5 research outputs found
āļāļĨāļāļāļāļāļēāļĢāđāļāđāļāļāļĨāļļāđāļĄāļĒāđāļāļĒāļĢāļ°āļāļąāļāđāļĄāđāļĨāļāļļāļĨāđāļāļĄāļ°āđāļĢāđāļāļāļĢāļ°āđāļāļēāļ°āļāļąāļŠāļŠāļēāļ§āļ°āļāļĩāđāļĢāļļāļāđāļāđāļēāļāļąāđāļāļāļĨāđāļēāļĄāđāļāļ·āđāļ āđāļāļĒāļāļēāļĢāļāļąāļāļāļĨāļļāđāļĄāļĢāļ°āļāļąāļāļāļēāļĢāđāļŠāļāļāļāļāļāļāļāļāļĒāļĩāļāļāđāļāļāļēāļĢāļāļģāļāļēāļĒāļāļēāļĢāļĢāļāļāļāļĩāļāđāļĨāļ°āļāļēāļĢāļāļāļāļŠāļāļāļāļāđāļāļāļēāļĢāļĢāļąāļāļĐāļē
Thesis (Ph.D., Health Sciences, Faculty of Medicine)--Prince of Songkla University, 2022Recently discovered molecular classifications for urothelial bladder cancer appeared to be promising prognostic and predictive biomarkers. It is a major challenge for clinical work to study the molecular subtypes of BC. Outcome of bladder cancer (BC) treatment still need establish and explored the molecular subtypes of bladder cancer and potential clusters. The present study was conducted to evaluate the prognostic impact of molecular subtypes assessed by mRNA expression in a consecutively collected, mono-institutional muscle-invasive bladder cancer (MIBC) cohort, performed by unsupervised clustering and validate subtypes of our institutional cohort with data from The Cancer Genome Atlas (TCGA) and possible to correlate the mRNA expression with tumor molecular subtype membership. Our overall goal was to determine whether mRNA expression have shown significant difference in specific molecular subtypes and correlation with clinical outcomes. Molecular subtyping of muscle-invasive bladder cancer (MIBC) predicts disease progression and treatment response. However, present subtyping techniques are based primarily on transcriptomic analysis, which is relatively expensive. Subtype classification of protein levels by immunohistochemistry (IHC) are more affordable and feasible to perform in a general pathology laboratory. Recent data demonstrated that GATA3, CK20, CK5/6, and CK14 protein levels were correlated with MIBC molecular subtypes. We aimed to evaluate the correlation of those IHC markers with survival outcomes after radical cystectomy in Thai patients. Moreover, we aim to evaluate molecular subtypings by mRNA expression analysis.
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Method
30 MIBC were pathologically re-evaluated and molecular subtypes were assessed on mRNA. Fresh-frozen primary tumor samples from a single cohort in Songklanagarind hospital who underwent radical cystectomy between 2015 and 2020. First, we screened the expression profiles of differentially genes expression and of BC by comparing DEG and principle component analysis with K-mean clustering. Moreover, external validation set from the Cancer Genome Atlas (TCGA) database was done by using significant gene expression. We used the complete TCGA dataset with our subtype gene expression and assign TCGAâs bladder cancers to molecular subtypes. Taken together, we explored the molecular subtypes and their outcome treatment of BC. Institutional cohort (n= 30 MIBC) and The Cancer Genome Atlas (TCGA)- dataset (n=231 MIBC) were subtyped using unsupervised genes and analyzed for predicting of survival, cancer-specific survival (CSS), overall-survival (OS), and recurrenceâfree survival (RFS). Moreover, we evaluated the IHC-based subtypes in MIBC, as classified by GATA3, CK20, CK5/6, and CK14 expression in 132 MIBC patients who underwent radical cystectomy followed by adjuvant chemotherapy (2008â2016). All individual markers and clinicopathological parameters were analyzed against treatment outcomes after radical cystectomy and some selected tissues were sent for whole transcriptome sequencing and clustering from mRNA expression.
