Expressions of glucose transporter genes are diversely attenuated and significantly associated with prostate cancer progression.

Prostate cancer is a health-threaten disease in men worldwide, however, lacking is the reliable biomarkers for patient management. Aberrant metabolic events including glucose metabolism are involved in prostate cancer progression. To examine the involvement of glucose metabolic pathways in prostate cancer, we analyzed the expression profiles of glucose transporter family genes using multiple RNA-seq datasets. Our results showed that three SLC2A family genes (SLC2A4/5/9) were significantly downregulated in primary prostate cancers compared to their benign compartments. These down-regulated expressions were inversely correlated with their gene promoter methylation and genome abnormalities. Among these three SLC2A genes, only SLC2A4 showed a significantly reverse correlation with all clinicopathological parameters, including TNM stage, disease relapse, Gleason score, disease-specific survival, and progression-free interval. In addition, the expression levels of these three genes were strongly correlated with anti-cancer immune cell filtration in primary prostate cancers. In a group of patients with early-onset prostate cancers, SLC2A4 also showed a strong negative correlation with multiple clinicopathological parameters, such as tumor mutation burden, biochemical relapse, pre-surgical PSA levels, and Gleason score but a positive correlation with progression-free interval after surgery. In metastatic castration-resistant prostate cancers (CRPC), SLC2A9 gene expression but not SLC2A4 or SLC2A5 genes showed a significant correlation with androgen receptor (AR) activity score and neuroendocrinal (NE) activity score. Meanwhile, SLC2A2/9/13 expression was significantly elevated in CRPC tumors with neuroendocrinal features compared to those without NE features. On the other hand, SLC2A10 and SlC2A12 gene expression were significantly reduced in NEPC tumors compared to CRPC tumors. Consistently, SLC2A10/12 expression levels were significantly reduced in castrated animals carrying the LuCaP35 xenograft models. Survival outcome analysis revealed that SLC2A4 expression in primary tumors is a favorable prognostic factor and SLC2A6 is a worse prognostic factor for disease-specific survival and progression-free survival in prostate cancer patients. In conclusion, our results suggest that SLC2A4/6 expressions are strong prognostic factors for prostate cancer progression and survival. The significance of SLC2A2/9/13 over-expression during NEPC progression needs more investigation.

High-Z-Sensitized Radiotherapy Synergizes with the Intervention of the Pentose Phosphate Pathway for In Situ Tumor Vaccination.

In situ tumor vaccination is preliminarily pursued to strengthen antitumor immune response. Immunogenic tumor cell death spontaneously releases abundant antigens and adjuvants for activation of dendritic cells, providing a paragon opportunity for establishing efficient in situ vaccination. Herein, Phy@PLGdH nanosheets are constructed by integrating physcion (Phy, an inhibitor of the pentose phosphate pathway (PPP)) with layered gadolinium hydroxide (PLGdH) nanosheets to boost radiation-therapy (RT)-induced immunogenic cell death (ICD) for potent in situ tumor vaccination. It is first observed that sheet-like PLGdH can present superior X-ray deposition and tumor penetrability, exhibiting improved radiosensitization in vitro and in vivo. Moreover, the destruction of cellular nicotinamide adenine dinucleotide phosphate (NADPH) and nucleotide homeostasis by Phy-mediated PPP intervention can further amplify PLGdH-sensitized RT-mediated oxidative stress and DNA damage, which correspondingly results in effective ICD and enhance the immunogenicity of irradiated tumor cells. Consequently, Phy@PLGdH-sensitized RT successfully primes robust CD8+ -T-cell-dependent antitumor immunity to potentiate checkpoint blockade immunotherapies against primary and metastatic tumors.

Hypermethylation of the SPARC promoter and its prognostic value for prostate cancer.

Secreted protein acidic and rich in cysteine (SPARC) is a secreted matricellular glycoprotein and plays a key role in the development of many tissues and organ types. However, the role of SPARC in prostate cancer (PCa) is still controversial. The aim of the present study was to investigate the abnormalities in the expression of SPARC and its promoter hypermethylation in prostate cancers and in correlated clinicopathological profiles. We examined the hypermethylation of the SPARC promoter as a potential mechanism for suppressing SPARC in PCa. The clinicopathological correlation between SPARC and its promoter expression and the prognostic significance of the aberrantly expressed genes were evaluated to identify novel biomarkers of PCa. SPARC expression was decreased in PCa cell lines, which correlated with hypermethylation of the SPARC promoter. Treatment with the demethylating agent 5-Aza-Cdr restored SPARC expression. Seventy percent (145 of 207) of the primary tumors exhibited SPARC hypermethylation, while only 2.6% was found in normal prostate mucosa (n=38). In PCa cases, SPARC hypermethylation was correlated with a poorer prognosis (P=0.005; relative risk 2.659, 95% CI, 1.433­4.562). Our findings revealed potential diagnostic markers of PCa based on specific hypermethylated CpG sites and also provided new insights of SPARC as a novel biomarker and/or treatment modality for prostate cancer.

