A New Fuzzy Modeling Framework for Integrated Risk Prognosis and Therapy of Bladder Cancer Patients

This paper presents a new fuzzy modelling approach for analysing censored survival data and finding risk groups of patients diagnosed with bladder cancer. The proposed framework involves a new procedure for integrating the frameworks of interval type-2 fuzzy logic and Cox modelling intrinsically. The output of this synergistic framework is a risk score/prognostics index which is indicative of the patient's level of mortality risk. A threshold value is selected whereby patients with risk scores that are greater than this threshold are classed as high risk patients and vice versa. Unlike in the case of black-box type modelling approaches, the paper shows that interpretability and transparency are maintained using the proposed fuzzy modelling framework

The patients' experience of a bladder cancer diagnosis: a systematic review of the qualitative evidence.

PURPOSE: Bladder cancer (BC) is a common disease with disparate treatment options and variable outcomes. Despite the disease's high prevalence, little is known of the lived experience of affected patients. National patient experience surveys suggest that those with BC have poorer experiences than those with other common cancers. The aim of this review is to identify first-hand accounts of the lived experiences of diagnosis through to survivorship. METHOD: This is a systematic review of the qualitative evidence reporting first-hand accounts of the experiences of being diagnosed with, treated for and surviving bladder cancer. A thematic analysis and 'best-fit' framework synthesis was undertaken to classify these experiences. RESULTS: The inconsistent nature of symptoms contributes to delays in diagnosis. Post-diagnosis, many patients are not actively engaged in the treatment decision-making process and rely on their doctor's expertise. This can result in patients not adequately exploring the consequences of these decisions. Learning how to cope with a 'post-surgery body', changing sexuality and incontinence are distressing. Much less is known about the quality of life of patients receiving conservative treatments such as Bacillus Calmette-Guerin (BCG). CONCLUSIONS: The review contributes to a greater understanding of the lived experience of bladder cancer. Findings reflect a paucity of relevant literature and a need to develop more sensitive patient-reported outcome measures (PROMs) and incorporate patient-reported outcomes in BC care pathways. IMPLICATIONS FOR CANCER SURVIVORS: Collective knowledge of the patients' self-reported experience of the cancer care pathway will facilitate understanding of the outcomes following treatment

How to treat a patient with T1 high-grade disease and no tumour on repeat transurethral resection of the bladder?

A relatively young (64-yr old) long-term heavy smoker but otherwise very healthy man is diagnosed with a primary unifocal left-side tumour (urothelial, T1 high grade), but no lymphovascular invasion and no variant histology. We discuss whether treatment with intravesical bacillus Calmette-Guérin vaccine will be sufficient or early radical cystectomy is at least equally preferred regarding patient benefit, safety, and quality of life. Patient summary A patient with a single high-grade T1 bladder tumour without aggressive features (eg, lymphovascular invasion or variant tumour aspects) will be adequately treated with bacillus Calmette-Guérin intravesical therapy delivered into the bladder, followed by 3 yr of maintenance. However, all decisions should be taken with the patient in a shared decision-making process, including a discussion regarding removal of the bladder

Reduced Expression of miRNA-27a Modulates Cisplatin Resistance in Bladder Cancer by Targeting the Cystine/Glutamate Exchanger SLC7A11

Purpose: Resistance to cisplatin-based chemotherapy is a major obstacle to bladder cancer treatment. We aimed to identify microRNAs (miRNA) that are dysregulated in cisplatin-resistant disease, ascertain how these contribute to a drug-resistant phenotype, and how this resistance might be overcome. Experimental Design: miRNA expression in paired cisplatin-resistant and -sensitive cell lines was measured. Dysregulated miRNAs were further studied for their ability to mediate resistance. The nature of the cisplatin-resistant phenotype was established by measurement of cisplatin/DNA adducts and intracellular glutathione (GSH). Candidate miRNAs were examined for their ability to (i) mediate resistance and (ii) alter the expression of a candidate target protein (SLC7A11); direct regulation of SLC7A11 was confirmed using a luciferase assay. SLC7A11 protein and mRNA, and miRNA-27a were quantified in patient tumor material. Results: A panel of miRNAs were found to be dysregulated in cisplatin-resistant cells. miRNA-27a was found to target the cystine/glutamate exchanger SLC7A11 and to contribute to cisplatin resistance through modulation of GSH biosynthesis. In patients, SLC7A11 expression was inversely related to miRNA-27a expression, and those tumors with high mRNA expression or high membrane staining for SLC7A11 experienced poorer clinical outcomes. Resistant cell lines were resensitized by restoring miRNA-27a expression or reducing SLC7A11 activity with siRNA or with sulfasalazine. Conclusion: Our findings indicate that miRNA-27a negatively regulates SLC7A11 in cisplatin-resistant bladder cancer, and shows promise as a marker for patients likely to benefit from cisplatin-based chemotherapy. SLC7A11 inhibition with sulfasalazine may be a promising therapeutic approach to the treatment of cisplatin-resistant disease

Prospective Implementation of Enhanced Recovery After Surgery Protocols to Radical Cystectomy