Result
Unsupervised consensus hierarchical clustering applied to gene expression data and identified 3 molecular subtypes. These subtypes were associated with distinct clinicopathological characteristics and molecular expression. The clustering was validated in the TCGA dataset. We identified different clinical characteristics and identified 3 molecular subtypes MIBC specimens from cohort dataset successfully. In multivariable analyses, N- stage, T-stage, M-stage and/or age predicted CSS/OS and/or cisplatin- based adjuvant- chemotherapy response. In the TCGA-dataset, publications report that subtypes risk-stratify patients for OS. For IHC study section, the result showed that the mean patient age was 65.6 years, and the male to female ratio was 6.8:1. Positive IHC expression rates of GATA3, CK20, CK5/6, and CK14 were 80.3%, 50.8%, 42.4%, and 28.0%, respectively. The 5-year overall survival (OS) was 27.0% (95% confidence interval (CI) 19.6%â35.0%). Only GATA3 and CK5/6 were significantly associated with survival outcome (log-rank p-values = 0.004 and 0.02). GATA3 and CK5/6 were then used to establish subtypes, which were luminal (GATA+
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and CK5/6â, 38.6%), basal (GATAâ and CK5/6+, 12.9%), mixed (GATA+ and CK5/6+, 37.9%), and double-negative (GATAâ and CK5/6â, 10.6%). Patients with the mixed subtype had a significantly better 5-year OS at 42.8%, whereas patients with the double-negative subtype had the worst prognosis among the four groups (5-year OS 7.14%). In the multivariable analysis, lymph node status and subtype independently predicted survival probability. The double-negative subtype had a hazard ratio of 3.29 (95% CI 1.71â6.32).
Conclusion
The results further reinforce the conclusion that the molecular subtypes of bladder cancer are distinct disease entities with specific molecular subtype. In our cohorts/subtyping- classifications, clinical and novel molecular subtypes for predicting outcome of treatment. For immunohistochemistry subtyping using GATA3 and CK5/6 was applicable in MIBCs, and patients with the double-negative subtype were at the highest risk and may require more intensive therapy and mRNA subtyping by mRNA expression must showed the significant relationship with survival rate.āļāļāļāļģ:
āļĄāļ°āđāļĢāđāļāļāļĢāļ°āđāļāļēāļ°āļāļąāļŠāļŠāļēāļ§āļ°āļāļāļīāļāļāļĩāđāļĢāļļāļāđāļāđāļēāļāļĨāđāļēāļĄāđāļāļ·āđāļ (muscle invasive bladder cancer) āđāļāđāļāļĄāļ°āđāļĢāđāļāļāļĢāļ°āđāļāļēāļ°āļāļąāļŠāļŠāļēāļ§āļ°āļāļāļīāļāļāļĩāđāļĄāļĩāļāļ§āļēāļĄāļĢāļļāļāđāļĢāļ āļĒāļēāļāļāđāļāļāļēāļĢāļĢāļąāļāļĐāļē āđāļĨāļ°āļāļąāļāļĢāļēāļāļēāļĢāļĢāļāļāļāļĩāļāļāđāļģ āđāļāļāļąāļāļāļļāļāļąāļ āļāļēāļĢāļĻāļķāļāļĐāļēāđāļāļĢāļ°āļāļąāļāđāļĄāđāļĨāļāļļāļĨāđāļāļ·āđāļāļŦāļēāļĢāļđāļāđāļāļāļāļāļāļĄāļ°āđāļĢāđāļāļāļĩāđāļŠāļąāļĄāļāļąāļāļāđāļāļąāļāļāļąāļāļĢāļēāļĢāļāļāļāļĩāļāđāļĨāļ°āļāļēāļĢāļāļāļāļŠāļāļāļāļāđāļāļĒāļēāļāļķāļāļĄāļĩāļāļ§āļēāļĄāļŠāļģāļāļąāļāļāđāļāļāļēāļĢāļĢāļąāļāļĐāļē āđāļāļāļēāļāļ§āļīāļāļąāļĒāļāļīāđāļāļāļĩāđāļāļķāļāļŠāļāđāļāļĻāļķāļāļĐāļēāļāļēāļĢāđāļāđāļāļāļĨāļļāđāļĄāļĒāđāļāļĒāļāļāļāļĄāļ°āđāļĢāđāļāļāļĢāļ°āđāļāļēāļ°āļāļąāļŠāļŠāļēāļ§āļ°āļāļāļīāļāļāļĩāđāļĢāļļāļāđāļāđāļēāļāļĨāđāļēāļĄāđāļāļ·āđāļāđāļāļ·āđāļāļŦāļēāļĢāļđāļāđāļāļāļāļ§āļēāļĄāļŠāļąāļĄāļāļąāļāļāđāļāļĩāđāļāļēāļāļāđāļ§āļĒāđāļāļāļēāļĢāļĢāļąāļāļĐāļēāļāļĩāđāļĄāļēāļāļĒāļīāđāļāļāļķāđāļ āļāļēāļĢāļĻāļķāļāļĐāļēāļāļķāļāļāļēāļĢāđāļŠāļāļāļāļāļāļāļāļ mRNA āđāļāļĢāļđāļāđāļāļ transcriptome āļāļ°āđāļŦāđāļāļĨāļāļēāļĢāļĻāļķāļāļĐāļēāļāļĩāđāļĄāļĩāļāļ§āļēāļĄāđāļĄāđāļāļĒāļģāļŠāļđāļ āļāļēāļāļāļĩāļĄāļ§āļīāļāļąāļĒāļāļķāļāđāļāđāļāļģāļāļēāļĢāļĻāļķāļāļĐāļēāļĢāļđāļāđāļāļāļāļēāļĢāđāļŠāļāļāļāļāļāđāļāļĢāļđāļāđāļāļ transcriptome āļāļ§āļāļāļđāđāļāļąāļāļāļēāļĢāđāļŠāļāļāļāļāļāļĢāļ°āļāļąāļāđāļāļĢāļāļĩāļāļāļāļāļāļąāļ§āļāđāļāļāļĩāđāļāļēāļāļāļĩāļ§āļ āļēāļ 4 āļāļāļīāļāļāļĩāđāļĄāļĩāļāļēāļĢāļĢāļēāļĒāļāļēāļāļ§āđāļēāļĄāļĩāļāļ§āļēāļĄāļŠāļąāļĄāļāļąāļāļāđāļāļąāļāļāļēāļĢāđāļāđāļāļāļāļīāļāļāļāļāđāļāļĨāļĨāđāļĄāļ°āđāļĢāđāļāļāļĢāļ°āđāļāļēāļ°āļāļąāļŠāļŠāļēāļ§āļ°āļāļāļīāļāļĢāļļāļāđāļāđāļēāļāļąāđāļāļāļĨāđāļēāļĄāđāļāļ·āđāļāđāļāļĢāļđāļāđāļāļ transcriptome analysis āđāļāđāđāļāđ GATA3, CK20, CK5/6 āđāļĨāļ° CK14
āļ§āļīāļāļĩāļāļēāļĢāļĻāļķāļāļĐāļē:
āļĢāļđāļāđāļāļāļāļēāļĢāļĻāļķāļāļĐāļēāļĢāļēāļĒāļĒāđāļāļāļŦāļĨāļąāļāđāļāļĒāđāļāđāļāļĢāļ§āļāļĢāļ§āļĄāļāđāļāļĄāļđāļĨāļāļđāđāļāđāļ§āļĒāļĄāļ°āđāļĢāđāļāļāļĢāļ°āđāļāļēāļ°āļāļąāļŠāļŠāļēāļ§āļ°āļāļĩāđāļĢāļļāļāđāļāđāļēāļāļąāđāļāļāļĨāđāļēāļĄāđāļāļ·āđāļ āđāļāđāļāļĢāļ§āļāļĢāļ§āļĄāļĄāļđāļĨāļāļąāļāļāļąāļĒāļāļēāļāļāļĨāļīāļāļīāļāļāļēāļāđāļ§āļāļĢāļ°āđāļāļĩāļĒāļāđāļĨāļ°āļāļąāļāļāļąāļĒāļāļēāļāļāļĨāļīāļāļīāļ āļāļģāļāļēāļĢāļāļģāļāļīāđāļāđāļāļ·āđāļāļĄāļ°āđāļĢāđāļāļĄāļēāļāļģāļāļēāļĢāļĒāđāļāļĄāļāļēāļĢāđāļŠāļāļāļāļāļāļĢāļ°āļāļąāļāđāļāļĢāļāļĩāļ 4 āļāļąāļ§ GATA3, CK20, CK5/6 āđāļĨāļ° CK14 āļāđāļ§āļĒāļāļēāļĢāļāļģāđāļāļ tissue microarray āđāļĨāļ°āļĄāļĩāļāļēāļĢāļŠāđāļāļāļĢāļ§āļāļāļīāđāļāđāļāļ·āđāļāļĄāļ°āđāļĢāđāļāļāļĢāļ°āđāļāļēāļ°āļāļąāļŠāļŠāļēāļ§āļ°āļŠāđāļāļāļĢāļ§āļ mRNA āļāđāļ§āļĒāļāļēāļĢāđāļāđāļāļāļ·āđāļāđāļāļ·āđāļāļāļāļīāļ Fresh frozen tissue āđāļĨāļ°āļŠāđāļāļāļĢāļ§āļāļŦāļēāļāļēāļĢāđāļŠāļāļāļāļāļāļāļāļāļĒāļĩāļāļĢāļ°āļāļąāļ RNA