Self-assembled albumin nanoparticles for combination therapy in prostate cancer.

Resistance to regular treatment strategies is a big challenge in the treatment of castration-resistant prostate cancer. Combination of photothermal and photodynamic therapy (PTT/PDT) with chemotherapy offers unique advantages over monotherapy alone. However, free drugs, such as photosensitizers and chemotherapeutic agents, lack tumor-targeted accumulation and can be easily eliminated from the body. Moreover, most of the PTT drugs are hydrophobic and their organic solvents have in vivo toxicity, thereby limiting their potential in clinical translation. Herein, simple multifunctional nanoparticles (NPs) using IR780 (a near-infrared dye) and docetaxel (DTX)-loaded nanoplatform based on human serum albumin (HSA) (HSA@IR780@DTX) was developed for targeted imaging and for PTT/PDT with chemotherapy for the treatment of castration-resistant prostate cancer treatment. In this platform, HSA is a biocompatible nanocarrier that binds to both DTX and IR780. DTX and IR780, as hydrophobic drug, can induce the self-assembly of HSA proteins. Transmission electron microscopic imaging showed that NPs formed by self-assembly are spherical with a smooth surface with a hydrodynamic diameter of 146.5±10.8 nm. The cytotoxicity of HSA@IR780@DTX NPs with or without laser irradiation in prostate cancer cells (22RV1) was determined via CCK-8 assay. The antitumor effect of HSA@IR780@DTX plus laser irradiation was better than either HSA@IR780@DTX without laser exposure or single PTT heating induced by HSA@IR780 NPs under near-infrared laser, suggesting a significant combined effect in comparison to monotherapy. Near-infrared fluorescence imaging showed that HSA@IR780@DTX NPs could preferentially accumulate in tumors. In vivo therapeutic efficacy experiment showed that xenografted prostate tumors on mice treated with HSA@IR780@DTX plus near-infrared laser irradiation were completely inhibited, whereas tumors on mice treated with chemotherapy alone (HSA@DTX and HSA@IR780@DTX without laser) or PTT/PDT alone (HSA@IR780 with laser) showed moderate growth inhibition. Overall, HSA@IR780@DTX NPs showed notable targeting and theranostic potential for the treatment of castration-resistant prostate cancer.

MiR-199a-3p suppresses proliferation and invasion of prostate cancer cells by targeting Smad1.

OBJECTIVES: This study was intended to analyze effects of miR-199a-3p and Smad1 on proliferation, migration and invasion of prostate cancer (PCa) cells. RESULTS: MiR-199a-3p was significantly decreased in PCa tissues in comparison to that in adjacent normal tissues (P < 0.05). Over-expressed miR-199a-3p markedly suppressed proliferation and invasion of PCa cells (P < 0.05). MiR-199a-3p was negatively correlated with Smad1 expression, and overexpression of Smad1 could antagonize the effects of miR-199a-3p on PCa cells. MATERIALS AND METHODS: The PCa tissues and their adjacent normal tissues were collected from 54 PCa patients. Expressions of miR-199a-3p and Smad1 mRNA in tissues and cells were evaluated with real-time quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry assay was used to detect Smad1 protein expressions. The target relationship between miR-199a-3p and Smad1 was assessed by luciferase reporter assay. The PCa cell lines (i.e. PC-3 cells) were transfected with miR-199a-3p mimics and Smad1-cDNA. MTT and Transwell assays were applied to detect proliferative, migratory and invasive abilities of PCa cells. CONCLUSIONS: MiR-199a-3p suppressed proliferation and invasion of PCa cells by targeting Smad1.

Transperineal cryotherapy for unresectable muscle invasive bladder cancer: preliminary experience with 7 male patients.

