MIR145 Core Promoter Methylation in Pretreatment Cell-Free DNA: A Liquid Biopsy Tool for Muscle-Invasive Bladder Cancer Treatment Outcome.

PURPOSE: The lack of personalized management of bladder cancer (BlCa) results in patients' lifelong post-treatment monitoring with invasive interventions, underlying the urgent need for tailored and minimally invasive health care services. On the basis of our previous findings on miR-143/145 cluster methylation in bladder tumors, we evaluated its clinical significance in pretreatment cell-free DNA (cfDNA) of patients with BlCa. MATERIALS AND METHODS: Methylation analysis was performed in our screening cohort (120 patients with BlCa; 20 age-matched healthy donors) by bisulfite-based pyrosequencing. Tumor recurrence/progression for patients with non-muscle-invasive bladder cancer, and progression and mortality for patients with muscle-invasive bladder cancer (MIBC) were used as clinical end point events in survival analysis. Bootstrap analysis was applied for internal validation of Cox regression models and decision curve analysis for assessment of clinical benefit on disease prognosis. RESULTS: Decreased methylation of MIR145 core promoter in pretreatment cfDNA was associated with short-term disease progression (multivariate Cox: hazard ratio [HR], 2.027 [95% CI, 1.157 to 3.551]; P = .010) and poor overall survival (multivariate Cox: HR, 2.098 [95% CI, 1.154 to 3.817]; P = .009) of patients with MIBC after radical cystectomy (RC). Multivariate models incorporating MIR145 promoter methylation in cfDNA with tumor stage clearly ameliorated patients' risk stratification, highlighting superior clinical benefit in MIBC prognostication. CONCLUSION: Reduced pretreatment cfDNA methylation of MIR145 core promoter was markedly correlated with increased risk for short-term progression and worse survival of patients with MIBC after RC and adjuvant therapy, supporting modern personalized and minimally invasive prognosis. Methylation profiling of MIR145 core promoter in pretreatment cfDNA could serve as a minimally invasive and independent predictor of MIBC treatment outcome and emerge as a promising marker for blood-based test in BlCa.

Clinical implications of single cell sequencing for bladder cancer.

Bladder cancer (BC) is the 10th most common cancer worldwide, with about 0.5 million reported new cases and about 0.2 million deaths per year. In this scoping review, we summarize the current evidence regarding the clinical implications of single-cell sequencing for bladder cancer based on PRISMA guidelines. We searched PubMed, CENTRAL, Embase, and supplemented with manual searches through the Scopus, and Web of Science for published studies until February 2023. We included original studies that used at least one single-cell technology to study bladder cancer. Forty-one publications were included in the review. Twenty-nine studies showed that this technology can identify cell subtypes in the tumor microenvironment that may predict prognosis or response to immune checkpoint inhibition therapy. Two studies were able to diagnose BC by identifying neoplastic cells through single-cell sequencing urine samples. The remaining studies were mainly a preclinical exploration of tumor microenvironment at single cell level. Single-cell sequencing technology can discriminate heterogeneity in bladder tumor cells and determine the key molecular properties that can lead to the discovery of novel perspectives on cancer management. This nascent tool can advance the early diagnosis, prognosis judgment, and targeted therapy of bladder cancer.

Challenges and technical aspects in the management of muscle invasive bladder cancer as retrograde radical cystectomy with ileal conduit.

