62 research outputs found

    A proof-of-concept study on endoscopic ultrasound-guided biopsy of detrusor muscle in porcine bladders

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    IntroductionConventionally, we rely on transurethral resection of bladder tumour (TURBT) for local staging of muscle-invasive bladder cancer (MIBC). However, the procedure is limited by its staging inaccuracy which may delay the definitive treatment of MIBC.MethodsWe conducted a proof-of concept study on endoscopic ultrasound (EUS)-guided biopsy of detrusor muscle in porcine bladders. Five porcine bladders were used in this experiment. Upon EUS, four layers of tissue including the mucosa (hypoechoic), submucosa (hyperechoic), detrusor muscle (hypoechoic) and serosa (hyperechoic) could be identified.ResultsA total of 37 EUS-guided biopsies were taken from 15 sites (three sites per bladder), and the mean number of biopsies taken from each site was 2.47±0.64. Among the 37 biopsies, 30 of them (81.1%) obtained detrusor muscle in the biopsy specimen. For the per biopsy site analysis, detrusor muscle was obtained in 73.3% if only one biopsy was taken, and 100% if two or more biopsies were taken from the same biopsy site. Overall, detrusor muscle was successfully obtained from all 15 biopsy sites (100%). No bladder perforation was observed throughout all biopsy processes.ConclusionEUS-guided biopsy of the detrusor muscle could be performed during the initial cystoscopy session, thus expediting the histological diagnosis and subsequent treatment of MIBC

    Catalog of prognostic tissue-based biomarkers in patients treated with neoadjuvant systemic therapy for urothelial carcinoma of the bladder: a systematic review

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    PURPOSE The present systematic review aimed to identify prognostic values of tissue-based biomarkers in patients treated with neoadjuvant systemic therapy (NAST), including chemotherapy (NAC) and checkpoint inhibitors (NAI) for urothelial carcinoma of the bladder (UCB). MATERIAL AND METHODS The PubMed, Web of Science, and Scopus databases were searched in August 2020 according to the PRISMA statement. Studies were deemed eligible if they compared oncologic or pathologic outcomes in patients treated with NAST for UCB with and without detected pretreatment tissue-based biomarkers. RESULTS Overall, 44 studies met our eligibility criteria. Twenty-three studies used immunohistochemistry (IHC), 19 – gene expression analysis, three - quantitative polymerase chain reaction (QT PCR), and two – next-generation sequencing (NGS). According to the currently available literature, predictive IHC-assessed biomarkers, such as receptor tyrosine kinases and DNA repair pathway alterations, do not seem to convincingly improve our prediction of pathologic response and oncologic outcomes after NAC. Luminal and basal tumor subtypes based on gene expression analysis showed better NAC response, while claudin-low and luminal-infiltrated tumor subtypes did not. In terms of NAI, PD-L1 seems to maintain value as a predictive biomarker, while the utility of both tumor mutational burden and molecular subtypes remains controversial. Specific genomic alterations in DNA repair genes have been shown to provide significant predictive value in patient treated with NAC. QT PCR quantification of specific genes selected through microarray analysis seems to classify cases regarding their NAC response. CONCLUSION We believe that the present systematic review may offer a robust framework that will enable the testing and validation of predictive biomarkers in future prospective clinical trials. NGS has expanded the discovery of molecular markers that are reflective of the mechanisms of the NAST response

    Laser Ablation Efficiency, Laser Ablation Speed, and Laser Energy Consumption During Lithotripsy: What Are They and How Are They Defined? A Systematic Review and Proposal for a Standardized Terminology

