Prof. M.C.Bansal MBBS,MS,MICOG,FICOG Professor OBGY Ex-Principal & ControllerJhalawar Medical College & Hospital Mahatma Gandhi Medical College, Jaipur.
Introduction Fibroids(Myoma, Leiomyoma,Fibromyoma) 5-20% women in their reporductive age are reported to have fiboroids. Most common Monoclonal Benign tumors of uterus arising in the smooth muscle cells of myometrium. Contain large aggregation of extracellular matrix consisting of collagen, elastin, fibronectin and proteoglycan. Each fibroid is derived from smooth muscle cells rests ,either from vessel wall or uterine musculature
Incidence Most common----77% specimen of hysterectomy were having Fibroids invariable number ,size (micro-macro) and site. Sonographic survey in35-49yrs aged Africo- American women reported Fibroids in 60% while about 80% among the women > 50 yrs. of age. White women have lower prevalence---40%at age 35 and almost 70% by age 50.
etiology Precise cause of Fibroids is not known. Advances have been made in understanding the molecular biology of these benign tumors and there dependence on genetic, hormonal and growth factors . (A) Genetic Fibroids are monoclonal and about 40% have chromosomal abnormalities that include-(a) translocations between chromosomes 12 and14.(b) deletions of chromosome 7(c) Trisomy of chromosome 12 in large tumors. 60% may have yet undetected mutations
Etiology Genetic more than 100 genes were found to be up- down regulated in fibroid cells. Many of them appear to regulate cell growth, proliferation, differentiation and mitogenesis. Genetic differences between fibroid and Leiomyosarcomas indicate that Leiomyosarcomas do not result due to malignant changes in fibroids .
Etiology (B) Hormones - Both increase in number and responsiveness of receptors for estrogen and progesterone appear to promote fibroid growth, as these are rarely found before puberty, develop and increase during reproductive period of life and so also during pregnancy, regress after menopause/ bilateral oophorectomy. Found more with hyper estrogenic states like obesity, increases after ERT therapy in menopausal women, endometriosis, Cancer endometrium, an ovulatory infertility and early menarche. Decreased incidence are found in athletes with low body mass, increased parity. estrogen induces increased expression of progesterone receptors thus promoting oncogenic effect of progesterone.
Etiology Hormones Progesterone is most important in pathogenesis of fibroids, which have more concentration of receptors A & B as compared to normal myometrium. Highest mitotic counts are found in fibroid cells when progesterone concentration is also high. GnRH agonist decrease the size of fibroid. Concurrent Progesterone and GnRH therapy prevent regression in size of fibroid. Anti progesterone RU486 reduces the growth of fibroids. Estrogen dependent- never develop before puberty, regress after menopause, newer tumor seldom develop after menopause,
Etiology(C) Growth Factor Growth factors, proteins polypeptides produced locally by smooth muscle cells and fibroblasts appear to promote growth of fibroids primarily by increasing extracellular matrix. Many growth factors are participating in proliferation and growth of cells of fibroid Tumor Growth Factor-Beta, Basic- Fibroblast Growth Factor,increased DNA synthesis, Epidermal Growth factor, Platelet Derived Growth Factor, Insulin like growth factor, PRL,Vascular endothelial factor etc
PathologyGross +A typical myoma is a well circumscribed tumor with a pseudo-capsule. Cut surface is pinkish white and has a whorled appearance.+Capsule consists of connective tissue which fixes tumor withmyometrium.+Vessels that supply Blood to tumor lie in capsule and send radialbranch to tumor Hence central part of tumor is comparatively lessvascular ,thereby degenerative changes are noticeable in center.Calcification at the periphery and spreads inwards along thevessels(Tombstone).Microscopic Tumor consists of bundles of plane cells, separatedby varying amount of fibrous strands . Areas of embryonic muscletissue may be present.
Risk Factors Age – incidence increases with age till on set of menopause. Endogenous Hormonal factors Early menarche ,late menopause, hyper-estrogenic states & increased expression and responsiveness of progesterone receptors A & B. Family History—1st degree relatives are having 3.5 times more risk of developing fibroids. Ethnicity—Black women develop fibroids 2.9 times more than white women. Body weight—risk of fibroid increase by 21% with each 10 kg increase in body weight. Increase bioavailable estrogen explains it well. Diet—diet rich in red meat, ham, beef increase the risk of fibroids while diet with green leafy vegetables decrease the risk.
