Cardiovascular and Interventional Radiology - CIRSE

Prostatic Artery Embolization for Enlarged Prostates Due to Benign Prostatic Hyperplasia. How I Do It Francisco C. Carnevale & Alberto A. Antunes

CardioVascular and Interventional Radiology ISSN 0174-1551 Cardiovasc Intervent Radiol DOI 10.1007/s00270-013-0680-5

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Author's personal copy Cardiovasc Intervent Radiol DOI 10.1007/s00270-013-0680-5

REVIEW/STATE OF THE ART

Prostatic Artery Embolization for Enlarged Prostates Due to Benign Prostatic Hyperplasia. How I Do It Francisco C. Carnevale • Alberto A. Antunes

Received: 29 March 2013 / Accepted: 28 May 2013 Ó Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2013

Abstract Prostatic artery embolization (PAE) has emerged as an alternative to surgical treatments for benign prostatic hyperplasia (BPH). Patient selection and refined technique are essential for good results. Urodynamic evaluation and magnetic resonance imaging are very important and technical limitations are related to elderly patients with tortuous and atherosclerotic vessels, anatomical variations, difficulty visualizing and catheterizing small diameter arteries feeding the prostate, and the potential risk of bladder and rectum ischemia. The use of small-diameter hydrophilic microcatheters is mandatory.

Patients can be treated safely by PAE with low rates of side effects, reducing prostate volume with clinical symptoms and quality of life improvement without urinary incontinence, ejaculatory disorders, or erectile dysfunction. A multidisciplinary approach with urologists and interventional radiologists is essential to achieve better results.

Keywords Benign prostatic hyperplasia Prostatic artery embolization Cone-beam CT and LUTS

F. C. Carnevale Interventional Radiology Unit, University of Sao Paulo Medical School, Av. Dr. Ene´as de Carvalho Aguiar, 255, Sa˜o Paulo, SP 05403-001, Brazil F. C. Carnevale (&) Rua Teodoro Sampaio, 352/17, 05406-000 Sa˜o Paulo, Brazil e-mail: fcarnevale@uol.com.br A. A. Antunes Division of Urology, University of Sao Paulo Medical School, Av. Dr. Ene´as de Carvalho Aguiar, 255, Sa˜o Paulo, SP 05403-001, Brazil e-mail: antunesuro@uol.com.br

Introduction Lower urinary tract symptoms (LUTS) are common complaints resulting from BPH, and approximately half of all men with a histologic diagnosis of BPH have moderate to severe LUTS. Symptoms include nocturia, urinary frequency, urgency, decreased urine flow rates, hesitancy, and incomplete bladder emptying. Over time, urine retention may cause an increase in urinary tract infections (UTIs), bladder or kidney damage, bladder stones, or incontinence [1–3]. Watchful waiting is a management strategy in which the patient is monitored by his physician but receives no active intervention for BPH and is the preferred management strategy for patients with mild symptoms [4].

As first-line treatment, a-blockers, 5a-reductase inhibitors, and combination therapy have all proven effective, in both trials and clinical practice. Alpha-blocker therapy is based on the hypothesis that clinical BPH is partly caused by alpha1-adrenergic-mediated contraction of prostatic smooth muscle, resulting in bladder outlet obstruction [5, 6]. A 5 alpha-reductase inhibitor has demonstrated both efficacy and safety reducing the size of the prostate and BPH symptoms and can increase the peak urinary flow rate and reduce BPH symptoms [7, 8]. Nevertheless, medical therapy does not work for everyone. The most common side effects of these agents are orthostatic hypotension, dizziness, tiredness, retrograde ejaculation, and nasal congestion.

Surgical intervention is an appropriate treatment option for patients with moderate-to-severe LUTS and for patients who have developed acute urinary retention (AUR) or other BPH-related complications [9–11]. Transurethral resection of the prostate (TURP) is still the ‘‘gold standard’’ of interventional treatment for small prostates and open prostatectomy typically is performed on patients with prostate volumes greater than 80–100 g. One complication of TURP

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Author's personal copy F. C. Carnevale, A. A. Antunes: How I Do PAE for BPH

is TUR syndrome, a dilutional hyponatremia that occurs when irrigant solution is absorbed into the bloodstream.

