Vaginal cuff recurrence after radical cystectomy: an under - studied site of bladder cancer relapse

Vaginal cuff recurrence of tumor following radical cystectomy is a rare site of disease recurrence, however it has never been specifically studied. The aim of the study is to evaluate incidence, risk factors, and long-term oncologic outcomes of vaginal cuff recurrence in a cohort of female patients treated with radical cystectomy for invasive urothelial carcinoma of the bladder

Overcoming Drug Resistance and Treating Advanced Prostate Cancer.

Most of the prostate cancers (PCa) in advanced stage will progress to castration-resistant prostate cancer (CRPC). Within CRPC group, 50-70% of the patients will develop bone metastasis in axial and other regions of the skeleton. Once PCa cells spread to the bone, currently, no treatment regimens are available to eradicate the metastasis, and cancer- related death becomes inevitable. In 2012, it is estimated that there will be 28,170 PCa deaths in the United States. Thus, PCa bone metastasis-associated clinical complications and treatment resistance pose major clinical challenges. In this review, we will present recent findings on the molecular and cellular pathways that are responsible for bone metastasis of PCa. We will address several novel mechanisms with a focus on the role of bone and bone marrow microenvironment in promoting PCa metastasis, and will further discuss why prostate cancer cells preferentially metastasize to the bone. Additionally, we will discuss novel roles of several key pathways, including angiogenesis and extracellular matrix remodeling in bone marrow and stem cell niches with their relationship to PCa bone metastasis and poor treatment response. We will evaluate how various chemotherapeutic drugs and radiation therapies may allow aggressive PCa cells to gain advantageous mutations leading to increased survival and rendering the cancer cells to become resistant to treatment. The novel concept relating several key survival and invasion signaling pathways to stem cell niches and treatment resistance will be reviewed. Lastly, we will provide an update of several recently developed novel drug candidates that target metastatic cancer microenvironments or niches, and discuss the advantages and significance provided by such therapeutic approaches in pursuit of overcoming drug resistance and treating advanced PCa

Giant growth rate in nano-oxidation of p-silicon surfaces by using ethyl alcohol liquid bridges

We demonstrate that local oxidation nanolithography can be performed in liquid environments different from aqueous solutions with a significant improvement in the aspect ratio of the fabricated motives. Here, we perform a comparative study of noncontact atomic force microscopy oxidation experiments in water and ethyl alcohol. The growth rate of local oxides can be increased by almost an order of magnitude by using oxyanions from ethyl alcohol molecules. We propose that the enhanced growth rate is a consequence of the reduction of the trapped charges within the growing oxide. The present results open the possibility of using local oxidation nanolithography to directly fabricate vertical oxide structures while keeping lateral sizes in the nanometer range.This work was supported by the European Commission (MONA-LISA, G5RD-2000-00349).Peer reviewe

Robot-assisted Radical Cystectomy Versus Open Radical Cystectomy: A Systematic Review and Meta-analysis of Perioperative, Oncological, and Quality of Life Outcomes Using Randomized Controlled Trials

