bening prostatic hyperplasia

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Origin al Article: Clinic al Inves tigati on Benign prostatic hyperplasia: Clinical benets on Three-Dimensional ultrasound eXtended Imaging (3D-XI) Salah Elwagdy, 1 Elhakim Samy, 2 Moussa Sayed 3 and A-Hassan Gamal 4 Departments of  1 Radiology,  2 Pathology,  3 Urosurgery and  4 Anatomy, Azhar University, Cairo, Egypt. Objectives:  T o prospectively eval uate whether  trans-rectal Three-Dimensional eXtended Imaging (3D XI) allows characterization of the pr osta te gla nd in cases of isolat ed benign pro state hyp erp las ia (BPH) so as to elu cid ate the motive for dis cr epa ncy of pos tvo idi ng res idu al urine. Methods:  The stud y wa s conduc ted acc ording to the sta nda rds of the loc al ethi cs commi ttee . Pa tients gav e inf orme d consent. Dis closing the 3D XI dis pla y of the pr osta tic ure thr a and pr osta tic gla nd zones was a pre limina ry ess enti al. The stud y inc lud ed 113 men wit h a cli nic al dia gnos is of BPH in whom transurethral resection of the prostate was planned. Patients aged from 52 to 75 years (mean 63). Other causes of infravesical obstructive uropathy and prostate neoplastic involvement were excluded. All patients were evaluated by three-dimensional Trans-Rectal Ultrasound using 3D XI methods. Patients were grouped according to the postvoiding residual urine volume into three groups, less and more than 100 mL and urine retention. Results:  3D XI providedexcellent resolutionand diagnosticauthor ity of prostate gla nd ana tomy and forthe app raisal of BPHmorphology . The balance and type of nodular eruption proved responsible for the severity of symptoms aspires by extra-axial nodular effect upon the prostate urethra. The 3D XI analysis regarding the nodular stromal to glandular ratio compared to the histopathological results proved effectual in 98.3% of stromal-dominant, 100% in glandular-dominant and 93.3% in mixed type hyperplasia. Conclusions:  The severity of symptoms among men with BPH showed an associa tion with the nodular credence, highlighted by 3D XI as a supportive tool in characterizing BPH. Key words: 3D XI, BPH, characterization, three-dimensional, ultrasound. Introduction Benign prostatic hyperplasia, one of the most common diseases among aging men, can be associated with bothersome lower urinary tract symptoms that affect the quality of life by interfering with normal daily activities and sleep patterns. 1,2 Many urologis ts conside r assess ment of the postvoiding residual urine (PVR) an important examination in patients with benign pros- tate hype rplasia. 3–5 Se ver al stud ies ha ve bee n as we ll pub lish ed assessing the si gni cance of PVR less or more than 100 mL. 5–8 Authors concluded that the nding of a signicant amount of PVR might draw the clinician’s attention to impaired micturition, but does not dene the type of disorder or its grade. However, they approved its importance in isolated benign prostate hyperplasia, if higher than 100 mL. In 1998 Watanabe 9 reported an important principle explaining the variance of PVR in cases with BPH, as mostly related to the elasticity of the prostatic surgical capsule. By means of conventional TRUS, he referred to only two parameters, measuring of the presumed circle area ratio (PCAR), which is considered a necessary condition and PVR as a sufc ient condition. This of course has made it rather easy to compr e- hend the pathophysiology of BPH. Ansari et al . in 2000 10  by means of magne tic resona nce imaging (MRI) also appro ved this belief . They rep orte d tha t the contai ner ‘sur gic al cap sule ’, insi de whi ch the se nodule s de vel op, compre sses the gro wing nodu les insi de it, thus causing the compression of the urethra, and consequently the severity of the clinical symptoms. They also considered the inner gland ratio,  protrusion of t he prostatic gland i nto the bladder and the presence of the surgical capsule as the most important factors in bladder outlet obstruc- tion; the probability of outlet stenosis increases in patients with more than two of these criteria. McNeal (1990) 11 was the pioneer in describing the recent pathology of BPH, as occurrin g not uniforml y throughout the gland but develop - ing as a nodular eruption in the transitional zone close to the prostatic urethra, more frequently the peri-urethral region and to a lesser extent involving the central zone. The appeal of sonography lies in the fact that it is a non-invasive, cost-effective technique and easily adapted to routine ofce use. 12–14 From the radiological point of view, there are two important subdivi- sions of the prostate: the peripheral zone and the central gland. Using this terminology, the central gland includes both transitional and central zones and it is not generally possible to differentiate these by conven- tional TRUS. 15,16 The reason is frequently because the surface visual- ization of ultrasound image contains many small speckles (artifacts) so that the proper interesting image parts and minute details of ultrasound anatomy are not denite. 17,18 This was one of the main ongoing needs for technical developments capable of improving ultrasound image resolution without disturbing real time display. The development has started with the introduction of three-dimensional ultrasound (3D US) into the imaging eld and is  particularly robust with the recent advances of dynamic interactive speckle reduction. 19–21 In the present study, we used Three-Dimensional eXtended Imaging (3D XI) technology, which is a software update of 3D US, as a com-  prehensive modality to try to correlate symptoms in isolated BPH through charact erization of nodular balance alongside the prostat ic urethra and the nodular type-dominance in aging men, through which further studies may advance. To our kno wle dge, no pre vious studies addressing the value of 3D XI in isolate d BPH have bee n pub lished bef ore the pre sent investigation. Correspondence: Salah Elwagdy , Azhar University – Uro-Radiology , 133, Shubra st., 11242, Cairo, Egypt. Email: salah_ [email protected] Received 9 July 2007; accepted 6 December 2007. Online publication 18 February 2008 International Journal of Urology (2008) 15, 332339 doi: 10.1111/j.1442-2042.2008.01988.x, 332  © 2008 The Japanese Urological Association

