We evaluated the interpretation of multiparametric magnetic resonance imaging of the prostate in routine clinical care. Diagnostic accuracy depends on the Prostate Imaging Reporting and Data System score and the radiologist.
Objective
Discovery of curative therapies for renal cell carcinoma (RCC) is hampered by lack of authentic preclinical models. Tumorgrafts, generated by direct implantation of patient-derived tissues into mice, have demonstrated superior ability to predict therapeutic response. We evaluated “tissue slice grafts” (TSGs) as an improved tumorgraft model of RCC.
Materials and methods
Cores of fresh RCC were precision-cut at 300 μm and implanted under the renal capsule of RAG2−/− γC−/− mice. Engraftment rate, histology, biomarker expression, genetic fidelity, and metastatic potential were evaluated. Magnetic resonance imaging (MRI) was tested as a noninvasive method to measure tumor volume, and response to a targeted therapy was determined.
Results
All 13 cases of RCC engrafted and displayed characteristic histology and biomarkers. TSG volume quantified noninvasively by MRI highly correlated with graft weights, providing a unique tool for monitoring orthotopic growth. Moreover, in 2 cases, cancer cells from TSGs metastasized to clinically relevant sites, including bone. Microarray analysis and DNA sequencing demonstrated a high degree of correlation of global gene expression and von Hippel-Lindau (VHL) status between TSGs and parental tumors. Treatment of TSGs with sunitinib significantly decreased graft weight and mean vessel density compared with controls.
Conclusion
The TSG model of RCC faithfully recapitulates tumor pathology, gene expression, genetic mutation, and drug response. The high engraftment rate and metastatic potential of this authentic model, in conjunction with the ability to generate large first-generation animal cohorts and to quantitate tumor volume at the orthotopic site by MRI, proffer significant advantages compared with other preclinical platforms.
Background
It is generally assumed that if a man does not regain urinary continence or erectile function within 12 mo of radical prostatectomy (RP), then the chance of subsequent recovery is low.
Objective
To determine the probability of achieving good urinary function (UF) or erectile function (EF) up to 48 mo postoperatively in men who reported poor UF or EF at 12 mo after RP.
Design, setting, and participants
We identified 3187 patients who underwent RP from 2007 through 2013 at a tertiary institution and had extended multidisciplinary follow-up with patient-reported UF and EF scores at ≥12 mo.
Intervention
Open or minimally invasive RP.
Outcome measurements and statistical analysis
Primary outcome was good UF as defined by a urinary score ≥17 (range: 0–21) or good EF as defined by a modified International Index of Erectile Function-6 score ≥22 (range: 1–30). The probability of functional recovery beyond 12 mo was determined by Kaplan-Meier analyses.
Results and limitations
Among patients incontinent at 12 mo, the probability of achieving good UF at 24, 36, and 48 mo was 30%, 49%, and 59%. In patients experiencing erectile dysfunction at 12 mo, the probability of recovering EF at 24, 36, and 48 mo was 22%, 32%, and 40%. On multivariable analyses, 12-mo functional score and age were associated with recovery, but only score was consistently significant.
Conclusions
Men with incontinence or erectile dysfunction at 12 mo have higher than anticipated rates of subsequent functional improvement. Probability of recovery is strongly influenced by score at 12 mo. Further research should address the impact of ongoing multidisciplinary follow-up care on our observed rates of recovery.
Patient summary
Many prostate cancer patients continue to recover urinary and erectile function after 12 mo. The level of functional recovery by 12 mo is associated with long-term recovery and should be discussed by the physician and patient when deciding on rehabilitative interventions.
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