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Journal of Vascular and Interventional... Jul 2024To compare spatial distributions of radiopaque glass (RG) microspheres, trisacryl gelatin (TAG) microspheres, and polyvinyl alcohol (PVA) foam particles within a planar...
PURPOSE
To compare spatial distributions of radiopaque glass (RG) microspheres, trisacryl gelatin (TAG) microspheres, and polyvinyl alcohol (PVA) foam particles within a planar in vitro microvascular model of the hyperplastic hemiprostate.
MATERIALS AND METHODS
A microvascular model simulating hyperplastic hemiprostate was perfused with a water-glycerin mixture. A microcatheter was positioned distal to the model's prostatic artery origin and embolic particles (RG: 50 μm, 100 μm, and 150 μm; TAG: 100-300 μm and 300-500 μm; and PVA: 90-180 μm and 180-300 μm) were administered using a syringe pump. Microscopic imaging and subsequent semantic segmentation were performed to quantify particle distributions within the models. Distal penetrations were quantified statistically via modal analysis of the particle distributions.
RESULTS
Maximum distal penetration was observed for RG 50, followed by RG 100 and then TAG 100-300 and RG 150. TAG 300-500, PVA 90-180, and PVA 180-300 particles exhibited the lowest distal penetrations. The distal penetration metrics between groups were significantly different (p < 0.05) except between TAG 100-300 and RG 150 and between PVA 90-180 and PVA 180-300.
CONCLUSIONS
Comparing the spatial distributions of embolic particles in an in vitro microvascular model simulating the hyperplastic hemiprostate revealed that noncompressible particles and those with narrower size calibrations and smaller relative diameters exhibited higher degrees of distal packing. The embolization front was less distinct for particles with wider size calibrations, which resulted in smaller, more distal emboli along with larger, more proximal emboli. PVA and TAG 300-500 particles both exhibited relatively low overall distal penetration.
PubMed: 38960127
DOI: 10.1016/j.jvir.2024.06.028 -
Actas Urologicas Espanolas Jul 2024In recent years, various aspects of prostate cancer (PC) management have undergone significant changes, including the implementation of therapeutic strategies such as...
In recent years, various aspects of prostate cancer (PC) management have undergone significant changes, including the implementation of therapeutic strategies such as the use of new hormonal agents like abiraterone, apalutamide, enzalutamide or darolutamide and the incorporation of next generation imaging techniques (NGI). However, the evidence regarding the role of NGI and the therapeutic decision-making based on their findings is not solid. Following the methodology of the Advanced Prostate Cancer Consensus Conference (APCCC), a multidisciplinary expert consensus was developed to address controversial questions concerning the use of NGI and clinical management in four priority scenarios: localized PC, PC after radical prostatectomy, PC after radiotherapy with curative intent, and metastatic hormone-sensitive PC. This consensus represents the opinions of medical oncology, radiation oncology and urology physicians and provides useful recommendations for clinical practice.
PubMed: 38960063
DOI: 10.1016/j.acuroe.2024.06.005 -
Kidney International Jul 2024Patient navigators enable adult patients to circumnavigate complex health systems, improving access to health care and outcomes. Here, we aimed to evaluate the effects...
Patient navigators enable adult patients to circumnavigate complex health systems, improving access to health care and outcomes. Here, we aimed to evaluate the effects of a patient navigation program in children with chronic kidney disease (CKD). In this multi-center, randomized controlled trial, we randomly assigned children (aged 0-16 years) with CKD stages 1-5 (including children on dialysis or with kidney transplants), from low socioeconomic status backgrounds, and/or residing in remote areas, to receive patient navigation at randomization (immediate) or at six months (waitlist). The primary outcome was self-rated health (SRH) of participating children at six months, using intention to treat analysis. Secondary outcomes included caregivers' SRH and satisfaction with health care, children's quality of life, hospitalizations, and missed school days. Repeated measures of the primary outcome from baseline to six months were analyzed using cumulative logit mixed effects models. Semi-structured interviews were thematically evaluated. Of 398 screened children, 162 were randomized (80 immediate and 82 waitlist); mean age (standard deviation) of 8.8 (4.8) years with 64.8% male. SRH was not significantly different between the immediate and wait-listed groups at six months. There were also no differences across all secondary outcomes between the two groups. Caregivers' perspectives were reflected in seven themes: easing mental strain, facilitating care coordination, strengthening capacity to provide care, reinforcing care collaborations, alleviating family tensions, inability to build rapport and unnecessary support. Thus, in children with CKD, self-rated health may not improve in response to a navigator program, but caregivers gained skills related to providing and accessing care.
PubMed: 38959996
DOI: 10.1016/j.kint.2024.05.031 -
International Journal of Surgery Case... Jun 2024Fournier's gangrene is a urological emergency associated with high mortality and morbidity. Severe gangrene resulting in pelvic bone and lower limb involvement are...
