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1.  Change in serum sodium level predicts clinical manifestations of transurethral resection syndrome: a retrospective review 
BMC Anesthesiology  2015;15:52.
Patients undergoing transurethral resection (TUR) of the prostate are at risk of TUR syndrome, generally defined as having cardiovascular and/or neurological manifestations, along with serum sodium concentrations less than or equal to 125 mmol/l. As these symptoms can also occur in patients with serum sodium greater than 125 mmol/l, this study aimed to investigate the relationship between serum sodium concentrations and neurological manifestations of TUR syndrome.
Data on patients who underwent TUR of the prostate under local anesthesia over an 8-year period were retrospectively reviewed. Based on their cardiovascular and neurological manifestations, patients were divided into two groups: a symptomatic and an asymptomatic group. Logistic regression analysis was used to detect the risk factors for being symptomatic. Receiver operator characteristic (ROC) curve analysis was used to determine the optimal cutoff value of estimated change in serum sodium level that could predict the development of clinical manifestation of TUR syndrome.
Of the 229 patients, 60 showed symptoms. Serum sodium level correlated with neurological score (Spearman’s correlation coefficient > 0.5). Logistic regression detected that the risk factors for being symptomatic were serum sodium level variables, operation time longer than or equal 90 min, and presence of continuous drainage from the bladder. ROC curve analysis showed that a change in serum sodium level of 7.4 mmol/l was the optimal cutoff value, with a sensitivity of 0.72, a specificity of 0.87, and an area under the curve (AUC) of 0.87. ROC curve analysis also showed that a 7.0% change in serum sodium level was optimal for this parameter, with a sensitivity of 0.70, a specificity of 0.89, and an AUC of 0.87.
Changes in serum sodium concentration of > 7 mmol/l and of > 7% could predict the development of cardiovascular and neurological manifestations, which were assumed to be symptoms of TUR syndrome.
PMCID: PMC4419475  PMID: 25927332
Transurethral resection of prostate; Transurethral resection syndrome; Dilutional hyponatremia
2.  E74-like factor inhibition induces reacquisition of hormone sensitiveness decreasing period circadian protein homolog 1 expression in prostate cancer cells☆ 
Prostate International  2015;3(1):16-21.
Initiating as an androgen-dependent adenocarcinoma, prostate cancer (PCa) gradually progresses to a castrate-resistant disease following androgen deprivation therapy with a propensity to metastasize.
In order to resolve the mechanism of castrate-resistant PCa, we performed a cDNA-microarray assay of two PCa cell lines, LNCaP (androgen dependent) and C4-2 (androgen independent). Among them, we focused on a novel Ets transcription factor, E74-like factor 5 (ELF5), the expression level of which was extremely high in C4-2 in comparison with LNCaP both in the microarray analysis and real-time polymerase chain reaction analysis, and investigated the biological role in acquisition of androgen-refractory PCa growth.
Western blot analysis and morphological analysis using confocal immunofluorescence microscopy demonstrated that ELF5 was expressed mainly in cytosol both in LNCaP and C4-2. Inhibition of ELF5 expression using ELF5-small interfering RNA in C4-2 induced decreased expression of androgen receptor corepressor, period circadian protein homolog 1, and MTT assay of C4-2 after ELF5 small interfering RNA transfection showed the same cell growth pattern of LNCaP.
Our in vitro experiments of cell growth and microarray analysis have demonstrated for the first time that decreased expression of period circadian protein homolog 1 due to ELF5 inhibition may induce the possibility of reacquisition of hormone sensitiveness of PCa cells. We suggest that ELF5 could be a novel potential target for the treatment of hormone-refractory PCa patients.
PMCID: PMC4495571  PMID: 26288799
Castrate-resistant disease; Prostate cancer
3.  Prediction of clinical manifestations of transurethral resection syndrome by preoperative ultrasonographic estimation of prostate weight 
BMC Urology  2014;14:67.
This study aimed to investigate the relationship between preoperative estimated prostate weight on ultrasonography and clinical manifestations of transurethral resection (TUR) syndrome.
