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Diagnosing Deep Endometriosis Using Transvaginal Elastosonography

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Abstract

Transvaginal ultrasound (TVUS) and MRI are currently two mainstream imaging techniques used to diagnose deep endometriosis (DE) with comparable accuracy, but there is still ample room for improvement. As endometriotic lesions progress to fibrosis concomitant with the increase in tissue stiffness, transvaginal elastosonography (TVESG) is well-suited for diagnosing DE. To test the hypothesis that lesional stiffness as measured by TVESG correlates with the extent of lesional fibrosis, the markers of progression, hormonal receptor expression, and vascularity, we recruited 30 patients suspected to have DE who went through pelvic examination, TVUS and/or MRI, and TVESG and were ultimately diagnosed by histology. Their lesional tissue samples were subjected to immunohistochemistry analysis of markers for epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), estrogen and progesterone receptors (ERβ and PR), microvessel density (MVD), and vascularity, as well as quantification of lesional fibrosis. We found that pelvic examination, TVUS, and MRI detected 83.3%, 66.7%, and 83.3% of all DE cases, respectively, while TVESG detected them all. The lesions missed by pelvic exam, TVUS and MRI were significantly smaller than those detected but nonetheless had higher lesional stiffness. Lesional stiffness correlated closely and positively with the extent of lesional fibrosis, negatively with the markers of EMT, MVD, vascularity, and PR expression, but positively with the marker for FMT and ERβ. Thus, through the additional use of information on differential stiffness between DE lesions and their surrounding tissues, TVESG improves diagnostic accuracy, provides a ballpark estimate on the developmental stage of the lesions, and may help clinicians choose the best treatment modality.

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References

  1. Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril. 1997;68:585–96.

    Article  CAS  PubMed  Google Scholar 

  2. Koninckx PR. Biases in the endometriosis literature. Illustrated by 20 years of endometriosis research in Leuven. Eur J Obstet Gynecol Reprod Biol. 1998;81:259–71.

    Article  CAS  PubMed  Google Scholar 

  3. Koninckx PR, Ussia A, Adamyan L, Wattiez A, Donnez J. Deep endometriosis: definition, diagnosis, and treatment. Fertil Steril. 2012;98:564–71.

    Article  PubMed  Google Scholar 

  4. Tosti C, Pinzauti S, Santulli P, Chapron C, Petraglia F. Pathogenetic Mechanisms of Deep Infiltrating Endometriosis. Reprod Sci. 2015.

  5. Ballester M, Belghiti J, Zilberman S, Thomin A, Bonneau C, Bazot M, et al. Surgical and clinical impact of extraserosal pelvic fascia removal in segmental colorectal resection for endometriosis. J Minim Invasive Gynecol. 21:1041–8.

  6. Van den Bosch T, Van Schoubroeck D. Ultrasound diagnosis of endometriosis and adenomyosis: state of the art. Best Pract Res Clin Obstet Gynaecol. 2018;51:16–24.

    Article  PubMed  Google Scholar 

  7. Bazot M, Bornier C, Dubernard G, Roseau G, Cortez A, Darai E. Accuracy of magnetic resonance imaging and rectal endoscopic sonography for the prediction of location of deep pelvic endometriosis. Hum Reprod. 2007;22:1457–63.

    Article  PubMed  Google Scholar 

  8. Abrao MS, Goncalves MO, Ajossa S, Melis GB, Guerriero S. The sonographic diagnosis of deep endometriosis. J Ultrasound Med. 2009;28:408–9 author reply 9-10.

    Article  PubMed  Google Scholar 

  9. Guerriero S, Ajossa S, Minguez JA, Jurado M, Mais V, Melis GB, et al. Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in uterosacral ligaments, rectovaginal septum, vagina and bladder: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2015;46:534–45.

    Article  CAS  PubMed  Google Scholar 

  10. Guerriero S, Ajossa S, Orozco R, Perniciano M, Jurado M, Melis GB, et al. Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in the rectosigmoid: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2016;47:281–9.

    Article  CAS  PubMed  Google Scholar 

  11. Guerriero S, Saba L, Pascual MA, Ajossa S, Rodriguez I, Mais V, et al. Transvaginal ultrasound vs magnetic resonance imaging for diagnosing deep infiltrating endometriosis: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2017;51:586–95.

