Tag Keun Yoo

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.

Relationship between Intravesical Prostatic Protrusion and Postoperative Outcomes in Patients with Benign Prostatic Hyperplasia

Purpose To evaluate the significance of intravesical prostatic protrusion (IPP) for predicting postoperative outcomes in patients with benign prostatic hyperplasia. Materials and Methods A total of 177 patients with a possible follow-up of at least 6 months who were treated with transurethral resection of the prostate (TURP) were analyzed. We divided the patients into two groups on the basis of the degree of IPP: the significant IPP group (IPP≥5 mm, n=74) and the no significant IPP group (IPP<5 mm, n=103). We analyzed postoperative changes in parameters, such as the International Prostate Symptom Score (IPSS), IPSS quality-of-life (QoL) score, maximum urinary flow rate (Qmax), and postvoid residual urine (PVR). The IPSS was subdivided into voiding (IPSS-v) and storage (IPSS-s) symptoms. Multivariate logistic regression analysis was performed to identify whether IPP could predict surgical outcomes of TURP. Results Preoperative parameters were not significantly different between the two groups except for total prostate volume and transitional zone volume. Postoperative changes in IPSS, IPSS-v, IPSS-s, and QoL score were higher in the significant IPP group than in the group with no significant IPP. Changes in Qmax and PVR were not significantly different between the two groups. Multivariate logistic regression analysis (after adjustment for age, prostate-specific antigen level, total prostate volume, and transitional zone volume) revealed that the odds ratios (95% confidence interval) of decreased IPSS and IPSS-s in the significant IPP group were 3.43 (1.03 to 11.44) and 3.51 (1.43 to 8.63), respectively (p=0.045 and 0.006, respectively). Conclusions Significant IPP is an independent factor for predicting better postoperative outcomes of IPSS and IPSS-s.

Desmopressin Add-On Therapy for Refractory Nocturia in Men Receiving α-Blockers for Lower Urinary Tract Symptoms

PURPOSE Alpha-blockers improve lower urinary tract symptoms associated with benign prostatic obstruction. Nocturia, a storage symptom, is a common complaint in men. However, it does not fully respond to α-blocker therapy, likely due to its multifactorial pathophysiology. We evaluated the efficacy and safety of desmopressin as add-on therapy for refractory nocturia in men previously treated with an α-blocker for lower urinary tract symptoms. MATERIALS AND METHODS Eligible patients were men 50 years old or older with lower urinary tract symptoms and persistent nocturia despite α-blocker treatment for a minimum of 4 weeks. The optimum dose of oral desmopressin was determined during a 4-week dose titration period and this dose was maintained for 24 weeks. Flow volume charts, International Prostate Symptom Score total and subscores, uroflowmetry and post-void residual urine volume were assessed. RESULTS A total of 216 patients were enrolled in the study. Of these patients there were 158 (76%) with nocturnal polyuria, 15 (7.2%) with decreased nocturnal bladder capacity and 35 (16.8%) with nocturia due to both causes. The number of nocturnal voids significantly decreased from a baseline mean of 7.0 to 5.7 episodes for 3 days at the 24-week visit. The average International Prostate Symptom Score total and subscore significantly decreased by 4 weeks and were maintained at 24 weeks. In patients younger than 65 years, International Prostate Symptom Score voiding subscores were significantly improved at 24 weeks compared to those age 65 years or older. CONCLUSIONS Desmopressin add-on therapy for refractory nocturia in men previously treated with an α-blocker for lower urinary tract symptoms improved voiding symptoms as well as nocturia, storage symptoms.

Laparoendoscopic Single-Site Ureterolithotomy for Upper Ureteral Stone Disease: The First 30 Cases in a Multicenter Study

PURPOSE We evaluated the usefulness of laparoendoscopic single-site (LESS) ureterolithotomy with a homemade single port device for upper ureteral stones in patients in whom previous shockwave lithotripsy or ureteroscopic stone surgery had failed or the stone was suspected to be impacted. PATIENTS AND METHODS LESS ureterolithotomy was performed on 30 patients by using a homemade single port device composed of an Alexis wound retractor and surgical glove. The mean age of the patients was 42.47±11.15 years (range 24-65 y), and the male-to-female ratio was 13:17. The mean stone diameter was 1.77±0.47 cm. One patient underwent a bilateral operation for bilateral ureteral stones. RESULTS The LESS surgery was converted to conventional laparoscopic surgery in one case. The mean operative time was 110.43±43.75 minutes. The mean length of hospital stay was 3.40±1.54 days. None of the patients used patient-controlled anesthesia, and none presented with major complications. The visual analog pain scale score improved significantly by postoperative day 7 (from 6.87±1.61 preoperatively to 1.67±1.16; P<0.001), and 28 (93.3%) patients said they were satisfied with the postoperative outcome. Postoperative radiologic evaluation revealed that the stones had been removed completely in 28 cases. There were no cases of urinary leakage. CONCLUSION LESS ureterolithotomy using a homemade single port device can be considered to be a feasible and safe alternative to conventional laparoscopic ureterolithotomy.

