1. RECENT ADVANCES
IN
FIBROID MANAGEMENT
BY-
Prof. M.C.Bansal
MBBS., MS., FICOG., MICOG.
Founder Principal & Controller,
Jhalawar Medical College & Hospital Jjalawar.
MGMC & Hospital , sitapura ., Jaipur
2. • Also referred to as LEIOMYOMA
• These are benign tumours arising from the smooth muscle layer of the
uterus, called the MYOMETRIUM
• Can occur as Single or Multiple in number.
• If occur as multiple fibroids and if the uterus
contains too many leiomyomata to count, it is referred
to as DIFFUSE UTERINE LEIOMYOMATOSIS
• The malignant version is extremely uncommon & termed
as LEIOMYOSARCOMA.
LEIOMYOSARCOMA
4. Fibroids are Monoclonal tumors and approximately 40 to 50%
show karyotypically detectable chromosomal abnormalities.
When multiple fibroids are present they frequently have unrelated genetic
defects.
Specific mutations of the MED12 protein have been noted in 70 percent of
fibroids.
Current working hypothesis is that Genetic Predispositions, Prenatal Hormone
exposure and the effects of Hormones, Growth factors and Xenoestrogens cause
fibroid growth.
Known risk factors include- African American descent,
PCOS, Diabetes, Hypertension, Nulliparity, Obesity.
5. Fibroid growth is strongly dependent on Estrogen and Progesterone.
Both estrogen and progesterone are usually regarded as growth-promoting they
will also cause growth restriction in some circumstances.
Fibroids rarely grow during pregnancy despite very high steroid hormone levels
and pregnancy appears to exert a certain protective effect, partly due to interaction
between estrogen & oxytocin receptor.
Estrogen and Progesterone have a Mitogenic effect on leiomyoma cells & also act
by influencing (directly and indirectly) a large number of growth factors, cytokines
and apoptotic factors as well as other hormones.
6. MEDICAL MANAGEMENT
1.NSAID’s & HAEMATINICS for sympttomatic benefit.
2.OCP’s to reduce uterine bleeding and cramps.
3.LEVONORGESTREL IUD’s- highly effective in reducing bleeding & other
sympttom reduction.
4.DANAZOL (Anti Androgen)- effective use in shrinkage of fibroids. However,
use limited in lieu of side effects.
Temporary reduction by opposing estrogen.
5. Add Back Regime with Tibolone, Raloxifen, Progsterones alone, Oestrogen
alone, Combined oestrogen & pregesterone.
7. 7. PROGESTERONE ANTAGONIST (Mifepristone)
Effective in reducing size in control pilot studies.
Long term safety however, remains yet to be established.
8. MANAGEMENT
BODY CERVIX
ASYMPTTOMATIC SYMPTTOMATIC
Size <12 weeks. MEDICAL SURGICAL
Size >12 weeks.
Diagnosis certain.
Diagnosis uncertain.
Unexplained infertility.
REGULAR H/o abortion.
SUPERVISION Pedunculated
SURGERY
Size increases. oSize stationary.
Symptoms appear. oSymptom less.
SURGERY FOLLOW UP
9. SYMPTTOMATIC
MEDICAL SURGICAL
INDICATIONS TREATMENT
1.Symptomatic pt. Treat anaemia- Haematinics.
2.Perimenopausal Fibrinolytics- Tranexemic acid.
female
Antiprogesterone- Mifepristone
3.Women desiring ( RU 486)
children & retaining
uterus. Anti androgenic- Danazol.
4.For correction of Gnrh agonist- Goserlin, Luporelin
anemia before surgery. Naferelin, Buserelin.
5.To decrease size & Gnrh antagonist- Cetrorelix, Ganirelix.
vascularity of tumors. Pg synthetase inh- NSAID’s.
12. SURGICAL MANAGEMENT
a)MYOMECTOMY- best for infertility patients.
b)HYSTERECTOMY.
c)MYOLYSIS.
d)LAPROTOMY.
e)MORCELISATION AND REMOVAL BY PIECE-MEAL TECHNIQUE.
13.
14.
15.
16. Uterine Artery Embolization (UAE) is a procedure where an interventional
radiologist uses a catheter to deliver small particles that block the blood supply to
the uterine body.
