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1.  Approach via a small retroperitoneal anterior subcostal incision in the supine position for gasless laparoendoscopic single-port radical nephrectomy: initial experience of 42 patients 
BMC Urology  2014;14:29.
Gasless laparoendoscopic single-port surgery (GasLESS) for radical nephrectomy (GasLESSRN) in the flank position is a minimally invasive treatment option for patients with T1–3 renal cell carcinoma (RCC). However, RCC patients considered suitable for supine positioning rather than flank positioning for radical nephrectomy are occasionally encountered. This study evaluated the safety and feasibility of approach via a small retroperitoneal anterior subcostal incision (RASI) in the supine position for GasLESSRN (RASI-GasLESSRN) on the basis of our initial experience.
RASI-GasLESSRN was performed on 42 patients with RCC or suspected RCC from 2011–2013. The RASI, which was 6 cm long in principle, was made parallel to the tip of the rib from the lateral border of rectus abdominis muscle toward the flank in the supine position. The specimen was extracted via the RASI using a retrieval device. All procedures were performed retroperitoneally under flexible endoscopy with reusable instruments and without carbon dioxide insufflation or insertion of hands into the operative field.
RASI-GasLESSRN was successfully performed in all patients without complications. The mean incision length was 6.3 cm, mean operative time was 198 minutes, and mean blood loss was 284 mL. All 42 patients were classified as Clavien grade I. The mean times to oral feeding and walking were 1.1 and 2 days, respectively. The mean number of postoperative days required for patients to be dischargeable was 3.7 days.
The approach via a small RASI in the supine position for GasLESSRN is a safe and feasible technique. RASI-GasLESSRN in the supine position is an alternative minimally invasive treatment option, especially for RCC patients considered suitable for supine positioning.
PMCID: PMC3977956
Retroperitoneal anterior subcostal incision; Supine position; Renal cell carcinoma; Radical nephrectomy; Laparoendoscopic single-port surgery; Gasless laparoendoscopic single-port surgery
2.  Organ-specific and tumor-size-dependent responses to sunitinib in clear cell renal cell carcinoma 
BMC Urology  2014;14:26.
Tyrosine kinase inhibitors (TKIs) have been used as standard therapy for patients with advanced renal cell carcinoma (RCC). However, information on factors predicting response to treatment with TKIs is lacking. This study aimed to assess the association between initial tumor size, involved organs, pre-treatment C-reactive protein (CRP) levels, and reduction in tumor size in patients with clear cell RCC (CCRCC) treated with sunitinib.
Patients with advanced CCRCC with target lesions with a maximum diameter ≥ 10 mm treated with sunitinib were evaluated. The tumor diameter representing the best overall response was designated as the post-treatment tumor diameter.
A total of 179 lesions in 38 patients were analyzed. Organ-specific analysis demonstrated that pre-treatment diameter of lung metastatic lesions had a moderate inverse association with percent reduction in post-treatment tumor diameter (R = 0.341). Lung lesions showed significantly greater percent reductions in diameter than liver and kidney lesions (P = 0.007 and 0.002, respectively). Furthermore, based on a CRP cut-off level of 2.0 mg/dl, mean tumor size reduction was significantly greater in patients with low CRP levels than in patients with high CRP levels in lesions with diameters < 20 mm (P = 0.002). CRP level had no effect on mean size reduction in lesions with a diameter ≥ 20 mm.
Patients with CCRCC with smaller lung metastatic lesions and lower CRP levels may achieve greater percent reductions in tumor size with sunitinib therapy than patients with extra-pulmonary lesions, large lung lesions, and/or higher CRP levels.
PMCID: PMC3975282  PMID: 24612599
Advanced renal cell carcinoma; Sunitinib; Tumor size; Tumor response; C-reactive protein
3.  Effects of surgeon variability on oncologic and functional outcomes in a population-based setting 
BMC Urology  2014;14:25.
Oncologic and functional outcomes after radical prostatectomy (RP) can vary between surgeons to a greater extent than is expected by chance. We sought to examine the effects of surgeon variation on functional and oncologic outcomes for patients undergoing RP for prostate cancer in a European center.
The study comprised 1,280 men who underwent open retropubic RP performed by one of nine surgeons at an academic institution in Sweden between 2001 and 2008. Potency and continence outcomes were measured preoperatively and 18 months postoperatively by patient-administered questionnaires. Biochemical recurrence (BCR) was defined as a prostate-specific antigen (PSA) value > 0.2 ng/mL with at least one confirmatory rise. Multivariable random effect models were used to evaluate heterogeneity between surgeons, adjusting for case mix (age, PSA, pathological stage and grade), year of surgery, and surgical experience.
Of 679 men potent at baseline, 647 provided data at 18 months with 122 (19%) reporting potency. We found no evidence for heterogeneity of potency outcomes between surgeons (P = 1). The continence rate for patients at 18 months was 85%, with 836 of the 979 patients who provided data reporting continence. There was statistically significant heterogeneity between surgeons (P = 0.001). We did not find evidence of an association between surgeons’ adjusted probabilities of functional recovery and 5-year probability of freedom from BCR.
Our data support previous studies regarding a large heterogeneity among surgeons in continence outcomes for patients undergoing RP. This indicates that some patients are receiving sub-optimal care. Quality assurance measures involving performance feedback, should be considered. When surgeons are aware of their outcomes, they can improve them to provide better care to patients.
PMCID: PMC3975576  PMID: 24602348
Prostate cancer; Radical prostatectomy; Erectile function; Urinary function
4.  Simvastatin improves the sexual health-related quality of life in men aged 40 years and over with erectile dysfunction: additional data from the erectile dysfunction and statin trial 
BMC Urology  2014;14:24.
