Treatment of benign prostatic hyperplasia using transurethral split of the prostate with a columnar balloon catheter.

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Journal of Endourology Treatment of benign prostatic hyperplasia using transurethral split of the prostate surgery with a columnar balloon catheter (doi: 10.1089/end.2014.0207) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.

1 Treatment of benign prostatic hyperplasia using transurethral split of the prostate surgery with a columnar balloon catheter Running title: transurethral split of the prostate with columnar balloon catheter Weiguo Huang1#*,MM, Yinglu Guo2#,MM, Guofeng Xiao3,BM, Xiang Qin4,MM 1 Urinary Surgery, the Affiliated Drum Tower Hospital of Nanjing University, Nanjing 210008, China 2 Urinary Surgery, the First Hospital of Peking University, Beijing 100034, China. 3 General Manager, Nanjing Shuangwei Biotechnology Co.LTD, Nanjing 210061, China 4 Vice-General Manager, Nanjing Shuangwei Biotechnology Co.LTD, Nanjing 210061, China Weiguo Huang and Yinglu Guo should be regarded as co-first authors. *Corresponding author: Weiguo Huang Address: Urinary Surgery, the Affiliated Drum Tower Hospital of Nanjing University, No.321 Zhongshan Road, Nanjing 210008, China Tel: +86-025-83791799

Fax: +86-025-83791799

E-mail: [email protected]

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2 Abstract Transurethral dilatation of the prostate (TUDP) with a spherical balloon catheter is a traditional treatment to benign prostatic hyperplasia (BPH) patients. However, TUDP has been abandoned in clinical application because of its unsatisfying treatment benefit and severe complications. In this study, we redesigned an improved TUDP surgery, named transurethral split of the prostate (TUSP), by replacing the spherical balloon with a columnar balloon. To evaluate the clinical therapeutic effect, we compared the lower urinary tract symptoms (LUTS) of BPH patients after TUSP treatment and analyzed the urethra through CT films. Animal experiments were performed on aged dogs to investigate the urine function and electromyography (EMG) changes. Histopathology was used to evaluate the inflammation and injury. Additionally, collagen content was detected by Trichrome Masson. TUSP attenuated LUTS and reconstructed urethra in BPH patients. The attenuation of LUTS was reflected in terms of LUTS parameters such as Qmax, post-void residual urine volume (PVR), quality of life (QOL) score and International Prostate Symptom Score (IPSS). TUSP expanded the urethra in experimental dogs by splitting the prostate tissues and decreasing the collagen content, with maintenance of normal urinary function and EMG characteristics. The successful clinical application of TUSP with significant therapeutic effect and limited complications made TUSP an ideal choice for the BPH patients. Keywords: benign prostatic hyperplasia; transurethral dilatation; columnar balloon catheter; splitting; lower urinary tract symptoms; collagen

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3 Introduction Benign prostatic hyperplasia (BPH) is associated with abnormal amplications of epithelial and stromal cells in the prostate gland 1. With the expansion of aging populations worldwide, BPH has become an important public health problem for their induction of lower urinary tract symptoms (LUTS), which interfere with daily activities and life quality of aging males 2. In recent decades, many surgical methods have been developed for treating BPH 3. So far, transurethral resection of the prostate (TURP) is considered to be the gold-standard treatments of BPH 4. However, the traditional TURP surgery carries out resections and leads to longer hospital stay and higher medical cost 5. Therefore, TURP treatment of BPH requires good physical status as well as good economic conditions of the patients, making its application difficult in developing countries. Burhenne and his colleagues began animal experiments and clinical research on transurethral dilatation of the prostate (TUDP) as early as 1984 6. Application of balloon dilatation to BPH patients was firstly reported in the United States in 1987 by Castaneda 7

. Due to the simple operation and less invasive, TUDP was once popular and carried out

worldwide 8. However, further clinical researches showed uncertain therapeutic effect of balloon dilatation method on BPH as most patients suffered from recurrent urethral obstruction and various complications 1 year after TUDP surgery 9. Therefore, the TUDP surgery was gradually abandoned in the treatment of BPH patients. In this study, we improved the TUDP surgery by redesigning the balloon catheter and operated a transurethral dilatation surgery. The improved TUDP surgery was named transurethral split of the prostate (TUSP) due to the split of prostate capsule during surgery. Compared with traditional TUDP, TUSP replaced the spherical balloon catheter with a columnar balloon catheter. 3

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4 We demonstrated that application of the columnar balloon catheter was effective and therapeutic in the clinical research including 113 cases of benign prostatic hyperplasia. Practice of TUSP surgery on animals also confirmed that widening the urethral with transurethral prostatic columnar balloons was safe and feasible. To investigate the mechanisms by which TUSP treated BPH, we performed histopathology of prostatic tissues from experimental animals and found that TUSP expanded the urethra via tearing the prostatic tissues and decreasing the collagen content.