The records of patients who underwent TUR of the prostate under regional anesthesia over a 6-year period were retrospectively reviewed. TUR syndrome is usually defined as a serum sodium level of < 125 mmol/l combined with clinical cardiovascular or neurological manifestations. This study focused on the clinical manifestations only, and recorded specific central nervous system and cardiovascular abnormalities according to the checklist proposed by Hahn. Patients with and without clinical manifestations of TUR syndrome were compared to determine the factors associated with TUR syndrome. Receiver operating characteristic curve analysis was used to determine the optimal cutoff value of estimated prostate weight for the prediction of clinical manifestations of TUR syndrome.
This study included 167 patients, of which 42 developed clinical manifestations of TUR syndrome. There were significant differences in preoperative estimated prostate weight, operation time, resected prostate weight, intravenous fluid infusion volume, blood transfusion volume, and drainage of the suprapubic irrigation fluid between patients with and without clinical manifestations of TUR syndrome. The preoperative estimated prostate weight was correlated with the resected prostate weight (Spearman’s correlation coefficient, 0.749). Receiver operator characteristic curve analysis showed that the optimal cutoff value of estimated prostate weight for the prediction of clinical manifestations of TUR syndrome was 75 g (sensitivity, 0.70; specificity, 0.69; area under the curve, 0.73).
Preoperative estimation of prostate weight by ultrasonography can predict the development of clinical manifestations of TUR syndrome. Particular care should be taken when the estimated prostate weight is > 75 g.
PMCID: PMC4143887  PMID: 25128188
TUR syndrome; Hyponatremia; Transurethral resection of prostate
4.  Single session of high-intensity focused ultrasound for localized prostate cancer: treatment outcomes and potential effect as a primary therapy 
World Journal of Urology  2013;32(5):1339-1345.
To investigate the treatment outcomes of a single-session high-intensity focused ultrasound (HIFU) using the Sonablate® for patients with localized prostate cancer.
Biochemical failure was defined according to the Stuttgart definition [a rise of 1.2 ng/ml or more above the nadir prostate-specific antigen (PSA)] and the Phoenix definition (a rise of 2 ng/ml or more above the nadir PSA). Disease-free survival rate was defined using the Phoenix criteria and positive follow-up biopsy.
A total of 171 patients were identified. Fifty-two (30.4 %) patients were identified to be with D’Amico low risk, 47 (27.5 %) with intermediate risk, and 72 (42.1 %) with high risk. In the median follow-up time of 43 months, there was 44 (25.7 %) and 36 (21.1 %) patients experienced biochemical failure for Stuttgart and Phoenix definition with mean (±SD) time to failure of 17.8 ± 2.1 and 19.4 ± 2.3 months, respectively. A total of 44 (25.7 %) patients were diagnosed as disease failure. Cox multivariate analysis revealed PSA nadir level (PSA cutoff = 0.2 ng/ml; HR = 9.472, 95 % CI 4.527–19.820, p < 0.001) and D’amico risk groups [HR = 3.132 (95 % CI 1.251–6.389), p = 0.033] were the predictor for failure in single-session HIFU.
Single-session HIFU treatment using the Sonablate® seems to be potentially curative approach. When treated carefully with neoadjuvant hormonal therapy or preoperative transurethral resection of the prostate, higher-risk disease might be able to choose this minimally invasive procedure as primary therapy.
PMCID: PMC4176571  PMID: 24270943
HIFU; Localized prostate cancer; Single-session treatment; Outcome
5.  Post-operative urothelial recurrence in patients with upper urinary tract urothelial carcinoma managed by radical nephroureterectomy with an ipsilateral bladder cuff: Minimal prognostic impact in comparison with non-urothelial recurrence and other clinical indicators 
Oncology Letters  2013;6(4):1015-1020.