Objective: To evaluate long-term outcomes in patients homogenously treated with radical cystectomy and ileal conduit for muscle invasive bladder cancer. METHODS: The retrospective study was conducted at the Urology Department of Pakistan Kidney and Liver Institute and Research Centre, Lahore, Pakistan, and comprised data from December 25, 2017, to January 16, 2023, related to patients who underwent radical cystectomy with ileal conduit with or without neo-adjuvant and adjuvant radiation, chemotherapy, or immunotherapy for papillary urothelial carcinom of the bladder. Clinical trajectory, histopathological characteristics and long-term clinical outcomes were noted. Data was analysed using SPSS 20. RESULTS: In our study of 40 patients with muscle invasive bladder cancer, males predominated (32, 80%), with a median age of 57.4 years (IQR: 29-80). Diagnosis was early in 5 (12.5%) patients with varying haematuria durations, while 34 (85%) patients had a smoking history. Comorbidities included hypertension in 17 (42.5%) patients, diabetes in 1 (2.5%) patient, both hypertension and diabetes in 9 (22.5%) patients and a combination of hypertension, diabetes, and ischaemic heart disease in 3 (7.5%) patients. Transurethral resection was performed once in 13 (32.5%) patients and multiple times in 27 (67.5%) patients. Additionally, 5 (12.5%) patients received immunotherapy, 11 (27.5%) patients underwent non-adjuvant radiation, and 14 (35%) patients received non-adjuvant chemotherapy. Papillary urothelial carcinoma was the predominant histological subtype among 37 (92.5%) patients. Patients receiving chemotherapy had significantly better overall survival (p=0.02). No significant differences were noted in recurrence or survival by therapy modality (p>0.05). These findings highlight the significance of early diagnosis, tailored treatments, and comorbidity management in muscle invasive bladder cancer patients. Age stratification revealed significant survival differences across groups (χ²=10.923, df=3, p= 0.012). Analysis by complications did not show age-related survival variations (χ² =3.978, df = 3, p=0.264). Conclusion: Achieving excellent long-term survival in MIBC patients requires a multidisciplinary approach, emphasizing early diagnosis, tailored treatment, and adherence to guidelines and protocols.

The Prognostic Value of the Combination of the Prognostic Nutritional Index and the Lymphocyte:Monocyte Ratio for the Prediction of Patients with Muscle-Invasive Bladder Cancer.

OBJECTIVE: To explore the efficacy of combining the prognostic nutritional index (PNI) and the lymphocyte:monocyte ratio (LMR) for patients with muscle-invasive bladder cancer (MIBC). METHODS: Of 172 patients who were diagnosed with MIBC in our hospital, 94 were eligible for the study. The clinical data of the 94 patients with MIBC were collected. The patients were divided according to the optimal cut-off values for the preoperative PNI and LMR into a low-PNI subgroup (PNI <44.15, 52 patients), a high-PNI subgroup (PNI ≥44.15, 42 patients), a low-LMR subgroup (LMR <2.98, 50 patients) and a high-LMR subgroup (LMR ≥2.98, 44 patients). The area under the receiver operating characteristic (ROC) curve (AUC) was used to analyse the efficacy of the PNI and the LMR in predicting the prognosis of patients with MIBC. Univariate and multivariate logistic regression analyses were performed to evaluate prognostic factors for patients with MIBC. Kaplan-Meier (K‒M) survival analysis was used for overall survival (OS) analysis to explore the ability of the PNI combined with the LMR to predict the prognosis of patients with MIBC. RESULTS: The optimal cut-off values for the preoperative PNI and the preoperative LMR were 44.15 and 2.98, respectively, on the basis of ROC curves. ROC curve analysis revealed that the PNI (AUC = 0.720, sensitivity 65.9%, specificity 74.50%, Youden index 0.399) and the LMR (AUC = 0.724, sensitivity 65.9%, specificity 70.0%, Youden index 0.395) both had good prognostic efficacy for patients with MIBC. The results of univariate and multivariate logistic regression analyses showed that preoperative PNI <44.15 was an independent risk factor for OS in patients with MIBC (p = 0.027). Based on K‒M survival curve analysis, patients with PNI <44.15 and LMR <2.98 had the shortest OS (p = 0.00002). CONCLUSIONS: Low preoperative PNI and LMR values are indicative of poor prognosis in patients with MIBC. The efficacy of their combination was better than that of the factors independently.

Assessment of interleukin 17A and 23 in the course of bladder cancer and selected benign urological diseases.

Several cytokines have been indicated to be significantly involved in urological diseases. Interleukin 17A (IL-17A) and interleukin 23 (IL-23) have recently received attention for their involvement in inflammatory diseases and cancers. The aim of the study was to show changes in the level of pro-inflammatory interleukins IL-17A and IL-23 in patients with bladder cancer (BC) and selected urological diseases. An important cognitive aspect was to study the interdependencies between the studied interleukins and to assess their diagnostic value for such diseases. The material for the study was urine sample from patients with BC, urinary tract infection (UTI), urolithiasis, benign prostatic hyperplasia (BPH), US (urethral stricture), which was compared to the urine sample of healthy people without urological disorders. Interleukin concentrations were measured by the immunoenzymatic method. The levels of IL-17A and IL-23 in the urine of patients with BC, UTI, BPH and US were significantly higher compared to the control group. Statistically significant differences were found in the level of both interleukins compared to the control group in all diseases except urolithiasis. IL-17A and IL-23 correlated with each other in patients with all urological diseases except urolithiasis. The results of the conducted studies showed that selected urological diseases changed the levels of IL-17A and IL-23 in the urine of patients. The observations made confirmed the participation of these interleukins in the course of the urological diseases, especially in BC, and allowed to classify them as potentially useful parameters for diagnostic purposes.