CONTEXT: Differences in recovery, oncological, and quality of life (QoL) outcomes between open radical cystectomy (ORC) and robot-assisted radical cystectomy (RARC) for patients with bladder cancer are unclear. OBJECTIVE: This review aims to compare these outcomes within randomized trials of ORC and RARC in this context. The primary outcome was the rate of 90-d perioperative events. The secondary outcomes included operative, pathological, survival, and health-related QoL (HRQoL) measures. EVIDENCE ACQUISITION: Systematic literature searches of MEDLINE, Embase, Web of Science, and clinicaltrials.gov were performed up to May 31, 2022. EVIDENCE SYNTHESIS: Eight trials, reporting 1024 participants, were included. RARC was associated with a shorter hospital length of stay (LOS; mean difference [MD] 0.21, 95% confidence interval [CI] 0.03-0.39, p = 0.02) than and similar complication rates to ORC. ORC was associated with higher thromboembolic events (odds ratio [OR] 1.84, 95% CI 1.02-3.31, p = 0.04). ORC was associated with more blood loss (MD 322 ml, 95% CI 193-450, p < 0.001) and transfusions (OR 2.35, 95% CI 1.65-3.36, p < 0.001), but shorter operative time (MD 76 min, 95% CI 39-112, p < 0.001) than RARC. No differences in lymph node yield (MD 1.07, 95% CI -1.73 to 3.86, p = 0.5) or positive surgical margin rates (OR 0.95, 95% CI 0.54-1.67, p = 0.9) were present. RARC was associated with better physical functioning or well-being (standardized MD 0.47, 95% CI 0.29-0.65, p < 0.001) and role functioning (MD 8.8, 95% CI 2.4-15.1, p = 0.007), but no improvement in overall HRQoL. No differences in progression-free survival or overall survival were seen. Limitations may include a lack of generalization given trial patients. CONCLUSIONS: RARC offers various perioperative benefits over ORC. It may be more suitable in patients wishing to avoid blood transfusion, those wanting a shorter LOS, or those at a high risk of thromboembolic events. PATIENT SUMMARY: This study compares robot-assisted keyhole surgery with open surgery for bladder cancer. The robot-assisted approach offered less blood loss, shorter hospital stays, and fewer blood clots. No other differences were seen

Robot-assisted Radical Cystectomy Versus Open Radical Cystectomy: A Systematic Review and Meta-analysis of Perioperative, Oncological, and Quality of Life Outcomes Using Randomized Controlled Trials

© 2023 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)Context: Differences in recovery, oncological, and quality of life (QoL) outcomes between open radical cystectomy (ORC) and robot-assisted radical cystectomy (RARC) for patients with bladder cancer are unclear.  Objective: This review aims to compare these outcomes within randomized trials of ORC and RARC in this context. The primary outcome was the rate of 90-d perioperative events. The secondary outcomes included operative, pathological, survival, and health-related QoL (HRQoL) measures.  Evidence acquisition: Systematic literature searches of MEDLINE, Embase, Web of Science, and clinicaltrials.gov were performed up to May 31, 2022.  Evidence synthesis: Eight trials, reporting 1024 participants, were included. RARC was associated with a shorter hospital length of stay (LOS; mean difference [MD] 0.21, 95% confidence interval [CI] 0.03–0.39, p = 0.02) than and similar complication rates to ORC. ORC was associated with higher thromboembolic events (odds ratio [OR] 1.84, 95% CI 1.02–3.31, p = 0.04). ORC was associated with more blood loss (MD 322 ml, 95% CI 193–450, p < 0.001) and transfusions (OR 2.35, 95% CI 1.65–3.36, p < 0.001), but shorter operative time (MD 76 min, 95% CI 39–112, p < 0.001) than RARC. No differences in lymph node yield (MD 1.07, 95% CI –1.73 to 3.86, p = 0.5) or positive surgical margin rates (OR 0.95, 95% CI 0.54–1.67, p = 0.9) were present. RARC was associated with better physical functioning or well-being (standardized MD 0.47, 95% CI 0.29–0.65, p < 0.001) and role functioning (MD 8.8, 95% CI 2.4–15.1, p = 0.007), but no improvement in overall HRQoL. No differences in progression-free survival or overall survival were seen. Limitations may include a lack of generalization given trial patients.  Conclusions: RARC offers various perioperative benefits over ORC. It may be more suitable in patients wishing to avoid blood transfusion, those wanting a shorter LOS, or those at a high risk of thromboembolic events.  Patient summary: This study compares robot-assisted keyhole surgery with open surgery for bladder cancer. The robot-assisted approach offered less blood loss, shorter hospital stays, and fewer blood clots. No other differences were seen.Peer reviewe

