No abstract

Cancer is a major leading cause of disease-related death in the world. The severe impact of cancer can be attributed to poor understanding of the mechanisms involved in earliest steps of the metastatic cascade, specifically invasion into the surrounding stroma and intravasation into the blood capillaries. However, conducting integrated biological studies of invasion and intravasation have been challenging, within in vivo models and traditional in vitro assay, due to difficulties in establishing a precise tumor microenvironment. To that end, in this work, a novel 3D microfluidic platform comprised of concentric three-layer cell-laden hydrogels for simultaneous investigation of breast cancer cell invasion and intravasation as well as vasculature maturation influenced by tumor-vascular crosstalk is developed. It was demonstrated that the presence of spontaneously formed vasculature enhance MDA-MB-231 invasion into the 3D stroma. Following invasion, cancer cells are visualized intravasating into the outer vasculature. Additionally, invading cancer cells significantly reduce vessel diameter while increasing permeability, consistent with previous in vivo studies. Major signaling cytokines involved in tumor-vascular crosstalk that govern cancer cell invasion and intravasation are further identified. Taken together, this platform will enable unique insights of critical biological events within the metastatic cascade, with significant potential for developing efficient cancer therapeutics.

Objectives To evaluate if the obesity paradox, wherein obesity portends worse overall prognosis for a disease but improved outcomes for patients receiving immunotherapy, exists for patients receiving bacillus Calmette–Guérin (BCG) in a contemporary cohort. Patients and Methods We performed an Institutional Review Board‐approved database review to identify patients with non‐muscle‐invasive bladder cancer (NMIBC) completing at least an induction course of BCG. Clinicopathological variables collected included: body mass index (BMI), medications, and diabetes mellitus (DM). Outcomes of interest included: recurrence‐free (RFS), progression‐free (PFS), cancer‐specific (CSS), and overall survival (OS). Univariate and multivariate modelling were used to evaluate the association between outcomes and clinical factors. Results A total of 579 patients (median follow‐up 4.6 years) received BCG induction for NMIBC; 90% had high‐grade disease (47.2% clinical stage T1). In all, 75.7% of patients were overweight or obese and 18% had DM. Aspirin, statins, metformin and β‐blockers were used in 34%, 42%, 11%, and 29% of patients, respectively. Overweight and obese patients had improved PFS, CSS and OS. DM was associated with worse RFS. Medications of interest had no association with outcomes. Conclusion Elevated BMI is associated with improved outcomes in patients with NMIBC treated with BCG immunotherapy. Patients with DM are at increased risk of recurrence. These findings support a potential obesity paradox in bladder cancer. Evaluation of the underlying mechanism and the role of global patient assessment, counselling, and risk factor modification are warranted.

No abstract

Background: Guideline indications for restaging transurethral resection (reTUR) for high-grade (HG) Ta bladder tumors vary due to a paucity of data. Objective: To investigate guideline-based, risk-adapted approaches to reTUR for HG Ta lesions. Design, setting, and participants: An institutional review of HG Ta patients who received adequate bacillus Calmette-Guérin (BCG) from 2000 to 2019 was conducted. Outcome measurements and statistical analysis: Guideline criteria for reTUR were used to stratify patients. Kaplan-Meier product limits estimated survival. Cox regression and log-rank tests identified association of variables with survival. Results and limitations: Of the 209 patients with HG Ta bladder cancer, 104 (50%) underwent reTUR, which identified residual disease in 39 patients (38%). Only one patient (1%) was upstaged to pT1 on reTUR. In all unstratified HG Ta patients, reTUR was associated with improved progression-free survival (p = 0.050) and recurrence-free survival (RFS; p = 0.003). The 5-yr RFS for patients who underwent versus those who did not undergo reTUR based on AUA guidelines was 73% (95% confidence interval 63-81%) versus 52% (40-62%), and for those who underwent versus those who did not undergo reTUR based on EAU guidelines was 76% (61-86%) versus 22% (4-49%). In 45 patients meeting both AUA high-risk criteria (large, multifocal tumors) and EAU criteria (lack of detrusor muscle) for reTUR, lack of restaging was associated with over a two-fold increase in recurrence (67% vs 15%, p = 0.002) and progression (25% vs 6%, p = 0.109). Data were limited by selection bias unaccounted for in selecting candidates for reTUR. Conclusions: Restaging TUR in all HG Ta patients, regardless of risk stratification, was associated with improved outcomes. The benefit of reTUR was most notable in high-risk patients without muscle in the index specimen, consistent with