Other complications that have been reported are erectile dysfunction, ejaculatory disorders, irritative voiding symptoms, bladder neck contracture, blood transfusion, UTI, hematuria, early urinary incontinence, stenosis of the urethra, and symptoms recurrence. There also is a greater risk of blood loss, transfusion, and longer hospital stay associated with open prostatectomy than TURP [4]. Recently, minimally invasive techniques, such as transurethral microwave thermotherapy, interstitial laser thermoablation, transurethral needle ablation, and water-induced thermotherapy, have been indicated to treat complications of BPH [12, 13].

Embolization of prostate arteries has been used for many years to control serious bleeding after biopsy or prostatectomy [14–16]. The first published case in which it was recognized that prostatic artery embolization (PAE) could have a therapeutic affect on BPH was in 2000 by DeMeritt et al. [17]. The first intentional treatment of BPH with PAE in humans was done by Carnevale et al. [18] in June 2008 and published in 2010. They performed PAE for two patients with AUR due to BPH who were refractory to treatment with selective a-blockers were being managed with long-term indwelling catheters and were waiting for surgery. The same investigators published midterm followup data for these two patients in 2011 confirming the efficacy of the procedure [19]. Other authors have shown their initial results with PAE to assess the efficacy, durability, and adverse event rates performing PAE in symptomatic patients due to enlarged prostates [20].

The purpose of this paper is to report our team’s methods and outcomes for PAE as a primary alternative treatment for patients with LUTS, based on our preclinical studies in dogs and initial clinical experience in 2008.

Patient Selection A multidisciplinary team of interventional radiologists, diagnostic radiologists, and urologists is involved in patient selection and follow-up. Candidates for PAE must be on the waiting list for TURP (prostate size ranging from 30 to 90 g) or open surgery ([90 g) and refractory to or intolerant of selective alpha-blockers or/and 5-alpha reductase.

Patients usually stop medication the day of PAE. The International Prostate Symptom Score (IPSS; evaluated as mild, moderate, and severe) and the International Index of Erectile Function (IIEF; evaluated as severe, moderate, mild-to-moderate, mild, and no dysfunction) are used by our medical team as assessment tools (Tables 1 and 2). Patients with malignancy and any other cause of voiding dysfunction are excluded. To assess a baseline

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quality of life (QoL), patients complete a QoL questionnaire that includes the question, ‘‘If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that?’’ Answers range from terrible, unhappy, mostly dissatisfied, mixed, mostly satisfied, pleased, and delighted.

Figure 1 illustrates the flow diagram used by our group for PAE. Before intervention, the urologist orders digital rectal examination (DRE), prostate specific antigen (PSA), and prostate biopsy, if concern is indicated. The following patients should undergo prostate biopsy with a minimum of 12 cores and have a negative histopathology report before treatment by PAE: (a) patients with DRE findings suspicious for prostate cancer; (b) patients with baseline PSA levels [10 ng/mL; (c) patients with baseline PSA levels [2.5 ng/mL and B10 ng/mL and free PSA \25 % of total PSA. Patients with cystoscopy findings suspicious for bladder cancer must undergo biopsy and have a negative histopathology. Multiparametric magnetic resonance of the prostate may help in selected cases.

General contraindications for PAE are bladder atonia, neurogenic bladder disorder, or other neurological disorder that is impacting bladder function (e.g., multiple sclerosis), urethral stricture, bladder neck contracture, sphincter abnormalities, urinary obstruction due to causes other than BPH, large bladder diverticula or stones, chronic renal failure, or other potentially confounding bladder or urethral disease or condition.

Patients with AUR and indwelling catheters are instructed to exchange urinary catheters every month to reduce the risk of UTI. Active UTI is a contraindication for PAE. Patients do not routinely receive continuous antibiotic due to AUR, but if they have been medicated we maintain the treatment. If prostate biopsy was performed patients must wait 30 days to undergo PAE. In patients with AUR, the catheter is removed and urodynamic studies are attempted to establish a baseline.

Investigations follow the urodynamic practice standards of the International Continence Society [21]. Infravesical obstruction (IVO) is defined as a bladder outlet obstruction index (BOOI) [40. The calculation to determine BOOI uses the detrusor muscle pressure (Pdet) at maximum urinary flow rate (Qmax) and is represented by the equation BOOI ¼ Pdet @ Qmax 2Qmax [22].

