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LEIOMYOMAOLEH :
KEYNE MONINTJAKARINA GIOVANI
YULINCE TAMBONOPMAYA
FRANSISCA ANCELIA
ANATOMY
UTERUS (1)
• Uterus is situated in the pelvic cavity between the bladder anteriorly and the rectum posteriorly
• Almost the entire posterior wall of the uterus is covered by visceral peritoneum.
• The upper portion of the anterior wall of the uterus reflects forward onto the bladder dome to create the vesicouterine pouch
UTERUS (2)
• The lower portion of this peritoneum forms the anterior boundary of the pouch of Douglas.
• The lower portion of the anterior uterine wall is united to the posterior wall of the bladder by a well-defined loose layer of connective tissue. This is the vesicouterine space.
UTERUS (3)
• The uterus is described as being pyriform or pear-shaped• It consists of two major parts:
– an upper triangular portion (the body or corpus)– a lower (the cervix) which projects into the vagina.
UTERUS (4)
• The uterus of adult nulliparous women measures 6 to 8 cm in length as compared with 9 to 10 cm in multiparous women.
• In nonparous women, the uterus averages 50 to 70 g and in parous women it averages 80 g or more
CERVIX (1)
• The cervical portion of the uterus is fusiform and open at each end by small apertures (the internal and external os)
• The lower vaginal portion of the cervix is called the portio vaginalis.
• Before childbirth, the external cervical os is a small, regular, oval opening
CERVIX (2)
• After labor the orifice is converted into a transverse slit that is divided anterior and posterior lips of the cervix.
• If torn deeply during delivery the cervix may heal in such a manner that it appears to be irregular, nodular, or stellate.
ENDOMETRIUM• This is a mucosal layer
which lines the uterine cavity in non pregnant women. It is a thin, pink, velvet like membrane.
• The endometrium normally varies greatly in thickness. It is composed of surface epithelium, glands, and interglandular mesenchymal tissue in which there are numerous blood vessels
MYOMETRIUM
• This is composed of bundles of smooth muscle united by connective tissue in which there are many elastic fibers.
• The interlacing myometrial fibers that surround the myometrial vessels are integral to control of bleeding from the placental site during the third stage of labor.
LIGAMENT
• Round Ligament• Broad Ligament• Infundibulopelvic Ligament or suspensory ligament of the
ovary• Cardinal Ligament or transverse cervical ligament or
Mackenrodt ligament• Uterosacral Ligament
BLOOD VESSEL
• Artery iliaca interna Artery uterine
• Aorta Artery ovarian
• Iliaca vein uterine vein
• Pampiniform plexus vein ovarian
LYMPHATIC
• Lymphatics from the cervix terminate mainly in the internal iliac nodes
• The lymphatics from the uterine corpus are distributed to two groups of nodes– Internal iliac nodes– Para-aortic lymph nodes
INNERVATION
• Pelvic nerve, consist of :– Sympathetic nervous system 11th and 12th thoracic
nerve roots transmit the painful stimuli of contraction to the central nervous system
– Parasympathetic nervous systems made up of a few fiber from second, third, and fourth sacral nerve
– Cerebrospinal
DEFINITION
Definition
• Leiomyomas are the most frequently seen tumors of the female reproductive system.
• Leiomyomas, also known as uterine myomas, Fibroids, or fibromas.
• They are firm, compact tumors that are made of smooth muscle cells and fibrous connective tissue that develop in the uterus.
