Male GU Disorders Flashcards

Question

Mumps GU Effects

Answer 1

* Testicular involvement is **more frequent in adults** (20-30%) than in children * **Unilateral orchitis** usually follows parotiditis * _Histology_: edema and infiltration of lymphocytes, plasma cells and MΦ * Process is patchy w/in the testis and _usually does not result in infertility_

Answer 2

* Most common cause of **male infertility (37%)** * Congenital **absence or insufficiency of valves in internal spermatic vein** leads to **reflux** * Causes **varix-like distention in the pampiniform plexus** * _More frequent in the left side_ * Left spermatic vein → left renal vein * 8-10 cm longer than right * Courses b/t superior mesenteric artery and aorta * Right spermatic vein → inferior vena cava * Treatment: **surgical excision** * Recovery of spermatogenesis in up to 80% of pts

Answer 3

* _Types:_ * Infantile (8%) * Adults (92%) * **Bell-clapper abnormality** * Tunica vaginalis reflected from spermatic cord vs anterior portion of testis * Results in lack of connections to scrotal wall * 10% men * Torsion may occur w/ **trauma** or **exertion**, but can also happen **during sleep** * _Clinical:_ * **Sudden severe testicular pain**, followed by **scrotal tenderness** * ± Swelling, leukocytosis, nausea, fever * Urologic emergency * _Histology:_ * First 6 hours: **congestion, edema, and hemorrhage** but the germinal cells appear viable * After 6 hours: **hemorrhagic infarction** * _Dx_: Need to obtain **Doppler US** if torsion suspected to evaluate blood flow * _Treatment:_ * **Surgical correction w/in 4-6 hrs** might salvage the testis * Bell-clapper abnl is b/l ⇒ requires contralateral orchiopexy

Answer 4

**The consistent inability to achieve and/or maintain an erection or erection satisfactory for intercourse.** * Very common condition with many men * Undiagnosed for many reasons * _Multifactorial etiology_: **vascular, neurologic, DM, trauma, surgery, meds, psychological, HTN, HLD** * **ED prevalence** **↑** **with age** * Hx is essential for diagnosing ED accurately * Must differentiate from **premature ejaculation** and **situational issues** * Work up includes PE, measurement of **serum testosterone levels**

Answer 5

_Drugs Associated with ED include:_ * **Estrogens, Antiandrogens** * **Antihypertensives**: Clonidine, methyldopa, HCTZ, β-blockers, Spironolactone, Diuretics * **Psychotropics**: MAOi, TCAs, antidepressants, phenothiazine, benzodiazepines, SSRIs * **CNS depressants**: sedatives, narcotics, alcohol * **Alcohol, Marijuana, Narcotics, Cigarettes, Cocaine** * H2 blockers, anticholinergics, Atropine, lipid-lowering agents, NSAIDs * Cytotoxic drugs, Ketoconazole

Answer 6

* **Muscles of the arteries and sinusoids relax** * Erectile tissue **fills w/ blood** at arterial pressure * Compression of the **plexus of subtunical arteries** ⇒ **↓** **venous outflow** * **Detumescence** occurs through the reversal of this process

Answer 7

* _Erection_ * Extrinsic factors via **supraspinal pathways** + **neurotransmission** ⇒ ∆ cavernosal artery tone * _Central neural input_ is an absolute requirement * **NANC (nonadrenergic noncholinergic) system** * Key neural pathway * Releases **nitric oxide (NO)** * _Within cavernosal smooth muscle cells:_ NO ⇒ ⊕ guanylate cyclase ⇒ ↑ cGMP ⇒ ↓ intracellular Ca²⁺⇒ relaxation ⇒ engorgement * _Detumescence_ * Cyclic GMP broken down 1° by **phosphodiesterase-5** * Partly accounts for detumescence * **Norepi** released from **SNS nerves** plays a larger role * cAMP & cGMP involved in smooth muscle relaxation * Work via kinases ⇒ ℗ of proteins that leads to: * Opening of K⁺ channels ⇒ hyperpolarization * Sequestration of intracellular Ca²⁺ by ER * ⊗ Voltage-dependent Ca²⁺ channels ⇒ ⊗ Ca²⁺influx * Activation of myosin phosphatase

