Variant histologies of urothelial carcinoma: Does it change the survival outcomes in patients managed with radical cystectomy?

OBJECTIVE: To investigate the impact of variant histologies (VH) of urothelial carcinoma (UC) on survival outcomes after radical cystectomy (RC). MATERIALS AND METHODS: Data from 181 patients with UC treated with RC between January 2013 and December 2019 at a single tertiary care referral center were retrospectively accessed. All RC specimens were assigned by genitourinary dedicated pathologists. Overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS) were evaluated using the Kaplan-Meier methodology and the Cox proportional hazards regression. RESULTS: Of 181 patients, 43.1% (n = 78) had VH, with the most common being squamous differentiation (n = 29), followed by mixed variants (n = 18), micropapillary variant (n = 10) and other subtypes (n = 21). The median (range) follow-up was 35 (18-59) months. Kaplan-Meier survival analysis shows that median OS and DS were significantly worse for VH patients (78 vs 31 months, p = 0.038; not reached vs 42 months; p = 0.016). At 5 years, VH was associated with a 12% and 14% decrease in OS and DSS, respectively. No significant statistical difference between the two groups was reached regarding RFS. However, after adjusting for confounders, such as, demographics characteristics, comorbidities and pathological features, VH were not associated with any survival outcomes. CONCLUSIONS: Our study evidenced the high incidence of bladder cancers with VH. Although clearly associated with features of more aggressive behavior, VH had not any significant impact in survival expectancies when all confounders are adjusted in multivariate analyses.

Intramuscular Etofenamate versus Diclofenac in the Relief of Renal Colic : A Randomised, Single-Blind, Comparative Study.

OBJECTIVE: To compare the efficacy and adverse effects of intramuscular etofenamate and intramuscular diclofenac in the relief of acute renal colic. PATIENTS AND METHODS: A multicentre, randomised, single-blind study was performed in 119 patients admitted to the emergency room for renal colic. Patients were assigned to treatment with either etofenamate 1000mg or diclofenac 75mg, both administered intramuscularly. Pain was self-assessed using a 4-point verbal rating scale (VRS) and a visual analogue scale (VAS) just before drug administration and 30, 60, 120 and 240 min later. RESULTS: The two groups were similar with regard to baseline characteristics. The percentages of patients who reported an improvement in the VRS at 60 min post-administration (primary variable) were 84.5% with etofenamate and 83.3% with diclofenac (p = 0.73). At the other timepoints (30, 120 and 240 min), the proportions of patients improved were, respectively, 69.5%, 82.6% and 79.3% in the etofenamate group, and 75.0%, 81.7% and 80.0% in the diclofenac group. The VAS score showed a statistically significant improvement in both groups, but no differences between groups were found.Analgesic rescue medication was required by 11 (18.6%) patients in the etofenamate group and by 12 (20.0%) patients in the diclofenac group. Mild to moderate adverse events were reported by 3.4% of patients receiving etofenamate and by 5.0% of patients receiving diclofenac. CONCLUSION: Etofenamate and diclofenac were similarly effective and tolerated in the relief of acute renal colic.

Temsirolimus improves cytotoxic efficacy of cisplatin and gemcitabine against urinary bladder cancer cell lines.

OBJECTIVES: To analyze the cytotoxic action of temsirolimus using 3 established human bladder cancer cell lines and to assess whether temsirolimus potentiates the anticancer activity of gemcitabine and cisplatin. METHODS: Temsirolimus (500, 1,000, 2,000, and 4,000 nM), in isolation, and combined with gemcitabine (100 nM) and cisplatin (2.5 µg/ml), was given to 5637, T24, and HT1376 bladder cancer cell lines. Cell proliferation, autophagy, early apoptosis, and cell cycle distribution were analyzed after a 72-hour period. The expression of mammalian target of rapamycin baseline, Akt, and their phosphorylated forms, before and after treatment with temsirolimus, was evaluated by immunoblotting. RESULTS: Temsirolimus slightly decreased the bladder cancer cell proliferation in all 3 cell lines. No significant differences in the expression of mammalian target of rapamycin, Akt, and their phosphorylated forms because of temsirolimus exposure were found in the 3 cell lines. As part of a combined regime along with gemcitabine, and especially with cisplatin, there was a more pronounced antiproliferative effect. This pattern of response was similar to the other parameters analyzed (increased autophagy and apoptosis). Also, in the combined regime, an enhanced cell cycle arrest in the G0/G1 phase was observed. The non-muscle invasive 5637 bladder cancer cell line was most sensitive to both combinations. CONCLUSIONS: Temsirolimus makes a moderate contribution in terms of cell proliferation, apoptosis, and autophagy. However, it does potentiate the activity of gemcitabine and particularly cisplatin. Therefore, cisplatin- or gemcitabine-based chemotherapy regimen used in combination with temsirolimus to treat bladder cancer represents a novel and valuable treatment option, which should be tested for future studies in urinary bladder xenograft models.