An evaluation of morphological and functional multi-parametric MRI sequences in classifying non-muscle and muscle invasive bladder cancer

Objectives: Our goal is to determine the ability of multi-parametric magnetic resonance imaging (mpMRI) to differentiate muscle invasive bladder cancer (MIBC) from non-muscle invasive bladder cancer (NMIBC). Methods: Patients underwent mpMRI before tumour resection. Four MRI sets, i.e. T2-weighted (T2W) + perfusion-weighted imaging (PWI), T2W plus diffusion-weighted imaging (DWI), T2W + DWI + PWI, and T2W + DWI + PWI + dif-fusion tensor imaging (DTI) were interpreted qualitatively by two radiologists, blinded to histology results. PWI, DWI and DTI were also analysed quantitatively. Accuracy was determined using histopathology as the reference standard. Results: A total of 82 tumours were analysed. Ninety-six percent of T1-labeled tumours by the T2W + DWI + PWI image set were confirmed to be NMIBC at histopathology. Overall accuracy of the complete mpMRI protocol was 94% in differentiating NMIBC from MIBC. PWI, DWI and DTI quantitative parameters were shown to be significantly different in cancerous versus non-cancerous areas within the bladder wall in T2-labelled lesions. Conclusions: MpMRI with DWI and DTI appears a reliable staging tool for bladder cancer. If our data are validated, then mpMRI could precede cystoscopic resection to allow a faster recognition of MIBC and accelerated treatment pathways. Key Points: • A critical step in BCa staging is to differentiate NMIBC from MIBC. • Morphological and functional sequences are reliable techniques in differentiating NMIBC from MIBC. • Diffusion tensor imaging could be an additional tool in BCa staging

Robotic intracorporeal urinary diversion: practical review of current surgical techniques

In this practical review, we discuss current surgical techniques reported in the literature to perform Intracorporeal Urinary Diversion (ICUD) after Robotic Radical Cystectomy (RARC), emphasizing criticisms of single approaches and making comparisons with Extracorporeal Urinary Diversion (ECUD). Although almost 97% of all RARCs use an ECUD, ICUD is gaining in popularity, in view of its potential benefits (i.e., decreased bowel exposure, etc.), although there are a few studies comparing ICUD and ECUD. Analysing single experiences and the data from recent metanalyses, we emphasize the current critiques to ICUD, stressing particular technical details which could reduce operative time, lowering the postoperative complications rate, and improving functional outcomes. Only analysis of long-term follow-up data from large-scale homogeneous series can ascertain whether robotic intracorporeal urinary diversion is superior to other approaches

Multiparametric MRI of the bladder: inter-observer agreement and accuracy with the Vesical Imaging-Reporting and Data System (VI-RADS) at a single reference center

Objectives: To evaluate accuracy and inter-observer variability using Vesical Imaging-Reporting and Data System (VI-RADS) for discrimination between non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Methods: Between September 2017 and July 2018, 78 patients referred for suspected bladder cancer underwent multiparametric MRI of the bladder (mpMRI) prior to transurethral resection of bladder tumor (TURBT). All mpMRI were reviewed by two radiologists, who scored each lesion according to VI-RADS. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each VI-RADS cutoff. Receiver operating characteristics curves were used to evaluate the performance of mpMRI. The Ƙ statistics was used to estimate inter-reader agreement. Results: Seventy-five patients were included in the final analysis, 53 with NMIBC and 22 with MIBC. Sensitivity and specificity were 91% and 89% for reader 1 and 82% and 85% for reader 2 respectively when the cutoff VI-RADS > 2 was used to define MIBC. At the same cutoff, PPV and NPV were 77% and 96% for reader 1 and 69% and 92% for reader 2. When the cutoff VI-RADS > 3 was used, sensitivity and specificity were 82% and 94% for reader 1 and 77% and 89% for reader 2. Corresponding PPV and NPV were 86% and 93% for reader 1 and 74% and 91% for reader 2. Area under curve was 0.926 and 0.873 for reader 1 and 2 respectively. Inter-reader agreement was good for the overall score (Ƙ = 0.731). Conclusions: VI-RADS is accurate in differentiating MIBC from NMIBC. Inter-reader agreement is overall good. Key Points: • Traditionally, the local staging of bladder cancer relies on transurethral resection of bladder tumor. • However, transurethral resection of bladder tumor carries a significant risk of understaging a cancer; therefore, more accurate, faster, and non-invasive staging techniques are needed to improve outcomes. • Multiparametric MRI has proved to be the best imaging modality for local staging; therefore, its use in suitable patients has the potential to expedite radical treatment when necessary and non-invasive diagnosis in patients with poor fitness

VI-RADS Scoring Criteria for Alternative Risk-adapted Strategies in the Management of Bladder Cancer During the COVID-19 Pandemic

This ability to differentiate non–muscle-invasive from muscle invasive BCa was used to predict BCa upstaging at repeat TURBT in a recent prospective series (area under the receiver operating characteristic curve 0.93, 95% CI 0.87– 0.97) and therefore VI-RADS has been proposed for avoiding repeat TURBT according to the European Association of Urology guidelines. This may be particularly useful in cases lacking muscularis propria in the specimen or in the setting of a unifocal, small, high-grade Ta/T1 tumor, for which a preoperative VI-RADS score of 1–2 may indicate a low likelihood of tumor understaging and therefore patients may be quickly directed to appropriate adjuvant intravesical therapy for follow-up. This relatively safe approach might minimize potential exposure to COVID19 infection by avoiding a second hospital admission for a surgical procedure that is not devoid of possible complication

