Sharma, Vidit

Context.— Epithelioid angiomyolipomas (eAMLs) are rare tumors of the kidney that occur in patients with tuberous sclerosis complex or in a sporadic setting; a subset of these tumors exhibit metastatic behavior. Objective.— To analyze molecular profiling data to identify pathogenic alterations in rare cases of metastatic eAML, and to identify immunohistochemistry (IHC)-based surrogate markers. Design.— Molecular profiling data from the American Association for Cancer Research GENIE registry was accessed for 23 patients with angiomyolipomas, and 9 of 16 patients with eAMLs in our institutional registry were evaluated with next-generation sequencing. IHC was performed to screen for alterations of P53, RB, and ATRX for all 16 institutional cases. Results.— Combined alterations of 5 tumor-suppressor genes (TP53, ATRX, RB1, APC, and NF1) were identified using next-generation sequencing in 7 of 8 (88%) patients with metastatic disease compared to a single patient with nonmetastatic disease (RB1 variant of uncertain significance; 1 of 24, 4%). No cases with abnormal IHC results were identified in 11 patients with nonmetastatic disease compared to 3 of 5 patients with metastatic disease. Conclusions.— Our results show that the majority of metastatic eAMLs have mutations of 5 tumor-suppressor genes (TP53, ATRX, RB1, APC, and NF1), while these are rare in patients with nonmetastatic disease. Furthermore, IHC for P53, RB, and ATRX may serve as a screen for a subset of these alterations in resource-limited settings. These findings, if validated in larger data sets, have the potential to predict metastatic behavior in eAMLs.

Objective: The aim of this study was to develop a risk score utilizing C-reactive protein (CRP) and procalcitonin to better predict a clinical infection for patients with obstructive urolithiasis. Methods: A retrospective review was performed of patients presenting to the emergency room from December 2017 to February 2019 and who underwent upper urinary tract decompression due to concern for infection in the setting of obstructing urolithiasis. Over 30 clinical parameters were assessed and a composite risk score was created. Univariate and multivariate, forward, stepwise regression analyses were performed to identify predictors of true urinary tract infection (UTI). Results: Ninety-eight patients met inclusion criteria, of which a true UTI was identified in 50 (51%). The standard model of serum white blood cells >15 or temperature >38°C had an area under curve (AUC) of only 0.67 to predict UTI. A multivariable regression-based 4-point risk score (1 point for each of the following: positive urinary Gram stain, perinephric fat stranding on CT, serum CRP >21.95, and serum procalcitonin >0.36) had an AUC of 0.91 to predict UTI. Individually, these components had an AUC of 0.68, 0.68, 0.80, and 0.77, respectively. The chances of confirmed UTI were 8%, 11%, 68%, and 100% for risk scores of 0, 1, 2, and 3 to 4, respectively ( p < 0.001). Conclusions: Only 50% of patients with a suspected UTI and an obstructing stone were ultimately confirmed to have a UTI. A risk score consisting of Gram stain, perinephric fat stranding, CRP, and procalcitonin can improve UTI prediction and warrants further study.

Objective To investigate the long‐term utility of adjuvant therapy after radical prostatectomy ( RP ) for prostate cancer with seminal vesicle invasion ( SVI ; pT 3b), as the published data are conflicting. Patients and Methods Patients with SVI during RP and pelvic lymph node dissection at two major referral centres from 1986 to 2014 were included. Kaplan–Meier analyses and multivariable Cox regressions were used to determine if adjuvant radiotherapy ( aRT ) and adjuvant hormonal therapy ( aHT ) were predictors of biochemical recurrence ( BCR ), cancer‐specific mortality ( CSM ) and overall mortality ( OM ). Subset analyses were performed for pN 0 patients and pN + patients. Results Overall, 3 279 patients with prostate cancer and SVI were included with a median follow‐up of 148 months. Considering the whole SVI population, 1 387 (42%) received no adjuvant therapy, 1 179 (36%) received aHT , 461 (14.1%) received aRT , while 252 (7.7%) received both aHT and aRT . The 10‐year BCR , CSM , and OM rates were 64%, 14%, and 27%, respectively. In the overall population, aRT and aHT were predictors of BCR , CSM and OM (all P < 0.04). When only pT 3bN0 patients were considered, aHT was a significant multivariate predictor of BCR [hazard ratio ( HR ) 0.50, P < 0.001), CSM ( HR 0.62, P = 0.01) and OM ( HR 0.75, P = 0.004). Conversely, aRT was not associated with survival outcomes (all P > 0.05). When only the subgroup pT 3bN+ was considered, the use of aRT was related to an improvement in CSM ( HR 0.65, P = 0.03) and OM (HR 0.78, P = 0.03). Conclusions aHT + aRT seems to be effective in pT 3b patients. However, when stratified according to the presence of nodal metastases, aHT remains effective only in the node‐negative subgroup, while aRT remains effective only in the node‐positive subgroup. Further data including prospective trials are warranted to study the utility of adjuvant therapies in this setting.