possible leak in the post operative period.

Twenty nine patients had to return to theatre with an overall rate of 0.28%. These included the 3 bladder and 4 bowel patients mentioned above. Other issues included 7 post operative bleeds, 7 abscesses and infected areas, 2 patients who ultimately had no abnormality detected, 1 patient with a small bowel obstruction following a bowel resection, 1 omental herniation at a trocar site, 1 perforation at a hysteroscopic myomectomy, a vault dehiscence in a patient who initiated sexual activity in the early post operative period following a hysterectomy, a recurrent Bartholin’s abscess and 1 patient who had a microscopic needle identified in the recovery room following laparoscopic tubal reversal with a needle which had initially been counted as outside the patient.
There were no patient deaths. The overall major complication rate was 0.36% (38/10423). The rate per laparoscopy was 0.64% (35/5487). Specifically for endometriosis cases the rate was 0.78% (13/1674).

Associate Professor Cooper believes this complication profile is appropriate for the type of surgery he performs and is happy to discuss this analysis.

What time of day is best for your operation?

Occasionally patients ask if they can be put in a particular time on a list usually first in the morning. I usually attempt to accommodate these requests although other considerations such as the availability of equipment, staffing and health issues of other patients also come into play. More recently I was reading the book “Thinking Fast and Slow” by Daniel Kahneman. Some of this work resulted in the 2011 Noble Memorial Prize in Economics for Kahneman. In the book he describes a paper published in The Proceedings of the National Academy of Sciences describing how Shai Danziger and colleagues followed 8 Israeli judges for 10 months as they ruled on over 1000 applications made by prisoners to parole boards. The plaintiffs were asking either to be allowed out on parole or to have the conditions of their incarceration changed. The team found that at the start of the day the judges granted around two thirds of the applications before them and as the hours passed that number fell sharply and eventually reaching zero. The clemency returned after each of two daily breaks during which the judges retired for food. The approval rate shot back up to near its original value before falling again as the day wore on. Kahneman opined that this decision process mostly related to blood sugar levels.

Judgement day

If true this finding casts significant concern on the structure of the judicial system and clearly many others also. The situation can probably be stretched to the operating theatre and the performance of a surgeon during the course of the day. It is tempting to think that food is a major issue but other studies as outlined in an article aired in The Economist  reveal that decision making is mentally taxing and if forced to keep deciding things people tend to get tired and start looking for easy answers. Whilst it would be nice to consider surgeons as simply technicians clearly they are humans and subject to all sorts of biases which may interfere with decision making.

The medical literature has attempted to look at performance after surgeons have been on call the night before with variable outcomes. I am not aware of any strong studies from a surgical perspective in relation to meals and rests during the day although common sense suggests it is probable that surgeons perform better after a rest and a meal. My personal view is that some degree of exercise before a list is also beneficial. I suspect those patients wanting to be first on the list are asking the right question. It is probably best for patients to have their surgery either first in the morning or immediately after a lunch break.

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11 months ago
How Does Surgical Volume Affect Gynecologic Surgery Outcomes?

More evidence that low volume surgeons have more problems: https://t.co/gw77JTNAao

Dr Kaunitz suggests an honest self-assessment of our experience level when planning for surgical care of our patients.

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