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.
The genomic and immunologic profiling of renal cell carcinoma (RCC) has provided the impetus for advancements in systemic treatments using combination therapy - either with immune check point ...inhibitor (ICI) + ICI or with ICI + targeted therapy. This approach has been examined in several landmark trials, treating both clear cell (ccRCC) and nonclear cell (nccRCC) histologies. In this review, we highlight systemic therapy advancements made in this new decade, the 2020s.
Targeting the programmed death receptor 1/PD-L1 pathway has created more tolerable and effective immunotherapy regimens, expanding the applications of ICIs. These new applications, paired with trial data, include ICI monotherapy in nccRCC and adjuvant pembrolizumab in resected, high-risk RCC. In addition, ICI + ICI and ICI + TKI combination therapy have demonstrated oncologic efficacy in advanced ccRCC and sarcomatoid RCC. Similar progress has been noted regarding new targeted therapies. Along the hypoxia inducible factor pathway, belzutifan has received FDA approval in von Hippel-Lindau-associated RCC. In addition, in papillary RCC, agents such as cabozantinib target the MET proto-oncogene pathway and have demonstrated impressive oncologic outcomes.
The 2020s utilize the molecular profiling of advanced RCC as a scaffold for recent trials in immunotherapy and targeted therapies. Going forward, emphasizing patient-reported outcomes and careful clinical trial construction remain critical to improve systemic therapy in RCC.
Purpose of Review
Rezum® is a novel convection-based thermal therapy for benign prostatic hyperplasia (BPH) induced lower urinary tract symptoms (LUTS). This review provides an overview of its ...safety, efficacy, cost, and potential role in the paradigm of BPH/LUTS therapies.
Recent Findings
Data regarding Rezum® stems primarily from one large randomized controlled trial of 197 patients with 4 years of follow-up. The efficacy and safety of Rezum® is further supported by 4 additional studies including 1 prospective pilot study, 1 crossover study, and 2 retrospective studies. Durable improvements in IPSS (47–60%), QoL (38–52%), Qmax (45–72%), and PVR (11–38%) were seen without causing deterioration of sexual function.
Summary
Rezum® offers a cost-effective and safe approach to treating BPH/LUTS and should be considered as a possible first-line therapy for patients with moderate to severe symptoms.
We present a case of chemotherapy refractory spindle cell rhabdomyosarcoma of the lower urinary tract in a 15-month-old female that ultimately required consolidative surgery with cystectomy, ...urethrectomy, ovarian-sparing hysterectomy, bilateral salpingectomy, anterior vaginal wall resection, and bilateral pelvic lymph node dissection. Genitourinary reconstruction was performed by ileal conduit creation and vaginoplasty. After completion of her maintenance postoperative chemotherapy regimen, the patient has remained disease-free for approximately 27 months.
To systematically review and perform a meta-analysis on the safety and efficacy of endovascular therapy in the treatment of the two most common etiologies of vasculogenic erectile dysfunction (ED): ...veno-occlusive dysfunction (VOD) and arterial insufficiency (AI).
PubMed, Web of Science, ScienceDirect, and Scopus databases were searched for published English literature regarding endovascular ED treatments. Case series (n ≥ 3) were included. Multiple data points were obtained, including demographic data, etiology, diagnosis method, imaging studies, treatment approach, technical success, clinical success, complications, and follow-up.
Sixteen relevant articles were obtained and a total of 212 patients with VOD and 162 with AI were identified. The VOD cohort were treated either percutaneously (60.4%; n = 128) or after surgical exposure of the deep dorsal vein (33.5%, n = 71), or it was unspecified (6.1%; n = 13). The most common embolic used was n-butyl cyanoacrylate (51.9%; n = 109). Meta-analysis found an overall clinical success rate of 59.8% in VOD patients. Complications occurred in 5.2% of patients (n = 11), with 9 considered to be mild and 2 considered to be severe. The AI cohort contained 162 patients most commonly treated via stenting of the internal pudendal artery (40.1%; n = 65). Meta-analysis found an overall clinical success rate of 63.2% in AI patients. Complications occurred in 4.9% of patients (n = 8), with 4 considered to be mild and 4 considered to be severe.
