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Pathogenesis of prolapse;

Pathogenesis of prolapse;. Prof Mark Vierhout UMC St Radboud Nijmegen Netherlands. Birth?. Evolution?. Age?. Genetic. Race. Menopause. COPD. Pelvic floor dysfunction. Age. Social class. Smoking. Parity. Education. SURGERY. Work. Obesity. Bony pelvis. Collagen.

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Pathogenesis of prolapse;

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  1. Pathogenesis of prolapse; Prof Mark Vierhout UMC St Radboud Nijmegen Netherlands

  2. Birth? Evolution? Age?

  3. Genetic Race Menopause COPD Pelvic floor dysfunction Age Social class Smoking Parity Education SURGERY Work Obesity Bony pelvis Collagen

  4. Distribution by Age group Mean 8.3% Mean 30.8%

  5. Lifetime risk for operation for POP is 11% Olsen et al 1997

  6. Distribution of Pelvic Organ Prolapse > stage 1: 40% > stage 1: 50% Nygaard 2004 Slieker-ten Hove et al. ICS/IUGA 2004 (4) N = 653 Swift 2000 N = 497

  7. Incidence operative correction of POP • USA 1.3/1000/jr(Olsen) • UK 1.6/1000/jr(Mant) • Netherlands 1.3/1000/jr (SIG)

  8. Cost of Surgical procedures for POP

  9. Family history and prolapse Chiaffarino 1999 • Setting: Clinical patients • 108 cases • 100 controls • Mothers 27.6% vs 10.6% (RR 3.2) • Sisters 30.0% vs 16.2% (RR 2.4%)

  10. Family and prolapse (Vierhout et al. Case controls. 2002) • Setting: outpatients gynecological patients • 72 cases vs 56 controls • Mothers 56% vs 20% (RR2.8) • Sisters 42% vs 7% (RR 6.0) • Mother and sister 24% vs 0% (RR…) • >1 sister 5 vs 0% (RR ….)

  11. Jack Int Urogyn J 2005 • 28 women with stage 3-4 <55 years • 10 women with positive family history • They calculated a five time increase in risk for sisters. • “Dominant inheritance pattern with high penetrance”

  12. Brielle onderzoekMethods Patients • All women aged 45 to 85 in a small town (2750) • Questionnaire • Response rate 51% (n=1398) • Instruments • UDI6 • EQ-5D • Questionnaires on pelvic floor disorders and sexual activity • Did or does your mother suffer from prolapse?

  13. Baseline characteristics

  14. Prolapse symptoms in the study group

  15. 23% of symptomatic women had symptomatic mother • 10% of asymptomatic women had symptomatic mother • Relative risk of 2.3(95% CI 1.2-4.6)

  16. Multivariate analysis

  17. Conclusions Brielle study • Familial transmission of POP is prominent • There is a threefould increased risk of having (had) a mother with POP in symptomatic women vs asymptomatic women. • Smoking, overweight, heavy physical work and menopause were not found to be correlated with POP

  18. Twin studies(Dietz-ultrasound) • 46 monozygotictwins • 24 dizychotic twins • Total 178 women • Bladder neck mobility on Valsalva by perineal ultrasound.(Oblique Bladder neck mobility)(OBNM)

  19. Monozygotic twins r=0.61 • Dizygotic twins r=0.15 • Sisters r=0.21 • HeritabilIty explained 59%(38-74%) of the variance

  20. How about race?

  21. Womens Health Initiativen=27.342 women • Age RR 1.36 • BMI RR 1.40 • Apple shape RR 1.17 • Smoking current RR 0.81 • Alcohol(>7/wk) RR 0.64 • HRT(past) RR 0.84

  22. Womens Health Initiativen=27.342 womenAny prolapse: • White 40% • Black 29% • Asian 50% • Hispanics 26%

  23. POP surgery in the USA 1997 • 225,964 women underwent surgery in 1997 • = ( 22.7/100.000) • White/black ratio: 3.0 Brown et. Al. AJOG 2002;186:712-6

  24. Urinary incontinence in black and white women • 541 women ; age 42-50 years. • (Median 47 yrs) • 31% had regular incontinence • White/black ratio: 1.78 Burgio et al J Urol 1991;146:1255-9

  25. Urinary symptoms in black, hispanic and white women. Sze et. Al. Obstet Gynecol 2002;99:572-5

  26. Pelvic floor area in black vs white women • Forty black and 40 white pelvis compared Baragi et al 2002 AJOG;187:111-5