If the procedure is done for the treatment of uterine fibroids, it is also
called Uterine Fibroid Embolization (UFE).(UFE)
Under local anesthesia a catheter is introduced into the femoral artery at the groin
and advanced under radiographic control into the uterine artery.
There microparticules (spheres or beads) are released which will block the vessel.
Due to collateral circulation the uterus will not necrose even if both
arteries are occluded.
The procedure is not a surgical intervention and allows the uterus to be kept in
place, the patient being discharged after 24 hours.
17. Serious adverse effects are approximately four times less frequent than
for hysterectomy.
Adverse effects include- death from embolism, or septicemia (the presence
of pus-forming or other pathogenic organisms, or their toxins, in the blood or
tissues) resulting in multiple organ failure.
Infection from tissue death of fibroids, leading to endometritis (infection of
the uterus) resulting in lengthy hospitalization.
Misembolization from microspheres or polyvinyl alcohol (PVA) particles
flowing or drifting into organs or tissues where they were not intended to be,
causing damage to other organs or other parts of the body.
Ovarian damage resulting from embolic material migrating to the ovaries.
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Loss of ovarian function, infertility, and loss of orgasm.
18. Failure of embolization surgery- continued fibroid growth, regrowth within four
months.
Menopause - iatrogenic, abnormal, cessation of menstruation and follicle
stimulating hormones elevated to menopausal levels.
Post-Embolization Syndrome (PES) - characterized by acute and/or chronic
pain, temperatures of up to 102 degrees, malaise, nausea, vomiting and severe night
sweats.
Foul vaginal odour coming from infected, necrotic tissue which remains inside the
uterus.
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20.
21.
22.
23. Radiofrequency Ablation (RFA) has been extensively researched as a
treatment option for uterine fibroids.
A minimally invasive procedure that involves inserting a needle-like device into
the fibroid through the abdomen and heating it with low frequency electrical current.
It is called as THE HALT’S METHOD.
It's currently in phase-three clinical trials—the last phase & awaits approval for
uterine fibroids.
25. • The Halt procedure involves three small incisions.
•One is to insert the laparoscopic camera so the surgeon can see inside the
abdomen.
•Second is to insert an intra-abdominal ultrasound probe, which can determine the
size and location of fibroids.
•Third incision is for the Halt Device, a needle electrode that penetrates the fibroid
and burns the cells, which are eventually reabsorbed by the body. The device also
cauterizes the incision to minimize bleeding.
•The procedure, which requires general anesthesia, can take several hours
depending on how many fibroids are found. But patients can go home the same day.
• Potential downsides are similar to other minimally invasive surgeries
26. In the current trial, investigators are ablating fibroids larger than one centimeter
and only six at a time.
They are studying whether the procedure reduces heavy menstrual bleeding and
improves quality of life, not comparing it with other methods.
Treatment within the trial is free to qualifying women. Subjects must be over 25
years old and not interested in having more children.
The next projected benefit is aimed at restoring the fertility of the females being
treated under the same method.
27. Approved for use by the FDA in October 2004.
Highly precise medical procedure that applies high-intensity focused sonic
energy to locally heat & destroy the diseased/damaged tissue, via ablation.
Ultrasound can be focused,
either via a Lens (polystyrene lens),
a Curved Transducer,
or a Phased Array,
or Any Combination Of The Three,
into a small focal zone,
in a similar way to focusing light
through a magnifying glass
focusing light rays to a point.
28. FOCUSSING OF RAYS
The ultrasound beam can be focused :
1.Geometrically , for example with a lens or with a spherically
curved transducer.
2.Electronically , by adjusting the relative phases of elements in an array
of transducers (a "phased array").
By dynamically adjusting the electronic signals to the elements of a phased array,
the beam can be steered to different locations, and aberrations in the ultrasound
beam due to tissue structures can be corrected.
29. An acoustic wave propagates through the tissue, part of it is absorbed and converted
to heat.
With focused beams, a very small focus can be achieved deep in tissues (usually on
the order of millimeters, with the beam having a characteristic “cigar shape” in the
focal zone, where the beam is longer than it is wide along the transducer axis)
Tissue damage occurs as a function of both :-
a) the temperature to which the tissue is heated
b) how long the tissue is exposed to this heat level in a metric referred to as
"thermal dose".
dose"
30.