BACKGROUND: Radical cystectomy (RC) with pelvic lymph node dissection (PLND) and urinary diversion (UD) is considered the standard treatment for muscle invasive bladder cancer (MIBC). In a part of patients, RC procedure is aborted due to unresectable disease, other followed treatment like systemic chemotherapy, radiotherapy or cryotherapy may be a better option. The aim of present study was to report the preliminary results of transperineal cryotherapy for unresectable muscle invasive bladder cancer. METHODS: From January 2011 to August 2013, 7 male patients with pT4b unresectable bladder cancer underwent bilateral ureterocutaneostomy. Two performed a pelvic lymph node dissection (PLND). Then primary transperineal cryosurgery for preserved bladder at the guidance of transrectal ultrasound (TRUS) was performed. All patients underwent a dual freeze-thaw cycle using third-generation cryotechnology with ultrathin 17-gauge cryoneedles. Computer tomography (CT) and/or magnetic resonance image (MRI)were performed at 3 month intervals after cryosurgery to determine whether progression or recurrence occurred. RESULTS: All cryosurgery was performed successfully, mean operation time was 76.43 ± 25.12 min (range 50-120 min), mean blood loss was 19.29 ± 15.92 ml (range 5-50 ml). Mean hospital stay was 3.86 ± 1.68 day (range 2-7 days). No operative related deaths occurred. Four patients dead due to the metastasis disease at the follow up time of 8, 15, 18 and 37 months, respectively. Six patients received postoperative therapy, of whom 5 patients were treated with combined chemoradiation, and the other one received chemotherapy alone. The progression free survival (PFS) of the 7 patients was 22.00 ± 14.61 months (range 3-40 months). The one, two and three year overall survival (OS) was 85.7%, 57.1% and 42.9%, respectively. CONCLUSION: Our results suggest that cryosurgery combination with chemoradiotherapy provide a safe and effective alternative method for unresectable pT4b bladder cancer. Longer follow-up is necessary to determine the sustained efficacy.

Assessment of free-hand transperineal targeted prostate biopsy using multiparametric magnetic resonance imaging-transrectal ultrasound fusion in Chinese men with prior negative biopsy and elevated prostate-specific antigen.

BACKGROUND: To evaluate the role of free-hand transperineal targeted prostate biopsy using multiparametric magnetic resonance imaging-transrectal ultrasound (mpMRI-TRUS) fusion in Chinese men with repeated biopsy. METHODS: A total of 101 consecutive patients suspicious of prostate cancer (PCa) at the mpMRI scan and with prior negative biopsy and elevated PSA values were prospectively recruited at two urological centers. Suspicious areas on mpMRI were defined and graded using PI-RADS score. Targeted biopsies (TB) were performed for each suspicious lesion and followed a 12-core systematic biopsy (SB). Results of biopsy pathology and whole-gland pathology at prostatectomy were analyzed and compared between TB and SB. The risk for biopsy positivity was assessed by univariate and multivariate logistic regression analysis. RESULTS: Fusion biopsy revealed PCa in 41 of 101 men (40.6%) and 25 (24.8%) were clinically significant. There was exact agreement between TB and SB in 74 (73.3%) men. TB diagnosed 36% more significant cancer than SB (22 vs 13 cases, P = 0.012). When TB were combined with SB, an additional 14 cases (34.1%) of mostly significant PCa (71.4%) were diagnosed (P = 0.036). TB had greater sensitivity and accuracy for significant cancer than SB in 26 men with whole-gland pathology after prostatectomy. PI-RADS score on mpMRI was the most powerful predictor of PCa and significant cancer. CONCLUSIONS: Free-hand transperineal TB guided with MRI-TRUS fusion imaging improves detection of clinical significant PCa in Chinese men with previously negative biopsy. PI-RADS score is a reliable predictor of PCa and significant cancer.

Self-assembled tumor-targeting hyaluronic acid nanoparticles for photothermal ablation in orthotopic bladder cancer.

