WWOX Modulates ROS-Dependent Senescence in Bladder Cancer.

The tumor-suppressor gene, WW domain-containing oxidoreductase (WWOX), has been found to be lost in various types of cancers. ROS result as a tightly regulated signaling process for the induction of cell senescence. The aim of this study was to investigate the role of WWOX in the regulation of ROS and cell senescence, which is intriguing in terms of the possible mechanism of WWOX contributing to bladder cancer. In this study, we used the AY-27 rat bladder tumor cell line and F344 orthotopic bladder tumor models to reveal the pro-senescence effects of WWOX and the corresponding underlying mechanism in bladder cancer. WWOX-overexpressing lentivirus (LV-WWOX) remarkably stimulated cellular senescence, including increased senescence-associated secretory phenotype (SASP) formation, enlarged cellular morphology, and induced SA-ß-Gal-positive staining. A further mechanism study revealed that the pro-senescence effect of LV-WWOX was dependent on increased intercellular reactive oxygen species (ROS) generation, which subsequently triggered p21/p27. Moreover, LV-WWOX significantly inhibited the tumor size by 30.49% in the F344/AY-27 rat orthotopic model (p < 0.05) by activating cellular senescence. The expression of p21 was significantly enhanced in the orthotopic bladder tumors under WWOX treatment. The orthotopic bladder tumors in the groups of rats verified the effect in vivo. Our study suggests that WWOX, an ROS-dependent senescence-induced gene, could be further studied for its therapeutic implications in bladder cancer.

A Hydrogel-Based Epirubicin Delivery System for Intravesical Chemotherapy.

This study aimed to examine the efficacy of epirubicin-loaded gelatin hydrogel (EPI-H) in the treatment of superficial urothelium carcinoma. Hydrogel was prepared by Schiff base-crosslinking of gelatin with glutaraldehyde. EPI-H exhibited high entrapment efficiency (59.87% ± 0.51%). EPI-H also increased epirubicin accumulation in AY-27 cells when compared with the effect of aqueous solutions of epirubicin (EPI-AQ); respective epirubicin-positive cell counts were 69.0% ± 7.6% and 38.3% ± 5.8%. EPI-H also exhibited greater cytotoxicity against AY-27 cells than that of EPI-AQ; IC50 values were 13.1 ± 1.1 and 7.5 ± 0.3 µg/mL, respectively. Cystometrograms showed that EPI-H reduced peak micturition, threshold pressures, and micturition duration, and that it increased bladder compliance more so than EPI-AQ. EPI-H enhanced epirubicin penetration into basal cells of urothelium in vivo, whereas EPI-AQ did so only to the umbrella cells. EPI-H inhibited tumor growth upon intravesical instillation to tumor-bearing bladder of F344 rats, inducing higher levels of caspase-3 expression than that observed with EPI-AQ treatment; the number of caspase-3 positive cells in treated urothelium carcinoma was 13.9% ± 4.0% (EPI-AQ) and 34.1% ± 1.0%, (EPI-H). EPI-H has value as an improved means to administer epirubicin in intravesical instillation treatments for bladder cancer.

Use dose bricks concept to implement nasopharyngeal carcinoma treatment planning.

PURPOSE: A "dose bricks" concept has been used to implement nasopharyngeal carcinoma treatment plan; this method specializes particularly in the case with bell shape nasopharyngeal carcinoma case. MATERIALS AND METHODS: Five noncoplanar fields were used to accomplish the dose bricks technique treatment plan. These five fields include (a) right superior anterior oblique (RSAO), (b) left superior anterior oblique (LSAO), (c) right anterior oblique (RAO), (d) left anterior oblique (LAO), and (e) superior inferior vertex (SIV). Nondivergence collimator central axis planes were used to create different abutting field edge while normal organs were blocked by multileaf collimators in this technique. RESULTS: The resulting 92% isodose curves encompassed the CTV, while maximum dose was about 115%. Approximately 50% volume of parotid glands obtained 10-15% of total dose and 50% volume of brain obtained less than 20% of total dose. Spinal cord receives only 5% from the scatter dose. CONCLUSIONS: Compared with IMRT, the expenditure of planning time and costing, "dose bricks" may after all be accepted as an optional implementation in nasopharyngeal carcinoma conformal treatment plan; furthermore, this method also fits the need of other nonhead and neck lesions if organ sparing and noncoplanar technique can be executed.