The Effects of Hyaluronic Acid and Carboxymethylcellulose in Preventing Recurrence of Urethral Stricture After Endoscopic Internal Urethrotomy: A Multicenter, Randomized Controlled, Single-Blinded Study

BACKGROUND To evaluate the effects of hyaluronic acid (HA) and carboxymethylcellulose (CMC) on the recurrence of urethral stricture after treatment with endoscopic internal urethrotomy (EIU). METHODS A total of 120 patients underwent EIU for urethral stricture. Recruited patients were randomly divided into two groups: group A and B. Patients in group A (60 patients, experimental group) received HA/CMC instillation and patients in group B (60 patients, control group) received lubricant instillation after internal urethrotomy. Each patient was evaluated at 4 weeks (V1), 12 weeks (V2), and 24 weeks (V3) after the surgery. The effectiveness of HA/CMC instillation was evaluated based on the International Prostate Symptom Score/Quality of Life, peak urine flow rate, voided volume and postvoiding residual urine volume. The visual analogue scale (VAS) pain score and degree of satisfaction were also determined for each participant. RESULTS Among 120 initial participants, 53 patients in group A and 48 patients in group B had completed the experiment. VAS pain scores were 0.67±0.76 and 3.60±1.52 (p<0.001), and degrees of satisfaction were 0.28±0.50 and 0.80±0.81 in group A and group B at 1 month after surgery (p=0.001). The recurrence of urethral stricture was observed in five cases (9.4%) in group A and 11 (22.9%) in group B (p=0.029). CONCLUSIONS HA/CMC instillation during EIU may decrease the incidence of urethral stricture recurrence. In addition, the use of HA/CMC was effective in reducing pain during the early postoperative period without an adverse effect.

Factors associated with continuing medical therapy after transurethral resection of prostate.

OBJECTIVE To report the clinical characteristics of patients who have persistent lower urinary tract symptoms (LUTS) after surgery for benign prostatic hyperplasia (BPH) and continue their medical therapy postoperatively. MATERIALS AND METHODS We retrospectively studied 372 patients who underwent transurethral resection of prostate for LUTS/BPH in 8 institutions to determine the differences between patients who continued LUTS/BPH medications for >3 months after surgery and those who did not. Preoperative, intraoperative, and postoperative clinical parameters were assessed. The Student t test and chi square test were used to compare each parameter between patient groups. Multivariate logistic regression analysis was performed to identify risk factors for persistent LUTS and continuing medical therapy after surgery. RESULTS There were 205 patients (55.1%) who continued their LUTS/BPH medications for >3 months postoperatively. They reported poorer International Prostate Symptom Scores and uroflowmetry results after surgery. Multivariate analysis showed that age >70 years (odds ratio [OR], 2.474; P = .001), history of diabetes (OR, 1.949; P = .040), history of cerebrovascular accident (OR, 5.932; P = .001), any previous LUTS/BPH medication use (OR, 5.384; P = <0.001), and previous antimuscarinic drug use (OR, 2.962; P = .016) were significantly associated with symptom persistency and continuing medical therapy. CONCLUSION Many patients have persistent voiding dysfunction after surgical treatment for LUTS/BPH. Older age, history of diabetes, history of cerebrovascular accidents, and preoperative antimuscarinic drug uses are possible risk factors.

Clinical and Urodynamic Significance of Morphological Differences in Intravesical Prostatic Protrusion

