En-bloc resection of bladder tumour as primary treatment for patients with non-muscle-invasive bladder cancer: routine implementation in a multi-centre setting.

PURPOSE: To investigate the technical success rate and 30-day complications of en-bloc resection of bladder tumour (ERBT) upon routine implementation regardless of tumour size. METHODS: This is a prospective, multi-centre, study on routine implementation of ERBT for patients with bladder tumours requiring transurethral surgery. Surgeons were allowed to cross over to conventional transurethral resection of bladder tumour (TURBT) when necessary. We performed an analysis for patients who had ERBT/TURBT as the definitive treatment. Study outcomes included the technical success rate of ERBT and 30-day complication rate. Multivariate logistic regression analysis was performed to investigate for predictors of a successful ERBT and factors associated with 30-day complications. RESULTS: A total of 135 patients were included in this study. The majority of the patients (80.0%) had bladder tumours of ≤ 3 cm. ERBT was successful in 99 patients, resulting in an overall technical success rate of 73.3%. When stratified according to tumour size, the technical success rates of ERBT were 94.3%, 82.2%, 75%, 84.3% and 29.6% for bladder tumour sizes of < 1 cm, 1.01-2 cm, 2.01-3 cm, ≤ 3 cm and > 3 cm respectively. Upon multivariate analysis, tumour size was the only significant factor predicting the success of ERBT (OR 0.920, 95% CI 0.882-0.960, p < 0.001). Moreover, ERBT was not a significant factor associated with 30-day complications. CONCLUSION: EBRT achieved a good technical success rate for the majority of patients with bladder tumours ≤ 3 cm. Regardless of tumour size, EBRT-first approach was safe to implement into routine clinical practice.

The cardiovascular risk factors in men with lower urinary tract symptoms.

OBJECTIVE: It has been hypothesized that endothelial dysfunction and pelvic atherosclerosis may contribute to lower urinary tract symptoms (LUTS). We assessed the relationship between cardiovascular risk factors and LUTS severity in male patients presented to urology clinic. METHODS: It is a cross-sectional study on patients who presented between 2013 and 2015 with LUTS. A total of 1176 male patients were encountered, and 966 were included for analysis after excluding patients with urinary tract malignancy, urethral stricture, bladder stone and history of urinary tract surgery. Cardiovascular risk factors including components of Framingham risk score, body mass index, uroflowmetry, International Prostate Symptoms Score, fasting blood glucose and serum prostate-specific antigen (PSA) were assessed. Correlation between Framingham risk score, cardiovascular risk factors and severity of LUTS was investigated. RESULTS: Multinomial logistic regression analysis showed that severe LUTS significantly associated with Framingham score (P = 0.008) and its components of total cholesterol (OR = 1.318; P = 0.010) and age (OR = 1.032; P = 0.006) compare with mild symptoms. Framingham risk score was found to correlate with storage symptoms (CC = 0.083; P < 0.0001) but not voiding symptoms (CC = - 0.029; P = 0.185). CONCLUSIONS: Severity of LUTS and storage symptom significantly increases Framingham risk score, particularly with the components of total cholesterol level and age.

Genomic instability in laminopathy-based premature aging.

Premature aging syndromes often result from mutations in nuclear proteins involved in the maintenance of genomic integrity. Lamin A is a major component of the nuclear lamina and nuclear skeleton. Truncation in lamin A causes Hutchinson-Gilford progerial syndrome (HGPS), a severe form of early-onset premature aging. Lack of functional Zmpste24, a metalloproteinase responsible for the maturation of prelamin A, also results in progeroid phenotypes in mice and humans. We found that Zmpste24-deficient mouse embryonic fibroblasts (MEFs) show increased DNA damage and chromosome aberrations and are more sensitive to DNA-damaging agents. Bone marrow cells isolated from Zmpste24-/- mice show increased aneuploidy and the mice are more sensitive to DNA-damaging agents. Recruitment of p53 binding protein 1 (53BP1) and Rad51 to sites of DNA lesion is impaired in Zmpste24-/- MEFs and in HGPS fibroblasts, resulting in delayed checkpoint response and defective DNA repair. Wild-type MEFs ectopically expressing unprocessible prelamin A show similar defects in checkpoint response and DNA repair. Our results indicate that unprocessed prelamin A and truncated lamin A act dominant negatively to perturb DNA damage response and repair, resulting in genomic instability which might contribute to laminopathy-based premature aging.

Urine spermine and multivariable Spermine Risk Score predict high-grade prostate cancer.