Materials and methods BHP patients This study enrolled 113 patients who received the TUSP surgery between March 2006 and March 2011. The patients aged 68-94 years, with an average age of 74.6 years. All of the patients had lower urinary tract obstruction caused by BPH, with durations ranging from 5 to 15 years. They also had different degrees of major organ diseases, such as pulmonary insufficiency of 27 cases, high blood pressure, coronary heart disease or cardiac insufficiency of 53 cases, diabetes of 21 cases, mild-to-moderate kidney function damage of 9 cases, cerebrovascular sequela of 3 cases, and chronic cerebral infarction of 4 cases. Among the 113 BPH patients, eight patients were eliminated from prostate cancer with anal inspection and transrectal prostatic biopsy; five patients were after TURP, and one patient was after an invasive operation, but recur rented. Improved columnar balloon catheter Fig. 1 shows the structure of improved columnar balloon catheter applied in TUSP surgery. The columnar balloon catheter comprises an internal balloon and an external balloon, with a maximum diameter up to 38 mm when expanding. During the TUSP surgery, the external 4

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5 balloon expanded bladder neck and prostatic urethra while the internal balloon expanded membranous urethra, both with 0.3 Mpa pressure. There were different sizes of the columnar balloon catheters (balloon length ranging from 8 to 12 cm; internal diameter ranging from 3.2 to 3.8 cm); the sizes were selected according to the sizes of patients’ prostates and the length of posterior urethrae. The balloon with internal diameter of 3.2 cm and the length of 8 cm was applied for the prostate with the volume less than 40 ml, 3.5 cm and 9 cm for 40-60 ml, 3.6 cm and 10 cm for 60-80 ml, 3.7 cm and 11 cm for 80-100 ml, and 3.8 ml and 11-12 cm for that larger than 100 ml. Human surgical methods Various sizes of transurethral catheters were chosen according to the prostate volume and bladder PVR (post-void residual urine volume) after preoperative routine physical examination and symptomatic treatment on medical complications. With low spinal anesthesia and epidural aneathesia, patients were placed in lithotomy position followed by urethral expansion using metal expander. The columnar catheter was inserted into the bladder and then pulled out gradually. Appropriate position of the catheter was confirmed by the breakthrough feeling when the locating protrusion passing through the membranous external sphincter. In the proper position, the locating protrusion could be touched at the skin edge of perineum and the internal balloon was localized in the membranous urethra. Then the internal and external balloons were expanded gradually to 0.3 MPa by injecting sterile water into the capsules. The injection tube was closed when the internal balloon was positioning in membranous urethra and the external balloon positioned in prostatic urethra. The average time of this operation was about 10 minutes. Six hours after the operation, the pressure in the balloons was gradually reduced, and the catheter 5

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6 was removed several days (range, 3 to 5 days) later. CT films were pictured by GE Hispeed dual. Experimental animals Ten male dogs whose tooth age was 8 years were provided by the Animal Center of Peking University. All experiments involving dogs were approved by the Animal Care and Use Committee at Peking University. The 10 male dogs were randomly divided into the TUSP group and control group, with 5 dogs per group. Animal surgical methods Dogs in the TUSP group were anesthetized by sodium pentothal and a lower abdominal incision was made to expose the extraperitoneal bladder and prostate. Concentric electrodes were positioned at the external urethral sphincter under the prostatic apex. The changes of bladder pressure and EMG during the post-voiding process after bladder instillation were recorded using the BIOPAC multi-channel EMG recorder. 2% lidocaine gel was squeezed into the urethra to prevent urethrospasm. The columnar balloon catheter was used to expand the bladder neck, prostatic urethra and membranous urethra for 5 minutes with a pressure of 0.3 Mpa. Then the pressure was reduced to 0.1 Mpa, and the balloon in the membranous urethra was forced into the posterior urethra for 24 hours. Finally, the columnar catheter with no pressure was set as the urinary catheter for a week. Examinations were performed one week after the expanding. Both bladder pressure and electromyography were detected before the animals were sacrificed. The dogs in control group didn’t receive any surgeries. The detailed surgical process and analysis in control group and TUSP group are shown in Table 1. Functional and pathological analysis Cystoscopy, leak point pressure measurement and EMG measurement were performed on the 6

