Histology of the vaginal wall in women with pelvic organ prolapse
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1 Histology of the vaginal wall in women with pelvic organ prolapse Dr Laurent de Landsheere Belgian Menopause Society, may, 2018
2 Histology of the vaginal wall Introduction Histology of the vaginal wall in women with POP Histological properties Bioméchanical properties Histology of the vaginal wall in post-menopause Laser rejuvenation New trend or real benefit?
3 Histology of the vaginal wall Introduction Histology of the vaginal wall in women with POP Histological properties Bioméchanical properties Histology of the vaginal wall in post-menopause Laser rejuvenation New trend or real benefit?
4 Introduction Histology of the vaginal wall Non kerat squamous epithelium Vaginal mucosa Lamina propria Dense connective tissue - Collagen - Elastin Muscularis Muscularis Smooth muscle cells Connective tissue Adventice Adventice Loose connective tissue
5 Introduction Histology of the vaginal wall Specific stainings Hematoxylin eosin, Orcein and Miller for Elastin, Masson s Trichrome Immuno-histochemistry Smooth muscle cells, Collagen fibers Hématoxyline Eosine α-smooth Actin (α-sma) Orcéine Trichrome de Masson
6 Introduction Collagen Collagen I : large and strong fibers, mechanical resistance Collagen III : smaller fibers, low tensile strengh (mobile organs) Collagen V : small fibers of lower tensil strengh Collagen I, III and V copolymerize to form hybrid fibrils. Immuno-marquage du Collagène III (grossissement X40)
7 Introduction Elastin Key architectural elements of connective tissues that are subject to mechanical strain and expansile forces, important for the maintenance of vaginal structural integrity Low rigidity fibers Large ability of extensibility and recoil, without rupture Coloration à l orcéine (grossissement X40)
8 Introduction Collagen - Elastin
9 Histology of the vaginal wall Introduction Histology of the vaginal wall in women with POP Histological properties Bioméchanical properties Histology of the vaginal wall in post-menopause Laser rejuvenation New trend or real benefit?
10 Pelvic organ prolapse Pelvic organ prolapse Definition Descent of the pelvic organs from their normal position Cystocele
11 Pelvic organ prolapse Risk factors Facteurs acquis Vieillissement, ménopause Obésité, constipation, tabac, sport Hystérectomie Facteurs génétiques Marfan, Ehlers-Danlos, Cutis Laxa Altération métabolisme MEC (collagène, élastine) Facteurs liés à la reproduction Multiparité, macrosomie Traumatismes obstétricaux (Forceps, )
12 Pelvic organ prolapse Anatomical apects The maintain of pelvic floor, resultance of 3 systems Level 1 Suspension of vaginal apex Cardinal and sacro-uterine ligaments Level 2 Cohesion between vagina and levator ani aponeurosis Endopelvic fascia, arcus tendineus Level 3 Support of inferior third vagina Perineal muscles, perineal body Les niveaux et les moyens de fixité du vagin, d après DeLancey, 1993 The vagina and its connections play an important in the pelvi-perineal balance
13 Pelvic organ prolapse Histological aspects What are the changes in the vaginal tissue in case of POP? Contradictory results or no in total collagen content or collagen III density or no in elastin density High variability in the methodology
14 ! Pelvic organ prolapse Study of the histological properties Tissue collection Mid vagina and Apical vagina Urètre Urètre Vessie PAROI VAGINALE ANTERIEURE Utérus Vagin Col utérin PAROI VAGINALE POSTERIEURE Anus Anus Rectum
15 Pelvic organ prolapse Morphometric analysis of vaginal tissue Individualization of the vaginal layers Epithélium Lamina propria Couche musculaire Immuno-marquage par α-sma, grossissement X10 (LBTD)
16 Pelvic organ prolapse Morphometric analysis of the vaginal tissue Measurement of smooth muscle cells density in the muscularis layer Immuno-marquage par α-sma, grossissement X10 (LBTD) Densité cellules musculaires lisses dans la couche musculaire
17 Pelvic organ prolapse Morphometric analysis of the vaginal tissue Measurement of vessels density in lamina propria and muscularis Densité de vaisseaux dans la lamina propria Immuno-marquage par α-sma, grossissement X10 (LBTD) Densité de vaisseaux dans la couche musculaire
18 Pelvic organ prolapse Morphometric analysis of the vaginal tissue Measurement of elastin density in the lamina propria and muscularis Densité d élastine dans la lamina propria Coloration des fibres élastiques par l orcéine, grossissement X10 (LBTD) Densité d élastine dans la couche musculaire
19 ! Pelvic organ prolapse Morphometric analysis of the vaginal tissue Comparison between Mid vagina and apical vagina Urètre Urètre Vessie PAROI VAGINALE ANTERIEURE Utérus Vagin Col utérin PAROI VAGINALE POSTERIEURE Anus Rectum Portion moyenne du vagin Anus Région péricervicale
20 Pelvic organ prolapse Changes in elastin density in different locations of the vaginal wall in women with pelvic organ prolapse de Landsheere L. et al, Int. Urogynecol. J, 2014
21 Pelvic organ prolapse Changes in elastin density in different locations of the vaginal wall in women with pelvic organ prolapse Anterior Region 0.1 * Prolapsus Control Significant decrease of elastin density in the most dependent portion of the vaginal wall de Landsheere L. et al, Int. Urogynecol. J, 2014
22 Pelvic organ prolapse Biomechanical properties of vaginal tissue Uniaxial traction testing until rupture A B Instron 5882 Rubod et al, J Urol, 2007