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    Context Laser performance for lithotripsy is currently reported using units of measurement such as J/mm3, mm3/J, mm3/s, s/mm3, and mm3/min. However, there are no current standardized definitions or terminology for these metrics. This may lead to confusion when assessing and comparing different laser systems. Objective The primary objective was to summarize outcome values and corresponding terminology from studies on laser lithotripsy performance using stone volume in relation to time or energy. The secondary objective was to propose a standardized terminology for reporting laser performance metrics. Evidence acquisition A systematic review of the literature was conducted using the search string (“j*/mm3” OR “mm3/j*” OR “mm3/s*” OR “s*/mm3” OR “mm3/min*” OR “min*/mm3” AND “lithotripsy”) on Scopus, Web of Science, Embase, and PubMed databases. Study selection, data extraction, and quality assessment were performed independently by two authors. Evidence synthesis A total of 28 studies were included, covering holmium:yttrium-aluminum-garnet (Ho:YAG), MOSES, and thulium fiber laser (TFL) technologies. Laser energy consumption values reported for the studies ranged from 2.0 – 43.5 J/mm3 in vitro and from 2.7 – 47.8 J/mm3 in vivo, translating to laser ablation efficiency of 0.023 – 0.500 mm3/J and 0.021 – 0.370 mm3/J, respectively. Laser ablation speeds ranged from 0.3 – 8.5 mm3/s in vivo, translating to lasing time consumption of 0.12 – 3.33 s/mm3. Laser efficacy ranged from 4.35 – 51.7 mm3/min in vivo. There was high heterogeneity for the terminology used to describe laser performance for the same metrics. Conclusions The range of laser performance metric values relating stone volume to energy or time is wide, with corresponding differing terminology. We propose a standardized terminology for future studies on laser lithotripsy, including laser ablation efficiency (mm3/J), laser ablation speed (mm3/s), and laser energy consumption (J/mm3). Laser efficacy (mm3/min) is proposed as a broader term that is based on the total operative time, encompassing the whole technique using the laser. Patient summary We reviewed studies to identify the units and terms used for laser performance when treating urinary stones. The review revealed a wide range of differing units, outcomes, and terms. Therefore, we propose a standardized terminology for future studies on laser stone treatment. Keywords UreteroscopyPercutaneous nephrolithotomyLaserStone diseaseLithotripsyPerformanceUrolithiasi

    Intravesical Therapy in Patients with Intermediate-risk Non–muscle-invasive Bladder Cancer: A Systematic Review and Network Meta-analysis of Disease Recurrence

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    Context Patients with intermediate-risk non–muscle-invasive bladder cancer (NMIBC) may pose a clinical dilemma without an agreed evidence-based decision tree for personalized treatment. Objective To perform a systematic review and network meta-analysis (NMA) to summarize available evidence on the oncologic outcomes of intravesical therapy in patients with intermediate-risk NMIBC. Evidence acquisition The MEDLINE, EMBASE, and ClinicalTrials.gov databases were searched in October 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies were deemed eligible if they reported on oncologic outcomes in patients with intermediate-risk NMIBC treated with transurethral resection of bladder tumor with and without intravesical chemotherapy or bacillus Calmette-Guérin (BCG) immunotherapy. Evidence synthesis Twelve studies were included in a qualitative synthesis (systematic review); three were deemed eligible for a quantitative synthesis (NMA). An NMA of five different regimens was conducted for the association of treatment with the 5-yr recurrence risk. Chemotherapy with maintenance was associated with a lower likelihood of 5-yr recurrence than chemotherapy without maintenance (odds ratio [OR] 0.51, 95% credible interval [CI] 0.26–1.03). Immunotherapy, regardless of whether a full- or reduced-dose regimen, was not associated with a significantly lower likelihood of 5-yr recurrence when compared with chemotherapy without maintenance (OR 0.90, 95% CI 0.39–2.11 vs OR 0.93, 95% CI 0.40–2.19). Analysis of the treatment ranking revealed that chemotherapy with maintenance had the lowest 5-yr recurrence risk (P score 0.9666). Conclusions Our analysis indicates that chemotherapy with a maintenance regimen confers a superior oncologic benefit in terms of 5-yr recurrence risk compared to chemotherapy without maintenance in patients with intermediate-risk NMIBC. Regardless of the dose regimen, immunotherapy with BCG does not appear to be superior to chemotherapy in patients with intermediate-risk NMIBC in term of disease recurrence. However, owing to the lack of comparative studies, there is an unmet need for well-designed, large-scale trials to validate our findings and generate robust evidence on disease recurrence and progression. Patient summary A maintenance schedule of chemotherapy reduces the rate of long-term recurrence of bladder cancer that has not invaded the bladder muscle. Chemotherapy inserted directly into the bladder and immunotherapy without maintenance schedules seem to have limited benefit in preventing cancer recurrence