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7 experimental dogs both before the surgery and before their sacrifices. The diameter of the prostatic urethra (1 cm above the colliculus seminalis) was detected after the dogs were sacrificed. The bladder neck, prostatic urethra, membranous urethra and urethral sphincter were collected from sacrificed dogs for H&E staining. Trichrome Masson was performed to detect the difference of collagen content between the expanding group and the control group. Statistical analysis All data were expressed as the mean ± standard deviation (SD). Statistical analysis was performed using Biostatistics ver.3 software. The t-tests were used to calculate the p values. Significance was defined as p < 0.05.

Results TUSP surgery attenuated LUTS and reconstructed urethra in BPH patients A total of 113 BPH patients with an average prostate volume of 46.8 ± 9.2 mL, which was detected by transrectal ultrasound, were included in the study. The mean peak urine flow rate (Qmax), PVR, baseline quality of life (QOL) score and International Prostate Symptom Score (IPSS) was 7.4 ± 1.6 mL/s, 78 ± 10.2 mL, 4.8 ± 0.2 and 21.6 ± 4.4, respectively, in BPH patients before surgery. The mean prostate specific antigen (PSA) level was ranged from 0.8 ng/mL to 18.6 ng/mL. All patients received transurethral dilatation with a columnar balloon catheter and the average operation time was 10 minutes. Patients were followed up for 3-24 months after surgery. Qmax, PVR, QOL score and IPSS were determined at each visit. The mean Qmax was increased to 15.8 ± 2.1 mL/s while the mean PVR decreased into 22 ± 8.1 mL after surgery. The significant elevation of Qmax and reduction of PVR indicated the recovered LUTS in BPH 7

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8 patients after TUSP. The mean QOL score and IPSS was reduced to 1.4 ± 0.3 and 6.8 ± 1.2, respectively. The characteristics of BPH patients before and after transurethral dilatation are shown in Table 2. Significant improvements in terms of Qmax, PVR, QOL and IPSS were observed after TUSP. After TUSP surgery, 5 patients had stress urinary incontinence; however, the symptom disappeared within 2 days. Until August 2011, the longest follow up duration for the patients after TUSP surgery lasted up to 5 years. Only 2 cases subjected to recurrent urethral obstruction at 3 years after operation due to an inaccurate positioning and an incorrect selection of catheter size. Until September 2014, 99 patients were successfully followed up and the follow up duration ranged from 38 to 98 months. The symptoms of the 2 cases were improved after the second TUSP surgery. Besides, no other case reported dysuria until the end of the follow up time. Medical CT films were used to analyze anatomic and image parameters of urethra. As shown in Fig. 2, the prostate tissue pressed the urethra and the urethral lumen was invisible before TUSP surgery. Shortly after the TUSP surgery, the balloon expanded the posterior urethra. The anterior fibromuscular stroma and prostate capsule were split to both the sides, leading to decompression of the prostatic urethra. After recovery, CT films showed that most of the prostate tissue closed again but at the top joint part, a crater-like hole was remained where the urethra was reconstructed. TUSP surgery expanded urethra in BPH dogs with the maintenance of normal urinary function and EMG characteristics We then investigated the therapeutic effect of TUSP on BPH on aged dogs. Histology showed the aged male dogs had BPH under normal states (Fig. 3A). After TUSP, the prostate capsule was 8

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9 split and the urethra was expanded significantly (Fig. 3B). The prostatic urethra diameter increased significantly after TUSP, indicating the TUSP induced expansion of the prostatic urethra (Fig. 3C). As TURP might cause complications such as urine leakage10, changes of urodynamics and EMG were accessed after TUSP