Erectile dysfunction is prevalent in men over 40 years, affecting their quality of life and that of their partners. The aims of this study were:
a) To evaluate the internal reliability of the male erectile dysfunction specific quality of life (MED-QoL) scale and explore its factor structure.
b) To evaluate the effect of simvastatin on subscales of the MED-QoL in men over forty years with erectile dysfunction.
This is a double blind randomised controlled trial of 40 mg simvastatin or placebo given once daily for six months to men over forty years with untreated erectile dysfunction, who were not at high cardiovascular risk and were not on anti-hypertensive or lipid-lowering medication. 173 eligible men were recruited from 10 general practices in East of England. Data were collected at two points over 30 weeks.
We report on the factor structure of MED-QoL, the internal reliability of the scale and the derived subscales, and the effect of simvastatin on MED-QoL subscales.
An initial analysis of the MED-QoL items suggested that a number of items should be removed (MED-QoL-R). Exploratory factor analysis identified three subscales within the MED-QoL-R which accounted for 96% of the variance, related to feelings of Control, initiating Intimacy, and Emotional response to erectile dysfunction. The alpha value for the revised scale (MED-Qol-R) was >0.95 and exceeded .82 for each subscale. Regression analysis showed that patients in the placebo group experienced a significantly reduced feeling of Control over erectile dysfunction than those in the statin group. Those in the placebo group had significantly lower Emotional response than those in the statin group at the close of trial, but there was no significant treatment effect on Intimacy.
Our revised MED-QoL-R identified three subscales. Secondary analysis showed a significant improvement in sexual health related quality of life, specifically in relation to perception of control and emotional health in men with untreated erectile dysfunction given 40 mg simvastatin for six months.
Trial registration
Current Controlled Trials ISRCTN66772971.
PMCID: PMC3945996  PMID: 24593269
Erectile dysfunction; Statins; Sexual health quality of life; Randomised controlled trial
5.  BMC Urology reviewer acknowledgement, 2013 
BMC Urology  2014;14:15.
Contributing reviewers
The editors of BMC Urology would like to thank all our reviewers who have contributed to the journal in Volume 13 (2013).
PMCID: PMC3936807  PMID: 24575719
6.  Key considerations for the experimental training and evaluation of cancer odour detection dogs: lessons learnt from a double-blind, controlled trial of prostate cancer detection 
BMC Urology  2014;14:22.
Cancer detection using sniffer dogs is a potential technology for clinical use and research. Our study sought to determine whether dogs could be trained to discriminate the odour of urine from men with prostate cancer from controls, using rigorous testing procedures and well-defined samples from a major research hospital.
We attempted to train ten dogs by initially rewarding them for finding and indicating individual prostate cancer urine samples (Stage 1). If dogs were successful in Stage 1, we then attempted to train them to discriminate prostate cancer samples from controls (Stage 2). The number of samples used to train each dog varied depending on their individual progress. Overall, 50 unique prostate cancer and 67 controls were collected and used during training. Dogs that passed Stage 2 were tested for their ability to discriminate 15 (Test 1) or 16 (Tests 2 and 3) unfamiliar prostate cancer samples from 45 (Test 1) or 48 (Tests 2 and 3) unfamiliar controls under double-blind conditions.
Three dogs reached training Stage 2 and two of these learnt to discriminate potentially familiar prostate cancer samples from controls. However, during double-blind tests using new samples the two dogs did not indicate prostate cancer samples more frequently than expected by chance (Dog A sensitivity 0.13, specificity 0.71, Dog B sensitivity 0.25, specificity 0.75). The other dogs did not progress past Stage 1 as they did not have optimal temperaments for the sensitive odour discrimination training.
Although two dogs appeared to have learnt to select prostate cancer samples during training, they did not generalise on a prostate cancer odour during robust double-blind tests involving new samples. Our study illustrates that these rigorous tests are vital to avoid drawing misleading conclusions about the abilities of dogs to indicate certain odours. Dogs may memorise the individual odours of large numbers of training samples rather than generalise on a common odour. The results do not exclude the possibility that dogs could be trained to detect prostate cancer. We recommend that canine olfactory memory is carefully considered in all future studies and rigorous double-blind methods used to avoid confounding effects.
PMCID: PMC3945616  PMID: 24575737
Prostate cancer; Cancer detection dogs; Cancer odour; Olfactory memory; Multiple sample learning
7.  TOT Approach in stress urinary incontinence (SUI) – outcome in obese female 
BMC Urology  2014;14:20.
Only limited data are available on the outcome of tension-free obturator tape (TOT) procedures in overweight and obese women. We would like to verify the objective and subjective outcomes of TOT in women with a higher body mass index (BMI).
We evaluated the records of 116 patients who had undergone TOT, stratifying by BMI into normal weight (n = 31), overweight (n = 56), and obese (n = 29) groups. We compared pre- and postoperative evaluations, including subjective and objective outcome of TOT, complications, and quality of life assessed by validated questionnaires (ICIQ-SF and KHQ).
The median follow-up was 21 months. There were no significant differences between different groups in terms of objective cure rate and subjective success, quality of life scores and postoperative complications.
Our data demonstrate that TOT procedure is safe and effective. BMI did not influence the outcome of TOT procedures at a median of 21 months after surgery and represents no contraindication for continence surgery. The success of the outcome of TOT procedure in females and the occurrence of complications are not negatively affected by obesity.
PMCID: PMC3936697  PMID: 24552585
Body mass index; Obesity; Obese female; Stress urinary incontinence; Transobturator tape (TOT)
8.  Hem-O-Lok clip: a neglected cause of severe bladder neck contracture and consequent urinary incontinence after robot-assisted laparoscopic radical prostatectomy 
BMC Urology  2014;14:21.