BACKGROUND: To investigate the role of urine spermine and Spermine Risk Score in prediction of high-grade prostate cancer (HGPCa, ISUP grade group ≥2). METHODS: Nine hundred and five consecutive men with elevated PSA were prospectively recruited from two hospitals. Core analyses focused on consecutive men with PSA 4-20 ng/mL (n = 600). Pre-biopsy urine without prior prostatic massage was analyzed for spermine level with ultra-high performance liquid chromatography with triple quadrupole mass spectrometer (UPLC-MS/MS). The proportions of PCa and HGPCa were compared across different spermine ranges. Logistic regressions were used to form different models, and their performances were compared using area under curve (AUC) and decision curve analysis (DCA). RESULTS: PCa and HGPCa were diagnosed in 30.8% (185/600) and 17.2% (103/600) men, respectively, and were significantly associated with lower urine spermine levels. Between the lowest and highest quartiles of spermine results, a threefold increase in PCa risk (49.3% vs. 16.7%) and 3.5-fold increase in ISUP grade group ≥2 PCa risk (31.3% vs. 8.7%) were observed. Multivariate analysis showed PSA, prostate volume (PV), digital rectal examination (DRE), and spermine, which were independent predictors for PCa and HGPCa, and a Spermine Risk Score with these factors achieved the highest AUC of 0.78 for PCa and 0.82 for HGPCa. At 90% sensitivity for HGPCa, 36.7% biopsies and 24.4% ISUP grade group 1 diagnoses could have been avoided, with a negative predictive value of 95.4%. DCA revealed net clinical benefit of the Spermine Risk Score. Internal validation with bootstrapping showed good discrimination and calibration. CONCLUSION: Urine spermine and Spermine Risk Score identified men at higher risk of HGPCa and reduced unnecessary biopsies.

Sectoral cancer detection and tolerability of freehand transperineal prostate biopsy under local anaesthesia.

BACKGROUND: To investigate the feasibility of a freehand transperineal (TP) systematic prostate biopsy protocol under local anaesthesia (LA) and the value of different sectors in diagnosing prostate cancer (PCa). METHODS: A total of 611 consecutive freehand TP biopsies under LA in 2 hospitals were prospectively evaluated. Cancer detection rate in each of the four different sectors (anterior, mid, posterior, basal) was recorded to evaluate the value of each sector. Procedure tolerability was assessed by pain score and complications were documented. RESULTS: Systematic biopsies were performed in 556 out of 611 men with a median of 20 (IQR 12-24) biopsy cores taken. The median PSA was 9.9 (Inter-quartile range[IQR] 6.4-16.2) ng/mL, and 89.0% were first biopsies. All PCa and ISUP grade group (GG) ≥ 2 PCa (HGPCa) were diagnosed in 41.4% (230/556) and 28.2% (157/556) biopsies respectively. 77.0% HGPCa was diagnosed in ≥2 sectors. Single-sector HGPCa was predominantly found in anterior or posterior sector. Omitting base sector would have missed 1.5% (1/65) HGPCa out of the 219 cases with ≥24-core biopsies performed. Further omission of mid sector would have missed 3.1% (2/65) HGPCa and 7.4% (7/94) ISUP GG1 PCa (in which 3/7 involved 2 sectors). LA TP biopsy was well tolerated and the mean pain scores of the different steps of the procedure were between 1.9-3.1 (out of 10). Post-biopsy fever occurred in 0.3% of patients (2/611) and no sepsis was reported. The risk of urinary retention in men with ≥20 cores in ≥60 ml prostate was 7.8% (14/179), compared with 1.7% (7/423) in other groups (p < 0.001). CONCLUSIONS: TP sectoral prostate biopsy under LA was well tolerated with minimal sepsis risk. Basal sector biopsies had minimal additional value to HGPCa detection and its omission can be considered.

Involvement of both endoplasmic reticulum and mitochondria in photokilling of nasopharyngeal carcinoma cells by the photosensitizer Zn-BC-AM.

Photodynamic therapy (PDT) is recently developed as an effective treatment for malignant disease. In PDT, the photosensitizer eradicates tumour by induction of apoptosis. In this study, we investigated the mechanistic actions of a recently developed second generation photosensitizer, Zn-BC-AM, on nasopharyngeal carcinoma (NPC) cells. Zn-BC-AM was found to localize in the mitochondria, endoplasmic reticulum (ER), and golgi body. Photoactivation of Zn-BC-AM loaded NPC cells resulted in a rapid collapse of mitochondrial membrane potential (Deltapsim) (15 min), followed by the release of cytochrome c (1 h), and activation of caspases-9 and -3 (4 h). Expression of ER chaperones Bip/Grp78 and Grp94, and ER resident lectin-like chaperone calnexin (CNX) was also enhanced in PDT-stressed NPC cells. Caspase-12, an important caspase involved in ER stress-induced apoptosis, was also activated. Inhibition of Ca2+ uptake into mitochondria by ruthenium red (RR) or loading the cells with EGTA-AM, an agent that buffers intracellular Ca2+ released from ER, resulted in a significant reduction of Zn-BC-AM PDT-induced cell death. These observations suggest that both ER and mitochondria are the subcellular targets of Zn-BC-AM. Effective activation of ER- and mitochondria-mediated apoptotic pathways is responsible for Zn-BC-AM PDT-induced NPC cell death.