āļāļąāđāļāđāļĒāļāđāļāđāļāļāļĨāļļāđāļĄāļĒāđāļāļĒāļĢāļ°āļāļąāļāđāļĄāđāļĨāļāļļāļĨāđāļāļĄāļ°āđāļĢāđāļāļāļĢāļ°āđāļāļēāļ°āļāļąāļŠāļŠāļēāļ§āļ°āļāļĩāđāļĢāļļāļāđāļāđāļēāļāļąāđāļāļāļĨāđāļēāļĄāđāļāļ·āđāļ (molecular subtypings of MIBC) āđāļāļĒāļāļēāļĢāļāļąāļāļāļĨāļļāđāļĄāļĢāļ°āļāļąāļāļāļēāļĢāđāļŠāļāļāļāļāļāļāļāļāļĒāļĩāļāļāđāļāļāļēāļĢāļāļģāļāļēāļĒāļāļēāļĢāļĢāļāļāļāļĩāļ āđāļĨāļ°āļāļēāļĢāļāļāļāļŠāļāļāļāļāđāļāļāļēāļĢāļĢāļąāļāļĐāļē
āļāļĨāļāļēāļĢāļĻāļķāļāļĐāļē:
āđāļāļĒāļāļĨāļāļēāļĢāļĻāļķāļāļĐāļēāļāļāļ§āđāļē āļāļēāļāļāļģāļāļ§āļāļāļīāđāļāđāļāļ·āđāļāļāļĩāđāđāļāđāļĒāđāļāļĄ IHC āļāļģāļāļ§āļ 132 āļāļąāļ§āļāļĒāđāļēāļ āļāļēāļĒāļļāđāļāļĨāļĩāđāļĒāļāļāļāļāļđāđāļāđāļ§āļĒāļāļ·āļ 65.6 āļāļĩ āļāļąāļāļĢāļēāļāļēāļĢāđāļŠāļāļāļāļāļāļāļāļ IHC āļāļĩāđāđāļāđāļāļāļ§āļāļāļāļ GATA3, CK20, CK5/6 āđāļĨāļ° CK14 āļāļ·āļ 80.3%, 50.8%, 42.4% āđāļĨāļ° 28.0% āļāļēāļĄāļĨāļģāļāļąāļ āļĄāļĩāđāļāļĩāļĒāļ GATA3 āđāļĨāļ° CK5/6 āđāļāđāļēāļāļąāđāļāļāļĩāđāļĄāļĩāļāļ§āļēāļĄāļŠāļąāļĄāļāļąāļāļāđāļāļĒāđāļēāļāļĄāļĩāļāļąāļĒāļŠāļģāļāļąāļāļāļąāļāļāļĨāļĨāļąāļāļāđāļāļēāļĢāļĢāļāļāļāļĩāļ§āļīāļ (āļāđāļē log-rank p-values = 0.004 āđāļĨāļ° 0.02) āļāļēāļāļāļąāđāļ GATA3 āđāļĨāļ° CK5/6 āļāļđāļāđāļāđāđāļāļ·āđāļāļŠāļĢāđāļēāļāļāļāļīāļāļĒāđāļāļĒ āļāļķāđāļāđāļāđāđāļāđ āļāļĨāļļāđāļĄ luminal (GATA+ āđāļĨāļ° CK5/6â, 38.6%) āļāļĨāļļāđāļĄ basal (GATAâ āđāļĨāļ° CK5/6+, 12.9%) āļāļĨāļļāđāļĄāļāļŠāļĄ (GATA+ āđāļĨāļ° CK5/6+, 37.9%) āđāļĨāļ°āļāļĨāļļāđāļĄ double negative (GATAâ āđāļĨāļ° CK5/6â, 10.6%) āļāļđāđāļāđāļ§āļĒāļāļĩāđāđāļāđāļāļāļāļīāļāļĒāđāļāļĒāđāļāļāļāļŠāļĄāļĄāļĩāļāļąāļāļĢāļēāļāļēāļĢāļĢāļāļāļāļĩāļ§āļīāļāļāļĩāđ 5 āļāļĩāļāļĩāđāļāļĩāļāļķāđāļāļāļĒāđāļēāļāļĄāļĩāļāļąāļĒāļŠāļģāļāļąāļāļāļĩāđ 42.8% āđāļāļāļāļ°āļāļĩāđāļāļđāđāļāđāļ§āļĒāļāļĩāđāđāļāđāļāļāļāļīāļāļĒāđāļāļĒāđāļāļ double-negative āļĄāļĩāļāļēāļĢāļāļĒāļēāļāļĢāļāđāđāļĢāļāļāļĩāđāđāļĒāđāļāļĩāđāļŠāļļāļāđāļāļŠāļĩāđāļāļĨāļļāđāļĄāļĄāļĩāļāļąāļāļĢāļēāļāļēāļĢāļĢāļāļāļāļĩāļ§āļīāļāļāļĩāđ 5 āļāļĩ 7.14%
āļāļĨāļāļēāļĢāļĻāļķāļāļĐāļēāđāļāļ·āđāļāļāļāđāļāļāļāļāļāļīāđāļāđāļāļ·āđāļāļĄāļ°āđāļĢāđāļāļāļĢāļ°āđāļāļēāļ°āļāļąāļŠāļŠāļēāļ§āļ°āļāļĩāđāļĄāļĩāļāļēāļĢāļĢāļļāļāđāļāđāļēāļāļąāđāļāļāļĨāđāļēāļĄāđāļāļ·āđāļāļāļģāļāļ§āļ 30 āļāļąāļ§āļāļĒāđāļēāļ āļāļēāļĢāđāļāđāļāļāļĨāļļāđāļĄāļĒāđāļāļĒ mRNA āđāļāđāļ unsupervised clustering āļāļāļāđāļāđāļ 3 āļāļĨāļļāđāļĄāļāļ·āļ cluster 1 āļāļķāļ 3 āļāļķāđāļāđāļāđāļĨāļ°āļāļĨāļļāđāļĄāļĄāļĩāļāļēāļĢāđāļŠāļāļāļāļāļāļāļāļāļĒāļĩāļāļāļĩāđāļĄāļĩāļāļ§āļēāļĄāđāļāļāļāđāļēāļāļāļąāļ āđāļĨāļ°āļāļēāļāļāļđāđāļ§āļīāļāļąāļĒāđāļāđāđāļāđāļāđāļāļĄāļđāļĨāļāļđāđāļāđāļ§āļĒāļāļēāļāļāļēāļāļāđāļāļĄāļđāļĨ TCGA āđāļāđāļēāđāļāđāļāļīāđāļĄāđāļāļīāļĄ āļāļķāđāļāļāļāļ§āđāļēāļāļēāļĢāļāļąāļāļāļĨāļļāđāļĄ transcriptome āđāļāļĢāļđāļāđāļāļāļāļĩāđāļĄāļĩāļāļ§āļēāļĄāļŠāļąāļĄāļāļąāļāļāđāļāļąāļāļāļąāļāļĢāļēāļāļēāļĢāļĢāļāļāļāļĩāļ§āļīāļāđāļāļāļđāđāļāđāļ§āļĒāļĄāļ°āđāļĢāđāļāļāļĢāļ°āđāļāļēāļ°āļāļąāļŠāļŠāļēāļ§āļ°āđāļāļāļĢāļļāļāđāļāđāļēāļāļĨāđāļēāļĄāđāļāļ·āđāļ