Hem-o-lok clips are widely used during robot-assisted and laparoscopic radical prostatectomy to control the lateral pedicles. There are a few reports of hem-o-lok clip migration into the bladder or vesico-urethral anastomosis and only four cases of hem-o-lok clip migration resulting into bladder neck contracture. Herein, we describe the first case, to our knowledge, of hem-o-lok clip migration leading to severe bladder neck contracture and subsequent stress urinary incontinence.
Case presentation
A 62-year-old Caucasian man underwent robot-assisted laparoscopic radical prostatectomy for a T1c Gleason 8 prostate cancer. One month after surgery the patient was fully continent; however, three months later, he presented with acute urinary retention requiring suprapubic drainage. Urethroscopy showed a hem-o-lok clip strongly attached to the area between the vesico-urethral anastomosis and the urethral sphincter and a severe bladder neck contracture behind it. Following cold-knife urethral incision and clip removal, the bladder neck contracture was widely resected. At 3-month follow-up, the patient voided spontaneously with a peak flow rate of 9.5 ml/sec and absence of post-void residual urine, but leaked 240 ml urine at the 24-hour pad test. To date, at 1-year follow-up, his voiding situation remains unchanged.
The present report provides further evidence for the risk of hem-o-lok clip migration causing bladder neck contracture, and is the first to demonstrate the potential of such complication to result into stress urinary incontinence.
PMCID: PMC3938024  PMID: 24555468
Laparoscopy; Complications; Prostatectomy; Foreign body
9.  Sixteen years post radiotherapy of nasopharyngeal carcinoma elicited multi-dysfunction along PTX and chronic kidney disease with microcytic anemia 
BMC Urology  2014;14:19.
The hypothalamic–pituitary (h-p) unit is a particularly radiosensitive region in the central nervous system. As a consequence, radiation-induced irreversible, progressively chronic onset hypopituitarism (RIH) commonly develops after radiation treatments and can result in variably impaired pituitary function, which is frequently associated with increased morbidity and mortality.
Case presentation
A 38-year-old male subject, previously having received radiotherapy for treatment of nasopharygeal carcinoma (NPCA) 16 years ago, appeared at OPD complaining about his failure in penile erection, loss of pubic hair, atrophy of external genitalia: testicles reduced to 2×1.5 cm; penile size shrunk to only 4 cm long. Characteristically, he showed extremely lowered human growth hormone, (HGH, 0.115 ng/mL), testosterone (<0.1 ng/mL), total thyroxine (tT4: 4.740 g/mL), free T4 (fT4, 0.410 ng/mL), cortisol (2.34 g/dL); lowered LH (1.37 mIU/mL) and estradiol (22 pg/mL); highly elevated TSH (7.12 IU/mL). As contrast, he had low end normal ACTH, FSH, total T3, free T3, and estriol; high end normal prolactin (11.71 ng/mL), distinctly implicating hypopituitarism-induced hypothyroidism and hypogonadism. serologically, he showed severely lowered Hb (10.6 g/dL), HCT (32.7%), MCV (77.6 fL), MCH (25.3 pg), MCHC (32.6 g/dL), and platelet count (139×103/L) with extraordinarily elevated RDW (18.2%), together with severely lowered ferritin (23.6 ng/mL) and serum iron levels; highly elevated total iron binding capacity (TIBC, 509 g/dL) and transferrin (363.4 mg/dL), suggesting microcytic anemia. Severely reduced estimated glomerular filtration rate (e-GFR) (89 mL/mim/1.73 m2) pointed to CKD2. Hypocortisolemia with hyponatremia indicated secondary adrenal insufficiency. Replacement therapy using androgen, cortisol, and Ringer’s solution has shown beneficial in improving life quality.
To our believe, we are the first group who report such complicate PTX dysfunction with adrenal cortisol insufficiency concomitantly occurring in a single patient.
PMCID: PMC3931662  PMID: 24520983
Radiotherapy; Hypopituitarism; Hypothyroidism; Hypogonadism; Adrenal insufficiency; Chronic kidney disease; Microcytic anemia
10.  Comparison of surgical technique (Open vs. Laparoscopic) on pathological and long term functional outcomes following radical prostatectomy 
BMC Urology  2014;14:18.
Few studies to date have directly compared outcomes of retropubic (RRP) and laparoscopic (LRP) radical prostatectomy. We investigated a single institution experience with RRP and LRP with respect to functional and pathological outcomes.
168 patients who underwent RRP were compared to 171 patients who underwent LRP at our institution. Pathological and functional outcomes including postoperative urinary incontinence and erectile dysfunction (ED) of the two cohorts were examined.
Patients had bilateral, unilateral and no nerve sparing technique performed in 83.3%, 1.8% and 14.9% of cases for RRP and 23.4%, 22.8% and 53.8% of cases for LRP, respectively (p < 0.001). Overall positive surgical margin rates were 22.2% among patients who underwent RRP compared to 26.5% of patients who underwent LRP (p = 0.435). Based upon pads/day, urinary continence postoperatively was achieved in 83.2% and 82.8% for RRP and LRP, respectively (p = 0.872). Analysis on postoperative ED was limited due to lack of information on the preoperative erectile status. However, postoperatively there were no differences with respect to ED between the two cohorts (p = 0.151). Based on ICIQ-scores, surgeons with more experience had lower rates of postoperative incontinence irrespective of surgical technique (p = 0.001 and p < 0.001 for continuous and stratified data, respectively).
RRP and LRP represent effective surgical approaches for the treatment of clinically localized prostate cancer. Pathological outcomes are excellent for both surgical techniques. Functional outcomes including postoperative urinary incontinence and ED are comparable between the cohorts. Surgeon experience is more relevant than surgical technique applied.
