Discontinuation rates and inter-injection interval for repeated intravesical botulinum toxin type A injections for detrusor overactivity.

OBJECTIVE: To report discontinuation rates, inter-injection interval and complication rates after repeated intravesical botulinum toxin type A for the treatment of detrusor overactivity. METHOD: Patients with urodyamically proven detrusor overactivity who had two or more botulinum toxin type A injections in the period 2004-2011 at Freeman Hospital, Newcastle Upon Tyne, UK, were considered for the present study. Discontinuation rates, complication rates and interval between botulinum toxin type A treatments were retrospectively analyzed. RESULTS: Overall, 125 patients (median age 53 years, range 19-83 years) were included in the analysis. The female-to-male ratio was 2.4:1 and median follow up was 38 months. A total of 96 patients had idiopathic detrusor overactivity, whereas 29 had neurogenic detrusor overactivity. A total of 667 injections were carried out, with 125 patients receiving two injections, 60 receiving three injections, 28 receiving four injections, 14 receiving five injections, three receiving six injections, three receiving seven injections and two receiving eight injections. The mean interval (±standard deviation) between the first and second injection (n = 125) was 17.6 months (±10.4), between the second and third (n = 60) was 15.7 ± 7.4 months, between the third and fourth (n = 28) was 15.4 ± 8.6 months, and between the fourth and subsequent injections (n = 22) was 11.6 ± 4.5 months. A total of 26% required intermittent catheterization, and 18% developed recurrent urinary tract infections. There was a discontinuation rate of 25% at 60 months. CONCLUSION: Repeated botulinum toxin type A injections represent a safe and effective method for managing patients with idiopathic detrusor overactivity and neurogenic detrusor overactivity. We have shown that the inter-injection interval remains unchanged up to five injections.

External validation of four nephrometry scores for trans-peritoneal robotic partial nephrectomy.

INTRODUCTION: External validation of four nephrometry scores (NS): Centrality index (C-index), arterial based complexity (ABC), preoperative aspects and dimensions used for an anatomical (PADUA) and radius expohytic/endophytic nearness anterior/posterior location (RENAL) scoring systems in patients who have undergone trans-peritoneal robotic assisted partial nephrectomy (RAPN). MATERIAL AND METHODS: A prospective database for RAPN has been maintained. Individual NSs were performed on 3-dimensional reconstructions of MDCT/MRI studies retrospectively by a board certified uroradiologist. Univariate Cox Proportional-Hazard Regression Analysis was performed for each NSs to valuate its predictability for the following parameters: Warm Ischemia Time (WIT), Estimated Blood Loss (EBL), Operative Time (OT), Complication Rates and Positive Margin Rates. RESULTS: 78 RAPNs were performed for suspected renal malignancies. The mean OT, EBL and WIT time was 186.5 minutes (SD - 33.8), 125.5 mls (SD - 188.91) and 16.7 minutes (SD - 5.6) respectively. The overall complication rate was 20.5% (16/78) of which only 2.6% (2/78) were Clavien Grade 3 or higher complications. The mean change in creatinine change at Day - 1 was 12.54 µmol/L (SD - 18.05). On the Cox regression analysis only the Centrality index predicted prolonged WIT with statistical significance: C-Index (0.02), ABC (0.2), PADUA (0.2), RENAL (0.9). ABC predicted operative time with statistical significance: C-index (0.45), ABC (0.0004), PADUA (0.25), RENAL (0.3). None of the NSs could predict overall complication: C-index (0.5), ABC (0.2), PADUA (0.13), RENAL (0.5). None of the NSs predicted EBL: C-index (0.3)0, ABC (0.8), PADUA (0.2), RENAL (0.7). None of the NSs predicted Positive Margin Rates: C-index (0.4), ABC (0.4), PADUA (0.9), RENAL (0.8). CONCLUSIONS: C-index was able to predict prolonged WIT. ABC was a strong predictor of OT. PADUA and RENAL were poor predictors for all measured parameters.

Early vs. standard unclamping technique in minimal access partial nephrectomy: a meta-analysis of observational cohort studies and the Lister cohort.