Purpose The objectives of this study were to evaluate whether morphologic differences correlated with urodynamic and clinical characteristics in patients with benign prostatic hyperplasia (BPH) with intravesical prostatic protrusion (IPP) of trilobar or bilobar adenoma. Materials and Methods Between January 2008 and June 2009, 72 male patients who had undergone transurethral resection (TUR) owing to BPH with IPP were included in this study. They underwent preoperative urodynamic studies, the International Prostate Symptom Score (IPSS)/quality of life (QoL), maximal flow rate (Qmax), post-voiding residual urine volume (PVR), transrectal ultrasonography (TRUS), and serum prostate-specific antigen (PSA) measurement. The patients were classified into 2 groups (the trilobar and bilobar adenoma groups) on the basis of video findings during the TUR operation. Results The trilobar and bilobar adenoma groups consisted of 37 patients and 35 patients, respectively. The Mean±SD IPP, prostate volume (PV), and transition zone volume of the trilobar and bilobar adenoma groups were 11.8±5.2 mm and 9.0±3.8 mm (p=0.014), 81.1±25.8 g and 59.3±22.5 g (p<0.001), and 49.6±20.6 g and 34.8±19.4 g (p=0.003), respectively. The Mean±SD PSA, bladder contractility index (BCI), and bladder outlet obstruction index (BOOI) were 4.6±2.5 ng/ml and 3.5±1.7 ng/ml (p=0.042), 119.8±33.4 and 87.7±24.4 (p<0.001), and 62.6±29.5 and 44.6±20.4 (p=0.005), respectively. There were no significant differences in IPSS/QoL, Qmax, PVR, acute urinary retention, or detrusor overactivity in the 2 groups. Conclusions IPP has two morphologic types of trilobar or bilobar enlargement. The PV, BOOI, and BCI were significantly smaller in the bilobar adenoma group than in the trilobar adenoma group.

Efficacy and Safety of Tadalafil 5 mg Administered Once Daily in Korean Men with Erectile Dysfunction: A Prospective, Multicenter Study.

Purpose The aim of this study was to evaluate the efficacy of a daily dose of tadalafil 5 mg as well as its safety for the cardiovascular system in men with erectile dysfunction. Materials and Methods This study included a total of 162 men who were administered a daily dose of tadalafil 5 mg between April and December of 2009. A total of 127 men completed the 8-week clinical trial. The International Index of Erectile Function (IIEF)-5, blood pressure, and heart rate were measured before treatment with tadalafil (V1) and 4 (V2) and 8 weeks (V3) after treatment with tadalafil. Adverse effects were assessed at V1, V2, and V3. In cases in which the International Prostate Symptom Score (IPSS) was ≥8 at V1, maximal flow rate (Qmax) and postvoid residual volume (PVR) were measured. Results The IIEF-5 values were 11.25±3.18, 14.56±3.79, and 16.91±3.56 at V1, V2, and V3, respectively, with significant improvement (V1 vs. V2, p<0.001; V1 vs. V3, p<0.001). The IPSS values were 10.59±5.56, 9.07±6.06, and 8.15±6.10 at V1, V2, and V3, respectively, and the differences were statistically significant (V1 vs. V2, p<0.001; V1 vs. V3, p<0.001). There were no significant differences in blood pressure or heart rate. Adverse effects were observed in 7 men (5.51%) at V2 and in 5 men (3.94%) at V3. Conclusions Tadalafil 5 mg administered once-a-day may be effective in improving erectile function. Adverse effects on the cardiovascular system may be minimal. In addition, it is believed that this may also be effective in improving voiding symptoms.

Inhibition of androgen receptor expression with small interfering RNA enhances cancer cell apoptosis by suppressing survival factors in androgen insensitive, late stage LNCaP cells.

Introduction.The aim was to evaluate the changes of androgen receptor (AR) expression quantitatively and to identify influence of AR on cancer related survival markers in LNCap cell line. Materials and Methods. We compared expressions of AR, heat shock protein 27 (HSP27), clusterin (CLU), glucose-related protein 78 (GRP78), and cellular FLICE-like inhibitory protein (c-FLIP) and their genes between es-LNCaP (less than 33 times subcultured, L-33), ls-LNCaP (over 81 times subcultured, H-81), and si-LNCaP (AR siRNA transfected ls-LNCaP) by Western blotting and RT-PCR. Results. The expressions of AR, HSP27, CLU, GRP78, and c-FLIP were increased in ls-LNCaP compared with es-LNCaP (AR, 157%; HSP27, 132%; CLU, 146%; GRP78, 138%; c-FLIP, 152%). However, in si-LNCaP cell line, protein expressions were reversed to the level of es-LNCaP cell lines (25, 102, 109, 98, and 101%), and gene expressions on real-time PCR were also reversed to the expression level of es-LNCaP (ls-LNCaP: 179, 156, 133, 123, and 167%; si-LNCaP: 22, 93, 103, 112, and 107%). Conclusions. This finding suggests that androgen receptor can be related to the increased expression of cancer related survival markers such as HSP27, GRP78, CLU, and c-FLIP in late stage prostate cancer, and also inhibition of AR gene can be a therapeutic target in this stage of cancer.

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.