EPIDEMIOLOGY
Epidemiology
• Prevalance of Uterine myoma : 10-20% women • Prevalance Rate:
– approximate 1 in 20– 13.6 million people in USA
• Uterine myoma are the number 1 reason for hysterectomy in the US
Source : The National Women’s Health Information Center, CDC
Epidemiology
• Peak incidence of uterine myoma is 35-50 years old (shows an relationship between myoma uteri and estrogen)
Incidence in world 20-40%
Incidence in Indonesia
2,39%-11,7%
CLASSIFICATION
• Subserosal
from myocytes adjacent to the uterine serosa, the growth is directed outward.• Intramural
situated in the middle layer of the uterine muscle• Submucous
proximate to the endometrium and grow toward and bulge into the endometrial cavity• Pedunculated
attached only by a stalk to their progenitor myometrium• Intraligamentary
subserosal variants that attach themselves to nearby pelvic structures from which they derive vascular support
RISK FACTOR
Risk Factor
Age
Early
Menarche
Family History
Race
Obesity
Risk Factor
» Women are most likely to be diagnosed with leiomyomas during their 40s; however, it is not clear whether this is because of increased formation or increased leiomyoma growth secondary to hormonal changes during this time.
Age
Early
Menarche
Family History
Race
Obesity
Risk Factor
» Early age at menarche results in an increased cumulative exposure to estrogen and progesterone and a higher lifetime number of cell divisions in the myometrium, increasing the probability of cellular mutation.
» Age at menarche is inversely associated with risk of uterine leiomyoma. Menarche occuring at age 10 years or older was associated with 50% increase in risk for leiomyoma confirmes by hysterectomy compared with menarche occuring at age 12 years or older.
Age
Early
Menarche
Family History
Race
Obesity
Risk Factor
Age
Early
Menarche
Family History
Race
Obesity
• Having a family member with Leiomyoma increases your risk.• First-degree relatives of women with myomas have a 2.5 times increased risk of developing leiomyomas. • Women reporting myomas in two first-degree relatives are more than twice as likely to have strong expression of VEGF-a (a myoma-related growth factor) than women who have leiomyomas but no family history.
Risk Factor
» African-American women are more likely to develop leiomyomas than white women.
» Study found that the Val/Val genotype of an enzyme essential to estrogen metabolism, catechol-O-methyltransferase (COMT), is found in 47% of African American women but only 19% of white women. Women with this genotype are more likely to develop myomas, which may explain the higher prevalence of myomas among African-American women.
Age
Early
Menarche
Family History
Race
Obesity
• African-American women are more likely to develop leiomyomas than white women.
• Study found that the Val/Val genotype of an enzyme essential to estrogen metabolism, catechol-O-methyltransferase (COMT), is found in 47% of African American women but only 19% of white women. Women with this genotype are more likely to develop myomas, which may explain the higher prevalence of myomas among African-American women.
Risk Factor
» Obesity increases conversion of adrenal androgens to estrogene and decreases sex hormone–binding globulin. The result is an increase in biologically available estrogen, which may explain an increase in myoma prevalence and/ or growth.
» Obesity is associated with uterine Leiomyomas. The risk of obese women developing leiomyoma is 2-3 times greater than women of average weight.
» The risk of myomas increased 21% with each 10 kg increase in body weight and with increasing body mass index. Similar findings have been reported in women with greater than 30% body fat.
Age
Early
Menarche
Family History
Race
Obesity
PATHOLOGIC APPEARANCE
Gross• Nodular structures• Ovel/round shaped• Pearly white• Firm consistency• On cut-surface : whorled
pattern• Thin outer connective tissue
layer
Histologically• Elongated smooth muscle
cells aggregated in bundles (swirl and intersect one another)
• Mitotic activity is rare
Degeneration Process
Degeneration develops frequently in leiomyomas because of the limited blood supply .
Acute painNo intrinsic
vascular organization
Lower arterial density
Vulnerable to hypoperfusion and ischemia
Cytogenetics • Single progenitor myocyte • Primary mutation : unknown, but identifiable karyotypic
defects• Chromosomes 6, 7, 12, and 14 correlate with rates
and direction of tumor growth
ROLE OF HORMONES
• Uterine leiomyomas are estrogen-and progesterone-sensitive tumors
• Develop : reproductive years • Regress ina size : after menopause• Sex steroid hormones mediate effect
- Stimulating or inhibiting transcription
- Production of cellular growth factors
Leiomyomas themselves create
a hyperestrogenic environment
(growth and maintenance)
A greater density of estrogen receptors
(greater estradiol binding)
Convert less estradiol to the
weaker estrone
Involves higher levels of cytochrome P450
aromatase
(catalyzes the conversion of androgens to estrogen in a
number of tissues)
Increased BMI
(Obesity)
Early Menarch
e
Race(African-
American)
Hereditary
The risk factors associated with leiomyoma development and in formulating treatment plans.
