Visible and Invisible (Occult) Endometriosis

Endometriosis is a chronic disease characterized by endometrial tissue located outside of the uterine cavity and is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology of endometriosis is still elusive. Once generated within pelvis due to retrograde entry of menstrual debris, peritoneal endometriotic lesions time-dependently change their color appearance resulting from certain biochemical change within lesions. A variable pattern of endometriotic lesions within pelvis can be detected by laparoscopy as visible peritoneal endometriosis. It is generally believed that besides ovarian steroid hormones, the growth of endometriosis can be regulated by innate immune system in pelvic microenvironment by their interaction with endometrial cells and immune cells. We conducted a series of studies in perspectives of pelvic inflammation that is triggered primarily by bacterial endotoxin (lipopolysaccharide, LPS) and is mediated by Toll-like receptor 4 (TLR4) and showed their involvement in the growth regulation of visible peritoneal endometriosis. Even with the careful eye of an expert surgeon, we may sometimes miss to detect peritoneal lesion within peritoneal cavity or deep into peritoneum. In such a case, random collection of normal peritoneum may carry the possibility to identify some hidden endometriotic lesions by microscopy and these lesions can be named as invisible endometriosis. Here, we discuss the color appearance of peritoneal lesions, role of innate immune system in visible endometriosis, and finally our recent findings on invisible microscopic endometriosis and their biological and clinical significance. Access this chapter Tax calculation will be finalised at checkout Purchases are for personal use only Similar content being viewed by others