Risk Factors Exercise – women doing regular exercise (7hrs per week) are at low risk than those who do not do exercise. OCS --- no definite relationship. ERT—variable reports—no increase, minimal increase, more increase when progesterones were added. Pregnancy—pre-existing fibroids may enlarge, undergo red degeneration. Increased parity is associated with lower incidence of fibroid. Smoking---decreases by decreased conversion of androgen to estrone caused by inhibition of aromatase enzyme by nicotine, increased 2- hydroxylation of estradiol, increased level of serum sex hormone binding Globulins. Tissue injury—may increase the incidence probably by increasing local production of tissue growth factors--?
Symptoms Asymptomatic Fibroid size<4cm / uterine size <12 cm(50%) Abnormal uterine bleeding menorrhagia > 64% woman present with heavy blood loss in gushes needing more pads or tampons on the day of heaviest blood loss. Metro menorrhagia present in cases of infected / ulcerated fibroid polyp. Infertility Pain Dysmenorrhoea., slight discomfort to colicky pain in suprapubic region, low backache. Degenerated / torsion of fibroid may cause Acute abdomen /pelvic pain. Urinary symptoms Increased uterine volume due to fibroids may cause pressure and obstructive effect on urinary tract (frequency, nocturia, urgency, uti ) Secondary symptoms progressive anaemia due to chronic blood loss -- CHF, ill-health, loss of appetite and work capacity. Some patients rarely develop polycythemia due to erythropoiten production. Abdominal Lump.
Natural History of Fibroids Most fibroid grow slowly - 9% growth rate over 12 months, more depending on growth factors rather than hormones. Growth rate decreases after age 35 yrs in white women, but not in blacks. Most of them regress with onset of menopause. Rapid uterine fibroid growth in premenopausal age almost never indicate sarcomatous change. O.5% women with pre-exisiting fibroid may develop pain and bleeding in their postmenopausal age, as their fibroid might have under gone sarcomatous changes. Fibroids may become calcified in menopausal women. Fibroids may develop variety of degenerative changes.
Degenerative Changes Subserosal fibroid sessile pedunculated torsion acute abdominal pain. Detached wandering fibroid get attached to other peritoneal structure parasite Fibroid. Hyaline degeneration Fatty degeneration Red degeneration (Aseptic Necrobiosis) in pregnancy, postpartum Saponification Cystic degeneration Calcification Hemorrhagic, torsion Sarcomatous changes Infection/ulceration of pedunculated fibroid Association with endometrial Ca, endometriosis, follicular enlargement of ovaries. Inversion of uterus
Diagnosis PA Examination—fibroid with uterus larger than 12-14 wks. of gestation are well palpable per abdomen . Enlarged uterus may be as big as term pregnancy. Surface is irregular nodular, bossed, firm, no Braxton Hick contractions, no palpable fetal parts , movements and no fetal heart sound . uterine soufflé due to increased blood supply to uterus may be audible, it has to be differentiated from umbilical soufflé.
DiagnosisPelvic Examination Enlarged uterus due to fibroids is of variable size, irregular surface, nodular or bossed . Associated cystic enlargement of ovary may be noted. Enlarged uterus is firm and non-tender, freely mobile— up and down, side to side till it incarcerates in pelvis. Enlarged uterus and cervix move together.
Imaging For symptomatic women, consideration of conservative therapy, non invasive procedure or surgery often depends on an accurate assessment of the size, number and position of fibroids. TVS Saline infusion USG, Hysteroscopy, MRI can be done. Sub mucous fibroids were best identified by MRI (100%sensitivity, 91% specificity ) SIS (sensitivity 90%, specificity 89% ) Hysteroscopy (sensitivity 82%, specificity 87%). MRI allows evaluation of number, size location and proximity to bladder, rectum, tubal opening in uterine cavity and endometrium, thus helping in planning surgery.
ImagingSonography is the most readilyavailable and least costly todifferentiate fibroids from otherpelvic pathology . It is reasonablyreliable for evaluation of uterus with< 375 cc volume and 3-4 or fewerfibroids.
Figo Leiomyoma classification systemSubmucosal 0 1 Pedunculated Intracvity < 50% intramural 2 >50% intramural 0 other 3 Contacts endometrium., 100% intramural 4 Intramural 5 subserosal >50% intramural 6 subserosal <50% intramural 7 subserosal pedunculated 8 other(specify.,cervical,parasiticHybrid Two numbers are listed separated byLaiomyomas(impact both 2-5 hyphen.by convension , the 1st reffers toendometrium and serosa) the relatioship with endometrium while 2nd torelationship with serosa submucosal and subserosal , each lessthan half the diameter in the endometrim and peitoneal cavities
Fertility and Fibroids Presence of submucous fibroids decrease fertility and removing them increases fertility. Sub serous and intramural fibroid do not effect fertility but their removal may increase fertility depending on their location. Myomectomy carries risk of anesthesia, surgery , infection, post- operative adhesions, likelihood of increased cesarean delivery, rupture of myomectomy scar, expanse of surgeries and time for recovery. Therefore until submucous, intramural fibroids are surely found to be the prime cause of infertility and repeated abortion, myomectomy is advised and it will increase chances of fertility.
