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Uterine Leiomyomata

DR_FIROUZABADI

commonly termed fibroids the most common benign tumors of the

female genital tract and likely are the most common soft tissue tumors of all.

200,000 hysterectomies and 20,000 myomectomies annually in the United States.

50% of women having identifiable fibroids at menopause.

Clinical Presentation

While fibroids can cause symptoms at any age after puberty, they typically do so in the early to mid 30s.

The symptoms caused by leiomyomatavary depending on the size, number, and location of the tumors.

TABLE 55.1 Symptoms of Leiomyomata

* *Menorrhagia*Dysmenorrhea*Pelvic pressure (pressure on adjacent pelvic viscera)

Urinary frequencyConstipationDyspareunia

*Infertility*Repetitive pregnancy loss

First trimesterSecond and third trimester (preterm labor)

*Abdominal Distension

oligomenorrhea, regardless of the amount, or metrorrhagia does not suggest fibroids but rather an underlying endocrine abnormality (e.g., anovulation).

Furthermore, the typical scenario encountered with fibroids is not a sudden heavy bleeding episode but rather gradually increasing menstrual bleeding, paralleling tumor growth.

Leiomyomata may undergo rapid enlargement during pregnancy, outstripping their blood supply and resulting in central avascular necrosis, the so-called red degeneration. The pain may be severe, requiring hospitalizationand narcotics, but rarely puts a pregnancy at risk.

Ph/E

Anatomic Features Leiomyomata are benign, sex steroid-

responsive, smooth muscle tumors of the uterus originating as clonal expansions of individual myometrial cells.

The histology is virtually indistinguishable from normal myometrium except for a discrete circular whorling pattern with the cellularity and mitotic activity being highly variable.

Leiomyosarcomas do not arise from preexisting leiomyomata and present much later in life, well after menopause.

Types of leiomyoma

There is virtually no neovascularity within fibroids

Collateral vascular channels are comparably maximally engorged and may represent a surgical challenge.

Influence of Sex Steroids

There is little doubt that the growth of leiomyomata is dependent on sex steroids as they:

(a) are not noted prior to puberty.(b) typically regress after menopause.(c) possess sex steroid receptors (estrogen

and progesterone).

(d) often dramatically enlarge during pregnancy when estrogen and progesterone levels are very high.

(e) can be made to shrink with medically induced hypogonadism.

myomatous tissue has the same number of estrogen receptors but a higher number of progesterone receptors than the adjacent normal myometrium.

Situations that increase lifetime exposure to estrogen such as obesity and early menarche are associated with increased risk with the interval from the last delivery inversely related to risk.

oral contraceptives

hormone replacement therapy

Tamoxifen

Genetic Inheritance Pattern

more than 40% of first-degree female relatives of women with leiomyomata

common in all races, especially black women

the most frequent indication for gynecologic surgery.

multifactorial genetic inheritance pattern

Molecular Mechanisms and Genetic Dysregulation monoclonal neoplasms

The most common aberrant patterns are translocations between chromosomes 12 and 14 (larger myomas), deletions of the short arm of chromosome 7 (smaller tumors), and rearrangements of the long arm of chromosome 6.

Impact of Leiomyomata on Reproduction

TABLE 55.2 Mechanisms of Infertility with Leiomyomata

*Impaired implantationSubmucousIntracavitaryEnlarged uterine cavity volume

*Impaired tubal transportObstructionDistension

Intramural leiomyomata and ART first-trimester pregnancy loss, preterm labor, or intrauterine growth restriction

abruption placental classic cesarean delivery The need to perform a cesarean following

myomectomy needs to be considered in any risk-benefit analysis.

Diagnostic StudiesThe majority of leiomyomata are detected on pelvic examination

performed because of gynecologic symptoms. The uterus is typically noted to be enlarged and irregular on bimanual examination.

It is important to distinguish leiomyomata from other pelvic masses, and it may be difficult to do so in the presence of a large uterus.

This is most easily done with an endovaginal or abdominalultrasound scan, as the leiomyomata appear echogenic with similar acoustic impedance to the normal myometrium.