Strathy JH, Molgaard CA, Coulman CB. Endometriosis and infertility: a laparoscopic study of endometriosis among fertile and infertile women. Fertil Steril. 1982;38:667–72. Sampson J. Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol. 1927;14:422–9. Thomas EJ, Prentice A. The etiology and pathogenesis of endometriosis. Reprod Med Rev. 1992;1:21–36. Nisolle M, Casanas-Rouz F, Donnez J. Immunohistochemical analysis of proliferative activity and steroid receptor expression in peritoneal and ovarian endometriosis. Fertil Steril. 1997;68:912–9. Meyer R. Ueber den Stand der Frage der Adenomyositis und Adenomyom im Allgemeinen und insbesonderes ueber Adenomyositis seroepithelialis und Adeno-myometritis sarcomatosa. Zbl Gynaekol. 1919;36:745–50. Oosterlynck DJ, Cornillie FJ, Waer M, Vandeputte M, Koninckx PR. Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium. Fertil Steril. 1991;56:45–51. Lessey BA, Damjanovich L, Coutifaris C. Integrin adhesion molecules in the human endometrium. Correlation with the normal and abnormal menstrual cycle. J Clin Invest. 1992;90:188–95. van der Linden PJQ, van der Linden EPM, de Goeij AFPM, Ramaekers FC, Dunselman GAJ. Expression of integrins and E-cadherin in cells from menstrual effluent, endometrium, peritoneal fluid, peritoneum, and endometriosis. Fertil Steril. 1994;61:85–90. Langendonckt AV, Casanas-Roux F, Dolmans M-M, Donnez J. Potential involvement of hemoglobin and heme in the pathogenesis of peritoneal endometriosis. Fertil Steril. 2002;77:561–70. Khan KN, Masuzaki H, Fujishita A, Kitajima M, Sekine I, Ishimaru T. Higher activity by opaque endometriotic lesions than non-opaque lesions in women with endometriosis. Acta Obstet Gynecol Scand. 2004;83:375–82. Halme J, Becker S, Haskill S. Altered maturation and function of peritoneal macrophages: possible role in pathogenesis endometriosis. Am J Obstet Gynecol. 1987;156:783–9. Khan KN, Masuzaki H, Fujishita A, Kitajima M, Sekine I, Ishimaru T. Differential macrophage infiltration in early and advanced endometriosis and adjacent peritoneum. Fertil Steril. 2004;81:652–61. Halme J, White C, Kauma S, Estes J, Haskill S. Peritoneal macrophages from patients with endometriosis release growth factor activity in vitro. J Clin Endocrinol Metab. 1988;66:1044–9. Khan KN, Masuzaki H, Fujishita A, Kitajima M, Kohno T, Sekine I, Matsuyama T, Ishimaru T. Regulation of hepatocyte growth factor by basal and stimulated-macrophages in women with endometriosis. Hum Reprod. 2005;20:49–60. Khan KN, Kitajima M, Hiraki H, Fujishita A, Sekine I, Ishimaru T, Masuzaki H. Toll-like receptors in innate immunity: role of bacterial endotoxin and toll-like receptor 4 (TLR4) in endometrium and endometriosis. Gynecol Obstet Invest. 2009;68:40–52. Khan KN, Kitajima M, Hiraki K, Yamaguchi N, Katamine S, Matsuyama T, Fujishita A, Nakashima M, Ishimaru T, Masuzaki H. Escherichia coli contamination of menstrual blood and effect of bacterial endotoxin on endometriosis. Fertil Steril. 2010;94(7):2860–3.e3. Asea A, Rehli M, Kabingu E, Boch JA, Bare O, Auron PE, Stevenson MA, Calderwood SK. Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem. 2002;277:15028–34. Khan KN, Kitajima M, Imamura T, Hiraki K, Fujishita A, Sekine I, Ishimaru T, Masuzaki H. Toll-like receptor 4 (TLR4)-mediated growth of endometriosis by human heat shock protein 70 (Hsp70). Hum Reprod. 2008;23:2210–9. Khan KN, Kitajima M, Inoue T, Tateishi S, Fujishita A, Nakashima M, Masuzaki H. Additive effects of inflammation and stress reaction on Toll-like receptor 4-mediated growth of endometrioid stromal cells. Hum Reprod. 2013;28:2794–803. Kajihara H, Yamada Y, Kanayama S, Furukawa N, Noguchi T, Haruta S, Yoshida S, Sado T, Oi H, Kobayashi H. New insights into the pathophysiology of endometriosis: from chronic inflammation to danger signals. Gynecol Endocrinol. 2011;27(2):73–9. Khan KN, Kitajima M, Hiraki H, Fujishita A, Sekine I, Ishimaru T, Masuzaki H. Immunopathogenesis of pelvic endometriosis: role of hepatocyte growth factor, macrophages and ovarian steroids. Am J Reprod Immunol. 2008;60:383–404. Khan KN, Masuzaki H, Fujishita A, Kitajima M, Sekine I, Matsuyama T, Ishimaru T. Estrogen and progesterone receptor expression in macrophages and regulation of hepatocyte growth factor by ovarian steroids in women with endometriosis. Hum Reprod. 2005;20:2004–13. Murphy AA, Green WR, Bobbie D, dela Cruz ZC, Rock JA. Unsuspected endometriosis documented by scanning electron microscopy in visually normal peritoneum. Fertil Steril. 1986;46:522–4. Nisollle M, Paindaveine B, Bourdone A, Berliere M, Casanas-Rous F, Donnez J. Histologic study of peritoneal endometriosis in infertile women. Fertil Steril. 1990;53:984–8. Redwine DB. ‘Invisible’ microscopic endometriosis: a review. Gynecol Obstet Invest. 2003;55:63–7. Donnez J, Langendonckt AV. Typical and subtle atypical presentations of endometriosis. Curr Opin Obstet Gynecol. 2004;16:431–7. Khan KN, Fujishita A, Kitajima M, Hiraki K, Nakashima M, Masuzaki H. Occult microscopic endometriosis: an undetectable finding by laparoscopy in normal peritoneum. Hum Reprod. 2014;29(3):462–72. Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98(3):511–9. Gaetje R, Kotzian S, Herrmann G, Baumann R, Starzinski-Powitz A. Nonmalignant epithelial cells, potentially invasive in human endometriosis, lack the tumor suppressor molecule E-cadherin. Am J Pathol. 1997;150:461–7. Sasson IE, Taylor HS. Stem cells and the pathogenesis of endometriosis. Ann N Y Acad Sci. 2008;1127:106–15. Redwine DB. Mülleriosis: the single best fit model of origin of endometriosis. J Reprod Med. 1988;33:915–20.

I gratefully thank Dr. Michio Kitajima of Nagasaki University Hospital and Dr. Akira Fujishita of Saiseikai Nagasaki Hospital for their kind assistance in sample collection; Prof. Masahiro Nakashima of Atomic Bomb Disease Institute, Nagasaki for his experimental advice; and Prof. Hideaki Masuzaki of Nagasaki University Hospital for reading/advice. Author information Authors and Affiliations Corresponding author Editor information Editors and Affiliations Rights and permissions Copyright information © 2014 Springer Japan About this chapter Cite this chapter Khan, K.N. (2014). Visible and Invisible (Occult) Endometriosis. In: Harada, T. (eds) Endometriosis. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54421-0_3 Download citation DOI: https://doi.org/10.1007/978-4-431-54421-0_3 Published: Publisher Name: Springer, Tokyo Print ISBN: 978-4-431-54420-3 Online ISBN: 978-4-431-54421-0 eBook Packages: MedicineMedicine (R0)