31. ADVANTAGES
1) No Scar.
2) Can be done as a day procedure.
3) Short hospital stay.
4) Least chances of infection, other post-op complications.
5) Early resuming of daily activities.
6) Interferes least with everyday life of the women.
7) Can be done in multiple sittings for a large sized fibroid.
8) Repeating the procedure has lowest risks, as compared to
surgical options.
32. Selective Progesterone Receptor Modulator (SPRM)
for emergency contraception within 120 hours
(5 days) after an unprotected intercourse or
contraceptive failure.
Ulipristal acetate is available by prescription only
in the U.S. and Europe, but without a prescription
in India.
Mounting evidence suggests that Ulipristal Acetate may be useful in the management
of uterine fibroids.
33. As a SPRM, Ulipristal Acetate has partial agonistic as well as antagonistic effects
on the progesterone receptor.
It also binds to the glucocorticoid receptor, but has no relevant affinity to the
estrogen, androgen and mineralocorticoid receptors.
Phase II clinical trials suggest that the mechanism might consist of blocking or
delaying ovulation and of delaying the maturation of the endometrium.
34. An investigational Selective Progesterone
Receptor Modulator (SPRM).
In 2005, Phase III trials were discontinued due
to endometrial changes in patients.
However, recent evidence states experimental
use in treatment of fibroids has shown favorable
results.
35. Asoprisnil (10 and 25 mg daily for 3 months) has been studied in women with
symptomatic fibroids scheduled for hysterectomy.
Uterine blood flow (determined by resistance index and pulsatility index) and
volumes of the largest fibroid and the uterus were assessed.
The intensity and frequency of menstrual bleeding were recorded on
a menstrual pictogram.
The increased pulsatility index and the significantly increased resistance index
observed indicated a decrease in uterine artery blood flow.
Analysis of menstrual pictogram scores showed a significant decrease in
frequency and intensity of bleeding compared with placebo.
36. ⱷ Even with all the available options, recurrence of sympttoms / pathology is not
an uncommon finding.
ⱷ Thus, permanent reduction of the fibroid is an upscale challenge.
ⱷ Recent evidence suggests that, fibroids develop as an over expression of p14Arf
Gene.
Gene
This drives a negative feedback loop between, p53 & MDM2 genes, which
governs the fate of each individual fibroid.
ⱷ NUTLIN -3, a known MDM2 antagonist, was thus used to oppose the
proliferative activity in cell cultures from fibroids.
ⱷ Interestingly, antagonizing MDM-2, also stimulates Senescence Gene-
p21 & Apoptosis Gene- BAX, in vitro.
37. A. Randomised clinical ‘EMMY’ (EMbolisation versus HysterectoMY) multi-centre
control trial prospectively looked at health-related quality of life outcomes for
hysterectomy and UAE at intervals up to 24 months, with regards to mental and
physical health, urinary function, and overall patient satisfaction.
The only significant difference between the groups was that patients who
underwent hysterectomy were more satisfied with the received treatment than
women who underwent UAE.
38. B. ‘HOPEFUL’ (Hysterectomy Or Percutaneous Embolisation For Uterine
Leiomyomata),
Leiomyomata)
retrospective multi-centre cohort study, assessed the treatment of symptomatic
uterine fibroids with either hysterectomy or UAE and compared efficacy, safety,
and cost-effectiveness.
Complications and cost were less in the UAE group, even when retreatment
(with uterine preservation) was taken into consideration.
Women undergoing UAE (compared to hysterectomy for symptomatic uterine
fibroids in a randomised trial) have been reported to have a faster recovery time
but were at risk of treatment failure in 9-20% of cases.
Ovarian reserve may be affected by both hysterectomy and UAE.
Although permanent loss of ovarian function after UAE usually affects those aged
over 45, there may be impaired ovarian function in younger patients.
A recent prospective observational study evaluating long-term efficacy and
complications of UAE after 5-7 years has shown that this is a beneficial treatment
for women wishing to avoid hysterectomy (satisfaction rate of 88%)