Urodynamic evaluation, transrectal or suprapubic ultrasound (US) and magnetic resonance imaging (MRI) baselines are established for each patient. Although urodynamic testing is an invasive procedure it is very important for patient selection. Some patients have infravesical obstruction due to enlarged prostates in association with bladder disorders and detrusor muscle hypocontractility. These patients are not good candidates for PAE.

Author's personal copy F. C. Carnevale, A. A. Antunes: How I Do PAE for BPH Table 1 International Prostate Symptom Score (IPSS) according to the American Urological Association (AUA) [4] Not at all

Less than 1 time in 5

Less than half the time

About half the time

More than half the time

Almost always

0

1

2

3

4

5

0

1

2

3

4

5

0

1

2

3

4

5

0

1

2

3

4

5

0

1

2

3

4

5

0

1

2

3

4

5

None

1 Time

2 Times

3 Times

4 Times

5 or More Times

0

1

2

3

4

5

Your score

Incomplete emptying Over the past 4 weeks, how often have you had a sensation of not emptying your bladder completely after you finish urinating?

Frequency Over the past 4 weeks, how often have you had to urinate again less than 2 h after you finished urinating?

Intermittency Over the past 4 weeks, how often have you found you stopped and started again several times when you urinate?

Urgency Over the past 4 weeks, how difficult have you found it to postpone urination?

Weak stream Over the past 4 weeks, how often have you had a weak urinary stream?

Straining Over the past 4 weeks, how often have you had to push or strain to begin urination?

Your score

Nocturia Over the past month, many times did you most typically get up to urinate from the time you went to bed until the time you got up in the morning?

Imaging Protocol Ultrasound prostate volume is measured by standard transabdominal view or transrectal US if prostate biopsy is necessary. Prostate vascularization can be visualized using Doppler and transabdominal US measures postvoid residual urine volume, and bladder and prostate volume. Bladder evaluation comprises measurement of wall thickness and its characteristics such as the presence of diverticula, trabeculations, and other possible findings, such as polyps, calculus, or other lesions. Protrusion of the median lobe is measured using the Prostate Protrusion Index (IPP) and prostate volume is measured using three incidences. For transrectal US, the patient is positioned in the left-lateral position ensuring that the knees are bent up towards the chest. We do not use lithotomy position but it is an option.

MRI of the prostate pre and post PAE can be performed either on 1.5 or 3.0 T magnet, using a phased array coil. An endorectal coil is not necessary. Main sequences are a T2weighted turbo/fast spin echo sequence (TSE, FSE, FRFSE), and a dynamic pre- and post-contrast T1-weighted volumetric

interpolated sequences (LAVA, VIBE, THRIVE). No breathhold is required. Parallel imaging (ASSET, I-PA T, SENSE) can be used to reduce sequence time. We suggest a slice thickness of 4 mm for 1.5 T or 3 mm for 3 T. For the dynamic T1 sequence, we recommend a pre-contrast and 15–20 sequential post-contrast phases (with no temporal gap), 15–25 s each phase, and contrast medium injection should start together with the first sequence acquisition. Total sequence time can range from 4 to 6 min. A Gadoliniumbased contrast medium must be infused using a power injector at a dose of 0.1 mL/kg (or 0.2 mL/kg), followed by 20 mL of saline flush. Prostate measurements (cephalocaudal, transverse, and anteroposterior) were obtained and volume was calculated by the ellipse formula.

Computed tomography with contrast can be useful to identify the characteristics of the main artery supplying the prostate and any arterial atherosclerotic lesion or obstruction that could contraindicate or make the intervention more difficult. We have not used it because some anatomical information can be achieved with MRI and mainly because we advocate the need to study and/or catheterize

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Author's personal copy F. C. Carnevale, A. A. Antunes: How I Do PAE for BPH Table 2 International Index of Erectile Function (IIEF) according to the American Urological Association (AUA) [4] International Index of Erectile Function (IIEF) questionnaire 0

1

2

3

4

5

1. Over the past 4 weeks, how often were you able to get an erection during sexual activity?

No sexual activity

Almost never/ never

A few times (much less than half the time)

Sometimes (about half the time)

Most times (much more than half the time)

Almost always/ always

2. Over the past 4 weeks, when you had erections with sexual stimulation, how often were your erections hard enough for penetration?

