RECENT ADVANCES INFIBROID 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 LEIOMYOMA• These are benign tumours arising from the smooth muscle layer of theuterus, called the MYOMETRIUM• Can occur as Single or Multiple in number.• If occur as multiple fibroids and if the uteruscontains too many leiomyomata to count, it is referredto as DIFFUSE UTERINE LEIOMYOMATOSIS• The malignant version is extremely uncommon & termedas LEIOMYOSARCOMA. LEIOMYOSARCOMA
Fibroids are Monoclonal tumors and approximately 40 to 50%show karyotypically detectable chromosomal abnormalities. When multiple fibroids are present they frequently have unrelated geneticdefects. Specific mutations of the MED12 protein have been noted in 70 percent offibroids. Current working hypothesis is that Genetic Predispositions, Prenatal Hormoneexposure 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 theywill also cause growth restriction in some circumstances.Fibroids rarely grow during pregnancy despite very high steroid hormone levelsand pregnancy appears to exert a certain protective effect, partly due to interactionbetween estrogen & oxytocin receptor. Estrogen and Progesterone have a Mitogenic effect on leiomyoma cells & also actby influencing (directly and indirectly) a large number of growth factors, cytokinesand apoptotic factors as well as other hormones.
MEDICAL MANAGEMENT1.NSAID’s & HAEMATINICS for sympttomatic benefit.2.OCP’s to reduce uterine bleeding and cramps.3.LEVONORGESTREL IUD’s- highly effective in reducing bleeding & othersympttom 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, Oestrogenalone, 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 CERVIXASYMPTTOMATIC 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
SYMPTTOMATIC MEDICAL SURGICALINDICATIONS TREATMENT1.Symptomatic pt. Treat anaemia- Haematinics.2.Perimenopausal Fibrinolytics- Tranexemic acid.female Antiprogesterone- Mifepristone3.Women desiring ( RU 486)children & retaininguterus. Anti androgenic- Danazol.4.For correction of Gnrh agonist- Goserlin, Luporelinanemia before surgery. Naferelin, Buserelin.5.To decrease size & Gnrh antagonist- Cetrorelix, Ganirelix.vascularity of tumors. Pg synthetase inh- NSAID’s.
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) is a procedure where an interventionalradiologist uses a catheter to deliver small particles that block the blood supply tothe uterine body. If the procedure is done for the treatment of uterine fibroids, it is alsocalled Uterine Fibroid Embolization (UFE).(UFE) Under local anesthesia a catheter is introduced into the femoral artery at the groinand 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 botharteries are occluded. The procedure is not a surgical intervention and allows the uterus to be kept inplace, the patient being discharged after 24 hours.
Serious adverse effects are approximately four times less frequent thanfor hysterectomy. Adverse effects include- death from embolism, or septicemia (the presenceof pus-forming or other pathogenic organisms, or their toxins, in the blood ortissues) resulting in multiple organ failure. Infection from tissue death of fibroids, leading to endometritis (infection ofthe uterus) resulting in lengthy hospitalization.Misembolization from microspheres or polyvinyl alcohol (PVA) particlesflowing 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. R D A V E E E E T F F C S S R D A V E E E E T F F C S SLoss of ovarian function, infertility, and loss of orgasm.
Failure of embolization surgery- continued fibroid growth, regrowth within fourmonths.Menopause - iatrogenic, abnormal, cessation of menstruation and folliclestimulating hormones elevated to menopausal levels. Post-Embolization Syndrome (PES) - characterized by acute and/or chronicpain, temperatures of up to 102 degrees, malaise, nausea, vomiting and severe nightsweats. Foul vaginal odour coming from infected, necrotic tissue which remains inside theuterus.
Radiofrequency Ablation (RFA) has been extensively researched as atreatment option for uterine fibroids. A minimally invasive procedure that involves inserting a needle-like device intothe fibroid through the abdomen and heating it with low frequency electrical current. It is called as THE HALT’S METHOD. Its currently in phase-three clinical trials—the last phase & awaits approval foruterine fibroids.
• The Halt procedure involves three small incisions.•One is to insert the laparoscopic camera so the surgeon can see inside theabdomen.•Second is to insert an intra-abdominal ultrasound probe, which can determine thesize and location of fibroids.•Third incision is for the Halt Device, a needle electrode that penetrates the fibroidand burns the cells, which are eventually reabsorbed by the body. The device alsocauterizes the incision to minimize bleeding.•The procedure, which requires general anesthesia, can take several hoursdepending 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 centimeterand only six at a time. They are studying whether the procedure reduces heavy menstrual bleeding andimproves quality of life, not comparing it with other methods. Treatment within the trial is free to qualifying women. Subjects must be over 25years old and not interested in having more children. The next projected benefit is aimed at restoring the fertility of the females beingtreated under the same method.
Approved for use by the FDA in October 2004. Highly precise medical procedure that applies high-intensity focused sonicenergy 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 lightthrough a magnifying glassfocusing light rays to a point.
FOCUSSING OF RAYSThe ultrasound beam can be focused :1.Geometrically , for example with a lens or with a sphericallycurved transducer.2.Electronically , by adjusting the relative phases of elements in an arrayof 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 ultrasoundbeam due to tissue structures can be corrected.
An acoustic wave propagates through the tissue, part of it is absorbed and convertedto heat. With focused beams, a very small focus can be achieved deep in tissues (usually onthe order of millimeters, with the beam having a characteristic “cigar shape” in thefocal 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"
ADVANTAGES1) 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 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 managementof uterine fibroids.
As a SPRM, Ulipristal Acetate has partial agonistic as well as antagonistic effectson the progesterone receptor. It also binds to the glucocorticoid receptor, but has no relevant affinity to theestrogen, androgen and mineralocorticoid receptors. Phase II clinical trials suggest that the mechanism might consist of blocking ordelaying ovulation and of delaying the maturation of the endometrium.
An investigational Selective ProgesteroneReceptor Modulator (SPRM).In 2005, Phase III trials were discontinued dueto endometrial changes in patients.However, recent evidence states experimentaluse in treatment of fibroids has shown favorableresults.
Asoprisnil (10 and 25 mg daily for 3 months) has been studied in women withsymptomatic fibroids scheduled for hysterectomy. Uterine blood flow (determined by resistance index and pulsatility index) andvolumes of the largest fibroid and the uterus were assessed. The intensity and frequency of menstrual bleeding were recorded ona menstrual pictogram. The increased pulsatility index and the significantly increased resistance indexobserved indicated a decrease in uterine artery blood flow. Analysis of menstrual pictogram scores showed a significant decrease infrequency and intensity of bleeding compared with placebo.
ⱷ Even with all the available options, recurrence of sympttoms / pathology is notan 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 p14ArfGene.GeneThis drives a negative feedback loop between, p53 & MDM2 genes, whichgoverns the fate of each individual fibroid.ⱷ NUTLIN -3, a known MDM2 antagonist, was thus used to oppose theproliferative activity in cell cultures from fibroids.ⱷ Interestingly, antagonizing MDM-2, also stimulates Senescence Gene-p21 & Apoptosis Gene- BAX, in vitro.
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.
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%)