Use of nanoparticles to monitor human mesenchymal stem cells transplanted into penile cavernosum of rats with erectile dysfunction.

PURPOSE: This study was performed to examine the treatment of erectile dysfunction by use of superparamagnetic iron oxide nanoparticles-labeled human mesenchymal stem cells (SPION-MSCs) transplanted into the cavernous nerve injured cavernosa of rats as monitored by molecular magnetic resonance imaging (MRI). MATERIALS AND METHODS: Eight-week-old male Sprague-Dawley rats were divided into three groups of 10 rats each: group 1, sham operation; group 2, cavernous nerve injury; group 3, SPION-MSC treatment after cavernous nerve injury. Immediately after the cavernous nerve injury in group 3, SPION-MSCs were injected into the cavernous nerve injured cavernosa. Serial T2-weighted MRI was done immediately after injection and at 2 and 4 weeks. Erectile response was assessed by cavernous nerve stimulation at 2 and 4 weeks. RESULTS: Prussian blue staining of SPION-MSCs revealed abundant uptake of SPION in the cytoplasm. After injection of 1×10(6) SPION-MSCs into the cavernosa of rats, T2-weighted MRI showed a clear hypointense signal induced by the injection. The presence of SPION in the corpora cavernosa was confirmed with Prussian blue staining. At 2 and 4 weeks, rats with cavernous nerve injury had significantly lower erectile function than did rats without cavernous nerve injury (p<0.05). The group transplanted with SPION-MSCs showed higher erectile function than did the group without SPION-MSCs (p<0.05). The presence of SPION-MSCs for up to 4 weeks was confirmed by MRI imaging and Prussian blue staining in the corpus cavernosa. CONCLUSIONS: Transplanted SPION-MSCs existed for up to 4 weeks in the cavernous nerve injured cavernosa of rats. Erectile dysfunction recovered and could be monitored by MRI.

Efficacy and tolerability of combined medication of two different antimuscarinics for treatment of adults with idiopathic overactive bladder in whom a single agent antimuscarinic therapy failed.

OBJECTIVE: Recent studies have investigated a combination of two antimuscarinics for adult neurogenic bladder managed with clean intermittent catheterization or pediatric refractory overactive bladder (OAB). We assessed the efficacy and tolerability of this strategy in adults with idiopathic OAB. METHODS: We reviewed 49 patients with idiopathic OAB who received combined antimuscarinic medication. Patients had serially received different kinds of antimuscarinics as monotherapy, but wished to take combined medication due to a lack of sufficient subjective improvement in urgency, even with dosage escalation. Efficacy was measured by changes of episodes of urgency, daytime voiding, nocturia and mean voided volume before and after the addition of the second antimuscarinic. RESULTS: The mean duration of combined medication was 9.3 months. After adding the second antimuscarinic, urgency per day decreased from 3.8 to 1.9 (p < 0.001) and daytime voiding decreased from 10.4 to 7.4 (p < 0.001). The number of nocturia episodes and the mean voided volume also improved, although there was no statistical significance. Efficacy did not differ between the 29 cases, with non-selective and non-selective drugs and 20 cases with non-selective and M3 selective drugs. Thirty-three (67.3%) patients reported to have benefited from combined medication. Maximal flow rate and post-void residual volume did not change in either of the sexes. Eleven (22.4%) patients discontinued the combination due to continued ineffectiveness and dry mouth. CONCLUSION: This retrospective study suggests that combined medication can help adults with refractory idiopathic OAB. Combined medication was tolerated in most of our patients.

Mesenchymal stem cells overexpressing hepatocyte growth factor (HGF) inhibit collagen deposit and improve bladder function in rat model of bladder outlet obstruction.