    Article  Google Scholar 

  12. Nisenblat V, Bossuyt PM, Farquhar C, Johnson N, Hull ML. Imaging modalities for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2016;2:CD009591.

    PubMed  Google Scholar 

  13. Hudelist G, English J, Thomas AE, Tinelli A, Singer CF, Keckstein J. Diagnostic accuracy of transvaginal ultrasound for non-invasive diagnosis of bowel endometriosis: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2011;37:257–63.

    Article  CAS  PubMed  Google Scholar 

  14. Exacoustos C, Malzoni M, Di Giovanni A, Lazzeri L, Tosti C, Petraglia F, et al. Ultrasound mapping system for the surgical management of deep infiltrating endometriosis. Fertil Steril. 2014;102:143–50 e2.

    Article  PubMed  Google Scholar 

  15. Bazot M, Darai E. Diagnosis of deep endometriosis: clinical examination, ultrasonography, magnetic resonance imaging, and other techniques. Fertil Steril. 2017;108:886–94.

    Article  PubMed  Google Scholar 

  16. Zhang Q, Duan J, Liu X, Guo SW. Platelets drive smooth muscle metaplasia and fibrogenesis in endometriosis through epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation. Mol Cell Endocrinol. 2016;428:1–16.

    Article  PubMed  CAS  Google Scholar 

  17. Duan J, Liu X, Guo S-W. The M2a macrophage subset may be critically involved in fibrogenesis of endometriosis in mouse. Reprod BioMed Online. 2018;37:254–68.

    Article  CAS  PubMed  Google Scholar 

  18. Benagiano G, Guo SW, Puttemans P, Gordts S, Brosens I. Progress in the diagnosis and management of adolescent endometriosis: an opinion. Reprod Biomed Online. 36:102–14.

  19. Liu X, Yan D, Guo SW. Sensory nerve-derived neuropeptides accelerate the development and fibrogenesis of endometriosis. Hum Reprod. 2019;34:452–68.

    Article  CAS  PubMed  Google Scholar 

  20. Liu X, Zhang Q, Guo SW. Histological and Immunohistochemical characterization of the similarity and difference between ovarian Endometriomas and deep infiltrating endometriosis. Reprod Sci. 2017;25:329–40.

    Article  PubMed  Google Scholar 

  21. Yan D, Liu X, Guo SW. Neuropeptides substance P and calcitonin gene related peptide accelerate the development and Fibrogenesis of endometriosis. Sci Rep. 2019;9:2698.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Anaf V, Chapron C, El Nakadi I, De Moor V, Simonart T, Noel JC. Pain, mast cells, and nerves in peritoneal, ovarian, and deep infiltrating endometriosis. Fertil Steril. 2006;86:1336–43.

    Article  PubMed  Google Scholar 

  23. Anaf V, El Nakadi I, Simon P, Van de Stadt J, Fayt I, Simonart T, et al. Preferential infiltration of large bowel endometriosis along the nerves of the colon. Hum Reprod. 2004;19:996–1002.

    Article  CAS  PubMed  Google Scholar 

  24. Bazot M, Detchev R, Cortez A, Amouyal P, Uzan S, Darai E. Transvaginal sonography and rectal endoscopic sonography for the assessment of pelvic endometriosis: a preliminary comparison. Hum Reprod. 2003;18:1686–92.

    Article  PubMed  Google Scholar 

  25. Odagiri K, Konno R, Fujiwara H, Netsu S, Yang C, Suzuki M. Smooth muscle metaplasia and innervation in interstitium of endometriotic lesions related to pain. Fertil Steril. 2009;92:1525–31.

    Article  PubMed  Google Scholar 

  26. Shiina T, Nightingale KR, Palmeri ML, Hall TJ, Bamber JC, Barr RG, et al. WFUMB guidelines and recommendations for clinical use of ultrasound elastography: part 1: basic principles and terminology. Ultrasound Med Biol. 2015;41:1126–47.

    Article  PubMed  Google Scholar 

  27. Gennisson JL, Deffieux T, Fink M, Tanter M. Ultrasound elastography: principles and techniques. Diagn Interv Imaging. 2013;94:487–95.