PMCID: PMC3922887  PMID: 24506815
Prostate cancer; Erectile dysfunction; Incontinence; Radical prostatectomy; Laparoscopic prostatectomy
11.  Targeting HOX transcription factors in prostate cancer 
BMC Urology  2014;14:17.
The HOX genes are a family of transcription factors that help to determine cell and tissue identity during early development, and which are also over-expressed in a number of malignancies where they have been shown to promote cell proliferation and survival. The purpose of this study was to evaluate the expression of HOX genes in prostate cancer and to establish whether prostate cancer cells are sensitive to killing by HXR9, an inhibitor of HOX function.
HOX function was inhibited using the HXR9 peptide. HOX gene expression was assessed by RNA extraction from cells or tissues followed by quantitative PCR, and siRNA was used to block the expression of the HOX target gene, cFos. In vivo modelling involved a mouse flank tumour induced by inoculation with LNCaP cells.
In this study we show that the expression of HOX genes in prostate tumours is greatly increased with respect to normal prostate tissue. Targeting the interaction between HOX proteins and their PBX cofactor induces apoptosis in the prostate cancer derived cell lines PC3, DU145 and LNCaP, through a mechanism that involves a rapid increase in the expression of cFos, an oncogenic transcription factor. Furthermore, disrupting HOX/PBX binding using the HXR9 antagonist blocks the growth of LNCaP tumours in a xenograft model over an extended period.
Many HOX genes are highly over-expressed in prostate cancer, and prostate cancer cells are sensitive to killing by HXR9 both in vitro and in vivo. The HOX genes are therefore a potential therapeutic target in prostate cancer.
PMCID: PMC3942264  PMID: 24499138
Prostate cancer; HXR9; HOX; PBX
12.  Retroperitoneal laparoscopic technique in treatment of complex renal stones: 75 cases 
BMC Urology  2014;14:16.
In most hospitals, several options for the management of renal stones are available: shockwave lithotripsy, endourologic treatment, or surgery. Choice of treatment is based on the anatomic characteristics of the patient, and the location and size of the stones. In this study we assessed a retroperitoneal laparoscopic technique for treatment of complex renal stones.
Seventy-five patients, including 53 men and 22 women with a mean age of 47.8 years (range 18–74 y), underwent retroperitoneal laparoscopy for the treatment of complex renal stones between July 2006 and November 2012 in our hospital.
The retroperitoneal laparoscopic procedures for treatment of complex renal stones were completely successful in 73 cases, while 2 cases converted to open surgery. The operative time was 85–190 min with a mean of 96 min. The estimated blood lost was 20–400 mL with a mean of 80 mL. After the operation 7 patients experienced urinary leakage. Ultrasonography, x-ray of the kidney, ureter and bladder, and intravenous urography were reviewed at post-procedural follow-up at 6–82 months. No hydronephrosis aggravation was found, and there was no calculus recurrence.
The merits of retroperitoneal laparoscopy for the treatment of complex renal stones include sparing the nephron, less bleeding, short hospitalization, quick postoperative recovery, and controllable procedure after training Success depends on the experience of surgeons and judicious selection of cases.
PMCID: PMC3918106  PMID: 24491207
Retroperitoneal laparoscopic technique; Complex renal stones; Ureteroscope; Treatment
13.  ANKS1B is a smoking-related molecular alteration in clear cell renal cell carcinoma 
BMC Urology  2014;14:14.
An association between cigarette smoking and increased risk of clear cell renal cell carcinoma (ccRCC) has been established; however, there are limited data regarding the molecular mechanisms that underlie this association. We used a multi-stage design to identify and validate genes that are associated with smoking-related ccRCC.
We first conducted a microarray study to compare gene expression patterns in patient-matched ccRCC and normal kidney tissues between patients with (n = 23) and without (n = 42) a history of smoking. Analyses were first stratified on obesity status (the other primary risk factor for ccRCC) and then combined and analyzed together. To identify genes where the fold change in smokers relative to non-smokers was different in tumor tissues in comparison to patient-matched normal kidney tissues, we identified Affymetrix probesets that had a significant tissue type-by-smoking status interaction pvalue. We then performed RT-PCR validation on the top eight candidate genes in an independent sample of 28 smokers and 54 non-smokers.
We identified 15 probesets that mapped to eight genes that had candidate associations with smoking-related ccRCC: ANKS1B, ACOT6, PPWD1, EYS, LIMCH1, CHRNA6, MT1G, and ZNF600. Using RT-PCR, we validated that expression of ANKS1B is preferentially down-regulated in smoking-related ccRCC.
We provide the first evidence that ANKS1B expression is down regulated in ccRCC tumors relative to patient-matched normal kidney tissue in smokers. Thus, ANKS1B should be explored further as a novel avenue for early detection as well as prevention of ccRCC in smokers.
PMCID: PMC3944917  PMID: 24479813
14.  Long-term results of radical prostatectomy with immediate adjuvant androgen deprivation therapy for pT3N0 prostate cancer 
BMC Urology  2014;14:13.
Radical prostatectomy is used to treat patients with clinically localized prostate cancer, but there have been few reports of its use in locally advanced disease. We evaluated the long-term results of radical prostatectomy and immediate adjuvant androgen deprivation therapy in Japanese patients with pT3N0M0 prostate cancer.