Clinical performance and utility of a noninvasive urine-based methylation biomarker: TWIST1/Vimentin to detect urothelial carcinoma of the bladder.

Traditional clinical modalities for diagnosing bladder urothelial carcinoma (BUC) remain limited due to their invasive nature, significant costs, discomfort associated with cystoscopy, and low sensitivity to urine cytology. Therefore, there is an urgent need to identify highly sensitive, specific, and noninvasive biomarkers for the early detection of this neoplasm. Hypermethylated TWIST1/Vimentin promoter may be a noninvasive biomarker using urine sample. We assessed the TWIST1/Vimentin promoter methylation status in urine samples using the Methylated Human TWIST1 and Vimentin Gene Detection Kit (Jiangsu MicroDiag Biomedicine Co., Ltd., China). The samples were collected from five groups: group 1 consisted of patients with BUC, group 2 contained other patients with urologic tumors, group 3 consisted of patients with benign diseases (e.g., urinary tract infections, lithiasis, and benign prostatic hyperplasia), Group 4 included UTUC (upper tract urothelial carcinoma) patients and group5 comprised healthy individuals. The study encompassed 77 BUC patients, and we evaluated the degree of methylation of the TWIST1/Vimentin gene in their urine samples. Notably, TWIST1/Vimentin positivity was significantly elevated in comparison to groups 2, 3 and 5 (all p < 0.001) at a rate of 77.9%, but no significant difference was observed when compared to group 4. In the relationship between TWIST1/Vimentin methylation and clinicopathological features of BC patients from our center, we found there was no significant association between TWIST1/Vimentin status and proteinuria and/or hematuria, and hypermethylation of TWIST1 / VIM genes was found in both high and low tumor grade and in both non-muscle invasive bladder cancer (stages Tis, Ta, or T1) and muscle-invasive bladder cancer (stage T2 or above). In the multivariable analysis for cancer detection, a positive TWIST1/Vimentin methylation were significantly linked to a heightened risk of BC. Moreover, TWIST1/Vimentin promoter methylation demonstrated an ability to detect BUC in urine samples with a sensitivity of 78% and a specificity of 83%. Our findings reveal that hypermethylation of the TWIST1/Vimentin promoter occurs in bladder urothelial carcinoma, and its high sensitivity and specificity suggest its potential as a screening and therapeutic biomarker for urothelial carcinoma of the bladder.

Recurrent bladder leiomyoma: a case report.

BACKGROUND: Bladder leiomyomas are rare benign growths in the bladder, comprising less than 0.5% of bladder tumors with only 250 cases reported globally. They are more common in women. This case involves a 70-year-old woman with recurrent leiomyoma, presenting with lower urinary tract symptoms and painless hematuria. A recurrent bladder leiomyoma is rarely reported, making its presence exceptionally rare. CASE PRESENTATION: A 70-year-old Pakistani woman with hypertension and diabetes presented with lower urinary tract symptoms (LUTS) and painless hematuria. She had a history of similar symptoms in 2010, leading to a diagnosis of bladder leiomyoma via cystoscopy and biopsy. Imaging studies revealed a substantial 3.7 × 4 × 4.0 cm isodense mass with calcifications at the bladder base, along with bladder wall thickening and diverticula. Pathological examination during Transurethral Resection of Bladder Tumor (TURBT) confirmed the presence of bladder tissue with smooth muscle, ruling out malignancy. Immunohistochemical studies supported the diagnosis. A successful TURBT was performed, and the patient recovered well. DISCUSSION: Recurrent bladder leiomyoma is a rarely-discussed topic in medical literature. This article primarily aims to review existing studies and present a detailed case study, shedding light on this rare phenomenon.

Clinical effectiveness of a multitarget urine DNA test for urothelial carcinoma detection: a double-blinded, multicenter, prospective trial.