No sexual activity

Almost never/ never

A few times (much less than half the time)

Sometimes (about half the time)

Most times (much more than half the time)

Almost always/ always

3. Over the past 4 weeks, when you attempted sexual intercourse, how often were you able to penetrate (enter) your partner?

Did not attempt intercourse

Almost never/ never

A few times (much less than half the time)

Sometimes (about half the time)

Most times (much more than half the time)

Almost always/ always

4. Over the past 4 weeks, during sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner?

Did not attempt intercourse

Almost never/ never

A few times (much less than half the time)

Sometimes (about half the time)

Most times (much more than half the time)

Almost always/ always

5. Over the past 4 weeks, during sexual intercourse, how difficult was it to maintain your erection to completion of intercourse?

Did not attempt intercourse

Extremely difficult

Very difficult

Difficult

Slightly difficult

Not difficult

6. Over the past 4 weeks, how do you rate your confidence that you could get and keep an erection?

Did not attempt intercourse

Very low

Low

Moderate

High

Very high

Your score

Fig. 1 Diagram of benign prostatic hyperplasia diagnosis and treatment. DRE Digital Rectal Examination, PSA Prostate Specific Antigen, IPSS International Prostate Symptom Score, IIEF International Index of Erectile Function, QoL Quality of Life, AUA American Urological Association, US Ultrasound, MRI Magnetic Resonance Imaging, UDN Urodynamic Study

any suspect artery with potential for feeding the prostate.

We also need to be concerned about the use of the additional dose of contrast medium in this group of elderly

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patients relative to the benefit. All of this information can be achieved by performing a pelvic arteriogram during the day of the procedure.

Author's personal copy F. C. Carnevale, A. A. Antunes: How I Do PAE for BPH

PAE Technique Benign prostatic hyperplasia treatment with PAE requires a well-trained interventional radiologist because of the complex prostatic vascular anatomy and the potential for complications in elderly patients with atherosclerosis, very thin prostatic arteries and comorbidities. Intervention is performed under local anesthesia on an outpatient basis at the interventional radiology suite after patients have signed informed consent. A 400 mg intravenous dose of ciprofloxacin is given prior to the procedure followed by 500 mg orally twice a day for 7 days after PAE. Patients also receive nonopioid analgesic and nonsteroidal antiinflammatory medications after embolization, if necessary.

Intervention can be performed via either unilateral femoral arterial approach. Femoral pulses should be examined before choosing the best puncture site.

To provide good orientation to the prostate site and related structures in the pelvis, a Foley balloon is introduced into the bladder in every patient and the balloon is filled with a mixture of 30 % iodinated contrast medium and 70 % normal saline solution (Fig. 2). It is used just during the procedure and gives both a better image and understanding of the prostate, the internal iliac artery branches and related structures to avoid nontarget embolization complications. It is an excellent landmark during the procedure and we have not observed any severe complications due to its use. It also can be a reference if using cone-beam CT and patients do not need to strain to void after procedure.

Fig. 2 Posterior–anterior Rx showing the Foley balloon (F) placed in the bladder and filled with saline and contrast medium and its relationship with the rectum (arrows)

Knowing the vascular anatomy of the prostate is essential for clinical practice. Due to many arterial anastomoses and branches to related pelvic structures, various nomenclatures have been used for the arteries supplying the prostate. Names, such as inferior vesical artery (IVA), prostato-vesical artery, vesico-prostatic artery, and prostatic artery, can be found in publications [23, 24]. We consider the IVA as the main prostate artery, according to the urologists’ nomenclature. It usually arises as the second or third branch of the anterior trunk of the internal iliac artery (Fig. 3). Generally one main prostatic artery is found on each side in that position, but the main prostatic artery or aditional prostatic branches arising from the superior vesical, internal pudendal, obturator, and middle rectal arteries also can be found in some patients (Fig. 4).

