Reconstructive Management Pearls for the Transgender Patient.

PURPOSE OF REVIEW: A growing number of transgender patients are seeking gender-affirming genital reconstructive surgery (GRS). These complex procedures have high complication rates. We describe common surgical pitfalls in GRS and approaches for minimizing complications. RECENT FINDINGS: Penile inversion vaginoplasty has been associated with excellent cosmetic and functional outcomes. A robotic-assisted dissection may minimize risk of rectal injury. As a younger transgender population chooses pubertal suppression, alternative sources for lining the vaginal canal, such as enteric vaginoplasties, may be more widely utilized. Since adoption of microvascular techniques in phalloplasty, transmasculine individuals have potential for a sensate neophallus and penetrative intercourse. Urethral complications are common and challenging to manage; techniques using flap coverage may minimize ischemia-related strictures. Innovations in prosthesis placement require adaptations to neophallus anatomy. A growing number of transgender individuals are seeking genital reconstruction. Ongoing innovation in surgical technique is needed to improve patient outcomes.

IKK inhibition by BMS-345541 suppresses breast tumorigenesis and metastases by targeting GD2+ cancer stem cells.

We have identified that the ganglioside GD2 is a marker for breast cancer stem cells (BCSCs), and that targeting the enzyme GD3 synthase (GD3S, which regulates GD2 biosynthesis) reduces breast tumorigenesis. The pathways regulating GD2 expression, and their anomalous functions in BCSC, are unclear. Proteomic analysis of GD2+ and GD2- cells from breast cancer cell lines revealed the activation of NFκB signaling in GD2+ cells. Dose- and time-dependent suppression of NFκB signaling by the small molecule inhibitor BMS-345541 reduced GD2+ cells by > 90%. Likewise, BMS-345541 inhibited BCSC GD3S expression, mammosphere formation, and cell migration/invasion in vitro. Breast tumor-bearing mice treated with BMS-345541 showed a statistically significant decrease in tumor volume and exhibited prolonged survival compared to control mice, with a median survival of 78 d for the BMS-345541-treated group vs. 58 d for the controls. Moreover, in an experimental metastases model, treatment with BMS-345541 reduced the lung metastases by > 5-fold. These data suggest that GD2 expression and function,and NFκB signaling, are related, and they control BCSCs tumorigenic characteristics. Thus, the suppression of NFκB signaling by BMS-345541 is a potentially important advance in controlling breast cancer growth and metastases.