Life Stages Week 5-7

myoepithelial lobular stains (2)

P63, SMM (smooth muscle myosin)

The following parameters are particularly important for assessing the risk of recurrence and/or spread of tumor (prostate cancer): (4)

Gleason score (determined as described above, but may differ from the biopsy Gleason score due to more extensive sampling of tumor) Extraprostatic extension (does the tumor grow beyond the prostatic fibromuscular stroma? if so, how far?). Margin status (does the tumor extend to the surgical margin?) Lymph node status (has the tumor spread to lymph nodes?)

Vacuum erection device

--Cylinder/pump placed over penis creates closed chamber; pump creates vacuum, drawing blood into corpora cavernosa --Constrictive elastic ring then placed at base of penis to restrict flow of suctioned blood

total skin-sparing mastectomy

--Extension of skin-sparing mastectomy --Preservation of entire skin envelope and nipple-areolar complex --Nipple tissue excision --2 staged operation. 1st stage mastectomy and tissue expanders. 2nd stage formal reconstruction with implants or autologous tissue.

greatest predictor of an ADR

#medications taken (any new sign/symptom = ADR until otherwise ruled out)

how do I know which drugs I should worry about? ADRs

'Red Flag' medication recognition § Beer's List is a good place to start List of potentially inappropriate medications § START/STOPP* criteria § See Module 1 for other medication classes § E.g. - Anti-cholinergic medications in table 6 of syllabus.

three categories of benign breast lesions

- Nonproliferative - Proliferative without atypia - Proliferative with atypia

infection as cause of hematuria

--Cystitis: Dysuria, frequency, malodorous urine --Pyelonephritis: Fever, sepsis, flank pain --Evaluate with UA for RBC, WBC, nitrate, esterase and Urine culture for sensitivities Treat based on culture results --Simple UTI: Non-febrile, non-recurrent UTI in a patient with female genitalia: 3 days of appropriate antibiotic -- Complex UTI: Febrile, recurrent, and/or in a patient with male genitalia: 7 days of appropriate antibiotic n Longer treatment course indicated in pyelonephritis

How would you evaluate the lower urinary tract (bladder and urethra)?

--Cystoscopy (scope into the bladder) --A cytology test is often times performed at the same time to screen for malignant cells -High specificity but low sensitivity

Surgical options for BPH - Holmium Laser Enucleation (2)

--Dissects enlarged prostate tissue away from peripheral zone using a laser --Lower bleeding risk but requires careful anatomical delineation

5-Alpha Reductase Inhibitors (eg Finasteride, Dutasteride) for BPH

-- Inhibit conversion of T to DHT in prostate --Take 3-6 months for maximum efficacy -- Work best in large prostates (> 40 mL) -- Associated with a decrease in risk of BPH progression -- Controversy regarding prostate cancer risk -- Side effects include decreased libido, ED

Transitional Cell Cancers (bladder cancer) risk factors (5)

--*Cigarette smoking (50% of cases)* --Arylamine exposure (20-25% of cases) --rubber, dyes --Pelvic radiation --Cyclophosphamide

neoadjuvant/adjuvant chemotherapy (breast cancer)

--12 cycle of Taxol follow by 4 cycle of Adriamycin/Cytoxan (DD) or 4 X 4 cycles n Taxotere/Cytoxan 4-6 cycles. --Sometimes if unresponsive Gemcitabine or Carboplatin is added. --Monoclonal antibiotic therapy -Herceptin/Perjeta --Tyrosine Kinase inhibtors -Laptinab. --Hormonal Therapy with Tamoxifen or Aromatase inhibitors.

Hematuria is present when:

--Blood is seen in the urine -Differentiate menstrual bleeding and foods/meds that may color urine (eg beets, pyridium) --3 or more RBC per high powered field on microscopy

How would you evaluate the upper urinary tract (kidneys and ureters)?

--CT scan --Most definitive test is CT Urogram, consisting of non-con, renal, and delayed phase images What if CT scan or contrast is not an option? --MRI with/without contrast --Ultrasound --Retrograde Pyelography

Detumescence

--Cessation of NO production from neurons and endothelium and restoration of sympathetic tone dominance --Initial increase in intracavernous pressure with contraction of arteries against closed venous system --Gradual decline in intracavernous pressure with restoration of venous outflow

workup for RCCA

--Cross Sectional contrast enhanced imaging if not done already --Consider percutaneous fine needle biopsy if there is ambiguity regarding diagnosis --Labs (CBC, CMP) --Consider Chest X-ray

Risk factors for testis cancer (4)

--Cryptorchidism: 10-40x higher incidence --Klinefelters syndrome (XXY) --Previous testicular tumor - bilateral GCT (synchronous or metachronous) occurs in 3% of patients.

other options to treat BPH (3)

--Transurethral incision of the prostate (TUIP) --Urolift - pins prostate out of urethral lumen --Rezum-steam injection into prostate

contraindications to breast conservation

--Extensive DCIS --Large tumors/Small breasts --? Young Age --Advanced Stage (III/IV) --Poor access to radiotherapy --Genetic status-possible &from another lecture...: • Unable to have follow-up • Contraindication to radiation • Large tumor relative to breast/poor cosmesis • Extensive intraductal component

radiation therapy of breast cancer

--External beam radiation --Brachytherapy (internal sources) --The process: meeting with radiation oncologist, simulation, treatment planning, treatment --Treatment plans, effectiveness, tolerability and side effects dependent on type and location of tumor(s) and individual characteristics of person being treated (age, wellness) (eg breast, whole brain, abdominal radiation)

Hydrocele

--Fluid-filled pocket between layers of tunica vaginalis --Common and may be self-limited in neonates --Typically slowly progressive in older men --Treatment not mandatory but may be considered for bother from mass effect or pain

Surgical options for BPH - Transurethral Resection of the Prostate (TURP) (4)

--Gold standard surgical procedure --Produces durable results --Risks include but not limited to surgical complications, sexual dysfunction, worsening urgency, rare incontinence --Prior to alpha blockers, accounted for 25% of the clinical volume of practicing urologists

vascular risk factors for ED (6)

--High blood pressure >130/85 mm Hg --High Triglycerides >150 mg/dL --Low HDL cholesterol <40 mg/dL --Diabetes blood sugar >110 mg/dL --Obesity BMI >30 & Waist >40 inches --Lack of Exercise - Less than 3 METs activity per week

common sexual problems in men (4)

--Hypoactive Sexual Desire: Absence or notable decrease in frequency of desire for sex causing bother --Premature Ejaculation: Ejaculation within 2 minutes of penetration* associated with both minimal sense of control AND bother --Delayed Ejaculation/Anorgasmia: Distressing delay/absence in ejaculation and/or orgasm --Erectile Dysfunction: Inability to attain or maintain an erection adequate for satisfactory sexual intercourse

Facts on testis cancer

--Incidence: 3/100,000 men per year (5,500 new cases annually). --Most common malignancy in men aged 15-35. Accounts for 12% cancer deaths in ages 20-35. --Race: rare in Asians and Blacks, highest incidence in Scandinavians (6/100,000) --One of the most curable solid malignancies (1970's - <50% survival, 1990's - 90%)

neoadjuvant chemotherapy (breast cancer)

--Locally advanced breast cancer, larger than 2.5CM, skin or muscle involvement. --Axillary lymph node metastasis. --Triple negative breast cancer. --Patient would like breast conservation and avoid a mastectomy.

testosterone and sex

--Low T has been linked to sexual issues in both men and women --Maintenance of corporal smooth muscle content & neuronal integrity in men --Sexual appetitive role --The clearest sexual impact of T supplementation is on libido --There is evidence that T levels may influence response to ED therapy

causes of hematuria

--Malignancy -Renal, Bladder, Ureteral, rarely prostate or urethral --Medical Renal Disease -Presence of casts, protein, dysmorphic RBC is suggestive --Nephrolithiasis -Typically associated with renal colic --Infection -Cystitis, Pyelonephritis --Trauma -Degree of hematuria may not correspond to degree of trauma --BPH --Miscellaneous -Arteriovenous malformations, Heavy Exercise, Interstitial Cystitis

Testicular Fracture

--May occur after scrotal trauma --Sonogram may reveal disruption of tunica and/or hematocele

sentinel mode biopsy

--Most studies now report both an accuracy and localization rate of 95% or better --In most referral centers, sentinel node biopsy is the standard of care --Radioisotope, Blue dye, magtrace.

Treatment for urinary stones

--Observation +/- medical treatment with tamsulosin -Stones < 4 mm likely to pass, 5-10 mm 50:50, 11+ mm unlikely --Alkalinize urine and dissolve: for uric acid only -Potassium citrate -Sodium bicarbonate --Surgery -Cystoscopy with Stent -Extracorporeal shock wave -Ureteroscopy and lithotripsy -Percutaneous Nephrolithotomy --Emergent urinary diversion required for cases of obstructing stone in setting of fever, worsening renal function, or refractory pain/nausea

Orgasm physiology

--Occurs in the brain and is distinct from the pelvic events --Orgasm may occur without ejaculation in men --Current understanding of the neurophysiology of orgasm is poor --Oxytocin and dopamine appear to play important roles

Tadalafil for BPH

--Primarily an ED drug but has symptomatic efficacy for BPH --No objective changes in urine parameters

contraindications to breast radiation

--Prior lung, chest wall, breast irradiation --pregnancy --inability to achieve negative margins --collagen vascular disease eg lupus --anticipated poor compliance with treatment schedule --complications: -Fatigue -skin erythema, pain, edema -long-term: rib fractures, 2nd malignancy, lung, heart tissue exposure

Treatment of RCCA

--Radical nephrectomy - with/without resection of adrenal gland -May require venous thrombectomy/IVC resection if involved -Laparoscopic/robotic/open --Partial nephrectomy -Laparoscopic/robotic/open --Percutaneous cryoablation/RFA

Alpha Blockers (eg Tamsulosin, Terazosin, Doxazosin) for BPH (3)

--Relax bladder outlet --Quick onset of action --Side effects include orthostasis, anejaculation

Surgical options for BPH - Transurethral laser ablation (2)

--Relies on laser to vaporize rather than shave out prostate tissue --Lower bleeding risk but some potential for tissue sloughing

Squamous Cell Cancer (bladder cancer) risk factors (2)

--Schistosomiasis --Chronic UTI or catheter

Oral agents for ED (4)

--Sildenafil - March 1998 --Vardenafil - August 2003 --Tadalafil - November 2003 --Avanafil - April 2012 All block PDE 5 to up CGMP. • SHOULD NOT BE TAKEN WITH NITRATES! • Relative contraindication in men taking alpha blockers • Should be taken per protocol • 1-2 hours before sexual activity • Empty Stomach/Low Lipid Content • Require Sexual Stimulation! Principle Side Effects : • Congestion • Headache • Flushing • Visual Changes • Myalgia • Dyspepsia • Rare Serious Side Effects/Priapism

lumpectomy - breast conservation decision

--Tumor size relative to breast size --Age --Family history and genetic status --Co-morbid problems, collagen vascular disease, mental status --Previous radiation exposure

strong indications for BPH surgery (4)

--Urinary retention refractory to maximal medications --Recurrent infection --Worsening renal function --Hydronephrosis due to retention

male breast cancer

--Usually present at a more advanced stage --earlier invasion into the chest wall --M:F ratio is 1:130. 4% of breast cancers. --almost always invasive ductal, ER(+) risk factors: -radiation to chest wall -BRCA2

systemic therapy (breast cancer)

--Who gets chemotherapy? patients with higher risk of occult metastases (TIPPING) --menopausal status, age, stage, grade, estrogen, progesterone receptor status, her-2-neu, size of tumor, lymph node status --Genomic profiling: Oncotype dx®, Mammaprint® nBalance benefit, risk (risk tolerance) and patient preference

AUA Guidelines on Hematuria

--Young patients with scant microhematuria and without risk factors are recommended surveillance u Middle aged patients (men 40-59 and women 50-59) and those with moderate tobacco history or 11+ RBC on microscopy are recommended sonogram with cystoscopy --Older patients (>60), those with heavy tobacco use, and patients with gross hematuria are recommended CT urogram and cystoscopy

adverse drug reactions considerations (3)

--adherence (cultural? education? economic?) --new medications (recent transitions in care?) --accurate med list? check chart/emr, local pharmacy, call caregiver

optimize adherence and understanding

--affording medications --med calendars --med education (in native language whenever possible) --reminders --the patient, the caregiver --adherence tools (blister packs, retail/outpatient pharmacies will fill 2-4 weeks at a time w/ chronic meds only) --functional interventions (medisets - don't assume they know how to use)

BPH can be serious (7)

--bladder stones --urinary retention --bladder infections --hematuria --bladder diverticulum --irreversible symptoms --renal failure

pharmacodynamics in the elderly (2 main categories of drugs to look at for 2 physiologic reasons)

--dec. baroreceptor response (stiff vessels don't adjust well) -> falls, hip fractures so pay attention to: diuretics (ex. hctz, furosemide), BPH meds (ex. terazosin), Cardiac meds, Erectile meds) --inc. sensitivity to anticholinergic affects in CNS (causing dry mouth, urinary retention, constipation, confusion/delerium) so pay attention to: antihistamines, overactive bladder agents, tricyclic antidepressants, muscle relaxants

Crockcroft-Gault equation

--easy to calculate --basis for most dosing changes --(140-age) x weight (in kg) / (72 x serum creatinine (mg/dL)) --for women: x .85 This yields Cockcroft-Gault Clearance Creatinine (Clcr)

Geriatrics Assessment (8)

--functional status (ADLs, IADLS) --mood (PHQ9 or GDS) --social and financial support --goals of care --mobility --polypharmacy --fall risk (TUG) --advance care pref.