Identifying and Catheterizing the Prostatic Arteries Initial pelvic angiography is performed using a pump injection (20 mL; 10 mL/s) to evaluate iliac vessels and the prostate arteries during arterial and late phases. After crossing the aortic bifurcation, selective digital subtraction arteriogram of the internal iliac artery is performed with a 5-French vertebral or cobra-2 catheter (12 mL; 4 mL/s) to better assess the blood supply to the prostate. The 5-French diagnostic catheter should be placed at the common

Fig. 3 DSA under ipsilateral oblique view with the 5-French vertebral catheter placed at the main trunk of the left internal iliac artery showing its posterior and anterior branches. The inferior vesical artery (white arrows) arises as the second branch and give branches to the inferior portion of the Foley balloon

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Fig. 4 A The left inferior vesical artery (arrow) originates from the obturator artery (arrow head) and gives branches to the left prostate lobe; B Relationship of the Foley balloon with the left prostate lobe arteries after catheterization of the left inferior vesical artery (arrow) under left oblique view. C Relationship of the Foley balloon and the

left prostate lobe arteries under posterior–anterior view. Typical corkscrew pattern of the intraprostatic arteries (arrowhead) and the median lobe arteries (arrow). D Late phase showing the left prostate lobe parenchyma under posterior–anterior view

internal iliac trunk to avoid missing any branch arising from the anterior and posterior division. It is not uncommon to find an IVA arising as a common pedicle with the superior vesical artery (also called umbilical artery) as the first branch of the anterior division. The 5-French Robert’s catheter (RUCÒ—Cook Inc., USA) can be used but, due to its long curve, we have observed less torquability and pushability with the microwire when using the coaxial system. For the ipsilateral internal iliac artery catheterization the Simmons I or II catheter (Merit Medical System, Inc., USA) can be used, but we prefer to work with the same vertebral catheter making a Waltman loop because, if necessary, it can be used as a regular vertebral catheter to get more torquability and pushability.

The best aspect to identify the IVA and all possible accessory branches to the prostate is the 25°–55° ipsilateral oblique view. A caudal view (10°–20°) can help to identify some bladder branches. This perspective, with the help of the Foley balloon filled with contrast, gives a better understanding of all five anterior branches and gives

orientation to the prostatic arteries. After performing the internal iliac arteriogram, attention should be given to the arteries feeding the area immediately below the balloon. In this view, the branches of the anterior division will be straightened, the prostate branches stay in the anterior, and the rectal branches in the posterior position, respectively.

The PROVISO acronym (internal Pudendal, middle Rectal, Obturator, Vesical Inferior and Superior under Oblique view) is a very useful trick to remember the names of the arteries and the best perspective during arteriogram (Fig. 5).

Catheterization of the IVA is performed using the same ipsilateral oblique perspective under the roadmap technique. With the microcatheter placed into the IVA, arteriography is performed by manually injecting 2–3 mL of contrast medium. The ipsilateral oblique view is useful for identifying any colateral branches, the small group of arteries feeding the urethra, the central gland, and the capsular arteries. The posterior–anterior view is more anatomical and helps to identify some contralateral prostate

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Fig. 6 Illustration showing the ideal positioning of the distal tip of the microcatheter (asterisk) for a safe and effective direct flow embolic agent injection during prostatic artery embolization

Fig. 5 A Illustration showing the ‘‘PROVISO’’ arteries and their relationship with the prostate using the Foley balloon as a guide under the ipsilateral Oblique view. (F The Foley balloon placed into the bladder, Sv superior vesical, IV inferior vesical, mR middle rectal, Ob obturator, iP internal pudendal, ig inferior gluteal, sg superior gluteal, ls lateral sacral, il iliolumbar). B Internal iliac DSA showing the PROVISO acronym (P internal pudendal, R middle rectal, O obturator, VI inferior vesical and S superior vesical under Oblique view

lobe branches and the parenchymal phase. After checking both views, the microcatheter should go deeply into the IVA at the ostium of the prostatic arteries and embolization is performed under direct flow (Fig. 6). Care must be taken with the position of the tip of the microcatheter to avoid spasm or dissection of the tiny intraprostatic branches.

Concerning the position of the microcatheter for embolization, we define it as distal embolization when the microcatheter tip is placed at the origin of the intraprostatic branches (Fig. 7) compared with proximal embolization when the microcatheter tip is at the origin or initial traject

of the IVA. In this proximal position, there is a higher risk of nontarget embolization, especially to the rectum or bladder. Diagnostic arteriogram in this position is very important to identify the prostatic branches, to avoid nontarget embolization and to occlude any colaterals and shunts, if necessary (Fig. 8). Cone-beam CT can be very useful to understand the pelvic anatomy and identify the bladder and rectal branches avoiding complications (Fig. 9).