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Methods

All patients gave written informed consent and were informed in detail

about our procedures for diagnostic fulfillment according to the proto-

col of this study, which was approved by the local hospital ethics

committee. One hundred and thirteen consecutive patients aged from

52 to 75 years (mean 63 years) with a clinical diagnosis of BPH in

whom transurethral resection of the prostate (TURP) was planned – 

were examined by 3D XI modality.

Patients with other causes of infravesical obstructive uropathy were

excluded. Patients with proved prostatic neoplastic focal lesion after 

 pathology confirmations of specimens obtained by systematic   trans-

rectal ultrasound guided biopsy were also excluded. Prostatic specific

antigen (PSA) levels were 3.1 up to 4.9 ng/mL (mean, 3.7 ng/mL).

Three-dimensional Trans-Rectal Ultrasound(3D-TRUS) procedures

The study was achieved by means of the 3D US machine (MEDISON-

Accuvix-XQ) provided with 3D XI software for extended thin sectional

 panoramic appraisal of the prostate gland. Examinations were per-

formed with a 3D endocavitary motorized-sweep probe (5–8 MHz). We

routinely acquired the entire prostate for every patient in a single 3D

volume. XI Multi-Resolution (XI MR) computed maneuvers and inter-

 pretations of volumes were fulfilled after the patient left the examina-

tion room.

Estimation of the prostate volume (PV) and PVR in all cases were

measured using 3D calculations – VOCAL-imaging program (Virtual

Organ Computer-aided AnaLysis). Volume  =  1/2[åni  =  2(Ai-1  +  Ai) á

di-1].

3DUS display methods

The reconstructed 3D XI image data set was networked to the work-

station (Sonoview II). We used two formats. First, the Multi-Slice View(MSV), the milestone of 3D XI technology, which is a computed 

tomography of the acquired volume, in which the set of a single volume

viewed as sequences of 2D US images in axial, coronal or transverse

 planes. The thickness of images in a series can also be manipulated 

from fractions of a millimeter to a few millimeters thick. Second, we

used the XI MR, which is a sophisticated form of interactive image

speckle removal with a scale of enhancement providing stronger, very

thin images. 3D XI Image quality was optimized by using algorithms to

vary opacity, transparency, part selection and depth.