    A systematic review and meta-analysis on delaying surgery for urothelial carcinoma of bladder and upper tract urothelial carcinoma: Implications for the COVID19 pandemic and beyond

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    © 2022 Leow, Tan, Tan, Tan, Chan, Tikkinen, Kamat, Sengupta, Meng, Shariat, Roupret, Decaestecker, Vasdev, Chong, Enikeev, Giannarini, Ficarra and Teoh. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/Purpose: The COVID-19 pandemic has led to competing strains on hospital resources and healthcare personnel. Patients with newly diagnosed invasive urothelial carcinomas of bladder (UCB) upper tract (UTUC) may experience delays to definitive radical cystectomy (RC) or radical nephro-ureterectomy (RNU) respectively. We evaluate the impact of delaying definitive surgery on survival outcomes for invasive UCB and UTUC. Methods: We searched for all studies investigating delayed urologic cancer surgery in Medline and Embase up to June 2020. A systematic review and meta-analysis was performed. Results: We identified a total of 30 studies with 32,591 patients. Across 13 studies (n = 12,201), a delay from diagnosis of bladder cancer/TURBT to RC was associated with poorer overall survival (HR 1.25, 95% CI: 1.09–1.45, p = 0.002). For patients who underwent neoadjuvant chemotherapy before RC, across the 5 studies (n = 4,316 patients), a delay between neoadjuvant chemotherapy and radical cystectomy was not found to be significantly associated with overall survival (pooled HR 1.37, 95% CI: 0.96–1.94, p = 0.08). For UTUC, 6 studies (n = 4,629) found that delay between diagnosis of UTUC to RNU was associated with poorer overall survival (pooled HR 1.55, 95% CI: 1.19–2.02, p = 0.001) and cancer-specific survival (pooled HR of 2.56, 95% CI: 1.50–4.37, p = 0.001). Limitations included between-study heterogeneity, particularly in the definitions of delay cut-off periods between diagnosis to surgery. Conclusions: A delay from diagnosis of UCB or UTUC to definitive RC or RNU was associated with poorer survival outcomes. This was not the case for patients who received neoadjuvant chemotherapy.Peer reviewe

    A Systematic Review of Circulating Tumor Cells Clinical Application in Prostate Cancer Diagnosis

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    The purpose of the review is to summarize the recent data on circulating tumor cells (CTC) use in clinical practice. We performed a systematic literature search using two databases (Medline and Scopus) over the past five years and the following terms: (CTC OR “circulating tumor cells” OR “liquid biopsy”) AND prostate. The primary outcome was CTC predictive value for prostate cancer (PC) progression and survival. The secondary outcomes were the CTC predictive value for therapy response and the results of CTC detection depending on the assessment method. In metastatic PC, the CTC count showed itself to be a prognostic marker in terms of clinically important features, namely survival rates and response to treatment. CTC concentration was significantly associated with the overall survival and progression-free survival rates. A strong association between the overall survival or progression-free survival rate and CTC concentration could be observed. Variant-7 androgen receptors-positive (AR-V7-positive) patients showed a poor response to androgen receptor signaling (ARS) inhibitors, but this did not compromise their response to taxanes. In localized PC, only positive Cluster of Differentiantion 82 protein (CD82+) correlated with a higher survival rate. CTC count and AR-V7 expression showed itself to be a valuable biomarker for survival in metastatic PC and response to ARS-inhibitors. CTC diagnostic performance for localized PC or for screening and early detection is not high enough to show additional value over the other biomarkers
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