Microscopic endometriosis Impact on our understanding of the disease and its surgery

Philippe R. Koninckx, M.D., Ph.D., Jacques Donnez, M.D., Ph.D., Ivo Brosens, M.D., Ph.D.

Volume 105, Issue 2, Pages 305-306


Reflections on “Bowel occult microscopic endometriosis” and “Mapping of endometriosis microimplants surrounding deep endometriosis nodules infiltrating the bowel” by Roman et al.

  • Kanchanadevi

    We would like to congratulate the authors for this
    enlightening article on endometriosis. As mentioned here, even though the
    knowledge on the existence of this disease is very old, the insight and
    evidences about the pathophysiology and why it happens only in some women when
    the retrograde menstruation seems to be a common occurrence is very scarce.
    Studies on bio –markers have also highlighted a possible association but not a
    cause and effect relationship. In this situation where the etiology ,pathophysiology
    of endometriosis is unknown and the disease progression cannot be predicted, except
    in conditions where endometriotic lesions lead to ureteric or bowel
    obstruction, offering radical procedures to remove the endometriotic lesion not
    only leads to morbidity1,2,3, it often leads to reduced ovarian
    reserve itself. In any situation our motto should be as per hippocratic oath. We
    have registered this concern in our article on early diagnosis of endometriosis4.


    Kanchana Devi.B,DNB,FRM

    Department of
    Andrology and Reproductive Medicine

    Chettinad Hospital
    and Research Institute, South India.


    1.Darai E,Ziberman S et al,Urological morbidity of
    colorectal resection for endometriosis Minervamed 2012 Feb;103(1):63-72

    2.De Ciccoc,Corona R et al, Bowel resection for deep
    endometriosis : a systematic review ,BJOG 2011,Feb;118(3):265-91

    3.Bonneau L,Ziberman Set al,Incidence of pre and post
    operative urinary dysfunction associated with deep infiltrating endometriosis:
    relevance of urodynamic tests and therapeutic implications Minerva Ginecol 2013

    4. Pandiyan N, Surya P et al ,Early diagnosis of
    endometriosis – Quo Vadis? Chettinad Health City Medical Journal.2015;

    • Philippe Koninckx

      Dear Dr Kanchanadevi

      Thank you for your comment.
      Could you send me a pdf of ref 4 since I have no access. I need this in order to answer your question.


      Phillipe Koninckx

      • Kanchanadevi

        Dear Dr.Philippe Koninckx,
        Thank you for your communication.The link of this article is as follows.http://www.chcmj.ac.in/journal/pdf/vol4_no2/Early.pdf
        Thank you
        Dr.Kanchana Devi

        • Philippe Koninckx

          Dear Dr Khan,

          Thank you for your remarks and for the article.

          We have read with great interest your excellent article1
          confirming occult endometriosis implants in macroscopically normal looking peritoneum
          of women with and without endometriosis. The concept of these lesions has been
          discussed for 25 years without much clinical implications. Also the finding of
          these lesions in lymph nodes did not seem clinically important. This has
          changed with the 2 articles of Roman’s group2;3
          finding these lesions in the bowel wall. Now these lesions are and will be used
          in the debate whether a bowel resection is necessary in order to be complete. We
          wanted to stress that unfortunately we cannot distinguish today between
          microscopical lesions that will disappear spontaneously or remain dormant and
          those that eventually will progress to typical, cystic and deep lesions.

          A second goal was to extend this concept to subtle lesions
          for which there is to the best of our knowledge, no evidence that they cause
          pain or infertility. There is no evidence of progression into more severe
          lesions : this is postulated and seems logic but the evidence is still not available.
          For this reason we consider that it is unclear whether a therapy should be
          given at all. Pragmatically, however, if
          it takes during surgery 2 seconds to vaporise them with a CO2 laser without risk or side effect we prefer to do.

          We intentionally avoided to extend the discussion to
          typical, cystic and deep lesions. As suggested 15 years ago, I am a believer the
          Endometriotic disease theory4,
          which consider typical, cystic and deep lesions as benign tumors following a
          cellular incident/mutation. We also avoided
          the discussion on biochemical markers. According to the views explained It does
          not seem logic that a marker could detect normal endometrial cells outside the
          uterus. Lesions containing abnormal cells however could open the possibility to
          find a marker.

          Philippe R. Koninckx,
          Jacques Donnez and Ivo Brosens

          Reference List

          1. Khan KN, Fujishita A, Kitajima M, Hiraki K, Nakashima M, Masuzaki
          H. Occult microscopic endometriosis: undetectable by laparoscopy in normal
          peritoneum. Hum Reprod. 2014;29:462-472.

          2. Badescu A, Roman H, Aziz M, Puscasiu L, Molnar C, Huet E et al. Mapping
          of bowel occult microscopic endometriosis implants surrounding deep
          endometriosis nodules infiltrating the bowel. Fertil Steril. 2016;105:430-434.

          3. Roman H, Hennetier C, Darwish B, Badescu A, Csanyi M, Aziz M et
          al. Bowel occult microscopic endometriosis in resection margins in deep
          colorectal endometriosis specimens has no impact on short-term postoperative
          outcomes. Fertil Steril. 2016;105:423-429.