Computerized tomography and magnetic resonance imaging(MRI) may prove useful in selected circumstances , but they are much more expensive and yield little more useful information than office sonography.

Diagnostic Imaging Techniques1.Endovaginal ultrasonography

2.Sonohysterography3.Hysterosalpingography4.Hysteroscopy5.Computerized tomography6.Magnetic resonance imaging

Diagnostic Studies (cont’d)sonography:The proximity of the leiomyomata to the endometrial

cavity can usually be demonstrated by taking advantage of the acoustic differences between normal myometrium, fibroid tumors, and the endometrial cavity.

The endometrial stripe is a reliable marker of the endometrial cavity, and finding a smooth, continuous endometrial stripe with normal underlying myometrium between the cavity and any fibroids suggests that they are not submucosal.

Diagnostic Studies (cont’d)Simultaneously injecting saline into the

endometrial cavity while performing an endovaginal ultrasound examination (sonohysterography) improves the ability to delineate submucous and intracavitary leiomyomata.

However, it is not possible to distinguish an endometrial polyp from an intracavitary myoma by virtually any imaging technique.

Diagnostic Studies (cont’d)Hysterosalpingography is often undertaken if

infertility is present concurrently, as this technique can identify intracavitary tumors or a large but otherwise normal endometrial cavity caused by the stretching the normal myometrium around leiomyomata .

This radiographic technique has the added advantage of determining tubal patency as well.

Diagnostic Studies (cont’d)Increasingly, office hysteroscopy is being

used when tubal patency is not an issue, as this technique allows clear differentiation between leiomyomata and other intracavitary pathology such as endometrial adhesions, uterine septae, and endometrial polyps.

Diagnostic Studies (cont’d)Adenomyosis can occasionally be difficult to

distinguish clinically from leiomyomata.Imaging studies may not be helpful. The true diagnosis only made at surgery.MRI has been reported to be useful in

differentiating adenomyosis from leiomyomata.

When to TreatDespite the fact that fibroids are responsible for a

large number of gynecologic surgeries, treating these benign tumors requires the same risk-benefit analysis as any other therapeutic decision.

Often, simply using a prostaglandin synthetaseinhibitor or oral contraceptives will adequately relieve the symptoms.

When to Treat (cont’d)It may be appropriate to remove asymptomatic,

extremely large leiomyomata in an effort to prevent anticipated reproductive problems.

Large tumors that fill the pelvis can impinge on the pelvic sidewalls, causing hydronephrosis, and their removal is critical to prevent renal impairment.

When to Treat (cont’d)The growth characteristics of individual fibroids remain

highly unpredictable. Many have limited growth potential.

Some leiomyoma have already experienced rapid growth and have undergone aseptic necrosis and replacement by fibrosis, so they have no further growth potential and will not regress after menopause.

Many fibroids may gradually enlarge and cause symptoms well before the anticipated regression at menopause.

When to Treat (cont’d)Gradually worsening dysmenorrhea and menorrhagia

are more frequently linked than other symptoms.

When these symptoms are mild, nonsteroidal anti-inflammatory agents and oral contraceptives are often useful.

When to Treat (cont’d)Location of the fibroids is important with regard to the

development of symptoms: The closer the proximity to the endometrial cavity, the greater

and earlier the symptoms are observed. Intramural, submucosal, and intracavitary fibroids are far more

likely to be responsible for dysmenorrhea and menorrhagia than pedunculated or subserosal myomas. Severe symptoms may warrant intervention at a relatively small size, particularly when an intracavitary or submucosal fibroid is present.

Similarly, the closer to the serosal surface the fibroids are located, the larger the size will be attained before being detected. Indeed, some extremely large leiomyomata will not be associated with any symptoms aside from increased abdominal girth.

When to Treat (cont’d)Because the bladder is adjacent to the uterus, the

most frequent symptom associated with a large myomatous uterus is increased urinaryfrequency.

Rarely, compression of the colon against the sacrum may cause difficulty with defecation; however, more often than not, complaints of constipation are not completely relieved by removing or shrinking the leiomyomata.