Bladder cancer is one of the most frequent malignancies in the urinary system. Radical cystectomy is inevitable when bladder cancer progresses to a muscle-invasive disease. However, cystectomy still causes a high risk of death and a low quality of life (such as ureter-abdomen ostomy, uroclepsia for ileal-colon neobladder). Therefore, more effective treatments as well as bladder preservation are needed. We developed self-assembled tumor-targeting hyaluronic acid-IR-780 nanoparticles for photothermal ablation in over-expressing CD44 (the receptor for HA) bladder cancer, which show high tumor selectivity, high treatment efficacy, good bioavailability, and excellent biocompatibility. The nanoparticles demonstrated a stable spherical nanostructure in aqueous conditions with good mono-dispersity, and their average size was 171.3±9.14nm. The nanoparticles can be degraded by hyaluronidase when it is over-expressed in bladder cells; therefore, they appear to have a hyaluronidase-responsive "OFF/ON" behavior of a fluorescence signal. HA-IR-780 NPs also showed high photothermal efficiency; 2.5, 5, 10 and 20µg/mL of NPs had a maximum temperature increase of 11.2±0.66°C, 18.6±0.75°C, 26.8±1.11°C and 32.3±1.42°C. The in vitro cell viability showed that MB-49 cells could be efficiently ablated by combining HA-IR-780 NPs with 808nm laser irradiation. Then, in vivo biodistribution showed the HA-IR-780 NPs are targeted for accumulation in bladder cancer cells but have negligible accumulation in normal bladder wall. The photothermal therapeutic efficacy of HA-IR-780 NPs in the orthotopic bladder cancer model showed tumors treated with NPs had a maximum temperature of 48.1±1.81°C after 6min of laser irradiation. The tumor volume was approximately 65-75mm3 prior to treatment. After 12days, the tumor sizes for the PBS, PBS plus laser irradiation and HA-IR-780 NPs-treated groups were 784.75mm3, 707.5mm3, and 711.37mm3, respectively. None of the tumors in the HA-IR-780 NPs plus laser irradiation-treated group were visible to the naked eye. A toxicity study showed HA-IR-780 NPs (2.5-20mg/kg, i.v.) were nontoxic and safe for in vivo applications. HA-IR-780 nanoparticles address current clinical challenges, treating locally aggressive lesions and preserving the bladder. They have enormous potential to improve the bladder cancer treatment strategies in clinic. STATEMENT OF SIGNIFICANCE: 1) Bladder cancer is one of the most frequent malignancies in the urinary system. Radical cystectomy is inevitable while bladder cancer progress to muscle-invasive disease. 2) We developed self-assembled tumor-targeting hyaluronic acid-IR-780 nanoparticles for photothermal ablation in over-expressing CD44 (the receptor for HA) bladder cancer. 3) Photothermal therapeutic efficacy of HA-IR-780 NPs in orthotopic bladder cancer model showed tumors were completely ablated. 4) HA-IR-780 nanoparticles address current clinical challenges, treating locally aggressive lesions as well as for bladder preservation.

Perineural invasion status, Gleason score and number of positive cores in biopsy pathology are predictors of positive surgical margin following laparoscopic radical prostatectomy.

This study was designed to define possible preoperative predictors of positive surgical margin after laparoscopic radical prostatectomy. We retrospectively analyzed the records of 296 patients with prostate cancer diagnosed by prostate biopsy, and eventually treated with laparoscopic radical prostatectomy. The prognostic impact of age, prostate volume, preoperative prostate-specific antigen, biopsy Gleason score, maximum percentage tumor per core, number of positive cores, biopsy perineural invasion, capsule invasion on imaging, and tumor laterality on surgical margin was assessed. The overall positive surgical margin rate was 29.1%. Gleason score, number of positive cores, perineural invasion, tumor laterality in the biopsy specimen, and prostate volume significantly correlated with risk of positive surgical margin by univariate analysis (P < 0.05). Gleason score (odds ratio [OR] = 2.286, 95% confidence interval [95% CI] = 1.431-3.653, P = 0.001), perineural invasion (OR = 4.961, 95% CI = 2.656-9.270, P < 0.001), and number of positive cores (OR = 4.403, 95% CI = 1.878-10.325, P = 0.001) were independent predictors of positive surgical margin at the multivariable logistic regression analysis. Patients with perineural invasion, higher biopsy Gleason scores and/or a large number of positive cores in biopsy pathology had more possibility of capsule invasion. The positive surgical margin rate in patients with capsule invasion (49.5%) was much higher than that with localized disease (17.8%). In contrast, prostate volume showed a protective effect against positive surgical margin (OR = 0.572, 95% CI = 0.346-0.945, P = 0.029). Gleason score, perineural invasion, and number of positive cores in the biopsy specimen were preoperative independent predictors of positive surgical margin after laparoscopic radical prostatectomy while prostate volume was a protective factor against positive surgical margin.

miR-138-5p contributes to cell proliferation and invasion by targeting Survivin in bladder cancer cells.