Answer 8

* First try **lifestyle changes** or if possible, **termination of drugs** which may cause ED * **5-Phosphodiesterase Inhibitors** ⇒ mainstay of therapy * Therapeutic effect is via nitric oxide pathway resulting in smooth muscle relaxation and vasodilation * Effective in 60% of men * **Testosterone (T) replacement therapy** * Topical gels or injections * Gels better: more convenient & provides steady-state T levels * T can stimulate existing prostate CA & exacerbate BPH * No evidence that T replacement causes cancer or BPH * **Penile injection therapy with vasoactive agents** * **Vacuum device** * **Penile prosthesis** * **Sexual counseling for psychogenic ED**

Answer 9

* **Injected into base of the penis** * There are minimal pain fibers in the penis * **Takes 5-10 min to work** * Response rate is **excellent** * Drugs can be effective if PO meds fail * Most common AE is **pain @ injection site** * **Fibrotic episodes** are rare

Answer 10

**Vasodilator** * 1^st drug approved for ED as an injection * Intraurethral form available * Less effective and may cause burning and itching

Answer 11

Contains phentolamine, papaverine, and prostaglandin E1 * **Phentolamine** ⇒ ⊗ α-adrenergic receptors which can cause constriction * **Papaverine** ⇒ vasorelaxation either directly or via ⊗ of phosphodiesterase * **PGE1** ⇒ ↑ cAMP * Combo allows pharmacologic synergy * Each agent used @ lower concentration ⇒ **↓ penile fibrosis**

Answer 12

* \> 50 phosphodiesterase enzymes in the body * **5 PDE enzymes in penile tissues** * Most prominent form is **PDE-5**, found in the _corpus cavernosum_ * AEs of PDE-5 inhibitors attributed to ⊗ of enzyme in other tissues * _Mechanism of action:_ * ⊗ PDE-5 ⇒ **potentiates relaxant effects** necessary for erection _initiated by NO release_ from autonomic nerves of PNS and vascular endothelium * ⊗ PDE-5 ⇒ **prevents degradation of cGMP** ⇒ potentiates relaxation of corporeal arterial and sinusoidal smooth muscle * _Contraindications:_ * Recent hx of **CVA, MI, low BP, unstable angina, severe cardiac failure, severe liver impairment and/or ESRD**

Answer 13

Phosphodiesterase-5 Inhibitor * _Pharmacodynamics:_ * **Onset of action usu. hour after PO ingestion** * High fat meals ↓ rate of absorption * Recommended that drug be taken 1 hour before sexual intercourse and not w/ heavy meals * T_½ 4-6 hrs * **Duration of effect 4-5 hrs** * _Pharmacokinetics:_ * Degraded in liver by **cytochrome P-450 3A4 and 2C9** * Pts w/ hepatic dysfunction, \> 65 y/o, or taking cytochrome P-450 inhibitors will have ↑ levels * Ex. of drugs that inhibit the same P-450 system: grapefruit juice, cimetidine, erythromycin * Ritonavir inhibits both P-450s * _Efficacy:_ * **70% of pts** will get an erection even w/ comorbidities such as CAD/PVD * ↓ Response in diabetics * Some pts may switch to injectables b/c rigidity of erection is greater * Oral form is more convenient * _Adverse effects:_ * **Headache** (16%), **flushing** (10%), **dyspepsia** (6%), **nasal congestion** (4%), **altered vision** (3%), and **diarrhea** * Visual disturbance: subtle change in color perception (**blue aura**) * **Priapism** * Only occurred if sildenafil used in combo w/ other therapies for ED * _Interactions and contraindications:_ * Can **potentiate effect of NO donors** ⇒ life-threatening hypotension * Caution in pts taking **α-blockers** * Caution in pts w/ **coronary related problems** * ? Ass. w/ **Nonarteritic anterior ischemia optic neuropathy (NAION)**