Collection of tissue specimens

The complex zonal anatomy led us to believe that a single technique

could not be used to obtain specific tissue from the zones. For each

zone, the sampling techniques were standardized. Apart from the six

systematic biopsies prior to the patient’s selection, another two biopsies

were obtained guided by live 3D-TRUS, thus allowing direct sampling

of the transitional and central zone nodular lesions. Then, during the

TURP, several tissue samples were also collected from the same patient

with a resectoscope loop biopsy. All tissue specimens were fresh prior 

to fixation in formalin, signifying where tissue samples were obtained.

Groups

Patients were grouped according to PVR into three groups, less and 

more than 100 mL and urine retention according to the agreed limits 5–8

0

50

100

150

200

250

N

(mean)

PV

(mean)

PVR

Group I

Group II

Group III

R

PA

Fig. 1   Chart showing the variance of postvoiding residual urine (PVR) in

relation to the prostatic volume and mean age. N, Number of patients in

each group; PA, Patient age (mean); PV, Prostate volume (average); PVR,

average; R+ arrow, Urine retention.

a

b

CZ

PZ

TZ

Fig. 2   Normal three-dimensional ultrasound (3D US) anatomy of the pro-

staticurethra.(a) 3D sagittal trans-section along the courseof the prostatic

urethra, revealing the prostate urethra (arrows) and its ventral-curve.

Arrowhead points to the bladder neck. (b) Sagittal   trans-section of the

prostate gland along the anatomical location of the prostatic urethra

(arrows) during micturition (voiding). The bladder neck (arrow heads) and

urethra (arrows) during voiding are wide and smoothly sloped. BN, Bladder

neck; UB, Urinary bladder; PR, Prostate gland.

3D XI of senile benign prostate

© 2008 The Japanese Urological Association 333

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Both XI MR and histopathological specimens were blindly inter-

 preted. Imaging impressions finally compared to the histopathological

results of specimens obtained after TURP.

The recorded positive values included:

1   Assessment of image quality.

2   The relationship between the enlarged prostate gland to the volumeof PVR.

3   Nodular mapping and characterization according to histopathologi-

cal reports.

4   Demonstrating the effect of BPH nodules upon the prostatic

urethra.

Image analysis

Readability and diagnostic efficacy of images were undertaken using

computer software (HIT-Telepax). Analysis of the XI MR images was

carried out by comparing echo-intensity values for stromal  vs glandular 

tissue obtained by using computer software (Genstat 9).

Results

 None of the suspected cancerous or other causes of lower bladder outlet

obstructive uropathy was included in this study.

The normal 3D XI display of the prostatic urethra and the prostate

gland zones with diagrammatic illustrations designed by the working

group (Figs 2,3) was a preliminary essential.

The prevalence of histopathological benign prostate hyperplasia and symptoms enrolled in our study was usually found in patients older 

than 50 years.

Our records of the three groups concluded that the prostate gland in

a significant proportion of cases is distinctly enlarged (>60 cm3) with

an estimated PVR of less than 100 mL. On the other hand, prostate

enlargement (<60 cm3) may come in the company of big volumes of 

PVR up to urine retention.

XI MR proved capable of localization of the prostate urethral course

and the morphology of the BPH nodules. XI MR could explain the

changes of the transitional zone (TZ) and the central zone (CZ) of the

 prostate gland according to the balance of nodular eruption alongside

of the prostatic urethra; scheduled in Table 1.

a

N

b

N

BN

Fig. 4   61 year-old manwho presentedwith urine retention.(a) Multi-Slice

View (MSV) frame in transverse axis of the prostate showing a solitary

nodule (N) encroaching upon the prostate urethra during micturition trial

into the condom catheter. The bladder neck is wide and represented as an

anechoic crescent-shape. (b) XI Multi-Resolution (XI MR) Image of the same

case showing the nodule in the coronal plane. The bladder neck (BN) is

wide. The prostate urethra (arrows) is deviated to the right demonstrating

the nodular compression effect upon the prostate urethra.

