**4.1 Benigne Prostate Gland Hyperplasia (BPH)**

This noninfectious disease of the prostate gland only occurs in intact male dogs with endocrinally active testicles. The disease counts for 50% of all prostate diseases [9]. The incidence increases with increasing age; however, in rare cases, BPH can occur at the age of 2–3 years [28]. Sonographical and in part clinical symptoms usually can be seen in 80% of male dogs at the age of 5 years [11, 12, 20], and in >95% of males at the age of >9 years [11]. The hyperplastic increase in size is caused by:


Dihydrotestosterone is the active form of testosterone and produced from testosterone by the enzyme 5α-reductase. The activity of the enzyme increases in the aging dog, especially in the glandular epithelial cells; therefore, the hyperplasia mainly concerns the glandular epithel and less the stroma [30, 31]. In one experiment, BPH could be produced by long-term application of 5α-androstan-3aα, 17ß-Diol (3α-Diol), in combination with 17ß-Estradiol. 3α-Diol is produced by reduction from DHT and/ or 17ß reduction from androsterone; it stimulates the intracellular cAMP production in the prostate gland [32]. In another experiment, the testosterone concentration was doubled on days 21 and 42, with the same effect [33]. The experiment points toward

the impact of these hormones and an eventual change in the enzyme and metabolic activity inside the aging gland. The role of local growth factors and relaxin is still not sufficiently investigated.

Prolactin was detected in prostate secretions of dogs with BPH and with higher concentrations than in healthy dogs; during the development of the prostate, prolactin contributes to growth and differentiation [29].

As a further predisposing factor, the breed was previously mentioned; large breeds seem to be more often concerned [34–36] and in a recent study, the Rhodesian Ridgeback was shown to be predisposed, pointing toward a genetic cause [35]. Some authors suggest a breed-specific pituitary prolactin secretion, which lacks evidence so far but deserves better investigation [35, 37].

#### *4.1.1 Clinical symptoms*

The disease starts with centrifugal increase in size; sonographically, changes in echogenicity and cystic caverns become visible. Clinical symptoms develop later on [18]. Therefore, the BPH can be termed a physiological process in aging dogs, until clinical symptoms occur (Tsutsu et al. 2000).

The first clinical sign mostly is serosanguinous preputial discharge not associated with urination; this discharge occurs because of vessel damages in the hyperplastic, well-perfused tissue [38].

The secretions reach the urinary bladder via the pars disseminata causing a bloody admixture of the urine [9, 38]. In breeding dogs, a changed composition of the prostate secretions causes an increase in pH, a decrease in motility, and bloody prostate secretions [39, 40]. Later on, morphological aberrations of spermatozoa occur [19]. BPH may cause reversible infertility. Abdominal pain because of the enlarged gland is seldom [9, 19]. The centrifugal growth of the gland causes compression of the urethra and can cause dysuria, dyschezia, stranguria, and even anuria; however, the latter is seldom [11, 41], and urination problems were seen in only 27% of dogs with BPH in one study [9]. Defecation problems more frequently occur, especially in advanced stages of BPH due to compression of the rectum, leading to acute constipation in extreme cases [19, 42].

#### *4.1.2 Diagnosis*

For an accurate diagnosis, a case history, a clinical-andrological examination of the dog including digital rectal palpation and abdominal sonography are obligatory. Furthermore, examination of urine and semen, as well as cytological examination of the prostate gland secretions can be helpful. Zambelli et al. [43] used the parameters anorexia, loss of weight, degree of tenesmus and dysuria, urinary incontinence, preputial discharge, and hematuria for clinical grading of the BPH in 4 grades, with grade 1 corresponding to asymptomatic BPH.

Digital-rectal examination reveals a symmetric increase in size, normal consistency, and no painfulness; large intraprostatic cysts may cause asymmetry [38].

*Sonography* is a good method for diagnosis of BPH in dogs; however, it should always be combined with further clinical methods [44]. The quality of the examination is variable and dependent on the quality of the pictures, and the reproducibility of the measurements [45], as well as the position of the probe [9]. Sonographical parameters are size, structure, echogenicity, and abnormal structures such as cysts, abszesses, mineralization, asymmetry of the lobi, etc [18, 46] (**Figure 1**).

#### **Figure 1.**

*Sonography (B-mode) of the physiological prostate. Prostate gland of a healthy 5-year-old beagle, the white arrows mark the contour. The size was 3 × 2 cm (L × W), the structure of the gland is homogenous, the echogenicity is physiological, and the anechoic line in the middle is the urethra.*

The volume of the gland correlates with the body weight [47] and can be calculated when length (L), width (W), and height (H) were measured by using a formula; for example,

Measured L × W × H × 0.523/estimated volume (0.33 × body weight in kg × 3.28). In dogs with BPH, this ratio will be > 2.5 [48].

### *4.1.2.1 Sonography*

With B-mode sonography, the prostate with BPH appears enlarged, and the parenchyma is homogenous and hyperechogenic. Intraprostatic cysts of different sizes are frequent (Abb.3), and paraprostatic cysts sometimes occur [8, 12, 18, 45] (**Figure 2**). Cysts are round, thin-walled structures with anechoic contents and distal increases in echogenicity [45].

When using special doppler-sonographical methods like power or pulse-wave Doppler sonography in dogs, the examined vessels [49], as well as previous ejaculations and medications, have to be considered; a sexual rest before the examination is recommended [50]. The case history should reveal whether a gonadotropin-releasing-hormone(GnRH) analogon was applicated previously, which will change the findings considerably [51].