Gestational trophoblastic tumors (4 types)

--invasive mole --choriocarcinoma --placental site trophoblastic tumor --epithelioid trophoblastic tumor

Questions for POP (PLUSS)

--pelvic exam (lube bc GSM) --lithotomy vs. standing, bearing down vs. not (leakage?) --Urinary incontinence (urinary stress incontinence? urge incontinence?) --Surgical history --Sexual history

w/ hospitalization of older patients, look for (4)

1) AKI 2) Hypoglycemia 3) volume status 4) functional decline: prolonged hospitalization, increased institutionalization/loss of independence, higher health care expenditures, higher readmission rates, and higher mortality

Most cases of invasive ductal carcinoma fall into three major molecular subtypes with certain associated clinical features:

1) Hormone receptor-positive (ER-, PR- positive), HER2-negative or "luminal" breast cancer is the most common form of invasive breast cancer, accounting for 50-65% of cases. Typical patient groups are older women, BRCA2 mutation carriers, and, in rare cases, men. Almost all well-differentiated carcinomas fall into this category. Tumors in these patients express genes that are directly regulated by hormone receptors. Therefore, hormone therapy is a mainstay of treatment. 2) HER2-positive (hormone receptor positive or negative) is the second most common molecular subtype (about 20%). These cancers are more common in young women and TP53 mutation carriers, and tend to be poorly differentiated. These patients are treated with trastuzumab (Herceptin). 3) ER-negative, PR-negative, HER2-negative ("triple negative") accounts for about 15% of invasive ductal carcinomas. This subtype tends to occur in young women and women of African and Hispanic ancestry. These tumors tend to be poorly differentiated and often behave aggressively, with a poorer prognosis than the hormone receptor-positive luminal tumors, and with some genetic similarities to serous ovarian carcinomas, including association with germline BRCA1 mutation. These patients are treated with chemotherapy.

UCLA 3 item loneliness scale

1) I feel left out 2) I feel isolated 3) I lack companionship 1. hardly ever 2. sometimes 3. often 3-5 not lonely, 6-9 lonely

Advanced care directives (2)

1) Living will 2) Appointment of health care proxy

Penile erection / tumescence

1) NO-mediated relaxation of arterioles to the penile corpora 2) mechanical compression of venous outflow channels against the tunica of the corpora by the expanding erectile tissues

4 types of incontinence

1) Overactive bladder -> leak -> Urge UI 2) Overactive Outlet -> retention -> overflow (obstructive) UI 3) Underactive bladder -> retention -> overflow (atonic/neurogenic) UI 4) Underactive outlet -> leak -> stress UI

7 domains of delirium prevention

1) orientation protocols (clocks, calendars, windows) 2) cognitive stimulation (family visits) 3) Early mobilization, minimize restraints and tethering 4) Prevent sleep deprivation 5) communication methods and adaptive equipment (eyeglasses, hearing aids, appropriate interpretation) 6) avoid/treat medical conditions 7) manage pain

5 domains for managing uncertainty

1) patient preference 2) interpreting the evidence 3) estimate prognosis 4) determine clinical feasibility 5) create and communicate optimal therapy and care plans

Counteracting Ageism, ask about (5)

1) sex, HIV, substance use 2) No elderspeak! don't infantalize. 3) don't lower expectations or limit preventative care 4) avoid over or under treatment 5) internalized ageism w/in patients should be addressed

History questions for LUTS (6)

1) voiding diary 2) fever, dysuria, foul odor? (UTI) 3) Hematuria / weight loss / tobacco use (cancer?) 4) constipation (obstruction?) 5) intake of caffeine, carbonation, alcohol, acidic foods? (bladder irritant -> symptom exacerbation?) 6) history of urethral/bladder surgery or trauma (stricture -> obstructive voiding?)

diagnostics for LUTS (6)

1)PSA (help r/o cancer) 2) DRE (estimate prostate size and r/o nodules suspicious for cancer) 3) UA/culture (UTI) 4) post void residual (r/o urinary retention) 5) Urodynamics (overactive detrusor or obstructive voiding?) 6) Uroflowmetry (indicate obstruction w/ voiding)

relative risk reduction

1-(abs risk1/abs risk2) = (1-relative risk)

3 classes of meds not friendly to geriatric patients

1. Anticholinergics (ex: antihistamines, tricyclic antidepressants, bladder medications) 2. Antipsychotics (ex: Haldol) 3. Benzodiazepines (ex: Lorazepam) *All affect central nervous system -> deliriogenic!*

Bladder Cancer (3)

1. Classic Appearance is an anemone-like polypoid mass 2. More aggressive tumors may have a sessile appearance 3. Carcinoma in situ is confined to mucosa but portends high risk of progression

hormone therapy of breast cancer

1. Estrogen acts as a growth stimulant for breast epithelial cells. 2. Breast Cancer cells often retain functional estrogen receptors. 3. Depriving the cells of estrogen can result in cancer cell death.

6 interventions to help w/ fall risk

1. Group-based exercise classes 2. Home-based exercise training 3. Tai ChiE. Gradual withdrawal of psychotropic medication 4. Vitamin D supplementation* (measure in blood first, don't supplement if not low) 5. Cataract surgery (if individual has cataracts) 6. Home safety assessment (by occupational or physical therapist) with modification of risks discovered

optimize medication adherence (2)

1. Identify/Evaluate/Assess - looked for adverse drug events and polypharmacy 2. Develop A Game Plan for you patient - Emphasize adherence & understanding - Remove barriers for patients - Empower patient

Aging-related changes reduce compensatory BP control (3)

1. Local Mechanisms-Endothelial and Ventricle (reduced compliance of vessels and ventricle, endothelial dysfunction--less ability to constrict) 2. global neural mechanisms Baroreflex-sympathetic and parasympathetic (blunted baroreceptor reflex--inappropriate compensation with HR or contractility) 3. Renal-endocrine mechanisms (inappropriate RAS response & alteration in renal perfusion)

Two pathways to endometrial cancer pathogenesis

1. Normal endometrium -> estrogen -> atypical hyperplasia -> endometrioid carcinoma 2. Normal endometrium -> ? -> Carcimoma in Situ -> serous carcinoma

3 main factors leading to inc. risk for adverse drug effects in the elderly

1. Polypharmacy 2. lower adherence 3. altered physiology

optimize prescribing (2)

1. keep med list short --is there a continued indication for every medication? 2. Keep it sweet --once daily = 80% adherence, 4x/day = 50% adherence 3. start low and go slow - when starting new medications

Number needed to screen

1/(abs risk1 - abs risk2)

low-risk stones

1st time stone former w/o: --Family history of stones --GI/Bone disease --Gout --Recurrent UTI --Nephrocalcinosis --DM II --Obesity Screening Evaluation: BMP, Ca, Uric Acid, UA

Skilled Nursing Facility (SNF)

3+ ADL needs if custodial care, skilled needs if sub-acute care (short term) provides: nursing, rehabilitation access to MD for acute and longitudinal f/u, meals, room/board cost: medicaid, out of pocket, medicare if acute rehab needs. Medicare pays 100 days, Medical/caid needed for LTC.

USPTF Grading Scale (ABCDI)

A - offer or provide this service (high certainty big benefit) B - offer or provide this esrvice (high certainty moderate benefit) C - offer or provide this service for selected patients depending on individual circumstances (at least moderate certainty that net benefit is small) D - Discourage use of this service (recommends against) I - current evidence is insufficient, read clinical considerations, if service offered patients should understand uncertainty.

ADME changes for older adults

A: absorption (Drug-binding interactions (zinc, calcium iron, multivitamin), inc. exposure of drug and its metabolites) D: distribution (inc. fat, dec. H20, often less protein to bind drugs) M: Metabolism (dec. Liver mass, blood flow, & enzymes ; but interactions common) E: Elimination (gfr slows down in elderly, equation doesn't work as well for them. Use the Crockroft & Gault equation, tho it may overestimate)

Invasive ductal carcinoma versus ductal carcinoma in situ

ADH indicates increased risk of invasive breast cancer in either breast DCIS has many possible outcomes including no progression, or, progressing to invasive ductal carcinoma

why do people get kidney stones? (5)

Minerals in solution crystalize when they should be soluble --Gout/Gouty diathesis/malignancy (uric acid high) --Hyperparathyroidism (calcium high) --Chronic diarrhea state (calcium low, oxalate absorption high) --Urinary citrate too low --DEHYDRATION!

invasive ductal carcinoma

About 75% of breast cancers are invasive ductal carcinoma. The second most common type is invasive lobular carcinoma, accounting for about 10% of cases. Rare subtypes of breast cancer also exist, which are not mentioned in this lecture. Inflammatory breast carcinoma is a clinical diagnosis that refers to rapidly growing advanced invasive ductal carcinoma, in which the tumor spreads to and blocks the lymphatic vessels in the skin. This results in erythema, swelling, and thickening of the skin, with a characteristic "peau d'orange" appearance.

sexual desire/arousal disorder

Absence or reduction in 3 or more of the following: • Interest • Thoughts/fantasies • Sexual activity • Excitement/pleasure • Response to cues • Genital sensations Etiologies: • Meds: SSRIs, OCPs • Psych: depression, quality of relationship, stress • Hormone status

orgasmic disorders

Absence/reduced orgasm after sufficient sexual stimulation and arousal • Meds (SSRIs) • Hormonal (OCPs, menopause) • Anatomical, psychological

Systemic therapy for breast cancer

Adjuvant chemotherapy is given for about six months after surgery to target residual microscopic disease. Neoadjuvant chemotherapy may be given prior to surgery to shrink the primary tumor and reduce the size of the lesion that needs to be removed. Chemotherapy results in side effects such as nausea, fatigue, hair loss, and bone marrow suppression.

Targeting Aging: key points

Aging is a definable, measurable biological process Aging affects health in several ways, both related to and independent of "disease" Calendar age is only an approximation of physiological or biological aging Aging occurs throughout the adult lifespan Geriatric syndromes are key examples of integrative effects of aging on health

lynch syndrome & endometrial cancer

All women with endometrial cancer should be evaluated for the possibility of Lynch Syndrome • Tumor testing after clinical screening including personal & family medical history • Tumor testing on all cases diagnosed before age 60 • Tumor testing on all cases of endometrial cancer

Medications ED (disorders, mechanism)

Anti-HTN's, CNS active agents, EtOH, smoking, chemotherapy Central suppression, hormonal suppression, vascular

Vascular ED (disorders, mechanism)

Atherosclerosis, HTN, DM, trauma Impaired arterial flow or leak

Health Literacy

Avg adult >65 = 5th grade reading lev el LHL in ~60% To detect: --med review: name, describe what each is for and how to take it Avoid jargon, avoid >2-3 concepts in a single visit, use visual aids, use teach-back thought to occur <8th grade reading level >1/3 of paid caregivers have it

high penetrance mutations -> hereditary breast cancer (4)

BRCA1 & BRCA2: Hereditary breast and ovarian cancer (37-85% lifetime risk for breast, 15-40% for ovarian; BRCA1 often triple negative; BRCA2 mutation increases pancreas, fallopian tube, stomach, colon, and prostate cancer risk TP53: Li-Fraumeni: breast cancer, sarcoma, adrenocortical ca, leukemia, prostate ca PTEN: Cowden: breast cancer (lifetime risk 25-50%), benign hamartomas, fibrocystic breasts, thyroid ca, endometrial ca CDH1: Hereditary diffuse gastric ca, invasive lobular breast ca, lung ca, salivary gland ca, colorectal ca

Diagnosing ED (focus on basic)

Basic evaluation of sexual dysfunction --Sexual, medical, and psychosocial history --Focused physical examination --Total Testosterone, Glucose, lipids, serum chemistries Optional investigations --Psychological and/or psychiatric assessment --Other laboratory investigations --Specialized erectile function testing u Neurologic testing

ADLS (9) (TETCH BDGW)

Bathing, dressing, grooming, toileting, transferring, walking, clim bing stairs, eating, hygiene

DDx for a renal mass

Benign --Fluid-filled: -Simple Cyst -Abscess -Pyelonephritis --Solid -Angiomyolipoma (AML) - benign tumor w/ fat, smooth muscle, blood vessels -Oncocytoma Malignant -Renal Cell Carcinoma -Transitional Cell Carcinoma -Metastases

Differential diagnosis of acute scrotum (4 categories)

Benign -Hydrocele -Spermatocele -Varicocele Infection -Orchitis -Epididymitis -Abscess Emergent -Spermatic Cord Torsion -Trauma -Fournier's Gangrene Malignant -Testicular cancer

most common causes of palpable breast masses

Benign (many kinds are most common!!) but you want to be worried about: • Ductal carcinoma in situ • Invasive carcinoma • Sarcoma, including phyllodes tumor

treatment of serous ovarian tumors

Benign tumors can be excised, resulting in complete cure. Borderline serous tumors may stay localized and asymptomatic, or may spread to involve the peritoneal surfaces as noninvasive implants (surface deposits of tumor), resulting in symptoms after several years. Even low grade serous carcinomas tend to progress slowly. In contrast, women with high-grade serous carcinomas often have widespread metastasis at the time of presentation, resulting in poor prognosis.

BRCA1 or BRCA2

Between 5 and 10% of women with breast cancer have a germline mutation in BRCA1 or BRCA2, resulting in an estimated lifetime risk of developing cancer of 40-85%. BRCA mutation carriers with a history of breast cancer have an increased risk of disease in the contralateral breast of up to 5% per year. Men with BRCA2 mutations also have an increased risk of breast cancer. Mutations in BRCA1 or BRCA2 also result in an increased risk of ovarian cancer and prostate cancer; there may be a risk of certain other cancers as well, such as fallopian tube or peritoneal cancer. After a BRCA gene mutation has been identified, other family members can be referred for genetic counseling.

changes in the elderly when sick

Blood Pressure § Systolic BP tends to rise, diastolic BP less rise -> widened pulse pressure (systolic-diastolic pressure) Heart Rate § Rest: age related changes minimal at rest § Stress/Exercise: maximum heart rate decreases with age Respiratory Rate (RR) § Normal aging: minimal change § Illness: particularly useful in pneumonia • RR >24 may be most sensitive sign in older adults

survivorship and metastases (breast cancer)

Breast cancer survivors receive close clinical follow-up, including annual or even more frequent mammograms and evaluation of the breast and chest wall for possible recurrence. Metastatic breast cancer tends to involve the bones, chest wall, lymph nodes, lungs, and liver. The median survival time for patients with metastatic carcinoma is about 2 years. Radiation treatment may be given to specific sites of metastasis, and systemic therapy is employed as well. Pain management is also an important part of treatment of symptoms in order to improve quality of life.

