Hee Ju Cho

Benign Prostatic Hyperplasia: from Bench to Clinic

Benign prostatic hyperplasia (BPH) is a prevalent disease, especially in old men, and often results in lower urinary tract symptoms (LUTS). This chronic disease has important care implications and financial risks to the health care system. LUTS are caused not only by mechanical prostatic obstruction but also by the dynamic component of obstruction. The exact etiology of BPH and its consequences, benign prostatic enlargement and benign prostatic obstruction, are not identified. Various theories concerning the causes of benign prostate enlargement and LUTS, such as metabolic syndrome, inflammation, growth factors, androgen receptor, epithelial-stromal interaction, and lifestyle, are discussed. Incomplete overlap of prostatic enlargement with symptoms and obstruction encourages focus on symptoms rather than prostate enlargement and the shifting from surgery to medicine as the treatment of BPH. Several alpha antagonists, including alfuzosin, doxazosin, tamsulosin, and terazosin, have shown excellent efficacy without severe adverse effects. In addition, new alpha antagonists, silodosin and naftopidil, and phosphodiesterase 5 inhibitors are emerging as BPH treatments. In surgical treatment, laser surgery such as photoselective vaporization of the prostate and holmium laser prostatectomy have been introduced to reduce complications and are used as alternatives to transurethral resection of the prostate (TURP) and open prostatectomy. The status of TURP as the gold standard treatment of BPH is still evolving. We review several preclinical and clinical studies about the etiology of BPH and treatment options.

Experience with robot-assisted laparoscopic radical prostatectomy at a secondary training hospital: operation time, treatment outcomes, and complications with the accumulation of experience.

Purpose To investigate the learning curve and outcomes of robot-assisted laparoscopic radical prostatectomy (RALP) performed by a relatively lower volume surgeon at a secondary training hospital. Materials and Methods The medical records and the surgery video recordings of 100 patients who underwent RALP by a single surgeon between March 2010 and January 2013 were reviewed. The first 10 cases were grouped into period 1, cases 11 to 40 into period 2, cases 41 to 70 into period 3, and cases 71 to 100 into period 4. The interval between the operations, the operative time for each step of the surgery, the total console time, and the operative outcomes were investigated. Results The mean interval between surgeries was 10.6±9.3 days. The console time decreased progressively after the first 10 cases and reached under 3 hours after 75 cases. The time taken to begin dissection of the dorsal vein complex, for the division of the bladder neck, for lateral dissection with neurovascular bundle preservation, and for apex dissection decreased significantly with experience, although the time for vesicourethral anastomosis did not. The margin-positive rate of stage T2 patients was 27.4% (20/73), and the transfusion rate was 50% in period 1 patients and 3.3% in period 4 patients. No major complications occurred. Conclusions It is difficult to shorten the learning curve of surgeons in secondary training hospitals owing to the smaller number of cases and the irregular surgical intervals. Although the operation time was relatively longer, the surgical outcome and complication rates were comparable with those of surgeons at larger hospitals.

Effect of Transurethral Resection of the Prostate Based on the Degree of Obstruction Seen in Urodynamic Study

Purpose We retrospectively investigated the effect of transurethral resection of the prostate (TURP) on the basis of the degree of obstruction seen in preoperative urodynamic study in patients with benign prostatic hyperplasia (BPH) who complained of lower urinary tract symptoms (LUTS). Materials and Methods The subjects of this study were 285 patients who were diagnosed with BPH with LUTS and who subsequently underwent TURP. The Abrams-Griffiths number was calculated from the urodynamic results to divide the patients into the following groups: unobstructed, equivocal, and obstructed. There were 26 patients (9.1%) in the unobstructed group, 98 patients (34.4%) in the equivocal group, and 161 patients (56.5%) in the obstructed group. The preoperative and postoperative uroflowmetry, residual urine, International Prostate Symptom Score (IPSS), and quality of life (QoL) score were compared between the three groups to evaluate the outcome of the treatment. Results The reduction in the IPSS was 14.4 in the obstructed group, which was higher than the reductions of 12.7 in the equivocal group and 9.5 in the unobstructed group, but this difference was not statistically significant (p=0.227). The QoL score was also not significantly different across the three groups (p=0.533). The postoperative maximum flow rate was significantly improved in all three groups. The obstructed group had an improvement of 7.8±7.2 mL/s, which was higher than the improvement of 3.7±6.2 mL/s in the unobstructed group (p=0.049) but was not significantly different from the improvement of 5.6±6.9 mL/s in the equivocal group (p=0.141). Conclusions TURP led to an improvement in the maximum flow rate and LUTS even in BPH patients without BOO. Therefore, TURP can be expected to improve LUTS in BPH patients without definite urodynamic obstruction.