Preparation and characterization of gelatin-based mucoadhesive nanocomposites as intravesical gene delivery scaffolds.

This study aimed to develop optimal gelatin-based mucoadhesive nanocomposites as scaffolds for intravesical gene delivery to the urothelium. Hydrogels were prepared by chemically crosslinking gelatin A or B with glutaraldehyde. Physicochemical and delivery properties including hydration ratio, viscosity, size, yield, thermosensitivity, and enzymatic degradation were studied, and scanning electron microscopy (SEM) was carried out. The optimal hydrogels (H), composed of 15% gelatin A175, displayed an 81.5% yield rate, 87.1% hydration ratio, 42.9 Pa·s viscosity, and 125.8 nm particle size. The crosslinking density of the hydrogels was determined by performing pronase degradation and ninhydrin assays. In vitro lentivirus (LV) release studies involving p24 capsid protein analysis in 293T cells revealed that hydrogels containing lentivirus (H-LV) had a higher cumulative release than that observed for LV alone (3.7-, 2.3-, and 2.3-fold at days 1, 3, and 5, resp.). Lentivirus from lentivector constructed green fluorescent protein (GFP) was then entrapped in hydrogels (H-LV-GFP). H-LV-GFP showed enhanced gene delivery in AY-27 cells in vitro and to rat urothelium by intravesical instillation in vivo. Cystometrogram showed mucoadhesive H-LV reduced peak micturition and threshold pressure and increased bladder compliance. In this study, we successfully developed first optimal gelatin-based mucoadhesive nanocomposites as intravesical gene delivery scaffolds.

Polymorphisms of TP53 are markers of bladder cancer vulnerability and prognosis.

OBJECTIVES: We have reported previously that the TP53 codon72 polymorphism (rs1042522) is associated with the incidence and invasiveness of bladder cancer in a Han Chinese population. Using an enlarged sample, we investigated the role of rs1042522 and of tagSNPs that were predicted to be in linkage disequilibrium with codon72 in relation to the incidence, invasiveness, and prognosis of bladder cancer. METHODS AND MATERIALS: A sample of 201 patients and 311 controls without cancer were genotyped for 5 tagSNPs using tetra-primer ARMS and/or an allele-specific PCR technique. RESULTS: The genotyped data were analyzed using Haploview 4.2, and a 10,000-permutation test showed that the rs9895829G allele (P = 0.003) and the rs1788227C allele (P = 0.027) were both associated with the incidence of bladder cancer. With respect to haplotype associations, after the data were adjusted for age, the haplotypes GTT (P = 0.001) and GGTC (P < 0.001) were correlated with a low incidence of bladder cancer. In contrast, none of the TP53 haplotypes were associated significantly with high tumor grade or muscle invasiveness. On the basis of Cox regression analysis, haplotype CGCC and invasiveness were associated with cancer-related death. Structural equation modeling showed that haplotypes GGCC and CGCC played opposing roles with respect to bladder cancer-related death; haplotype GGCC was a protective factor, whereas haplotype CGCC was a risk factor. CONCLUSIONS: The TP53 codon72 polymorphism appears to play a crucial role in determining the association between TP53 haplotype and the incidence and prognosis of bladder cancer. Further functional assays to confirm whether these TP53 haplotypic variants interact with the proteins N-Myc and NDRG is necessary.

Changes in quality of life among prostate cancer patients after surgery.

