Ovarian Cancer Epidemiology (Obstetrics, Gynecology) PowerPoint Presentation

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Geriatric Gynecology Michael S. Policar, MD, MPH Dept of OB,GYN, and Reproductive Sciences UCSF School of Medicine policarm@obgyn.ucsf.edu

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Geriatric Gynecology: Outline Post menopausal bleeding Genital skin conditions Urinary incontinence What’s (usually) not necessary…cervical cancer screening

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Cervical Cancer Screening * If 3 normal and no abnormal pap results in the prior 10 yrs SD: sexual debut (age at first vaginal intercourse ) LBC: liquid based cytology

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Discontinuation of Screening Women aged 65 years and older represent 14.3% of the United States’ population but have 19.5% of new cases of cervical cancer In white women new-onset cervical cancer peaks in the middle of the fifth decade of life and then decreases The peak incidence in Hispanics is in the early 70s Asian or Pacific Island ethnicity the incidence peaks in the late 70s The incidence of cervical cancer continues to increase throughout life in African American women in the US ACOG Practice Bulletin No. 109, Dec 2009

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Discontinuation of Screening in Women With a Cervix Screening may be discontinued at age 70 years (ACS) or 65 years (USPSTF) in low risk women after 3 consecutive negative screening tests in the prior decade Continue routine cervical cytology examinations Sexually active older women with multiple partners, as there is some risk for new HPV infection and CIN Women with a previous history of abnormal cytology If screening is discontinued, risk factors should be assessed during the annual examination to determine if reinitiating screening is appropriate ACOG Practice Bulletin No. 109, Dec 2009

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Discontinuation of Screening in Women Who Have Undergone Total Hysterectomy If the hysterectomy was for benign indications and no history of high-grade CIN, discontinue routine screening Women who had high-grade CIN lesions before hysterectomy can develop VaIN or carcinoma at the vaginal cuff years later If a history of CIN 2-3 —or in whom a negative history cannot be documented—should continue to be screened even after their period of post-treatment surveillance The screening interval may then be extended, there are no good data to support or refute discontinuing screening ACOG Practice Bulletin No. 109, Dec 2009

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Postmenopausal Bleeding (PMB) Differential Diagnosis Hormonal Exogenous estrogens: hormone therapy (HT) Endogenous estrogens: acute stress, estrogen-secreting ovarian tumor Anatomic Atrophic vaginitis, foreign body Endometrial hypoplasia (atrophy) Endometrial hyperplasia Uterine cancer: endometrial adenocarcinoma, corpus sarcoma Cervical cancer: squamous, adenocarcinoma

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Endometrial Cancer: Risk Factors Age: peak incidence 72 years old 3x higher than 50-54 years old 2% of endometrial cancers in women <40 y.o. Chronic unopposed estrogen (E) exposure Related to E-level and duration of exposure High body mass index (BMI)…obesity Menopause >52 y.o.(2.4x); low parity (2-3x) E- secreting tumor (granulosa-theca tumor) Exogenous sources: ET, tamoxifen

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Endometrial Cancer: Risk Factors Diabetes (RR= 2.8) Hypertension (RR= 1.5) Personal or family history of breast or colon cancer HNPCC (Hereditary Non-Polyposis Colon Cancer) 5% of all endometrial cancers HNPCC women have 22-50% lifetime risk of endometrial cancer ACS endometrial cancer screening guidelines (2001) Annual EMB starting at 35 years old Prophylactic hysterectomy and BSO after childbearing

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Postmenopausal Bleeding: Evaluation If not using HT, evaluation is required by either Endometrial biopsy (EMB), or Endovaginal ultrasound (normal stripe is < 5 mm) If using HT, endometrial biopsy (EMB) to evaluate Cont Combined -EPT: persistent bleeding > 3 months after HT initiation Cont Sequential -EPT: persistent unscheduled bleeding Single episode of PMB; limited time and volume; explained Observation is an acceptable option If recurrent, endometrial evaluation is mandatory

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Ultrasound Diagnosis of Endometrial Hyperplasia

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Technique of EMB Bimanual exam to evaluate uterine axis, size Cleanse cervix with antiseptic S-l-o-w-l-y apply tenaculum ( + local anesthetic) Use of the sampling device Choose correct type (rigidity) of sampler “Crack” stylet to ensure easy movement Gently advance to fundus; expect resistance at internal os Note depth of sounding with side markings Pull back stylet to establish vacuum