āļŠāļĢāļļāļāļāļĨāļāļēāļĢāļĻāļķāļāļĐāļē:
āļāļēāļĢāđāļāđāļāļāļĨāļļāđāļĄāļĒāđāļāļĒāđāļāļĒāđāļāđ GATA3 āđāļĨāļ° CK5/6 āđāļāđāđāļāđāļāļąāļ MIBCs āđāļĨāļ°āļāļđāđāļāđāļ§āļĒāļāļĩāđāļĄāļĩ subtype āđāļāļ double-negative āļĄāļĩāļāļ§āļēāļĄāđāļŠāļĩāđāļĒāļāļŠāļđāļāļŠāļļāļ āļŠāđāļ§āļāļāļēāļĢāđāļāđāļāļāļĨāļļāđāļĄāļĒāđāļāļĒāļāļāļ mRNA āļāļēāļāļāļēāļĢāļ§āļīāđāļāļĢāļēāļ°āļŦāđāđāļāļĒāđāļāđāļāđāļāļĄāļđāļĨāļāļēāļāļāļąāļ§āļāļĒāđāļēāļāļāļĩāđāļĻāļķāļāļĐāļēāđāļāđāļāļāļāļāļāļĨāļļāđāļĄāđāļŦāļĄāđāđāļāđāđāļāđāļ 3 āļāļĨāļļāđāļĄāļĒāđāļāļĄāļāļĩāđāļĄāļĩāļāļąāļĒāļŠāļģāļāļąāļāđāļĨāļ°āļāļĢāļ°āļĒāļļāļāļāđāđāļāđāļāļąāļāļāđāļāļĄāļđāļĨāļāļđāđāļāđāļ§āļĒāļāļēāļāļāļēāļāļāđāļāļĄāļđāļĨāļāļ·āđāļ āļŠāļēāļĄāļēāļĢāļāļāļāļĢāļđāļāđāļāļāļāļ§āļēāļĄāļŠāļąāļĄāļāļąāļāļāđāļāļąāļāļāļąāļāļĢāļēāļāļēāļĢāļĢāļāļāļāļĩāļāđāļāđāļāļĒāđāļēāļāļĄāļĩāļāļąāļĒāļŠāļģāļāļąāļāļāļēāļāļŠāļāļīāļ
Prostatic schwannoma discovered after laparoscopic radical prostatectomy: A case report with literature review
Background Schwannomas originating in the prostate are extremely rare. We present a case of prostatic schwannoma in a 66âyearâold male with lower urinary tract symptoms. Preoperative evaluation revealed a prostatic mass, and the definitive diagnosis was made through laparoscopic radical prostatectomy. Case presentation A 66âyearâold male presented with persistent lower urinary tract symptoms for 5âyears and a prostateâspecific antigen level of 0.63âng/mL. MRI showed a wellâdefined solid cystic mass in the posterolateral basal right peripheral zone, causing superior displacement of the right seminal vesicle. Laparoscopic radical prostatectomy was performed, confirming a periprostatic schwannoma. Conclusion This case highlights the rarity of prostatic schwannomas and their association with lower urinary tract symptoms. MRI plays a crucial role in identifying prostatic masses, while laparoscopic radical prostatectomy can serve as a diagnostic and therapeutic approach for prostatic schwannomas. Increased awareness of this rare entity is essential for accurate diagnosis and optimal management
Molecular Subtyping in Muscle-Invasive Bladder Cancer on Predicting Survival and Response of Treatment