UR 

a

b

Fig. 5   59 year-old man who presented with weak stream and frequency.

PVR  =   91 mL. (a) Multi-Slice View (MSV) frame of the prostate showing

markedly enlarged prostate, with two balanced lateral nodules (N). (b) XI

Multi-Resolution (XI MR) Image at MSV set of the same case after factors

adjustment, showing the nodular (N) compression effect (arrows-direction)

upon the prostatic urethra (UR).

3D XI of senile benign prostate

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Accuracy of XI MR in nodular detection and characterization real-

ized about 98.2% referenced to histopathological reports. Diagnostic

accuracy of 3D XI in nodular detection compared to the histopatho-

logical type intended in Table 2.

The severity of the patients’ symptoms reported in our series was in

association with prominent big peri-urethral nodules in two patients

(Fig. 4), bilateral symmetrical prominent nodules in three patients

(Fig. 5) and multiple small bilateral unbalanced nodules in 11 patients (Fig. 6), all of which were noted to have PVR more than

100 mL up to retention. The less severe symptoms were in the company

of multiple bilateral balanced micronodular patterns in 53 patients out

of 113 (46.9%), irrespective of the prostate volume.

Image sequence on XI MR showed that the variations in echo-

intensity of the prostate gland nodules in cases with BPH are feasible

for correlation in the direction of histopathology. We noticed that the

echo-intensity of the BPH nodules increased when the ratio of stromal

elements within the nodules proved dominant (Fig. 7). On the other 

hand, equal ratios of stromal and glandular components of BPH

nodules are sometimes coexistent (Fig. 8) and mostly reflect variance in

echo-intensities. As early as the eruption of BPH nodules, XI-MR 

images proved reliable in justifying early detection of glandular-

dominant BPH (Fig. 9).

Histopathological examination of the specimens obtained during

live 3D-TRUS and after TURP showed stromal-dominant hyperplasia

in 58 patients (51.3%), glandular-dominant in 40 instances (35.4%)

and mixed hyperplasia in 15 patients (13.3%). The accuracy of XI

MR in nodular detection and characterization referenced to histo-

 pathological reports was about 98.2%. Two cases exceeding the age

of 70 years presented with an indwelled Foley’s catheter were missed 

 by XI MR in correlation with the pathological type. Both were of 

stromal-dominant hyperplasia. XI MR impressions compared to his-

topathological results and the effect upon the prostatic urethra are

 presented in Table 3.

DiscussionThe prevalence and incidence of clinical problems secondary to and 

associated with BPH have been increasing as the population ages. 23

BPH is an all-inclusive term for a heterogeneous group of distinct

 pathological entities that feature variable changes of the stromal and 

glandular elements.10,11 Caine et al .24 have proposed that bladder outlet

obstruction in BPH involves both static and dynamic components. The

static component of obstruction is related to primary prostatic enlarge-

ment, whereas the dynamic component is related to the tone of the

 prostatic smooth muscle.

The present prospective study was designed to evaluate the useful-

ness of 3D XI as an update of 3D US imaging in assessing its clinical

 benefits in isolated BPH, and to evaluate what findings are mostly

related to the degree of symptoms severity.We agree with Watanabe (1998)9 and Ansari  et al . (2000)10 that the

inner gland ratio, protrusion into the bladder, and presence of surgical

capsule are important factors in the probability of outlet stenosis,

increasing in patients with more than two of these criteria. However, we

noticed through 3D XI characterization of the container within the

surgical capsule that the nodular balance and type alongside the

 prostatic urethra has additional effects upon the PVR volumes and 

symptoms severity. In our series, symptoms could be accounted as

transpires in unbalanced nodular hyperplasia in 14.2% of cases, rather 

than balanced nodular eruption (85.8%).