INTRODUCTION AND IMPORTANCE
Fournier's gangrene is a urological emergency associated with high mortality and morbidity. Severe gangrene resulting in pelvic bone and lower limb involvement are extremely rare.
CASE PRESENTATION
We report a rare case of Fournier's gangrene that is complicated by necrotising fasciitis of the lower limb and osteomyelitis of the pelvic bone, in a patient with previous prostatic adenocarcinoma. The patient was promptly resuscitated, started on broad spectrum antibiotics and then underwent an emergent surgical debridement, followed by multiple relook debridement and definitive reconstruction. Throughout the patient's hospitalisation, he was managed in a multidisciplinary team involving surgeons from different specialities, physicians and allied health staff.
CLINICAL DISCUSSION
Extension of Fournier's gangrene into distant structures is rare but serious complications. To date, there is only one other case reported in literature. The relationship between prior prostatic malignancy and Fournier's gangrene can be explored in subsequent studies.
CONCLUSION
We present a rare case of Fournier's gangrene with pelvic and distal limb involvement. We highlight the possible yet devastating complications of this disease and discuss treatment options available for the holistic management of patients with Fournier's gangrene.
PubMed: 38959612
DOI: 10.1016/j.ijscr.2024.109974 -
European Journal of Radiology Jul 2024
PubMed: 38959558
DOI: 10.1016/j.ejrad.2024.111585 -
International Immunopharmacology Jul 2024Prostate cancer remains a prominent challenge in oncology, with advanced stages showing poor prognosis. The tumor microenvironment (TME), and particularly...
BACKGROUND
Prostate cancer remains a prominent challenge in oncology, with advanced stages showing poor prognosis. The tumor microenvironment (TME), and particularly tumor-associated macrophages (TAMs), plays a crucial role in disease progression. This study explores the single-cell transcriptomics of prostate cancer, determines macrophage heterogeneity, identifies prognostic gene markers, and assesses the role of PPIF in TAMs.
METHODS
Single-cell RNA sequencing data from the GEO database (GSE176031) and transcriptome data from the TCGA were processed to characterize cell populations and identify prognostic genes in prostate cancer. Macrophage subpopulations were examined through clustering, followed by gene set scoring based on migration, activation, and proliferation. PPIF expression in macrophages was investigated using multiplex immunofluorescence staining on matched prostate cancer and adjacent non-tumoral tissues.
RESULTS
The single-cell analysis identified 9,178 cells, categorized into 10 principal cell types, with macrophages constituting a significant part of the immune microenvironment. Four macrophage subgroups demonstrated distinct functional pathways: phagocytic, immune-regulatory, and proliferative. A total of 39 genes correlated with prostate cancer prognosis were identified, of which 10 carried the most significant prognostic information. Peptidylprolyl Isomerase F (PPIF) expression was significantly higher in TAMs from tumor tissue than normal tissue, indicating its potential regulatory role in the immune microenvironment.
CONCLUSION
The intricate cellular architecture of the prostate cancer TME has been elucidated, with a focus on macrophage heterogeneity and functional specialization. Prognostic genes, including PPIF, were associated with survival outcomes, providing potential therapeutic targets. PPIF's prominent expression in TAMs may serve as a lever in cancer progression, warranting further investigation as a biomarker and a molecule of interest for therapeutic targeting within the prostate cancer milieu.
PubMed: 38959543
DOI: 10.1016/j.intimp.2024.112599 -
Cancer Research Jul 2024The TP53 tumor suppressor is frequently altered in lethal, castration-resistant prostate cancer (CRPC). However, to date there are no effective treatments that...
The TP53 tumor suppressor is frequently altered in lethal, castration-resistant prostate cancer (CRPC). However, to date there are no effective treatments that specifically target TP53 alterations. Using transcriptomic and metabolomic analyses, we showed here that TP53-altered prostate cancer (PCa) exhibits an increased dependency on asparagine and overexpresses asparagine synthetase (ASNS), the enzyme catalyzing the synthesis of asparagine. Mechanistically, loss or mutation of TP53 transcriptionally activated ASNS expression, directly as well as via mTORC1-mediated ATF4 induction, driving de novo asparagine biosynthesis to support CRPC growth. TP53-altered CRPC cells were sensitive to asparagine restriction by knockdown of ASNS or L-asparaginase treatment to deplete the intracellular and extracellular sources of asparagine, respectively, and cell viability was rescued by asparagine addition. Notably, pharmacological inhibition of intracellular asparagine biosynthesis using a glutaminase inhibitor and depletion of extracellular asparagine with L-asparaginase significantly reduced asparagine production and effectively impaired CRPC growth. This study highlights the significance of ASNS-mediated metabolic adaptation as a synthetic vulnerability in CRPC with TP53 alterations, providing a rationale for targeting asparagine production to treat these lethal prostate cancers.
