Biocompatible gold nanoparticles designed to absorb light at wave-lengths of high tissue transparency have been of particular interest for biomedical applications. The ability of such nanoparticles ...to convert absorbed near-infrared light to heat and induce highly localized hyperthermia has been shown to be highly effective for photothermal cancer therapy, resulting in cell death and tumor remission in a multitude of preclinical animal models. Here we report the initial results of a clinical trial in which laser-excited gold-silica nanoshells (GSNs) were used in combination with magnetic resonance–ultrasound fusion imaging to focally ablate low-intermediate-grade tumors within the prostate. The overall goal is to provide highly localized regional control of prostate cancer that also results in greatly reduced patient morbidity and improved functional outcomes. This pilot device study reports feasibility and safety data from 16 cases of patients diagnosed with low- or intermediate-risk localized prostate cancer. After GSN infusion and high-precision laser ablation, patients underwent multiparametric MRI of the prostate at 48 to 72 h, followed by postprocedure mpMRI/ultrasound targeted fusion biopsies at 3 and 12 mo, as well as a standard 12-core systematic biopsy at 12 mo. GSN-mediated focal laser ablation was successfully achieved in 94% (15/16) of patients, with no significant difference in International Prostate Symptom Score or Sexual Health Inventory for Men observed after treatment. This treatment protocol appears to be feasible and safe in men with low- or intermediate-risk localized prostate cancer without serious complications or deleterious changes in genitourinary function.
Tumor heterogeneity is common in cancer, however recent studies have applied single gene expression signatures to classify bladder cancers into distinct subtypes. Such stratification assumes that a ...predominant transcriptomic signature is sufficient to predict progression kinetics, patient survival and treatment response. We hypothesize that such static classification ignores intra-tumoral heterogeneity and the potential for cellular plasticity occurring during disease development. We have conducted single cell transcriptome analyses of mouse and human model systems of bladder cancer and show that tumor cells with multiple lineage subtypes not only cluster closely together at the transcriptional level but can maintain concomitant gene expression of at least one mRNA subtype. Functional studies reveal that tumor initiation and cellular plasticity can initiate from multiple lineage subtypes. Collectively, these data suggest that lineage plasticity may contribute to innate tumor heterogeneity, which in turn carry clinical implications regarding the classification and treatment of bladder cancer.
Prostate cancer is a widespread problem among men, with >160 000 new cases in 2017 alone. Androgen deprivation therapy is commonly used in prostate cancer treatment to block androgens required for ...cancer growth, but disease relapse after androgen deprivation therapy is both common and severe. Changes in androgen receptor signaling from androgen deprivation therapy have been linked to therapeutic resistance and tumor progression. Resistant cells can become reprogrammed to undergo epithelial–mesenchymal transition, a phenotypic switch from benign, epithelial cells to a mobile cell with mesenchymal traits. In these cells, attachment to their epithelial cell layer is no longer required for survival. Anoikis is a form of cell death that occurs when detachment from other cells and the basement membrane occurs. Epithelial cells have been shown to undergo epithelial–mesenchymal transition, avoid anoikis induction and progress to a metastatic phenotype. In prostate cancer progression to advanced disease, epithelial–mesenchymal transition induction (characterized by loss of epithelial cellular attachment protein E‐cadherin) correlates with a higher Gleason score, tumor progression, increased metastasis and higher biochemical recurrence. The concept of interfacing epithelial–mesenchymal transition with anoikis in the tumor microenvironment landscape will be discussed here, with focus on the significance of the functional exchange between the two processes in therapeutic targeting of advanced disease. The current evidence on the impact of loss of cell–cell contact, acquisition of chemoresistance, immune escape and metastatic spread in advanced tumors in response to transforming growth factor‐β on prostate cancer metastasis will be also discussed. The signaling cross‐talk between transforming growth factor‐β and androgen receptor signaling will be interrogated as a new therapeutic platform for the development of combination strategies to impair prostate cancer metastasis.
Objective
To examine the prevalence of patient preference for male or female urologic provider and explore which patient characteristics influence this preference.