23 Stress Pelvic organ prolapse Biomechanical properties of vaginal tissue Stress strengh curves Very high interindividual variability Non linear relationship between stress and strain 6 patientes Tissu vaginal Strengh Rubod et al, J Urol, 2007
24 Pelvic organ prolapse Biomechanical behaviour Non linear behaviour hyperelastic Mooney-Rivlin Model C 1 σ = 2 (λ 1 / λ 2 ) [C 0 + C 1 (λ / λ 3)] C 0 Rigidity at low deformation C 0 C 1 Rigidity at high deformation Rubod et al, Int Urogynecol J, 2008
25 Pelvic organ prolapse Propriétés biochimiques du tissu vaginal Propriétés biochimiques du tissu vaginal de Landsheere L. et al, Int. Urogynecol. J, 2015
26 Pelvic organ prolapse Significant inverse correlation between C 0 and the elastin/collagen ratio in the lamina propria
27 Pelvic organ prolapse The biomechanical properties of vaginal tissue are variable from one patient to another and the main predictor of the rigidity of the vagina is the density of elastin
28 Pelvic organ prolapse Conclusion POP is a common pathology and its pathophysiology is multifactorial A loss of elasticity of the vaginal tissue results, in biomechanics, by a greater rigidity tissue Elastin is a key element in maintaining the integrity of the vagina
29 Histology of the vaginal wall Introduction Histology of the vaginal wall in women with POP Histological properties Bioméchanical properties Histology of the vaginal wall in post-menopause Laser rejuvenation New trend or real benefit?
30 Histology of the vagina in Menopause Anatomical and physiological changes Decrease estrogen levels and aging Vulvo-vaginal atrophia (Genitourinary Syndrome) - Thinning of the top layer of superficial apithelial cells - Loss of elasticity of the vaginal epithelium - Increase subepithelial connective tissue (lamina propria) - Loss of rugae - Shortening and narrowing of the vaginal canal - Decrease in vaginal secretions - Increase in vaginal PH to > 5 JAMA, 2016
31 Histology of the vagina in Menopause Clinical manifestation of genitourinary Syndrome Vaginal atrophy Dryness Burning Pain, irrirtations, especially during sexual intercourse Discharge, bleeding Urinary symptoms Increase urinary frequency Urge incontinence Infection JAMA, 2016
32 Post-ménopause Lifetime changes of the vaginal tissue The Vaginal mucosa (A) Pre-menopausal, (B) Moderate atrophy, (C) Severly atrophic Uptodate, 2018 Tadir et al, Laser in surgery, 2017
33 Post-ménopause Lifetime changes of the vaginal tissue (sheep) Epithelium and lamina propria PAS = Periodic Acid Shiff : detection of glycogen (Dark superficial purpel layer) The thickness of glycogen staining epithelial layers changed with puberty and menopause. The epithelium was markedly thicker after multiple deliveries. Hympanova et al, manuscript submited
34 Post-ménopause Lifetime changes of the vaginal tissue (sheep) Vaginal dimensions increase during adolescence, peak at reproductive levels, and decrease sharply after ovariectomy. One year after first delivery, the distal vagina gets more compliant, yet this is reversed later in life. The lamina propria and muscularis thickened in puberty and in nulliparous. Semiquantitative collagen assessment demonstrated a lower collagen and higher elastin content after first and multiple deliveries. Hympanova et al, manuscript submited
35 Histology of the vagina in Menopause Conclusion The main changes related to menopause consists in Vaginal atrophy, caused by estrogen loss (genito-urinary syndrome) Shrotening and narrowing of the vagina Lower vaginal contractility Higher collagen and lower elastin density Impact on the biomechanical properties of the vaginal wall (> POP) The lifetime changes in the Sheep vaginal are similar to those observed in women
36 Histology of the vaginal wall Introduction Histology of the vaginal wall in women with POP Histological properties Bioméchanical properties Histology of the vaginal wall in post-menopause Laser rejuvenation New trend or real benefit?
37 Laser rejuvenation Laser Rejuvenation Alternative to first line approach improving vaginal atrophy and dryness by inducing New collagen and elastic fiber production Neovascularisation Improvement of vaginal tissue trophism in general New concept «adapted» from results in dermatology or cosmetic surgery
38 Laser rejuvenation Aim of laser rejuvenation To revitalize and restore elasticity and moisture of the vaginal mucosa Topic estrogens Pelvic floor muscles training Hyaluronic acids Via «non invasive» energy based system
39 Laser rejuvenation Laser rejuvenation Plethora of energy-based devices... Laser CO2 Monalisa, Femilift, Alma Erbium (YAG) Radiofrequency...Paucity of well conduct clinical studies...
40 Laser rejuvenation Laser rejuvenation Histogical hanges in the vaginal wall
41 Laser rejuvenation Laser rejuvenation Histological changes in the vaginal wall
42 Laser rejuvenation Laser rejuvenation
43 Laser rejuvenation Conclusion Gain in interest of laser therapy as a non-hormonal treatment for GSM Laser therapy alleviate vaginal dryness, dyspareunia (and urinary symptoms?) More well-conducted morphometric studies are needed to assess the changes related to laser therapy RCT are needed to compare laser with other therapies, as well as the duration of therapeutic effects or repeat applications
44 Laser rejuvenation Conclusion And To Avoid...
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