Answer 14

Phosphodiesterase-5 Inhibitor All aspects are similar to sildenafil

Answer 15

Phosphodiesterase-5 Inhibitors * _Pharmacokinetics and pharmacodynamics:_ * T_½18 hrs (longer than Sildenafil and Vardenafil) * **Duration of effect 36 hrs** * **Onset of action maybe slightly longer** * Plasma concentration **unaffected by food** * Similar effects in regard to **cytochrome P-450** * _Efficacy:_ * Similar efficacy but longer duration of action * Pts may prefer Tadalafil over Sildenafil * _Adverse effects:_ * **Similar to the other two** * Drug has greatest selectivity of PDE5 vs PDE3A * **Potentially less cardiac effects** * Greater selectivity for PDE5 vs PDE6 (found in the retina) * **Potentially less visual effects**

Answer 16

* Pts failing one inhibitor **may respond to another in the class** * Tx should not be considered a failure unless they _have not responded to the maximum dose_ * Some pts may respond to **continuous dosing** * Some pts may require **androgen replacement therapy**

Answer 17

* Centrally acting agent * **Dopamine D1/D2 agonist** * Works at the level of the _hypothalamus_ * Sublingual formulation works **within 20 min** * _Efficacy_: **~ 50% as effective as PDE inhibitors** * _Adverse effects_: **nausea, headache, yawning, and dizziness**

Answer 18

**Less than 1% of all tumors in men** _Types:_ * **Germ cell neoplasms (94%)** * Intratubular germ cell neoplasia (CIS) * Seminomatous Tumors * Seminoma * Spermatocytic seminoma * Non-Seminomatous Germ Cell Tumors (NSGCT) * Embryonal carcinoma * Yolk sac tumor (endodermal sinus tumor) * Teratoma * Mature * Immature * Choriocarcinoma * **Gonadal stromal (sex-cord) neoplasms (5%)** * Leydig cell tumor * Sertoli cell tumor * Granulosa cell tumor * Mixed/undifferentiated sex cord tumors * Gonadoblastoma * Germ cell-stromal-sex cord tumor * **Lymphomas (1%)**

Answer 19

* _Prevalence:_ * Most common tumor in men **age 15-34** * Causes 10% of cancer deaths * _Incidence:_ * 6/100k males in the US per yr * **White to black ratio of 5:1** * _Risk factors:_ * **Cryptorchidism, dysgenetic gonads** * Hx of germ cell tumor on contralateral side * Vasectomy does not ↑ risk

Answer 20

* **Strong familial predisposition** * Fathers and sons of pts have **4x risk** * Brothers of pts have **8-10 x risk** * _Several genetic loci linked to this risk_ * Gene encoding **ligand** for receptor tyrosine kinase **KIT and BAK** * Inducer of apoptotic cell death * Cytogenetic changes in **chromosome 12 and 1** are seen * Esp. **isochromosome of short arm 12i** (12p) ⇒ pathognomonic for germ cell tumor

Answer 21

* **Seminomatous** * Cells _resemble primordial germ cells_ * **Non-Seminomatous** * _Undifferentiated cells_ * Can resemble cells along embryonal stem cell line, yolk sac line, choriocarcinoma, or teratoma

Answer 22

**CIS** = Intratubular Germ Cell Neoplasia * Precursor lesion for most _germ cell carcinomas_ * **Seminoma, embryonal carcinoma, teratocarcinoma, mixed germ cell tumors** * _Not present in_: yolk sac tumors, benign teratomas, spermatocytic seminomas * ITGCN appears to **arise in utero** * Stays dormant until puberty * Then can progress to **seminoma** or **non-seminoma GCT**

Answer 23

* **Most common type of germ cell tumor** * Corresponds to _dysgerminoma_ in the ovary * Clinical presentation: * **3^rd to 4^thdecade**, rare in children in its pure form * **Painless enlargement** * _Behavior and prognosis:_ * Tend to **grow locally** * \< 10% of stage I tumors (confined to the testis) have LN metastases at presentation * **If only surgical treatment**: 16% relapse * Can spread to retroperitoneal LNs * Tumor is **exquisitely** **radiosensitive** w/ cure rates of 95% for stage I patients

