Chest computed tomography for staging renal tumours: validation and simplification of a risk prediction model from a large contemporary retrospective cohort.

OBJECTIVES: To externally validate a nomogram recently proposed by Larcher et al. (BJU Int. 2017; 120: 490) and to develop a simplified model with comparable accuracy to guide on the need for staging chest computed tomography (CT) for patients with new renal masses. PATIENTS AND METHODS: We analysed the data of 1082 consecutive patients with unilateral enhancing renal masses referred to urology multidisciplinary team meetings at two centres between 2011 and 2017. All patients underwent a staging chest CT at diagnosis. We fitted multivariable logistic regression models and tested the Larcher model performance using area under the receiver-operating curve (AUC), calibration and decision curve analysis. RESULTS: Forty-two patients (3.9%) had a positive chest CT. The Larcher nomogram had an AUC of 83.8% (95% confidence interval [CI] 77.1-90.6), but was only moderately well calibrated (calibration-in-the-large = -0.61, slope = 0.82). Specifically, the nomogram overestimated the risk of positive chest CT, and the magnitude of miscalibration increased with increasing predicted risks. Using a stepwise backward approach, a new model was developed including tumour size, nodal stage and systemic symptoms. Compared with the Larcher model, the new model had a similar AUC (82.7% [95% CI 75.5-90.0]), but improved calibration and clinical net benefit. The predicted risk of positive chest CT was <1% in the low-risk group and 1.9-79.9% in the high-risk group. CONCLUSION: The Larcher nomogram is an accurate prediction tool that was moderately well calibrated with our dataset. However, our simplified model has similar accuracy and uses more objective variables available from referral, so may be easier to incorporate into clinical practice. The low-risk group from our model (tumour size ≤4 cm and no systemic symptoms) had a risk of positive chest CT <1%, suggesting these patients may forego chest CT.

Quantification of phase I/II metabolizing enzyme gene expression and polycyclic aromatic hydrocarbon-DNA adduct levels in human prostate.

BACKGROUND: Studies of migrant populations suggest that dietary and/or environmental factors play a crucial role in the etiology of prostatic adenocarcinoma (CaP). The human prostate consists of the peripheral zone (PZ), transition zone (TZ), and central zone (CZ); CaP occurs most often in the PZ. METHODS: To investigate the notion that an underlying differential expression of phase I/II genes, and/or the presence of polycyclic aromatic hydrocarbon (PAH)-DNA adducts might explain the elevated PZ susceptibility, we examined prostate tissues (matched tissue sets consisting of PZ and TZ) from men undergoing radical retropubic prostatectomy for CaP (n = 26) or cystoprostatectomy (n = 1). Quantitative gene expression analysis was employed for cytochrome P450 (CYP) isoforms CYP1A1, CYP1B1, and CYP1A2, as well as N-acetyltransferase 1 and 2 (NAT1 and NAT2) and catechol-O-methyl transferase (COMT). RESULTS: CYP1B1, NAT1, and COMT were expressed in all tissue sets; levels of CYP1B1 and NAT1 were consistently higher in the PZ compared to TZ. Immunohistochemistry confirmed the presence of CYP1B1 (nuclear-associated and primarily in basal epithelial cells) and NAT1. Normal tissue from 23 of these aforementioned 27 matched tissue sets was analyzed for PAH-DNA adduct levels using antiserum elicited against DNA modified with r7,t8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE). PAH-DNA adduct levels were highest in glandular epithelial cells, but a comparison of PZ and TZ showed no significant differences. CONCLUSION: Although expression of activating and/or detoxifying enzymes may be higher in the PZ, PAH-DNA adduct levels appear to be similar in both zones. Therefore, factors other than PAH-DNA adducts may be responsible for promotion of tumor formation in the human prostate.

Does urodynamic verification of overactive bladder determine treatment success? Results from a randomized placebo-controlled study.

OBJECTIVE: To determine whether subjects with or with no detrusor overactivity (DO) determined by urodynamic assessment respond differently to treatment with the antimuscarinic agent tolterodine (extended release formulation, ER). SUBJECTS AND METHODS: Adult subjects with urinary frequency (average >or=8 voids/24 h) and urgency with or without urgency urinary incontinence (UUI) underwent urodynamic assessment and were stratified according to whether they had DO (positive urodynamics) or not (negative urodynamics). Subjects in each urodynamic stratum were randomized to receive tolterodine-ER (4 mg once daily) or placebo for 12 weeks. Diary cards were completed for 7 days before each study visit (at baseline, week 4, and week 12). The volume per void was recorded for 3 of the 7 days. RESULTS: The difference between the positive and negative urodynamic groups in mean change in volume voided between baseline and 12 weeks was 5.38 mL (95% CI, -93 mL to +15.71 mL). This difference is within the pre-stipulated range defined for equivalence (+/-20 mL, P = 0.31). There was also no significant difference in the change from baseline to 12 weeks between the urodynamics groups in mean number of voids per day or UUI episodes. However, there was significant improvement in the treatment group compared with the placebo group, in the number of voids per 24 h (P = 0.003) and in the mean change in volume voided (P = 0.03), from baseline to 12 weeks, but not in UUI episodes (P = 0.35). CONCLUSIONS: Urodynamics status could not predict treatment outcomes between patients treated with tolterodine-ER or placebo. The results add support to evidence suggesting that urodynamic assessment is not a prerequisite for the treatment of overactive bladder (OAB). Therefore, we recommend that anticholinergic treatment may be initiated to patients with OAB symptoms without the need for urodynamics studies.

A simple validated scale to measure urgency.