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Tips for Internal Os Stenosis Pain relief Use para-cervical or intra-cervical block Intrauterine instillation of lidocaine Cervical dilation Freeze endometrial sampler to increase rigidity Grasp sampler with sponge forceps 3-4 cm from tip Use cervical “os finder” device Use small size Pratt or Hegar dilators Give sublingual or vaginal misoprostol to soften cervix 4 hours before procedure

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Postmenopausal Bleeding: Management Atrophic vaginitis: topical estrogen Chronic endometritis: + antibiotics Polyp: observe or hysteroscopic excision Depends upon size, persistent bleeding symptoms Cystic hyperplasia or endometrial atrophy Observe or very low estrogen dose CC-EPT Simple endometrial hyperplasia Continuous high dose progestin; re-biopsy in 4 mos Atypical endometrial hyperplasia: hysterectomy Endometrial cancer: hysterectomy + XRT

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Genital Skin Itching Infections Candidiasis Tinea cruris Dermatitis Psoriasis Seborrheic dermatitis Eczema Dermatoses Lichen sclerosus Lichen simplex chronicus (LSC) LS + LSC Neoplasms Vulvar Intraepithelial neoplasia (VIN) Paget’s Disease

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Vulvar Candidiasis Vulva will be very itchy; often excoriated Presentation Erythema + satellite lesions Occasionally: thrush, LSC thickening if chronic Diagnosis: skin scraping KOH, candidal culture Treatment Topical antifungal therapy daily for 7-14 days, or fluconazole 150 mg PO repeat in 3 days Plus: TAC 0.1% or 0.5% ointment QD-BID

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Vulvar Candidiasis

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Tinea Cruris: “Jock Itch” Asymmetric lesions on proximal inner thighs Plaque rarely involves scrotum; not penile shaft Well demarcated red plaques with accentuation of scale peripherally; no satellite lesions Fungal folliculitis: papules, nodules or pustules within area of plaque Treatment Mild: topical azoles BID x10-14d, terbinafine Severe: fluconazole 150 mg QW for 2-4 weeks If inflammatory, add TAC 0.1% on 1st 3 days

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Contact Dermatitis Irritant contact dermatitis (ICD) Elicited in most people with a high enough dose Rapid onset vulvar itching (hours-days) Allergic contact dermatitis (ACD) Delayed hypersensitivity 10-14 days after first exposure; 1-7 days after repeat exposure Atopy, ICD, ACD can all present with Itching, burning, swelling, redness Small vesicles or bullae more likely with ACD

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Contact Dermatitis Common contact irritants Urine, feces, excessive sweating Saliva (receptive oral sex) Repetitive scratching, overwashing Detergents, fabric softeners Topical corticosteroids Toilet paper dyes and perfumes Hygiene pads (and liners), sprays, douches Lubricants, including condoms

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Contact Dermatitis: Treatment Exclude contact with possible irritants Restore skin barrier with sitz baths, compresses After hydration, apply a bland emollient White petrolatum, mineral oil, olive oil Short term mild-moderate potency steroids TAC 0.1% BID x10-14 days (or clobetasol 0.05%) Fluconazole 150 mg PO weekly Cold packs: gel packs, peas in a “zip-lock” bag Doxypin or hydroxyzine (10-75 mg PO) at 6 pm Replace local estrogen, if necessary If recurrent, refer for patch testing

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ISSVD 1987: Vulvar Dermatoses ISSVD: International Society for the Study of Vulvar Disease

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2006 ISSVD Classification of Vulvar Dermatoses No consensus agreement on a system based upon clinical morphology, path physiology, or etiology Include only non-Neoplastic, non-infectious entities Agreed upon a microscopic morphology based system Rationale of ISSVD Committee Clinical diagnosis  no classification needed Unclear clinical diagnosis  seek biopsy diagnosis Unclear biopsy diagnosis  seek clinic pathologic correlation

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2006 ISSVD Classification of Vulvar Dermatoses

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Lichen Sclerosus: Natural History Most common vulvar dermatosis Prevalence: 1.7% in a general GYN practice Cause: autoimmune condition Bimodal age distribution: older women and children, but may be present at any age Chronic, progressive, lifelong condition

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Lichen Sclerosus: Natural History Most common in Caucasian women Can affect non-vulvar areas Part (or all) of lesion can progress to VIN, differentiated type Predisposition to vulvar squamous cell carcinoma 1-5% lifetime risk (vs. < 0.01% without LS) LS in 30-40% women with vulvar squamous cancers