    Article  PubMed  Google Scholar 

  28. Srinivasa Babu A, Wells ML, Teytelboym OM, Mackey JE, Miller FH, Yeh BM, et al. Elastography in chronic liver disease: modalities, techniques, limitations, and future directions. Radiographics. 2016;36:1987–2006.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Cosgrove D, Piscaglia F, Bamber J, Bojunga J, Correas JM, Gilja OH, et al. EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography. Part 2: clinical applications. Ultraschall Med. 2013;34:238–53.

    Article  CAS  PubMed  Google Scholar 

  30. Mezzi G, Ferrari S, Arcidiacono PG, Di Puppo F, Candiani M, Testoni PA. Endoscopic rectal ultrasound and elastosonography are useful in flow chart for the diagnosis of deep pelvic endometriosis with rectal involvement. J Obstet Gynaecol Res. 2011;37:586–90.

    Article  PubMed  Google Scholar 

  31. Schiffmann ML, Schafer SD, Schuring AN, Kiesel L, Sauerland C, Gotte M, et al. Importance of transvaginal ultrasound applying elastography for identifying deep infiltrating endometriosis - a feasibility study. Ultraschall Med. 2014;35:561–5.

    Article  CAS  PubMed  Google Scholar 

  32. Fawzy M, Amer T. Efficacy of transabdominal sonoelastography in the diagnosis of caesarean section scar endometrioma: a pilot study. J Obstet Gynaecol. 2015;35:832–4.

    Article  CAS  PubMed  Google Scholar 

  33. Wozniak S, Czuczwar P, Szkodziak P, Wozniakowska E, Milart P, Paszkowski M, et al. Elastography improves the accuracy of ultrasound in the preoperative assessment of abdominal wall endometriosis. Ultraschall Med. 2015;36:623–9.

    Article  CAS  PubMed  Google Scholar 

  34. Batur A, Yavuz A, Ozgokce M, Bora A, Bulut MD, Arslan H, et al. The utility of ultrasound elastography in differentiation of endometriomas and hemorrhagic ovarian cysts. J Med Ultrason. 2016;43:395–400.

    Article  Google Scholar 

  35. Herek D, Karabulut A, Agladioglu K. Usefulness of transabdominal real-time sonoelastography in the evaluation of ovarian lesions: preliminary results. Br J Radiol. 2016;89:20160173.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Liu X, Ding D, Ren Y, Guo SW. Transvaginal Elastosonography as an imaging technique for diagnosing Adenomyosis. Reprod Sci. 2018;25:498–514.

    Article  PubMed  Google Scholar 

  37. Liu X, Shen M, Qi Q, Zhang H, Guo SW. Corroborating evidence for platelet-induced epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in the development of adenomyosis. Hum Reprod. 2016;31:734–49.

    Article  CAS  PubMed  Google Scholar 

  38. Shen M, Liu X, Zhang H, Guo SW. Transforming growth factor beta1 signaling coincides with epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in the development of adenomyosis in mice. Hum Reprod. 2016;31:355–69.

    Article  CAS  PubMed  Google Scholar 

  39. Guo SW. Fibrogenesis resulting from cyclic bleeding: the holy grail of the natural history of ectopic endometrium. Hum Reprod. 2018.

  40. Liu X, Zhang Q, Guo SW. Histological and Immunohistochemical characterization of the similarity and difference between ovarian Endometriomas and deep infiltrating endometriosis. Reprod Sci. 2018;25:329–40.

    Article  PubMed  Google Scholar 

  41. Ding D, Cai X, Zheng H, Guo SW, Liu X. Scutellarin suppresses platelet aggregation and stalls Lesional progression in mouse with induced endometriosis. Reprod Sci. 2018;1933719118817661.

  42. Zhang Q, Duan J, Olson M, Fazleabas A, Guo SW. Cellular changes consistent with epithelial-Mesenchymal transition and fibroblast-to-Myofibroblast Transdifferentiation in the progression of experimental endometriosis in baboons. Reprod Sci. 2016;23:1409–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sigrist RMS, Liau J, Kaffas AE, Chammas MC, Willmann JK. Ultrasound Elastography: review of techniques and clinical applications. Theranostics. 2017;7:1303–29.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Abrao MS, Goncalves MO, Dias JA Jr, Podgaec S, Chamie LP, Blasbalg R. Comparison between clinical examination, transvaginal sonography and magnetic resonance imaging for the diagnosis of deep endometriosis. Hum Reprod. 2007;22:3092–7.

