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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

Menarche

Family History

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.

Menarche

Family History

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.

Menarche

Family History

Obesity

Risk Factor

Menarche

Family History

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.

Menarche

Family History

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.

Menarche

Family History

Obesity

PATHOLOGIC APPEARANCE

Gross• Nodular structures• Ovel/round shaped• Pearly white• Firm consistency• On cut-surface : whorled

pattern• Thin outer connective tissue

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

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

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

• Acquired dysmenorrhea

• Severe: Degeneration, torsion, uterine contractions

• Pelvic impaction nerve impingement

Infertility

• Sole abnormality• Abortion• Long-standing

infertility, recurrent pregnancy wastage w/ leiomyomas myomectomy

Laboratory Findings

Leukocytosis, elevated ESR

Endometritis, carneus, septic generation

Complicated leiomyoma

Anemia

Bleeding & Infection

Uterine leiomyoma

Imaging

Symmetrical, well-defined, hypoechoic,

heterogenous

Color Doppler

Saline-infusion sonography

Calcific alterations

Urinary system impingement

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

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

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

Surgical Management

• 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

• Resection of submucous, pedunculated

leiomyomas through a hysteroscope

• Improve fertility rate, menorrhagia

Surgical Management

THANK YOU

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