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Lichen Sclerosus: Findings Symptoms Most commonly, itching Often irritation, burning, dyspareunia, tearing 58% of newly-diagnosed patients are asymptomatic Signs Thin white “parchment paper” epithelium Fissures, ulcers, bruises, or submucosal hemorrhage Changes in vulvar architecture: loss of labia minora, fusion of labia, phimosis of clitoral hood Depigmentation (white) or hyperpigmentation in “keyhole” distribution: vulva and anus Introital stenosis

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Hyperpigmentation due to scarring Loss of labia minora “Early” Lichen Sclerosus

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Lichen Sclerosus Fissures Thin white epithelium

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Agglutination of clitoral hood Loss of labia minora Introital narrowing Parchment paper epithelium “Late” Lichen Sclerosus

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68 year old woman with urinary obstruction Labial agglutination over urethral meatus

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Lichen Sclerosus: Treatment Biopsy mandatory for diagnosis if <50 years old Preferred treatment Clobetasol 0.05% ointment QD x4 weeks, then QOD x4 weeks, then twice-weekly for 4 weeks Taper to med potency steroid (or clobetasol) 2-4 times per month for life Explain “titration” regimen to patient, including management of flares and recurrent symptoms 30 gm tube of ultrapotent steroid lasts 3-6 mo Monitor every 3 months twice, then annually

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Lichen Sclerosus: Treatment Second line therapy Pimecrolimus, tacrolimus Retinoids, potassium para-aminobenzoate Testosterone (and estrogen or progesterone) ointment or cream no longer recommended Explain chronicity and need for life-long treatment Adjunctive therapy: anti-pruritic therapy Antihistamines, especially at bedtime Doxypin, at bedtime or topically If not effective: amitriptyline, desipramine PO Perineoplasty may help dyspareunia, fissuring

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Lichen Simplex Chronicus = Squamous Cell Hyperplasia Cause: an irritant initiates a “scratch-itch” cycle LSC classified as Primary (idiopathic) Secondary (superimposed upon lichen sclerosus, candida vulvitis; vulvar contact dermatitis) Presentation: always itching; burning, pain, and tenderness Thickened leathery red (white if moisture) raised lesion In absence of atypia, no malignant potential If atypia present , classified as VIN

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Lichen Simplex Chronicus

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L. Simplex Chronicus: Treatment Removal of irritants or allergens Treatment Triamcinolone acetonide (TAC) 0.1% ointment BID x4-6 weeks, then QD Other moderate strength steroid ointments Intralesional TAC once every 3-6 months Anti-pruritics Hydroxyzine (Atarax) 25-75 mg QHS Doxepin 25-75 mg PO QHS Doxepin 5% cream; start QD, work up

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Lichen Sclerosus + LSC “Mixed dystrophy” deleted in 1987 ISSVD System 15% all vulvar dermatoses LS is irritant; scratching  LSC Consider: LS with plaque, VIN, squamous cell cancer of vulva Treatment Clobetasol x12 weeks, then steroid maintenance Stop the itch!!

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Vulvar Intraepithelial Neoplasia (VIN):Prior to 2004 Grading of VIN-1 through VIN-3, based upon degree of epithelial involvement The mnemonic of the 4 P’s Papule formation: raised lesion (erosion also possible, but much less common) Pruritic: itching is prominent “Patriotic”: red, white, or blue (hyperpigmented) Parakeratosis on microscopy

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ISSVD 2004: Squamous VIN VIN 1 is not a cancer precursor; abandon use of term Instead, use “condyloma” or “flat wart” Combine VIN-2 and VIN-3 into single “VIN” diagnosis Two distinct variants of VIN VIN, usual type Warty type Basaloid type Mixed warty-basaloid VIN, differentiated (simplex) type

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ISSVD 2004:VIN, Usual Type Includes (old) VIN -2 or -3 Usually HPV-related (mainly type 16) More common in younger women (30s-40s) Often asymptomatic Lesions usually elevated and have a rough surface, although flat lesions can be seen Often multifocal (incl periurethral and perianal areas) and multicentric in 50% Strongly associated with cigarette smoking Regression is less likely and progression to invasion more likely with the basaloid type

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VIN, Differentiated (Simplex) Type Includes (old) VIN 3 only Usually in older women with LS, LSC, or LP Not HPV related Less common than usual type Patients usually are symptomatic, with a long history of pruritus and burning Findings Red, pink, or white papule; rough or eroded surfaces A persistent, non-healing ulcer More likely to progress to SCC of vulva than warty-basaloid type