Atheroscletotic disease, thin, tortuous vessels, and lack of knowledge regarding all prostatic arterial vessels can contribute to increase procedure time. The use of small diameter hydrophilic microcatheters is mandatory and can facilitate the catheterization of the prostatic arteries, decreasing the procedure and fluoroscopy times. We have used microcatheters smaller than 2.4 Fr in combination with 0.014- or 0.016-inch shapable hydrophylic microwires without continuous flushing. Roadmapping is used for the catheterization of prostatic arteries. When vasospasm occurs nitroglycerin can be used but has limited usefulness due to severe atherosclerosis in these arteries. Sometimes proceeding to the contralateral side may be a good strategy while waiting for vasospasm relief.

Embolization Varying embolic agents can be used. Based on our initial preclinical studies with dogs in 2007, experience with fibroid embolization, and desire for predictable handling and location of embolization we have used EmbosphereÒ Microspheres (Biosphere Medical, Roissy, France) with excellent technical and clinical results after more than 5 years of follow-up in the initial patients. We have used

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Author's personal copy F. C. Carnevale, A. A. Antunes: How I Do PAE for BPH

Fig. 7 A DSA under left oblique view showing the anterior and posterior branches of the left internal iliac artery and the relationship of the left inferior vesical artery feeding the inferior portion of the Foley balloon (arrow). Conventional arteriogram of the left prostate lobe after distal catheterization of the left inferior vesical artery showing the relationship of the prostatic arterial branches with the

Foley balloon under B ipsilateral oblique view and C posterior– anterior view. In this case, part of the right prostate lobe is opacified through the left branches (arrows). D DSA under left oblique view with stasis of the left inferior vesical artery (arrow) after embolization of the prostatic arteries

300–500 lm and 100–300 lm EmbosphereÒ Microspheres. To each 2-mL syringe of microspheres, we add 10 mL of iodinated contrast medium and 10 mL of saline, resulting in a total volume of 22 mL of 50 % contrast and 50 % normal saline solution. We believe that using high dilution and very slow injection is essential to avoid early proximal occlusion and to achieve the goal of diffuse gland parenchymal ischemia. The mixture is injected slowly under fluoroscopic guidance. We use a 1-cc injection syringe for embolization, reducing fluoroscopy exposure as much as possible, because embolization takes time. It requires at least 10–15 min to achieve the desired endpoint.

We suggest waiting 3–5 min after initial stasis to assess potential recanalization and flush the microcatheter with saline trying to pack the microspheres inside the prostate. If continued forward flow observed more embolic agent may be injected. At the end of the embolization, a venous phase and blush can be observed, and we consider total stasis as the endpoint. In general, one 2-mL syringe of microspheres has been enough for bilateral PAE. After achieving a good endpoint, the microcatheter should be pulled back to the origin of the IVA and a manual injection run performed for

final control and to look for additional prostatic branches.

If any doubt concerning other feeders to the prostate exists, follow-up arteriogram should be performed using a pump with the 5-French catheter at the common internal iliac artery to check for any further blood supply to the prostate.

If any accessory prostatic branch is not embolized, poor long-term clinical results may occur, including reduced prostate shrinkage and return of LUTS symptoms. Embolization is performed on the contralateral side using the same technique. Bilateral inferior vesical arteries and any other prostatic branches should be embolized to achieve optimal prostate ischemia, resulting in volume reduction for better long-term results.

The most time-consuming procedure is the identification and catheterization of the branches of the anterior internal iliac artery and identification of the relationship of these vessels with the prostate. In addition, the embolic agent injection to achieve stasis requires time. After the learning curve with the prostatic vascular anatomy and using appropriate microcatheters and microwires the average procedure can be performed in approximately 90–120 min.