Upper urinary tract urothelial carcinoma (UTUC) is a rare disease, and novel prognostic factors for patients who have undergone a radical nephroureterectomy (RNU) for UTUC have been studied intensely. To the best of our knowledge, the prognostic value of urothelial recurrence in patients with UTUC has not been previously described in studies. The present study compared the prognostic value of urothelial and non-urothelial recurrence in patients with UTUC of the kidney and ureter managed by surgery. The inclusion criteria consisted of a diagnosis of non-metastatic UTUC (any T stage, N0–1 and M0) and receipt of an RNU with an ipsilateral bladder cuff as the primary treatment. Of the 153 patients that were screened for the study, comprehensive clinical and pathological data was available for 103 patients, who were consequently included in the analysis. Overall survival (OS) and cancer-specific survival (CSS) times were estimated. A multivariate analysis was performed using the Cox regression model. The median follow-up period was 29 months (interquartile range, 14–63 months). The patient population was comprised of 71 males (68.9%) and 32 females (31.1%). A total of 32 patients (31.1%) showed non-urothelial recurrence, while 38 patients (36.9%) exhibited urothelial recurrence and 33 patients (32.0%) exhibited no recurrence. When comparing the risk parameters between the non-urothelial recurrence categories, the factors of pathological grade, microvascular invasion, lymphatic invasion and pT classification showed significant differences. However, there were no significant differences between the urothelial recurrence categories. No significant difference was observed between the OS and CSS times within the urothelial recurrence categories (P=0.3955 and P=0.05891, respectively), but significant differences were identified in the non-urothelial recurrence categories (P<0.0001 and P<0.0001, respectively). Among the other relevant descriptive pre-operative characteristics in the multivariate analysis, only non-urothelial recurrence remained associated with a worse CSS [P=0.002; hazard ratio (HR) 9.512]. The results show that urothelial recurrence has a minimal prognostic value in patients with UTUC managed by RNU with an ipsilateral bladder cuff.
PMCID: PMC3796430  PMID: 24137456
non-urothelial recurrence; upper urinary tract urothelial carcinoma; prognosis
6.  Induction of erythropoietin increases the cell proliferation rate in a hypoxia-inducible factor-1-dependent and -independent manner in renal cell carcinoma cell lines 
Oncology Letters  2013;5(6):1765-1770.
Erythropoietin (Epo) is a potent inducer of erythropoiesis that is mainly produced in the kidney. Epo is expressed not only in the normal kidney, but also in renal cell carcinomas (RCCs). The aim of the present study was to gain insights into the roles of Epo and its receptor (EpoR) in RCC cells. The study used two RCC cell lines, Caki-1 and SKRC44, in which Epo and EpoR are known to be highly expressed. The proliferation rate and expression level of hypoxia-inducible factor-1α (HIF-1α) were measured prior to and following Epo treatment and under normoxic and hypoxic conditions. To examine whether HIF-1α or Epo were involved in cellular proliferation during hypoxia, these proteins were knocked down using small interfering RNA (siRNA) in Caki-1 and SKRC44 cells. The results demonstrated that Epo enhanced the proliferation of the Caki-1 and SKRC44 cells. HIF-1α expression was increased upon the induction of hypoxia in the Caki-1 cells, but remained unaffected in the SKRC44 cells. The proliferation rate was increased under hypoxic conditions in the Caki-1 cells, but was decreased in the SKRC44 cells. Under hypoxic conditions, the proliferation of the Caki-1 cells was significantly reduced by the knock-down of HIF-1α or Epo, while the proliferation of the SKRC44 cells was significantly suppressed by the knock-down of Epo, but not HIF-1α. In conclusion, these data suggest that the induction of Epo may accelerate the proliferation of the RCC cell lines in either a HIF-1α-dependent or -independent manner.
PMCID: PMC3701060  PMID: 23833638
erythropoietin; renal cell carcinoma; hypoxia-inducible factor-1
7.  Comparable effect with minimal morbidity of low-dose Tokyo 172 strain compared with regular dose Connaught strain as an intravesical bacillus Calmette–Guérin prophylaxis in nonmuscle invasive bladder cancer: Results of a randomized prospective comparison 
Urology Annals  2013;5(1):7-12.
The aim was to compare patients' morbidity and response of bacillus Calmette–Guérin (BCG) prophylaxis after the intravesical instillation of low-dose Tokyo 172 strain and regular dose Connaught strain in patients with nonmuscle invasive bladder cancer (NMIBC).
Patients and Methods:
This was a randomized, active-controlled, open-label, monocenter study. Thirty-eight, NMIBC patients were treated sequentially, in a random order, with low-dose Tokyo 172 strain and regular dose Connaught strain, receiving each therapy for 6 weeks. A total of 18 and 20 patients were randomly assigned to a Tokyo 172 strain arm and a Connaught strain arm, respectively. Complication, morbidity, and recurrence-free survival (RFS) after each treatment were compared.