We retrospectively reviewed 128 patients with pT3N0M0 prostate cancer who underwent radical prostatectomy at our institute from 2000 to 2006. All pT3N0 patients were treated with adjuvant androgen deprivation therapy shortly after radical prostatectomy. Immediate adjuvant androgen deprivation therapy was continued for at least 5 years. Twenty-three were excluded because of preoperative hormonal therapy, missing data, or others. Death from any cause, death from prostate cancer, clinical recurrence and hormone-refractory biochemical progression were analyzed by Kaplan-Meier graphs. Relative risks of progression were estimated using Cox proportional hazards models with 95% confidence intervals.
The 10-year hormone-refractory biochemical progression-free survival rate was 88.3% and the cancer-specific survival rate was 96.3% after a median follow-up period of 8.2 years (range 25.6-155.6 months). Higher clinical stage (p = 0.013), higher Gleason score at biopsy (p = 0.001), seminal vesicle invasion (p = 0.003) and microlymphatic invasion (p = 0.006) were predictive factors for hormone-refractory biochemical progression by univariate analyses. Multivariate analyses identified Gleason score at biopsy (p = 0.027) and seminal vesicle invasion (p = 0.030) as independent prognostic factors for hormone-refractory biochemical progression. None of the patients with clinical T1 cancers (n = 20), negative surgical margin (n = 12), or negative perineural invasion (n = 11) experienced hormone-refractory biochemical progression.
Radical prostatectomy with immediate adjuvant androgen deprivation therapy may be a valid treatment option for patients with pT3N0M0 prostate cancer.
PMCID: PMC3912934  PMID: 24476554
Adjuvant androgen deprivation therapy; Pathological T3; Prognosis; Prognostic factor; Prostate cancer; Radical prostatectomy
15.  Targeting CXCR4 with CTCE-9908 inhibits prostate tumor metastasis 
BMC Urology  2014;14:12.
CXCL12/CXCR4 transactivation of epidermal growth factor family receptors in lipid raft membrane microdomains on cell surface is thought to mediate tumor growth and subsequent development of metastatic disease. CTCE-9908 is a known inhibitor of CXCR4. Herein, we tested the efficacy of CTCE-9908 in inhibiting prostate cancer cell growth, invasion, and metastasis.
We used a panel of in vitro assays utilizing human prostate cancer cell lines and an in vivo orthotopic prostate cancer model to assess the anti-tumoral activity of CTCE-9908.
We demonstrated that (a) CTCE-9908 treatment resulted in no significant change in the growth of PC-3 and C4-2B cells; (b) 50 μg/ml of CTCE-9908 inhibited the invasive properties of PC-3 cells; (c) 25 mg/kg of CTCE-9908 did not alter primary tumor growth but it did significantly reduce total tumor burden in the animal including the growth of prostate and soft tissue metastases to lymph node and distant organ tissues. Histological analysis showed that CTCE-9908 treatment resulted in tumor necrosis in primary prostate tumors and no significant change in proliferation of tumor cells as measured by Ki-67 staining; (d) CTCE-9908 inhibited the tumor angiogenesis as measured by CD34 positive vessels in tumors.
These data suggest that CXCR4 inhibition by CTCE-9908 decreases the invasion potential in vitro, which then translated to a reduction of tumor spread with associated reduction in angiogenesis. Hence, CTCE-9908 may prove to be an efficacious novel agent to prevent and treat the spread of metastatic prostate cancer.
PMCID: PMC3912255  PMID: 24472670
CTCE-9908; CXCR4; CXCL12; Chemoinvasion and prostate cancer progression
16.  Treatment efficacy and tolerability of intravesical Bacillus Calmette-Guerin (BCG) - RIVM strain: induction and maintenance protocol in high grade and recurrent low grade non-muscle invasive bladder cancer (NMIBC) 
BMC Urology  2014;14:11.
BCG-RIVM strain was used in many treatment protocols for non-muscle invasive bladder cancer only as induction courses. Cho et al. (Anticancer Res 2012) compared BCG-RIVM induction and 'standard' maintenance (Lamm et al., J Urol. 2000) to mitomycin C. They found no statistically significant differences regarding disease recurrence and progression. The purpose of our study was to determine the efficacy & tolerability of this specific BCG RIVM strain, using six-weekly, induction course and single monthly instillations as maintenance for one year, in high risk recurrent, multifocal low grade and multifocal high grade pTa/pT1, CIS transitional cell carcinoma of bladder.
From 2003 - 2012, BCG-naive patients treated with intravesical BCG-RIVM for high-risk multifocal NMIBC were identified. Transurethral resection of bladder tumor (TURBT) and re-staging TURBT within six weeks, was done for accurate staging and complete elimination of disease. A six-weekly induction course, started 2-3 weeks after the last TURBT, followed by monthly maintenance protocol for one year. Recurrence, progression, cystectomy free survivals, cancer specific and over-all survival were determined.
Sixty evaluable patients - median age 63, median follow-up 3.98 years. Forty-two patients (70%) completed BCG-RIVM treatment as planned. BCG termination was necessary in 18 patients (30%). Recurrence occurred in 16 patients (26.7%) at a median follow-up of 24.2 months while progression occurred in five patients (8.3%) at a median follow-up of 33 months. Recurrence-free survival and progression-free survival rates were 73% and 92% respectively. Cystectomy was performed in seven patients (12%) with a cystectomy-free survival of 88%. There were no cancer specific deaths. Two patients died of other causes (3.3%). The overall survival rate was 97%.
Our study is the first to show the clinical efficacy and tolerability of BCG-RIVM strain in the management of high risk NMIBC when given in a schedule of six-weekly induction with monthly maintenance for one year. Our maintenance protocol, achieved equivalent recurrence-free, progression-free, disease specific survival and overall survival to the reported literature and the more intense three-years South West Oncology Group (SWOG) protocol.