Fibroid and Pregnancy Prevalence of fibroids in pregnancy is 18% based on 1st trimester USG Most of fibroids do not increase significantly in pregnancy. Red degeneration of fibroids occurs in 5% cases. Patient develops pain, fever, local tenderness of fibroid, increased TLC and DLC.Bed rest, analgesics and plenty of fluids are needed to treatthem.Influence of fibroids on pregnancy Abortions ,Malpresentation, malposition, IUGR, PROM, Premature onset oflabour pains, uterine inertia, inco-ordinated uterine action,prolonged labor obstructed labor due to cervical fibroid orincarcerated fibroid, APH (abruptio, placenta praevia), AtonicPPH, P Sepsis, inversion of uterus, sub involution of uterus.Rupture of Myomectomy scar .
Treatment Watchful Waiting Medical Therapy NSAID, GnRH- Agonists. GnRH- Antagonist, Alternative therapy. Surgical Treatment options - (a)Myomectomy—Laparotomy, laparoscopy, Hysteroscopy, cesarean section and concurrent myomectomy. (b)Uterine Artery Embolization and occlusion. (c)Endometrial ablation.
Watchful WaitingNot having treatment for fibroids rarely results in harm,except women with severe anemia from fibroid relatedmenorrhagia or hydronephrosis from uretericobstruction caused by massive fibroid pressing over.Therefore, for women who are asymptomatic or havingmild to moderate discomfort with fibroids, watch fullmay allow treatment to be deferred, perhaps indefinitely.A woman approaching menopause, watchful waitingmay be considered, because there is limited time todevelop new symptoms and after menopause bleeingstops and fibroid decrease in size..
Medical Therapy Non steroidal Anti inflammatory drugsNSAIDS found tohave minimal or no effect in controlling menorrhagia due tofibroids and no decrease in size of fibrids.GnRH Agonist Treatment with GnRh Agonist decreaseuterine volume, fibroid volume and bleeding. Monthly GnRHAgonist given for 6 months reduced fibroid volume by 30% andtotal uterine volume by 35%.bleeding also decreased well.Following discontinuation of GnRH –A , uterine volume andmenses returns with in 4--8 weeks,2/3rd women remainedasymptomatic for 8-12 months. 95% women developed sideeffects of hypo estrogen--- iatrogenic menopuase andoseoporosis.Add back therapy given concurrently reduces theseside effcts.GnRH-a is recommended as temporary treatment forpremenopausal women with heavy menorrhagia.
Medical TreatmentGnRH –Antagonist Immediatesuppression of endogenous GnRh by dailySC injection 0f Ganirelix results in 30%reduction in fibroid volume with in 3 wks.Patient develops Hypo estrogenicsymptoms. Availability of long actingcompounds might be considered formedical treatment prior to surgery.
Medical TreatmentProgesterone mediatedTherapyReduction in fibroid sizefollowing treatment with progesterone –blocking drug MIFEPRISTONE is similar tothat due to GnRH –a. Controlled trial withmifepristone therapy( for 6 months) found48% reduction in size of uterus. 28%patientdeveloped endometrial hyperplasia due tounopposed action of estrogen
Medical Treatment Progesterone releasing IUCD Mirena-Levonorgestrel releasing IUCD may be a reasonable treatment for selected women of child bearing age with fibroid associated menorrhagia and interested to have contraception. 85% of such women returned to their normal bleeding with in 3 months and 40% developed reversible amenorrhea at the end of 1.5-2years .
Medical Treatment at least for 12 weeks Alternative Medical Treatment Chinese herbal medicine Kuie Chi –Fu –Ling –wan found to complete resolution of fibroids (19%), decrease in size in34%, increase in 4% , 95% got relief from menorrhagia and 94% from dysmenorrhea (study group consisted of 110 women with fibroids <10cm ). 14% women preferred hysterectomy during the 4 year period of study.
Preoperative management (1) severe anemia can be rapidly corrected by recombinant forms erythropoietin alpha or epoetin250 iu/kg weekly for 3 weeks and parentral iron therapy along with folic acid, vitamin C, protein suplementation. (2)Auto transfusion / donor blood transfusion (3)Control of bleedingGnRH agonist therapy (4)Control of associated medical problems like hypertension, CHF, Asthma, uti, kidney or liver illness.