Bladder outlet obstruction (BOO) caused by collagen deposit is one of the most common problems in elderly male. This study was performed to examine the capability of human mesenchymal stem cells (MSCs) overexpressing hepatocyte growth factor (HGF) to inhibit collagen deposition in rat model of bladder outlet obstruction (BOO). HGF is known for its antifibrotic effect and the most promising agent for treating bladder fibrosis. BM3.B10 stable immortalized human MSC line (B10) was transduced to encode human HGF with a retroviral vector was prepared (B10.HGF). Two weeks after the onset of BOO, B10, and B10.HGF cells were injected into the rat's bladder wall. After 4 weeks, bladder tissues were harvested and Masson's trichrome staining was performed. Transgene expression in HGF-expressing B10 cells was demonstrated by reverse transcriptase polymerase chain reaction and immunohistochemical staining, and the high levels of HGF secreted by B10.HGF cells was confirmed by ELISA. The mean bladder weight in BOO rats was 5.8 times of the normal controls, while in animals grafted with B10.HGF cells, the weight was down to four times of the control [90.2 ± 1.6 (control), 89.9 ± 2.8 (sham), 527.9 ± 150.9 (BOO), 447.7 ± 41.0 (BOO + B10), and 362.7 ± 113.2 (BOO + B10.HGF)]. The mean percentage of collagen area increased in BOO rats, while in the animals transplanted with B10.HGF cells, the collagen area decreased to the normal control level [12.2 ± 1.3, (control), 12.8 ± 1.1 (sham), 26.6 ± 2.7 (BOO), 19.9 ± 6.0 (BOO + B10), and 13.3 ± 2.1 (BOO + B10.HGF)]. The expression of collagen and TGF-b protein increased after BOO, while the expression of HGF and c-met protein increased in the group with B10.HGF transplantation after BOO. Intercontraction interval decreased after BOO, but it recovered after B10.HGF transplantation. Maximal voiding pressure (MVP) increased after BOO, and it recovered to levels of the normal control after transplantation of B10.HGF cells. Residual urine volume (RU) increased after BOO, but the RU increase was not reversed by transplantation of B10.HGF cells. Human MSCs overexpressing HGF inhibited collagen deposition and improved cystometric parameters in bladder outlet obstruction of rats. The present study indicates that transplantation of MSCs modified to overexpress HGF could serve as a novel therapeutic strategy against bladder fibrosis in patients with bladder outlet obstruction.

Inhibition of collagen deposit in obstructed rat bladder outlet by transplantation of superparamagnetic iron oxide-labeled human mesenchymal stem cells as monitored by molecular magnetic resonance imaging (MRI).

Bladder outlet obstruction (BOO) caused by collagen deposit is one of the most common problems in elderly males. The present study is to investigate if human mesenchymal stem cells (MSCs) are capable of inhibiting collagen deposition and improve cystometric parameters in bladder outlet obstruction in rats. Human MSCs were labeled with nanoparticles containing superparamagnetic iron oxide (SPION), and transplanted in rat BOO lesion site. Forty 6-week-old female Sprague-Dawley rats were divided into four groups (group 1: control, group 2: sham operation, group 3: BOO, and group 4: BOO rats receiving SPION-hMSCs). Two weeks after the onset of BOO, 1 × 10(6) SPION-hMSCs were injected into the bladder wall. Serial T2-weighted MR images were taken immediately after transplantation of SPION-labeled human MSCs and at 4 weeks posttransplantation. T2-weighted MR images showed a clear hypointense signal induced by the SPION-labeled MSCs. While the expression of collagen and TGF-ß protein increased after BOO, the expression of both returned to the original levels after MSC transplantation. Expression of HGF and c-met protein also increased in the group with MSC transplantation. Maximal voiding pressure and residual urine volume increased after BOO but they recovered after MSC transplantation. Human MSCs transplanted in rat BOO models inhibited the bladder fibrosis and mediated recovery of bladder dysfunction. Transplantation of MSC-based cell therapy could be a novel therapeutic strategy against bladder fibrosis in patients with bladder outlet obstruction.

A Case of Bladder Cancer Found during a Workup for Urge Incontinence.

Irritative urinary symptoms may suggest the possibility of bladder cancer. We report a case of metastatic bladder cancer that was discovered during a workup for urge incontinence in a 65-year-old woman with a history of stomach cancer. She had a medical history of gastrectomy due to stomach cancer 4 years previously. The patient complained of urgency unresponsive to anticholinergic therapy. Cystoscopy revealed the presence of suspicious bladder mucosal lesions that were biopsied. The pathology was consistent with metastatic signet-ring cell adenocarcinoma. This case suggests that irritative urinary symptoms can be the first clinical manifestation in patients with bladder cancer.

The 5-year functional outcomes after radical prostatectomy: a real-life experience in Korea.

We investigated the functional outcomes regarding erectile function and urinary continence up to 5 years following radical prostatectomy (RP) in a cohort of Korean men. We retrospectively analyzed the clinicopathologic data of 85 Korean men who received open uni- or bilateral nerve-sparing RP for clinically localized prostate cancer and were followed up for at least 5 years postoperatively. From medical records, patients' status regarding urinary and erectile function at baseline and postoperative followups after RP was assessed. At 24 and 60 months after RP, proportions of subjects continent (no pads used) were 89.4% and 97.6%, respectively (P = 0.007). Excluding subjects (n = 24) who preoperatively reported having severe erectile dysfunction or lacked relevant informations, proportions of subjects capable of having vaginal intercourse regardless of erectile aid usage were 47.5% and 37.7% at 24 and 60 months from RP, respectively (P = 0.022). Patient's age at surgery (P = 0.047) and salvage radiation therapy (P = 0.026) were observed to be significant predictors of having erections sufficient for intercourse at 60 months from RP in multivariate analysis. Our results showed that while patients' postoperative status regarding urinary continence at 2 years from RP is generally maintained or improved at 5 year point, erectile function was observed to significantly declined from 2 years to 5 years following RP. Such decline in erectile function following RP may be more significant among men who were relatively older at surgery or those who received salvage therapy during postoperative follow-ups.

