?? ??? ????? ???? ??? Uterine Leiomyomata

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?? ??? ????? ???? ???Uterine
Leiomyomata

• 
  DR_FIROUZABADI

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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.

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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 leiomyomata vary depending
  on the size, number, and location of the tumors.

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TABLE 55.1 Symptoms of
Leiomyomata

• MenorrhagiaDysmenorrheaPelvic pressure
  (pressure on adjacent pelvic viscera)   Urinary
  frequency   Constipation   DyspareuniaInfertil
  ityRepetitive pregnancy loss   First
  trimester   Second and third trimester (preterm
  labor)Abdominal Distension

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• 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.

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• 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 hospitalization and narcotics,
  but rarely puts a pregnancy at risk.

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Ph/E
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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.

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

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Types of leiomyoma
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• There is virtually no neovascularity within
  fibroids
• Collateral vascular channels are comparably
  maximally engorged and may represent a surgical
  challenge.

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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).

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• (d) often dramatically enlarge during pregnancy
  when estrogen and progesterone levels are very
  high.
• (e) can be made to shrink with medically induced
  hypogonadism.

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

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• 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.

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• oral contraceptives
• hormone replacement therapy
• Tamoxifen

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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

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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.

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Impact of Leiomyomata on ReproductionTABLE
55.2 Mechanisms of Infertility with Leiomyomata

• Impaired implantation   Submucous   Intracavita
  ry   Enlarged uterine cavity volumeImpaired
  tubal transport   Obstruction   Distension

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• 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.

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Diagnostic Studies

• The 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
  abdominal ultrasound 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.

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Diagnostic Imaging Techniques

• 1.Endovaginal ultrasonography2.Sonohysterography
  3.Hysterosalpingography4.Hysteroscopy5.Computeri
  zed tomography6.Magnetic resonance imaging

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Diagnostic Studies (contd)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.

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Diagnostic Studies (contd)

• 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.

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Diagnostic Studies (contd)

• 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.

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Diagnostic Studies (contd)

• 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.

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Diagnostic Studies (contd)

• 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.

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When to Treat

• Despite 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 synthetase
  inhibitor or oral contraceptives will adequately
  relieve the symptoms.

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When to Treat (contd)

• 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.

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When to Treat (contd)

• 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.

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When to Treat (contd)

• 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.

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When to Treat (contd)

• 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.

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When to Treat (contd)

• Because the bladder is adjacent to the uterus,
  the most frequent symptom associated with a large
  myomatous uterus is increased urinary frequency.
• 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.

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Selecting the Appropriate Therapy

• When 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.

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Selecting the Appropriate Therapy (contd)

• 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 .

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Selecting the Appropriate Therapy (contd)

• When the preservation of future childbearing is
  desired, a myomectomy is the primary choice.

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Extirpative Options

• Endoscopic techniques   Laparoscopically
  assisted supracervical hysterectomy   Laparoscopi
  cally assisted total hysterectomy   Laparoscopic
  myomectomy   Hysteroscopic resection of
  leiomyomataAbdominal approach   Supracervical
  hysterectomy   Total hysterectomy   MyomectomyV
  aginal approach   Hysterectomy   Myomectomy  

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Hysterectomy

• When
• 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.

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Hysteroscopic Myomectomy

• Most intracavitary leiomyomata and a substantial
  number of submucous leiomyomata can be resected
  via surgical hysteroscopy in an ambulatory
  setting.

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Abdominal Myomectomy

• When symptomatic leiomyomata are not amenable to
  a hysteroscopic approach, an abdominal approach
  usually is required.

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Abdominal Myomectomy (contd)

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

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Minimally Invasive Myomectomy

• Pedunculated, serosal, and selected intramural
  leiomyomas can be dissected free from the
  surrounding myometrium, morcellated, and the
  incision closed via laparoscopy.

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Recurrence of Leiomyomata

• Since 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 removed
• The length of follow-up.

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Recurrence of Leiomyomata (contd)

• Indeed, between 10 and 25 of women undergoing
  myomectomies require another surgical procedure
  within the next decade.

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Recurrence of Leiomyomata (contd)

• Isolated large fibroids have lower recurrence
  rates than when multiple small tumors are
  present, despite an overall smaller volume of
  leiomyomata .

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Postoperative Pelvic Adhesions

• The 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.

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Non-extirpative Options

• Myolysis   UAE   MRI-guided HIFUMedically
  induced hypogonadism   GnRH agonist   GnRH
  agonist with add-back? therapy

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Medical Suppression

• Many 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.

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Medical Suppression (contd)

• 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.

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Medical Suppression (contd)

• 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 vaginal bleeding
  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.

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Myolysis

• There 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.

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Myolysis (contd)

• The aseptic necrosis may cause significant pain
  in the immediate post-treatment interval,
  comparable to that observed with degeneration of
  leiomyomata seen in pregnancy.

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Myolysis (contd)

• Myolysis should be confined to those women who
  are not interested in subsequent pregnancy until
  well-designed, long-term comparative trials
  demonstrate safety.

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Uterine Artery Embolization

• When 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 .

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UAE (contd)

• 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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Thanks for your nice attention
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Adenomyosis
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Definition

• A 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.

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Four primary theories

• Heredity
• Trauma
• Hyperestrogenemia
• Viral 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.

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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 adenomyosis patients in comparison
  to normal people

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Clinical features1

• Asymptomatic
• Classic symptoms
• secondary dysmenorrhea
• abnormal 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.

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Endometrial 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

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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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Thanks