PubMed: 38959335
DOI: 10.1158/0008-5472.CAN-23-2910 -
Science Translational Medicine Jul 2024Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address...
Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.
Topics: Animals; Male; Dogs; Humans; Prostate; Ionic Liquids; Drug Delivery Systems; Mice; Prostatic Neoplasms; Swine; Injections; Cell Line, Tumor; Ablation Techniques
PubMed: 38959326
DOI: 10.1126/scitranslmed.adn7982 -
JAMA Network Open Jul 2024Prostate cancer, a leading cause of cancer death among men, urgently requires new prevention strategies, which may involve targeting men with an underlying genetic...
IMPORTANCE
Prostate cancer, a leading cause of cancer death among men, urgently requires new prevention strategies, which may involve targeting men with an underlying genetic susceptibility.
OBJECTIVE
To explore differences in risk of early prostate cancer death among men with higher vs lower genetic risk to inform prevention efforts.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used a combined analysis of genotyped men without prostate cancer at inclusion and with lifestyle data in 2 prospective cohort studies in Sweden and the US, the Malmö Diet and Cancer Study (MDCS) and the Health Professionals Follow-Up Study (HPFS), followed up from 1991 to 2019. Data were analyzed between April 2023 and April 2024.
EXPOSURES
Men were categorized according to modifiable lifestyle behaviors and genetic risk. A polygenic risk score above the median or a family history of cancer defined men at higher genetic risk (67% of the study population); the remaining men were categorized as being at lower genetic risk.
MAIN OUTCOMES AND MEASURES
Prostate cancer death analyzed using time-to-event analysis estimating hazard ratios (HR), absolute risks, and preventable deaths by age.
RESULTS
Among the 19 607 men included for analysis, the median (IQR) age at inclusion was 59.0 (53.0-64.7) years (MDCS) and 65.1 (58.0-71.8) years (HPFS). During follow-up, 107 early (by age 75 years) and 337 late (after age 75 years) prostate cancer deaths were observed. Compared with men at lower genetic risk, men at higher genetic risk had increased rates of both early (HR, 3.26; 95% CI, 1.82-5.84) and late (HR, 2.26; 95% CI, 1.70-3.01) prostate cancer death, and higher lifetime risks of prostate cancer death (3.1% vs 1.3% [MDCS] and 2.3% vs 0.6% [HPFS]). Men at higher genetic risk accounted for 94 of 107 early prostate cancer deaths (88%), of which 36% (95% CI, 12%-60%) were estimated to be preventable through adherence to behaviors associated with a healthy lifestyle (not smoking, healthy weight, high physical activity, and a healthy diet).
CONCLUSIONS AND RELEVANCE
In this 20-year follow-up study, men with a genetic predisposition accounted for the vast majority of early prostate cancer deaths, of which one-third were estimated to be preventable. This suggests that men at increased genetic risk should be targeted in prostate cancer prevention strategies.
Topics: Humans; Male; Prostatic Neoplasms; Middle Aged; Aged; Genetic Predisposition to Disease; Sweden; Prospective Studies; Risk Factors; United States; Life Style; Cohort Studies
PubMed: 38958976
DOI: 10.1001/jamanetworkopen.2024.20034 -
International Urology and Nephrology Jul 2024Bladder neck contracture after transurethral resection of the prostate is a common complication but without clear predisposing factors. In this prospective study, we...
PURPOSE
Bladder neck contracture after transurethral resection of the prostate is a common complication but without clear predisposing factors. In this prospective study, we evaluated the perioperative risk factors associated with bladder neck contracture after bipolar transurethral resection of the prostate.
METHODS
The study included 391 patients who were admitted for bipolar transurethral resection of the prostate between October 2020 to October 2023 by three experienced surgeons. Forty three patients had bladder neck contracture and their perioperative parameters were compared with randomly chosen 172 patients without bladder neck contracture.
RESULTS
There were no significant differences between the studied groups regarding the general and present history characteristics. Re-catheterization after transurethral resection of the prostate, post-operative recurrent urinary tract infection, resection speed, and associated urethral stricture were significantly higher among the bladder neck-contraction group (P < 0.05), while total PSA, total prostate weight, post void residual urine volume, resected gland weight, resection time and catheter duration were significantly lower among the bladder neck-contraction group (P < 0.05).
CONCLUSION
Bladder neck contracture after bipolar transurethral resection of the prostate is more common among patients with small fibrotic prostate, low total PSA, small post- void residual urine volume, those with a higher incidence of post-operative recurrent urinary-tract infection and patients with a higher incidence of re-catheterization after transurethral resection of the prostate.
PubMed: 38958852
DOI: 10.1007/s11255-024-04125-2