BACKGROUND: Quality of life (QoL) often is impacted after radical prostatectomy (RP) procedures. Although patients' QoL scores gradually improve after RP, changes in the QoL score over time after different RP procedures must be examined. OBJECTIVE: The aim of this study was to compare the changes in QoL over time of prostate cancer patients who were treated with open RP (ORP) or laparoscopic RP (LRP) procedures. METHODS: A longitudinal study design was used. A convenient sample of 67 prostate cancer patients was recruited after RP (ORP = 34, LRP = 33). QoL scores were assessed at 1, 3, and 6 months after RP using the University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI). RESULTS: With respect to the PCI mean score between the ORP and LRP groups, there were significant differences in overall PCI and urinary function at time 1 (1 month after RP). However, a mixed-design analysis of covariance on the overall PCI of the 2 groups over time indicated that, after controlling for nerve sparing, there were significant differences in the main effects for group and time, but no interaction effect. CONCLUSION: Results indicated that all patients' QoL scores improved over time. Laparoscopic RP patients' overall scores were better than ORP patients' scores, but this may be due to unmeasured preoperative differences in this nonrandom sample, and thus, these findings cannot be attributed to treatment differences alone. IMPLICATIONS FOR PRACTICE: Patients' QoL after either RP surgery is likely to drop but is regained by 6 months. This information should be given to patients undergoing RP who are deciding between various RP procedures.

Bilateral renal myxoid perineuriomas.

A perineurioma is a benign tumor of the peripheral nervous system which is composed of perineurial cells. Perineuriomas commonly develop as extraneural tumors from soft tissues and less commonly have intraneural localization. This case report describes a 25-year-old man with large bilateral renal masses that were diagnosed as perineuriomas. After surgical excision, the patient recovered fully and had no evidence of recurrence at the 1- and 2-year follow-up examinations.

Effects of early pelvic-floor muscle exercise for sexual dysfunction in radical prostatectomy recipients.

BACKGROUND: Sexual dysfunction is common after radical prostatectomy (RP). Although pelvic-floor muscle exercise (PFME) has been recommended for sexual dysfunction, the optimal time for starting exercises after this surgery and the effects of exercise still need to be examined. OBJECTIVES: The present study was intended to explore the prevalence of sexual dysfunction and to assess the efficacy of PFME in sexual dysfunction following RP. METHODS: Participants were randomly distributed into an experimental group (n = 35) or a control group (n = 27). The experimental group took part in PFME as part of regular daily activities after catheter removal post-RP. The control group was taught the exercise in the third month after RP. We followed up the participants at 1, 3, 6, 9, and 12 months. RESULTS: All of the patients experienced a severe degree of sexual dysfunction after receiving RP. A t test showed a significant difference in the sexual function mean score between the experimental and control groups at 6 and 12 months. A mixed-model analysis indicated that, after a controlled surgical approach, there was a significant difference in group effect. The experimental group's sexual function was better than the control group's sexual function. CONCLUSION: This study demonstrates that early PFME is an effective intervention for sexual dysfunction in prostatectomy patients. The results can help healthcare providers to include this intervention in patients' discharge plans. IMPLICATIONS FOR PRACTICE: Patient sexual dysfunction after an RP is common. Nurses should evaluate and manage patients' sexual dysfunction and promote the early return of patients' potency.

Comparison of health-related quality of life between subjects treated with radical prostatectomy and brachytherapy.

