Faculty Bibliography

Treatment paradigms for patients with upper tract urothelial carcinoma (UTUC) are typically extrapolated from studies of bladder cancer despite their distinct clinical and molecular characteristics. The advancement of UTUC research is hampered by the lack of disease-specific models. Here, we report the establishment of patient derived xenograft (PDX) and cell line models that reflect the genomic and biological heterogeneity of the human disease. Models demonstrate high genomic concordance with the corresponding patient tumors, with invasive tumors more likely to successfully engraft. Treatment of PDX models with chemotherapy recapitulates responses observed in patients. Analysis of a HER2 S310F-mutant PDX suggests that an antibody drug conjugate targeting HER2 would have superior efficacy versus selective HER2 kinase inhibitors. In sum, the biological and phenotypic concordance between patient and PDXs suggest that these models could facilitate studies of intrinsic and acquired resistance and the development of personalized medicine strategies for UTUC patients.

The engraftment of human tumor tissues into immunodeficient host mice to generate patient-derived xenograft (PDX) models has become increasingly utilized for many types of cancers. By capturing the unique genomic and molecular properties of the parental tumor, PDX models enable analysis of patient-specific clinical responses. PDX models are an important platform to address the contribution of inter-tumoral heterogeneity to therapeutic sensitivity, tumor evolution, and the mechanisms of treatment resistance. With the increasingly important role played by targeted therapies in urological malignancies, the establishment of representative PDX models can contribute to improved facilitation and adoption of precision medicine. In this review of the evolving role of the PDX in urothelial cancer and kidney cancer, we discuss the essential elements of successful graft development, effective translational application, and future directions for clinical models.

PURPOSE/OBJECTIVE:To evaluate patient satisfaction (with emphasis on preoperative education) with radical cystectomy for bladder cancer at our institution, the University of Missouri Hospital, qualitatively in order to identify specific areas where improvements can be made. MATERIALS AND METHODS/METHODS:We developed a patient survey that used open-ended questions to identify positive and negative experiences that contributed to patient satisfaction. We administered the survey to radical cystectomy patients who met inclusion criteria and agreed to participate. We recorded, transcribed and qualitatively coded the responses. We identified four themes under which both positive and negative responses were placed, and constructed two diagrams to better illustrate contributors to patient experience and satisfaction. RESULTS:We identified 25 patients who met inclusion criteria. Of those, 13 participated in the survey. Regarding overall experience, 92.3% of patients rated their care as excellent or good. Regarding preoperative education, 76.9% of patients reported they definitely or somewhat received enough information on what to expect after surgery, and 76.9% definitely received enough guidance on how to care for themselves after surgery. From qualitative coding of patient responses to open-ended questions, we identified preoperative preparation, delivery of care, caregiver availability, and patient-centered care as themes that contributed positively and negatively to patient experience. CONCLUSION/CONCLUSIONS:Although the overall patient satisfaction could be perceived as high (92.3%), qualitative analysis revealed several areas where improvements can be made to improve patient experience with radical cystectomy at our institution. As previously expected, preoperative preparation was a contributor.

Our recently reported phase III trial demonstrated that patients undergoing nephron-sparing surgery (NSS) with an estimated glomerular filtration rate (eGFR) of ≥45 ml/min/1.73 m² who received mannitol had no improvement in renal function at 6 mo compared with those who received placebo. Some authors have suggested that benefit is restricted to subgroups, such as those with comorbidities. We assessed whether preoperative eGFR, or other patient and surgical factors modified the effect of mannitol on postoperative outcomes at 6 mo and with extended follow-up. We also assessed whether mannitol was associated with differences in long-term GFR years after surgery. No significant difference between the mannitol or placebo groups (mean eGFR difference: 1.4; 95% confidence interval: -2.6, 5.3; p = 0.5) was found in the 134 patients with known eGFR at 3 yr after NSS. At both 6 mo and 3 yr, the effect of mannitol was not significantly modified by patient or surgical factors including preoperative eGFR. In summary, we validated our original trial conclusions by finding that intraoperative use of mannitol does not improve either short- or long-term renal function in patients undergoing NSS. Specifically, there is no evidence that comorbidities, including lower preoperative eGFR, modify the effect of mannitol. PATIENT SUMMARY: Use of mannitol at the time of partial nephrectomy does not improve either short- or long-term renal function even in patients with comorbidities, including lower preoperative renal function. The routine use of intraoperative mannitol should be discontinued.

CONTEXT:Age-adjusted death rates for heart disease are higher in rural areas than in urban areas. Lay advisors could potentially facilitate improvement in cardiovascular health outcomes. The aim of this systematic review and meta-analysis is to estimate lay advisor intervention effects on cardiovascular health metrics in rural populations. EVIDENCE ACQUISITION:Searches of databases including MEDLINE, CINAHL, and Scopus from 1975 through October 2017 retrieved 323 citations, of which 272 abstracts were reviewed. Two authors independently abstracted data from eligible studies. Analysis was conducted in March 2018. EVIDENCE SYNTHESIS:=0.00%). Most studies had normal baseline blood pressure and cholesterol levels before intervention, and no significant effects were noted for these outcomes. Diverse types of measures used for diet, physical activity, and smoking precluded statistical synthesis. CONCLUSIONS:Lay advisor interventions had significant positive effects on glycemic control and BMI for rural residents; however, further rigorous studies are needed in U.S. rural populations, and elements of effective lay advisor interventions require further investigation.