Selecting the Appropriate TherapyWhen clear indications for treatment are

present, the most critical questions to ask before making a therapy decision pertain to (a) whether future reproduction is desired (b) how soon menopause can be anticipated.

Selecting the Appropriate Therapy (cont’d)As a simple hysterectomy represents a

definitive cure, this is an attractive option for many symptomatic women when:

1. maintenance of reproduction is not desired, 2. menopause is not imminent,

3. and more conservative measures have failed to alleviate the symptoms .

Selecting the Appropriate Therapy (cont’d)When the preservation of future childbearing

is desired, a myomectomy is the primary choice.

Extirpative OptionsEndoscopic techniques

Laparoscopically assisted supracervical hysterectomyLaparoscopically assisted total hysterectomyLaparoscopic myomectomyHysteroscopic resection of leiomyomata

Abdominal approachSupracervical hysterectomyTotal hysterectomyMyomectomy

Vaginal approachHysterectomyMyomectomy

HysterectomyWhen:future childbearing is not desired, the symptoms are severe enough to warrant

treatment, and the woman has no contraindications, a simple hysterectomy is often chosen.

Hysteroscopic MyomectomyMost intracavitary leiomyomata and a

substantial number of submucousleiomyomata can be resected via surgical hysteroscopy in an ambulatory setting.

Abdominal MyomectomyWhen symptomatic leiomyomata are not

amenable to a hysteroscopic approach, an abdominal approach usually is required.

Abdominal Myomectomy (cont’d)

An elective cesarean section is the preferred route of delivery for the vast majority of women with a previous abdominal myomectomy.

Minimally Invasive MyomectomyPedunculated, serosal, and selected intramural

leiomyomas can be dissected free from the surrounding myometrium, morcellated, and the incision closed via laparoscopy.

Recurrence of LeiomyomataSince there is a genetic basis for the

development of leiomyomata, even when all of the palpable leiomyomata have been surgically removed, the rate of recurrence and/or persistence with continued growth has been variably reported to be as high as 30% to 40%, depending on the:

Number of tumors removedThe length of follow-up.

Recurrence of Leiomyomata (cont’d)Indeed, between 10% and 25% of women

undergoing myomectomies require another surgical procedure within the next decade.

Recurrence of Leiomyomata (cont’d)Isolated large fibroids have lower recurrence

rates than when multiple small tumors are present, despite an overall smaller volume of leiomyomata .

Postoperative Pelvic AdhesionsThe frequency of postoperative adhesions following

myomectomy exceeds 50% and can result in reduced fertility, pain, or bowel obstruction.

Careful surgical technique to minimize the degree of surgical trauma,

confining the incisions to the anterior uterine surface so as to prevent contact with the bowel and adnexal structures, and

covering the posterior uterine incisions with surgical barriers ,

have been advocated to minimize the rate of postoperative adhesions.

Non-extirpative OptionsMyolysis

UAEMRI-guided HIFU

Medically induced hypogonadismGnRH agonistGnRH agonist with “add-back” therapy

Medical SuppressionMany medicinal agents have been considered

for the treatment of symptomatic leiomyomata, including:

1.estrogen antagonists, 2.progesterone antagonists (mifepristone),

3.androgens (danazol), 4.pituitary down-regulation with GnRH

agonists.

Medical Suppression (cont’d)Hypogonadism cannot be sustained for a

prolonged interval because of the significant side effects such as:

vasomotor hot flashes, accelerated bone loss, genital tract atrophy, and loss of the cardiovascular protection.

Medical Suppression (cont’d)The important question to ask is, “What is the

goal of medical suppression?” Currently, the most relevant clinical use of

GnRH agonists is to stop excessive vaginalbleeding and improve the hemogram prior to surgery or in order to delay surgery to correct other medical problems that are posing an increased surgical risk.

MyolysisThere have been many attempts at inducing

therapeutic necrosis of cells within the center of a fibroid (e.g., myolysis), thereby shrinking the tumor size, relieving symptoms, and preventing progressive growth of the tumors.

Myolysis (cont’d) The aseptic necrosis may cause significant

pain in the immediate post-treatment interval, comparable to that observed with degeneration of leiomyomata seen in pregnancy.