There was no significant difference in the 1-year RFS rate in patients treated with Tokyo 172 strain and Connaught strain (72.2% vs. 83.5%, respectively; P = 0.698). There were no significant differences in adverse events between the arms. Severe adverse events (>Grade 3) were seen in 15% of the Connaught strain group while no severe adverse events were observed as a result of Tokyo 172 strain.
Our results indicated that low-dose Tokyo 172 strain decreased adverse events although it was not significant, and the RFS difference was not statistically significant between the two arms. Further investigation is warranted.
PMCID: PMC3643329  PMID: 23662001
Bacillus Calmette–Guérin; bladder cancer; intravesical instillation; Tokyo 172 strain
8.  Immunotherapy of Genitourinary Malignancies 
Journal of Oncology  2012;2012:397267.
Most cancer patients are treated with some combination of surgery, radiation, and chemotherapy. Despite recent advances in local therapy with curative intent, chemotherapeutic treatments for metastatic disease often remain unsatisfying due to severe side effects and incomplete long-term remission. Therefore, the evaluation of novel therapeutic options is of great interest. Conventional, along with newer treatment strategies target the immune system that suppresses genitourinary (GU) malignancies. Metastatic renal cell carcinoma and non-muscle-invasive bladder caner represent the most immune-responsive types of all human cancer. This review examines the rationale and emerging evidence supporting the anticancer activity of immunotherapy, against GU malignancies.
PMCID: PMC3317259  PMID: 22481927
9.  Urinary continence following laparoscopic radical prostatectomy: Association with postoperative membranous urethral length measured using real-time intraoperative transrectal ultrasonography 
Oncology Letters  2011;3(1):181-184.
Urinary incontinence is a major complication following radical prostatectomy. The aim of the present study was to assess the association between urinary continence following laparoscopic radical prostatectomy (LRP) and various factors measured using real-time intraoperative transrectal ultrasonography (TRUS). Patients (n=53) with localized prostate cancer underwent LRP in combination with real-time intraoperative TRUS navigation and were evaluated for urinary continence for more than 6 months following LRP. Prostate size, membranous urethral length (MUL) and bladder-urethra angle were measured using real-time intraoperative TRUS immediately before and after surgery. Urinary continence was regained by 4, 15 and 27 patients 1, 3 and 6 months after LRP, respectively. Longer postoperative MUL was significantly correlated with recovery of urinary continence 1, 3 and 6 months after LRP. In addition, an increase in difference between preoperative and postoperative MUL was also associated with superior continence. No correlation was observed between postoperative MUL and the rate of tumor-positive surgical margins. Larger prostate volume was correlated to postoperative continence 6 months after surgery. Shorter operation time and less blood loss resulted in postoperative urinary continence 1 month after LRP. Preoperative MUL, bladder-urethra angle, age and body mass index had no correlation with urinary continence. Postoperative MUL was the most significant factor for early recovery of urinary continence following LRP. These results indicate that preservation of longer urethra during surgery may be recommended without tumor-positive surgical margins.
PMCID: PMC3362547  PMID: 22740877
urinary continence; membranous urethral length; laparoscopic radical prostatectomy; transrectal ultrasonography
10.  Curcumin Potentiates the Antitumor Effects of Gemcitabine in an Orthotopic Model of Human Bladder Cancer through Suppression of Proliferative and Angiogenic Biomarkers 
Biochemical pharmacology  2009;79(2):218-228.