Background Multimodal enhanced recovery after surgery (ERAS) regimens have improved outcomes from colorectal surgery. Objective We report the application of ERAS to patients undergoing radical cystectomy (RC). Design, setting, and participants Prospective collection of outcomes from consecutive patients undergoing RC at a single institution. Intervention Twenty-six components including prehabilitation exercise, same day admission, carbohydrate fluid loading, targeted intraoperative fluid resuscitation, regional local anaesthesia, cessation of nasogastric tubes, omitting oral bowel preparation, avoiding drain use, early mobilisation, chewing gum use, and audit. Outcome measurements and statistical analysis Primary outcomes were length of stay and readmission rate. Secondary outcomes included intraoperative blood loss, transfusion rates, survival, and histopathological findings. Results and limitations Four hundred and fifty-three consecutive patients underwent RC, including 393 (87%) with ERAS. Length of stay was shorter with ERAS (median [interquartile range]: 8 [6–13] d) than without (18 [13–25], p 0.1). Multivariable analysis revealed ERAS use was (p = 0.002) independently associated with length of stay. Conclusions The use of ERAS pathways was associated with lower intraoperative blood loss and faster discharge for patients undergoing RC. These changes did not increase readmission rates or alter oncological outcomes. Patient summary Recovery after major bladder surgery can be improved by using enhanced recovery pathways. Patients managed by these pathways have shorter length of stays, lower blood loss, and lower transfusion rates. Their adoption should be encouraged

Quality indicators for bladder cancer services : a collaborative review

Context There is a lack of accepted consensus on what should constitute appropriate quality-of-care indicators for bladder cancer. Objective To evaluate the optimal management of bladder cancer and propose quality indicators (QIs). Evidence acquisition A systematic review was performed to identify literature on current optimal management and potential quality indicators for both non–muscle-invasive (NMIBC) and muscle-invasive (MIBC) bladder cancer. A panel of experts was convened to select a recommended list of QIs. Evidence synthesis For NMIBC, preoperative QIs include tobacco cessation counselling and appropriate imaging before initial transurethral resection of bladder tumour (TURBT). Intraoperative QIs include administration of antibiotics, proper safe conduct of TURBT using a checklist, and performing restaging TURBT with biopsy of the prostatic urethra in appropriate cases. Postoperative QIs include appropriate receipt of perioperative adjuvant therapy, risk-stratified surveillance, and appropriate decision to change therapy when indicated (eg, unresponsive to bacillus Calmette-Guerin). For MIBC, preoperative QIs include multidisciplinary care, selection for candidates for continent urinary diversion, receipt of neoadjuvant cisplatin-based chemotherapy, time to commencing radical treatment, consideration of trimodal therapy as a bladder-sparing alternative in select patients, preoperative counselling with stoma marking, surgical volume of radical cystectomy, and enhanced recovery after surgery protocols. Intraoperative QIs include adequacy of lymphadenectomy, blood loss, and operative time. Postoperative QIs include prospective standardised monitoring of morbidity and mortality, negative surgical margins for pT2 disease, appropriate surveillance after primary treatment, and adjuvant cisplatin-based chemotherapy in appropriate cases. Participation in clinical trials was highlighted as an important component indicating high quality of care. Conclusions We propose a set of QIs for both NMIBC and MIBC based on established clinical guidelines and the available literature. Measurement of these QIs could aid in improvement and benchmarking of optimal care of bladder cancer. Patient summary After a systematic review of existing guidelines and literature, a panel of experts has recommended a set of quality indicators that can help providers and patients measure and strive towards optimal outcomes for bladder cancer care

Molecular subtyping of bladder cancer using Kohonen self-organizing maps

Kohonen self-organizing maps (SOMs) are unsupervised Artificial Neural Networks (ANNs) that are good for low-density data visualization. They easily deal with complex and nonlinear relationships between variables. We evaluated molecular events that characterize high- and low-grade BC pathways in the tumors from 104 patients. We compared the ability of statistical clustering with a SOM to stratify tumors according to the risk of progression to more advanced disease. In univariable analysis, tumor stage (log rank P = 0.006) and grade (P < 0.001), HPV DNA (P < 0.004), Chromosome 9 loss (P = 0.04) and the A148T polymorphism (rs 3731249) in CDKN2A (P = 0.02) were associated with progression. Multivariable analysis of these parameters identified that tumor grade (Cox regression, P = 0.001, OR.2.9 (95% CI 1.6–5.2)) and the presence of HPV DNA (P = 0.017, OR 3.8 (95% CI 1.3–11.4)) were the only independent predictors of progression. Unsupervised hierarchical clustering grouped the tumors into discreet branches but did not stratify according to progression free survival (log rank P = 0.39). These genetic variables were presented to SOM input neurons. SOMs are suitable for complex data integration, allow easy visualization of outcomes, and may stratify BC progression more robustly than hierarchical clustering

Changing current practice in urology: Improving guideline development and implementation through stakeholder engagement

Effective stakeholder integration for guideline development should improve outcomes and adherence to clinical practice guidelines