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

• Also referred to as LEIOMYOMALEIOMYOMA

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

• Can occur as SingleSingle or MultipleMultiple in number.

• If occur as multiple fibroids and if the uterus contains too many leiomyomata to count, it is referred to as  DIFFUSE UTERINE LEIOMYOMATOSISDIFFUSE UTERINE LEIOMYOMATOSIS

• The malignant version is extremely uncommon & termed as LEIOMYOSARCOMALEIOMYOSARCOMA.

TYPES OF FIBROIDS

PEDUNCULATED

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.

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.

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

MANAGEMENT

BODY CERVIX

ASYMPTTOMATIC SYMPTTOMATIC

MEDICAL SURGICAL Size <12 weeks.Diagnosis certain.

REGULAR SUPERVISION

Size >12 weeks.Diagnosis uncertain.Unexplained infertility.H/o abortion.Pedunculated

SURGERY

Size increases.Symptoms appear.

oSize stationary.oSymptom less.

SURGERYSURGERY FOLLOW UPFOLLOW UP

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.

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.

SURGICAL OPTIONS

MYOMECTOMYMYOMECTOMY HYSTERECTOMYHYSTERECTOMYMYOLYSISMYOLYSIS EMBOLOTHERAPYEMBOLOTHERAPY

ENDOSCOPY

LAPAROTOMY

LAPROSCOPIC MYOMECTOMY

HYSTEROSCOPIC RESECTION OF SUBMUCOUS MYOMA

1. Electrocautery

2. Laser.

3. Cryo

CERVICAL FIBROIDCERVICAL FIBROID

SUPRAVAGINALVAGINAL

MYOMECTOMY

HYSTERECTOMY

MYOMECTOMY

POLYPECTOMY

SURGICAL MANAGEMENTa)MYOMECTOMY- best for infertility patients.

b)HYSTERECTOMY.

c)MYOLYSIS.

d)LAPROTOMY.

e)MORCELISATION AND REMOVAL BY PIECE-MEAL TECHNIQUE.

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.

If the procedure is done for the treatment of uterine fibroids, it is also called Uterine Fibroid Embolization (UFE)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 Due to collateral circulation the uterus will not necrose even if both arteries are occluded.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.

ADVERSE EFFECTS ADVERSE EFFECTS 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.

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.

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.

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

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• The Halt procedure involves three small incisions.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

In the current trial, investigators are ablating fibroids larger than one larger than one centimeter and only six at a time. 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.

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 LensLens (polystyrene lens),

a Curved TransducerCurved Transducer,,

or a Phased ArrayPhased Array,,

or Any Combination Of The ThreeAny 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.

FOCUSSING OF RAYSFOCUSSING OF RAYSThe 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.

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”“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""thermal dose".

ADVANTAGESADVANTAGES1) 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.

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

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.

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

Asoprisnil (10 and 25 mg daily for 3 months)(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 The intensity and frequency of menstrual bleeding were recorded on a menstrual pictogram.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.

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 p14p14ArfArf Gene Gene.This drives a negative feedback loop between, p53p53 & MDM2MDM2 genes, which governs the fate of each individual fibroid.

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

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

A. Randomised clinical ‘EMMY’ (EMbolisation versus HysterectoMY)‘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.

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