11, 12

. The leak point pressures in the

expanding group before and after TUSP were comparable and showed no significant difference when compared with the control group (Fig. 3D). Analysis on EMG of urethral sphincter in live dogs showed that the urethral sphincter displayed intermittent high tension EMG activities during urine storage and low tension resting potential during micturition (Fig. 3E). The EMG of urethral sphincter after TUSP was similar with that before TUSP, though the frequency and amplitude of EMG after TUSP were slightly higher. Therefore, the TUSP surgery expanded urethra while maintaining the normal urinary function and EMG characteristics. TUSP surgery induced inflammation and decreased collagen contents To further investigate the mechanisms involving in the therapy of BPH, sections were prepared from prostatic tissues of experimental dogs. Histology analysis (Fig. 4A) showed inflammation, bleeding and necrosis at the prostatic urethra, prostatic stroma, bladder neck and membranous urethra. Mucosa shed in the prostatic urethra, bladder neck and membranous urethra. Necrosis and denaturation of smooth muscle were observed at the prostatic stroma and membranous urethra. Fibers in the prostate capsule were bled. We also detected the content of collagen which played an important role in BPH. Consistent with previous studies in mice demonstrating the collagen was abundant in aging prostate13, we found collagen was abundant in the bladder neck, prostatic urethra and urethral stroma of control dogs (Fig.4B, upper row). However, the content of collagen was much less in the bladder neck, prostatic urethra and urethral stroma of expanding 9

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10 dogs after TUSP (Fig. 4B, bottom row). Thus, we suspect the expansion of urethra may be integrated effect of multiple factors. TUSP induced urethral inflammation, denaturation of smooth muscle fibers and decreased production of collagen, all of which impaired the contractility of prostatic tissues. Peripheral tissues then filled the dehiscence of prostate capsule, excluding the retraction of prostatic stroma which led to the expansion of urethra.

Discussion Aged males usually have BPH and secondary LUTS, which decrease their life quality seriously 2. TUDP used to be a popular treatment for BPH patients but was finally abandoned because of its invalid therapeutic effect 9. In this study, we designed a new catheter by changing the shape of balloon from sphere into column and operated a TUSP surgery. The clinical trials showed enormous advantages of TUSP treatment to BPH patients. The parameters of LUTS such as the mean Qmax, the mean PVR, QOL score and the mean IPSS all returned to normal levels after TUSP. TUSP constructed urethra in BPH patients. Previous study showed a clear correlation between prostatic occlusion of the urethra and the presence of a middle lobe

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, whether the

existence of a middle lobe will affect the therapeutic effect of the TUSP surgery is unknown and needs further investigation. Animal experiments also demonstrated the TUSP surgery expanded the urethra with normal urinary function and EMG characteristics. Both prostate capsule disruption and collagen reduction occurred after TUSP surgery. However, due to the defect of CT, we are unable to conclude which process happened anteriorly and the causality between the two processes. We suspect that both processes contribute to preventing the folding of prostate tissues and its capsule 10

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11 to maintain a long-term patulous urethra. Though the current opinion on the “golden standard” and primary surgery for BPH patients is TURP during which resection is necessary

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, the high

fee, large wound areas, special instruments and following complications limit the application of TURP, especially in developing countries

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. Our research on TUSP surgery demonstrated BPH

caused LUTS could be cured without excising the gland. The point to treat BPH caused LUTS is whether the urethra is expedited or not. The columnar balloon catheter in TUSP surgery consists of an internal balloon to expand the bladder neck and prostatic urethra, and an external balloon to expand the urethral sphincter. As long as the obstructive parts are expanded or released, dysuria problems might be resolved. Additionally, the prostate capsule was split at the top joint part of prostate during surgery which may prevent the recurrence of BPH. Therefore, the highlight of the TUSP technique is: it treated the LUTS caused by BPH through splitting the prostate capsule and expanding the urethra, which not only avoided resection but also showed significant curative effect. We have performed the TUSP surgery on animals and clinical practices since 2006, and the TUSP technique has matured to be a safe surgery without causing voiding dysfunction. The key to a successful TUSP surgery is choosing correct size and accurate positioning of transurethral catheters. Two cases had recurrent urethral obstruction at 3 years after operation, which might suggest that it was benefit for patients to receive CT detection of the prostate and urethra during 3 to 4 years after TUSP surgery. The remaining balloon after expansion and gradually reduced pressure benefited hemostasis. The catheter was retained in the urethra without pressure for urinary catheterization, which prevented the urine leakage. Furthermore, TUSP breaks the penalty field of touching membranous urethra without damaging nerves and urethral sphincter. 11