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WhiteVIN

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VIN, usual (basaloid) type

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VIN: warty-basaloid type

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Vulvar Intraepithelial Neoplasia

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Hyperpigmented VIN

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Vulvar Intraepithelial Neoplasia Precursor to vulvar cancer, but low “hit rate” Greater risk of invasion if immunocompromised (steroids, HIV), >40 years old, previous lower genital tract neoplasia Treatment Wide local excision (few lesions), laser ablation Topical agents: 5FU cream, imiquimod Skinning or simple vulvectomy Recurrence is common (48% at 15 years) Smoking cessation may reduce recurrence rate

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Indications for Vulvar Biopsy Papular or exophtic lesions, except obvious condylomata Thickened lesions (biopsy thickest region) to differentiate VIN vs. LSC Hyperpigmented lesions (biopsy darkest area), unless obvious nevus or lentigo Ulcerative lesions (biopsy at edge), unless obvious herpes, syphilis or chancroid Lesions that do not respond or worsen during treatment In summary: biopsy whenever diagnosis is uncertain

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Tips for Vulvar Biopsies Where to biopsy Homogeneous : one biopsy in center of lesion Heterogeneous: biopsy each different lesions Skin local anesthesia Most lesions will require ½ cc. lidocaine or less Epinephrine will delay onset, but longer duration Use smallest, sharpest needle: insulin syringe Inject anesthetic s-l-o-w-l-y Alternative: 4% liposomal lidocaine (30 minutes) or EMLA (60 minutes) pre-op

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Stretch skin; twist 3 or 4 mm Keyes punch back-and-forth until it “gives” into fat layer

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Tips for Vulvar Biopsies Lift circle with forceps or needle; snip base Hemostasis with AgNO3 stick or Monsel’s solution Silver nitrate will not cause a tattoo Suturing the vulva is almost never necessary Separate pathology container for each area biopsied

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Urinary Incontinence (UI) “Involuntary loss of urine that is objectively demonstrable and is a social or hygienic problem” 25% (under 60) to 35-40% (over 50) adult women Chronic urinary incontinence Social seclusion Increased risk of falls (26%), fracture (34%) Three times more nursing home admits $3,565 per individual with severe incontinence Cost for women was 3x higher than for men Twice as high for women older than 65 years compared with women younger than 65 years More than all cancer care for women

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Types and Causes of UI

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Urinary Urge Incontinence (UUI) AKA: Detrusor overactivity, detrusor instability, uninhibited bladder, or overactive bladder Bladder muscle involuntarily contracts during the filling of the bladder before reaching capacity Urge incontinence is more common in older adults Creates a sensation of urinary urgency and frequency before urine is lost Causes Infection, menopause, drugs, multiple sclerosis Idiopathic in most cases

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Urinary Stress Incontinence (USI) Pressure inside the bladder exceeds urethral pressure Due to relaxation of the muscles and ligaments in the pelvis, owing to childbirth and aging Onset mainly in women younger than 60 years Losses of small amounts of urine with activities that increased intra-abdominal pressure Coughing, sneezing, running, laughing Intercourse No warning of leakage

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Less Common Causes of UI Mixed Incontinence Stress and urge incontinence at the same time Overflow Incontinence Bladder overflows because it can't be fully emptied Result of bladder blockage, injury, nerve damage (diabetes, MS) Reduced stream, dribbling, unsuccessful voiding Anatomic Conditions Tract from bladder into vagina (fistula)

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Medications Causing UI Urge UI Diuretics, caffeine, alcohol Stress UI ACE inhibitors (cough) a-adrenergic blockers (decreased urethral tone) Overflow incontinence Anticholinergics Narcotics Antidepressants a-adrenergic agonists beta-blockers Calcium channel blockers

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3 Incontinence Questions (3IQ) 1. During the last 3 months, have you leaked urine, even a small amount? 2. If yes, do you have… Stress UI: physical activity, coughing, sneezing, lifting, or exercise Urge UI: urge, feeling need to empty but could not get to the toilet fast enough Other: don’t know 3. Which type of UI do you have most often: stress, urge, mixed (equal), other

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Initial Visit Simple Diagnosis - 3 IQ, UA (not urine culture) Reasonable expectations Ask the patient what she wants! Consider a diary Time/ toilet void /leak accident/fluid intake Fluid adjustment Educate & Empower! Patient information Bedside commode (falls & fracture prevention)

