Paradigm Shifting Research: Key Studies in Urologic Oncology.

BACKGROUND: Genitourinary malignancies have a substantial impact on men and women in the USA as they include three of the ten most common cancers (prostate, renal, and bladder). Other urinary tract cancers are less common (testis and penile) but still have profound treatment implications related to potential deficits in sexual, urinary, and reproductive function. Evidenced-based practice remains the cornerstone of treatment for urologic malignancies. METHODS: The authors reviewed the literature in consideration of the four top articles influencing clinical practice in the prior calendar year, 2022. RESULTS: The PROTECT trial demonstrates favorable 15-years outcomes for active monitoring of localized prostate cancer. The SEMS trial establishes retroperitoneal lymph node dissection as a viable option for patients with seminoma of the testis with limited retroperitoneal lymph node metastases. CheckMate 274 supports adjuvant immunotherapy following radical cystectomy for muscle-invasive bladder cancer with a high risk of recurrence. Data reported from the IROCK consortium reinforce stereotactic ablative radiotherapy as an option for localized renal cell carcinoma. CONCLUSION: The care for patients with urologic cancers has been greatly improved through advances in surgical, medical, and radiation oncologic treatments realized through prospective randomized clinical trials and large multicenter collaborative groups.

Label-Free and High-Throughput Removal of Residual Undifferentiated Cells From iPSC-Derived Spinal Cord Progenitor Cells.

The transplantation of spinal cord progenitor cells (SCPCs) derived from human-induced pluripotent stem cells (iPSCs) has beneficial effects in treating spinal cord injury (SCI). However, the presence of residual undifferentiated iPSCs among their differentiated progeny poses a high risk as these cells can develop teratomas or other types of tumors post-transplantation. Despite the need to remove these residual undifferentiated iPSCs, no specific surface markers can identify them for subsequent removal. By profiling the size of SCPCs after a 10-day differentiation process, we found that the large-sized group contains significantly more cells expressing pluripotent markers. In this study, we used a sized-based, label-free separation using an inertial microfluidic-based device to remove tumor-risk cells. The device can reduce the number of undifferentiated cells from an SCPC population with high throughput (ie, >3 million cells/minute) without affecting cell viability and functions. The sorted cells were verified with immunofluorescence staining, flow cytometry analysis, and colony culture assay. We demonstrated the capabilities of our technology to reduce the percentage of OCT4-positive cells. Our technology has great potential for the "downstream processing" of cell manufacturing workflow, ensuring better quality and safety of transplanted cells.

Enterovirus-A71 preferentially infects and replicates in human motor neurons, inducing neurodegeneration by ferroptosis.

Enterovirus A71 (EV-A71) causes Hand, Foot, and Mouth Disease and has been clinically associated with neurological complications. However, there is a lack of relevant models to elucidate the neuropathology of EV-A71 and its mechanism, as the current models mainly utilize animal models or immortalized cell lines. In this study, we established a human motor neuron model for EV-A71 infection. Single cell transcriptomics of a mixed neuronal population reveal higher viral RNA load in motor neurons, suggesting higher infectivity and replication of EV-A71 in motor neurons. The elevated RNA load in motor neurons correlates with the downregulation of ferritin-encoding genes. Subsequent analysis confirms that neurons infected with EV-A71 undergo ferroptosis, as evidenced by increased levels of labile Fe2+ and peroxidated lipids. Notably, the Fe2+ chelator Deferoxamine improves mitochondrial function and promotes survival of motor neurons by 40% after EV-A71 infection. These findings deepen understanding of the molecular pathogenesis of EV-A71 infection, providing insights which suggest that improving mitochondrial respiration and inhibition of ferroptosis can mitigate the impact of EV-A71 infection in the central nervous system.

Long-Term Results of Bladder Preservation with Twice-Daily Radiation plus 5-Flourouracil/Cisplatin or Daily Radiation plus Gemcitabine for MIBC - Updated Report of NRG/RTOG 0712: A Randomized Phase 2 Trial.

PURPOSE: 5-FU/cisplatin and twice-daily radiation (FCT) or gemcitabine and once daily radiation (GD) are effective chemoradiation (CRT) regimens for bladder sparing treatment of muscle-invasive bladder cancer (MIBC). This trial evaluated these regimens and demonstrated efficacy with either regimen at 3 years. With further follow-up, longer term results are reported here. METHODS AND MATERIALS: Patients with cT2-4a MIBC were randomized to FCT or GD. Patients had a transurethral resection and induction CRT to 40 Gy. Patients with a complete response (CR) received consolidation CRT to 64 Gy. Others had cystectomy. Adjuvant gemcitabine/cisplatin chemotherapy was administered. The primary endpoint was freedom from distant metastasis (FDM). This updated analysis reports 7-year data. Toxicity and efficacy endpoints, including bladder intact distant metastasis free survival (BI-DMFS) were also assessed. RESULTS: From 12/2008 to 4/2014, 70 patients were enrolled; 66 eligible for analysis, 33 per arm. Median follow-up was 9.1 years for eligible living patients. At 7 years, FDM was 65% and 73% for FCT and GD, respectively. BI-DMFS was 58% (95% CI: 41 - 76) and 68% (95% CI: 51-84), respectively. The post-hoc hazard ratio of 0.75 (95% CI: 0.37-1.55) showed no difference between treatments (p=0.44). Overall survival at 7 years was 48% and 59%. There were 4 and 5 cystectomies performed for FCT and GD, respectively. In the FCT arm, there were 5 (16%), 1 (3%) and 0 grade 3, 4 and 5 late toxicities reported. In the GD arm, there were 7 (23%), 0 and 0. CONCLUSIONS: Both regimens maintained high FDM rates at 7 years. Cystectomy rates were low and overall survival rates high on both arms. Late toxicity rates were low. Either gemcitabine and daily radiation or a cisplatin-based regimen are effective bladder sparing therapies.

The effects of VY closure on lip morphology after Le Fort I maxillary advancement: A systematic review.

VY closure of the Le Fort 1 incision may commonly be indicated to mitigate the lip shortening effects of maxillary advancement. The objective of this systematic review was to investigate if VY closure prevents lip shortening when compared with conventional continuous closure (CS) methods, in patients who underwent le fort 1 maxillary advancement. PubMed, Embase, and Cochrane Library databases were accessed. Hand searching was also performed. Observational studies, non-randomised and randomized controlled trials were included if Le Fort 1 maxillary advancement was performed to correct a dentofacial deformity. Comparisons were made between VY and CS, and morphological changes to the upper lip were evaluated. The demographic data, study methodology, magnitude of maxillary movements and outcomes related to the lip morphology (length, vermillion exposure, thickness and angulation) were extracted. The search yielded 487 articles. Six studies were included after the application of the selection criteria. A total of 100 and 94 patients received CS and VY respectively. VY was not found to reliably prevent lip shortening. VY was more likely to mitigate lip shortening when there is a large maxillary advancement. It was consistent for a protrusive or "rolled-out" lip morphology to occur after a VY closure. This was demonstrated by the increase in lip vermillion exposure, thickness, and angulation. VY closure was a useful adjunctive technique in patients undergoing large maxillary advancements to mitigate the lip shortening effect from the procedure. Surgeons who employ this technique must also be aware of the consequence of a more protrusive lip with increased vermillion exposure and assess if this would be aesthetically desirable for the individual patient.