Prostate Embolization: New Treatment Option for BPH Howard M. Richard, III, MD Disclosures None Off label discussion > yup Prostate From Greek

, prostates, literally "one who stands before", "protector", guardian" Sited at the base of bladder Prostate Function Secrete fluid that constitutes 30% of semen

volume Prostate secretions protect sperm Contains smooth muscle Helps expel semen during ejaculation Prostate Structure In healthy state > Walnut 11 grams > 7-11 grams Just below the bladder

Surrounds urethra Can be felt during a rectal exam Prostate Histology Glandular cells secrete prostatic fluid Myoepithelial cells contractile function

Subepithelial interstitial cells suport matrix Prostate Structure Secretory epithelium Prostatic secretion Fibro-elastic stroma

Smooth muscle Surrounds prostatic urethra Urethra merges with two ejaculatory ducts Prostate Function Male sexual response ejaculation

Secretions acidic, proteins, PSA, zinc Regulation Testosterone > produced in testes Prostate Pathology > Prostatitis

Inflammation > prostatitis Four categories I Acute prostatitis > ABX II Chronic prostatitis > ABX III Chronic non-bacterial prostatitis male chronic pelvic pain syndrome RX with alpha blockers, PT, psychotherapy, anxiolytics, nerve modulation

IV Leukocytosis > Rare BPH Benign prostatic hyperplasia hyperplasia of stromal and epithelial cells increase in the number of cells

Impinge on urethra Increase resistance to voiding BPH

Increasing resistance to urine flow Bladder has to work harder Hypertrophy of bladder Bladder instability Eventually, bladder enlarges, bladder thins and becomes atonic BPH symptoms Lower urinary tract symptoms (LUTS)

Storage or Voiding Storage Urgency Frequency Urge incontinence Nocturnal Incontinence Nocturia BPH symptoms Voiding symptoms

Hesitancy Poor Flow Intermittent stream Dribbling Poor bladder emptying Urinary retention Bladder Outlet Obstruction (BOO) Acute urine retention Can not pass urine

Pelvic pain Chronic retention Straining > overflow incontinence, hernia, hemorrhoids Urine stasis > Bladder stones Causes of BPH Androgens Testosterone

Dihydrotestosterone (DHT), a metabolite of testosterone Product of prostate enzyme 5-reductase, type 2-reductase, type 2 Estrogens > no link identified Failure in the spermatic venous drainage system* * 2008 Andrologia 40 (5-reductase, type 2): 273281 Causes of BPH

Androgens Testosterone Dihydrotestosterone (DHT), a metabolite of testosterone Product of prostate enzyme 5-reductase, type 2-reductase, type 2 Causes of BPH

Failure in the spermatic venous drainage system???? Increased hydrostatic pressure and local testosterone levels 100 fold over serum Dietary considerations High protein diet > Chinese study Alcohol intake> Japanese American study Metabolic syndrome

Obesity, diabetes, hypertension, inc. cholesterol Pathophysiology of BPH Glandular epithelial hypertrophy Stromal cells w/ muscular fibers hypertrophy Predominate component Ratio is unclear Purpose of growth is unclear May represent re-awakening in adulthood

of embryonic induction process?? Anatomic BPH Posterior urethral glands earliest growth between 30-5-reductase, type 20 Transitional zone Majority of late growth

Peripheral Zone Minimal growth Majority of prostate cancer BOO Static component Increased prostate volume Glandular proliferation Dynamic component

Increase in Smooth Muscle tone Impinge on urethra BOO > LUTS

Lower urinary tract symptoms frequency urgency nocturia difficulty initiating urination incomplete bladder emptying decreased urinary stream

BOO > LUTS International Prostate Symptom Score (IPSS) Questionnaire for symptom measurement 7 questions

LUTS Urodynamics Decreased peak urine flow rate Qmax Increase in post-void residual PVR LUTS Severity of symptoms > IPSS > 7 (Moderate) Incidence based on IPSS up to 40% over 5-reductase, type 20yr 90% of men between 5-reductase, type 20 and 80 suffer with some degree of LUTS