Urine-based testing is promising for noninvasive diagnosis of urothelial carcinoma (UC) but has suboptimal sensitivity for early-stage tumors. Herein, we developed a multitarget urine tumor DNA test, UI-Seek, for UC detection and evaluated its clinical feasibility. The prediction model was developed in a retrospective cohort (n = 382), integrating assays for FGFR3 and TERT mutations and aberrant ONECUT2 and VIM methylation to generate a UC-score. The test performance was validated in a double-blinded, multicenter, prospective trial (n = 947; ChiCTR2300076543) and demonstrated a sensitivity of 91.37% and a specificity of 95.09%. The sensitivity reached 75.81% for low-grade Ta tumors and exceeded 93% in high-grade Ta and higher stages (T1 to T4). Simultaneous identification of both bladder and upper urinary tract tumors was enabled with sensitivities exceeding 90%. No significant confounding effects were observed regarding benign urological diseases or non-UC malignancies. The test showed improved sensitivities over urine cytology, the NMP22 test, and UroVysion FISH alongside comparable specificities. The single-target accuracy was greater than 98% as confirmed by Sanger sequencing. Post-surgery UC-score decreased in 97.7% of subjects. Overall, UI-Seek demonstrated robust performance and considerable potential for the early detection of UC.

Enzyme-labeled liquid-based cytology (ELLBC): a new noninvasive diagnostic method for bladder cancers.

BACKGROUND: Based on liquid-based cytology, we performed an enzyme histochemical staining using acid phosphatase as a marker and termed it ELLBC. The aim of this study was to investigate the value of ELLBC in the diagnosis of bladder cancer. METHODS: Fifty patients who were initially diagnosed with suspected bladder cancers (hematuria or bladder irritation symptoms, urinary ultrasound suggestive of bladder mass) at the Second Affiliated Hospital of Anhui Medical University (Anhui, China) from January 2022 to December 2022 were selected as the study subjects, all of whom underwent ELLBC, CC, and histopathology Histopathology was used as the gold standard to calculate the diagnostic efficacy of ELLBC, CC and ELLBC combined with CC in bladder cancer. RESULTS: Histopathological examination revealed 35 positive cases in 50 patients, including 15 cases of high-grade uroepithelial carcinoma (HGUC) and 20 cases of low-grade uroepithelial carcinoma (LGUC.) The sensitivity of ELLBC was 82.86%, the specificity was 93.33%, the positive predictive value (PPV) was 96.67%, the negative predictive value (NPV) was 70.00%, and the accuracy was 86.00%; CC had a sensitivity of 37.14%, specificity of 80.00%, PPV of 81.25%, NPV of 35.29%, and accuracy of 50%; ELLBC combined with CC had a sensitivity of 88.57%, specificity of 73.33%, PPV of 88.57%, NPV of 73.33%, and accuracy of 84.00%. The sensitivity and specificity of ELLBC were higher than that of CC, and the difference was statistically significant (p < 0.05), ELLBC combined with CC achieved higher sensitivity, but the diagnostic accuracy decreased. For clinical staging, the diagnostic accuracy was 86.36% for ELLBC and 40.91% for CC in patients in Stage I, and 90.91% for ELLBC and 36.36% for CC in patients in Stage II. CONCLUSION: ELLBC has high clinical application value for the diagnosis of bladder cancer and can provide new options and methods for the early screening of bladder cancer.

Estimates of the lead time in screening for bladder cancer.

Some studies have suggested a survival benefit from early treatment of bladder cancer (BC). This benefit may be due in part to a "lead-time" bias (LT), i.e., the time interval between the detection of BC in asymptomatic individuals and the development of symptoms ("backward prolongation of survival"). To estimate the LT of BC, it was assumed that LT corresponds to the ratio between the prevalence of pre-symptomatic BC and the incidence of symptomatic BC. Data on the prevalence of pre-symptomatic BC were derived from published screening studies. Data on the annual incidence of symptomatic BC at the age and gender of the study populations were derived from national registries in the countries in the years in which the screening studies were conducted. The ratios of the prevalence of presymptomatic BC to the incidence of symptomatic BC ranged from 3.3 to 12.1 years when derived from screening for microhematuria, and from 1.8 to 5.3 years when derived from screening for urine cytology and cell markers. The estimates of the LT of BC derived from the ratios between its prevalence in asymptomatic persons and its incidence in the corresponding population were consistent with those previously reported in retrospective and prospective cohort studies. Since these estimates may account for the survival benefit from early treatment of BC, the gain of screening for BC remains uncertain and should be confirmed by controlled randomized trials.