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Fig. 8 A DSA under posterior-anterior view after catheterization of the left inferior vesical artery (IVA) showing the prostate parenchyma with branches feeding the bladder bilaterally (white arrows). B DSA under posterior–anterior view showing some prostatic branches and a collateral bladder branch that was embolized with a metalic microcoil (3 9 22 mm VortXÒ, Boston Scientific, Natick, USA) to avoid non-

target embolization to the bladder. C DSA after microcoil placement occluding the bladder branches with higher opacification of the left prostate lobe arteries (arrows). See the relationship of the Foley balloon with the median lobe arterial branches. D DSA after embolization of the prostatic arteries with total stasis of the inferior vesical artery (IVA) and patent bladder branches bilaterally

Fig. 9 Cone-beam CT using the Dyna CTÒ (Artis Zeego, Siemens, Erlangen) during PAE showing: A the inferior vesical artery (IVa) given a branch to the rectum posteriorly (middle rectal artery, white

arrow) and to the prostate (asterisk). Observe the prostatic branches immediately bellow the Foley balloon (F). B The black arrow shows air in the rectum opacified by the middle rectal artery

Postprocedure Management

disrupting the vascular site. If a vascular closure device is used resting time can be reduced. During this resting time after PAE, the use of the Foley balloon is very important, because patients can void normally without straining,

After the procedure, patients remain 4–6 h without moving the punctured leg to avoid bleeding complications from

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which reduces the risk of puncture site complications. The Foley catheter is removed after 2–4 h in patients without AUR and the patient is discharged home. Patients with AUR and chronic use of indwelling catheter are instructed to return 1 week later for removal of the indwelling catheter to attempt spontaneous voiding. If the catheter cannot be removed, another attempt is tried every week. We consider it a clinical failure if the patient cannot urinate spontaneously after 1 month.

Prostatic artery embolization is not a painful procedure, and patients typically receive oral hydration, nonopioid pain relievers, antibiotic, and nonsteroidal anti-inflammatory drugs, if needed. Proton pump inhibitor for gastric and duodenal protection is indicated. Dysuria and frequent urination are the most common symptoms immediately after PAE and usually last for 3–5 days. We have observed more dysuria when using 100–300 lm compared to 300–500 lm microspheres after embolization. We stop prostatic medication just after PAE. A few patients (\10 %) with dysuria after embolization are afraid of AUR and are instructed by their urologists to take alpha-blockers for 1 week. After this period, with consultation and medical examination, they stop. Patients keep in touch during the first week and return for consultation 1 month after the procedure.

Technical and Clinical Success and Complications We consider it a technical success when main bilateral prostatic arteries are embolized. The purpose of PAE is to produce as much gland ischemia as possible, because we have observed that better long-term clinical and urodynamic results are correlated with prostate ischemia.

Clinical success is defined by multiple criteria: removal of the Foley catheter in patients with AUR, LUTS symptom improvement according to the IPSS and QoL, and no sexual disorders or serious adverse events from the treatment. We have observed significant QoL improvement after PAE as reported by patient questionnaire, and objective urodynamic data corroborate these self-reported assessments. This improvement has been sustained over time. With more than 4 years of follow-up in some patients (mean, 13.5 months), we have observed initial clinical failure in only 2 % of 62 treated patients and recurrence of LUTS in 5 % after PAE. The single instance of clinical failure occurred in a patient who had a mean prostate reduction of 5 % after two bilateral embolizations and failure to remove the chronic indwelling catheter. He was referred for TURP and the surgeon stated this patient experienced a much smaller blood loss compared with historic TURP patients. Histology after TURP showed ischemic and necrotic areas

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related to the microspheres as expected. No patient in our series has presented with sexual disorders or erectile dysfunction as assessed by the IIEF questionnaire after intervention.

Prostate inflammation and ischemia postembolization are reflected in a PSA elevation immediately after the procedure. We have observed that 24 h after embolization, PSA increases by 10–20 times relative to the mean baseline values. By 1 month after embolization, mean PSA drops to normal values (50 % of the initial mean baseline) and is sustained over time, suggesting prostate cellular apoptosis after PAE. Our results have shown that higher PSA values at day 1 after PAE are correlated with better patient outcomes in patients with AUR, based on urodynamic evaluations and clinical follow-up [25].

Good clinical outcomes and improvements in urodynamic data, even in patients who underwent unilateral PAE, suggest that factors from PAE other than prostate reduction, such as prostate tissue change, can contribute to improving symptoms and better voiding. Only one patient with AUR managed with an indwelling catheter and treated by unilateral embolization has needed to undergo a second procedure due to LUTS recurrence 4 years after PAE, with good clinical results. This suggests that some patients can benefit even when only unilateral embolization is possible.