Molecular classifications for urothelial bladder cancer appear to be promising in disease prognostication and prediction. This study investigated the novel molecular subtypes of muscle invasive bladder cancer (MIBC). Tumor samples and normal tissues of MIBC patients were submitted for transcriptome sequencing. Expression profiles were clustered using K-means clustering and principal component analysis. The molecular subtypes were also applied to The Cancer Genome Atlas (TCGA) dataset and analyzed for clinical outcome correlation. Three molecular subtypes of MIBC were discovered, clusters A, B, and C. The most differentially upregulated genes in cluster A were BDKRB1, EDNRA, AVPR1A, PDGFRB, and TNC, while the most upregulated genes in cluster C were collagen-related genes, PDGFRB, and PRKG1. For cluster B, COL6A3, COL1A2, COL6A2, tenascin C, and fibroblast growth factor 2 were statistically suppressed. When the centroids of clustering on PCA were applied to TCGA data, the clustering significantly predicted survival outcomes. Cluster B had the best overall survival (OS), and cluster C was associated with poor OS but exhibited the best response to perioperative chemotherapy. Among all groups, cluster B had a better pathologic response to neoadjuvant chemotherapy (40%). Based on the results of the present study, the novel clusters of subtype MIBC appear potentially suitable for integration into clinical practice
Eucalyptus-Mediated Synthesized Silver Nanoparticles-Coated Urinary Catheter Inhibits Microbial Migration and Biofilm Formation
Catheter-associated urinary tract infections (CAUTIs) are significant complications among catheterized patients, resulting in increased morbidity, mortality rates, and healthcare costs. Foley urinary catheters coated with synthesized silver nanoparticles (AgNPs) using Eucalyptus camaldulensis leaf extract were developed using a green chemistry principle. In situ-deposited AgNPs with particle size ranging between 20 and 120 nm on the catheter surface were illustrated by scanning electron microscopy. Atomic force microscopy revealed the changes in surface roughness after coating with nanoparticles. The coated catheter could significantly inhibit microbial adhesion and biofilm formation performed in pooled human urine-supplemented media to mimic a microenvironment during infections (p 0.05). AgNPs-coated catheter exhibited broad-spectrum antimicrobial activity against important pathogens, causing CAUTIs with no cytotoxic effects on HeLa cells. A reduction in microbial viability in biofilms was observed under confocal laser scanning microscopy. A catheter bridge model