    Article  PubMed  Google Scholar 

  45. Zhang Q, Duan J, Liu X, Guo SW. Platelets drive smooth muscle metaplasia and fibrogenesis in endometriosis through epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation. Mol Cell Endocrinol 2016;In press. .

  46. Zhang Q, Liu X, Guo SW. Progressive development of endometriosis and its hindrance by anti-platelet treatment in mice with induced endometriosis. Reprod BioMed Online. 2017;34:124–36.

    Article  CAS  PubMed  Google Scholar 

  47. Liu X, Shen S, Qi Q, Zhang H, Guo S-W. Corroborating evidence for platelet-induced epithelial-Mesenchymal transition and fibroblast-to-Myofibroblast Transdifferentiation in the development of Adenomyosis. Hum Reprod. 2016;31:734–49.

    Article  CAS  PubMed  Google Scholar 

  48. Shen M, Liu X, Zhang H, Guo SW. Transforming Growth Factor β1 Signaling Coincides with -Mediated Epithelial-Mesenchymal Transition and Fibroblast-to-Myofibroblast Transdifferentiation in Drive the Development of Adenomyosis in Mice. Hum Reprod 2016;In press.

  49. Vigano P, Candiani M, Monno A, Giacomini E, Vercellini P, Somigliana E. Time to redefine endometriosis including its pro-fibrotic nature. Hum Reprod. 2018;33:347–52.

    Article  CAS  PubMed  Google Scholar 

  50. Chapron C, Tosti C, Marcellin L, Bourdon M, Lafay-Pillet MC, Millischer AE, et al. Relationship between the magnetic resonance imaging appearance of adenomyosis and endometriosis phenotypes. Hum Reprod. 2017;32:1393–401.

    Article  PubMed  Google Scholar 

  51. Marcellin L, Santulli P, Bortolato S, Morin C, Millischer AE, Borghese B, et al. Anterior focal Adenomyosis and bladder deep infiltrating endometriosis: is there a link? J Minim Invasive Gynecol. 2018;25:896–901.

    Article  PubMed  Google Scholar 

  52. Reid S, Lu C, Casikar I, Reid G, Abbott J, Cario G, et al. Prediction of pouch of Douglas obliteration in women with suspected endometriosis using a new real-time dynamic transvaginal ultrasound technique: the sliding sign. Ultrasound Obstet Gynecol. 2012;41:685–91.

    Article  Google Scholar 

  53. Vercellini P, Buggio L, Borghi A, Monti E, Gattei U, Frattaruolo MP. Medical treatment in the management of deep endometriosis infiltrating the proximal rectum and sigmoid colon: a comprehensive literature review. Acta Obstet Gynecol Scand. 2018.

  54. Szubert M, Zietara M, Suzin J. Conservative treatment of deep infiltrating endometriosis: review of existing options. Gynecol Endocrinol. 2018;34:10–4.

    Article  PubMed  Google Scholar 

  55. Yan D, Liu X, Guo S-W. Neuropeptides substance P and calcitonin gene related peptide accelerate the development and fibrogenesis of endometriosis. Sci Rep 2019;In press. .

  56. Chiocchini ALC, Sportoletti C, Comai G, Brocchi S, Capelli I, Baraldi O, et al. Correlation between renal cortical stiffness and histological determinants by point shear-wave elastography in patients with kidney transplantation. Prog Transplant. 2017;27:346–53.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Dr. Cai Chang and Na Hu from Shanghai Tumor Hospital, Fudan University, and Dr. Li Sun from Shanghai OB/GYN Hospital, Fudan University, for their expert assistance in the TVESG examination for the recruited DE patients. We thank an anonymous reviewer for his/her constructive comments and suggestions on an earlier version of this manuscript.

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Correspondence to Xishi Liu.

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This research was supported in part by grants 81530040 (SWG), 81771553 (SWG), and 81671436 (XSL) from the National Natural Science Foundation of China, and a grant from Ningbo Municipal Bureau of Science and Technology (2017A610169).

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Ding, D., Chen, Y., Liu, X. et al. Diagnosing Deep Endometriosis Using Transvaginal Elastosonography. Reprod. Sci. 27, 1411–1422 (2020). https://doi.org/10.1007/s43032-019-00108-2

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