BACKGROUND: Survivin (encoded by the gene BIRC5) plays an important role in the carcinogenesis of bladder cancer. Identifying miRNAs that target Survivin in the setting of bladder cancer will help to develop Survivin-based therapies for bladder cancer. METHODS: The expression levels of miR-138-5p and Survivin protein were measured in 12 resected bladder cancer specimens. The correlation between miR-138-5p and Survivin was further examined by evaluating Survivin expression in human bladder cancer cell lines that either overexpressed or knocked down miR-138-5p. A luciferase reporter assay was performed to test the direct binding of miR-138-5p to the target gene BIRC5. We also investigated the biological role of miR-138-5p targeting to Survivin in bladder cancer cell lines both in vivo and in vitro. RESULTS: In this study, we found that the Survivin protein was either absent or weakly expressed in normal adjacent tissues and consistently up-regulated in bladder cancer tissues; however, the mRNA levels did not vary as much, suggesting that a post-transcriptional mechanism was involved. Because microRNAs are powerful post-transcriptional regulators of gene expression, we used bioinformatic analyses to search for microRNAs that could potentially target BIRC5 in the setting of bladder cancer. We identified 2 specific targeting sites for miR-138-5p in the 3' untranslated region (3'-UTR) of BIRC5. We further identified an inverse correlation between miR-138-5p and Survivin protein levels in bladder cancer tissue samples. By overexpressing or knocking down miR-138-5p in bladder cancer cells, we experimentally confirmed that miR-138-5p directly recognizes the 3'-UTR of the BIRC5 transcript and regulates Survivin expression. Furthermore, the biological consequences of the targeting of BIRC5 by miR-138-5p were examined in vitro via cell proliferation and invasion assays and in vivo using a mouse xenograft tumor model. We demonstrated that BIRC5 repression by miR-138-5p suppressed the proliferative and invasive characteristics of bladder cancer cells and that miR-138-5p exerted an anti-tumor effect by negatively regulating BIRC5 in a xenograft mouse model. CONCLUSIONS: Taken together, our findings provide the first clues regarding the role of miR-138-5p as a tumor suppressor in bladder cancer by inhibiting BIRC5 translation.

Comparison of the complications of traditional 12 cores transrectal prostate biopsy with image fusion guided transperineal prostate biopsy.

BACKGROUND: To compare the complications of traditional transrectal (TR) prostate biopsy and image fusion guided transperineal (TP) prostate biopsy in our center. METHODS: Two hundred and fourty-two patients who underwent prostate biopsy from August 2014 to January 2015were reviewed. Among them, 144 patients underwent systematic 12-core transrectal ultrasonography (TRUS) guided prostate biopsy (TR approach) while 98 patients underwent free-hand transperineal targeted biopsy with TRUS and multi-parameter magnetic resonance imaging (mpMRI) fusion images (TP approach). The complications of the two groups were presented and a simple statistical analysis was performed to compare the two groups. RESULTS: The cohort of our study include242 patients, including 144 patients underwent TR biopsies while 98 patients underwentTP biopsies. There was no significant difference of major complications, including sepsis, bleeding and other complication requiring admissionbetween the two groups (P > 0.05). The incidence rate of infection and rectal bleeding in TR was much higher than TP (p < 0.05), but the incidence rate of perineal swelling in TP was much higher than TR (p < 0.05). There were no significant differences of minor complications including hematuria, lower urinary tract symptoms (LUTS), dysuria, and acuteurinary retention between the two groups (p > 0.05). CONCLUSION: The present study supports the safety of both techniques. Free-handTP targeted prostate biopsy with real-time fusion imaging of mpMRI and TR ultrasound is a good approach for prostate biopsy.

Percutaneous radiofrequency ablation with contrast-enhanced ultrasonography for solitary and sporadic renal cell carcinoma in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: The aim of this study was to assess the functional and oncologic outcomes of percutaneous radiofrequency ablation (RFA) with contrast-enhanced ultrasonography (CEUS) for renal cell carcinoma in patient with autosomal dominant polycystic kidney. METHODS: We performed a retrospective review of five patients with renal cell carcinoma (RCC) in autosomal dominant polycystic kidney disease (ADPKD) from January 2009 to December 2014 with a media follow-up of 33 months. The tumors were ablated with Cool-tip RFA system under the guidance of CEUS. Routine follow-up included contrast-enhanced computed tomography/magnetic resonance imaging (CT/MRI) and renal function tests. RESULTS: Media diameter of the treated renal tumors was 3.1 cm (range 1.7-5.2 cm). Initial ablation success rate was 4/5. After over 6 months contrast-enhanced CT/MRI follow-up after RFA, no patients experienced local tumor recurrence. No patients required dialysis in the periprocedural period. Minor complications only developed in two cases. There was no significant difference in estimated glomerular filtration rate (eGFR) between pre- and post-RFA. CONCLUSIONS: Our initial experience of this technique for RCC in ADPKD was favorable with good renal function preservation and oncologic outcomes. It may be a good choice for RCC in ADPKD.