Geroscience Mechanisms

Molecular damage: genome instability, macromolecular damage, loss of proteostasis, epigenetic dysregulation, telomere attrition Stress response: DNA repair, autophagy, mitophagy, unfolded protein response, nutrient sensing both of those -> consequences: mitochondrial dysfunction, cellular senescence, stem cell exhaustion, inflammation

invasive lobular carcinoma is associated w/

CDH1

Neurogenic ED (disorders, mechanism)

CVA, SCI, DM, pelvic surgery/radiation, trauma Decreased nerve impulse or transmission

Scientists have subdivided the prostate gland into various zones based on their differing biology

CZ = central zone, TZ = transition zone, PZ = peripheral zone prostate cancer usually arises in the peripheral zone.

Stone types (6)

Calcium Oxalate --Most common composition for renal stones Calcium Phosphate --More common in alkaline urine Uric Acid --Occur in patients with elevated uric acid and acidic urine n Radiolucent on plain film, typically apparent on CT Struvite (Magnesium Ammonium Phosphate) --"Infection Stones" produced by action of urease splitting bacteria (eg Proteus spp) Cystine --Hereditary stones from amino acid transporter defect Miscellaneous --Protease Inhibitors (Indinavir), Matrix Stones

Endometrial hyperplasia

Cause of abnormal uterine bleeding and frequently precedes development of the most common type of endometrial carcinoma, which is endometroid adenocarcinoma. defined as an increase in the quantity of endometrial glands relative to the stroma, with an increased gland:stroma ratio in comparison to normal proliferative endometrium. Inactivation of the PTEN tumor suppressor gene is found in about 20% of endometrial hyperplasias

PDE-2,3,4 inhibitors Papaverine Alprostadil injections

Cavernous nerve also release prostaglandin -> ↑cAMP -> smooth muscle relaxation *PDE-2,3,4 breaks down cAMP

Neurophysiology of sexual response

Central Nervous System --Medial preoptic area & paraventricular nucleus coordinate interpretation of erotic stimuli Sympathetic nervous system (SNS, T10-T12) - Vasoconstriction, opposes genital blood flow u Parasympathetic nervous system (PNS, S2-4) - Vasodilation, enhances genital blood flow Peripheral Nervous System --Pelvic Nerve (PNS) -> Cavernous Nerves --Hypogastric Nerve (SNS) -> Cavernous Nerves --Pudendal Nerve u Sensory afferents from the glans --Somatic motoneuronal projections to the ischiocavernous and bulbospongiosus muscles in men

Prostate-specific antigen

PSA is a serine protease that is produced by the prostate epithelium and is a component of semen, where its function is to liquify the seminal coagulum. PSA is produced by both benign and malignant prostate cells and is therefore not a specific marker for prostate cancer. PSA screening of older men has become extremely controversial in recent years.

Alternatives to surgery (BPH) (3)

Chronic indwelling Foley catheter --Simple but can be uncomfortabl Suprapubic tube --Minor surgical procedure to place Clean intermittent catheterization --Labor intensive but lower risk of infection and avoids having chronic drainage tube

Delirium - CAM

Confusion assessment method acute onset and fluctuating course AND inattention AND disorganized thinking OR altered level of consciousness

staging of breast cancer

DCIS is, by definition stage 0, sometimes referred to as Tis for in-situ. For pure DCIS, there is no lymph node involvement or metastasis. For invasive carcinoma, the overall TNM stage is determined by tumor size (T), lymph node involvement (N) and the presence of metastasis (M). A primary tumor of any size with direct extension to the chest wall and/or involvement of the skin is assigned a T4 stage.

DUCTAL CARCINOMA IN-SITU (DCIS)

DCIS typically presents as microcalcifications that are identified on a screening mammogram. In DCIS, neoplastic ductal cells fill the ducts, but do not invade through the basement membrane, hence the term carcinoma in-situ.

central mechanisms of ejaculation

PVN, MPOA, Nucleus Paragigantocellular, and lumbar spinothalamic tracts • 5-HT2c post-synaptic serotonin receptors inhibit ejaculation • Dopamine appears to have a stimulatory effect on ejaculation and sexual behaviour

Delirium prevention (6)

Delirium prevention trials demonstrated the effectiveness of intervention protocols in six areas: 1) orientation and cognitive stimulation for those with cognitive impairment, 2) early mobilization to avert immobilization, 3) interventions to prevent sleep deprivation, 4) communication methods and adaptive equipment (particularly eyeglasses and hearing aids) for vision and hearing impairment, 5) avoiding/monitoring use of problematic medications in older adults, including those with adverse side effects (antihistamines, benzodiazepines, antipsychotics, anti-nausea, overactive bladder agents, and muscle relaxants), and 6) managing pain. In Mrs. H's case, you could encourage/facilitate mobilization as soon as appropriate after surgery to reduce deconditioning, ensure she has her glasses and hearing aids, and minimize sleep deprivation by avoiding overnight vital sign checks, reducing nighttime noise, and overnight medication administration.

Studying age: worm genetics

Describe: Gradual, progressive, universal loss of function beginning after maturation Define: • Increasing probability of death Operationalize: • Lifespan of a worm under normal conditions

studying aging: multimorbidity

Describe: Gradual, progressive, universal loss of function beginning after maturation Define: • Susceptibility to disease • Accumulation of problems/deficits Operationalize: • Time to onset of additional major chronic disease

studying aging: cell division

Describe: Gradual, progressive, universal loss of function beginning after maturation Define: • Loss of reproductive capacity • Slowing/reduction in normal functions Operationalize: • Cell divisions of human cells in culture

questions for syncope vs. seizure (5)

Did you lose consciousness? If so, this is syncope and needs a syncope work-up. Did you feel lightheaded or as if you were going to faint? When severe, this is called pre-syncope, and patients describe it as the "world was going grey" or that "things were closing in," or that they had "tunnel vision." This may be a vasovagal episode. Common precipitants of vasovagal syncope include pain, straining for a bowel movement, prolonged standing, and being in a warm environment. Did you feel the room spinning around? This suggests vertigo. Did you lose urine or stool? This suggests that a seizure may be the cause of the fall, but not always. Did you bite your tongue/notice blood in your mouth after the fall? This also suggests a seizure might have occurred, but not always.

MOA three chemotherapeutic agents for breast cancer

Doxorubicin - anthracycline that inhibits DNA repair - intercalation into DNA and disruption of topoisomerase-IImediated DNA repair - generation of free radicals and their damage to cellular membranes, DNA and proteins • Cyclophosphamide - its metabolite forms irreversible DNA crosslinks ultimately leading to cell apoptosis • Paclitaxel - anti-microtubule agent - inhibits microtubule structures preventing cell division and replication

polypharmacy Rx cascade

Drug 1 -> ADR misinterpreted as new condition -> Drug 2 -> Adverse drug effect -> etc.

Erectile Dysfunction

ED is the inability to attain and/or maintain an erection sufficient for satisfying sexual activity Global prevalence estimate of 13-71% --Varies based on risk factors AND how the question is asked Will start to see atherosclerotic dz first in the small vessels of the penis, so can be a sign of later severe vascular disease

Uterine Cancer histology (most common types)

Endometrioid (75-80%) Serous (10%) Mucinous (5%) Clear Cell (4%) Sarcomas (3%)

Benign Prostatic Hyperplasia

Enlargement of the prostate with aging is a major clinical problem. Approximately 30% of men over fifty demonstrating moderate to severe symptoms, which can include urinary frequency, dysuria, and bacterial infections. The driver of benign prostatic hyperplasia is testosterone, as shown in Fig. 3. Testosterone from the testes is converted into the more active dihydrotestosterone (DHT) in the prostatic stromal cells, and DHT then promotes growth and/or survival of the prostatic stromal and epithelial cells. The result is hyperplasia of the prostatic glands and/or stroma, leading to obstruction of the prostatic urethra and the symptoms described above.

Bladder Cancer (Epidemiology, types and risk factors, workup, treatment)

Epidemiology - 5th most common malignancy - Males > females 3:1, peak age of incidence 60-70 yrs Types and risk factors - Transitional cell carcinoma: >90% • Cigarette smoking (50%), arylamine exposure (20-25%), pelvic radiation, cyclophosphamide - Squamous cell carcinoma: 5-9% • Chronic UTI/catheter, schistosomiasis Workup - Labs: CBC, CMP, UA, urine microscopy - Cystoscopy with simultaneous cytology Treatment - Transurethral resection of bladder +/- intravesical chemotherapy - Radical cystectomy

Testicular Cancer (Epidemiology, risk factors, presentation, workup, treatment)

Epidemiology - Most common malignancy in men ages 15-35 - Highest incidence in Scandinavians (6 per 100,000) Risk factors - Cryptorchidism, Klinefelter's syndrome, previous testicular tumor Presentation - Testicular swelling/nodule, dull ache, heavy sensation Workup - Tumor markers: hCG, AFP, LDH - Ultrasound - DO NOT BIOPSY Treatment - One of the most curable solid malignancies! - Radical orchiectomy and prosthesis

Evaluation for hematuria - Infection

Exam: CVAT Labs: UA, UCx

Evaluation for hematuria - BPH

Exam: DRE Labs: PSA Prostate biopsy

Lymph node status can be assessed by

FNA biopsy prior to surgery when the lymph node is palpable or is suspicious on imaging. The term axillary dissection refers to the surgical removal of the lymph nodes in the axilla along with the fibroadipose tissue. The major complication of this procedure is development of lymphedema of the arm, which can be debilitating.

Lower urinary tract - Filling & emptying

Filling: Bladder accommodates urine at low pressure Increased resistance 1. Urethral support 2. Urethral coaptation (the intrinsic property of the inside of the urethra to be closed at rest due to the tissues) 3. Urethral sphincter Emptying: coordinated contraction of bladder + dec. resistance at outlet

IADLS (8) (FH CLUMPS)

Finances, housework, cooking, laundry, use of the phone, managing meds, public transit, shopping

Penile Erection (4 stages)

Flaccid: Hypoxic, minimal blood flow Filling phase: increasing cavernosal blood flow Full erection: corporal bodies maximally engorged u Rigid erection: glans engorgement via contraction of the bulbospongiosus and ischiocavernous muscles

Evaluation of sexual dysfunction disorders

Focused History: - Ask about medications - Most relevant are SSRIs, OCPs - Ask patient to describe recent sexual experiences, relationships, practices, IPV screen - Surveys may be helpful - PMH, PSH, obstetric and gyn hx Physical Exam: - Look for signs of hormone deficiency or other causes - Pelvic floor muscle exam - Vulva and vagina • Q-tip test to localize pain abs: as indicated by H&P

intrinsic factors affecting: These are risk factors inherent to an individual. Many are medical conditions and age-related changes.

Gait or balance difficulty Muscle weakness (upper or lower extremity) Orthostatic/Postural Hypotension Parkinson's disease Strokes Neuropathy Vertigo Cognitive impairment/Dementia Depression Visual deficits, including cataracts and wearing multifocal (bifocals) lenses Osteoarthritis Rheumatic disease Atrial fibrillation Urinary incontinence

Falls-related physical exam (6)

Gait, balance, and mobility assessment Neurological function including cognitive evaluation: --Lower extremity peripheral nerves, Proprioception, Reflexes, Cerebellar function, Cogwheeling and rigidity, Nystagmus, Mental status/Cognitive Screen Muscle strength: Test lower extremities for strength and range of motion. Cardiovascular status:Heart rate and rhythm, Valvular dysfunction, Presence or absence of peripheral edema Visual acuity Foot and footwear examination

metabolic therapies: key points

Genetic screens in simple model organisms helped discover new biological pathways involved in regulating aging High-throughput automated technologies are now being applied to aging/longevity experiments in model organisms An intertwined network of metabolic pathways, involving genes/proteins as well as small molecule metabolites, regulate aging mechanisms Clinical trials that test aging interventions might involve healthpan or resilience frameworks, with outcomes including multimorbidity, functional decline, or geriatric syndromes

Sexual pain disorders

Genital pain associated with sexual stimulation • Vaginal atrophy (GSM, breastfeeding, POI, OCPs) • Inadequate lubrication • Vulvar vestibulitis

questions to ask about falls (6)

Getting a detailed description of the circumstances of the fall(s), frequency, symptoms at the time of the fall, injuries, and other consequences of the fall are all important to determine potential for recurrent falls and injuries. In addition to the above, other important questions include: 1. How many falls have you had in the past year? Having a history of falls indicates a higher risk of future falls. 2. Can you describe the circumstances surrounding each fall? Ask about details from just prior to the fall, including what time of day, what location, and what they were trying to do when they fell. 3. Were you able to get up when you fell? How long did that take? When a patient cannot get up after a fall, this can lead to serious medical consequences including dehydration and skin breakdown/pressure ulcers. 4. Did you have any injuries from your fall(s)? This is especially important if there was a head strike. 5. Have you limited your activities due to fear of falling? Fear of falling can lead to social isolation and reduced participation in daily tasks that the patient is worried will lead to falls. 6. Was there a new or hazardous environment that caused the fall? Uneven surfaces or a new or unfamiliar environment can be a cause of a mechanical fall. However, even if a patient reports "just" a mechanical fall, you should still consider the environment and how it might be modified to prevent future falls.