Prevalence and Risk Factors of Bladder Neck Contracture After Radical Prostatectomy

Purpose To evaluate the prevalence of bladder neck contracture (BNC) and its risk factors in patients undergoing radical prostatectomy in Korea. Materials and Methods We analyzed data from 488 patients with prostatic cancer who underwent radical prostatectomy performed by seven surgeons in seven hospitals, including 365 open radical prostatectomies (ORPs), 99 laparoscopic radical prostatectomies (LRPs), and 24 robot-assisted laparoscopic radical prostatectomies (RARPs). Patients with BNCs were compared with those without BNCs to identify the risk factors for BNC occurrence. Results Overall, BNCs occurred in 21 of 488 patients (4.3%): 17 patients (4.7%) who underwent ORP, 4 patients (4%) who underwent LRP, and no patients who underwent RARP. In the univariate analysis, men with BNCs had a longer length of time before drain removal (12 days vs. 6.8 days, p<0.001), which reflected urinary leakage through the vesicourethral anastomosis. In the multivariate analysis, the length of time before drain removal was the only predictor of BNC (odds ratio, 1.12; p=0.001). Intraoperative blood loss was higher in patients with BNC, but the difference was not statistically significant. Conclusions The most significant factor related to BNC occurrence after radical prostatectomy in our study was the length of time before drain removal, which reflects urinary leakage from the vesicourethral anastomosis. The proper formation of a watertight anastomosis to decrease urinary leakage may help to reduce the occurrence of BNC.

Silodosin for the treatment of clinical benign prostatic hyperplasia: safety, efficacy, and patient acceptability

α1-Adrenergic receptor antagonists are commonly used to treat male lower urinary tract symptoms and benign prostatic hyperplasia (BPH). We performed a literature search using PubMed, Medline via Ovid, Embase, and the Cochrane Library databases to identify studies on the treatment of BPH by silodosin. Silodosin is a novel α1-adrenergic receptor antagonist whose affinity for the α1A-adrenergic receptor is greater than that for the α1B-adrenergic receptor. Therefore, silodosin does not increase the incidence of blood pressure-related side effects, which may result from the inhibition of the α1B-adrenergic receptor. Patients receiving silodosin at a daily dose of 8 mg showed a significant improvement in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving a placebo. Silodosin also improved both storage and voiding symptoms, indicating that silodosin is effective, even during early phases of BPH treatment. Follow-up extension studies performed in the United States, Europe, and Asia demonstrated its long-term safety and efficacy. In the European study, silodosin significantly reduced nocturia compared to the placebo. Although retrograde or abnormal ejaculation was the most commonly reported symptom in these studies, only a few patients discontinued treatment. The incidence of adverse cardiovascular events was also very low. Evidence showing solid efficacy and cardiovascular safety profiles of silodosin will provide a good solution for the treatment of lower urinary tract symptoms associated with BPH in an increasingly aging society.

Comparison of an Indwelling Period Following Ureteroscopic Removal of Stones between Double-J Stents and Open-Ended Catheters: A Prospective, Pilot, Randomized, Multicenter Study

Purpose The aim of this study was to evaluate whether long-term, postoperative ureteral stenting is necessary after ureteroscopic removal of stones (URS) during an uncomplicated surgical procedure. Materials and Methods We prospectively examined 54 patients who underwent URS for lower ureteral stones from February 2010 to October 2010. Inclusion criteria were a stone less than 10 mm in diameter, absence of ureteral stricture, and absence of ureteral injury during surgery. We randomly placed 5 Fr. open-tip ureteral catheters in 26 patients and removed the Foley catheter at postoperative day 1. The remaining 28 patients received double-J stents that were removed at postoperative day 14 by cystoscopy under local anesthesia. All patients provided visual analogue scale (VAS) pain scores at postoperative days 1, 7, and 14 and completed the storage categories of the International Prostate Symptom Score (IPSS) at postoperative day 7. Results The VAS scores were not significantly different on postoperative day 1 but were significantly smaller in the 1-day ureteral catheter group at postoperative days 7 and 14 (p<0.01). All of the storage categories of the IPSS were significantly lower in the 1-day ureteral stent group (p<0.01). The ratio of patients who needed intravenous analgesics because of severe postoperative flank pain was not significantly different between the two groups (p=0.81). No patients experienced severe flank pain after postoperative day 2, and no patients in either group had any other complications. Conclusions One-day ureteral catheter placement after URS can reduce postoperative pain and did not cause specific complications compared with conventional double-J stent placement.

Efficacy of Alfuzosin After Shock Wave Lithotripsy for the Treatment of Ureteral Calculi