PMCID: PMC3909512  PMID: 24468269
Bladder cancer; BCG-RIVM; Intravesical; Maintenance
17.  Intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic prostate cancer: a systematic review and meta-analysis 
BMC Urology  2014;14:9.
Prostate cancer is the most common cancer in older men in the United States (USA) and Western Europe. Androgen deprivation (AD) constitutes, in most cases, the first-line of treatment for these cases. The negative impact of CAD in quality of life, secondary to the adverse events of sustained hormone deprivation, plus the costs of this therapy, motivated the intermittent treatment approach. The objective of this study is to to perform a systematic review and meta-analysis of all randomized controlled trials that compared the efficacy and adverse events profile of intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic hormone-sensitive prostate cancer.
Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The endpoints were overall survival (OS), cancer-specific survival (CSS), time to progression (TTP) and adverse events. We performed a meta-analysis (MA) of the published data. The results were expressed as Hazard Ratio (HR) or Risk Ratio (RR), with their corresponding 95% Confidence Intervals (CI 95%).
The final analysis included 13 trials comprising 6,419 patients with hormone-sensitive prostate cancer. TTP was similar in patients who received intermittent androgen deprivation (IAD) or continuous androgen deprivation (CAD) (fixed effect: HR = 1.04; CI 95% = 0.96 to 1.14; p = 0.3). OS and CSS were also similar in patients treated with IAD or CAD (OS: fixed effect: HR = 1.02; CI 95% = 0.95 to 1.09; p = 0.56 and CSS: fixed effect: HR = 1.06; CI 95% = 0.96 to 1.18; p = 0.26).
Overall survival was similar between IAD and CAD in patients with locally advanced, recurrent or metastatic hormone-sensitive prostate cancer. Data on CSS are weak and the benefits of IAD on this outcome remain uncertain. Impact in QoL was similar for both groups, however, sexual activity scores were higher and the incidence of hot flushes was lower in patients treated with IAD.
PMCID: PMC3913526  PMID: 24460605
Androgen deprivation; Prostate cancer; Systematic review
18.  Pathology of bladder cancer among diabetic patients undergoing radical cystectomy with a history of pioglitazone (Actos) use 
BMC Urology  2014;14:10.
Prospective studies suggested an association between pioglitazone (Actos) use and the development of bladder cancer. Cancer pathology among pioglitazone users has not been characterized. We chose to compare the surgical pathology among diabetic users and non-users, as well as non-diabetic patients who underwent radical cystectomy for bladder cancer.
Our single-center, prospectively-maintained bladder cancer database was reviewed. Patient demographics, surgical pathology, and outcomes were evaluated. Information regarding diabetic history and use of pioglitazone was determined from chart analysis and patient interview.
From April 2005 to October 2011, 204 patients undergoing radical cystectomy were identified. Of these, 33 (16.2%) were diabetic and 171 (83.8%) had no history of diabetes. Among diabetic patients, 9 (27.3%) had a history of pioglitazone use. Median duration of therapy was 14 (6–120) months. Pathology in non-diabetic patients was T1 in 17 (9.9%), T2 in 38 (22.2%), T3 in 44 (25.7%), and T4 in 31 (18.1%). Pathology among diabetic non-users was T1 in 1 (4.2%), T2 in 7 (29.2%), T3 in 7 (29.2%), and T4 in 4 (16.7%). Pathologic stage among diabetic users was T1 in 1 (11.1%), T2 in 3 (33.3%), T3 in 3 (33.3%), and T4 in 1 (11.1%). Lymph node involvement in non-diabetics, diabetic non-users, and diabetic users was 25.7%, 33.3%, and 33.3%, respectively. Cancer-specific death was seen in 60.3% of non-diabetics, 58.3% of diabetic non-users, and 75% of diabetic users.
Diabetics have similar stage distribution regardless of pioglitazone use. Lymph node metastases rates and cancer specific death were similar across all groups. Additional studies will serve to better characterize this relationship.
PMCID: PMC3937152  PMID: 24461081
Pioglitazone; Bladder cancer; Diabetes; Tumor stage
19.  A prostate biopsy strategy based on a new clinical nomogram reduces the number of biopsy cores required in high-risk patients 
BMC Urology  2014;14:8.
The nomograms used for prostate cancer risk assessment in Western countries are not directly applicable to Chinese males; consequently, we have developed a new model to evaluate the risk of them developing this disease.
A total of 1104 patients who had undergone trans-rectal ultrasound (TRUS)-guided 12 + 1-core prostate biopsy were retrospectively evaluated in the first stage of the study. Age, prostate-specific antigen (PSA), the free/total PSA ratio (f/t), digital rectal examination (DRE) findings, the presence of a hypoechoic mass revealed using ultrasound, ultrasonic detection of microcalcifications, prostate volume (PV) and PSA density were considered as predictive factors. Multiple logistic regression analysis involving a backward elimination selection procedure was used to select independent predictors. We compared positive rates regarding 6-core and 12-core biopsy schemes at different risk levels. In the second stage of the study, 238 cases were evaluated using our nomogram. In higher risk patients, we employed a 6 + 1 core biopsy. Positive rates in the first and second stages of the study were compared.
Age, the baseline median natural logarithm of PSA (Ln[PSA]), Ln(PV), f/t, rate of abnormal DRE findings and rate of hypoechoic masses detected using TRUS were the factors that were finally submitted into our nomogram. A significantly greater area under the receiver-operating characteristic curve was obtained for the nomogram than for PSA level alone (0.853 vs. 0.761). A cancer probability cutoff value of 0.5 suggested no significant difference between the 6-core and 12-core biopsy schemes at higher risk levels. In the second stage of the study we verified that in patients with a cancer probability cutoff value >0.5, a 6 + 1-core biopsy could be used without a reduction in the positive detection rate, and significantly reducing the number of biopsy cores required.
