Testosterone replacement therapy in patients with cachexia: a contemporary review of the literature.

INTRODUCTION: Patients with long-term chronic illnesses frequently present with hypogonadism, which is primarily managed through exogenous testosterone. These same patients also experience a high degree of cachexia, a loss of skeletal muscle and adipose tissue. OBJECTIVE: To perform a contemporary review of the literature to assess the effectiveness of testosterone replacement therapy (TRT) for managing chronic disease-associated cachexia. METHODS: We performed a PubMed literature search using MeSH terms to identify studies from 2000 to 2022 on TRT and the following cachexia-related chronic medical diseases: cancer, COPD, HIV/AIDS, and liver cirrhosis. RESULTS: From the literature, 11 primary studies and 1 meta-analysis were selected. Among these studies, 3 evaluated TRT on cancer-associated cachexia, 3 on chronic obstructive pulmonary disease, 4 on HIV and AIDS, and 2 on liver cirrhosis. TRT showed mixed results favoring clinical improvement on each disease. CONCLUSIONS: Cachexia is commonly observed in chronic disease states. Its occurrence with hypogonadism, alongside the shared symptoms of these 2 conditions, points toward the management of cachexia through the administration of exogenous testosterone. Robust data in the literature support the use of testosterone in increasing lean body mass, improving energy levels, and enhancing the quality of life for patients with chronic disease. However, the data are variable, and further studies are warranted on the long-term efficacy of TRT in patients with cachexia.

Ex-vivo microscopic oncotesticular sperm extraction: step-by-step surgical technique at time of radical orchiectomy.

OBJECTIVE: To demonstrate the intraoperative surgical techniques required for simultaneous radical orchiectomy and microscopic oncotesticular sperm extraction (m-OncoTESE) in a step-by-step fashion. DESIGN: Video presentation. SETTING: University Hospital (University of Chicago). PATIENTS: A 37-year-old man (status after right orchiectomy at another institution for stage II-C testicular seminoma with positive preoperative tumor markers) was referred for contralateral orchiectomy of multifocal left testis mass and fertility preservation. Semen analysis before, microscopic testicular sperm extraction during, and semen or testicular specimen analysis after the first orchiectomy were unable to identify any sperm. A postoperative analysis of the m-OncoTESE performed on the left testis resulted in the cryopreservation of 200,000 motile sperm for future assisted reproductive technology (i.e., in vitro fertilization or in vitro fertilization-intracytoplasmic sperm injection). INTERVENTIONS: Left radical orchiectomy and left m-OncoTESE. MAIN OUTCOME MEASURES: A comprehensive visual documentation of m-OncoTESE surgical techniques with concurrent commentary detailing the reasons behind each surgical step. A brief discussion on the background of m-OncoTESE and alternative fertility preservation methods accompanies the procedure. RESULTS: This video provides a step-by-step guide to performing an m-OncoTESE (proceeding a radical orchiectomy in a patient with testicular cancer) as a means of fertility preservation in an azoospermic patient. Successful extraction and cryopreservation of testicular spermatozoa were achieved after targeted ex-vivo testicular microdissection. CONCLUSIONS: Sperm extraction via m-OncoTESE is a viable option for azoospermic patients with testicular cancer undergoing radical orchiectomies. The use of preoperative imaging and microsurgical techniques facilitates and optimizes surgical dissection and sperm recovery.

Pediatric robotic urologic procedures: Indications and outcomes.

Introduction: Robotic-assisted laparoscopic surgery (RALS) has revolutionized minimally invasive surgery in pediatric urology. The robotic platform allows surgeons to maintain the benefits of laparoscopic surgery while having enhanced three-dimensional view, dexterity, range of motion, and control of high-resolution cameras. In this review, we summarize the indications and recent outcomes for various pediatric urologic RALS procedures to illustrate the current state of robotics in pediatric urology. Methods: We systematically searched the PubMed and EMBASE databases. We extrapolated and summarized recent evidence on RALS in pediatric urology patients, with an emphasis on indications and outcomes, with regard to the following procedures and search terms: pyeloplasty, kidney stone surgery, partial nephrectomy, nephroureterectomy, ureteral reimplantation, appendico-vesicostomy, augmentation cystoplasty, bladder neck reconstruction, and Malone antegrade continence enema. Additional Medical Subject Headings terms used to augment the search included "Treatment Outcome" and "Robotic Surgical Procedures." Results: Increasing usage of RALS has shown many benefits in perioperative and postoperative outcomes. In addition, there is growing evidence that robotic procedures in pediatric urology result in similar or better surgical outcomes when compared to the standard of care. Conclusions: RALS has shown considerable effectiveness in pediatric urologic procedures and may achieve surgical outcomes comparable to the standard approaches of open or laparoscopic surgery. However, larger case series and prospective randomized controlled trials are still necessary to validate the reported outcomes, in addition to cost analyses and studies on the surgical learning curve. We believe that the continuous evolution of robotic platforms will allow for enhanced care and quality of life for pediatric urology patients.

A Systematic Review of Partner Satisfaction After Penile Prosthesis with Special Emphasis on LGBTQ + Populations.