To evaluate if early unclamping (EUC) of the renal pedicle compromises perioperative outcomes in minimally invasive partial nephrectomy (PN). The cohort study includes all robot-assisted PN performed between September 2012 and September 2015 by a single surgeon at the Lister Hospital, Stevenage, UK. The systematic review and meta-analysis was performed according to the PRISMA guidelines identifying studies comparing EUC and standard unclamping (SUC) in either laparoscopic or robot-assisted PN. The Lister cohort prospectively reported 84 cases of robot-assisted PN (SUC = 22, EUC = 62) with a mean age of 58 years (SD = 11). The operative time (OT), estimated blood loss (EBL) and warm ischaemia time (WIT) were 186.5 min (SD = 33.8), 125.5 mls (SD = 188.91) and 16.7 min (SD = 5.6), respectively. The data from the Lister cohort were included in the meta-analysis. The systematic review identified four studies, encompassing 666 cases (313 SUC, 353 EUC), for inclusion in the final analysis. There was a statistically significant difference in WIT in favour of the EUC group [-10.59 min (95% CI -16.58, -4.60)]. Specifically, the reduction in WIT was more pronounced in laparoscopic PN (-15.43 min (95% CI -19.05, -11.81)), when compared with the robotic PN [-5.60 min (95% CI -5.70, -5.50)]. There was no statistical difference in OT [-3.97 min (95% CI -14.22, 6.28)]. EBL was found to be increased in the EUC group [71.39 ml (95% CI -0.78, 143.56)]. There was no statistically significant difference in transfusion rates or complications between the two groups. The EUC technique for robot-assisted PN appears to offer a safe limited period of WIT without compromising perioperative outcomes and morbidity.

Atypical Small Acinar Proliferation and High Grade Prostatic Intraepithelial Neoplasia: Should We Be Concerned? An Observational Cohort Study with a Minimum Follow-Up of 3 Years.

INTRODUCTION: Atypical small acinar proliferation (ASAP) and high grade prostatic intraepithelial neoplasia (HGPIN) are considered precancerous. We aimed to measure the rate of repeat biopsy and adenocarcinoma in patients with ASAP and HGPIN and identify any clinico-pathologic parameters at diagnosis of ASAP/HGPIN that are predictive of adenocarcinoma. MATERIALS AND METHODS: Patients with a diagnosis of ASAP/HGPIN with no previous or concomitant cancer were identified. Prostate specific antigen (PSA) and magnetic resonance imaging (MRI) changes were monitored. Re-biopsy was at clinician discretion. RESULTS: Nineteen were diagnosed with ASAP and 17 with HGPIN. Seven with ASAP (37%) and 6 with HGPIN (35%) underwent re-biopsy. Three (16%) with ASAP and 5 with HGPIN (29%) were diagnosed with adenocarcinoma. The difference in cancer detection rates between ASAP and HGPIN was not significant (p = 0.35). Five (14%) in total required definitive therapy for adenocarcinoma. Twenty-three (64%) did not undergo repeat biopsy. Parameters at diagnosis of HGPIN and ASAP, including PSA, prostate volume and PSA density, were compared between the cancer and non-cancer cohorts with none found to be predictive of adenocarcinoma. CONCLUSION: By monitoring PSA and MRI changes, we managed to spare re-biopsy in two-thirds of patients. Further evaluation is necessary to characterize a surveillance protocol in these populations.

The co-chaperone p23 promotes prostate cancer motility and metastasis.

Prostate cancer is an androgen receptor (AR)-dependent malignancy at initiation and progression, therefore hormone therapy is the primary line of systemic treatment. Despite initial disease regression, tumours inevitably recur and progress to an advanced castration-resistant state a major feature of which is metastasis to the bone. Up-regulation of AR cofactors and chaperones that overcome low hormone conditions to maintain basal AR activity has been postulated as a mechanism of therapy relapse. p23, an essential component of the apo-AR complex, acts also after ligand binding to increase AR transcriptional activity and target gene expression, partly by increasing chromatin-loaded holo-receptor-complexes. Immunohistochemical studies have demonstrated increased p23 expression in advanced prostate cancer. Here, we further characterise p23 roles in AR signalling and show that it modulates cytosolic AR levels in the absence of hormone, confirming a chaperoning function in the aporeceptor complex and suggesting p23 upregulates AR signalling at multiple stages. Moreover, p23 protein levels significantly increased upon treatment with not only androgen but also clinically relevant anti-androgens. This was in contrast to the HSP90 inhibitor 17-AAG, which did not modulate expression of the cochaperone - important given the HSP90-independent roles we and others have previously described for p23. Further, we demonstrate p23 is implicated in prostate cancer cell motility and in acquisition of invasiveness capacity through the expression of specific genes known to participate in cancer progression. This may drive metastatic processes in vivo since analysis of prostate tumour biopsies revealed that high nuclear p23 significantly correlated with shorter survival times and with development of metastases in patients with lower grade tumours. We propose that increased p23 expression may allow cells to acquire a more aggressive phenotype, contributing to disease progression, and that p23 is a plausible secondary target in combination with HSP90 inhibition as a potential therapy for advanced prostate cancer.