Aging (4)

Gradual, progressive, universal loss of function beginning after maturation --susceptibility to dz inc. --probability of death inc. --homeostenosis (loss of resilience to stressors) --loss of reproductive capacity

Define Aging for a study

Gradual, progressive, universal loss of function beginning after maturation • Susceptibility to disease • Increasing probability of death • Loss of resilience to stressors (homeostenosis) • Loss of reproductive capacity • Accumulation of problems/deficits • Slowing/reduction in normal functions

Evaluation for hematuria - Trauma

H&P

Evaluation for hematuria - Miscellaneous

H&P Labs: CBC, coags

HPV Type and cancer risk

HPV TYPE 6,11, 42-44 Low to nil 31,33,35,39,51- 53,58,59,66,68 Intermediate 16,18, 45, 56 High

Cervical cancer prevention

HPV vaccination before exposure to HPV § Bivalent (2vHPV): HPV16 and18 § Quadrivalent (4vHPV): HPV 6, 11, 16 and 18 § 9-valent (9vHPV): HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 CDC recs for vaccine: § Initiate routine HPV vaccination at age 11 or 12 years. § The vaccination series can be started beginning at age 9 years. § Vaccination is also recommended for females aged 13 through 26 years and for males aged 13 through 21 years who have not been vaccinated previously or who have not completed the 3-dose series § Males aged 22 through 26 years may be vaccinated

Evaluation for hematuria - malignancy

History: smoking, occupational exposures, travel hx Labs: CBC, CMP, UA, urine microscopy Imaging: CT, cystoscopy, pyelogram, MRI, CXR Percutaneous fine needle biopsy

Nerves involved in voiding (name, roots, function) (3)

Hypogastric T10 - L2 Sympathetic Relaxes detrusor Contracts internal sphincter Bladder filling Pelvic Splanchnic S2 - S4 Parasympathetic Contracts detrusor Relaxes internal sphincter Bladder emptying Pudendal S2 - S4 Somatic Controls external sphinct

Hormonal ED (disorders, mechanism)

Hypogonadism, hyperprolactinemia Inadequate NO release

advanced prostate cancer treatment

In cases where localized therapy is inadequate or has failed, androgen deprivation therapy is typically the treatment of choice. Options: leuprolide (a GnRH agonist that blocks LH/FSH release from the pituitary), abiraterone (which blocks androgen production by inhibiting the enzyme CYP17), and enzalutamide (which blocks androgen receptor function). While androgen deprivation therapy can induce remission, prostatic adenocarcinoma typically becomes resistant to the therapy over time and progresses. Additional therapeutic approaches in such cases include conventional chemotherapeutic agents such as docetaxel, targeted external beam radiation, and (in select cases) immunotherapy.

Epididymoorchitis

Infection (typically bacterial) of the epididymis and/or testicle --Typically associated with progressive pain, dysuria, urethral discharge --Unilateral swelling and tenderness superior to the testicle, possibly alleviated by elevation (Prehn's sign) --STI organisms most common in sexually active men --Coliform bacteria common in boys, older men, and men who have anal insertive sex --Treatment consists of appropriate antibiotic therapy (eg Cipro, doxy, CFTX)

Ovarian cancer risk factors x 2 + protective factors x 4

Infertility (with use of fertility drugs) 2.8 x Unprotected intercourse > 15 years 1.6 x Protective: Breast feeding 0.81 x Oral contraceptive pill use 0.66 x Tubal ligation 0.59 x Parity 0.47 x

Evaluation for hematuria - Medical renal disease

Labs: BUN, Cr, UA with microscopy

Evaluation for hematuria - Nephrolithiasis

Labs: serum and urine chemistries Imaging: KUB, renal ultrasound

Extrinsic factors affecting falls: Externally originating factors affecting the patient by interacting with the internal functions of the body.

Medications with CNS or Cardiovascular System effects Anxiolytics (e.g., Benzodiazepines) Anticonvulsants (e.g., Levetiracetam, Phenytoin) Antipsychotic medications (e.g., Haldol, Quetiapine) Anti-hypertensives (e.g., Labetalol, Hydrochlorothiazide) Sedatives (e.g., Zolpidem, Trazodone) Oral hypoglycemic agents (e.g., Metformin) Opioid pain medication (e.g., Oxycodone, Morphine, Vicodin) Diuretics (e.g., Furosemide) Alcohol Recreational drugs Environmental Factors: Consider hazards within the home as well as in the community Uneven surfaces/Pavement Clutter at home Tethers like oxygen tubing, IVs, or catheters Electrical cords Pets Throw rugs Wet floors Stairs, especially without handrails Poor lighting

when to screen PSA

Men ages 55-69: inform about potential benefits and harms of PSA screening, engage in personalized decision-making. Don't screen at or above 70.

Fournier's gangrene

Necrotizing Fascitis of Scrotum --Most common in poorly controlled diabetics --Patients present with fever, severe leukocytosis, scrotal crepitus, --Rapidly progressive with high mortality rate --Treatment is emergent wide surgical debridement

Causes of ED (5, memorize!)

Neurological --Radical pelvic surgery, MS, CVA, SCI, neuropathy Vascular --HTN, Dyslipidemia, DM, tobacco use Hormonal --Hypogonadism, hyperprolactinemia Medications --Antihypertensives, SSRI, hormonal agents, etc u Psychological/Relational --Anxiety, spectatoring, poor communication, deep seated issues pertaining to sex

who should get chemo? (breast cancer)

No chemotherapy benefit in low risk Chemotherapy associated with better disease free survival in high risk

Endometrial cancer risk factors x 7, protective x 2

Nulliparity, fertility evaluation 7.6 Polycystic ovary syndrome (chronic anovulation) 3 Unopposed estrogen therapy 2 to 10 Early menarche 2.4 Diabetes 2.0 Obesity 1.9-7.2 (Higher for higher BMI) Lynch Syndrome 22-50% Lifetime Risk Oral contraceptive pill use 0.60 Parity 0.54-0.32

Symptoms of BPH (Wise, Fun)

Obstructive • Weak Stream • Intermittency • Stranguria • Emptying Incompletely Irritative • Frequency • Urgency • Nocturia

What proportion of people 65 and older fall each year?

One-third of people aged over 65 years will fall each year. That number increases to about 50% for older adults who are >80 years old. Consequences: Injuries: Falls are the leading cause of death from injury in patients >65 years old ED and hospital use: 16% of ER visits and 7% of hospitalizations in older patients are for fall related injuries. Costs for a hospitalization related to falls are on average $17,483. Loss of independence: Falls are the major reason for 40% of nursing home placements. For an older person the risk of falling ranges from 8% with no risk factors to 78% for those with 4 or more risk factors. Therefore reducing risk factors is important!

therapies for orgasmic disorders (1) and sexual pain disorders (4)

Orgasmic Disorder • Substitute offending agents Sexual Pain (vaginal atrophy/GSM) • Vaginal estrogen (cream, ring, tab) • Ospemafine (SERM, targets vagina not endometrium) • Vaginal DHEA • Topical lidocaine

orthostatic hypotension diagnosis

Orthostasis is present if there is a decrease in systolic blood pressure of 20 mm Hg, or a decrease in diastolic blood pressure of 10 mm Hg WITHIN three minutes of standing compared with the sitting or supine blood pressure. Any drop of blood pressure during this time is a positive result, even if patient has recovery at 3 minutes. In older adults, pulse is not a reliable indicator of postural hypotension or low volume (in contrast with younger adults) because baroreceptor sensitivity diminishes with age and there is a high prevalence of use of medications such as beta blockers which diminish heart rate response.

Ovarian cancer survival

Overall: 78% at 1 year 47% at 5 years

cervical cancer survival

Overall: 87% at 1 year 69% at 5 years

Endometrial cancer survival

Overall: 88% at 5 years

Psychogenic ED (disorders, mechanism)

Performance anxiety, depression Loss of libido, overinhibition, impaired NO release ED is ~90% physiological, 10% psychological

Residential Care Facility for Elderly (RCFE)

Semi-independent, no need for frequent skilled medical care provides: socialization, IADL assistance, some ADL assistance for $$ cost: out of pocket, sometimes long-term care insurance

A.D.M.E.

Pharmacokinetics Absorption Distribution Metabolism Elimination

Foreskin issues (2)

Phimosis: Inability to retract foreskin PROXIMAL to the glans Paraphimosis: Inability to replace foreskin DISTAL to the glans

how to take orthostatic blood pressure

Place the patient in a supine position for at least 5 minutes to allow their blood pressure to stabilize, then check the blood pressure and pulse. Assist the patient to standing. After one minute of standing, the blood pressure should be taken with the patient's arm level with their heart. This requires the patient to either place the arm on your shoulder or for you to cradle the arm, so they do not have to use their muscles to hold the arm up. The arm should be relaxed. After the blood pressure is taken at one minute, the patient should continue to stand for an additional 2 minutes and the blood pressure and pulse should again be taken. Note any symptoms of dizziness with position change.

prostate cancer genetics (2 genes)

Prostate cancer is the most common type of cancer in men and usually occurs in men over the age of 50. Androgens drive the growth and survival of prostate cancer, at least in the early stages of the disease, and a number of genetic alterations have been found in prostate tumors. The most common of these is a fusion involving the TMPRSS2 and ERG genes, which fuses the androgen responsive promoter of the TMPRSS2 gene to the ERG transcription factor gene. This rearrangement, which is found in approximately half of all prostate cancers and has never been identified in other tumor types, leads to ERG overexpression and promotes tumor invasiveness.

Prostatitis

Prostatitis can be acute or chronic and can be infectious or noninfectious in etiology. Cases of clinically evident prostatitis are rarely biopsied, as histologic analysis is typically not helpful in guiding management. However, acute and chronic inflammation are quite often seen in prostate biopsies performed to evaluate for the presence of cancer. Such inflammation can sometimes lead to a bump in the patient's PSA level, thereby prompting clinical concern for cancer.

Formerly known as "The Internist's Tumor" due to numerous paraneoplastic syndromes (5)

RCCA --Hypertension --Hypercalcemia (10%) u --inc. erythropoietin --inc. LFTs with metastasis (Staufer syndrome) --Polycythemia

Radiation therapy for breast cancer

Radiation therapy can be applied to specific areas or the whole breast, and it may include the axilla, supraclavicular lymph nodes, and internal mammary lymph nodes. The extent and dose of radiation is determined by the stage of the breast cancer and other factors. For some patients, intra-operative radiation therapy (IORT) can be used to make sure any residual cancer is treated. Complications of radiation therapy include skin irritation and damage, bone marrow suppression, lymphedema, and heart damage - particularly for left-sided breast cancer. Additionally, there is a risk of secondary tumors including angiosarcoma, a malignant tumor of blood vessels that can develop many years after treatment.

cervical cancer treatment (advanced stage) (1)

Radiation with sensitizing chemotherapy ‒ External beam + brachytherapy (i.e. radiation from without and within)

high-risk stones

Recurrent stone former Child/Adolescent Solitary kidney 1st time stone former with any of the risk factors listed Metabolic Evaluation: 24 hour urine collection

proliferative lesions w/ atypia

Relative Risk is 4-5 - Atypical ductal hyperplasia • Excision recommended - Atypical lobular hyperplasia • Excision controversial; if mass associated then excise

SPIKES NURSE

Set up the interview Patient perceptions Invitation Knowledge Empathize w/ emotions Share strategy/summarize Name, Understand, Respect, Support, Explore

Penile Fracture

Rupture of the tunica albuginea of the penis • Occurs from forceful bending of the erect phallus • Most commonly in sexual context but other etiologies have been reported Evaluation: Exam for "eggplant" sign, sudden detumescence, pain • Consider US, MRI if diagnostic uncertainty Treatment: Surgical Repair

Program of All-Inclusive Care for Elders (PACE)

SNF eligible, safe at home during non-PACE hours. Services: PCP, coordination of specialty care, rehab, meals, ADLS (bathing, grooming), socialization cost: medicare and medicaid

Neural control of voiding

SNS from T10/11 to L2 (noradrenaline), hypogastric nerve PNS from S2-S4 (acetylcholine), pelvic nerve Somatic NS - S2-S4 pudendal nerve

SAIL

Simplify - Simplify drug regimens to reduce pill burden. Use medications that can be dosed once or twice daily. Use medications that can treat multiple conditions Adverse effects - Be familiar with adverse effects of medications. Choose medications that have broad therapeutic indices when possible. Discontinue a medication that is causing an adverse effect when possible Indication - Ensure each medication has an indication and a defined, realistic therapeutic goal. List - List the name and dose of each medication in the chart and share it with the patient and/or caregiver

Intracavernosal Injection

Smooth muscle-relaxing medication injected directly into the penis --Phentolamine --Papaverine --PGE1

late life depression main risk factors (3, 5)

Socioeconomic and psychiatric: --caregiving role --living alone --negative life events including bereavement Medical risk factors: --cognitive impairment/dementia --complex chronic illness (ex. cancer, lung disease, diabetes) --Arthritis and associated pain or neuropathy --Sensory impairment (ex. hearing, vision) --Age

Spermatic Cord Torsion

Sometimes abbreviated "Testicular Torsion" --Most common in pubscent boys Evaluation --Hard, horizontally oriented testicle, exquisitely painful --Differentiate from testicular appendage torsion --Localized pain w/ "Blue Dot" sign --More common in school age boys --Scrotal ultrasound is helpful but not essential Treatment: Surgical Exploration

senescent cells: key points

Study of a basic biological process (halting cell division) led to the discovery of senescent cells Senescent cells are an example of a consequence of aging common to many health problems that can be targeted Engineered mouse models provided proof-of-concept High-throughput drug screening identifies potential therapeutics

breast cancer TMN staging

T stage - T1 ≤ 2 cm - T2 2-5 cm - T3 >5 cm - T4 extends to chest wall and/or skin • N stage - N1 positive ipsilateral axillary node (level 1,2) - N2 fixed or matted axillary node (level 1,2) - N3 level 3 or infraclavicular node • M stage - Distant metastasis or not

prostate function

The prostate produces prostatic fluid, a component of semen that provides factors necessary for proper sperm function. The seminal vesicles produce seminal fluid, another component of semen

bladder composition

The superior surface, and the upper one to two centimeters of the posterior aspect of the bladder, covered by peritoneum, and this is shown here. The anterior bladder is extra peritoneal, and adjacent to the retropubic space, which is called the space of Retzius, that's this fatty area over here. And the bladder lining consists of transitional epithelium, or urothelium, that's supported by a layer of loose connective tissue called lamina propria. The bladder musculature is described as having three layers, the area of the bladder neck, an inner longitudinal, a middle circular and outer longitudinal layer. And the remainder of the bladder is composed of fibers that run in many directions, forming a sort of plexiform arrangement of detrusor bundles.

definition of a fall

The unintentional change in position resulting in a person coming to rest on the floor, ground, or another lower level.

fibroadenoma

This lesion contains epithelial and stromal components . An individual fibroadenoma can grow to more than 5 cm and can calcify, but most of them remain small at 1-2 cm, and about half involute spontaneously after pregnancy. On physical exam, fibroadenomas are well-demarcated, have smooth borders, and are mobile. On mammography, fibroadenomas are clearly delineated and stand out from the background fatty tissue. Grossly, they are well-circumscribed, firm, and nodular. Microscopically, they are composed of branching slit-like ducts or glands that are compressed by a mildly cellular stroma. Fibroadenoma has no associated risk of malignancy; it is generally painless

TIDE

Time - Allow sufficient time to address and discuss medication issues during each encounter. Individualize - Apply pharmacokinetic and pharmacodynamic principles to individualize medication regimens. Consider dose adjustments for renal and/or hepatic impairment. Start medications at lower doses than usual and titrate slowly. Drug interactions - Consider potential drug-drug and drug-disease interactions. Avoid potentially dangerous interactions, such as those that can increase the risk for torsades de pointes Educate - Educate the patient and caregiver regarding pharmacologic and nonpharmacologic treatments. Discuss expected medication effects, potential adverse effects, and monitoring parameters.

treating bladder cancer

Transurethral Resection of Bladder --Staging and Treatment --Cancer classified as high vs low grade --Depth of invasion is key determinant of next step --Ta/T1: Surveillance (+ BCG in high grade), consider re-resection particularly if no muscle in specimen --T2+: Radical Cystectomy with urinary diversion -- Consider neo-adjuvant chemo for large tumors --Bladder sparing protocols with TURBT, chemo and radiation exist but these are not standard of care in US

ovarian carcinoma types I and II

Type I tumors go through a benign-borderlinemalignant sequence resulting in low grade carcinoma. Type II tumors originate from ovarian inclusion cysts or fallopian tube epithelium and rarely show an identifiable precursor lesion before declaring themselves as carcinoma. They are usually of high-grade serous histology. STIC = serous tubal intraepithelial carcinoma.