AIMS AND OBJECTIVES: To evaluate the symptoms and self-assessment of quality of life in men with localised prostate cancer after having had a radical prostatectomy or brachytherapy treatment. BACKGROUND: Prostate cancer is a significant growing disease among men in Taiwan. Quality of life issues for the men who are living with this disease and the consequences of treatment. DESIGN: A postal questionnaire survey. METHODS: The study population came from one 1170-bed hospital in Kaohsiung County, Taiwan. Data was collected from 20 August 2007-20 November 2009. Seventy-eight men met the inclusion criteria. The researchers mailed a survey to each participant, which they completed at home and returned in a pre-stamped, addressed envelope. Sixty-four subjects participated and self-reported using a structured questionnaire. The reliability of overall prostate cancer index was 0.90 and 0.85, 0.93 and 0.72 for each subscale, respectively. RESULTS: The results indicate that the number of months post-treatment was positively correlated with urinary function and age was negatively correlated with sexual, bowel function and bowel bothers. One predictor (month post-treatment) was related to urinary function; one predictor (treatment method) was related to bowel function and four predictors (marital status, age, treatment method and month post-treatment) were related to sexual function. Findings showed that patients who received brachytherapy have better urinary functions, as compared with prostatectomy patients. CONCLUSION: Study findings suggest that healthcare providers should have a better understanding of patients' complications after treatment and this can ultimately raise the quality of life for prostate cancer patients. RELEVANCE TO CLINICAL PRACTICE: The impact of quality of life among post prostate cancer treatment is common. Urological nurses should therefore take the responsibility regarding the consequence of urinary incontinence and sexual function and seeking appropriate nursing interventions for these complications.

p53 codon 72 polymorphism as a progression index for bladder cancer.

The aim of this study was to calculate the positive predictive value (PPV) and negative predictive value (NPV) to determine whether p53 codon 72 can be used as a bladder cancer management index. Ninety-six patients diagnosed with bladed cancer and two control groups of 427 randomly sampled community participants and 142 non-cancerous individuals without a prior history of cancer were enrolled. After preliminary analysis, the convergent validity resulted in 96 patients from this study and 129 patients from our previous study. Results showed that these two groups were of the same population, and could be merged into one case group. Logistic regression showed that the Pro/Pro genotype was not statistically significantly associated with bladder cancer incidence using each sample set after adjustment by age and gender. Moreover, the Pro/Pro genotype was not associated with high-grade tumors (P=0.078), but was highly correlated to muscle-invasive tumors (P=0.002). Pro/Pro genotype carriers were estimated to have a 3.36-fold higher risk to develop invasive tumors compared to non-carriers. The NPV of the Pro/Pro genotype for invasive tumors was 88.00%, and the PPV was 31.91%. By Cox regression analysis, high-grade tumors were associated with recurrence (P=0.020, OR=1.83), whereas invasive tumors were associated with cancer-related death (P<0.001, OR=2.87). p53 codon 72 polymorphism is associated with bladder cancer progression rather than incidence and prognosis. The Pro/Pro genotype in p53 codon 72 polymorphism shows a high NPV for bladder cancer progression, thus, it can be used clinically as a progression index in bladder cancer management.

p53 codon 72 polymorphism was associated with vulnerability, progression, but not prognosis of bladder cancer in a Taiwanese population: an implication of structural equation modeling to manage the risks of bladder cancer.

INTRODUCTION: p53 codon 72 polymorphism has been reported to be associated with bladder cancer incidence, progression and prognosis, but the association is still under debate. A tentative model was constructed to evaluate the association between p53 codon 72 polymorphism and bladder cancer. SUBJECTS AND METHODS: In this study, a total of 554 participants were enrolled. The genotyping was carried out using PCR-RFLP and DNA direct sequencing. RESULTS: The genotype distribution of p53 codon 72 polymorphism was significantly different between bladder cancer patients and controls (p = 0.039). In logistic regression, diagnostic age and genotype Pro/Pro were the risk factors for developing an invasive tumor. A 4.526-fold risk was estimated for the patients with Pro/Pro genotype as opposed to non-Pro/Pro genotype to develop invasive tumors. However, the extent of p53 codon 72 polymorphism did not predict bladder cancer prognosis. CONCLUSIONS: A conceptual mode was constructed; in addition, the moderating and mediating analysis was also carried out in a structural equation model to resolve possible confounding effects. Taken together, p53 codon 72 polymorphism may be associated with bladder cancer incidence and progression, but not prognosis. Further study is needed to evaluate the usefulness of the constructed model in risk assessment.