Answer 24

* _Gross findings:_ * **Gray/white** cut surface * **Hemorrhage and necrosis** only seen in large tumors * _Histology:_ * **Typical** (85-90%) * **Uniform sheets** of **large uniform cells** interspersed w/ **prominent lymphocytic infiltrate** * Cells are **PAS-positive**, contain **glycogen** * **Anaplastic** (10%)

Answer 25

* _Epidemiology:_ * Accounts for 1-2% of all testicular neoplasms * **5% of all seminomas** * Occurs exclusively in **older men** * _Behavior and Prognosis:_ * **Slow growing** * Treated w/ surgical excision * Very rarely produces metastases

Answer 26

* _Gross:_ * Tend to be **larger** than seminomas * **Well-circumscribed**, **bulging** * **No necrosis or hemorrhage** * _Histology:_ * Tumor cells are arranged in **solid sheets separated by fine septa** * **No lymphocytic infiltrate** (differs from seminoma) * Cells **do not contain glycogen** (PAS ⊖) * **Atypical mitosis** can be seen

Answer 27

* Embryonal carcinoma * Teratocarcinoma * Mixed germ cell tumors * Composed of seminoma and immature teratoma

Answer 28

* _Demographics:_ * **Rare in its pure form** * Seen more often as a _component of a_**:** * **Teratoma** * See embryonal CA + **somatic tissues** and **extraembryonic tissues** like _yolk sac or trophoblastic epithelium_ * **Mixed germ cell tumor** * _Clinical presentation:_ * **25-35 y/o** * **Scrotal** **mass** and **some discomfort** * **10% w/ metastases** @ presentation * Can be hard to find 1° tumor in these pts * **70% w/ extended beyond testis** @ presentation * _Behavior and Prognosis:_ * **Highly aggressive tumors** * Tx is **surgical resection** followed by **chemotherapy** followed by **resection of residual tumor metastases** * **Prognosis varies w/ stage of the tumor** but is **good overall**

Answer 29

* _Gross:_ * **Large, irregular hemorrhagic, necrotic mass** * **Local extension to spermatic cord** is frequent * _Histology:_ * Varies depending on components * **Solid sheets, trabeculae, abortive glands, papillary and cleft-like spaces** * **No lymphoplasmacytic infiltrate** * Large cells w/ **high N/C ratios**, scanty cytoplasm * **Mitosis is abundant** * Cells can contain **AFP and HCG**

Answer 30

* _Demographics:_ * **Pure form seen only in infants** * Accounts for 2% of all testicular germ cell tumors * **#1 testicular tumor in infants and children** * _Behavior and Prognosis:_ * 16% w/ metastases @ diagnosis * **Prognosis is excellent**

Answer 31

* _Gross:_ * Tumors tend to be **large** * Compresses surrounding testis * Extend to epididymis * **Yellow or pale gray** * Can be **solid** or **microcystic** * **Hemorrhage** is frequent * _Histology:_ * **Lace-like (reticular)** network of **cuboidal "hobnailed" cells** * Various histologic patterns including: **microcystic, papillary, glandular, solid, and enteric glandular** * **Schiller-Duval bodies**: papillary structures resembling glomeruli (20% of cases) * _Intra and extracellular_ **hyaline globules** (**AFP or AAT**) (85% of cases) * AFP = Alpha-fetoprotein * AAT = Alpha1-antitrypsin

Answer 32

* _General Info and demographics:_ * **Germ cell neoplasm** * Differentiates along multiple lines * Produces a variety of histological patterns * **Pure benign teratomas** in testis _rare_ * 3% of germ cell tumors * Occur almost always **before puberty** * In contrast, **ovarian benign (mature) teratoma** is the most frequent germ cell tumor * Always occurs after puberty * _Behavior:_ * **Males**: even undifferentiated tumors won’t metastasize * **Females**: Immature mesenchymal components associated w/ aggressive behavior * _Clinical features:_ * Most occur **before age 4** * Can be present in the **undescended testis** * ↑ Levels of **hCG** and esp. **AFP** ⇒ look for NSGCT * _Behavior and Prognosis:_ * Children: behave as **benign tumors** * Adults: treat as a **malignant tumor**