Systematic Review of Complications of Prostate Biopsy

AbstractContextProstate biopsy is commonly performed for cancer detection and management. The benefits and risks of prostate biopsy are germane to ongoing debates about prostate cancer screening and treatment.ObjectiveTo perform a systematic review of complications from prostate biopsy.Evidence acquisitionA literature search was performed using PubMed and Embase, supplemented with additional references. Articles were reviewed for data on the following complications: hematuria, rectal bleeding, hematospermia, infection, pain, lower urinary tract symptoms (LUTS), urinary retention, erectile dysfunction, and mortality.Evidence synthesisAfter biopsy, hematuria and hematospermia are common but typically mild and self-limiting. Severe rectal bleeding is uncommon. Despite antimicrobial prophylaxis, infectious complications are increasing over time and are the most common reason for hospitalization after biopsy. Pain may occur at several stages of prostate biopsy and can be mitigated by anesthetic agents and anxiety-reduction techniques. Up to 25% of men have transient LUTS after biopsy, and <2% have frank urinary retention, with slightly higher rates reported after transperineal template biopsy. Biopsy-related mortality is rare.ConclusionsPreparation for biopsy should include antimicrobial prophylaxis and pain management. Prostate biopsy is frequently associated with minor bleeding and urinary symptoms that usually do not require intervention. Infectious complications can be serious, requiring prompt management and continued work into preventative strategies

Integrated Epigenome Profiling of Repressive Histone Modifications, DNA Methylation and Gene Expression in Normal and Malignant Urothelial Cells

Epigenetic regulation of gene expression is commonly altered in human cancer. We have observed alterations of DNA methylation and microRNA expression that reflect the biology of bladder cancer. This common disease arises by distinct pathways with low and high-grade differentiation. We hypothesized that epigenetic gene regulation reflects an interaction between histone and DNA modifications, and differences between normal and malignant urothelial cells represent carcinogenic events within bladder cancer. To test this we profiled two repressive histone modifications (H3K9m3 and H3K27m3) using ChIP-Seq, cytosine methylation using MeDIP and mRNA expression in normal and malignant urothelial cell lines. In genes with low expression we identified H3K27m3 and DNA methylation each in 20–30% of genes and both marks in 5% of genes. H3K9m3 was detected in 5–10% of genes but was not associated with overall expression. DNA methylation was more closely related to gene expression in malignant than normal cells. H3K27m3 was the epigenetic mark most specifically correlated to gene silencing. Our data suggest that urothelial carcinogenesis is accompanied by a loss of control of both DNA methylation and H3k27 methylation. From our observations we identified a panel of genes with cancer specific-epigenetic mediated aberrant expression including those with reported carcinogenic functions and members potentially mediating a positive epigenetic feedback loop. Pathway enrichment analysis revealed genes marked by H3K9m3 were involved with cell homeostasis, those marked by H3K27m3 mediated pro-carcinogenic processes and those marked with cytosine methylation were mixed in function. In 150 normal and malignant urothelial samples, our gene panel correctly estimated expression in 65% of its members. Hierarchical clustering revealed that this gene panel stratified samples according to the presence and phenotype of bladder cancer

Enhanced Recovery after Urological Surgery: A Contemporary Systematic Review of Outcomes, Key Elements, and Research Needs

Enhanced Recovery after Surgery (ERAS) programs are multimodal care pathways that aim to decrease intra-operative blood loss, decrease postoperative complications, and reduce recovery times

Hypermethylation of CpG islands and shores around specific microRNAs and mirtrons is associated with the phenotype and presence of bladder cancer

PURPOSE To analyze the role and translational potential for hypermethylation of CpG islands and shores in the regulation of small RNAs within urothelial cell carcinoma (UCC). To examine microRNAs (miR) and mirtrons, a new class of RNA located within gene introns and processed in a Drosha-independent manner. EXPERIMENTAL DESIGN The methylation status of 865 small RNAs was evaluated in normal and malignant cell lines by using 5-azacytidine and microarrays. Bisulfite sequencing was used for CpG regions around selected RNAs. Prognostic and diagnostic associations for epigenetically regulated RNAs were examined by using material from 359 patients, including 216 tumors and 121 urinary samples (68 cases and 53 controls). Functional analyses examined the effect of silencing susceptible RNAs in normal urothelial cells. RESULTS Exonic/UTR-located miRs and mirtons are most susceptible to epigenetic regulation. We identified 4 mirtrons and 16 miRs with CpG hypermethylation across 35 regions in normal and malignant urothelium. For several miRs, hypermethylation was more frequent and dense in CpG shores than islands (e.g., miRs-9/149/210/212/328/503/1224/1227/1229), and was associated with tumor grade, stage, and prognosis (e.g., miR-1224 multivariate analysis OR = 2.5; 95% CI, 1.3-5.0; P = 0.006). The urinary expression of epigenetically silenced RNAs (miRs-152/328/1224) was associated with the presence of UCC (concordance index, 0.86; 95% CI, 0.80-0.93; ANOVA P < 0.016). CONCLUSIONS Hypermethylation of mirtrons and miRs is common in UCC. Mirtrons appear particularly susceptible to epigenetic regulation. Aberrant hypermethylation of small RNAs is associated with the presence and behavior of UCC, suggesting potential roles as diagnostic and prognostic biomarkers