Dumbrava, Mihai G

AbstractBackgroundNeoadjuvant platinum‐based chemotherapy offers a modest survival advantage in muscle‐invasive bladder cancer (MIBC) for patients with pathologic response. B7‐H3 (CD276), an immune checkpoint overexpressed in various cancers, including urothelial‐cell carcinoma (UCC), has been associated with chemoresistance and poor oncologic outcomes. We aimed to explore if B7H3 expression on bladder biopsy samples was a predictive biomarker for pathologic response to neoadjuvant platinum‐based chemotherapy.MethodsThis was a retrospective cohort study among MIBC patients receiving neoadjuvant platinum‐based chemotherapy followed by radical cystectomy. All patients underwent routine preoperative biopsy of their tumour. Immunohistochemistry was used to evaluate B7‐H3 expression from pre‐operative specimens. The primary outcome of interest was pathologic complete response (pCR). Statistical analysis included Mann–Whitney U test, Fisher's exact test, Kaplan–Meier method, and Cox regression for survival analysis.ResultsAmong 87 patients analysed, high B7‐H3 expression was found in 44.8% (n = 39) of patients. The median follow‐up periods were similar between the high and low B7‐H3 groups (high expression; 4.29 years [SD 3.04], low expression 3.94 years [SD 3.04], p = 0.60). Only 20.5% of patients with high B7‐H3 expression achieved pCR, compared to 41.7% in the low expression group (p = 0.04). Cox regression showed no significant differences in recurrence‐free or cancer‐specific survival between the high and low B7‐H3 expression groups (p > 0.05).ConclusionHigh B7‐H3 expression is associated with a reduced likelihood of achieving pCR in MIBC patients undergoing neoadjuvant chemotherapy. This suggests B7‐H3's potential as a predictive biomarker for chemotherapy response. Further research is needed to explore the role of B7‐H3 on platinum‐based chemotherapy response in urothelial cancer.

AbstractPatient‐derived cancer organoids (PDOs) hold considerable promise for personalizing therapy selection and improving patient outcomes. However, it is challenging to generate PDOs in sufficient numbers to test therapies in standard culture platforms. This challenge is particularly acute for pancreatic ductal adenocarcinoma (PDAC) where most patients are diagnosed at an advanced stage with non‐resectable tumors and where patient tissue is in the form of needle biopsies. Here the development and characterization of microfluidic devices for testing therapies using a limited amount of tissue or PDOs available from PDAC biopsies is described. It is demonstrated that microfluidic PDOs are phenotypically and genotypically similar to the gold‐standard Matrigel organoids with the advantages of 1) spheroid uniformity, 2) minimal cell number requirement, and 3) not relying on Matrigel. The utility of microfluidic PDOs is proven by testing PDO responses to several chemotherapies, including an inhibitor of glycogen synthase kinase (GSKI). In addition, microfluidic organoid cultures are used to test effectiveness of immunotherapy comprised of NK cells in combination with a novel biologic. In summary, our microfluidic device offers considerable benefits for personalizing oncology based on cancer biopsies and may, in the future, be developed into a companion diagnostic for chemotherapy or immunotherapy treatments.

Abstract In the past decade, vascularized composite allotransplantation (VCA) has become clinical reality for reconstruction after face and hand trauma. It offers patients the unique opportunity to regain form and function in a way that had only been achieved with traditional reconstruction or with the use of prostheses. On the other hand, prostheses for facial and hand reconstruction have continued to evolve over the years and, in many cases, represent the primary option for patients after hand and face trauma. We compared the cost, associated complications, and long-term outcomes of VCA with prostheses for reconstruction of the face and hand/upper extremity. Ultimately, VCA and prostheses represent 2 different reconstructive options with distinct benefit profiles and associated limitations and should ideally not be perceived as competing choices. Our work adds a valuable component to the general framework guiding the decision to offer VCA or prostheses for reconstruction after face and upper extremity trauma.