Therefore, we think that neither the elasticity of the surgical capsule

nor the voluminous central gland are the standard compulsory factors

in symptom severity, since we have recorded some instances (16 out of 

113 patients) with small central glands in association with urine reten-

tion. The nodular balance proved mostly responsible for the severity of 

symptoms in those cases, aspires by extra-axial nodular effect upon the

 prostate urethra.

On the other hand, the symptom severity, when compared and cor-

related with the histopathological results, showed an intimate relation

 FF

TZ

CZ

a

b

c

Fig. 6   Moderately enlarged prostate in 63 year-old man who presented

with urine retention. (a) Coronal Multi-Slice View (MSV) with selective XI

Multi-Resolution (XI MR) (left) showing unbalanced nodular hyperplasia of

thetransitional (TZ) andcentral (CZ) zones.The urethral midline alignmentis

distorted (arrows). (b) Axial MSV with selective XI MR (lower right) showingthe conglomeration of nodules forming a bigger nodular structure (arrow).

(c) Coronal MSV with XI MR (left) after the indwelling of Foley’s catheter

released urine retention.

S ELWAGDY ET AL.

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to the nodular type. The symptom severity was more evident in cases

that proved histological stromal-dominant nodular hyperplasia (20.7%)

and mixed hyperplasia (20%) and the less severe symptoms were

recorded in glandular-dominant hyperplasia (2.5%).

Analyzing the nodular echo-intensities on 3D XI images compared 

to histopathology showed that the increase in echo-intensity of the

nodules is directly proportional to the ratio of stroma within the nodule.

The nodules may possibly show high or low echo-intensity compared to

the surrounding central gland parenchyma when the stromal or glan-

dular element of the nodules, respectively, is dominant. However, in

some older patients, the estimation of echo-intensities of the nodules is

not simple, because of the overall relative increase in echo-intensity of 

the central gland. In such instances, the isoechoic prostate nodules can be indirectly recognized by 3D XI’s computed MSV, through the dem-

onstration of the derangement of the course of the prostate urethra.

 Nevertheless, a more precise detection of isoechoic n odules is predict-

able during processing XI MR and manipulating the image factors

either by changing the threshold levels or gamma correction until the

demonstration of the nodules improved. Those factors are not stable in

every case, but they are dependant upon viewing the best choice of 

resolution.

3D XI proved diagnostic accuracy in 57 out of 58 cases with stromal-

dominant hyperplasia (98.3%) and 14 out of 15 instances (93.3%) in

mixed hyperplasia. However, the diagnostic accuracy showed 100% in

cases with glandular dominant hyperplasia.

In view of nodular characterization correlated to the severity of 

symptoms, 12 of 58 patients (20.7%) with stromal-dominant hyperpla-

sia had severe urethral stenosis. Whereas 31 of 40 patients (77.5%) with

glandular-dominant hyperplasia had none of the XI MR criteria for 

severe stenosis, they showed a PVR below 100 cm3, apart from eight

cases (20%) that showed stenotic figures of the prostatic urethra due to

unbalanced conglomeration of peri-urethral nodules. In addition,

 patients presenting with nodular hyperplasia resulting from a sizable

solitary adenoma or conglomeration of multiple small nodules devel-

oped a noteworthy compression effect proportional to the size of the

lesion. Quite the opposite, patients with huge prostates and an even

nodular eruption of the transitional and central zones had a non-

significant volume of PVR; hence, the clinical symptoms of BPHnodular effect were primarily dependant upon the pattern of nodular 

 balance bordering the prostatic urethra.

In the present study, the overall sensitivity of XI MR on BPH

characterization achieved 98.2%, which is a major improvement

over the levels reported with conventional 2D TRUS. Our results pro-

vided excellent resolution and diagnostic authority of internal pros-

tatic anatomy, detection of BPH nodules and their balance and 

information data regarding the ratio of stromal to glandular tissue in

the prostate.

Therefore, 3D XI as an upgrade of 3D US, is superior in the evalu-

ation of urinary outlet stenosis in patients with BPH, without being

restricted by high cost or limited availability.