PURPOSE: We validated a simple scale to measure urinary urgency. MATERIALS AND METHODS: The new 10-item scale was validated using data from experiments using a single group repeated measure design. A total of 475 patients, including 411 females and 64 males, with a mean age of 57.3 years who had been diagnosed with overactive bladder were treated with a bladder retraining regimen and antimuscarinic agent (10 mg oxybutynin controlled release per night or 4 mg tolterodine slow release per night). At each visit patient urge symptoms were recorded by the scale. Reported average daily frequency and incontinence episodes were also recorded. Of patients who were not satisfied with the symptoms 130 had 25 mg imipramine per night added to their prescription and in 130 treatment was changed to 10 mg solifenacin per night. RESULTS: Construct validity was tested by comparing the urgency scale to frequency and to incontinence (Spearman's rank correlation coefficient r = 0.38, p <0.001 and r = 0.15, p <0.001, respectively). Internal consistency showed Cronbach's alpha = 0.83. Test-retest reliability was determined in 30 patients and interobserver reliability was determined in 58 (Pearson's r = 0.99, p <0.001 and r = 0.99, p <0.001, respectively). Internal responsiveness in the imipramine add-on study in 130 patients showed a standardized response mean of 0.6 (p <0.001) and in the solifenacin swap study in 130 it showed a standardized response mean of 0.69, while external responsiveness showed a standardized response mean of 0.69 (each p <0.001). CONCLUSIONS: This scale succeeded in all validation studies. This new scale may prove useful for measuring between-drug differences in efficacy and for monitoring treatment responses in patients with overactive bladder. It now must be tested in a proper double-blind, randomized, controlled trial.

Retroperitoneal liposarcomas: a representative literature review occasioned by a rare case of laterelapse abdominal liposarcoma.

Soft tissue sarcomas (STS) are rare and heterogeneous tumours representing approximately 0.7%-1% of all adult tumours. In the adults and among the retroperitoneal sarcomas (RPS), Liposarcoma (LS) is the most common variant accounting for 12% -20% of all sarcomas and up to 45% of sarcomas at retroperitoneal localization. A rare case of LS relapsed after 15 years is giving the occasion to review the published literature and emphasise the followings concepts: 1) Despite extensive surgery remains the mainstay of treatment for localized STS at present, anatomical complexity and occult localization result in local recurrence in the majority of patients; 2) The role of imaging and tumour markers is still limited; 3) Indefinite prolonged surveillance is a key point of treatment; 4) Referral to tertiary centres with dedicated Retroperitonal Surgeons and Oncology expertise is mandatory.

Zero ischaemia partial nephrectomy: a call for standardized nomenclature and functional outcomes.

Nephron-sparing surgery for the removal of small renal masses delivers equivalent oncological outcomes and better functional outcomes compared with those associated with radical nephrectomy. All contemporary partial nephrectomy techniques including open, laparoscopic and robotic approaches involve the use of hilar clamping in order to facilitate haemostasis, and to enable accurate tumour excision and parenchymal reconstruction. Zero ischaemia was subsequently introduced as a technique to eliminate the renal ischaemia induced by hilar clamping. Following the introduction of zero ischaemia techniques, researchers have arbitrarily applied this term to techniques ranging from no use of clamping to selective clamping of renal arteries and/or veins, or their branches. Substantial variations exist in the way that zero ischaemia and other renal preservation techniques are described in the literature. Similarly, further diversity exists in the measurement and reporting of functional outcomes after surgery. The introduction of standard and reproducible classifications or guidelines will ensure consistency and uniformity. Establishing consensus on the terminology used to describe techniques and functional outcomes will not only facilitate improved communication and surgical practice, but will also enable critical appraisal of surgical techniques.

N-Acetyltransferase and sulfotransferase activity in human prostate: potential for carcinogen activation.

BACKGROUND: N-Acetyltransferases (NATs) and sulfotransferases (SULTs) are key phase II metabolizing enzymes that can be involved both in the detoxification and in the activation of many human promutagens and procarcinogens. METHODS AND RESULTS: We investigated the expression of NATs and SULTs in human prostate and tested their role in the activation the N-hydroxy (N-OH) metabolite of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a dietary carcinogen, to form DNA adducts. Western blotting showed detectable levels of NAT1, SULT1A1 and SULT1A3 with marked inter-individual variation. NAT2 and other SULT enzymes were not detectable. NAT1 was localized by immunohistochemistry to the cytoplasm of epithelial cells. The presence of acetyl Co-enzyme A (acetyl CoA) and 3'-phosphoadenosine-5'-phosphosulfate (PAPS), NAT and SULT cofactors, respectively, significantly increased the level of DNA adducts, detected by P-postlabelling analysis, in calf thymus DNA incubated with N-OH-IQ and prostate cytosolic fractions. The enhancement in the level of DNA adducts in the presence of PAPS correlated with the level of SULT1A1 protein. A single prostate cytosol with the SULT1A1*2/*2 genotype produced less DNA adducts than cytosols with the *1/*2 and *1/*1 genotypes. No significant correlation was observed between NAT1 protein level and the formation of DNA adducts, even in the presence of acetyl CoA. CONCLUSIONS: In conclusion, we demonstrated that NAT1, SULT1A1 and SULT1A3 are present in human prostate and that both enzyme classes significantly contribute to the activation of N-hydroxylated heterocyclic amines to DNA-damaging species in this tissue. Variation in expression levels, in combination with dietary and/or environmental exposure to carcinogens, could be influential in determining individual susceptibility to prostate cancer.

A pilot randomized double-blind placebo-controlled trial on the use of antibiotics on urinary catheter removal to reduce the rate of urinary tract infection: the pitfalls of ciprofloxacin.

OBJECTIVE: To assess if a short course of antibiotics starting at the time of the removing a short-term urethral catheter decreases the incidence of subsequent urinary tract infection (UTI). PATIENTS AND METHODS: Patients across specialities with a urethral catheter in situ for >/= 48 h and