Answer 33

* _Gross:_ * **Well-demarcated** * Can have **solid** and **cystic** components w/ other materials like **bone, cartilage, sebum, etc.** * _Histology:_ * **Cysts** lined by a **variety of epithelia** * Can see **skin** and **adnexal differentiation**, **immature and mature neural tissue**, **respiratory and intestinal tract differentiation**

Answer 34

* Account for **4-6% of all testicular neoplasms** * Can be pure forms of **Leydig, Sertoli or granulosa cells or mixed forms** * Do not have the same predisposing conditions as germ cell tumors

Answer 35

* Constitute **1-3% of all testicular neoplasms** * _Clinical findings:_ * **Testicular mass** * Can produce _↑_ _androgens and estrogens_ ⇒ ± **precocious puberty and gynecomastia** * _Behavior and Prognosis_ * Leydig cell tumors occurring in _children_ are **benign** * ~**10%** of this tumor in _adults_ are **malignant**

Answer 36

* _Gross_: * **Homogenous well-demarcated brown to light yellow mass** * Measures between 3-5cm * Extension to cord and rete is infrequent (15%) * _Histology_: * Architecture of **solid sheets, nests, or trabeculae** surrounded by **stroma** * **Polygonal cells** w/ **granular acidophilic, or vacuolated cytoplasm** * **Reinke crystals** in 25-40% of cases * **Lipofuscin** is seen in most

Answer 37

* _Epidemiology:_ * \< 1 % of all testicular tumors * Can be associated * **Undescended testis** * **Testicular feminization** * **Peutz-Jeghers syndrome** * _Clinical effects:_ * Can induce **endocrinologic changes** like Leydig cell tumors * _Behavior and prognosis:_ * **Grow locally** * Metastases are rare (\<10%)

Answer 38

* _Gross_: * **Small pale yellow or gray** w/ areas of **hemorrhage and necrosis** * _Histology_: * **Tubular arrangement** w/ _no lamina_ but surrounded by a **BM** * _Two histological variants:_ * **Tubules w/ eosinophilic masses** (sex cord tumor w/ annular structures) * **Large cell calcifying sertoli cell tumor**

Answer 39

* **Peripheral zone** * Located at _posterior and lateral aspect_ of gland * Constitutes 75% of the gland * Site of **≈ 70% of prostatic adenocarcinoma** * **Central zone** * Cone shaped structure * Surrounds the ejaculatory ducts * Apex at the verumontanum, base at area between the SV and the bladder * Constitutes 20% of the gland * **Transitional zone** * _Anteriorly_ located * Surrounds the urethra * Comprises 5% of the normal gland * Can markedly expand by a combination of **glandular and stromal hyperplasia** ⇒ **Benign Prostatic Hypertrophy (BPH)** * May cause obstruction of urinary flow by blocking urethral outflow tract

Answer 40

* **Epithelial-Stromal units** * Glands + adjacent connective tissue * Seen in all zones but not in: * Ejaculatory ducts * Vermontanum

Answer 41

* **Secretory cell** * Lines the lumen * **Basal Cell (Stem Cell)** * Between BM and secretory cell * Intermediate cells * Possible stem cells * Not yet fully defined

Answer 42

* Serine protease (gene at 19q13) * _Function_: liquefies the seminal coagulum, dissolves cervical mucous cap * **Almost exclusively by prostate gland** * Produced by _normal, hyperplastic and most neoplastic glands_ * Used as **serologic assay to follow prostatic CA** * Normal value \< 4.0 ng * Some experts believe in age adjustment of PSA values * Sensitivity 30-50%, specificity 50-80% ⇒ **not an ideal screening test** * _Can be elevated from non-cancerous conditions_: BPH, prostatitis, trauma, ejaculation, hormonal medications * **Must be combined w/ DRE for best screening** * **Prostate biopsy** next step to make dx

Answer 43

* **Acute inflammation of prostate** * Cause: bacterial infection via **urine** or **urothelium** * **GNRs**, most frequently E. coli * ↑ Incidence in immunosuppressed * Systemic sx of infection, usu. sudden onset * **Fever, chills, low back + perineal pain, urgency, dysuria** * Rectal exam: **swollen, tense gland**