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12 EMG represents the electrical activity of prostatic muscle and is associated with the dynamic component of patients with symptomatic BPH

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. In our study, EMG reveals a normal

myoelectric activity of urethral sphincter after an appropriate expansion of the obstructive part at urethral membrane by TUSP, which proves that TUSP may not induce a trauma of urethral sphincter or long-term incontinence, but plays a crucial role in sustaining a normal urinary function. The minimal hurt on patients’ physiology and psychology could prolong a longer average life expectancy for elder men and is a huge advantage of TUSP surgery.

Conclusion TUSP surgery fills in the blanks of solving urethral obstructive problems without scalpels. This technique preserved with minimal trauma, short operating time, and high safety coefficient. TUSP is an ideal choice for the patients who are infirm, intolerant or indisposed to resection surgeries.

Acknowledgments

Disclosures

none

none

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13 References 1.

Kulig K, Malawska B. Trends in the development of new drugs for treatment of

benign prostatic hyperplasia. Curr Med Chem 2006;13:3395-3416. 2.

Roehrborn CG. Current medical therapies for men with lower urinary tract

symptoms and benign prostatic hyperplasia: achievements and limitations. Reviews in urology 2008;10:14-25. 3.

Biester K, Skipka G, Jahn R, et al. Systematic review of surgical treatments for

benign prostatic hyperplasia and presentation of an approach to investigate therapeutic equivalence (non-inferiority). BJU international 2012;109:722-730. 4.

Pinheiro LC, Martins Pisco J. Treatment of benign prostatic hyperplasia. Tech

Vasc Interv Radiol 2012;15:256-260. 5.

Andersson KE. Treatment of lower urinary tract symptoms: agents for

intraprostatic injection. Scand J Urol 2013;47:83-90. 6.

Burhenne HJ, Chisholm RJ, Quenville NF. Prostatic hyperplasia: radiological

intervention. Work in progress. Radiology 1984;152:655-657. 7.

Castaneda F, Letourneau JG, Reddy P, et al. Alternative treatment of prostatic

urethral obstruction secondary to benign prostatic hypertrophy. Non-surgical balloon catheter prostatic dilatation. RoFo 1987;147:426-429. 8.

Wasserman NF, Reddy PK, Zhang G, et al. Experimental treatment of benign

prostatic hyperplasia with transurethral balloon dilation of the prostate: preliminary study in 73 humans. Radiology 1990;177:485-494. 9.

Vale JA, Miller PD, Kirby RS. Balloon dilatation of the prostate--should it have 13

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14 a place in the urologist's armamentarium? J R Soc Med 1993;86:83-86. 10. Losco G, Mark S, Jowitt S. Transurethral prostate resection for urinary retention: does age affect outcome? ANZ J Surg 2013;83:243-245. 11. Nitti VW, Kim Y, Combs AJ. Voiding dysfunction following transurethral resection of the prostate: symptoms and urodynamic findings. J Urol 1997;157:600-603. 12. Bianchi F, Cursi M, Ferrari M, et al. Quantitative EMG of external urethral sphincter in neurologically healthy men with prostate pathology. Muscle Nerve 2014. 13. Bianchi-Frias D, Vakar-Lopez F, Coleman IM, et al. The effects of aging on the molecular and cellular composition of the prostate microenvironment. PloS one 2010;5. 14. Din KE, Wildt MJD, Pf R, et al. The correlation between urodynamic and cystoscopic

findings

in

elderly

men

with

voiding

complaints.

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Urol

1996;155:1018–1022. 15. Li X, Pan JH, Liu QG, et al. Selective transurethral resection of the prostate combined with transurethral incision of the bladder neck for bladder outlet obstruction in patients with small volume benign prostate hyperplasia (BPH): a prospective randomized study. PloS one 2013;8:e63227. 16. Bisonni RS, Lawler FH, Holtgrave DR. Transurethral prostatectomy versus transurethral dilatation of the prostatic urethra for benign prostatic hyperplasia: a cost-utility analysis. Fam Pract Res J 1993;13:25-36. 17. Sahiner T, Atahan O, Aybek Z. Prostate electromyography: a new concept. Electromyogr Clin Neurophysiol 2000;40:103-107.