Mammograms will often detect calcifications without a mass lesion, which are not palpable

Typically, these represent ductal carcinoma in-situ (DCIS). When the mammographic abnormality is not palpable, a core biopsy is performed under mammographic guidance. This is referred to as a stereotactic core biopsy. Alternatively, the area with calcifications can be removed surgically. To guide the surgeon, a metallic wire is placed into the area of calcifications in the breast using mammographic guidance. The surgeon follows the wire to the lesion and removes the area of calcifications (wire localization biopsy). A newer method involves using magnetic beads, called seeds, instead of a guide wire. The seeds are placed by the radiologist around the area of calcifications. The surgeon uses a magnetometer to find the seeds and remove the tissue in that area.

three curves to the ureter that correlate with places where ureteral stones can get caught at

Ureteropelvic junction (UPJ) Crossing of the iliac vessels Ureterovesical junction (UVJ)

3 major choke points for stones

Ureterovesical Junction: Labial/scrotal pain Crossing of Iliacs: Lower abdominal pain/groin Ureteropelvic Junction: Flank pain

Sex counseling

Useful as monotherapy or as adjunctive treatment and may include: --Sexuality Education --Anxiety reduction/desensitization --Cognitive-behavioral interventions --Sexual stimulation techniques --Interpersonal assertiveness/couples' communication training

in late life depression, older adults display more

somatic symptoms more often than younger adults

Nonproliferative breast change (fibrocystic change)

a broad spectrum of lesions including: cystic change, duct ectasia, apocrine metaplasia, and secretory changes. These changes are thought to occur as a result of normal fluctuations in hormone levels. These patients may describe a lumpy-bumpy feeling to their breasts that is cyclical with their menses. There is no increase in cancer risk in patients with nonproliferative fibrocystic change.

Serous tumors present as

a mass projecting from the ovarian surface or as a multicystic lesion with a few fibrous-walled cysts that contain papillary (frondlike) epithelium.

homeostenosis

a normal, age-related decline in the body's physiologic reserves With aging, less physiologic reserves available to respond to stressors, leading to increased vulnerability to diseases and death

Prognostic versus predictive

a predictive test tells you if an intervention will work

Sentinel lymph node biopsy

a procedure used to identify and remove the draining lymph nodes nearest to the primary tumor, whether single or multiple lymph nodes. The goal of sentinel biopsy is to reduce the risk of lymphedema and identify patients who do not need complete axillary dissection. The sentinel lymph nodes are identified in the operating room by injecting a tracer material, such as dye and/or a radiotracer, near the primary tumor, and then locating the tracer as it flows into lymph nodes. If three or more sentinel lymph nodes harbor metastatic cancer, the patient will have a full lymph node dissection performed. If the sentinel nodes are negative for tumor, or only one or two sentinel nodes are positive for tumor, then no additional nodes are removed, and the risk of lymphedema is greatly reduced. For sentinel lymph node biopsy, the risk of lymphedema is approximately 3%.

Gleason score

a sum of the two most common Gleason patterns in the tumor - for example, a tumor that is mostly Gleason pattern 3 with a little Gleason pattern 4 would have a Gleason score of 3+4=7, Gleason scores can theoretically range from 2-10, but in modern practice, the Gleason scores reported on biopsy range from 6-10 (since Gleason patterns 1 and 2 cannot be reliably identified in small biopsies).

Indeterminate breast epithelial lesions include

atypical ductal hyperplasia (ADH) and lobular neoplasia.

grandparent caregiver

age>55 lives w/ child, primary caregiver, legal relationship (guardian/custody) or informal

Leiomyoma

aka fibroids, benign smooth muscle tumor that is common in the uterus. The tumor cells show very little cytologic atypia and only a few mitotic figures. Solitary leiomyomas or those that are few in number can be removed by myomectomy, which is a targeted surgical procedure that leaves the uterus intact. Hysterectomy (removal of the uterus) may be required to treat large or symptomatic leiomyomas.

many patients diagnosed with prostate cancer now forego therapy altogether and instead follow

an active surveillance protocol

Each breast is divided into

an upper outer quadrant, upper inner quadrant, lower outer quadrant, and lower inner quadrant. Clinically, about 45% of cancers are found in the upper outer quadrant, toward the axilla, where most of the glandular tissue is found. Remaining cancers are distributed in other quadrants or in a central or subareolar location. More specific terminology is used with a clock-face designation, dividing each breast into 12 sectors around the nipple, with 12:00 being vertical above the nipple. The distance of the lesion from the nipple is also recorded in centimeters.

anterior vs. posterior urethra

anterior urethra is anything from the perineal membrane to the meatus. the posterior urethra is anything from the bladder neck to the peritoneal membrane.

Gleason grading

architectural grading system that has been in use for decades, which stratifies the tumor into five grades based on its architectural appearance at low power. Low-grade tumor (grades 1-3) is composed of individual well-formed glands (Figs. 5 and 6), while higher grade tumor (grades 4 and 5) demonstrates more complex architecture that includes fused glands, cribriform glands, single cells, and solid nests of tumor.

TMN staging for endometrial cancer

based on how deeply the invasive tumor extends into the myometrium, with invasion into the outer half of the myometrium resulting in a higher stage, and on whether the tumor spreads beyond the uterus into adjacent organs (ovaries and tubes for example) or spreads to lymph nodes. Staging therefore requires careful assessment of the hysterectomy gross specimen at the time of surgery, with close communication between the surgical pathologist and surgical oncologist as to the clinical findings intraoperatively.

DCIS is treated with

breast-conserving surgery (lumpectomy). The risk of recurrence of DCIS can be calculated based on factors including: • patient age • size of the DCIS lesion • surgical margin status, with distance of at least 2 mm considered negative • presence of comedo necrosis, defined as central areas of dead cancer cells • and nuclear grade of DCIS, categorized as low, intermediate or high based on the extent of nuclear abnormalities in size and shape. Using this type of calculation, low-risk DCIS has a recurrence rate in the ipsilateral breast of less than 10%, while high-risk DCIS has a recurrence rate of greater than 50%.

detumescence

constriction of penile arterioles (PDE5)

Mucinous tumors

contains tall columnar cells with mucinous cytoplasm that secrete mucin.

1000/NNS

deaths averted / 1000 people

Proliferative fibrocystic change

defined by the presence of ductal hyperplasia. This is often referred to as usual ductal hyperplasia (UDH) to emphasize the absence of atypia in the lesion. There is a small increase in cancer risk in either breast (1.5 to 2-fold) with proliferative fibrocystic change

treatment of BPH

depends on the severity of symptoms. Reduction of fluid intake and alcohol and caffeine consumption may reduce symptoms. Medical treatments include α-blockers (to reduce the tone of the prostatic fibromuscular stroma) and 5-αreductase inhibitors (to reduce conversion of testosterone into DHT). If symptoms persist, transurethral resection of the prostate can be performed to remove the hyperplastic prostatic tissue impinging on the urethra. Numerous other modalities are available to ablate this tissue (including laser, hyperthermia, high-intensity ultrasound, etc). The net result of all of these procedures is a widening of the prostatic urethra and improved urine flow.

ADH

descriptive diagnosis made when an area of ductal hyperplasia does not meet criteria for diagnosis of ductal carcinoma in situ (DCIS), either by morphology or by size. In these cases, either the histologic changes are not well-developed enough for a definitive diagnosis of DCIS, or the area of concern is too small for a definitive diagnosis of DCIS. The concerning area is usually less than 0.2 cm in these cases. ADH is associated with a 4 to 5-fold increase in cancer risk in either breast.

Orthostasis

drop in SBP ≥ 20mmHg or DBP ≥ 10mmHg within 3 minutes of standing

how to differentiate between ductal and lobular carcinoma

ductular carcinoma has E-cadherin (stain for it!)

Home w/ home-based care (housecalls, HBPC)

homebound with medical needs able to be met at home provides: PCP, lab draws, urgent visits, procedures, SW coordination cost: insurance payments primarily medicare +/- medicaid/private insurance

PSA controversy

elevated PSA can also be caused by benign prostatic hyperplasia and prostatitis, leading to unnecessary biopsies. Furthermore, there is concern that PSA screening may identify many cancers that would have taken an indolent course, thereby leading to overtreatment. At the present time, the evidence seems to be swinging back in favor of PSA screening for men in the ~54-70 age range.

SIGECAPS

evaluate for depression - DSM symptoms check sleep, interest (loss), guilt, energy (lack), cognition/concentration, appetite, psychomotor, suicide can also use: PHQ9, geriatric depression scale

When to mammogram

every 2 years 50-74

The most common benign breast tumor in women is

fibroadenoma

'Classic' triad for Renal Cell Carcinoma (RCCA)

flank pain, hematuria, and mass --In the modern era an estimated of 2/3 of all localized RCC found 'incidentally' with the balance found on evaluation for hematuria

A1C targets in elderly

for older adults w multiple chronic illnesses, cognitive impairment or functional dependance, A1C <8.0-8.5. For ppl w/o these factors & w/ >8 yr life expectancy, A1C<7.5.

borderline tumors

formally recognized for more than 50 years and which fall between benign and malignant. Borderline ovarian tumors are noninvasive and have uncertain/low malignant potential. They occur in slightly older patients than do benign tumors, present at an early stage than do carcinomas, and have a favorable prognosis. However, over time, and even up to 20 years after initial therapy, certain ovarian borderline tumors can recur as carcinoma and may even lead to death. Close clinical follow-up is critical for patients with borderline ovarian tumors, including monitoring of the remaining ovary in patients who had only one ovary removed (unilateral oophorectomy) originally.

SLEWW

frailty syndrome > or equal to 3 of: --Slowness (TUG) --Low activity level (expends <270 kcal / week) --Exhaustion --Weakness (grip strength measured w/ hand dynameter) --Weight loss (>10 pounds unintentional in 1 year)

Endometrioid tumors

get their name from the presence of tubular glands that resemble endometrium. The morphology of these tumors is similar to the morphology of the tumors primary to the endometrium, but these tumors are primary to the ovary.

Non-atypical hyperplasia

has an increase in gland:stroma ratio with dilation and crowding of glands but lacks cytologic atypia. Progression to endometrioid adenocarcinoma occurs in about 1 to 3% over time.

Benign serous tumors

have a smooth and glistening cyst wall with no or very few, small papillary projections. They are classified based on their tissue components as cystadenomas (which contain mainly cystic areas), cystadenofibromas (which contain cystic and fibrous areas) and adenofibromas (which are mainly fibrous).

malignant glands in prostate

have darker cytoplasm than the surrounding benign glands and a small acinar architecture with no papillary infoldings. At high power, prominent nucleoli can be seen in many of the tumor cells, and no basal cells are identified surrounding the malignant glands (compare to the benign gland which is surrounded by a rim of basal cells).

borderline serous tumors

have more prominent papillary projections, while carcinomas have large areas of solid or papillary growth and may have prominent nodularity of the capsule. It is common for serous tumors to be bilateral (involving both ovaries). Microscopically, serous tumors have a cuboidal to columnar epithelial lining with abundant cilia in benign tumors.

Pelvic organ prolapse (POP)

herniation of pelvic organs to or beyond the vaginal walls

Detection of expression of the hormone receptors estrogen receptor (ER) and progesterone receptor (PR)

identifies cancers that will respond to hormone blocking therapy. Tamoxifen, a selective estrogen receptor modulator, is one mainstay of treatment for hormone receptor-positive tumors. It binds the estrogen receptor and blocks the effects of estrogen on breast tumors. In postmenopausal women, aromatase inhibitors are also used to treat hormone receptor-positive tumors. They work by blocking peripheral conversion of estrogen, so there is less estrogen to stimulate the tumor.

imaging for breast masses

if >30, mammogram and ultrasound, if <30, just ultrasound. Triple test for any solid masses.

UCSF-CAPRA system (prostate cancer)

incorporates patient age, PSA at diagnosis, Gleason score, clinical stage, and percent of biopsy cores involved with cancer to assess the risk posed by a given patient's tumor. With that information in hand, the urologist and patient can decide upon a course of action, which in the case of prostate cancer will typically be either active surveillance or definitive therapy such as prostatectomy or radiation therapy.