TROP-2, NECTIN-4 and predictive biomarkers in sarcomatoid and rhabdoid bladder urothelial carcinoma.

Introduction: The surface protein TROP-2/TACSTD2 and the cell adhesion protein NECTIN-4/NECTIN4 are responsible for the efficacy of anticancer therapies based on antibody-drug conjugates (ADC) targeting intracellular microtubules. In contrast with common histologic subtypes of bladder urothelial carcinoma (BUC), little is known of TROP-2 and NECTIN-4 expression in sarcomatoid and rhabdoid BUC. Aims: In this study, we aimed to analyze TROP-2 and NECTIN-4 expression and additional predictive biomarkers by immunohistochemistry and fluorescence in situ hybridization (FISH) on 35 undifferentiated BUC (28 sarcomatoid and 7 rhabdoid). Wide genomic investigation was also performed on 411 BUC cases of the PanCancer Atlas, focusing on genes related to the microtubule pathways. Results: Seven of 35 (20%) undifferentiated BUC showed expression of TROP-2. NECTIN-4 was expressed in 10 cases (29%). Seven cases (20%) co-expressed TROP-2 and NECTIN-4. HER-2 FISH was amplified in 5 cases (14%) while HER-2 immunoexpression was observed in 14 cases (40%). PD-L1 scored positive for combined proportion score (CPS) in 66% of cases and for tumor proportion score (TPS) in 51% of cases. Pan-NTRK1-2/3 was elevated in 9 cases (26%) and FGFR-2/3 was broken in 7 of 35 cases (20%). Of 28 sarcomatoid BUC, 9 (32%) were negative for all (TROP-2, NECTIN-4, PD-L1, HER-2, FGFR and pan-NTRK) biomarkers and 3 (11%) expressed all five biomarkers. Among cases with rhabdoid dedifferentiation, 1 of 7 (14%) showed activation of all biomarkers, whereas 2 of 7 (28%) showed none. The mRNA analysis identified microtubule-related genes and pathways suitable for combined ADC treatments in BUC. Conclusion: Sarcomatoid and rhabdoid BUC do harbor positive expression of the ADC targets TROP-2 or NECTIN-4 in a relatively modest subset of cases, whereas the majority do not. Different combinations of other positive biomarkers may help the choice of medical therapies. Overall, these findings have important clinical implications for targeted therapy for BUC.

Electronic Documentation of Intraoperative Observation of Cystoscopic Procedures Using the cMDX Information System.

PURPOSE: Accurate documentation of lesions during transurethral resection of bladder tumors (TURBT) is essential for precise diagnosis, treatment planning, and follow-up care. However, optimizing schematic documentation techniques for bladder lesions has received limited attention. MATERIALS AND METHODS: This prospective observational study used a cMDX-based documentation system that facilitates graphical representation, a lesion-specific questionnaire, and heatmap analysis with a posterization effect. We designed a graphical scheme for bladder covering bladder landmarks to visualize anatomic features and to document the lesion location. The lesion-specific questionnaire was integrated for comprehensive lesion characterization. Finally, spatial analyses were applied to investigate the anatomic distribution patterns of bladder lesions. RESULTS: A total of 97 TURBT cases conducted between 2021 and 2023 were included, identifying 176 lesions. The lesions were distributed in different bladder areas with varying frequencies. The distribution pattern, sorted by frequency, was observed in the following areas: posterior, trigone, lateral right and anterior, and lateral left and dome. Suspicious levels were assigned to the lesions, mostly categorized either as indeterminate or moderate. Lesion size analysis revealed that most lesions fell between 5 and 29 mm. CONCLUSION: The study highlights the potential of schematic documentation techniques for informed decision making, quality assessment, primary research, and secondary data utilization of intraoperative data in the context of TURBT. Integrating cMDX and heatmap analysis provides valuable insights into lesion distribution and characteristics.

A deep-learning workflow to predict upper tract urothelial carcinoma protein-based subtypes from H&E slides supporting the prioritization of patients for molecular testing.