A nomogram based on data from Chinese males was developed to predict the positive detection rate, ratio of positive cores and Gleason score at each risk level. According to this nomogram, a reasonable biopsy strategy could be constituted to reduce the number of biopsy cores required in subjects at high risk.
PMCID: PMC3893548  PMID: 24410803
Prostate cancer; Biopsy; Nomogram; Diagnosis
20.  Impact of prostate weight on perioperative outcomes of robot-assisted laparoscopic prostatectomy with a posterior approach to the seminal vesicle 
BMC Urology  2014;14:6.
To determine the effect of prostate weight on the preoperative and postoperative outcomes of robotic-assisted laparoscopic radical prostatectomy with a posterior approach to the seminal vesicle.
This retrospective study examined prospectively collected data on 219 robotic-assisted laparoscopic radical prostatectomies performed from May 2011 to February 2013. Patients were divided into four groups based on pathologic prostate weight: <30 g, 30–49 g, 50–79 g, and ≥80 g. Continence and sexual function were assessed using validated questionnaires.
Of the 219 patients, 19, 143, 51, and 6 had prostates weighing <30 g, 30–49 g, 50–79 g, and ≥80 g, respectively. Significant differences were found between the preoperative Gleason scores, total operative times, and robotic times of the groups. Both estimated blood loss and anastomosis time tended to be greater in the higher prostate weight groups, but the differences were not significant. No significant differences were observed in transfusion rate, length of catheterization, complication incidence, or positive surgical margins. The return of urinary function, as determined by questionnaire scores, was not affected by prostate weight.
Robotic-assisted laparoscopic radical prostatectomy can be performed safely and with similar perioperative outcomes, regardless of prostate weight. Indeed, oncological outcome, urinary continence, and complications were similar across the prostate weight groups, suggesting that robotic-assisted laparoscopic radical prostatectomy with a posterior approach to the seminal vesicle may be performed effectively on men with large prostates, despite greater surgical times.
PMCID: PMC3909347  PMID: 24400644
Median lobe; Prostate cancer; Radical prostatectomy; Robot-assisted surgery
21.  Long term follow-up in patients with initially diagnosed low grade Ta non-muscle invasive bladder tumors: tumor recurrence and worsening progression 
BMC Urology  2014;14:5.
We evaluated the clinical outcome of low grade Ta bladder cancer followed-up for a long period using the 2004 WHO grading system.
We retrospectively reviewed 190 patients with primary, low grade Ta bladder cancer. We defined worsening progression (WP) as confirmed high grade Ta, all T1 or Tis/concomitant CIS of bladder recurrence, upper urinary tract recurrence (UTR), or progression to equal to or more than T2. The associations between clinicopathological factors and tumor recurrence as well as WP pattern were analyzed. We also evaluated the late recurrence of 76 patients who were tumor-free for more than 5 years.
Tumor recurrence and WP occurred in 82 (43.2%) and 21 (11.1%) patients during follow-up (median follow-up: 101.5 months), respectively. WP to high grade Ta, all T1 or Tis/concomitant CIS was seen in 17 patients, and UTR and progression to equal to or more than T2 were seen in 2 and 2 patients, respectively. Multivariate analyses demonstrated that multiple tumor (p < 0.001, HR: 2.97) and absence of intravesical instillation (IVI) (p < 0.001, HR: 2.88) were significant risk factors for tumor recurrence while multiple tumor was the only risk factor for WP (p = 0.001, HR: 5.26). After a 5-year tumor-free period, 9 patients experienced late recurrence in years 5 and 10 and were diagnosed at a follow-up cystoscopy, however, only 2 patients recurred beyond 10 years and were found by gross hematuria. There were no significant risk factors of late recurrence.
Multiple tumor was a risk factor for both tumor recurrence and WP while IVI did not affect the occurrence of WP. Our results suggest that routine follow-up of patients with low grade Ta bladder cancer is needed up to 10 years from the initial diagnosis.
PMCID: PMC3913327  PMID: 24400640
Bladder cancer; Intravesical instillation; Recurrence; Progression
22.  Association between the hemodialysis adequacy and sexual dysfunction in chronic renal failure: a preliminary study 
BMC Urology  2014;14:4.
The core question of the study was whether adequately achieved HD affected the sexual dysfunction in women on hemodialysis (HD) with chronic renal failure (CRF).
Thirty-seven female patients on HD, including 18 women with adequate HD and 19 women with non-adequate HD, and 36 healthy controls were included in this study. Demographic and clinical variables, including the sexual hormones estradiol and testosterone, were recorded. Sexual function was assessed according to the Female Sexual Function Index (FSFI) and results were compared between groups. Adequate HD was defined as an average urea clearance of over 1.3 (Kt/V) over three consecutive months.
All domains of the FSFI questionnaire, with the exception of satisfaction, were higher in the control group than in the HD group. In comparing the adequate and non-adequate HD groups, there was no difference in any of the six domains of the FSDI questionnaire. Among the clinical variables, the number of menopausal women was higher in the HD group than in the control group (P = 0.023). Estradiol and testosterone levels were higher in the control group than in the HD group (P = 0.003, 0.027, respectively). The number of menopausal women and estradiol and testosterone levels showed no differences between the adequate and non-adequate HD groups. Correlation analysis between Kt/V and FSFI showed no significant relationship, but estrogen did show a significant relationship with FSFI (correlation coefficient = 0.399, P = 0.001).
HD adequacy alone does not have a significant impact on sexual dysfunction. Other treatments options should be considered to treat sexual dysfunction in women with CRF.