  27. Pelvic floor area in black vs white women White: 937 cm2 Black: 890 cm2 Difference overall :5.3% Difference post.: 10.4% Baragi et al 2002 AJOG;187:111-5

  28. Severe Perineal lacerations in various races • Black: 2.0% • White: 4.3% • Asian: 9.3% • Hispanic: 3.4% • Multivariate model: Asian OR 2.5(2.0-3.0) Goldberg Obstet Gynecol suppl

  29. Perineal lacerations in black’s vs whites. • 176 black women and 1633 white women. • 43% perineal lacerations in black’s and 59% in white’s • Shorter 2nd stage and lower birthweight in black’s. • Multivariable analysis: Black primi’s were twice as likely to deliver with intact perineum Howard et all. Obstet & Gynecol 2000;96:622-4

  30. Possible explanations for ethnic differences in incontinence and POP • Smaller circumference of pelvis • Deeper pelvis • Longer cervix with better attachments of ligaments • Connective tissue differences • Pelvic floor muscle differences. • Different obstetrical variables. • Different risk factors.

  31. Race and pelvic floor dysfunction; Conclusions • Black’s have less gsi than white’s. • Black’s have more DI than whites. • Black’s have less prolapse than white’s. • Black’s have different(smaller) pelvices than white’s • Black’s are probably more elastic and have stronger pelvic floor muscles.

  32. Collagen in POP • Several studies find lower total collagen contents in: Non support tissues • Skin thigh • Skin abdominal wall • Cervix • but also • Round ligament • Pubocervical fascia • Periurethral fascia

  33. Prevalence of POP in Ehlers-Danlos and Marfan (2002) • 20 patients identified. • Age 47 yrs • Nulliparous 45% • Urinary incontinence 45% • Prolapse 50% • Rectal prolapse 10% No data on collagen in different races!!

  34. Microarray gene profiling in 14 women with POP in cardinal ligaments • FNDC1, OLFML2B,PPL,IGJ,IGKC were more than 3 times overexpressed. • Suggesting: • Proteins related to extracellular matrix, intermediate filaments, immunoglobins for transport and immune system Liu ICS abstract 2005

  35. Visco Am J Obstet Gynecol 2003in pubococcygeus muscle • 12,266 genes compared • 260 genes overexpressed in pop • “may be related to structural proteins related to actine and myosine as well as the extracellular matrix proteins”

  36. Mean 8.3% Parity Parity and POP

  37. Modification of age on the effect of parity for UI but also for POP? Relative risk times 10

  38. Possibilities of damage to the pelvic floor during parturition • Damage to connective tissue • Vascular damage • Damage to nervous sytem • Direct muscular damage • Direct urethral injury

  39. Endocoil MRI after delivery

  40. Bladder neck at rest(Peschers’96)

  41. Direct injury to the muscles of the pelvic floor Central located nuclei Fibrosis Variation in fiber diameter Dimpfl ‘98

  42. JAMA April 10 2002

  43. Flow chart of the Hannah trial 2088 Planned CS Planned VD 1043assigned 1045 assigned 798 included 798 included 73 VD 342 CS 456 VD 725 CS

  44. Incontinence for urine by mode of delivery only(independent of planning) (Hannah et al 2002) Relative risk 0.60

  45. Tegerstedt Am J OG 2006;194:75-81 OR’s adjusted for age and parity(only parous women)

  46. OR’s adjusted for age and parity Tegerstedt AmJ OG 2006;194:75-81

  47. OR’s adjusted for age and parity Tegerstedt AmJ OG 2006;194:75-81

  48. The pelvic floor in pregnancy and delivery • In pregnancy lower urinary tract symptoms are common. • Vaginal delivery is related with the occurrence of urinary incontinence either starting directly postpartum or with a latent period. • This effect can be diminished by (elective) Caesarean Section but it is unclear how much. • All effects of pregnancy and delivery tend to dissapear with time

  49. The pelvic floor in pregnancy and delivery • Various obstetric variables are of influence but little is known how much and how these are influenced by each other. • The “damage”by vaginal delivery is mediated by neuromuscular, direct musculair and connective tissue damage. • Unknown is which is of greatest importance. • Little is known on direct damage to the urethral sphincter(as compared with the anal sphincter)

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