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Leiomyomas (Pathogenesis (hormonal theory (are hormonal –dependent tumours…
Leiomyomas
Pathogenesis
hormonal theory
- are hormonal –dependent tumours – oestrogen dependent , less progesterone dependent
(high concentration of estrogens = increased risk of myoma development)
(longer influence of estrogens = increased risk of myoma development)
- regression of myomas after GnRH drugs, after the menopause (despite HRT)
- more frequently in women having menstrual periods for a long
-
inflammatory theory
- Cytokines:
factors stimulating development:
induction of IGF 1 through ER alfa; VEGF expression IL- 8, R IL–8 in uterine myomas and surrounding tissue
- FGF, TGF - beta, GM – CSF
genetic theory
- aberrations in chromosoms 6,7,12,14- 40 % myomas
- heterogeneity of cytogenetic anomalies
- disorder in regulation of some genes HMG (high mobility protein): HMGA2, HMGA1
- Two distinct components to myoma development:
I.Transformation of normal myocyte into an abnormal
II.Growth of abnormal myocytes and creation of a tumor (clonal growth)
Malignant transformation- different way of development
Classification
Myomas
- single
- numerous - more frequent (uteus myomatosus)
Localisation
- primarily the development is intramural
- subserous – 50 %
- intramural – 30 %
- submucosus - 14 %
- uterine corpus > 90 %- cervix - 4 – 7 % - round ligament
-
Myoma nascens
- Submucosal myomas that can become pedunculated into the uterine cavity; may dilate the cervical canal and reach the vagina
- accompanied by abdominal pain that imitates contractions during labor and by abnormal bleeding
Symptoms
- Usually asymptomatic
- In 20-24 % women life-threatening symptoms or symptoms that decrease quality of life
- The intensity of symptoms and complains depend on: localisation of the tumors, size, number, intensity of growth, retrogressive changes in the myomas, coexistence of an infection
- in 30 % women. classified in 3 distinct categories:
-Abnormal uterine bleeding
menorrhagia, menometrorrhagia, metrorrhagia;
depend from the localisation of the tumours (submucosal)
+/- sec. anaemia concerns 1/3 – 1/2 patients
-reproductive dissorders ( fertility - ?; pathology of the time of pregnancy – pain, premature birth, premature detachment of the placenta; labour)
- Pelvic pressure and pain
mechanic pressure of the large uterus on the surrounding organs
urinary bladder (urinary symptoms like polyuria, incontinence)
urethra (incapability of miction)
ureter (obstruction – hydronephrosis)
intestine (ileus – very rare)
- Pain:
dysmenorrhoea, painful sexual intercourse – rare, acute pain that accompanies the torsion of a pedunculated myoma, as a result of pressure
- Other:
intraperitoneal bleeding – rare
infection – m. submucosal, m. nascens
Change in the shape of the abdominal wall
Treatment
surgery
- decision of the best procedure depends on:
age of the patient, preserving fertility, general state and co morbidities, number and localisation of the myomas, will of the patient
indications
- symptomatic myomas
- asymptomatic when their summed volume is comparable to an at least 12 –14 week pregnancy
- fast growth of myomas, or growth after the menopause
- submucosal
- causing infertility
- observed to grow intensively during HRT
- asymptomatic but giving big psychical discomfort
laparotomy
- TAH (total abdominal histerectomy) &/without BSO (bilateral salpingoooforectomy)
- Supracervical amputation of the uterine corpus &/without BSO
- Myomectomy
endoscopic (hysteroscopy, laparoscopy)
- Hysterectomy &/without BSO
- Supracervical amputation of the uterine corpus &/without BSO
- myomectomy
Vaginal surgery
- Myomectomy - pedunculated and submucosal myomas
- Vaginal hysterectomy &/without BSO
-
Small surgery technics
-
- Closing uterine arteries
transvaginal, in POP
- Laparoscopic coagulation of the uterine arteries
- Myolysis – electric, laser and cryotherapy
- FUS (focus ultrasound system)
hyperthermia in the tumour, necrosis
- Presurgical treatment (enable to use less invasive techniques)
Hormonal treatment
- GnRH Analogs (goserelin) agonistic – antagonistic.
Reduction of total volume of fibroids and uterine size after 6 months of treatment approximately 50% (30 - 70%), in selected cases
Side effects: vaginal dryness, hot flushes, excessive sweating, abnormal uterine bleeding, decreased bone mass, emotional lability, depression, lower libido, nausea, joint pain, headache
- Selective modulators - ER (Raloxifen)
antagonism against ER in uterus, antiproliferative effect, boosting apoptosis in myocytes, PR - antiproliferative effect, induction of apoptosis
- Ulipristal acetate (Esmya) selective modulator of progesterone receptor
indicated for the preoperative treatment of uterine fibroids in adult women in reproductive age
Reduction of fibroids volume (inhibition of cell proliferation and induction of apoptosis) after two 3-month cycles is approximately 50%
Myomas and pregnancy
- About 3% women with myomas have difficulties with fertility (over 2 years)
- Myomas in fertility:
primary infertility (submucosal – chronic inflammations, disturbances in endometrial transformation, mechanical blockade of the Fallopian tubes, abnormal vascularization of the myometrium,.increased contraction of the uterus)
ectopic pregnancy
miscarriage
- Abnormalities during pregnancy
bleeding, IUGR, premature birth, PROM
premature detachment of placenta
- Abnormalities during labour:
abnormal contraction of the uterus, inhibited progress of the labour – myoma as a barrier, abnormal contraction of the uterus after labour
- Complications in 10 – 30% pregnancies
- High risk pregnancy – special attention!
- There are many controversies concerning how myomas act during pregnancy
- Clinical observations – myomas may grow during pregnancy (8 -10 % cases)
- Growth of myomas is probably caused by the synergistic effect of E and hPL
treatment
the decision on operating a myoma in a pregnant uterus depends on the age of the pregnancy, localisation and diameter of the myomas, risk of restricted foetal development, defining if the myoma may be a barrier during labour,
Factors
-
reduce the risk
Multiparity, Early menopause, OC, Smoking, Green vegetables
aetiology
- not fully known
- monoclonal growth of smooth muscle cell smooth
muslce cell = myoblast or myometrial vessel wall cell
Atypical leiomyoma
- Smooth muscle tumor of uncertain malignant potential (STUMP)
- always requires differentiation with leiomyoma and smooth muscle sarcoma
- Multiform, atypical neoplastic cells with low mitotic activity and absence of thrombotic necrosis in the tumor-STUMP
- originate from smooth muscle cells
- Symptoms like in the "classic" uterine fibroids
- very rarely
Diagnosis
- Initial – interview, physical examination (gynecological examination – manual and with speculum– m. nascens), radiologic examinations (USG – TV, USG –TA , MRI, TK, histeroscopy, sonohisterography)
- Final – postoperative histopathological examination only
- We do not perform biopsy of fibroids
Differentiation
- Ovarian, Intestine tumours, Pregnancy, Abscessus of the pelvis, Sarcoma (pathological examination), Internal endometriosis (adenomyosis of the uterus), Endometrial polyp
- Most common benign utrine tumors in women of reproducive age, arising from the uterine corpus
- Occuring in 25-40% of women in reproductive age
- Usually diagnosed between 30-40 years of age
- In Afro-american commonly
- Well limited, solid tumors; diameter up to 15 cm or more; growing slowly
- Pseudocapsule
- frequently coexisting components of leiomyoma and fibroma
- Pathological examination – growth of myocytes (leiomyoma cellulare, leiomyoma epithelioides…)
-