Senior Apartments

independent, >55 y.o. provides: socialization, transportation, communal activities cost: percentages of income (for those who qualify)

The core biopsy is used to distinguish between

invasive and in-situ breast cancer.

lobular neoplasia

is a spectrum of changes that includes atypical lobular hyperplasia (ALH) and lobular carcinoma in-situ (LCIS). These changes represent a clonal growth of cells that originate from the lobule of the breast. Although LCIS includes the term "carcinoma" in the name, it is generally interpreted as an indeterminate lesion or marker of breast cancer risk, and is usually an incidental finding. Overall, lobular neoplasia carries a 4 to 12-fold increase in cancer risk in either breast.

Falls/complications of falls

leading cause of death from injury in patients > 65 yo § Hip fractures are highly predictive of loss of function and mortality! • 40% of older patients with hip fracture never return to their prefracture walking ability

DCIS is treated by

lumpectomy, with or without adjuvant radiation therapy. The goal is to excise the area of DCIS completely with negative surgical margins. In some cases, re-excisions are needed to obtain negative margins for the patient. The treatment of DCIS is an evolving area, with some patients opting for close clinical follow-up and monitoring rather than surgery, as discussed above.

Low grade serous carcinomas

may originate in ovarian serous borderline tumors,

PDE-5 inhibitors Sildenafil Tadalafil

medical management of ED Cavernous nerve and endothelial muscles release NO -> ↑cGMP -> smooth muscle relaxation -> cavernous arteries fill *PDE-5 breaks down cGMP

endometrioid adenocarcinoma

microscopically similar to atypical hyperplasia, but is diagnosed as endometrioid adenocarcinoma when there is increasing crowding and complexity of the glands leading to, crucial to the diagnosis, loss of endometrial stroma among the glands (i.e., back-to-back glands). Mutations in DNA mismatch repair genes are found in about 20% of sporadic tumors and may indicate the need for further testing for Lynch syndrome (germline mutations in DNA mismatch repair genes). In contrast, the more aggressive (type II) high-grade serous carcinomas show p53 mutations.

Endometrial carcinoma

most common invasive tumor of the female genital tract. Endometrial carcinomas have classically been broadly stratified into: • Type I, which are estrogen-dependent and generally less aggressive (prototype is endometrioid adenocarcinoma) • Type II, which are estrogen-independent and more aggressive (prototype is high grade serous carcinoma).

leiomyosarcoma

much rarer than leiomyomas. Clinically, they may be suspected if myometrial tumor growth is present in a menopausal women. symptoms/signs: abnormal uterine bleeding, a pelvic mass, and pelvic pain. Grossly, leiomyosarcomas may show more prominent soft, yellow necrosis and hemorrhage than do leiomyomas . They typically occur singly or as a larger dominant mass with smaller benign leiomyomas in the background. Microscopically, leiomyosarcomas are diagnosed based on the presence of two of three criteria: 1) cellular atypia, 2) increased mitotic activity, and 3) necrosis.

Benign epithelial lesions are categorized into 2 groups:

non-proliferative fibrocystic change and proliferative fibrocystic change.

Cervical Cancer Pathogenesis

normal -> HPV Infection (can persist here, regress, or progress to) -> Precancer (can regress, or progress to) -> cancer (via invasion) risk factors (6): correlates of exposure to HPV: age at first intercourse, number of sexual partners, condom use long-term OC use smoking multiparity HPV genotype

Penile prosthesis

option to treat ED use when med options fail

high grade serous carcinomas

originate in the fallopian tube fimbriae or from serous inclusion cysts in the ovary associated with p53 mutations and do not arise from the low grade serous tumors.

Classification of voiding pathology (4)

overactive bladder = leak overactive outlet = retention underactive bladder = retention underactive outlet = leak

pathologic stage of the tumor: prostate cancer

pT2 = tumor confined to prostate, pT3a = tumor invades beyond prostate, pT3b = tumor invades seminal vesicles, pT4 = tumor invades rectum, levator muscles, or pelvic wall (there is no pT1 for prostate cancer). Tumor present in regional lymph nodes is designated as pN1. The pathologic staging predicts the risk of recurrence and can be used to select additional therapy as needed; in many cases, no adjuvant therapy is required.

The most common symptoms described by patients with breast disorders are

pain, a palpable mass, lumpiness without a discrete mass, or nipple discharge.

causes of polypharmacy (3, 3)

patient factors: inc. chronic conditions, phsycho-social aspects, complex drug Tx. systemic factors: multiple prescribers, multiple pharmacies, prescribing cascade

Mastectomy is typically recommended for

patients with inflammatory carcinoma, for patients in whom lumpectomy will result in poor cosmetic outcome, patients with high genetic risk and for patients with underlying illness that prevents tolerance of radiation therapy.

POP treatment

pessaries or surgery, if symptomatic • Limited literature on older patients, largely excluded from trials • But similar operative risks and outcomes in older and younger patients

"triple test" for breast cancer

physical exam, breast imaging, and pathology.

POLST

physician order for life sustaining treatment

Grossly, endometrioid adenocarcinoma is

polypoid mass that lines the endometrium and invades into the myometrium. Tumor can extend directly into adjacent structures, with eventual lymph node spread and distant metastasis. Endometrioid adenocarcinomas are graded (grades 1-3) based on how extensively the glands coalesce to form solid epithelial proliferations, with grade 1 tumors showing numerous well-formed glands (less than or equal to 5% solid formation) and grade 3 tumors showing more than 50% solid formation.

Cervical cancer histology (most common cancers)

squamous cell (84%) Adenocarcinoma (9%) Adenosquamous (3) Clear Cell (1%) Other (3%)

Frailty

state of increased physiological vulnerability to stressors • Assessment -> Timed Up and Go • Poorer surgical outcomes

BRCA1 mutations

present in about 5% of ovarian cancer patients who are younger than 70; the risk of developing ovarian cancer in patients with either BRCA1 or BRCA2 mutations is 20 to 60% by age 70. Because of this large increase in ovarian cancer risk, women with BRCA mutations or with strong family histories of certain cancers are screened for ovarian cancer, and management with prophylactic removal of bilateral ovaries and fallopian tubes (risk-reducing salpingo-oophorectomy (RRSO)) is standard for those patients.

risk factors for sexual dysfunction

problem with sex causing distress or difficulties --physical and emotional health status --role of age --relationship length (inverse correlation) --mental health status --hormone status (chemo, surgical menopause)

Serous tumor

produces thin, clear or slightly discolored fluid secretions. these tumors are the most common ovarian malignancies (about 40% of all ovarian cancers). Within the serous category, about 70% of tumors are benign or borderline and 30% are malignant.

impacts of aging on health

risk for age-related diseases (ex. alzheimer's) + change in organ function due to age (ex. gfr going down over time) -> clinical impact due to overall aging -> disability, dependence, death

PPV vs. NPV vs. Specificity vs. Sensitivity

sensitivity: true positives over total w/ disease specificity: true negatives over total w/o disease PPV: true positives over total positives NPV: true negatives over total negatives

most common type of ovarian cancer

serous (37%) Endometrioid (18%) Undiff (14%) Borderline (12%)

The three major histologic types of epithelial tumors are

serous, mucinous, and endometrioid.

Lobular carcinoma is composed of

small, uniform cells that infiltrate in a single-file pattern and are not organized into glandular or tubular structures. The cells of lobular carcinoma (whether in-situ or invasive) lack expression of E-cadherin, a cell adhesion molecule, resulting in the single-file growth pattern.

risk factors for late life depression (3, 5)

socioeconomic and psychiatric: 1) caregiver role (25-50% family caregivers experience depression) 2) living alone 3) negative life events including bereavement Medical: 1) cognitive impairment/dementia 2) complex chronic illness (cancer, lung disease, cardiovascular disease, diabetes) 3) arthritis and associated pain or neuropathy 4) sensory impairment (ex. hearing, vision) 5) Age

uterine tumors (4)

• Endometrium • Corpus (sarcomas) • Cervix • Trophoblast (gestational)

Three modalities are commonly used in patients who are not eligible for active surveillance or whose tumors have progressed during active surveillance:

surgery (radical prostatectomy), external beam radiation, or brachytherapy (which involves implanting radioactive seeds throughout the prostate). All of these approaches can potentially be curative in the setting of organ-confined disease

For invasive ductal carcinoma

surgery is the mainstay of treatment. In addition, depending on the pathologic characteristics of the tumor, some patients will have adjuvant therapy which can include hormone blocking therapy, radiation therapy, and/or chemotherapy. For most patients, adjuvant therapy is given after the surgery to reduce the risk of recurrence or metastasis. Neo-adjuvant therapy (adjuvant therapy administered before surgery) is offered to select patients to shrink the tumor before surgery. Close consultation between the patient, the surgeon, and the other members of the treatment team is important for deciding between a lumpectomy or mastectomy, factoring in the patient's choice.

Geroscience Hypothesis

targeting fundamental aging processes might delayu, prevent, alleviate, or reverse a wide range of diseases and conditions for which age is the primary non-modifiable risk factor --operationalize aging --outcomes: time to 2nd/3rd major chronic dz, resilience, 'healthspan': multimorbidity, function, geriatric syndromes

Multimorbidity

the presence of multiple diseases in an individual patient that compound each other, resulting in collectively adverse effects on health function, and quality of life

development of serous borderline tumors and low grade serous carcinomas

thought to be a continuous pathway due to KRAS and BRAF mutations.

caregiver strain index

to assess caregiver stress --medicare does not cover pay for caregivers (excepting hospice) --medical -> IHSS (in-home support services) in home or shelter

Most staging surgeries for ovarian carcinomas consist of

total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymph node dissection. Omentectomy is performed because ovarian serous carcinomas have a propensity to spread to the adipose tissue of the omentum. Sampling of peritoneal/ascitic fluid to look for floating malignant cells is also performed. The pathologic stage (described in the pathology report after surgical staging) will inform next steps in treatment and management.

Cognitive impairment (screen, reversible causes, labs)

use MMSE or MOCA reversible causes: depression, metabolic or medical conditions ex. infection labs: CBC, CMP, TSH, B12, HIV, RPR

In addition to classification by molecular subtyping, gene profile tests are available (for classifying breast cancer) that

utilize microarray or RT-PCR methods

Characteristics of frailty (SLEWW)

weight loss, exhaustion, slowness, low activity level, weakness

PSA is useful after prostatectomy because

where would PSA come from if not pathologic source?

Atypical hyperplasia

which has an increase in gland:stroma ratio and cytologic atypia. The glands are typically crowded and show complex architecture such as branching, but endometrial stroma remains present among the glands. Atypical cells show loss of normal perpendicular orientation to the basement membrane (loss of nuclear polarity) and show cytologic changes such as rounding of the nuclei, open (vesicular) chromatin, and prominent nucleoli. It can be difficult to distinguish atypical hyperplasia from carcinoma (defined by loss of intervening endometrial stroma) on a biopsy specimen. Atypical hyperplasia is treated by hysterectomy or by a trial of progestin therapy and close clinical follow-up in younger women who want to preserve childbearing. The progression rate to carcinoma is high: up to 48% of women with atypical hyperplasia on biopsy are found to have carcinoma upon hysterectomy.

Detection of overexpression of the HER2 protein or amplification of the HER2 gene

will identify patients who can benefit from anti-HER2 treatment. HER2-positive tumors can be treated with the monoclonal antibody drug trastuzumab (Herceptin), which binds and inactivates the HER2 growth factor receptor, slowing tumor growth.

Cervical cancer early detection (stratified by age)

§ 2 screening approaches are currently in use in the USA • Cytology (Pap test) every 3 years • Cytology (Pap test) plus HPV testing every 5 years • HPV testing detects the high risk HPV types associated with cervical cancer § Start cervical cancer screening at age 21 § Women ages 21-29: Pap test every 3 years § Women ages 30-65: Pap test + HPV test every 5 years, or Pap test every 3 years § If no history of moderate or severe dysplasia, may stop screening after age 65 or after hysterectomy § Women with a history of cervical cancer should continue with annual surveillance

Endometrial Cancer early detection (3)

§ 90% of women with endometrial cancer present with postmenopausal bleeding § No satisfactory or cost-effective screening for endometrial cancer § Consider biopsy / ultrasound for Lynch / HNPCC family members

Ovarian cancer signs and symptoms (7)

§ Abdominal distension/bloating § Early Satiety/difficulty eating § Abdominal/pelvic pain § Urinary urgency/frequency § Constipation § Nausea § Anorexia

Endometrial cancer symptoms (3)

§ Abnormal bleeding or discharge § Postmenopausal bleeding § Pressure in pelvis

Non-specific symptoms characteristic of an "atypical" presentation in an older adult

§ Acute confusion (delirium) § New functional decline (eg change in mobility) § Change in behavior § Change in appetite § Generalized weakness § New or worsening fatigue § New urinary incontinence § A fall § Negative symptoms: absence of fever, pain

cervical cancer prognostic factors

§ Age § Stage § Grade § Histology § Size of tumor § Depth of invasion § Lymph node involvement § Vascular involvement

Endometrial cancer prognostic factors (8)

§ Age § Stage § Grade § Histology • Serous, clear cell § Depth of invasion § Lymph node involvement § Vascular involvement § Peritoneal cytology

Cervical Cancer Risk Factors (4)

§ Almost all cervical cancer is caused by a persistent infection with HPV, human papillomavirus § Most often affects women between ages 30-50, but younger and older women are also at risk § Smoking § Immunosuppression

CA-125 blood test

§ Antigen OC-125 is a high MW glycoprotein § Elevated in 80% of patients with ovarian cancer § Most likely to be elevated in advanced stages § Only elevated in 50% early stage disease § Also elevated in other benign conditions—menses, pregnancy, leiomyoma, endometriosis, PID § Useful in post-therapy follow-up

cervical cancer symptoms (3)

§ Bleeding after intercourse § Excessive discharge and abnormal bleeding between periods § Most women will have no symptoms

cervical cancer early detection facts (4)

§ Cervical cancer is uncommon before the age of 30 § Variable latency period for progression of dysplasia to cancer— usually years § 25% of cervical cancer cases is women over age 65 § 50% of women with cervical cancer have never had a Pap smear

Recurrent Ovarian Cancer

§ Chemotherapy § Secondary Cytoreduction in specific cases § Radiation therapy in select cases § Molecular targets for biological response • Bevacizumab • PARP inhibitors • Hormone therapy • Immunotherapy

risks of various procedures in old old (3 - and when would it help?)