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Journal of Endourology Treatment of benign prostatic hyperplasia using transurethral split of the prostate surgery with a columnar balloon catheter (doi: 10.1089/end.2014.0207) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof. Page 15 of 20

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Abbreviations

TUDP,Transurethral dilatation of the prostate; BPH, benign prostatic hyperplasia

TUSP; transurethral split of the prostate, EMG, electromyography; PVR,

QOL, baseline quality of life;

Figure legends

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post-void

residual urine volume; IPSS, International Prostate Symptom Score; Qmax, peak urine flow rate;


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Figure 1. The structure of the columnar balloon catheter.

(A) The schematic drawing of the columnar balloon catheter. (B) Pictures of the columnar

balloon catheter before (left) and after (right) the injection of sterile water.

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Figure 2. TUSP reconstructs urethra in BPH patients. (A) Representative CT film of the prostate and urethra in patients before TUSP surgery. (B) Representative CT film of the prostate and urethra in patients shortly after TUSP surgery. (C) Representative CT film of the prostate and urethra in patients. The red arrows indicate the urethra.

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Figure 3. TUSP expands urethra in BPH dogs while maintaining normal leak point pressure and EMG. (A) Representative photomicrographs of H&E-stained prostate from aged male dogs with BPH. (B) Representative photomicrographs of H&E-stained prostate capsule (the black arrows) and urethra (the hollow arrow) after TUSP surgery. (C) Statistical analysis of the urethral diameters in the control group and TUSP expanding group (n = 5 dogs /group; mean ± standard deviation; p < 0.01). (D) Statistical analysis of the leak point pressure in the control group and TUSP group before and after TUSP surgery. (n = 5 dogs /group; mean ± standard deviation). (E) Representative EMG of urethral sphincter before (upper row) and after (bottom row) TUSP surgery.

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Figure 4. TUSP induces prostate injury and decreases collagen content in BPH dogs. (A) Representative photomicrographs of H&E-stained prostatic urethra (upper left) , prostatic stroma (upper middle), prostate capsule (upper right), bladder neck (bottom left), membranous urethra (bottom middle) in dogs after TUSP surgery and prostate without TUSP surgery (bottom right). (B)Representative photomicrographs of Trichrome Masson stained bladder neck (left), prostate (middle) and urethral stroma (right) from control dogs (the upper row) and dogs after TUSP surgery (the bottom row).

Table 1. Surgical process and analysis in dogs divided into control group and TUSP group.

Expanding sites

Control group

TUSP group

None

Bladder neck Prostatic urethra Membranous urethra

High pressure

None

0.3 MPa, 5 minutes

None

0.1 MPa, 24 hours

expansion

Low pressure expansion

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Catheter retention

None

0 Pa,1 week

Analysis

Cystoscopy

Cystoscopy

Leak point pressure

Leak point pressure

EMG

EMG

Histopathology

Histopathology

EMG, electromyography.

Table 2. LUTS of BPH patients before and after TUSP surgery. Indicators

Before TUSP

Post TUSP

P value

Qmax (mL/s)

7.4 ±1.6

15.8 ±2.1

P < 0.001

PVR (mL)

78 ±10.2

22 ±8.1

P < 0.001

QoL

4.8 ±0.2

1.4 ±0.3

P < 0.001

IPSS

21.6 ±4.4

6.8 ±1.2

P < 0.001

Data presented as mean ± standard deviation. Qmax, maximal urinary flow rate; PVR, post voiding residual volume; QOL, quality of life; IPSS, International Prostate Symptom Score.

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Effect of transurethral split of the prostate using a double-columnar balloon catheter for benign prostatic hyperplasia: A single-center experience of 565 consecutive patients.

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Medical treatment of benign prostatic hyperplasia.

Conservative treatment of benign prostatic hyperplasia.

Use of Medical Therapy and Success of Laser Surgery and Transurethral Resection of the Prostate for Benign Prostatic Hyperplasia.

Medical treatment for benign prostatic hyperplasia.

Application of two micron laser vaporesection combined with transurethral resection of the prostate in treatment of benign prostatic hyperplasia: analysis of 340 cases.

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prostatitis).