demonstrated complete prevention of Proteus mirabilis migration by the coated catheter. Significant inhibition of ascending motility of Escherichia coli and P. mirabilis along the AgNPs-coated catheter was demonstrated in an in vitro bladder model (p 0.05). The results suggested that the AgNPs-coated urinary catheter could be applied as an alternative strategy to minimize the risk of CAUTIs by preventing bacterial colonization and biofilm formation
Comparing pentafecta outcomes between nerve sparing and non nerve sparing robot-assisted radical prostatectomy in a propensity score-matched study
Abstract Pentafecta (continence, potency, cancer control, free surgical margins, and no complications) is an important outcome of prostatectomy. Our objective was to assess the pentafecta achievement between nerve-spring and non-nerve-sparing robot-assisted radical prostatectomy (RARP) in a large single-center cohort. The study included 1674 patients treated with RARP between August 2009 and November 2022 to assess the clinical outcomes. Cox regression analyses were performed to evaluate the prognostic significance of RARP for pentafecta achievement, and 1:1 propensity score matching (PSM) was performed between the nerve-sparing and non-nerve-sparing to test the validity of the results. Pentafecta definition included continence, which was defined as the use of zero pads; potency, which was defined as the ability to achieve and maintain satisfactory erections or ones firm enough for sexual activity and sexual intercourse. The biochemical recurrence rate was defined as two consecutive PSA levelsâ>â0.2Â ng/mL after RARP; 90-day ClavienâDindo complicationsââĪâ3a; and a negative surgical pathologic margin. The median follow-up period was 61.3Â months (IQR 6â159Â months). A multivariate Cox regression analysis demonstrated that pentafecta achievement was significantly associated with nerve-sparing (NS) approach (1188 patients) (OR 4.16; 95% CI 2.51â6.9), pâ<â0.001), unilateral nerve preservation (983 patients) (OR 3.83; 95% CI 2.31â6.37, pâ<â0.001) and bilateral nerve preservation (205 patients) (OR 7.43; 95% CI 4.14â13.36, pâ<â0.001). After propensity matching, pentafecta achievement rates in the NS (476 patients) and non-NS (476 patients) groups were 72 (15.1%) and 19 (4%), respectively. (pâ<â0.001). NS in RARP offers a superior advantage in pentafecta achievement compared with non-NS RARP. This validation study provides the pentafecta outcome after RARP associated with nerve-sparing in clinical practice