RESUMO
Background: This systematic review and meta-analysis will review randomized control trials for localized bladder cancer, evaluating surgical and pathologic outcomes of ORC versus RARC. Methods: Randomized studies evaluating adults with non-metastatic bladder cancer who underwent a radical cystectomy. Randomized trials were selected for final review. Data was extracted and analyzed with Revman 5 software. The primary outcome was complication rates within 90 days. Secondary outcomes included postoperative quality of life, estimated intraoperative blood loss, and other perioperative outcomes. Continuous variables were reported using mean difference with 95% confidence intervals, and dichotomous variables were reported using risk difference with 95% confidence intervals with RARC as the experimental group and ORC as the reference group. Results: Of 134 articles screened, six unique randomized studies were selected. For Grade I-II complications, the risk ratio (RR) was 0.92 (95% CI [0.79,1.08], p = 0.33), and for Grade III-V complications, RR 0.93 (95% CI [0.73,1.18], p = 0.59). RARC resulted in decreased blood loss (95% CI [-438.08, -158.44], p < 0.00001) and longer operative time (95% CI [55.23, 133.13], p < 0.00001). Quality of life using the EORTC-QLQ-30 global health score at 3 months post-op appeared to favor RARC with a mean difference of 4.46 points (95% CI [1.78, 7.15], p = 0.001). Pathologic outcomes neither statistically nor clinically favored one modality, as there was no significant difference between mean lymph node yield (p = 0.49), positive lymph nodes (p = 1.00), and positive surgical margins (p = 0.85) between the surgical modalities. Conclusions: Although one surgical modality is not overtly superior, the choice may be decided by mitigating individual operative risk factors like intraoperative blood loss, operative time, post-operative quality of life, as well as institutional costs and learning curve among surgeons.
RESUMO
Complement protein C3dg, a key linkage between innate and adaptive immunity, is capable of stimulating both humoral and cell-mediated immune responses, leading to considerable interest in its use as a molecular adjuvant. However, the potential of C3dg as an adjuvant is limited without ways of controllably assembling multiple copies of it into vaccine platforms. Here, we report a strategy to assemble C3dg into supramolecular nanofibers with excellent compositional control, using ß-tail fusion tags. These assemblies were investigated as therapeutic active immunotherapies, which may offer advantages over existing biologics, particularly toward chronic inflammatory diseases. Supramolecular assemblies based on the Q11 peptide system containing ß-tail-tagged C3dg, B cell epitopes from TNF, and the universal T cell epitope PADRE raised strong antibody responses against both TNF and C3dg, and prophylactic immunization with these materials significantly improved protection in a lethal TNF-mediated inflammation model. Additionally, in a murine model of psoriasis induced by imiquimod, the C3dg-adjuvanted nanofiber vaccine performed as well as anti-TNF monoclonal antibodies. Nanofibers containing only ß-tail-C3dg and lacking the TNF B cell epitope also showed improvements in both models, suggesting that supramolecular C3dg, by itself, played an important therapeutic role. We observed that immunization with ß-tail-C3dg caused the expansion of an autoreactive C3dg-specific T cell population, which may act to dampen the immune response, preventing excessive inflammation. These findings indicate that molecular assemblies displaying C3dg warrant further development as active immunotherapies.