          4. Koninckx PR, Barlow D,
          Kennedy S. Implantation versus infiltration: the Sampson versus the endometriotic
          disease theory. Gynecol Obstet Invest. 1999;47 Suppl 1:3-9.

          • Khaleque N Khan, MD, PhD

            Dear Dr. Koninckx,

            Thank you for your kind response and interaction.

            I do agree with your logistic idea that vaporization of subtle lesions with CO2 laser could completely disappear them considering that it should not contribute any risk or side effect.
            But another risk is still there. A signal dormant cell if still persists could replicate rapidly in response to stress reaction by CO2 laser. This side effect of CO2 laser cannot be avoided.

            Another question still remains as you indicated we cannot distinguish whether OME lesions will disappear spontaneously or they remain dormant and time-dependently manifest as visible variable lesions. This is a difficult issue in clinical practice. We are now trying to reconfirm the study of Lessey BA et al. (J Vis. Exp. 70:e4313,2012) and establish if methylene blue dye test could be clinically useful in detecting OME lesions in normal looking peritoneum. If prevention is still better than cure, then disruption of peritoneal cell-cell contact with entry of inflammatory mediators into OME lesions and/or adjacent nerve fibers, a potential cause of pain, could be effectively managed by early detection of these hidden lesions using laparoscopy and methylene blue. Further studies are still awaiting to give us more information on this debating issue.

            Finally, it is always good to imagine that endometriosis is still an enigmatic disease and is driving all of us to find the main switch of endometriosis. This should be our main goal to decide the effective management and to find out proper bio-marker of this multi-factorial disease.

            I would appreciate if you could send me a PDF file of your article (Ref. 4).

            Thank you always for your outstanding contribution to reproductive science.

            Best regards,
            Khaleque Khan

            • Philippe Koninckx

              Dear Dr Khan,

              Reference 4 “Implantation versus infiltration: the Sampson
              versus the endometriotic disease theory” can be found on the website http://www.gynsurgery.org/recent-publications/ or directly at http://www.gynsurgery.org/wp-content/uploads//1999_pk_edt.pdf

              We share your concern that surgical trauma could reactivate ‘dormant’ microscopical endometriosis.
              – For this reason we do prefer CO2 laser vaporisation or excision for superficial endometriosis. Since “what you see is what you” do completeness is easier to ascertain. For the same reason we do not like coagulation since depth of coagulation cannot be controlled.
              – CO2 pneumoperitoneum is a surgical trauma by
              itself through mesothelial cell hypoxia 1 causing mesothelial cell retraction and bulging and acute inflammation of the
              entire peritoneal cavity 2. This together with other factors as desiccation, hyperoxia in open surgery and temperature
              are quantitatively the most important factor in adhesion formation which can be prevented by full conditioning 3;4. Our research over the last decade into this, was in fact initiated by the idea that mesothelial cell trauma could facilitate endometrial cell implantation. We did demonstrate that tumour cell implantation was enhanced by mesothelial cell damage through CO2 pneumoperitoneum and could be prevented by conditioning. 5
              – During deep endometriosis surgery following IVF with oocyte pick-up with puncture through a recto-vaginal nodule, a frozen
              pelvis with difficult surgery is almost invariably found suggesting
              reactivation. This was the topic of my presentation at the ESGE meeting in Amsterdam 2008. Unfortunately hard evidence is still lacking.

              To discuss the pathophysiology of endometriosis was beyond our comment in F&S. Briefly there is no solid evidence today of progression of ,endometriosis lesions from microscopic, to subtle, to typical, to cystic or deep lesions which is the hallmark of the Sampson hypothesis. It is unclear whether these ‘endometriotic cells are genetically normal or abnormal. Since
              deep and cystic endometriosis are clonal in origin, and since endometriosis is hereditary we favour the hypothesis that pathology starts with some genetic modification and subsequent development of typical, cystic or deep lesions. In order to mark the difference between “normal” microscopical and subtle lesions we proposed to call typical, cystic and deep lesions ‘Endometriotic disease’.

              Philippe R. Koninckx,

              Reference List
              1. Molinas CR, Campo R, Elkelani OA, Binda MM, Carmeliet P, Koninckx PR. Role of hypoxia inducible factors 1alpha and 2alpha in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in transgenic mice. Fertil Steril. 2003;80 Suppl 2:795-802.
              2. Corona R, Verguts J, Schonman R, Binda MM, Mailova K, Koninckx PR. Postoperative inflammation in the abdominal cavity increases adhesion formation in a laparoscopic mouse model. Fertil Steril. 2011;95:1224-1228.
              3. Koninckx PR, Ussia A, Adamyan L. The role of the peritoneal cavity in adhesion formation. Fertil Steril. 2012;97:1297.
              4. Koninckx PR, Corona R, Timmerman D, Verguts J, Adamyan L. Peritoneal full-conditioning reduces postoperative adhesions and pain: a randomised controlled trial in deep endometriosis surgery. J Ovarian Res. 2013;6:90.
              5. Binda MM, Corona R, Amant F, Koninckx PR. Conditioning of the abdominal cavity reduces tumor implantation in a laparoscopic mouse model. Surg Today. 2014.

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