Prognostic significance of undetectable ultrasensitive prostate-specific antigen nadir after radical prostatectomy.

OBJECTIVES: To investigate the prognostic significance of undetectable ultrasensitive prostate-specific antigen (PSA) nadir in patients who received radical prostatectomy (RP) for prostate cancer. METHODS: We reviewed records of 384 patients who received RP for prostate cancer and were followed for at least 2 years with ultrasensitive PSA testing. Undetectable ultrasensitive PSA level was defined as <0.001 ng/mL. Subjects were categorized according to PSA nadirs: <0.001 ng/mL (group 1), 0.001 ng/mL ≤ and < 0.02 ng/mL (group 2), 0.02 ng/mL ≤ and < 0.05 ng/mL (group 3), or ≥0.05 ng/mL (group 4). Multivariate analysis was performed to identify independent predictors of biochemical recurrence-free survival. A receiver operator characteristics (ROC) curve was used to assess performances of multivariate model in predicting biochemical recurrence. RESULTS: Overall, 206 (53.6%) patients showed undetectable ultrasensitive PSA nadir. Subjects of groups 1, 2, 3, and 4 demonstrated significant differences in biochemical recurrence-free survivals (log rank P <.001). In multivariate analysis, undetectable ultrasensitive PSA nadir (P <.001) was observed to be an independent predictor of biochemical recurrence-free survival along with preoperative PSA level (P = .030), pathologic stage (P = .014), and pathologic Gleason score (P = .042). Area under the ROC curve demonstrating predictive performances of the multivariate model, which included ultrasensitive PSA nadir, was significantly larger than that of the model without it (P <.001). CONCLUSIONS: Our results demonstrated that undetectable ultrasensitive PSA nadir is a useful predictor of biochemical recurrence-free survival among contemporary patients who received RP for prostate cancer.

Alteration of Antithrombin III and D-dimer Levels in Clinically Localized Prostate Cancer.

PURPOSE: We performed a comparative analysis of the plasma levels of antithrombin (AT) III, plasminogen, fibrinogen, and D-dimer among patients with and without clinically localized prostate cancer to investigate the clinical significance of the coagulation profile in prostate cancer. MATERIALS AND METHODS: A prospective study was performed in which plasma levels of AT III, plasminogen, fibrinogen, and D-dimer were assessed in patients before they underwent prostate biopsy. According to the results of the biopsy, the patients were categorized into the cancer group or the control group. Levels of the four coagulation factors were then compared between the cancer and control groups. Also, levels of the four coagulation factors were correlated with tumor stage and grade in the cancer group. RESULTS: The cancer group had significantly lower levels of AT III activity and higher plasma D-dimer levels than did the control group (p=0.007 and p=0.018, respectively). Within the cancer group, no significant differences were observed in the levels of AT III, plasminogen, fibrinogen, or D-dimer between those with a pathological Gleason score of >/=7 and otherwise. Regarding pathologic stage of prostate cancer, the subjects with organ-confined disease and those with extraprostatic extension of a tumor demonstrated no significant differences in the preoperative levels of the four coagulation factors analyzed. CONCLUSIONS: Our results suggest that plasma levels of AT III and D-dimer are altered in patients with prostate cancer. Further study is needed to elucidate the underlying mechanism and clinical significances of such a phenomenon among patients with clinically localized prostate cancer.

Efficacy of adjuvant gemcitabine-cisplatin chemotherapy: a comparative study between locally advanced transitional cell carcinoma of the bladder and upper urinary tract.

OBJECTIVE: To evaluate the comparative efficacy of adjuvant gemcitabine and cisplatin (GC) chemotherapy between patients with locally advanced transitional cell carcinoma (TCC) of the bladder and upper urinary tract. PATIENTS AND METHODS: From 2001 to 2005, we retrospectively selected a total of 64 patients with locally advanced TCC of the bladder and upper urinary tract who received at least 3 cycles of adjuvant GC chemotherapy. We compared disease-free and overall survival between the 2 groups. RESULTS: The recurrence rate was 30.3% in TCC of the bladder and 25.8% of the upper urinary tract (p = 0.633). Statistical analysis revealed that there was no significant difference in the disease-free or overall survival rate between TCC of the bladder and upper urinary tract treated with adjuvant GC chemotherapy. CONCLUSION: Under the circumstances of limited data about TCC of the upper urinary tract, this study may suggest that adjuvant GC chemotherapy in locally advanced TCC of the upper urinary tract is as effective as those of bladder.

Comparison of radiographic and pathologic sizes of renal tumors.