Materials and Methods
After ...obtaining hospital Institutional Review Board approval, a 14‐question survey in English and Spanish was administered across four general urology clinic sites in a single hospital system in New York City. The survey asked demographic questions and preference for a male or a female urologist. The survey included questions pertaining to the nature of the clinic visit and subsequent provider preference as well. Statistics were performed using Stata 16 (StataCorp, College Station, TX).
Results
A total of 540 patients completed the 14‐question survey. The vast majority of survey respondents identified as male (90%). The largest proportion demographic groups were those aged 41–60 (47%), Hispanic or Latino (43%), Catholic (47%), unemployed (40%) and those with a high school level of education (34%). Most patients (60%) did not have a preference for a specific gender provider, whereas 37% preferred a male provider, and 3% preferred a female provider. On univariate analysis, patient age 25–40, less than high school education level and lack of employment were significant predictors of provider gender preference (p < 0.05), with most patients indicating a male provider preference. On multivariate analysis of gender, age, education level and employment status, gender and education level were not significant predictors of preference, whereas age 25–40 and being unemployed were significant predictors (p < 0.05).
Conclusion
Patient gender, race and religion do not appear to influence their preference to be seen by a male or a female urologist in the clinic setting. However, patient age, unemployment and potentially educational attainment were significantly associated with a provider gender preference.
•The introduction of immune checkpoint inhibitors represents a paradigm shift in patients with urothelial carcinoma of the bladder (UCB).•Only a small subset of patients derive benefit from immune ...checkpoint inhibitors, underscoring the need to identify novel checkpoint targets.•Preclinical studies suggest T-cell immunoglobulin domain and mucin domain-containing molecule (TIM-3)and T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain as promising checkpoint targets.•Our work demonstrates the presence of UCB upregulates the inhibitory receptors TIM-3and T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain by natural killer and T cells in a tissue- and disease-stage-specific manner.•Natural Killer cell inhibition can be reversed with TIM-3 blockade in the peripheral blood of UCB patients causing enhanced cytokine production and the release of cytolytic effector molecules.
The resurgence of immunotherapy as an effective anticancer strategy has been coupled with more mature understandings of the underlying immune pathways and the development of novel immune checkpoint targets. The clinical development of antibodies first directed against cytotoxic T-lymphocyte–associated antigen 4, and later against program death 1, achieved durable disease control in a subset of patients across a large number of tumor types. Previous work demonstrates that targeting the programmed death 1 pathway alone does not result in complete restoration of T cell function and in some cancers, targeting this axis does not restore T cell function at all, suggesting a need to identify other molecules and inhibitory pathways that are involved in T cell exhaustion. In a comprehensive immune profiling study of patients with bladder cancer, we demonstrate T-cell immunoglobulin domain and mucin domain-containing molecule and T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain as possible targets as perhaps monotherapy or in combination with other immune checkpoint inhibitors.
Lower pole renal stones are associated with the lowest stone-free status of any location in the urinary tract during retrograde intrarenal surgery. Prior work has suggested displacing lower pole ...stones to a more accessible part of the kidney to improve stone-free status. We sought to prospectively compare the efficacy of laser lithotripsy in situ vs after displacement during retrograde intrarenal surgery for lower pole stones.
Between July 2017 and May 2022 patients undergoing retrograde intrarenal surgery for lower pole stones were randomized into an in situ or displacement group. Demographics, comorbidities, and operative parameters were documented. Primary outcome was stone-free status, determined by combination of abdominal x-ray and renal ultrasound at 30-day follow-up. Secondary outcomes included operative time, 30-day complications, emergency department visits, and readmissions.
A total of 138 patients (69 per group) were enrolled and analyzed. Baseline characteristics were similar between groups. Stone-free status significantly favored the displacement group over the in situ group (95% vs 74%,
= .003, n=62 in each group). Operative time, total laser energy usage, 30-day complications, and 30-day emergency department visits or hospital readmissions were similar between groups. On multivariate analysis only study group allocation was significantly associated with stone-free status (
= .024).
Basket displacement of lower pole stones results in a significantly higher stone-free status compared to in situ lithotripsy. The technique is simple, atraumatic, and requires no additional equipment costs and little additional operative time, making it a practical tool in the treatment of lower pole stones.
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