The effect of surgeon empathy and emotional intelligence on patient satisfaction.

We investigated the associations of surgeons' emotional intelligence and surgeons' empathy with patient-surgeon relationships, patient perceptions of their health, and patient satisfaction before and after surgical procedures. We used multi-source approaches to survey 50 surgeons and their 549 outpatients during initial and follow-up visits. Surgeons' emotional intelligence had a positive effect (r = .45; p < .001) on patient-rated patient-surgeon relationships. Patient-surgeon relationships had a positive impact on patient satisfaction before surgery (r = .95; p < .001). Surgeon empathy did not have an effect on patient-surgeon relationships or patient satisfaction prior to surgery. But after surgery, surgeon empathy appeared to have a significantly positive and indirect effect on patient satisfaction through the mediating effect of patients' self-reported health status (r = .21; p < .001). Our study showed that long-term patient satisfaction with their surgeons is affected less by emotional intelligence than by empathy. Furthermore, empathy indirectly affects patient satisfaction through its positive effect on health outcomes, which have a direct effect on patients' satisfaction with their surgeons.

Single-session laparoscopic total urinary tract exenteration without repositioning for multifocal urothelial carcinoma in dialysis-dependent patients.

OBJECTIVES: To report our experience of single-session, en bloc, laparoscopic total urinary tract exenteration in dialysis-dependent patients with multifocal urothelial carcinoma. METHODS: From June 2005 to April 2008, 5 dialysis-dependent patients (4 women and 1 man) diagnosed with synchronous upper urinary tract and bladder urothelial carcinoma underwent single-session, en bloc, laparoscopic total urinary tract exenteration. Bilateral nephroureterectomy was facilitated by rotating the operating table with or without alternative inflation of the tourniquet cuffs on either side of the patient's back to allow adequate spontaneous bowel displacement by gravity, thereby avoiding the need to reposition the patient. After completing bilateral nephroureterectomy, we performed radical cystectomy with the patient in the Trendelenburg position. All specimens, including the 2 kidneys, ureters, and bladder, were collected in an endobag and were intended to be retrieved using the Pfannenstiel incision in male patients and the vaginal route in the female patients. The demographic and perioperative information were collected and analyzed. RESULTS: All the laparoscopic procedures were completed successfully without major complications. Although 1 patient developed a minor complication owing to paralytic ileus, she recovered after conservative treatment. The continuity of all the urothelial epithelium was maintained intact throughout the procedure to avoid tumor spillage. CONCLUSIONS: In our experience, laparoscopic total urinary tract exenteration is a technically feasible and safe alternative modality to the open counterpart to treat dialysis-dependent patients with end-stage renal disease with multifocal urothelial carcinoma for experienced surgeons with advanced laparoscopic skills. Furthermore, it can be performed successfully without the need for repositioning the patient, and this probably decreased the incidence of associated complication in the high-risk patients.

An atrophic crossed fused kidney with an ectopic vaginal ureter causing urine incontinence.

An ectopic vaginal ureter is an infrequent cause of urinary incontinence. Most cases are associated with a duplex kidney in which the lower moiety ureter drains into the bladder. Occasionally, some cases of ectopic kidney with single vaginal ectopic ureter can occur. In this study, we present a case of chronic continuous urine incontinence caused by the extremely rare combination of a fused-crossed kidney and a single vaginal ectopic ureter. Laparoscopic nephroureterectomy was carried out smoothly and uneventfully. In our experience, laparoscopic navigation and surgery can be valuable tools to delineate and manage unusual congenital anomalies.

Optimization of epirubicin nanoparticles using experimental design for enhanced intravesical drug delivery.