Adverse events were evaluated for severity using the NCI CTCAE (Common Toxicity Criteria for Adverse Events) according to the National Institutes of Health (version 4.0; edition 5.28.2009) [26]. No serious complications or adverse events in performing PAE occurred in our series. Similar to any other visceral embolization, we have defined symptoms, such as nausea, vomiting, fever in the absence of infection, urethral burning, periprostatic or pelvic pain, very small amounts of blood in urine and/or mixed in the stool with mucus for 2–3 days, as ‘‘post-PAE syndrome’’. Because this post-PAE syndrome is mild and the embolization is performed under local anesthesia, patients can be discharged on the same day of the procedure. In our experience, the presence of a small amount of blood in the urine (8 %) or mixed in the stool (12 %) is likely to be the result of arterial communications between the prostate, bladder, and rectum. None of these incidents required treatment, and all resolved spontaneously. To avoid radiation injuries, any available dose-reducing features, such as low-dose fluoroscopy mode, collimators, and image-hold capabilities should be used.

Postprocedure Imaging and Follow-up Both US and MRI are useful methods of measurents before and after PAE, but we have observed greater variations in the US results and prefer MRI for this procedure (Fig. 10).

Author's personal copy F. C. Carnevale, A. A. Antunes: How I Do PAE for BPH

Fig. 10 T2-weighted MR (A) axial and sagittal (B) images before and 3 months after PAE, showing a reduction in the volume of the central gland, due to appearance of bilateral postprocedure infarcted areas (arrows in C and D)

Patients have demonstrated an average of greater than 30–40 % reduction in the prostate volume after PAE as measured by US and MRI during follow-up. Volume decrease was most evident during first 3 months after embolization and is sustained over time. Big prostates ([90 g) have observed higher reduction rate (40 %) compared with small prostates (30 %). Progressive reduction of the prostate volume occurs after embolization and infarcts have been seen in 70–80 % of the patients, exclusively in the prostatic central zone, mostly characterized by hyperintensity in T1-weighted images and predominant hypointensity in T2-weighted images and reduces progressively in size over time. Volume prostate reduction has been observed in patients with and without infarcts, but presence of infarcts is associated with greater volume reduction. No significant changes have been found in the prostatic peripheral zone.

After the PAE procedure, we suggest urodynamic studies every year and IPSS, IIEF, QoL questionnaires, PSA, US, and MRI for evaluation of effectiveness at 3 and 12 months, and every year thereafter. Urodynamic findings after PAE have demonstrated that maximum bladder capacity and maximum flow rates improved significantly.

Bladder tone also improved and patients obtained better Qmax with reduction of the Pdet and of the PVR. This means that patients void better, without straining and with less residual urine in the bladder after voiding [27].

Conclusions Prostatic artery embolization has emerged as an alternative to surgical treatments for BPH. Patient selection and refined technique are essential for good results. Technical limitations to this technique are related to elderly patients with tortuous and atherosclerotic vessels, anatomical variations, difficulty visualizing and catheterizing small diameter arteries feeding the prostate, and the potential risk of bladder and rectum ischemia. The presence of collateral shunts can be a concern.

We do believe that the IVA is the most important feeding vessel to be embolized and any other accessory branches should be identified and embolized bilaterally to achieve better results. Symptomatic patients due to BPH can be treated safely by PAE with low rates of side effects and can reduce prostate volume by an average of more than 30 %.

Overall, clinical improvement in LUTS assessed by IPSS, QoL, and urodynamic data is achieved without urinary incontinence, ejaculatory disorders, or erectile dysfunction.

Nevertheless, a multidisciplinary approach with urologists, diagnostic radiologists, and interventional radiologists is essential. Evaluation of larger numbers of patients in a controlled clinical trial is necessary to validate these techniques and confirm long-term outcomes.

Acknowledgments The authors thank Joaquim Mauricio da MottaLeal-Filho, Eduardo Muracca Yoshinaga, Vanessa Cristina de Paula

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Author's personal copy F. C. Carnevale, A. A. Antunes: How I Do PAE for BPH Rodrigues, Airton Mota Moreira, Octavio Meneghelli Galva˜o Gonc¸alves, Andre Moreira de Assis, Ronaldo Hueb Baroni, Antonio Sergio Zafred Marcelino, Luciana Mendes de Oliveira Cerri, Miguel Srougi and Giovanni Guido Cerri for their important collaboration.

Conflict of interest The authors declare that they have no conflicts of interest.

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