§ Colonoscopy: perforation, bleeding, stroke... § Tight blood pressure control: falls, fractures... § Tight sugar control: hypoglycemia, coma § Colorectal cancer screening >10 years § Tight blood pressure control > 2 years § Tight blood sugar control in diabetes > 8 years

cervical cancer diagnosis

§ Colposcopy for abnormal Pap smears § Biopsy abnormal lesions § MRI to evaluate for local invasion § PET CT or PET MRI to evaluate for metastatic disease

geriatric syndromes

§ Common health conditions that do not fit into discrete disease categories § Multifactorial etiologies -> reflect composites of dysregulation in multiple systems § Common risk factors among the syndromes § Highly prevalent § Substantial association with quality of life, functional decline, and increased morbidity and mortality

normal urination

§ Complex interplay of autonomic and somatic circuitry with the goal of maintaining a low pressure bladder during filling and periodic voluntary bladder emptying

cervical cancer treatment (early stage) (3)

§ Early Stage: Excision • Cone biopsy or radical trachelectomy for fertility preservation • Depth of invasion and size of tumor associated with lymph node involvement • Radical hysterectomy (with negative lymph nodes) and chemoradiation have equivalent survival for early stage disease

Ovarian cancer treatment

§ Early Stage: • Primary Staging, then Platinum-Paclitaxel chemotherapy ‒ Stage I: 3-6 cycles, depending on histology ‒ Stage II: 6 cycles § Advanced Stage Disease • Primary Surgery, then chemotherapy • Neoadjuvant chemotherapy, then surgery, then adjuvant chemotherapy • Consider maintenance chemotherapy (PARP inhibitors, bevacizumab)

endometrial cancer treatment (early stage) (4)

§ Early Stage: • Primary surgical staging (minimally invasive) • Adjuvant treatment depending on tumor distribution, prognostic factors, and completeness of surgical staging • Desiring future fertility: consider progestin therapy • Medically comorbidities: consider primary radiation versus progestin therapy

Endometrial cancer diagnosis (5)

§ Endometrial sampling—biopsy or D&C • Pap smear is not a screening test for endometrial dz § Consider ultrasound or CT if needed to assess uterine size § Consider MRI if needed to assess depth of myometrial invasion § Consider CA125 if serous histology § Consult with a gynecologic oncologist

Ovarian Cancer Staging

§ Exploratory laparotomy / laparoscopy § Peritoneal washings § Total hysterectomy § Bilateral salpingo-oophorectomy § Omentectomy § Pelvic & Para-aortic Lymphadenectomy § Peritoneal, Gutter, & Diaphragm evaluation

Normal bladder emptying

§ High-level vesical afferent activity (PNS) § Parasympathetic activation via Pelvic nerve • Detrusor contraction • Relaxation of outlet § Inhibition of external sphincter § Inhibition of sympathetic outflow

approach to geriatric syndromes (4)

§ Identify it § Focus on what matters to the patient § Medical and non-medical (environment, social, caregiver support) § Small changes can have big impact

Ovarian Cancer Risk Factors (5)

§ Increasing age § Family history of ovarian, fallopian tube, primary peritoneal cancer, or premenopausal breast cancer § Personal history of premenopausal breast cancer § Intertility / never becoming pregnant § Oral contraceptive pill use is protective

recurrent cervical cancer

§ Local recurrence: • Previously treated by surgery alone--> Radiation • Previously treated by radiation therapy--> Pelvic exenteration, rarely Radical hysterectomy § Metastatic disease: • Chemotherapy (platinum-taxane +/- bevacizumab) • Molecular targets for biological response ‒ Immunotherapy

Normal bladder filling/storage

§ Low pressure rise despite increase in volume (viscoelastic) § Sympathetic activation via Hypogastric nerve • Detrusor inhibition • Internal sphincter contraction § Somatic activation via Pudendal nerve • External sphincter contraction § Parasympathetic outflow inactive

prevention/treatment strategies for frailty (4)

§ Maintaining physical activity and muscle mass is critical in older adults at risk of frailty § Resistance, or strengthening, exercise is effective in increasing muscle mass, strength, and walking speed in frail older adults § Preventing immobility is critical § In many studies, nutritional supplementation appears to be effective only when added to exercise

Gestational trophoblastic tumors (5)

§ Molar pregnancies occur in about 1:1000 pregnancies. § Complete hydatidiform moles have higher malignant potential than partial hydatidiform moles. § Ultrasound imaging is fairly distinctive, with hCG being an excellent tumor marker. § Initial management is by uterine evacuation. § High risk Invasive mole and even metastatic choriocarcinoma respond well to chemotherapy, with good subsequent pregnancy outcomes as well.

Ovarian cancer and risk

§ Most women with risk factors for ovarian cancer will never actually get ovarian cancer. § Most women with ovarian cancer do not have any strong risk factors for the disease. § Up to 25% of ovarian cancer is hereditary. § All women with ovarian, tubal, peritoneal carcinoma should be considered for genetic counseling/testing.

Adverse drug reactions key points (4)

§ New symptoms = ADR until proven otherwise § Obtaining accurate med list (new meds, adherence) is KEY § Know databases to look up drug/disease interactions until you become familiar § Begin to recognize dangerous drug (Beer's list)

polypharmacy may increase (7)

§ Non-adherence § Adverse drug events (ADE) § Drug-drug interactions § Admissions § Geriatric Syndromes § cognitive impairment, falls, hip fractures, urinary incontinence, disability, and delirium § Mortality --HR 1.27-2.23

Elimination changes for the elderly

§ Normal sCr does not equal Normal GFR in elderly § Less muscle mass -> lower creatinine § "concealed" renal impairment in 14%, associated w/ ADR

Endometrial Cancer protective factors (2)

§ Parity § Progestin therapy • Oral Contraceptive Pills • Progestin intrauterine system

Ovarian Cancer Protective Factors (5)

§ Parity § Breast feeding § Use of birth control pills § Tubal ligation § Oophorectomy

Ovarian cancer early detection

§ Pelvic examination § Pelvic ultrasound § CA125 § Multimodality screening § Serial CA125 algorithms § New markers, genomics, proteomics

Accelerated aging in vulnerable populations (5)

§ Physiological changes occur at increased rate in vulnerable adults • Cognitive Impairment (1/4 of unhoused adults <24 on MMSE) • Falls (50% of unhoused adults) • Incontinence (50% of unhoused adults) • Functional Impairment (1/3 of unhoused adults unable to perform ADLS at age 50) • Depression

recurrent endometrial cancer (4)

§ Radiation therapy, especially for vaginal/pelvic recurrences § Chemotherapy (platinum-taxane +/- bevacizumab) § Molecular targets for biological response • Bevacizumab • Hormonal therapy • Immunotherapy • Trastuzumab § Occasionally, tumor resection

Diabetes in old age (3)

§ Risk of diabetes increases with age § Older adults with diabetes can expect a 10-year reduction in life expectancy and a mortality rate nearly twice that of people without diabetes. • Vascular complications such as atherosclerosis, neuropathies, loss of vision, and renal insufficiency.

Ovarian neoplasm treatment and prognosis

§ Serous Cystadenoma • Treatment: Cystectomy, USO • Survival 100% § Borderline Serous Tumor • Treatment: Usually Hyst BSO + excision extraovarian tumor • Survival 80-100% § Serous Carcinoma • Treatment: TAH BSO + debulking + chemotherapy (usually) • Survival 35% to > 80%

Ovarian Cancer Prognostic factors

§ Stage § Grade § Histology § Age / Performance Status § CA125 level § Presence of ascites § Largest tumor mass § Volume of residual disease § Platinum sensitivity § BRCA1/2 mutation status

Ovarian Cancer Surgery

§ Staging: to assess extent of disease, prognosis, treatment options § Cytoreduction/Debulking: to resect tumor to minimal (ideally microscopic) residual disease § May be partnered with neoadjuvant chemotherapy

Endometrial Cancer Risk Factors (8)

§ Taking estrogen alone without progesterone § Obesity § Later menopause § Diabetes § Never becoming pregnant § Hypertension § Family history of endometrial or colon cancer § Use of tamoxifen

Ovarian Cancer Diagnosis

§ Tumor markers • CA125, AFP, hCG, LDH, Inhibin B § Imaging • Ultrasound, MRI, CT, CXR § In general, an ovarian mass should not be biopsied § Strongly consider in a postmenopausal woman with pelvic mass, and elevated CA125 § Consult with a gynecologic oncologist

endometrial cancer staging (4)

§ Washings § Hysterectomy, removal of ovaries & tubes § Lymph node assessment (sentinel mapping vs. lymphadenectomy) • Based on grade, size of tumor, depth of invasion, histology, cervical involvement, adnexal involvement, suspicious lymph nodes by imaging

Suggestions for increasing adherence for all older adults include: (5)

· Using Medi-sets · Using retail pharmacies that provide bubble-packs for chronic medications · A medication calendar · On-line/smartphone applications for tech-savvy patients or providers · Using the "teach back" method to promote understanding and purpose of the treatment plan/medications

Treatment of Priapism

Ø Non-Ischemic Priapism: • Observation • Anti-androgens to reduce erections à allow for spontaneous fistula closure • Angioembolization vs Surgical Ligation Ø Ischemic Priapism: • Ice packs, exercise, ejaculation, terbutaline, pseudoephedrine are considered but seldom effective • Irrigation/Aspiration with saline • Intracavernous Injection of sympathomimetics (phenylephrine) • Surgical Shunt in severe cases

Priapism

Ø Persistent penile erection not associated with sexual arousal • Ischemic (95% of cases): Painful, rigid erection associated with blood disorders (SCD), advanced malignancy, drugs • Non-Ischemic: Usually painless, semi-rigid erection associated with history of trauma leading to AV fistula in the penile vasculature Ø Typically priapism subtypes can be characterized by history alone • Adjunct Diagnostics include Penile Blood Gas, Doppler Ultrasound

Transurethral therapy (MUSE)

Ø Small suppository applied to urethra Ø Advantages • Does not require needles • Independent of nerve supply Ø Disadvantages • Urethral pain • Partner discomfort • Modest Efficacy

Emptying (2)

‒ Bladder contraction of adequate strength and duration ‒ No obstruction

Filling (6)

‒ Normal capacity 400-500 cc ‒ Normal sensation ‒ Normal compliance (ΔV/ΔP) ‒ No leakage ‒ No bladder contractions ‒ Ability to postpone voiding until a socially appropriate time/place

neoadjuvant chemotherapy breast cancer

• Allows assessment of response to therapy and tailoring therapy due to lack of response • Allows tumor shrinkage and breast conservation • Offered to patients who will need chemotherapy regardless of surgical pathology • Common regimen - AC-T A - doxorubicin (Adriamycin) C - cyclophosphamide (Cytoxan) T - paclitaxel (Taxol)

mammaprint

• Analyzes a group of 70 genes • Reports a high or low risk for developing metastases within the 1st ten years after diagnosis • Used in ER positive or ER negative breast cancers

breast cancer take-aways

• Assess breast cancer risk • Always start with diagnostic imaging - Obtain needle biopsy if suspicious features • Breast cancer management depends on tumor biology - ER, PR, HER2 - Grade - Genomic risk - Age - Patient preference (shared decision making) and treat: Surgery, Systemic therapy, Radiotherapy, Genetic testing, Possible neoadjuvant approach

breast cancer high risk

• Average breast cancer risk is 12% over lifetime • There are two ways to be "high risk" - Genetic/familial risk à lifetime risk of breast cancer ≥ 20% • Applies to all women - Lifestyle/environmental/personal risk -> 5 year risk of breast cancer ≥ 1.7% • Applies to women over age 35

side effects doxarubicin / cyclophosphamide / paclitaxel

• Doxorubicin - cardiotoxicity - dilated cardiomyopathy • Cyclophosamide - hemorrhagic cystitis • Paclitaxel - peripheral neuropathy • All can cause hair loss, pancytopenia, nausea/vomiting

BRCA Mutation

• Early onset breast cancer linked to inherited predisposition on chromosome 17q21 identified by Mary-Claire King, PhD, and dubbed BRCA1 • BRCA1 and BRCA2 are important in DNA double strand break repair by homologous recombination • Homozygous BRCA2 mutation results in Fanconi anemia • Poly(ADP-ribose) polymerase (PARP) is involved in single strand break repair • BRCA deficient cells are dependent on PARP activity, and therefore synthetic PARP inhibitors are lethal with BRCA deficient tumors • BRCA mutations occur in <1% of general population, and in 2.5% Ashkenazi population

elderly pharmacokinetics summary (4)

• Elderly patients take many medications • Pharmacokinetic changes, primarily in excretion -> greater overall exposure to medication's adverse effects • Cockcroft & Gault is used to estimate GFR, but may over-estimate in elderly • Be cognizant of psychoactive and blood pressure medications enhanced potential for adverse reactions in the elderly

Endometrial cancer work-up (5)

• Endometrial sampling—biopsy or D&C (gold standard) - Pap smear is not a screening test for endometrial cancer • Consider ultrasound or CT if needed to assess uterine size • Consider MRI if needed to assess depth of myometrial invasion • Consider CA125 if serous histology • Consult with a gynecologic oncologist

Renal Cell Carcinoma (epidemiology, presentation, workup, treatment)

• Epidemiology - Males > females 2:1, peak age of incidence 40-60 yrs • Presentation - "Classic" triad: flank pain, hematuria, and palpable mass - Now commonly found incidentally - Paraneoplastic syndromes: HTN, hypercalcemia, ↑ EPO/polycythemia, ↑ LFT's with metastasis (Staufer syndrome) • Workup - Labs: CBC, CMP, UA, urine microscopy - Imaging: contrast-enhanced imaging (CT preferred), consider CXR - Percutaneous fine needle biopsy (if ambiguity regarding diagnosis) • Treatment: surgery - Partial/radical nephrectomy - Percutaneous cryoablation/radiofrequency ablation

Ovarian tumors (3)