Increased Risk Factor
Increased BMI
(Obesity)
Early Menarche
Race(African-
American)Hereditary
The risk factors associated with leiomyoma development and in formulating treatment plans.
Women giving birth at an early
age
Higher parity
Cigarette smoking
Decreased Risk Factor
Progestins The role of progesterone is both inhibitory and stimulatory effects.
Inhibitory Stimulatory
Exogenous progestins limit leiomyoma growth
(Goldzieher, 1966; Tiltman, 1985)
Progestins + agonist increased leiomyoma growth
(Carr, 1993; Friedman, 1994).
Medroxyprogesterone lower leiomyoma development
(Lumbiganon, 1996).
Antiprogestin (mifepristone) induces atrophy in most leiomyomas
(Murphy, 1993).
Women treated with gonadotropin-releasing hormone (GnRH) agonists,
leiomyomas typically decrease in size.
DIAGNOSIS
Approach to Diagnosis
Symptoms and Signs
ImagingLaboratory FIndings
Symptoms and Signs (1)
• Majority (2/3): asymptomatic• Symptoms (+) depend on the number, size, location,
situation, and status of the tumor• Gynecologic symptoms: bleeding, pain, pressure
sensation or infertility• PE: Firm, irregular but smooth, nodular masses attached
to the uterus.
Bleeding
• Menorrhagia• Premenstrual
spotting• Prolonged light flow• Anemia /
polycythemia
Pressure Effect
• Variable• Large tumors pelvic
congestion• Parasitic tumors
intestinal obstruction
Symptoms and Signs (2)
Pain
• Acquired dysmenorrhea
• Severe: Degeneration, torsion, uterine contractions
• Pelvic impaction nerve impingement
Infertility
• Sole abnormality• Abortion• Long-standing
infertility, recurrent pregnancy wastage w/ leiomyomas myomectomy
Symptoms and Signs (3)
Laboratory Findings
Leukocytosis, elevated ESR
Endometritis, carneus, septic generation
Complicated leiomyoma
Anemia
Bleeding & Infection
Uterine leiomyoma
Imaging
USG
Symmetrical, well-defined, hypoechoic,
heterogenous
Color Doppler
Saline-infusion sonography
X-Ray
Calcific alterations
Urinary system impingement
MRI
BEST MODALITY
Localization and detailing
Adenomyosis/ Leiomyoma/
Leiomyosarcoma
DIFFERENTIAL DIAGNOSIS
Differential Diagnosis
• Pregnancy• Adenomyosis• Leiomyosarcoma• Solid ovarian neoplasms• On imaging studies may be
confused with focal myometrial contraction• Consider: subinvolution, congenital anomalies, adherent
adnexa, omentum or bowel benign hypertrophy, and sarcoma or carcinoma
MANAGEMENT
Management
Consider:• number, • size, • location, • symptoms, • degeneration, • reproductive desires • general health, • proximity to menopause, • malignancy potential
Treatments:• Observation• Drug therapy• Uterine Artery
Embolization• Surgical
Observation
asymptomatic
Annual examination (4-6 months)
Pelvic examination
Sonographic surveillance
Drug Therapy
NSAIDs
Hormonal therapy
GnRH antagonist
Antiprogestin
Androgen
GnRH agonist
NSAIDs
Prostaglandin as mediator of symptoms
Hormonal therapy
Androgen
GnRH agonist
GnRH antagonist
Antiprogestin
Benefit = ??