PURPOSE OF REVIEW: Despite the current surgical advances and patients' satisfactions after penile prosthesis (PP) implantation, there has been paucity of data on reported partner satisfaction and their quality-of-life (QoL). Our objective was to summarize the current literature on partner satisfaction for both heterosexual and non-heterosexual populations, respectively. We specifically conducted a systematic review according to the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards, and stratified studies into three tiers by methodological rigor. RECENT FINDINGS: After an initial search of 172 articles, 33 studies met the inclusion criteria for the final review: 30 for heterosexual partner satisfaction, and 3 for LGBTQ patient satisfaction were included due to lack of published literature on partner satisfaction for LGBTQ patients. For heterosexual partner satisfaction, 10 studies were classified as Tier 1, 11 studies were classified as Tier 2, and 9 studies were classified as Tier 3. From an initial search of 13 records, three studies consisting of 272 patients met the inclusion criteria for our LGBTQ review. Across all the tiers, studies noted satisfaction rates between 50 and 90% and improved satisfaction and sexual QoL metrics compared to pre-surgery rates. That said, partner satisfaction rates were also consistently lower than patient satisfaction rates. Although the range of evidence quality varies, the available literature suggests significant improvements in and relatively high rates of partner satisfaction after PP implantation. Given the diversity of study designs and widespread use of non-validated or non-specific questionnaires in the current literature, future research should focus on prospective studies and/or data collection using validated, PP-specific questionnaires.

Aesthetic Penile Augmentation Procedures: A Comprehensive and Current Perspective.

PURPOSE OF REVIEW: Some men experience small penis syndrome (SPS), a body dysmorphic disorder in which a patient believes their penis to be small even when it is clinically average. As cosmetic surgery becomes more widely accepted, management of SPS may present a challenge for urologists. We aim to provide an updated review of aesthetic penile augmentation procedures. RECENT FINDINGS: Augmentation procedures range from invasive to noninvasive. Surgical solutions include grafts and flaps, suspensory ligament release, and suprapubic lipectomy. Minimally invasive solutions include injections of fillers (hyaluronic acid, polylactic acid, and polymethyl methacrylate). Noninvasive solutions include external devices such as vacuum pumps and traction devices. In the current climate, aesthetic penile augmentation is becoming a desirable option for many patients but remains clinically controversial. Our review summarizes recent and relevant studies and demonstrates the need for further research and consensus on penile augmentation procedures.

Hyaluronic acid fuels pancreatic cancer cell growth.

Rewired metabolism is a hallmark of pancreatic ductal adenocarcinomas (PDA). Previously, we demonstrated that PDA cells enhance glycosylation precursor biogenesis through the hexosamine biosynthetic pathway (HBP) via activation of the rate limiting enzyme, glutamine-fructose 6-phosphate amidotransferase 1 (GFAT1). Here, we genetically ablated GFAT1 in human PDA cell lines, which completely blocked proliferation in vitro and led to cell death. In contrast, GFAT1 knockout did not preclude the growth of human tumor xenografts in mice, suggesting that cancer cells can maintain fidelity of glycosylation precursor pools by scavenging nutrients from the tumor microenvironment. We found that hyaluronic acid (HA), an abundant carbohydrate polymer in pancreatic tumors composed of repeating N-acetyl-glucosamine (GlcNAc) and glucuronic acid sugars, can bypass GFAT1 to refuel the HBP via the GlcNAc salvage pathway. Together, these data show HA can serve as a nutrient fueling PDA metabolism beyond its previously appreciated structural and signaling roles.

GOT1 inhibition promotes pancreatic cancer cell death by ferroptosis.

Cancer metabolism is rewired to support cell survival in response to intrinsic and environmental stressors. Identification of strategies to target these adaptions is an area of active research. We previously described a cytosolic aspartate aminotransaminase (GOT1)-driven pathway in pancreatic cancer used to maintain redox balance. Here, we sought to identify metabolic dependencies following GOT1 inhibition to exploit this feature of pancreatic cancer and to provide additional insight into regulation of redox metabolism. Using pharmacological methods, we identify cysteine, glutathione, and lipid antioxidant function as metabolic vulnerabilities following GOT1 withdrawal. We demonstrate that targeting any of these pathways triggers ferroptosis, an oxidative, iron-dependent form of cell death, in GOT1 knockdown cells. Mechanistically, we reveal that GOT1 inhibition represses mitochondrial metabolism and promotes a catabolic state. Consequently, we find that this enhances labile iron availability through autophagy, which potentiates the activity of ferroptotic stimuli. Overall, our study identifies a biochemical connection between GOT1, iron regulation, and ferroptosis.

p53 Integrates Temporal WDR5 Inputs during Neuroectoderm and Mesoderm Differentiation of Mouse Embryonic Stem Cells.

How ubiquitous transcription factors (TFs) coordinate temporal inputs from broadly expressed epigenetic factors to control cell fate remains poorly understood. Here, we uncover a molecular relationship between p53, an abundant embryonic TF, and WDR5, an essential member of the MLL chromatin modifying complex, that regulates mouse embryonic stem cell fate. Wild-type Wdr5 or transient Wdr5 knockout promotes a distinct pattern of global chromatin accessibility and spurs neuroectodermal differentiation through an RbBP5-dependent process in which WDR5 binds to, and activates transcription of, neural genes. Wdr5 rescue after its prolonged inhibition targets WDR5 to mesoderm lineage-specifying genes, stimulating differentiation toward mesoderm fates in a p53-dependent fashion. Finally, we identify a direct interaction between WDR5 and p53 that enables their co-recruitment to, and regulation of, genes known to control cell proliferation and fate. Our results unmask p53-dependent mechanisms that temporally integrate epigenetic WDR5 inputs to drive neuroectoderm and mesoderm differentiation from pluripotent cells.