Upper tract urothelial carcinoma (UTUC) is a rare and aggressive, yet understudied, urothelial carcinoma (UC). The more frequent UC of the bladder comprises several molecular subtypes, associated with different targeted therapies and overlapping with protein-based subtypes. However, if and how these findings extend to UTUC remains unclear. Artificial intelligence-based approaches could help elucidate UTUC's biology and extend access to targeted treatments to a wider patient audience. Here, UTUC protein-based subtypes were identified, and a deep-learning (DL) workflow was developed to predict them directly from routine histopathological H&E slides. Protein-based subtypes in a retrospective cohort of 163 invasive tumors were assigned by hierarchical clustering of the immunohistochemical expression of three luminal (FOXA1, GATA3, and CK20) and three basal (CD44, CK5, and CK14) markers. Cluster analysis identified distinctive luminal (N = 80) and basal (N = 42) subtypes. The luminal subtype mostly included pushing, papillary tumors, whereas the basal subtype diffusely infiltrating, non-papillary tumors. DL model building relied on a transfer-learning approach by fine-tuning a pre-trained ResNet50. Classification performance was measured via three-fold repeated cross-validation. A mean area under the receiver operating characteristic curve of 0.83 (95% CI: 0.67-0.99), 0.8 (95% CI: 0.62-0.99), and 0.81 (95% CI: 0.65-0.96) was reached in the three repetitions. High-confidence DL-based predicted subtypes showed significant associations (p < 0.001) with morphological features, i.e. tumor type, histological subtypes, and infiltration type. Furthermore, a significant association was found with programmed cell death ligand 1 (PD-L1) combined positive score (p < 0.001) and FGFR3 mutational status (p = 0.002), with high-confidence basal predictions containing a higher proportion of PD-L1 positive samples and high-confidence luminal predictions a higher proportion of FGFR3-mutated samples. Testing of the DL model on an independent cohort highlighted the importance to accommodate histological subtypes. Taken together, our DL workflow can predict protein-based UTUC subtypes, associated with the presence of targetable alterations, directly from H&E slides.

Bladder cancer: An Update.

ABSTRACT: Bladder cancer, the 10th most common cancer globally, primarily manifests as urothelial cell carcinoma. Risk factors involve acquired genetic mutations and congenital predispositions, impacting diagnosis and management. This article discusses the risk factors, clinical presentation, and treatment strategies, with emphasis on providing comprehensive nursing support and patient education to patients with bladder cancer.

Amplification-Free Analysis of Bladder Cancer MicroRNAs on Wrinkled Silica Nanoparticles with DNA-Functionalized Quantum Dots.

Bladder cancer (BC) occurrence and progression are accompanied by alterations in microRNAs (miRNAs) expression levels. Simultaneous detection of multiple miRNAs contributes to the accuracy and reliability of the BC diagnosis. In this work, wrinkled silica nanoparticles (WSNs) were applied as the microreactor for multiplex miRNAs analysis without enzymes or nucleic acid amplification. Conjugated on the surface of WSNs, the S9.6 antibody was adopted as the universal module for binding DNA/miRNA duplexes, regardless of their sequence. Furthermore, single-stranded DNA (ssDNA) was labeled with quantum dots (QDs) for identifying a given miRNA to form QDs-ssDNA/miRNA, which enabled the specific capture of the corresponding QDs on the wrinkled surface of WSNs. Based on the detection of fluorescence signals that were ultimately focused on WSNs, target miRNAs could be sensitively identified to a femtomolar level (5 fM) with a wide dynamic range of up to 6 orders of magnitude. The proposed strategy achieved high specificity to obviously distinguish single-base mutation sequences and possessed multiplex assay capability. Moreover, the assay exhibited excellent practicability in the multiplex detection of miRNAs in clinical serum specimens.

Chronic pelvic pain and dysmenorrhea disguising a rare submucosal leiomyoma of the urinary bladder.

Representing 0.43% of all urinary bladder neoplasms, leiomyomas are rare mesenchymal tumours with a benign pathophysiology. There have only been approximately 250 cases published on this subject, necessitating further inquiry into this disease and effective management protocols. Treatment options may include a broad spectrum of surgical interventions, from minimally invasive resection to radical cystectomy, depending on the location, size and symptoms associated with the tumour. To date, few cases of leiomyoma have resulted in recurrence after removal, and zero have reported malignant transformation. Described here in detail is a woman in her early 40s who presented with a history of chronic pelvic pain and irregular vaginal bleeding. The urology team completed further evaluation after imaging discovered a concerning bladder lesion. Eventually, she underwent transurethral resection, with the subsequent pathology revealing a rare diagnosis of leiomyoma in the urinary bladder.