Drug Therapy
NSAIDs
Hormonal therapy
Combination oral contraceptive pills (COCs)
• Induce endometrial atrophy
• ↓ prostaglandin production
GnRH antagonist
Antiprogestin
Benefit = ??
Androgen
GnRH agonist
Drug Therapy
Synthetic Prolonged receptor binding
↑ level of LH & FSH
‘flare’
desensitisation
↓ esterogen ↓ progesterone
• ↓ vol. of uterus & leiomyoma
• ↓ pain• ↓ menorrhagia
NSAIDs
Hormonal therapy
GnRH antagonist
Antiprogestin
IM/SC
Androgen
GnRH agonist
Drug Therapy
Treatment stopped after 3-6 months
Regrow
↓ esterogen
• vasomotor symptoms• libido changes• vaginal epithelium dryness • ↓ bone density
Add-back therapy
Temporary agent only
NSAIDs
Hormonal therapy
GnRH antagonist
Antiprogestin
Androgen
GnRH agonist
Drug Therapy
Indications for Medical Treatment
Symptom NSAIDs COCsGnRH
Agonist
Dysmenorrhea + + +
Menorrhagia – + +
Dyspareunia – – +
Pelvic pressure – – +
Infertility – – +
NSAIDs
Hormonal therapy
GnRH antagonist
Antiprogestin
Androgen
GnRH agonist
Drug Therapy
NSAIDs
Hormonal therapy
Danazol,Gestrinone
• shrink leiomyoma,• improve bleeding
symptoms
Side effect • Acne• Hirsutism
GnRH antagonist
Antiprogestin
Not used as #1 line
Androgen
GnRH agonist
Drug Therapy
NSAIDs
Hormonal therapy
GnRH antagonist
Antiprogestin
Similar with GnRH agonist, but without flare
Cetrorelix & Nal-gluSC
Androgen
GnRH agonist
Drug Therapy
NSAIDs
Hormonal therapy
GnRH antagonist
Antiprogestin
Androgen
GnRH agonist
Mifepristone
Progesterone receptor-A
• ↓ leiomyoma volume• amenorrhea• pain relief• ↓ pressure symptoms
5, 10, 25, or 50 mg p.o daily (12 weeks)
Side effect• vasomotor
symptoms, • simple endometrium
hyperplasia • elevated liver enzyme
Drug Therapy
Uterine Artery Embolization -1
blood flow obstruction
ischemia necrosisAngiographic catheter
PVA
Uterine Artery Embolization -2
postprocedural symptoms (2 to 7 days)
• pelvic pain and cramping, • nausea and vomiting, • low-grade fever, • malaise
oral, intravenous, epidural, or patient-controlled analgesia
5 year post procedure 27% required other
invasive treatment
short term symptoms relief
Complications:
• Necrotic tissue might need
dilatation and evacuation
• Transient amenorrhea
• Embolisation & necrosis of
surrounding tissue (rare)
• Endometritis
• Sepsis
Surgical Management
Hysterectomy Myomectomy Hysteroscopy
• Definite & most common surgical treatment
• Vaginally, abdominally, laparoscopically
• >90% improved symptomps
• Oophorectomy is not necessary
• Consider uterine size & preoperative
hematocrit
• Preoperative GnRH may be advantageous
Hysterectomy Myomectomy Hysteroscopy
Surgical Management
Hysterectomy Myomectomy Hysteroscopy
• For symptomatic woman who:
– Decline hysterectomy
– Desire future childbearing
• Laparoscopically, hysteroscopically,
laparotomy incision
• Similar perioperative risk with hysterectomy
• Intra-abdominal adhesions and leiomyoma
recurrence are more common (15-40%)
Surgical Management
Hysterectomy Myomectomy Hysteroscopy
• Resection of submucous, pedunculated
leiomyomas through a hysteroscope
• Improve fertility rate, menorrhagia
Surgical Management
THANK YOU