UTERINE LEIOMYOMATA

Uterine LeiomyomataBenign tumor comprised mostly of smooth muscle cells

First described by Reinier De Graff1641

Most common tumor of the female pelvis

Represent 1/3 of all GYN admissions to hospitals

IncidenceUsually quoted 50% (Underestimate)Cramer and Patel100 serial UteriSectioned at 2mm77 of 100 had myomas84% had multiple myomas649 myomas found in allNo difference in incidence within pre or post menopausal uteri Am J Clin Pathol. 1990 Oct;94(4):435-8

IncidenceMore common in African-Americans than whiteTorpin et al. investigated 1741 UteriOverall incidence 3 times higher in blacksAlso tended to be largerAlso occurred at a younger ageJ Obstet Gynecol 1942;44:569

IncidenceCumulative incidence by age 50, > 80% for African American and nearly 70% for Caucasian women.

One in four women have at least one submucosal fibroid.

Overall prevalence of uterine fibroids increases with age from 3.3% in women 25-32 to 7.8% in women 33-40 years. Baird et al, Am J Obstet Gynecol 2003. Borgfeldt et al, Acta Obstet Gynecol Scand 2000.

EtiologyArise from a single muscle cell (monoclonal).

Proliferate under the influence of sex hormones, including estrogen, progesterone & androgens.

Effects of steroids are modulated by local growth factors. Rein et al, Am J Obst Gyne 1995. Ichimura et al, Fertil Steril 1998. Stewart et al, Obstet Gynec 1998. Wer et al, Fertil Steril 2002.

Etiology

Fibroblast growth factorVascular endothelial growth factorHeparin-binding epidermal growth factorPlatelet-derived growth factorTransforming growth factorParathyroid hormone-related proteinProlactin

GENETIC BASIS ?Twin studies [3]First-degree affected relatives [4,5]Race as risk factorHereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) [6]Cutaneous and uterine leiomyomataAt risk for papillary renal cell carcinoma (women > men) [7,8]Women: increased risk of leiomyosarcoma [7,8]Mutation in fumarate hydratase gene

EtiologyNevertheless fibroids are both estrogen and progesterone dependentOver expressed estrogen and progesterone receptors within fibroidsNoted to increase in size in high estrogen statesPregnancyHigh-dose OC useObesity

EtiologyRisk FactorsNurses Health Study II95,061 nurses completed questionnaires in 1989, 1991, 1993ObesityEarly menarcheNulliparityFertil Steril. 1998 Sep;70(3):432-9

Etiology Oral ContraceptivesHigh dose pills have been assoc. with stimulation of fibroid tumors

Smoking

PresentationMost fibroids do not cause symptoms.

20-50% experience tumor-related symptoms:

Menstrual dysfunctionBowel and bladder dysfunctionBulk effects

Such symptoms, account for up to 35% of all hysterectomies. Lefebvre et al, J Obstet Gynecol Can 2003. Myers et al, Agency for Health Care Research and Quality, 2001.

SymptomsPelvic PainMenstrual IrregularitiesGI complaintsBladder complaintsDyspareunia

Back painLeg painVascular symptomsInfertilityAsymptomatic

DiagnosisHistoryBimanual pelvic or abdominal examPelvic ultrasound - most commonMRI, HSG, sonohysterogram, hysteroscopy

Appearance

Appearance

Appearance

Degenerative ChangesDegenerative changes are reported in approximately two-thirds of all specimens, but most of them have no clinical significance. Hyaline degeneration- It is the most commonCystic degeneration Mucoid degeneration Fatty degeneration Carneous degeneration Calcification Sarcomatous degeneration(malignant transformation)

TreatmentExpectant management - most casesIndications for treatmentAbnormal uterine bleeding, causing anemiaSevere pelvic painLarge or multipleObscuring evaluation of adnexaUrinary tract symptomsPostmenopausal or rapid growth

Treatment ChoicesMedical therapiesMedroxyprogesterone (Provera)DanazolGnRH agonists (nafarelin acetate, Depot Lupron)

TreatmentRU486Anti-progestinHigh affinity to Progesterone and glucocorticoid receptorsMurphy et al (1995) showed decrease of volume an average 49%Recent reviews supports usage, but has been associated withHot flashesEndometrial hyperplasiaIs not associated with trabecular bone lossFertil Steril. 1995 Jul;64(1):187-90Obstet Gynecol. 2004 Jun;103(6):1331-6Clin Obstet Gynecol. 1996 Jun;39(2):451-60

TreatmentGestrinoneAntiestrogen/antiprogesteroneGnRH analoguesSuppresses pituitary mediated secretion of estrogensBasically treat 3-6 monthsExpect 50% reduction of uterine volume

Treatment ChoicesUterine Artery Embolization (UAE)

UAE

Within three months following embolization:45% and 55% reduction in total uterine and myoma volume.Reduction in symptoms in approximately 80% of women.

long- term data on durability and effects on fertility and pregnancy outcomes are very limited.Pron et al, Fertil Steril 2003Burbank et al, J Am Assoc Gynecol Laparosc 2000

The Elements of the flostat SystemU.S. FDA clearance of this device does not include the treatment of uterine leiomyomas

Flostat System

MR guided Focused Ultrasound

MyomectomyFirst performed by ?