Salvage cryotherapy with third-generation technology for locally recurrent prostate cancer after radiation therapy.

PURPOSE: To present the intermediate results of the use of third-generation cryotherapy as salvage treatment for locally recurrent prostate cancer after radiation therapy. METHODS: From January 2006 to July 2010, 32 patients with locally recurrent prostate cancer after radiotherapy underwent salvage cryoablation using third-generation technology. Biochemical recurrence-free survival (BRFS) was defined as the time period from salvage treatment to the date of biochemical recurrence (Phoenix definition of nadir +2 ng/ml). Complications were classified as grades 1-5 according to the modified Clavien system. Multivariate logistic regression analysis was performed to identify potential risk factors associated with recurrence after salvage cryotherapy. RESULTS: The median follow-up was 63 months (range 38-92). Mild complications (grades 1 and 2) included mild incontinence (9.4 %), acute rectal pain (31.3 %), hematuria (6.3 %), scrotal edema (9.4 %), urinary tract infection (3.1 %), lower urinary tract symptoms (15.6 %) and erectile dysfunction (57.1 %). Severe events (grade 3) included severe incontinence (3.1 %) and urethral sloughing (3.1 %). The rate of rectourethral fistula and urinary retention was absent. The 5-year overall survival was 92.3 %. The 5-year cancer-specific survival was 100 %. The 5-year BRFS rate using the Phoenix definition was 43.5 %. A multivariate analysis disclosed that PSA at cryoablation was the only predictive factor for biochemical recurrence. CONCLUSIONS: Salvage cryotherapy using third-generation technology offers a safe and effective alternative for locally recurrent prostate cancer after radiation therapy. Additional studies with longer follow-up are necessary to determine the sustained efficacy of this procedure.

Visualized intravesical floating hydrogel encapsulating vaporized perfluoropentane for controlled drug release.

Intravesical drug delivery is the main strategy for the treatment of bladder disorders. To reduce the relief arising from frequent intravesical instillation, mucoadhesive hydrogel was used for the controlled release of the drug. However, the viscosity of mucoadhesive gel might cause severe urinary obstruction and bladder irritation. To solve all these problems, a floating hydrogel delivery system was developed using perfluoropentane (PFP) as the floating agent. After intravesical instillation of the floating hydrogel, the increased temperature in bladder vaporized PFP, resulting in the generation of microbubbles in the hydrogel. Then, it can float in urine to avoid the urinary obstruction and bladder irritation. In this study, systematic experiments were conducted to investigate the influences of PFP vaporization on the morphology and floating ability of hydrogels. The floating process is much milder and safer than other floating methods published before. In addition, PFP had been used as contrast agent, which affiliated the monitoring of gels during the operation. Therefore, this new drug delivery system addresses the problems of conventional intravesical instillation and is promising for clinic use.

Focal cryoablation for unilateral low-intermediate-risk prostate cancer: 63-month mean follow-up results of 41 patients.

OBJECTIVE: To report (1) intermediate-term oncologic and functional outcomes of primary focal cryoablation (FC) in selected patients with clinically unilateral, low-intermediate-risk prostate cancer, and investigate (2) the impact of patient selection criteria at predicting outcomes after FC. MATERIALS AND METHODS: Forty-one patients with unilateral prostate cancer were treated with FC. Patients were stratified using the 2007 Task Force Focal Prostate Cancer Patient selection criteria (Task Force criteria). Posttherapy follow-up included questionnaires, PSA measurement, and TRUS-guided biopsies. RESULTS: Complete follow-up was available in 40 patients (median follow-up 63 months; range 12-92 months). Compared to precryotherapy PSA level (mean 7.1 ng/ml), postcryotherapy PSA level (mean 1.8 ng/ml) dropped by 75 % at 3 months (P < 0.0001) and this decline persisted throughout the follow-up period, with no significant difference seen across patient selection criteria (P = 0.859). The treatment failure rate was 10 % (4/40) with no significant difference seen across patient selection criteria (P = 0.832). Of 32 patients undergoing postcryotherapy biopsy, 7 (22 %) had positive biopsies (2 ipsilateral lobes, 5 contralateral lobes). Patients of Task Force criteria group were less likely to have positive biopsy in contralateral lobe than focal control group (P = 0.032). Complete continence (no pads) and potency sufficient for intercourse were documented in 97.6 and 76.9 % of patients, respectively. CONCLUSIONS: The intermediate-term oncologic efficacy of primary FC in selected patients with clinically unilateral, low-intermediate-risk prostate cancer appears favorable, and the side-effect profile is low. The 2007 Task Force criteria appear to reduce the positive biopsy rate in contralateral lobe after FC.