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Evaluation of UI: Urodynamics When are urodynamics necessary? When medical treatments fail Mixed incontinence Women who have failed UI surgery Before first UI surgery (?)…depends upon the surgeon! What is evaluated? Cystometrogram: check pressure bladder at different volumes of air or water Urethral pressure profile: bladder neck closure pressure, functional length, response to cough Uroflowmetry: flow rate to detect blockage Electromyogram: activity of the pelvic muscles

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Treatments for Urinary Incontinence Urge UI Urge suppression / distraction Quick pelvic contractions Behavioral: bladder training, timed voiding Medication Stress UI Pelvic floor exercises: Kegels, biofeedback Mechanical: pessary, urethral occlusion devices Surgery

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Hints from Heloise (Jeanette Brown, MD) Fluid Management Drink for thirst…not a marathon drinker! Avoid caffeine Pelvic Floor Contraction Squeeze your bottom like you are trying to hold back gas (should feel around your vagina as well) Hold for 2 seconds and relax for 2 seconds (increase each by 1 second each week until 10 seconds) Bladder Control Strategies Urge control: “freeze and squeeze” Stress control: “squeeze before you sneeze” or lift

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UUI: Behavioral Therapy Bladder Training Teaches an individual to resist the urge to void and gradually expand the intervals between voiding Effective for urge and overflow incontinence Timed Voiding Using biofeedback, the patient charts voiding and leaking From the patterns that appear in her chart, she can plan to empty her bladder before she would otherwise leak Toileting Assistance Scheduled toileting, habit training schedules, and prompted voiding to empty the bladder regularly

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Antispasmodics for UUI Side effects: dry mouth, constipation, drowsiness, blurred vision, dizziness Contraindications: narrow angle glaucoma, hepatic/renal disease

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Menopause and Urinary Incontinence Menopause is a major risk factor for both stress and urge incontinence Lack of estrogen results in bladder muscle weakness and thinning of the lining of the urethra, which causes improper closure Does estrogen replacement help? Reduces vaginal irritation and painful intercourse Inconsistent effect on urge incontinence Minimal or no effect on stress incontinence

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Urinary Tract Health & HT Local ET may benefit some women with urge incontinence who have vaginal atrophy Unclear if ET by any route is effective for overactive bladder Controversial if local ET can improve stress incontinence (systemic ET may worsen or provoke it) Local vaginal ET may reduce risk of recurrent UTI No HT product approved for urinary health in US/Canada NAMS position statement. Menopause 2008.

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USI: Pelvic Floor Exercises Kegel exercises “Clench the muscles you would use to stop the flow of urine. Hold the squeeze for 10 seconds, then relax” Performed 30-80 times daily for at least 8 weeks. Particularly helpful for younger women Biofeedback Instrument placed in vagina signals intensity of muscular squeeze Goal is for users to gain awareness and control of their pelvic muscles Used in conjunction with Kegel exercises

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USI: Pelvic Floor Exercises Vaginal Weight Training Small weights are held within the vagina by tightening the vaginal muscles Performed for 15 minutes, twice daily, 4-6 weeks Limited information on effectiveness Pelvic Floor Electrical Stimulation Mild electrical pulses stimulate muscle contractions Less effective than pelvic floor muscle exercises

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USI: Pessary with “Incontinence Knob”

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USI: Surgical Therapies Bulking Injections Contigen, Durasphere May need repeat injections periodically Needle bladder neck suspension procedures Tension-free vaginal tape (TVT) Vaginal approach; suture tethered to abdominal wall Older procedures: Stamey, Raz, and Pereyra

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USI: Surgical Therapies Abdominal sling operations Abdominal incision or laparoscopy Burch, Marshall-Marchetti procedure Anterior colporrhaphy (“anterior repair”) Vaginal surgery to treat cystocoele (but not USI) High failure rate after 5 or more years

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In Closing: What Should I Do? Occasional leak, not socially disabling Use liner pad as needed, “live with it” Frequent overactive bladder symptoms See PCP, OBGYN or Urologist for evaluation PFE, biofeedback, and timed voiding Trial of vaginal estrogen, oxybutnin, tolterodine, imipramine, imipramine + oxybutnin Urodynamics for mixed incontinence

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In Closing: What Should I Do? Stress incontinence Trial of PFE, pessary, mechanical device OBGYN or Urologist for evaluation Surgery Difficult cases, severe cases, or previous failure Seek-out uro-gynecologist, sub-specialist urologist, or university based “Continence Center” No drugs or surgery PFE, behavioral interventions, mechanical devices Absorbent pants

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