• Epithelial cell tumors • Sex cord-stromal tumors • Germ cell tumors

prevailing strategies for managing frailty

• Exclude any modifiable precipitating causes of frailty, including causes that are treatable or environmental • Improve the clinical manifestations of frailty, especially low physical activity, strength, exercise tolerance, and nutrition • Minimize the consequences of vulnerability, whether in terms of environmental risks, risks from low social support, or risks from stressors such as acute illness or injury, hospitalization, or surgery

Fine Needle Aspiration versus Core Needle Biopsy

• FNA obtains cells without surrounding stroma/architecture • Cannot determine whether carcinoma cells are contained within duct or have invaded beyond basement membrane - Therefore cannot distinguish between DCIS and IDC • Less morbid than core biopsy

Workup for incontinence

• Focused history - Frequency, severity of leakage, impact on life - Symptom questionnaires - Pt expectations of treatment • Focused physical exam - Pelvic Workup for Incontinence • Labs: - UA and UCx • Other diagnostic studies - Pad testing and/or voiding diary - Urodynamics - Post-void residual - Imaging - Cystoscopy

Surgical options for BPH - Simple Prostatectomy (open or robotic assist) (2)

• Generally reserved for very large prostates • Higher risk of incontinence and blood loss

systemic therapy for breast cancer

• Given to decrease the risk of distant recurrence • Types of systemic therapy - Endocrine therapy - Chemotherapy

endocrine therapy for breast cancer

• Given to decrease the risk of distant recurrence (and also reduces chance of second primary breast cancer) • Taken for 5-10 years • Tamoxifen - Selective estrogen receptor modulator • Aromatase inhibitor

Breast Imaging Reporting and Data System (BIRADS) (6)

• Gives classification and recommendation - BIRADS 1: negative - BIRADS 2: benign finding (benign appearing calcifications, calcifying fibroadenoma, oil cyst, lipoma, implant) - BIRADS 3: probably benign • Short interval follow up recommended (usually 6 months) • Risk of malignancy < 2% - BIRADS 4: suspicious • Consider biopsy (3-94% chance of malignancy) - BIRADS 5: high suggestive of malignancy • >95% chance of being malignancy - BIRADS 6: known malignancy

HER2 Positive Breast Cancer

• HER2 (Human Epidermal growth factor Receptor 2 ) is transmembrane growth factor receptor that activates intracellular signaling pathways • Ligand binding leads to HER protein dimerization and phosphorylation of intracellular tyrosine kinase domain • Essential for normal development of brain, skin, lung, GI tract • Overexpression of HER2 (either through gene amplification or upregulation of transcription) in mammary epithelium leads to increased proliferation and tumorigenic growth

most predictive risk factors for falls (11)

• Having fallen previously • Fear of falling • Gait or balance difficulty • Muscle weakness • Polypharmacy! • Cognitive impairment (impaired judgment, learning, memory) • Environmental hazards • Dizziness or orthostatic hypotension • Vision problems • Age > 80 • Problems doing activities of daily living

hereditary breast cancer

• Hereditary breast cancer accounts for 5-10% of all cases • Penetrance - High penetrance mutations: relative risk (RR) ≥ 5 - Moderate penetrance mutations: RR from ≥ 1.5 to < 5 - Low penetrance mutations: RR ≥ 1.01 and < 1.5 • Most genetic testing evaluates for high penetrance mutations

oncotype Dx (breast cancer)

• Includes expression profiling of 21 genes • Used in ER positive breast cancers only • Results - Chance of breast cancer recurrence - Benefit from chemotherapy versus hormone therapy alone

ultrasound features of breast malignancy (3)

• Irregular shape • Spiculated margins • Width-AP dimension <1.4 (wider is better)

General management of ED

• Lifestyle changes, medication changes • Oral medications • Vacuum erection devices • Urethral suppositories • Injection therapy • Penile implants • Vascular surgery

Ddx for hematuria (7)

• Malignancy - Renal, ureteral, bladder, rarely urethral or prostate • Infection - most common - Pyelonephritis, cystitis • Nephrolithiasis - Typically associated with renal colic - Types of stones: • Medical renal disease - Urine microscopy: casts, dysmorphic RBC's - Urine protein: elevated • Trauma • BPH • Miscellaneous - Bleeding disorders, arteriovenous malformations, heavy exercise, interstitial cystitis

risk factors for accelerated aging

• Marginal housing • Childhood adversity • Reduced access to healthcare • Substance use • Environmental exposure • Early onset of chronic illness

Pre-op factors to consider in older adults, among others:

• Medication review • Nutritional status • Delirium risk • Functional status • Decision making capacity • Patient's goals, values, preferences

when there are grandparent caregivers

• Monitor the well-being of the grandparent caregiver • Focus on safety • Provide anticipatory guidance based on experience and resources of the grandparent • Assess and counsel grandparents regarding social service supports and financial resources • Refer to local grandparenting support groups and resources

mastectomy vs. partial mastectomy

• NSABP B-06 - Randomized 1851 women to mastectomy, lumpectomy, lumpectomy w/radiation - Stage I-II - Tumors 4cm or less • Local recurrence rate at 20 year follow up - Lumpectomy alone 39% - Lumpectomy plus radiation 14% • No survival difference between lumpectomy, lumpectomy/radiation, or mastectomy

treatment for HER2 positive breast cancer

• Neoadjuvant chemotherapy for HER2 positive node positive disease • Chemotherapy regimen - TCH or AC-TH • TCH - Paclitaxel (Taxol), carboplatin, trastuzumab (Herceptin) • AC-TH - Doxorubicin (Adriamycin), cyclophosphamide, paclitaxel (Taxol), trastuzumab (Herceptin)

peripheral mechanisms of ejaculation

• Peripheral mechanisms: --Emission: Under the control of the sympathetic nervous system from T10-L2 nerve roots (hypogastric nerve) --Ejection: Under the control of the somatic nervous system from S2-4 nerves (pudendal nerve)

work-up of palpable breast mass

• Physical exam should characterize the lesion: - No abnormality present • reassure - A thickening without the characteristics of a dominant mass • Based on clinical suspicion, either re-evaluate in 2 months, or obtain imaging - Fibrocystic changes can fluctuate with menstrual cycle - A dominant mass with benign characteristics on palpation (mobile, rubbery, no skin dimpling) • Obtain imaging - A dominant mass with malignant characteristics • Obtain imaging AND biopsy regardless of imaging findings

endometrial cancer treatment (advanced stage) (2)

• Primary surgery (including debulking) • Chemotherapy and/or radiation therapy depending on tumor distribution, prognostic factors, residual disease

gene expression profiling (breast cancer)

• RNA based gene expression profiling of the tumor used to determine prognosis and predict response to systemic therapy

invasive breast cancer work up

• Referral to genetics if meet criteria (young age, triple negative tumor, high risk population, significant family history) • If symptomatic in any way or abnormal labs consider bone scan, abdomen/pelvis/chest CT • If clinical stage 3a (T3, N1, M0) obtain imaging to rule out metastatic disease regardless of symptoms - Bone scan, chest/abdomen/pelvis CT - Or whole body PET/CT

proliferative lesions w/o cellular atypia

• Relative Risk is 1.5-2 - Moderate or florid usual ductal hyperplasia - Intraductal papilloma - Sclerosing adenosis (distorted epithelial and myoepithelial cells and sclerotic stromal elements) - Fibroadenoma (well circumscribed, containing glandular and stromal elements) • If enlarging over time, consider Phyllodes tumor - Radial scar (central zone of fibroelastosis from which ducts and lobules radiate) • Excision recommended because of 10% upgrade rate

nonproliferative lesions (fibrocystic change)

• Relative Risk of breast cancer is 1 - Cysts - Papillary apocrine change - Epithelial related calcifications - Mild usual ductal hyperplasia

Therapies for sexual desire/arousal disorder (non-pharmacologic) (5)

• Sex education • Sex therapy (address relationship, psychosexual issues, recalibrate expectations) • Sexual enhancement devices/gels • Lubrication • Vaginal moisturizers

Grandparent caregivers have worse physical and mental health outcomes

• Social isolation • Financial vulnerability • Neglect own health ...yet there are benefits to both grandparent and grandchild

Therapies for sexual desire/arousal disorder (pharmacologic) (5)

• Substitute offending agents if possible (SSRIs) • Flibanserin (antidepressant) - FDA approved • Testosterone (patch, gel, cream) off label in postmenopausal pts • Bupropion off label • Sildenafil (Viagra) - off label, pts on SSRIs

treatment for invasive breast cancer

• Surgical therapy - Lumpectomy with radiation (breast conservation) - Mastectomy - Stage axilla with sentinel node biopsy • Chemotherapy - Usually given to patients with node positive disease - Usually given to patients with hormone receptor negative disease - Can be given before or after surgery • Radiation - Given after lumpectomy - Given to chest wall after mastectomy if large tumor, multiple positive nodes, young age, or other features predictive of high local recurrence

Pelvic organ prolapse evaluation (5)

• Symptoms relating to POP and effect on life • Urinary incontinence • Obstetric history • Sexual history • Surgical history

Trastuzumab (Herceptin)

• Targeted therapy for HER2 positive breast cancer • Monoclonal antibody to the extracellular domain IV of HER2 • Antibody binding has three effects: - Ubiquitination and degradation of HER2 - Antibody dependent cellular cytotoxicity - Blocking dimerization of HER2, leading to suppression of PI3K/Akt pathway • Overall results is suppression of tumor cell growth, proliferation, and survival • Side effects - cardiotoxicity (especially in patients who previously received anthracyclines like doxorubicin)

Molecular biology of sexual response (important)

• The *nitric oxide/cGMP/PDE5 pathway* is of primary importance in genital vasodilation • nNOS initiates vasodilation • eNOS maintains vasodilation • PDE5 is primary target of oral drugs for erectile dysfunction • Additional pathways are involved (inhibition of adrenergic signaling, acetylcholine release, etc)

subtypes of breast cancer

• Three main markers - Estrogen receptor (ER) - Progesterone receptor (PR) - HER2 • ER+PR+HER2 negative usually has best prognosis with longer disease free interval • ER-PR-HER2- (triple negative) - Higher incidence in BRCA mutation carriers • HER2 positive - Targeted therapy with monoclonal antibody against HER2 protein available (trastuzumab aka Herceptin)

Testis Cancer

• Typically present as painless nodule WITHIN the testicle • May present as distant metastasis • ~95% are germ cell tumors (eg seminoma, yolk sac, teratoma, embryonal, mixed) Evaluation: • Scrotal sonogram • AFP, HCG, LDH • Cross sectional imaging of chest/abdomen/pelvis Treatment: Radical Orchiectomy

Urinary tract imaging modalities

• Upper urinary tract: kidneys, ureters - CT scan (CT urogram ideal) - MRI (w/wo contrast), ultrasound, retrograde pyelography • Lower urinary tract - Cystoscopy (often accompanied by cytology test)

chemotherapy for breast cancer

• Usually given to patients with node positive disease • Always given to patients hormone receptor negative disease • Always given to patients with Her2 positive disease - Chemotherapy + Herceptin (monoclonal antibody against Human Epidermal growth factor Receptor 2) • Can be given before or after surgery - Before surgery is called neoadjuvant

Family history factors suggestive of BRCA mutation

• breast cancer diagnosed before the age of 50 • cancer in both breasts in the same woman • both breast and ovarian cancer in the same woman or in the same family • multiple breast cancers • two or more primary types of BRCA-related cancers in a single family member • cases of male breast cancer • Ashkenazi Jewish ancestry

clinical signs concerning for breast malignancy

• fixed or immobile (immovable) axillary lymph nodes, suggesting involvement by metastasis • nipple discharge • retraction of the nipple, suggesting an underlying infiltrative mass • skin thickening due to obstruction of dermal lymphatics by tumor. This skin thickening is referred to as peau d'orange, which is French for skin of an orange, as the skin becomes dimpled and thickened like an orange peel.

protective factors for breast cancer (4)

• history of pregnancy (full term) • early pregnancy (before age 30) • breast feeding • exercise (possibly due to reduction in obesity and estrogen levels) • risk-reducing mastectomy • risk-reducing oophorectomy or ovarian ablation

breast carcinoma risk factors

• increasing age • family history of breast cancer • endogenous estrogens (early menarche at <12 years or late menopause at >50 years, nulliparity, or older age at first birth) • exogenous hormones (high-dose oral contraceptives, combination estrogen plus progestin hormone replacement therapy) • alcohol and smoking • high-fat diet and obesity • personal history of breast cancer (in situ or invasive) • personal history of proliferative fibrocystic change, ADH, ALH, or LCIS • radiation exposure to the breast • major inheritance susceptibility (germline mutation of the BRCA1 and BRCA2 genes and other breast cancer susceptibility genes) • mammographic breast tissue density

Evaluation for breast cancer includes the following components (3):

• thorough clinical history and physical exam • breast imaging (ultrasound, mammography, MRI) • biopsy (fine needle aspiration, core needle, or excisional) • ancillary tests on biopsied tissue, including testing for estrogen receptor, progesterone receptor, and - when appropriate - HER2 (human epidermal growth factor receptor 2).

BPH Medical management (2 options) Medication, Mechanism, Time to effect, side effects

⍺-blockers: Tamsulosin Terazosin Doxazosin Alfuzosin --Blocks ⍺-adrenergic receptors within the prostate and bladder neck -> relaxation --1 week --Orthostatic hypotension 5⍺-reductase inhibitors: Finasteride Dutasteride --Blocks the enzyme that converts testosterone to DHT -> shrinkage of prostate --6 months

physical exam ovarian cancer (2)

● Pelvic mass on physical examination. ○ A solid, irregular, fixed pelvic mass is highly ● Presence of ascites or upper abdominal disease is concerning for advanced stage disease.

Ovarian cancer evaluation (4)

● Tumor markers ○ CA125, AFP, hCG, LDH, Inhibin B ● Imaging ○ Ultrasound, MRI, CT, CXR ● In general, an ovarian mass should not be biopsied ● Consult a gynecologic oncologist Strongly consider ovarian cancer in a postmenopausal woman with pelvic mass, and elevated CA125