Myolysis (cont’d)Myolysis should be confined to those women

who are not interested in subsequent pregnancy until well-designed, long-term comparative trials demonstrate safety.

Uterine Artery EmbolizationWhen menorrhagia is the primary clinical

symptom and either the surgical risk is judged unacceptable or the patient declines extirpative surgery, therapeutic embolization of the uterine arteries can be utilized to reduce symptoms. This strategy is to simultaneously deprive the uterus and the fibroids of their blood supply, induce necrosis, and reduce the symptoms .

UAE (cont’d)Since UAE has only been widely utilized for

only slightly over a decade, the long-term safety and efficacy remain to be demonstrated.

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Adenomyosis

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DefinitionA benign uterine condition in which endometrial glands and stroma are present within the uterine musculature

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Etiology The cause of adenomyosis is unknown uterine trauma

caesarean section tubal ligation pregnancy

Basal endometrial hyperplasia invading a hyperplastic myometrial stroma.

Four primary theories

HeredityTraumaHyperestrogenemiaViral transmission

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The thickened and spongy appearing myometrial wall of this sectioned uterus is typical of adenomyosis. There is also a small white leiomyoma at the lower left.

Adenomyosis, Hysterectomy Specimen

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Adenomyosis correlates with abnormal amounts of multiple substances, possibly indicating a causative link in its pathogenesis:

Endometrial IL-18 receptor mRNA and the ratio of IL-18 binding protein to IL-18 are significantly increased in adenomyosispatients in comparison to normal people

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Clinical features1 Asymptomatic

Classic symptoms：secondary dysmenorrheaabnormal uterine bleeding

Chronic pelvic pain may occur

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Clinical features2： Most common physical sign

a diffusely enlarged uterus

particularly tender during menstruation

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Diagnosis： History Pelvic examinations Ultrasonography MRI Serum markersCA-125 definitive diagnosis can only be made

from histological examination of a hysterectomy specimen

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Treatment Hormone therapy NSAIDs Hysterectomy the only uniformly

successful treatment for adenomyosis is necessary.

Endometr ial polyps

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Definition

Benign localised overgrowth of endometrial glands and stroma, covered by epithelium, projecting above the adjacent epithelium

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epidemiology 12-80 Years old Most occur in women in their 40s and 50s Endometrial polyps occur in up to 10% of

women It is estimated that they are present in 25% of

women with abnormal vaginal bleeding Large endometrial polyps can also be

associated with tamoxifen use(associated with a higher risk of neoplasia and different molecular alterations)

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Risk factors Risk factors include

• obesity• high blood pressure• history of cervical polyps• tamoxifen• hormone replacement therapy

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Pathological findings Sessile or pedunculated Size: 1mm and beyond – may fill the

endometrial cavity and project through the cervical os

red/brown color ,large ones can appear to be a darker red

May be multiple May originate anywhere, but most commonly

fundus

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etiology No definitive cause of endometrial polyps

is known

affected by hormone levels and grow in response to circulating estrogen

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symptoms They often cause no symptoms Where they occur, symptoms include

"spotting" between menstrual periods, or after menopause

irregular menstrual bleeding bleeding between menstrual periods excessively heavy menstrual bleeding vaginal bleeding after menopause If the polyp protrudes through the cervix into the

vagina, pain (dysmenorrhea) may result ٨٢

Diagnosis

vaginal ultrasound (sonohysterography)

hysteroscopy

dilation and curettage

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Treatment IntraUterine System containing levonorgestrel

in women taking Tamoxifen may reduce the incidence of polyps

Polyps can be surgically removed using curettage or hysterescopy

If it is a large polyp, it can be cut into sections before each section is removed

If cancerous cells are discovered, a hysterectomy may be performed

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Prognosis and complications

Endometrial polyps are usually benign although some may be precancerous or cancerous

About 0.5% of endometrial polyps contain adenocarcinoma cells

Polyps can increase the risk of miscarriage in women undergoing IVF treatment

Although treatments such as hysterescopy usually cure the polyp concerned, recurrence of endometrial polyps is frequent

Untreated, small polyps may regress on their own

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