Answer 44

* _Histology_ * **Acute inflammation in stroma** * **Gland destruction** * **Micro-abscesses** * _TURP Findings_ * **Acute inflammation** ≠ Symptomatic acute prostatitis * _Biopsy_ * May be a cause of **↑ PSA**

Answer 45

* **Bacterial** * H/O UTI, ⊕ culture * Proteus, Klebsiella, Enterobacter and Pseudomonas * **Non-bacterial** * No UTI, ⊖ culture * Affected population: adult men, any age * _Signs and sx_: **recurrent dysuria and nocturia, RBC & WBC in prostatic secretions, persistent pelvic pain** * **Not a cause of** **↑** **PSA**

Answer 46

* **Growth in the transitional zone of the prostate** * Probably a normal aging process * Affects nearly all men if you examine (DRE) the prostate * 50% men \> 50 y/o * Almost 100% by ≥90 yrs of age * Associated w/ **concomitant glandular atrophy**

Answer 47

* **Difficulty in initiating and termination or urination** * ↓ Force and caliber of stream * Seen in only 10-25% of the population * Usually seen by **60-70 y/o** * In 1990, there were over 400k TURPs for BPH * Now a very rare procedure

Answer 48

* **Cause unknown** * _Required factors:_ * **Testosterone source (testis)** * Men castrated before puberty do not show BPH * Regression of BPH w/ androgen ablation Rx * **Advancing age** * **Altered serum estrogen:testosterone ratio** * Normal E:T ratio ↓ w/ age as testosterone level drops * **When given w/ androgens, estrogen inhibits cell death**

Answer 49

* _Variable histology_ * **Glandular and stromal hyperplasia** * Atrophy * Lymphocytic infiltrate * **Largest nodules** **⇒** _periurethral_

Answer 50

* **Precursor lesion for adenocarcinoma (CA)** * _Peripheral zone_ lesion * Present in almost all prostates w/ CA * _Two-tiered grading system_ * **Low grade PIN** * Stratification of secretory cells, minimal atypia, small nucleoli, retained basal cell layer * Management: unchanged * **High grade PIN** * Marked stratification of secretory cells * Marked atypia * Prominent nucleoli * Discontinuous basal cell layer * Management: re-biopsy * CA found in 30-50%

Answer 51

* **Most common cancer in men**, 2^nd leading cause of cancer death in men * ~200k men are diagnosed each yr, 28k die * _Variable risk in US:_ **African American \> Whites \> Asians, Hispanics, Native Americans** * Most cancers present as **prostatism** (like BPH) * **Marked age-related ↑ in incidence** * 40x ↑ from 50 to 85 y/o * **Death rate has been declining** * Reason for decline uncertain * _Potential reasons include:_ * Early detection programs w/ DRE and PSA * Tx of localized disease * Environmental reasons: diet, supplements, exercise

Answer 52

* Most common presentation is **elevated PSA only / asymptomatic** * **Sx usually occur only w/ advanced disease** * Clinical prostatism * _20% of men_ w/ prostate CA have **normal PSA and abnormal digital rectal examination (DRE)** * **Both PSA and DRE needed to screen properly** * **Biopsy** makes definitive dx * Biopsy is performed in combo w/ **transrectal US**

Answer 53

* Neoplastic cells secrete ~3x \> vs normal cells * **Normal PSA 2.5-6.5 ng/ml** * Age dependent * 4 ng/ml considered ULN * PSA \< 4 ng/ml seen in ~20% of prostate CA * If PSA \< 4.0, ~20% have CA * If PSA \> 20, ~100% have CA * Causes of ↑ PSA: * _Benign_: **BPH, infarcts, acute prostatitis** * _Malignant_: **Adenocarcinoma** * Recommended PSA as a **marker to follow recurrence after tx**

Answer 54

* **PSA density (index)**: * Serum PSA value / gland volume (measured by transrectal US) * V = 0.52 x HxLxW * **PSA velocity** * ∆ Serum PSA over time * **Free PSA** * _Majority of PSA is bound to serum proteins:_ * **Alpha-1 anti-chymotrypsin** and **alpha-2 macroglobulin**