Progression to acute urine retention 6.8 episodes per 1000 general population 34.7 episodes per 1000 in men older than 70 LUTS

Treatment options Active surveillance Drug therapy Mechanical devices Surgical options Prostate embolization LUTS

Drug Therapy Alpha Blockers 5-reductase, type 2-Alpha reductase inhibitors Anti-cholinergics Phytotherapeutics LUTS Mechanical devices

stents indwelling catheters The Spanner Pain Required removal in 63% CAUTI LUTS

Surgical options Trans Urethral Resection Prostate (TURP) Gold standard Transurethral Laser Ablation Prostate Open prostatectomy Larger prostates TURP

Trans Urethral Resection of Prostate Gold standard Prostates less than 80-100 gm Overnight hospital stay TURP

Complications Urinary incontinence Decline in sexual function Erectile dysfunction Irritative voiding symptoms Bladder neck contracture Transfusion UTI Hematuria

Open Prostatectomy Reserved for prostate glands > 80-100 gm Major surgery

Weeks to recover Complications include erectile dysfunction Transfusions Stricture BPH > BOO > LUTS Initial symptoms are managed medically Invasive options reserved for patients whose symptoms worsen on medical management Surgical Indications

LUTS > Invasive RX Indication for surgery Renal insufficiency secondary to hydronephrosis Recurrent acute urine retention Intractable hematuria Repeated urinary tract infections Bladder stones

LUTS > Invasive RX Average prostate volume at presentation with surgical indications <30 gm 1987-1992 >60 gm 2003-2006 Improving medical management allows surgical indication symptoms to be put off while prostate continues to grow

Pelvic Embolization Prostatic embolization for hemorrhage Malignancy After TURP Trauma Reported from mid 1970s In 2000, Dr. Demerit* reported relief of BOO related to BPH following prostate embolization *J Vasc Interv Radiol 2000;11(6):767770.

BPH Improves after embo 76 yo Patient with BPH embolized for prostate bleeding Symptoms of BPH improve

BPH Improves after Embo Urinary symptoms score improved 24 before embolization decreased to 15-reductase, type 2 after four days and 13 at five and 12 months Prostate volume decreased 305-reductase, type 2 mL before embolization decreased to 190ml at 12 months ( 40% decrease) PSA decreased

40 ng/ml before embolization to 5-reductase, type 2 ng/ml at five months ( 90% decrease) Animal Experiments Dogs were given hormones to induce prostate hypertrophy* Half of the dogs were embolized Embolized dogs prostates shrank Histologically Gland atrophy, fibrosis, inflammatory cell

infiltration *J Vasc Interv Radiol 2009; 20:384390 Animal Experiments 1/2 of the pigs underwent prostate embo* Embolized prostates decreased in volume Histologic evaluation Fibrosis and gland atrophy Pigs were evaluated for sexual function after

embolization No difference between groups i.e., no change in sexual function after embolization *Radiology 2008: 246:783-789 Embolic agents Polyvinyl alcohol particles 200um Old school non-spherical Pisco et al

Embospheres Tris-acryl gelatin microspheres 300-5-reductase, type 200 um (Embospheres, Angiodymanics) Carnevale et al Embozene Embolic agents Embozene Microspheres Spherical, tightly

calibrated, biocompatible, non-resorbable, hydrogel beads coated with an inorganic perfluorinated polymer (Polyzene-F) coating Outcome Measures Prostatism > LUTS > IPSS & QOL scores Change in erectile function

International Index of Erectile Function (IIEF-5-reductase, type 2) BOO > Q max & PVR Prostate volume PSA reflects prostate volume IPSS Seven symptom categories hesitancy decreased urinary stream

intermittency sensation of incomplete emptying nocturia frequency urgency IPSS Seven symptom categories 0 - 5-reductase, type 2 points per category 0-7 mild

8-19 moderate 20-35-reductase, type 2 severe Quality of Life (QOL) score 0-6 How would it feel to spend rest of your life like this > 0 delighted to 6 terrible Complications Post procedure pain Non target embolization Colon

Bladder Radiation injury Non reported so far Complication Post embolization pain Bagla No pain after PAE