Accommodating heterogeneous missing data patterns for prostate cancer risk prediction

Objective: We compared six commonly used logistic regression methods for accommodating missing risk factor data from multiple heterogeneous cohorts, in which some cohorts do not collect some risk factors at all, and developed an online risk prediction tool that accommodates missing risk factors from the end-user. Study Design and Setting: Ten North American and European cohorts from the Prostate Biopsy Collaborative Group (PBCG) were used for fitting a risk prediction tool for clinically significant prostate cancer, defined as Gleason grade group greater or equal 2 on standard TRUS prostate biopsy. One large European PBCG cohort was withheld for external validation, where calibration-in-the-large (CIL), calibration curves, and area-underneath-the-receiver-operating characteristic curve (AUC) were evaluated. Ten-fold leave-one-cohort-internal validation further validated the optimal missing data approach. Results: Among 12,703 biopsies from 10 training cohorts, 3,597 (28%) had clinically significant prostate cancer, compared to 1,757 of 5,540 (32%) in the external validation cohort. In external validation, the available cases method that pooled individual patient data containing all risk factors input by an end-user had best CIL, under-predicting risks as percentages by 2.9% on average, and obtained an AUC of 75.7%. Imputation had the worst CIL (-13.3%). The available cases method was further validated as optimal in internal cross-validation and thus used for development of an online risk tool. For end-users of the risk tool, two risk factors were mandatory: serum prostate-specific antigen (PSA) and age, and ten were optional: digital rectal exam, prostate volume, prior negative biopsy, 5-alpha-reductase-inhibitor use, prior PSA screen, African ancestry, Hispanic ethnicity, first-degree prostate-, breast-, and second-degree prostate-cancer family history

Intravesical rAd-IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study.

Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10(11) viral particles (vp)/mL or 3 × 10(11) vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd-IFNα/Syn3 (1 × 10(11) vp/mL, n = 21; 3 × 10(11) vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd-IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd-IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy

Biological and prognostic implications of biopsy upgrading for high-grade upper tract urothelial carcinoma at nephroureterectomy

Objectives Technical limitations of ureteroscopic (URS) biopsy has been considered responsible for substantial upgrading rate in upper tract urothelial carcinoma (UTUC). However, the impact of tumor specific factors for upgrading remain uninvestigated. Methods Patients who underwent URS biopsy were included between 2005 and 2020 at 13 institutions. We assessed the prognostic impact of upgrading (low-grade on URS biopsy) versus same grade (high-grade on URS biopsy) for high-grade UTUC tumors on radical nephroureterectomy (RNU) specimens. Results This study included 371 patients, of whom 112 (30%) and 259 (70%) were biopsy-based low- and high-grade tumors, respectively. Median follow-up was 27.3 months. Patients with high-grade biopsy were more likely to harbor unfavorable pathologic features, such as lymphovascular invasion (p &lt; 0.001) and positive lymph nodes (LNs; p &lt; 0.001). On multivariable analyses adjusting for the established risk factors, high-grade biopsy was significantly associated with worse overall (hazard ratio [HR] 1.74; 95% confidence interval [CI], 1.10-2.75; p = 0.018), cancer-specific (HR 1.94; 95% CI, 1.07-3.52; p = 0.03), and recurrence-free survival (HR 1.80; 95% CI, 1.13-2.87; p = 0.013). In subgroup analyses of patients with pT2-T4 and/or positive LN, its significant association retained. Furthermore, high-grade biopsy in clinically non-muscle invasive disease significantly predicted upstaging to final pathologically advanced disease (&gt;= pT2) compared to low-grade biopsy. Conclusions High tumor grade on URS biopsy is associated with features of biologically and clinically aggressive UTUC tumors. URS low-grade UTUC that becomes upgraded to high-grade might carry a better prognosis than high-grade UTUC on URS. Tumor specific factors are likely to be responsible for upgrading to high-grade on RNU