Little progress has been made in the last three decades in the treatment of bladder cancer. Novel agents that are nontoxic and can improve the current standard of care of this disease are urgently needed. Curcumin, a component of Curcuma longa (also called turmeric), is one such agent that has been shown to suppress pathways linked to oncogenesis, including cell survival, proliferation, invasion and angiogenesis. We investigated whether curcumin has potential to improve the current therapy for bladder cancer, using an orthotopic mouse model. Whether examined by cell viability, curcumin potentiated the apoptotic effects of gemcitabine against human bladder cancer 253JBV cells in culture. Electrophoretic mobility shift assay revealed that curcumin also suppressed the gemcitabine-induced activation of the cell survival transcription factor NF-κB. In an orthotopic mouse model, bioluminescence imaging revealed that while curcumin alone significantly reduced the bladder tumor volume, maximum reduction was observed when curcumin was used in combination with gemcitabine (P<0.01 versus vehicle; P<0.01 versus gemcitabine alone). Curcumin also significantly decreased the proliferation marker Ki-67 and microvessel density (CD31) (P<0.01 versus vehicle; P<0.01versus gemcitabine alone), but maximum reduction occurred when it was combined with gemcitabine (P<0.01 versus vehicle; P<0.01versus gemcitabine alone). Curcumin abolished the constitutive activation of NF-κB in the tumor tissue; induced apoptosis, and decreased cyclin D1, VEGF, COX-2, c-myc and Bcl-2 expression in the bladder cancer tissue. Overall our results suggest that curcumin alone exhibits significant antitumor effects against human bladder cancer and it further potentiates the effects of gemictabine, possibly through the modulation of NF-κB signaling pathway.
PMCID: PMC3181149  PMID: 19682434
Curcumin; bladder cancer; NF-κB; gemcitabine
11.  Rapid Increase of the Serum PSA Level in Response to High-Intensity Focused Ultrasound Therapy may be a Potential Indicator of Biochemical Recurrence of Low- and Intermediate-Risk Prostate Cancer 
To determine the incidence and magnitude of the rapid increase in the serum PSA (riPSA) level after high-intensity focused ultrasound (HIFU) therapy for prostate cancer, and its correlation with clinical factors.
A total of 176 patients with localized prostate cancer underwent HIFU therapy. Serum riPSA was determined on the basis of the same criteria as those for “PSA bounce”, ie, an increase of ≥0.2 ng/ml with a spontaneous return to the prebounce level or lower. Patients were stratified according to neoadjuvant PSA level, T stage, risk group, age, Gleason score, pretreatment PSA level, post-treatment PSA nadir, and number of HIFU sessions.
riPSA was seen in 53% of patients during a median follow-up period of 43 months. A PSA nadir was achieved within 3 months for 85.1% of the treatments. In all cases, onset of riPSA was seen two days after HIFU therapy, and the median magnitude was 23.69 ng/ml. A magnitude of >2 ng/ml was seen in 89.4% of cases. Univariate analysis revealed that patients with riPSA were associated with usage of hormonal therapy and the post-treatment PSA nadir level. Multivariate Cox regression analysis revealed that riPSA and the number of HIFU sessions were predictors of biochemical recurrence. A significant statistical association was found between the presence of riPSA and the risk of biochemical failure only in the low- and intermediate-risk group.
Patients treated with HIFU who experience post-treatment riPSA may have an increased risk of biochemical recurrence, especially in non-high-risk patients.
PMCID: PMC3095026  PMID: 21603245
HIFU; prostate cancer; PSA
12.  Surgical correction of buried penis after traffic accident – a case report 
BMC Urology  2004;4:6.
Buried penis, most commonly seen in children, is particularly debilitating in adults, resulting in inability to void while standing and it also affects vaginal penetration. We report a case of buried penis due to a traffic accident, which caused dislocation of the fractured pubic bone that shifted inside and pulled the penis by its suspensory ligament.
Case presentation
A 55-year-old man was admitted to our hospital with a chief complaint of hidden penis while in the sitting position. He had suffered a pelvic fracture in a traffic accident four years previously, and his penis was covered with suprapubic fat when he was in a sitting position. He was unable to have sexual intercourse. We performed a penile lengthening procedure, including inverse V-Y-plasty of the dorsal skin of the penile root, suspensory desmotomy and fat removal, under general anesthesia. There was a good cosmetic result with satisfactory penile erection, which allowed successful sexual intercourse after surgery.
We performed penile elongation surgery with inverse V-Y-plasty of the dorsal skin of the penile root, suspensory desmotomy, and fat removal. Surgical treatment of buried penis achieves marked aesthetic and functional improvement, and benefits the majority of patients, resulting in satisfactory erection and successful sexual intercourse.
PMCID: PMC434514  PMID: 15182380
pelvic fracture; buried penis; V-Yplasty

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