Answer 55

* Unclear if **prostate cancer screening ↓ mortality** * Over dx ⇒ **significant morbidity** (ED, incontinence) w/ **questionable benefit to survival** * Several different screening recommendations exist (AUA, ACS, ACP) * _Pros and cons should be discussed w/ the individual pt_ * **PSA should not be included as a routine blood test** * **Consider patient’s age, medical conditions, life expectancy**

Answer 56

* _Grading system_ is **Gleason Score** based on **pathologic patterns on histology** * Architecture of glands * **TMN staging system** * Most common stage is **T1C** * Elevated PSA is only presenting feature * Imaging studies not very useful in low stage disease

Answer 57

_Gleason’s **Grading** System_ * **Based on architecture of glands** * _5-tiered system (patterns 1-5)_ * Most predominant pattern added to 2^nd most common pattern to assign a **score** * _Score range 2-10_ * **Gleason pattern 1**: Lobular masses, uniform small glands, no invasion outside the "lobule" * **Gleason pattern 2**: Lobular masses, irregular glands, minimal invasion * **Gleason pattern 3**: Irregular glands, infiltrative, cribriform and papillary patterns * **Gleason pattern 4**: Fusion of glands, sheets, infiltrative, some w/ clear cytoplasm * **Gleason pattern 5**: Sheets of anaplastic cells infiltrative, comedonecrosis _3-tiered **classification** based on Gleason score used for management:_ * **Low grade cancer**: Gleason scores 2-6 * **Intermediate grade cancer**: Gleason score 7 * **High grade cancer**: Gleason score 8-10

Answer 58

**TMN staging system** Most common stage is **T1C**

Answer 59

* **Slow doubling time** compared w/ other tumors * _Course determined by:_ * **Stage of disease** * **Life expectancy** * _For stage A1_: * Non-palpable carcinoma by rectal examination * Usu. incidentally found by TURP * ~16% will progress within the next 10 yrs if left alone * _In stage A2_: * Higher Gleason score and extensive disease * Still nonpalpable and discovered by TURP * ~50% will progress during the next 5 yrs if left untreated * _In stage B_: * Carcinoma palpated during DRE but confined to the prostate * Most of these will progress and should be treated * **85-90% 10-yr survival** if tx given for _early stage localized cancer_ * **Surveillance** still an option for some men * **Survival 18-24 months** in men w/ _metastatic cancer_

Answer 60

_Localized cancer with normal_ _life expectancy:_ * **Surgery** * Radical retropubic prostatectomy * Radical perineal prostatectomy * Laparoscopic/Robotic assisted prostatectomy * Surgery not proven superior w/ localized disease * **Radiation therapy** * Pt is not a good surgical candidate * Doesn’t want surgery * Surgery & radiation w/ similar 10-15 yr cure rates * **Hormonal therapy alone** * **Cryotherapy** * **Active surveillance/observation**

Answer 61

* Transrectal US guided * Transperineal placement of 6-8 CRYOprobes * Transperineal placement of 4-6 TEMP probes * Warming device to preserve urethra

Answer 62

* _Types of radiation:_ * **External beam radiation (XRT)** * **Brachytherapy (seeds)** * **High dose radiotherapy (HDR)** * _Combination therapy:_ * XRT + Hormonal Tx * Brachy + XRT ± Hormonal Tx * HDR + XRT ± Hormonal Tx

Answer 63

* Palliation, for those w/ **extension of CA beyond the prostate** * Based on prostate CA being **androgen (testosterone) sensitive** * ↓ Serum testosterone ⇒ shrinkage of CA via apoptosis * **Usually not curative** but _adds to effectiveness of Radiation Tx_ in certain pts * **Used as** **1°** **treatment in metastatic disease** * _Androgen ablation therapy_ * **Orchiectomy** * **Luteinizing hormone releasing hormone (LHRH)**

Answer 64

_Surgical/radiation risks_ include **urinary incontinence, erectile dysfunction and rectal/bowel complications** _Hormonal therapy (male menopause)_ can cause **cognitive decline, osteoporosis, vasomotor sx, loss of libido and erections**

Answer 65

Can use **PSA immunohistochemical stain** to determine that _origin of metastatic tumor is from prostate._ Metastasis to **bone** is characteristic.