PURPOSE: We investigated the difference between tumor sizes measured via preoperative computed tomography (CT) images and in surgical specimens during pathologic examinations in a contemporary cohort of patients who received extirpative surgery for renal tumors. METHODS: We reviewed records of 467 patients who received radical or partial nephrectomy for renal lesions suspicious for malignancy. For our study, only patients who underwent preoperative CT within 4 weeks of surgery were included. In all patients, radiographic tumor size, defined as the largest diameter of tumor measured via CT images, and pathologic tumor size, the largest diameter of tumor measured in surgical specimen, were compared and analyzed by various factors. RESULTS: Among total subjects, mean radiographic and pathologic tumor size were 4.56 +/- 2.99 and 4.49 +/- 3.23 cm, respectively (P = 0.399). When subjects were categorized according to radiographic tumor size (1-cm range), statistically significant difference (average of 2 mm) between radiographic and pathologic tumor size was observed only in the 4 to <5 cm range (P = 0.046). Among those with clear cell renal cell carcinoma, mean radiographic tumor size was significantly larger than pathologic size, but by only 1.4 mm (P = 0.012). Factors such as age, gender, body mass index, tumor stage, tumor grade, and tumor location were observed to have no significant impact on differences observed between radiographic and pathologic tumor size. CONCLUSIONS: Although actual size of renal mass can be generally overestimated by CT images, difference may be minimal and clinically insignificant in most cases.

Significance of postbiopsy hemorrhage observed on preoperative magnetic resonance imaging in performing robot-assisted laparoscopic radical prostatectomy.

OBJECTIVES: Due to lack of tactile feedback, dissection of surgical planes during delicate procedures of nerve-sparing robot-assisted laparoscopic radical prostatectomy (RALRP) can be hampered more by postbiopsy hematomas or adhesions compared with open surgery. Thus, we investigated association between extent of postbiopsy hemorrhage observed via preoperative magnetic resonance (MR) imaging with surgical difficulty of RALRP. METHODS: We reviewed records of 154 men who received prostate biopsy, MR imaging, and subsequently, nerve-sparing RALRP for clinically localized prostate cancer within 2 weeks of MR imaging. We scored degree of postbiopsy hemorrhage as shown on T1-weighted MR imaging (hemorrhage score) and analyzed potential association of hemorrhage score with variables representative of surgical difficulty (operative time, estimated blood loss, and margin positivity) and functional outcomes (urinary continence and erectile function). RESULTS: Among our subjects, total hemorrhage score demonstrated no significant associations with interval from biopsy to MR imaging (p = 0.210). In multivariate analyses, prostate volume and total hemorrhage score were observed to be significantly associated with operative time (p = 0.004 and 0.039, respectively) and estimated blood loss (p = 0.009 and 0.023, respectively). Patients' age and total hemorrhage score was observed to be independent predictor of the return of erectile function sufficient for vaginal intercourse at 6 months following RALRP (p = 0.003 and 0.036, respectively). CONCLUSIONS: Degree of postbiopsy hemorrhage observed in preoperative MR imaging may be predictive of surgical difficulty for RALRP. Such findings provide concrete evidences that aftereffects of prostate biopsy have significant impact on performing RALRP.

Effect of the dual 5alpha-reductase inhibitor, dutasteride, on serum testosterone and body mass index in men with benign prostatic hyperplasia.

OBJECTIVE: To investigate the effects of dutasteride on serum testosterone level and body mass index (BMI) in men who received medical therapy for benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: In all, 120 patients with BPH were randomized to three treatment groups: tamsulosin 0.2 mg/day (alpha-blocker group), dutasteride 0.5 mg/day (dutasteride group), or tamsulosin 0.2 mg plus dutasteride 0.5 mg/day (combination group) for 1 year. For all patients the BMI and serum testosterone levels were checked at baseline and after 1 year of treatment. RESULTS: Among the evaluable 107 patients, the dutasteride (33) and combination groups (37) had significantly greater increases in serum testosterone level (16.3% and 15%, respectively) than the alpha-blocker group (37; 0.3%) after 1 year of treatment (both P < 0.001). When analysed by baseline serum testosterone tertile, the increases in serum testosterone level among the dutasteride and combination group were greatest in the lowest tertile. For BMI, the dutasteride and combination group had mean decreases of 0.17 and 0.20 kg/m(2), respectively, at 1 year, whereas the alpha-blocker group had a mean increase of 0.04 kg/m(2). The decreases in BMI for the dutasteride and combination group were statistically significant only in the lowest tertile (P = 0.048 and 0.010, respectively). CONCLUSION: Our results show that dutasteride treatment in men with BPH led to a significant increase in serum testosterone level and a significant decrease in BMI among those with relatively lower baseline serum testosterone levels.