Fig. 7   Moderately enlarged prostate, with

postvoiding residual urine (PVR) of about

65 mL. (a) Coronal Multi-Slice View (MSV) set

with selected XI Multi-Resolution (XI MR)

image showing the balanced micronodularpattern of the transitional (TZ) and central (CZ)

zones of the prostate. The echo-intensity of

thenodules (arrows)is higheron therightthan

the left and relatively more coalescing on the

right. (b) The benign prostate hyperplasia

(BPH) nodulesin coronal plane arealmost even

on each side of the prostatic urethra, which is

represented midline position (arrowhead). The

bright echo-intensity of the nodular pattern is

noted and correlating with the histopathologi-

cal report of the overriding stromal element.

(c) Histopathology of the same case showing

stromal overgrowth.

TZ

CZ

a

b   c

3D XI of senile benign prostate

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Our study has resulted in three major findings. First, by reducing

the possibility of human error and reducing scan time, 3D XI can

improve the diagnostic acumen of ultrasound imaging and thus prove

advantageous to clinical practice. Second, 3D XI imaging technology

reflects sharp soft tissue characterization, which is capable of depicting

subtle tissue abnormality. The third is that our procedure is easy mobile

and non-invasive.

However, our study had some limitations. First, we evaluated only a

limited group of patients, and second, our study required training in the

3D XI methods and long previous experience using 3D US.

TZCZ

TZ

CZ

PZ

a

b

c

Fig. 8   Patient of almost 72 years, who presented with hesitancy, with

non-significant postvoiding residual urine (PVR) (51 mL). (a) Selected semi-

axial XI Multi-Resolution (XI MR) Image of the prostate gland, showing

extensive benign prostate hyperplasia (BPH) nodular eruption (arrows)

involvingthe transitionalzone (TZ) andthe central zone (CZ). The peripheral

zone (PZ) is attenuated. Asterisk: Midline prostatic urethra. (b) Coronal XI

MR showing low density nodules corresponding to overriding glandular

element at the transitional zone and other high density nodules of overrid-

ing stromal element at the central zone as correlated with the histopatho-

logical report. (c) Histopathology of the same case showing nearly equal

glandular & stromal hyperplasia.

TZ

CZ

PZ

UB

a

b

Fig. 9   52 year-old man who presented with micturition frequency. (a)

Selected XI Multi-Resolution Frame of the prostate showing mildlyenlarged

prostate and demonstrating early nodular eruption (arrows) of the transi-

tional zone. The micronodular eruption is of a low density pattern correlat-

ing with the overriding glandular element of early benign prostate

hyperplasia (BPH). CZ, Central zone; PZ, Peripheral zone; TZ, Transitional

zone; UB, Urinary bladder. (b) Histopathology of the same case showingPredominant glandular pattern.

S ELWAGDY ET AL.

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Conclusions

3D XI proved a supportive tool in the characterization of BPH. The

technology allows for the zonal description and consequently the accu-

rate appreciation of the figure of BPH. The balance and the type of 

nodular eruption proved to be mainly responsible for the severity of 

symptoms aspires by extra-axial nodular effect upon the prostate

urethra.

Acknowledgments

We would like to thank the clinicians who contributed their time filling

out the questionnaires for this study. We specify our deepest gratitude

to Ms. Julie Bartholomew, B. App. Sci., D.M.U. for her keen and 

sincere help through the entire study.

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Table 3   Histopathological correlation with XI Multi-Resolution (XI MR) mapping

Type

Number: n

Stromal-dominant

n  =  58 (51.3%)

Glandular-dominant

n  =  40 (35.4%)

Mixed

n  =  15 (13.3%)

Effect upon prostatic Severe 12 (20.7%) 1 (2.5%) 3 (20%)

Urethra detected by Moderate 32 (55.2%) 8 (20%) 4 (26.7%)

XI MR Mild 14 (24.1%) 31 (77.5%) 8 (53.3%)

Severe: up to urine retention. Moderate: PVR 100 mL. Mild: PVR 100 mL.

3D XI of senile benign prostate

© 2008 The Japanese Urological Association 339