An increase in perfusion of the gland was recorded in 8/16 dogs with BPH in one study, using pulse-wave Doppler sonography [46]. In another study, peak-systolic velocity (PSV) and end-diastolic velocity (EDV) were significantly higher in dogs with BPH than in healthy controls [52].

Contrast-enhanced sonography (CEUS) proved to be advantageous for evaluation of vascularization and perfusion of the canine prostate gland. For this method, ultrasoundcontrast agents (UCA) are injected intravenously. Unfortunately, the use of different UCA makes results from different studies difficult to compare [45]. In one study, healthy male dogs were injected with a micro-bubble UCA with the aim to obtain physiological reference values [53]. However, one study is not sufficient; the generation of reference values by using a large and comparable data pool, standardized methods, and settings is a big problem.

#### **Figure 2.**

*Sonography (B-mode) of a prostate gland with BPH. The prostate is high-grade enlarged (arrows), the structure is homogenous, and the echogenicity is increased. The dog showed bloody preputial discharge, stranguria, and defecation problems.*

In an earlier study, micro-bubble UCA and CEUS proved to be useful for detection of vessel damages and necrosis. Unfortunately, it is still not possible to differentiate between BPH and chronical and acute prostatitis, respectively [54]. However, together with further diagnostic methods, these sonographical tools provide worthful diagnostic findings.

Elastography is an interesting tool for evaluation of tissue consistency, the degree of elasticity, and rigidity. The principle is that the degree of deformation after pressure on a certain tissue is inversely proportional to the rigidity of this tissue [55]. Different methods such as acoustic radiation force impulse elastography (ARFI) [56] were evaluated in dogs. With qualitative ARFI, short acoustic impulses of high intensity are used for deformation of the tissue, then the data are converted into a statistic grey scale (Elastogram), revealing the rigidity of the examined tissue. With quantitative ARFI, an acoustic wave is sent in a certain region of the tissue, spreading at a certain velocity within this tissue, and dependent on the rigidity of the tissue. The measured velocity correlates to rigidity and viscoelasticity of the tissue [57]. For examination of the canine prostate gland with elastography, physiological values for different groups of age are available [56, 58, 59]. Unfortunately, no controlled study about the use in dogs with BPH is available. The method requires some training.

Echostructure analysis or computerized histogram analysis of sonographical pictures is a method well-known in human medicine for diagnosis of mammary tumors. Similarly in dogs, the method proved to be useful for the diagnosis of mammary carcinomas [60]. For this method, the gland is examined via B-mode sonography and the pictures are digitalized. Then so-called regions of Interest (ROI) are marked in the pictures (**Figure 3**) and objectively evaluated by using computer-assisted analysis. (software: for example ImageJ; Wayne Rasband, National Institutes of Health, Bethesda, Maryland, USA) The echostructure analysis provides information about brightness, micro- and macrotexture, homogeneity, and contrast differences within a certain tissue [60, 61]. In a previous study, the echostructure method was used to

#### **Figure 3.**

*Echostructure Analysis of the prostate gland, regions of interest (ROI). For the objective analysis of the digitalized, B-mode pictures, four quadrants of equal size have to be placed in the region of interest. The measures are performed automatically in these regions. Evaluation is performed by a special software.*

differentiate between BPH and chronical prostatitis. In dogs with BPH, the homogeneity of the gland tissue was significantly higher than in the dogs with chronical prostatitis [62].

### *4.1.2.2 X-ray*

X-ray of the canine prostate gland provides information about the size and situ of the gland. In healthy dogs, the diameter of the prostate is at a maximum 70% of the distance between the cranial margin of the pubic bone and the promontory of sacrum [63], an increase in size points toward BPH. By using a retrograde urethrocystogram, examination of the urethra is possible; the lumen can be confined by BPH, abscesses, or neoplasms [63]. In a previous study, power injection of a contrast medium during retrograde CT-urethrography improved the evaluation of the urethra; dilations of the urethra could be easier evaluated in relation to the degree of the filling of the urinary bladder [64].

Diseases of the prostate gland can be diagnosed by use of *computer tomography* (CT); data about the healthy canine prostate gland are available [65]. The appearance is round to ovoid, homogenous, and well definable, whereas capsule, stroma, and parenchyma cannot be well differentiated. In dogs with BPH, prostate megaly, decreased density, and heterogeneity of the tissue are characteristic; reference values for the size are available [66]. However, in the cited study, the groups were heterogeneous and the size of the dogs variable. The use of a contrast medium facilitates the diagnosis, especially evaluation of the median septum and the vascular system [65, 67]. In one study using contrast-CT, the results correlated well with the cytological findings [68]. An important advantage of CT is the possibility to recognize and localize metastases [66]. However, since the CT examinations have to be done under general anesthesia, examinations should only be done in suspected cases of prostatitis, carcinoma, or other masses.

A rather new method is the diffusion-weighted and perfusion-weighted *Magnet resonance Imaging* (MRI). In a recent study, the prostate gland of healthy beagles

was examined and physiological values for perfusion and diffusion were obtained [69]. electrical-conductivity-based MRI is a further method, helping to recognize changes in the canine prostate gland tissue by evaluating changes in the contrast [70]. Further MRI methods are available and will be discussed in the chapter about prostate carcinomas [71].