Purpose We evaluated the efficacy of alfuzosin for the treatment of ureteral calculi less than 10 mm in diameter after extracorporeal shock wave lithotripsy (ESWL). Materials and Methods A randomized, single-blind clinical trial was performed prospectively by one physician between June 2010 and August 2011. A total of 84 patients with ureteral calculi 5 to 10 mm in diameter were divided into two groups. Alfuzosin 10 mg (once daily) and loxoprofen sodium 68.1 mg (as needed) were prescribed to group 1 (n=41), and loxoprofen sodium 68.1 mg (as needed) only was prescribed to group 2 (n=44). The drug administration began immediately after ESWL and continued until stone expulsion was confirmed up to a maximum of 42 days after the procedure. Results Thirty-nine of 41 (95.1%) patients in group 1 and 40 of 43 (93.0%) patients in group 2 ultimately passed stones (p=0.96). The number of ESWL sessions was 1.34±0.65 and 1.41±0.85 in groups 1 and 2, respectively (p=0.33). The patients who required analgesics after ESWL were 8 (19.5%) in group 1 and 13 (30.2%) in group 2 (p=0.31). Visual analogue scale pain severity scores were 5.33±1.22 and 6.43±1.36 in groups 1 and 2, respectively (p=0.056). The time to stone expulsion in groups 1 and 2 was 9.5±4.8 days and 14.7±9.8 days, respectively (p=0.005). No significant adverse effects occurred. Conclusions The use of alfuzosin in combination with ESWL seems to facilitate stone passage and to reduce the time of stone expulsion but does not affect the stone-free rate.

Expression levels of heat shock protein 27 and cellular FLICE-like inhibitory protein in prostate cancer correlate with Gleason score sum and pathologic stage

Purpose Heat shock protein (HSP) 27 protects the cell by controlling apoptosis and immune reactions, and c-FLIP (cellular-FLICE inhibitory protein) inhibits apoptosis by inhibiting caspase-8 activity. We investigated the relationship of HSP27 and c-FLIP expression to prostate-specific antigen, Gleason score sum (GSS), and pathologic stage. Materials and Methods Samples from 163 patients between May 2004 and April 2010 were analyzed: 83 from patients that had underwent a radical prostatectomy, and 80 from those that underwent transurethral resection of the prostate to alleviate urinary symptoms from benign prostate hyperplasia. c-FLIP and HSP27 expression were observed by immunohistochemistry staining. Samples with less than 5% expression-positive cells were scored as 1, with 5%-50% were scored as 2, and with more than 50% were scored as 3. Local reactions were identified as 0.5 and evaluated. Results Both the presence of HSP27 within the tumor and the number of cancer cells positive for HSP27 were significantly correlated to GSS and pathologic stage (p<0.001, p=0.001, p<0.001, p<0.001). The same was true for c-FLIP expression (p<0.001). GSS was more highly correlated to HSP27 expression than to c-FLIP expression (r=0.814 for HSP27, r=0.776 for c-FLIP), as was pathologic stage (r=0.592 for HSP27, r=0.554 for c-FLIP). Conclusions In prostate cancer, higher GSS and a more advanced pathologic stage were associated with a higher likelihood of having a HSP27-positive tumor and more HSP27-positive tumor cells. HSP27 expression was correlated with GSS and prostate cancer stage. A more advanced pathologic stage corresponded to a higher likelihood of having a c-FLIP-positive tumor and more c-FLIP-positive tumor cells. HSP27 expression had a higher correlation with prostate cancer stage and GSS than c-FLIP expression did.

Comparison of alfuzosin 10 mg with or without propiverine 10 mg, 20 mg in men with lower urinary tract symptom and an overactive bladder: randomised, single-blind, prospective study

The efficacy and safety of treatment with alfuzosin 10 mg plus propiverine 10 or 20 mg in men with lower urinary tract symptoms (LUTS) and an overactive bladder were investigated.

The role of transurethral resection of the prostate for patients with an elevated prostate-specific antigen

Purpose The aim of this study was to define the clinical significance of transurethral resection of the prostate (TURP) in patients with benign prostate hyperplasia (BPH) and an elevated prostate-specific antigen (PSA) level. Methods We retrospectively evaluated patients with BPH, lower urinary tract symptoms (LUTS; International Prostate Symptom Score [IPSS]≥8), an elevated serum PSA level (≥4 ng/mL), and previous negative transrectal ultrasonography (TRUS) guided prostate biopsy. The PSA level after TURP was monitored by long-term follow-up. The tumor detection rate on resected prostate tissue, IPSS, maximal urinary flow rate (Qmax), and postvoid residual urine (PVR) were analyzed. Results One-hundred and eighty-six patients were enrolled. Histological examination of resected tissue by TURP revealed prostate cancer in 12 of these patients (6.5%). Among 174 patients without prostate cancer, the mean PSA level and the PSA normalization rate in 112 patients followed up at postoperative day (POD) 3 months were 1.26±0.13 ng/mL and 94.6%, respectively. The mean PSA level and the PSA normalization rate were 1.28±1.01 ng/mL and 95.7% in 47 patients at 1st year, 1.17±0.82 ng/mL and 97.1% in 34 patients at second years, and 1.34±1.44 ng/mL and 97.2% in 36 patients at third years of TURP. One patient showed a dramatic increase in the PSA level was diagnosed with prostate cancer at 7 years after TURP. IPSS, quality of life, Qmax, and PVR were improved significantly at POD 3 months compared to baseline (P<0.05), respectively. Conclusions TURP significantly reduced the serum PSA level, which was maintained for at least 3 years. This could be helpful to screen the prostate cancer using PSA value in the patient with previous negative biopsy and elevated PSA. In addition, TURP improves IPSS, Qmax, and PVR in patients with BPH, moderate LUTS, and an elevated PSA level.