Endovascular therapy for medically refractory ED is safe and may provide a treatment alternative to more invasive surgical management; however, conclusions are limited by the heterogeneity of clinical success definitions among the included studies.
To assess the incidence of postoperative arterial malformation (AM) and urine leak/urinoma (UL) after robotic partial nephrectomy (RPN) in a contemporary series and to evaluate risk factors for these ...complications.
All RPNs were queried from Institutional Review Board-approved retrospective and prospective nephrectomy databases. Demographics, perioperative variables, and postoperative complications were collected. Differences between cohorts were analyzed using univariate analysis. Postoperative complications were graded using the Clavien-Dindo system. UL was defined in the context of signs and symptoms of a collection with supporting evidence of urine collection through drainage or aspiration. AM was identified based on postoperative imaging indicative of arteriovenous fistula or pseudoaneurysm and/or requirement for selective embolization. Predictors of AM and UL were assessed by univariate analysis.
A total of 395 RPNs were performed by four urologists between January 2014 and October 2018. Tumor complexity, defined by nephrometry score, was significantly greater in the prospective cohort (
= 0.01). Overall incidence of postoperative complications was 5.6% with cohort-specific incidences of 5.3% and 5.8%. The retrospective cohort had a greater percentage of complications classified as ≥IIIa: 8/13 (61.5%)
2/8 (25%). Overall incidence of AM was 2.3% with cohort-specific incidence of 3.1% (7/225)
1.1% (2/170). Overall incidence of UL was 0.25% with cohort-specific incidence of 0.55% (1/225) and 0.0% (0/170). The difference in incidence of both complications between cohorts was significant (
< 0.05). No significant predictors for AM were identified.
The incidence of postoperative complications after RPN remains low (5.3%
5.8%, overall: 5.6%). UL and AM are becoming rarer with experience, despite increasing surgical complexity (0.55%
0%, 3.1%
1.1%).
Primary adrenal leiomyosarcoma, a malignant soft tissue tumour originating from the smooth muscle of the inferior vena cava and adrenal vein, is rarely described in the literature. Cases are often ...diagnosed at an advanced stage as the tumour is not hormone-producing. We describe a 70-year-old man who presented with lower extremity swelling and abdominal varices and was subsequently found to have a large adrenal mass on imaging. Our case is among the few reported primary adrenal leiomyosarcomas in which a CT-guided biopsy was used to aid in diagnosis.
As part of our efforts to develop new classes of tubulin inhibitor payloads for antibody–drug conjugate (ADC) programs, we developed a tubulysin ADC that demonstrated excellent in vitro activity but ...suffered from rapid metabolism of a critical acetate ester. A two-pronged strategy was employed to address this metabolism. First, the hydrolytically labile ester was replaced by a carbamate functional group resulting in a more stable ADC that retained potency in cellular assays. Second, site-specific conjugation was employed in order to design ADCs with reduced metabolic liabilities. Using the later approach, we were able to identify a conjugate at the 334C position of the heavy chain that resulted in an ADC with considerably reduced metabolism and improved efficacy. The examples discussed herein provide one of the clearest demonstrations to-date that site of conjugation can play a critical role in addressing metabolic and PK liabilities of an ADC. Moreover, a clear correlation was identified between the hydrophobicity of an ADC and its susceptibility to metabolic enzymes. Importantly, this study demonstrates that traditional medicinal chemistry strategies can be effectively applied to ADC programs.
The tubulysin class of natural products has attracted much attention from the medicinal chemistry community due to its potent cytotoxicity against a wide range of human cancer cell lines, including ...significant activity in multidrug-resistant carcinoma models. As a result of their potency, the tubulysins have become an important tool for use in targeted therapy, being widely pursued as payloads in the development of novel small molecule drug conjugates (SMDCs) and antibody–drug conjugates (ADCs). A structure-based and parallel medicinal chemistry approach was applied to the synthesis of novel tubulysin analogues. These efforts led to the discovery of a number of novel and potent cytotoxic tubulysin analogues, providing a framework for our simultaneous report, which highlights the discovery of tubulysin-based ADCs, including use of site-specific conjugation to address in vivo stability of the C-11 acetate functionality.
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