fibroid recent advances in management. pdf

Recent advances in management of leiomyomas

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LEIOMYOMA Also referred to as LEIOMYOMA

These are benign tumours arising from the smooth muscle layer of the uterus, called
the MYOMETRIUM

SingleMultiple 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
DIFFUSE UTERINE LEIOMYOMATOSISto as  DIFFUSE UTERINE LEIOMYOMATOSIS

The malignant version is extremely uncommon & termed
LEIOMYOSARCOMAas LEIOMYOSARCOMA.

2. TYPES OF
FIBROIDS
PEDUNCULATED

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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.

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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.

5. conventional
management
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MEDICAL MANAGEMENT

NSAID’s & HAEMATINICS for sympttomatic benefit.

OCP’s to reduce uterine bleeding and cramps.

LEVONORGESTREL IUD’s- highly effective in reducing bleeding & other
sympttom reduction.

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.

6. 7.PROGESTERONE ANTAGONIST (Mifepristone)
Effective in reducing size in control pilot studies.
Long term safety however, remains yet to be established.

7. MANAGEMENT
BODY CERVIX
ASYMPTTOMATIC
SYMPTTOMATIC
MEDICAL SURGICAL
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Size <12 weeks.
Diagnosis certain.
REGULAR
SUPERVISION
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Size >12 weeks.
Diagnosis uncertain.
Unexplained infertility.
H/o abortion.
Pedunculated
SURGERY
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Size increases.
Symptoms appear.
o
o
Size stationary.
Symptom less.
SURGERYSURGERY
FOLLOW UPFOLLOW UP

8. SYMPTTOMATIC
MEDICAL SURGICAL
INDICATIONS

1.Symptomatic pt.

2.Perimenopausal female

3.Women desiring
children & retaining uterus.

4.For correction of
anemia before surgery.

5.To decrease size &
vascularity of tumors.

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TREATMENT

Treat anaemia- Haematinics.

Fibrinolytics- Tranexemic acid.

Antiprogesterone- Mifepristone
( RU 486)

Anti androgenic- Danazol.

Gnrh agonist- Goserlin, Luporelin
Naferelin, Buserelin.

Gnrh antagonist- Cetrorelix, Ganirelix.
Pg synthetase inh- NSAID’s.
Progesterone releasing IUD.

9. SURGICAL OPTIONS
MYOMECTOMYMYOMECTOMY
HYSTERECTOMYHYSTERECTOMY
MYOLYSISMYOLYSIS
EMBOLOTHERAPYEMBOLOTHERAPY
ENDOSCOPY
LAPAROTOMY
LAPROSCOPIC
MYOMECTOMY
HYSTEROSCOPIC
RESECTION OF
SUBMUCOUS MYOMA
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2.
3.
Electrocautery

Laser.

Cryo

10. CERVICAL FIBROIDCERVICAL FIBROID
SUPRAVAGINAL
VAGINAL
MYOMECTOMY
HYSTERECTOMY
MYOMECTOMY
POLYPECTOMY

11. a)
b)
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d)
e)
SURGICAL MANAGEMENT

MYOMECTOMY- best for infertility patients.

HYSTERECTOMY.

MYOLYSIS.

LAPROTOMY.

MORCELISATION AND REMOVAL BY PIECE-MEAL TECHNIQUE.

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Uterine Artery Embolization (UAE)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.

Uterine Fibroid Embolization (UFE)
If the procedure is done for the treatment of uterine fibroids, it is also called 
Uterine Fibroid Embolization (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.
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.

16. ADVERSE EF
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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.

Loss of ovarian function, infertility, and loss of orgasm.

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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) 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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Radiofrequency Ablation (RFA) 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.

THE HALT’S METHOD. It is called as THE HALT’S METHOD.
 
It's currently in phase-three clinical trials—the last phase & awaits approval for
uterine fibroids.

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three small incisions. 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

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larger than one centimeter
and only six at a time.
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.

24. MRI GUIDED MRI GUIDED
FOCUSSED ULTRASOUNDFOCUSSED ULTRASOUND
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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,
Lenseither via a Lens (polystyrene lens),

Curved Transducer,a Curved Transducer,

Phased Array,or a Phased Array,

Any Combination Of The Three,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.

25. 1.
2.
FOCUSSING OF RAYSFOCUSSING OF RAYS

The ultrasound beam can be focused :

Geometrically , for example with a lens or with a spherically curved transducer.

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.

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An acoustic wave propagates through the tissue, part of it is absorbed and
converted to heat.

“cigar shape”
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

"thermal dose"
b) how long the tissue is exposed to this heat level in a metric referred to as
"thermal dose".

28. ADVANTAGESADVANTAGES

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No Scar.

Can be done as a day procedure.

Short hospital stay.

Least chances of infection, other post-op complications.

Early resuming of daily activities.

Interferes least with everyday life of the women.

Can be done in multiple sittings for a large sized fibroid.

Repeating the procedure has lowest risks, as compared to
surgical options.

29. ULIPRISTAL ACETATEULIPRISTAL ACETATEULIPRISTAL ACETATEULIPRISTAL ACETATE
Selective Progesterone Receptor Modulator (SPRM)
for emergency contraception within 120 hours
Selective Progesterone Receptor Modulator (SPRM)
for emergency contraception within 120 hours
(5 days) after an unprotected intercourse or
contraceptive failure.
(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.

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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.

31. ASOPRISNILASOPRISNIL
An investigational Selective Progesterone
Receptor Modulator (SPRM).
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.

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(10 and 25 mg daily for 3 months) 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 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.

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Even with all the available options, recurrence of sympttoms / pathology is not
an uncommon finding.

Thus, permanent reduction of the fibroid is an upscale challenge.

p14
Arf
Gene
Recent evidence suggests that, fibroids develop as an over expression of p14
Arf
Gene.
p53MDM2This drives a negative feedback loop between, p53 & MDM2 genes, which governs
the fate of each individual fibroid.

NUTLIN -3, a known MDM2 antagonist, was thus used to oppose the
proliferative activity in cell cultures from fibroids.
NUTLIN -3, a known MDM2 antagonist, was thus used to oppose the
proliferative activity in cell cultures from fibroids.

Interestingly, antagonizing MDM-2, also stimulates Senescence Gene- p21 &
Apoptosis Gene- BAX, in vitro.
Interestingly, antagonizing MDM-2, also stimulates Senescence Gene- p21 &
Apoptosis Gene- BAX, in vitro.

34. INTERESTING FACTSINTERESTING FACTS
INTERESTING FACTSINTERESTING FACTS
‘EMMY’ (EMbolisation versus HysterectoMY)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.

35. B.‘HOPEFUL’ (Hysterectomy Or Percutaneous Embolisation For Uterine
Leiomyomata)
‘HOPEFUL’ (Hysterectomy Or Percutaneous Embolisation For Uterine
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%)