The aim of this study was to develop poly(ethyl-2-cyanoacrylate) (PECA) epirubicin-loaded nanoparticles (EPI-NP). A 2(3) factorial design was adopted with the type of surfactant, surfactant concentration and the pH of the polymerization medium as independent variables. The particle size, entrapment efficacy and polydispersity index of eight formulations were then evaluated. Two optimal EPI-NP formulations, 2% Tween 80 EPI-NP (TW80 EPI-NP) and 0.5% pluronic F68 EPI-NP (F68 EPI-NP) at pH 2.5 were developed. The sizes of TW80 EPI-NP and F68 EPI-NP at maximum intensity were 90 and 220 nm, respectively. Both TW80 EPI-NP and F68 EPI-NP showed potent cytotoxicity against human bladder cancer T24 and RT4 cells, compared with aqueous solutions of epirubicin (EPI-AQ). The penetration and accumulation of EPI-NPs in pig urothelium were studied by tissue concentration-depth profiles and fluorescence microscopy. The cumulative amounts of epirubicin following EPI-AQ, TW80 EPI-NP and F68 EPI-NP treatments were 842.48+/-24.66, 1314.66+/-33.07 and 595.21+/-24.16 microg, respectively. The current study showed the successful development of urothelium adhesive and penetrative PECA EPI-NPs. This has potential for the in vivo application of epirubicin-loaded nanoparticles for intravesical instillation in bladder cancer therapy.

De novo urothelial carcinoma in a pediatric recipient of living donor kidney graft.

De novo urothelial carcinoma is relatively rare among post-transplant malignancies and never reported in pediatric kidney transplant recipients. In this paper, we reported one 12-yr-old male case with painless gross hematuria as the initial manifestation of de novo urothelial carcinoma in living donor graft pelvis. We emphasize the importance that cystoscopy and retrograde pyelography of native and transplant kidneys should be performed in all kidney transplant recipients with painless gross hematuria.

Use of collagen for endoscopic correction in complicated vesicoureteral reflux.

OBJECTIVE: Endoscopic treatment of children with primary vesicoureteral reflux (VUR) has become an alternative to long-term antibiotic prophylaxis and open surgery. The purpose of this study was to assess the efficiency and safety of endoscopic subureteral injections of collagen (STING) as a treatment for complicated VUR in children. MATERIAL AND METHODS: Twenty-five patients (41 ureteral units) underwent a modified STING procedure for the correction of complicated VUR. Of these patients, five (nine refluxing units) had Hutch's diverticulum, 10 (17 refluxing units) had a duplex system, eight (10 refluxing units) had ureterocele, one (three refluxing units) had a unilateral triple ureter and one (two refluxing units) had a bilateral single ectopic ureter. Of these 41 ureteral units, 14 had grade III VUR, 17 grade IV and 10 grade V. Fourteen refluxing units (30%) received one session of STING, which was successful, and 27 (70%) needed a second session. A follow-up voiding cystourethrogram was performed 3 months after each session of STING. RESULTS: The mean follow-up period was 24 months (range 3-36 months). Of these 41 refluxing units, 34 were treated successfully and regression or downgrading occurred in seven. Follow-up i.v. pyelography or sonography did not reveal any urinary tract obstruction. CONCLUSIONS: The results of this study showed that endoscopic correction of these complicated refluxing ureters may be the first choice of treatment, but the technique must be modified to suit each individual case.

Imaging findings in fibroepithelial polyps causing ureteropelvic junction obstruction: report of one case.

Fibroepithelial polyps causing ureteropelvic junction obstruction are rarely reported in the pediatric age group. We report a 9-year-old boy who had ureteropelvic junction obstruction that proved to be owing to benign fibroepithelial polyps. Intravenous pyelography showed hydronephrosis with filling defects at the left ureteropelvic junction. Operative exploration revealed several finger-like polypoid neoplasms obstructing the lumen. The involved segment was resected and a dismembered pyeloplasty was performed. Fibroepithelial polyps were diagnosed by histology. The clinical imaging findings, features and methods of surgical treatment of this rare lesion are discussed.