MyomectomyFirst performed by Washington and John Atlee, 1844May be approached in a variety of waysAbdominally (open)LaparoscopicHysteroscopicPrimarily for submucosal/intramural fibroids impacting the endometrial cavityVaginalPrimarily for pedunculated submucous fibroids

MyomectomyBiggest complication is blood loss

Treatment ChoicesHysterectomyVaginalAbdominal

MyomectomyBonney-1920s Uterine Artery Clamp

MyomectomyRubin-1930s Uterine TourniquetControlled hypotensionApplication of a tourniquet around the uterine arteries and IP

Myomectomy

MyomectomyVasopressinFirst reported by Dillon, 1962Synthetic Antidiuretic horomoneInduces local vasoconstriction lasting approximately 30 minutesBe carefulShould not be used in those with underlying cardiovascular diseaseMay induce water intoxicationEsp in those on Tricyclics

MyomectomyFrederick et al20 pts randomized to either Vasopressin or salineMedian blood loss 225cc compared to 675cc (P>0.001)50% of those using saline required transfusion vs none in the vasopressin group (P=0.03)Br J Obstet Gynaecol. 1994 May;101(5):435-7

MyomectomyIs Vasopressin better than tourniquets?Not reallyComparable blood lossShorter operating time?

Abdominal MyomectomyTechniqueAttempt to remove all fibroids through a single midline incisionAvoids vascular structures laterallyTissue surrounding the fibroid is compressed tightly forming a pseudocapsuleNo vascular bundle enters the myomaIdentification of and dissection along this plane will minimize blood lossCleavage planes may be altered in those who have been pretreated with GnRH analogue

Abdominal MyomectomyRepairing defectMulti layered approachDeep sutures to close dead spaceSecond imbricating layerClose serosa with a baseball stitch

May require removal of excess myometrial tissue to allow adequate closure

Laparoscopic MyomectomyLimitationsIndications fertility or not fertility?Uterine SizePrevious surgery or suspected adhesionsMyomectomyLocation of the fibroidsDeep intramuralLateral Number of the fibroidsSize of the fibroids> 8 cm consider laparotomy

Laparoscopic MyomectomyProcedurePlace of 3-4 operating portsInjection of VasopressinMay use endoloop for pedunculated fibroidsDissect out fibroid through single incision similar to open approach

Laparoscopic MyomectomyOther optionsMorcellationMyolysisElectrosurgicalLaserCryosurgeryAm J Obstet Gynecol. 2004 Mar;190(3):639-43

Laparoscopic MyomectomyTo close or not to close?Early studies suggested greater adhesion formation with closure of the serosaCase reports of adenomyosis after leaving defects openCase reports of uterine rupture after laparoscopic myomectomySuggest rates are higher in defects that arent closedInt J Fertil. 1991 Sep-Oct;36(5):275-80Fertil Steril. 1998 Jan;69(1):143-5J Am Assoc Gynecol Laparosc. 2004 Feb;11(1):92-3

Laparoscopic MyomectomyClosurePerformed just like abdominal myomectomy

Selective Uterine Artery OcclusionIntroduced in 1995 as a global treatment alternative to hysterectomy for women with symptomatic fibroids.Burbank et al, J Am Assoc Gynecol Laparosc 2000

MyolysisLaparoscopic myolysis, introduced in 1992.

The procedure of delivering energy to myomas in an attempt to desiccate them directly or disrupt their blood supply.

Uterine fibroids may shrink up to 80% of their total volume following the procedure.

The integrity and strength of the uterine wall has not been determined after this procedure.Lefebvre et al, J Obstet Gynecol Can 2003

MyolysisFertility and pregnancy outcomes after laparoscopic myolysis remain unknown.

Three cases of uterine rupture during the third trimester of pregnancy have been reported.

Further research is needed to determine the efficacy and safety of myolysis.

However, until then it remains an option for uterine preservation.Vilos et al, J Am Assoc Gynecol Laparosc 1998

Treatment ChoicesHysterectomyVaginalAbdominal

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