Carnavale Mild burning in urethra & retro-pubic area Responded to non-opiate non-steroidal antiinflammatory medications Resolved within first week Complication Bladder ischemia One patient developed pain during PAE He required surgical removal of ischemic are of bladder*

One patient developed hematuria after PAE MRI demonstrated region of hypo perfusion of bladder Reperfusion seen of 3 month MRI Complication Colon ischemia Rectal bleeding and /or diarrhea post UAE Symptoms resolve by third post embo day

Colonoscopy day 4 demonstrated rectal ulcers Repeat colonoscopy day 16 Ulcers disappeared without treatment Complication Radiation injury Average fluoro times 85-reductase, type 2 minutes No serious skin injuries One year follow up

Prostate Embolization Extended overnight observation basis Pre procedure Non-steroidal anti-inflammatory medication Anti-emetics Antibiotics Intravenous moderate conscious sedation and local anesthesia

Prostate Embolization Femoral artery access Selective catheterization of the bilateral internal iliac arteries Super selective catheterization of the prostatic arteries Angiography to verify location of prostate Prostate Embolization Prostate arteries anatomy*

Single PA in 5-reductase, type 27% of sides, 43% had two PAs *J Vasc Interv Radiol 2012; 23:14031415-reductase, type 2 Prostate Embolization Prostate artery can arise from* Internal pudendal artery 73 (34.1) Superior vesical artery 43 (20.1) Anterior common gluteal-pudendal trunk 38 (17.8) Obturator artery 27 (12.6)

Prostatorectal trunk 18 (8.4) Inferior gluteal artery 8 (3.7) Accessory pudendal artery 4 (1.9) Superior gluteal artery 3 (1.4) Prostate Embolization Prostate DSA Superior vesical artery Right anterior lateral

prostate artery Prostate Embolization Verification of prostate Minimize risk of non target embolization Colon or Bladder

Cone Beam CT Prostate Embolization Angiogram and cone beam CT demonstrate only partial filling of prostate consistent with two PAs Right posterior lateral PA arising from internal

pudendal artery Prostate Embolization Cone beam CT verifies opacification of the capsular and inferior lateral prostate gland Prostate Embolization

Embolization performed with Embozene Monitor for adequate embolization Monitor for non target embolization Monitor for collaterals that supply the prostate

Prostate Embolization DSA is used to identify the vascular bed Foley catheter in bladder marks the top of prostate Perfusing caudal tissue???

Prostate Embolization DSA is used to identify the vascular bed Foley catheter in bladder marks the top of prostate Perfusing RECTUM

Prostate Embolization DSA is used to identify the vascular bed Foley catheter in bladder marks the top of prostate Perfusing cephalad tissue???

Prostate Embolization DSA is used to identify the vascular bed Foley catheter in bladder marks the top of prostate Perfusing BLADDER Prostate Embolization

Post embolization Monitor for post embolization syndrome Pain Fever Monitor for complications Hematuria > Cystoscopy Hematochezia > Endoscopy Prostate Embolization

Follow up 2 week post op check Hematuria or hematochezia referral to Cystoscopy or proctoscopy 3 and 12 month follow up Repeat MRI, PSA, Urodymanics (Qmax and PVR), IPSS/QOL and IIEF-5-reductase, type 2 Results

IPSS and QOL 3 point decrease is significant Pisco reported 10 point ave decrease in IPSS IIEF-5-reductase, type 2 erectile function Expect no change Pisco reported an improvement post UAE Results Urodynamics

Qmax increases from 4.2 to 10.8 ml/sec PVR decreased from 103 to 5-reductase, type 28 at one year follow up Prostate Volume 40% decrease in volume at five months PSA Decrease from average 10.1 to 4.3

Discussion Number of procedures for LUTS has decreased with advances in Medical therapy Allows prostates to grow even larger before a surgical event occurs TURP remains the durable and effective GOLD standard Discussion TURP

Requires general or spinal anesthesia Significant complication Durability Ejaculatory disorders UAE > Opportunity Moderate sedation Fewer ejaculatory complications Jury is still out.

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