Floating Hydrogel with Self-Generating Micro-Bubbles for Intravesical Instillation.

Intravesical instillation is the main therapy for bladder cancer and interstitial cystitis. However, most drug solutions are eliminated from bladder after the first voiding of urine. To solve this problem, we proposed a floating hydrogel with self-generating micro-bubbles as a new delivery system. It floated in urine, avoiding the urinary obstruction and bladder irritation that ordinary hydrogels caused. In this study, we abandoned traditional gas-producing method like chemical decomposition of NaHCO3, and used the foamability of Poloxamer 407 (P407) instead. Through simple shaking (just like shaking SonoVue for contrast-enhanced ultrasound in clinical), the P407 solution will "lock" many micro-bubbles and float in urine as quickly and steadily as other gas producing materials. In vivo release experiments showed that drug was released continually from hydrogel for 10 h during the erosion process. Thus, the residence time of drug in bladder was prolonged and drug efficacy was improved. In vivo efficacy study using rabbit acute bladder injury model showed that prolonged drug residence time in bladder increased the efficiency of heparin in the protection of bladder mucosal permeability. Therefore, our floating hydrogel system with self-generating micro-bubbles was single-component, simply prepared and efficacy enhancing, successfully exempting users from worries on safety and clinical efficiency from bench to bedside.

[Clinical analysis of 49 cases with testicular torsion].

OBJECTIVE: To improve the diagnosis and treatment of testicular torsion. METHODS: The clinical features of 49 testicular torsion patients admitted to Department of Urology Nanjing Drum Tower Hospital from April 2008 to March 2014 were retrospectively analyzed, the average age was (21 ± 6) years (range 13-52 years).Forty-four cases underwent the color Doppler flow imaging of scrotum, demonstrated reduction of the testicular blood supply in 9 cases and loss of the testicular blood supply in 35 cases. Orchiectomy or orchiopexy was performed according to the testicular blood supply, the contralateral testis fixation was performed in all patients. A two-tailed Student's t-test was used to compare the data between two groups, Pearson correlation analysis was used to analyze the correlation of diurnal temperature and number of cases. RESULTS: All the patients with testicular torsion were Tunica-reversed, 38 (77.5%) cases occurred from November to April. The monthly incidence of testicular torsion was positively correlated with diurnal temperature (r = 0.6434, P = 0.024). Forty-four cases underwent the color Doppler flow imaging, demonstrated the reduction or loss of the testicular blood supply, and these patients were confirmed to be testicular torsion by surgical exploration. The salvage rates of testis in patients with testicular torsion were 2/2, 5/15, 2/9 and 4.2% (1/24) in those seeking medical attention within 6, 12, 24 hours and over 24 hours after the onset of pain. All the patients were followed up for 3 to 75 months, and no one experienced recurrent torsion. CONCLUSIONS: The incidence of testicular torsion is higher during the spring and winter, diurnal temperature change is associated with testicular torsion. The diagnostic rate of color Doppler flow imaging is high, which can be chosen as the primary method. Prompt recognition and treatment are necessary for testicular salvage.

[Laparoscopic radiofrequency ablation for centrally located renal tumors].