PMCID: PMC3925321  PMID: 24401120
Hemodialysis; Hemodialysis adequacy; Urea clearance; Female; Sexual dysfunction
23.  Functional aspects of silent ureteral stones investigated with MAG-3 renal scintigraphy 
BMC Urology  2014;14:3.
To investigate functional aspects of silent ureteral stones with special focus on obstruction and its relationship to renal anatomy. The present study is the first investigation of renal excretory function in patients with silent ureteral stones.
Patients with primarily asymptomatic ureteral stones underwent a mercapto-acetyltriglycine (MAG-3) renal scintigraphy prior to treatment, in addition to anatomic evaluation of renal units and serum creatinine levels. The primary outcome measure was the presence or absence of obstruction. Secondary outcome measures were kidney anatomy, grade of hydronephrosis, location of stones, stone size, and serum creatinine levels.
During a ten-year period, 14 patients (median age 52.6 years; range 37.3 to 80.7 years) were included in the study. The relative frequency of primarily asymptomatic ureteral stones among all patients treated for ureteral stones in the study period was 0.7%. Eleven renal units showed some degree of hydronephrosis while 3 kidneys were not dilated. On the MAG-3 scan, 7 patients had an obstruction of the ureter, 5 had no obstruction, and 2 had dysfunction of the kidney. A statistically significant correlation was established between the grade of obstruction and stone size (p = 0.02).
At the time of presentation, only 64.3% of the patients revealed an obstruction in the stone-bearing renal unit. The degree of hydronephrosis and renal function were very diverse in this subgroup of patients with ureteral stones. The onset of ureterolithiasis and the chronological sequence of obstruction remain unclear in patients who have never experienced symptoms due to their stones.
PMCID: PMC3909333  PMID: 24397735
Mercaptoacetyltriglycine; Scintigraphy; Stone disease; Urolithiasis; Ureter; Asymptomatic; Obstruction
24.  Cyclooxygenase-2 and B-cell lymphoma-2 expression in cystitis glandularis and primary vesicle adenocarcinoma 
BMC Urology  2014;14:2.
Although cystitis glandularis (CG) is a common benign urinary bladder epithelial abnormality, it remains unclear whether CG is a premalignant lesion. Cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) overexpression has recently been reported as a potential tumor initiator or promoter. We evaluated and compared COX-2 and Bcl-2 expression in CG, chronic cystitis (CC), and primary vesicle adenocarcinoma (ADC) tissues.
We conducted a retrospective study to investigate COX-2 and Bcl-2 levels in CG and ADC. We obtained tissue samples from 75 patients (including 11 cases of CC, 30 typical cases of CG (CGTP), 30 cases of intestinal CG (CGIT), and 4 cases of ADC) between 1989 and 2009 from the Surgical Pathology Archives of the No. 2 People’s Hospital of Zhenjiang, affiliated with Jiangsu University. COX-2 and Bcl-2 immunohistochemical staining was performed on all tissues. Nine normal bladder epithelial specimens were evaluated as control samples. Correlations between COX-2 and Bcl-2 expression in CG were also analyzed.
COX-2 and Bcl-2 expression was higher in the ADC group compared to other groups (p < 0.05). COX-2 and Bcl-2 levels were higher in the CGIT group compared to the CGTP group (p = 0.000 for both). The CGIT and CGTP groups both showed higher COX-2 expression compared to the CC group (p = 0.000 for both). There was no difference in Bcl-2 expression between the CGTP and CC groups (p = 0.452). Additionally, the difference in COX-2 and Bcl-2 expression between the control and CC groups was also insignificant (p = 0.668 and p = 0.097, respectively). Finally, we found that COX-2 and Bcl-2 levels were positively related (r = 0.648, p = 0.000).
COX-2 and Bcl-2 overexpression in the CG group suggests that CG, particularly the intestinal type, may be a premalignant lesion that converts into a tumor in the presence of carcinogens.
PMCID: PMC3880845  PMID: 24387269
Cyclooxygenase-2; Bcl-2; Cystitis
25.  The postoperative morbidity index: a quantitative weighing of postoperative complications applied to urological procedures 
BMC Urology  2014;14:1.
The reporting of post-operative complications in the urological field is lacking of a uniform quantitative measure to assess severity, which is essential in the analysis of surgical outcomes. The purpose of this study was to evaluate the feasibility of estimating quantitative severity weighing of post-operative complications after common urologic procedures.
Using a large healthcare system’s quality database, complications were identified in eleven common urologic procedures (e.g., insertion or replacement of inflatable penile prosthesis, nephroureterectomy, partial nephrectomy, percutaneous nephrostomy tube placement, radical cystectomy, radical prostatectomy, renal/ureteral/bladder extracorporeal shockwave lithotripsy (ESWL), transurethral destruction of bladder lesion, transurethral prostatectomy, transurethral removal of ureteral obstruction, and ureteral catheterization) from January 1, 2011 to December 31, 2011. Complications were classified by the Expanded Accordion Severity Grading System, which was then quantified by validated severity weighting scores. The Postoperative Morbidity Index (PMI) for each procedure was calculated where an index of 0 would indicate no complication in any patient and an index of 1 would indicate that all patients died.
This study included 654 procedures of which 148 (22%) had one or more complications. As would be expected, a more complex procedure like radical cystectomy possessed a higher PMI (0.267), while a simpler procedure like percutaneous nephrostomy tube placement possessed a lower PMI (0.011). The PMI of the additional nine procedures fell within the range of these PMIs. These PMIs could be used to compare surgeons, hospitals or procedures.
Quantitative severity weighing of post-operative complications for urologic procedures is feasible and may provide exceptionally informative data related to outcomes.
PMCID: PMC3893398  PMID: 24383457
Complication; Index; Postoperative; Quantitative; Urology

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