Myomectomy Safe alternate to hysterectomy for young women who even have large fibroid and want to retain uterus , fertility “The restoration and maintenance of physiological function is or should be the ultimate goal of surgery Victor Bonney -1931” In carefully selected women myomectomy may be safely accomplished at the time of LSCS by experienced surgeon instead of caesarean hysterectomy.
Myomectomy Indications Infertility caused by cornual fibroid blocking tube. Habitual abortion due to sub mucous fibroid.Treatment required. Pedunculated fibroid likely to undergo torsion. Fibroid > 12 weeks. Broad ligament fibroid pressing on ureter. Fibroid pressing over bladder causing retention of urine / infection. Rapidly growing uterine fibroid in post menopausal women.
Laparoscopic myomectomy-steps of operation: A. Fibromyoma uterus( subserous) not larger than 10 cm or4 in number, Infiltrated with Pitressin ; B. Incision taken onthe fibromyoma; C. Fibromyoma exposed; D. Myoma screwinserted to steady the myoma; E. Myoma dissected from itsbed; F. Edges of myoma bed approximated with interruptedVicryl sutures(Barbed). Removed myoma seen in POD; G.Myoma being morcellated; H. Tunnel in myoma afterremoval of cylindrical mass; I. Excised myoma cylinderbeing removed from the morcellator.
Disadvantages of laparoscopicmyomectomy More heaorrhage because of no applicability of myomectomy clamp / tornicate. Longer duration of operation—longer anesthesia. More chances of post operative adhesions – infertility, ch,. Abdominal pain, intestinal obstruction. Increased incidence of scar rupture in pregnancy/ labour due to impefect or inadequate suturing. Laparoscopic myomectomy may not be safer for infertile women. Unidentified or not removed small fibroid may grow later ---shoe up as recurrence.-
Hysteroscopic Myoma -resection Submucous fibroid < 1/3rd buried in myometrium to avoid uterine perforation. It can be excised either by electric cautery , laser or resectoscope. It is best done under laparoscopic guideance line to avoid myometrial perforation.
Complications gut. Myomectomy of Primary, reactionary or secondary haemorrhage. Trauma to urinary tract, Infection. Adhesions. Intestinal obstruction. Recurrence of fibroid or menorrhagia.
Uterine Artery Embolization(UAE) Ravina (1991) first performed it to reduce blood supply to fibroid, results in reduction in size, further growth of fibroid reduced and minimum menstrual blood loss. Menorrhagia reduced in 80-90 % , pressure symptoms in 40-70% and volume decreased by 50% at the end of 3 months.Contra indications Subserous and pedunculated fibroid necrosis and fall of tumor in peritoneal cavity. Very big fibroid are notsuitable, submucous fibroid is not cured. It does not help the infertilewomen rather it may increase the problem.Technique under LA bilateral UAE approach through percutaneousfemoral catheterization, using poly vinyl alcohol gel (PVA gel) particlesare injected in the artery supplying the fibroid.
Results and complications ofUAE Vascularity and size reduced by 40% at 6 weeks and 75% at the end of 1 year. Symptoms are relieved in 70% women.Post operative complications fever and infection,vaginal discharge and bleeding , unbearable ischaemicpain, pulmonary embolism, premature ovarian failure ifaccidental occlusion of ovarian vessels occur, fertility rateis reduced due to adhesions, failure due to incompletecoagulation caused by arterial spasm or tortuosity ofblood vessel.
Advantages Of UAE No major surgery. No intra-operative bleeding. Short hospital stay. No abdominal adhesions. 75-80% women suffering from menorrhagia are satisfied.
HysterectomyIndication Women over 40 years of age , multiparouswomen, complicated fibroids, unforeseen difficultiesduring myomectomy.Types of HysterectomyAbdominal-total, sub total, pan hysterectomy ,extended or wertheim’s hyserectomy when fibroid areassociated with carcinoma endometrium or cervix.Vaginal Hysterectomy.LAVH.
Newer techniques MRI guided per cutaneous laser ablation using High Intensity focused Ultrasound (HIFU) has been recently attempted – results are awaited. Laparoscopic myolysis optimal surgery in multiparous women by using Nd : YAG laser, cryo- probe or diathermy to coagulate subserous fibroid . The contraindication are similar to UAE. Cervical fibroids preoperative GnRH will shrink the fibroid. Fibroid enucleation will be easy to perform myomectomy / hysterectomy, thus reducing ureteric and bladder injury.
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