Construction of endothelial cell signatures for predicting the diagnosis, prognosis and immunotherapy response of bladder cancer via machine learning.

We subtyped bladder cancer (BC) patients based on the expression patterns of endothelial cell (EC) -related genes and constructed a diagnostic signature and an endothelial cell prognostic index (ECPI), which are useful for diagnosing BC patients, predicting the prognosis of BC and evaluating drug sensitivity. Differentially expressed genes in ECs were obtained from the Tumour Immune Single-Cell Hub database. Subsequently, a diagnostic signature, a tumour subtyping system and an ECPI were constructed using data from The Cancer Genome Atlas and Gene Expression Omnibus. Associations between the ECPI and the tumour microenvironment, drug sensitivity and biofunctions were assessed. The hub genes in the ECPI were identified as drug candidates by molecular docking. Subtype identification indicated that high EC levels were associated with a worse prognosis and immunosuppressive effect. The diagnostic signature and ECPI were used to effectively diagnose BC and accurately assess the prognosis of BC and drug sensitivity among patients. Three hub genes in the ECPI were extracted, and the three genes had the closest affinity for doxorubicin and curcumin. There was a close relationship between EC and BC. EC-related genes can help clinicians diagnose BC, predict the prognosis of BC and select effective drugs.

On relevant features for the recurrence prediction of urothelial carcinoma of the bladder.

BACKGROUND: Urothelial bladder cancer (UBC) is characterized by a high recurrence rate, which is predicted by scoring systems. However, recent studies show the superiority of Machine Learning (ML) models. Nevertheless, these ML approaches are rarely used in medical practice because most of them are black-box models, that cannot adequately explain how a prediction is made. OBJECTIVE: We investigate the global feature importance of different ML models. By providing information on the most relevant features, we can facilitate the use of ML in everyday medical practice. DESIGN, SETTING, AND PARTICIPANTS: The data is provided by the cancer registry Rhineland-Palatinate gGmbH, Germany. It consists of numerical and categorical features of 1,944 patients with UBC. We retrospectively predict 2-year recurrence through ML models using Support Vector Machine, Gradient Boosting, and Artificial Neural Network. We then determine the global feature importance using performance-based Permutation Feature Importance (PFI) and variance-based Feature Importance Ranking Measure (FIRM). RESULTS: We show reliable recurrence prediction of UBC with 82.02% to 83.89% F1-Score, 83.95% to 84.49% Precision, and an overall performance of 69.20% to 70.82% AUC on testing data, depending on the model. Gradient Boosting performs best among all black-box models with an average F1-Score (83.89%), AUC (70.82%), and Precision (83.95%). Furthermore, we show consistency across PFI and FIRM by identifying the same features as relevant across the different models. These features are exclusively therapeutic measures and are consistent with findings from both medical research and clinical trials. CONCLUSIONS: We confirm the superiority of ML black-box models in predicting UBC recurrence compared to more traditional logistic regression. In addition, we present an approach that increases the explanatory power of black-box models by identifying the underlying influence of input features, thus facilitating the use of ML in clinical practice and therefore providing improved recurrence prediction through the application of black-box models.

The association between paraneoplastic neurological syndromes (PNS) and urothelial carcinoma - A review of the literature.

Paraneoplastic neurological syndromes (PNS) are rare neurological disorders arising from malignancy-triggered autoimmunity, yet their association with urothelial carcinoma remains unclear. This systematic review intends to explore any connection, alongside patient/clinical features and management. A literature search identified 25 cases of bladder and upper tract carcinoma linked to PNS. Overall, while infrequent, a meaningful association between PNS and urothelial carcinoma was found in that 84% of cases met a 'possible'-or-'higher-likelihood' PNS diagnosis. Most cases presented with high-risk PNS phenotypes, predominantly cerebellar syndromes and encephalomyelitis/sensory neuronopathy, ∼17 months within cancer diagnosis/recurrence. Review findings suggest a female preponderance in suspected PNS despite higher male incidence of urothelial cancer. Main treatments consisted of surgery alongside chemotherapy or immunotherapeutics (IVIG and/or corticosteroids), which improved symptoms for a slight majority (60%). Ultimately, while common PNS-associated neoplasms should always first be excluded in suspected PNS, in the absence of alternative causes, urothelial carcinomas do merit clinical consideration.