OBJECTIVE: To study the safety and effectiveness of laparoscopic radiofrequency ablation for centrally located renal tumors. METHODS: From January 2009 to April 2013, thirteen patients who diagnosed as centrally located renal tumors were treated with laparoscopic radiofrequency ablation in the Department of Urology of Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School. All of the cases were T1aN0M0 stage, 9 patients were male, 4 were female, the mean age was 56 years (range, 38-73 years). All tumors were unilateral, eight lesions were in the left kidney and five in the right kidney. Intraoperative real-time ultrasound and temperature probes were used to guide the range of radiofrequency ablation. Ice saline was injected through ureteral catheter for cooling the collecting system. The postoperative serum creatinine and glomerular filtration rate (GFR) data were collected,all patients were followed up with enhanced CT or MRI.The pre- and post-operative date were compared by paired t test. RESULTS: All patients underwent laparoscopic radiofrequency ablation successfully. The mean operation time was (113±13) minutes and the mean blood loss was (99±23) ml. The mean pre- and post-operative serum creatinine was (71±11) µmol/L and (74±11) µmol/L, the mean pre- and post-operative GFR was (49±8) ml/min and (45±7) ml/min. There was no significant statistic difference between pre-operation and post-operation (t=-1.371 and 1.986, P>0.05). The mean follow-up was 37 months, range 12-63 months. No evidence of local recurrence or distant metastasis was found. CONCLUSIONS: Laparoscopic radiofrequency ablation for T1aN0M0 centrally located renal tumors could be performed safely with good outcomes. Intraoperative real-time ultrasound and temperature probes are helpful to control the range of radiofrequency ablation. Physical cooling of renal collecting system could reduce the occurrence of postoperative hydronephrosis and leakage of urine.

The application of PADUA scoring system for predicting complications of laparoscopic renal cryoablation.

PURPOSE: To evaluate the clinical application of preoperative aspects and dimensions used for anatomical (PADUA) scoring system in predicting perioperative surgical outcomes in patients undergoing laparoscopic cryoablation (LCA). METHODS: A total of 95 consecutive renal tumors treated with LCA between January 2007 and April 2013 were collected. Renal tumors were categorized into low- (6-7), moderate- (8-9), and high-complexity (10-13) groups according to PADUA indices. Demographics, perioperative variables, and complication rates were compared among three groups. Surgical conversion, blood loss >100 mL, tumor fracture, and incomplete ablation were regarded as intraoperative complications (IOCs). All postoperative complications (POCs) were graded using the Clavien-Dindo system. The risk for complications was assessed by univariate and multivariate logistic regression analyses. RESULTS: The estimated blood loss during LCA was associated with PADUA score. There were 17 (17.9%) IOCs and 20 (21.1%) POCs. Blood loss (>100 mL) was the most common IOC, which occurred in 10 (10.5%) patients. For POC, there were 15 (15.8%) minor complications (Clavien 1-2) and 5 (5.3%) major complications (Clavien 3a). Higher grade of PADUA scores was significantly correlated with the increase incidence of IOC and POC. The PADUA score was an independent predictive factor for POC, and the patients with moderate and high PADUA scores had an over sixfold and 17-fold higher risk compared to the patients with low scores, respectively. CONCLUSION: Our findings demonstrated, for the first time, the PADUA scoring system is an efficient assessment tool for predicting the perioperative complications in patients undergoing laparoscopic renal cryoablation.

Improved split renal function after percutaneous nephrostomy in young adults with severe hydronephrosis due to ureteropelvic junction obstruction.

PURPOSE: We evaluated percutaneous nephrostomy for adult kidneys with severe hydronephrosis due to ureteropelvic junction obstruction and less than 10% split renal function. MATERIALS AND METHODS: In this retrospective analysis we included patients who underwent percutaneous nephrostomy for unilateral ureteropelvic junction obstruction of the kidneys with hydronephrosis and less than 10% split renal function at our hospital between May 2009 and January 2012. Adults (age 18 years or greater) were divided into those 35 years or younger (young adults) and older than 35 years (older adults). The percutaneous nephrostomy remained in situ a mean ± SD of 6.62 ± 2.55 weeks and patients underwent repeat renography before pyeloplasty. When there was no significant improvement in split renal function (10% or greater) and drainage (greater than 400 ml per day), nephrectomy was performed. Otherwise pyeloplasty was performed. Patients were followed by renography, ultrasound and contrast computerized tomography at 3 and 6 months, at 1 year and annually thereafter. RESULTS: Of 53 patients 30 (56.6%) showed improvement after percutaneous nephrostomy drainage and urine output greater than 400 ml per day with percutaneous nephrostomy. Pyeloplasty was then performed. Of 29 young adults 24 (82.8%) showed improved split renal function vs 6 of 24 older adults (25%). Nephrectomy of the other 23 kidneys was performed. At a mean followup of 19.27 ± 7.82 months (range 12 to 36), no patient showed hypertension or urinary tract infection. CONCLUSIONS: Split renal function detected by renography may not accurately predict recovered, poorly functioning kidneys, especially in young adults. First observing the recoverability of hydronephrotic kidneys by percutaneous nephrostomy drainage and then preserving select kidneys may be an effective method to manage poorly functioning kidneys due to ureteropelvic junction obstruction.