Immediate lymph node extraction improves retrieval rate following axillary lymph node dissection: an effective approach to improving guideline-concordant breast cancer care in Nigeria.

Background: Axillary lymph node staging is essential for making therapeutic decisions and for prognostication. A minimum of ten lymph nodes is recommended for accurate staging. This study describes the process and outcomes of an audit cycle that resulted in a novel intervention instituted to improve concordance with guidelines. Methods: The study began with a retrospective audit of lymph node retrieval following axillary lymph node dissection (ALND). Subsequent phases evaluated the efficacy of immediate lymph node extraction before fixation by comparing the mean number of lymph nodes and the proportion of guideline-concordant cases to retrospective data and concurrent cases without the intervention. Results: The mean number of lymph nodes retrieved in the retrospective phase was 5.2, which is less than the recommended threshold. The intervention resulted in a significant increase in lymph node retrieval over the baseline rate (13.7 versus 5.2, p = 0.026). There was also a significantly higher number of lymph nodes following the intervention compared to concurrent cases managed during the same period without the intervention (13.7 versus 7.9, p = 0.004). The concordance rate was 89% in the intervention group compared to 47% in the non-intervention group (p = 0.019). There was no significant difference when the intervention was administered by either surgeons or pathologists (13.5 versus 12, p = 0.25). Conclusion: Immediate extraction of lymph nodes resulted in significant improvement of concordant lymph node retrieval in all phases of the study. We recommend that this practice be validated in larger cohorts for possible recommendation as an effective way of improving lymph node retrieval following ALND.

Novel Mouse Models of Bladder Cancer Identify a Prognostic Signature Associated with Risk of Disease Progression.

To study the progression of bladder cancer from non-muscle-invasive to muscle-invasive disease, we have developed a novel toolkit that uses complementary approaches to achieve gene recombination in specific cell populations in the bladder urothelium in vivo, thereby allowing us to generate a new series of genetically engineered mouse models (GEMM) of bladder cancer. One method is based on the delivery of adenoviruses that express Cre recombinase in selected cell types in the urothelium, and a second uses transgenic drivers in which activation of inducible Cre alleles can be limited to the bladder urothelium by intravesicular delivery of tamoxifen. Using both approaches, targeted deletion of the Pten and p53 tumor suppressor genes specifically in basal urothelial cells gave rise to muscle-invasive bladder tumors. Furthermore, preinvasive lesions arising in basal cells displayed upregulation of molecular pathways related to bladder tumorigenesis, including proinflammatory pathways. Cross-species analyses comparing a mouse gene signature of early bladder cancer with a human signature of bladder cancer progression identified a conserved 28-gene signature of early bladder cancer that is associated with poor prognosis for human bladder cancer and that outperforms comparable gene signatures. These findings demonstrate the relevance of these GEMMs for studying the biology of human bladder cancer and introduce a prognostic gene signature that may help to stratify patients at risk for progression to potentially lethal muscle-invasive disease. SIGNIFICANCE: Analyses of bladder cancer progression in a new series of genetically engineered mouse models has identified a gene signature of poor prognosis in human bladder cancer.