Potretzke, Aaron M.

ObjectivesTechnical limitations of ureteroscopic (URS) biopsy has been considered responsible for substantial upgrading rate in upper tract urothelial carcinoma (UTUC). However, the impact of tumor specific factors for upgrading remain uninvestigated.MethodsPatients who underwent URS biopsy were included between 2005 and 2020 at 13 institutions. We assessed the prognostic impact of upgrading (low‐grade on URS biopsy) versus same grade (high‐grade on URS biopsy) for high‐grade UTUC tumors on radical nephroureterectomy (RNU) specimens.ResultsThis study included 371 patients, of whom 112 (30%) and 259 (70%) were biopsy‐based low‐ and high‐grade tumors, respectively. Median follow‐up was 27.3 months. Patients with high‐grade biopsy were more likely to harbor unfavorable pathologic features, such as lymphovascular invasion (p < 0.001) and positive lymph nodes (LNs; p < 0.001). On multivariable analyses adjusting for the established risk factors, high‐grade biopsy was significantly associated with worse overall (hazard ratio [HR] 1.74; 95% confidence interval [CI], 1.10–2.75; p = 0.018), cancer‐specific (HR 1.94; 95% CI, 1.07–3.52; p = 0.03), and recurrence‐free survival (HR 1.80; 95% CI, 1.13–2.87; p = 0.013). In subgroup analyses of patients with pT2‐T4 and/or positive LN, its significant association retained. Furthermore, high‐grade biopsy in clinically non‐muscle invasive disease significantly predicted upstaging to final pathologically advanced disease (≥pT2) compared to low‐grade biopsy.ConclusionsHigh tumor grade on URS biopsy is associated with features of biologically and clinically aggressive UTUC tumors. URS low‐grade UTUC that becomes upgraded to high‐grade might carry a better prognosis than high‐grade UTUC on URS. Tumor specific factors are likely to be responsible for upgrading to high‐grade on RNU.

Introduction: The surgical technique for urinary stone removal is partly influenced by its fragility, as prognosticated by the clinician. This feasibility study aims to develop a linear regression model from CT-based radiomic markers to predict kidney stone comminution time in vivo with two ultrasonic lithotrites. Materials and Methods: Patients identified by urologists at our institution as eligible candidates for percutaneous nephrolithotomy were prospectively enrolled. The active engagement time of the lithotrite in breaking the stone during surgery denoted the comminution time of each stone. The comminution rate was computed as the stone volume disintegrated per minute. Stones were grouped into three fragility classes (fragile, moderate, hard), based on inverse of the comminution rates with respect to the mean. Multivariable linear regression models were trained with radiomic features extracted from clinical CT images to predict comminution times in vivo . The model with the least root mean squared error (RMSE) on comminution times and the fewest misclassification of fragility was finally selected. Results: Twenty-eight patients with 31 stones in total were included in this study. Stones in the cohort averaged 1557 (±2472) mm 3 in volume and 5.3 (±7.4) minutes in comminution time. Ten stones had nonmoderate fragility. Linear regression of stone volume alone predicted comminution time with an RMSE of 6.8 minutes and missed all 10 stones with nonmoderate fragility. A fragility model that included stone volume, internal morphology, shape-based radiomics, and device type improved RMSE to below 3.3 minutes and correctly classified 20/21 moderate and 6/10 nonmoderate stones. Conclusions: CT metrics-based fragility models may provide information to surgeons regarding kidney stone fragility and facilitate the selection of stone removal procedures.

Introduction: Patients who form kidney stones are typically advised to limit intake of nondairy animal protein. Plant-based meat products may be a processed substitute protein source for these patients and have recently gained popularity because of health concerns, increased retail availability, decreased environmental impact, and meat supply shortages during the COVID-19 pandemic. Despite these perceived benefits and tangential association with whole food plant-based diets, the potential lithogenic risks associated with these products are not well characterized. Methods: The U.S. Department of Agriculture database was queried with a sample of plant-based meat products widely available to U.S. consumers. Nutrient profile data were compiled and compared with animal protein data using standardized serving sizes. Primary protein sources were identified using verified ingredient lists. Oxalate content was extrapolated based on dietary data sources. Results: A total 47 plant-based meat products (16 beef, 11 pork, 10 chicken, and 10 seafood) were analyzed. Compared with their respective animal protein, most products contained on average fewer calories (plant-based beef 77%, pork 94%, chicken 86%, and seafood 83%) and less protein (plant-based beef 68%, pork 96%, chicken 53%, and seafood 54%). Most products used soy protein as the primary protein source (55%). Soy-based beef contained the highest average oxalate content (18 mg per serving), whereas soy-based seafood contained the lowest (7 mg). The most common non-soy protein source was pea protein (30%), containing trace amounts of oxalate. Sodium content was higher in most plant-based products overall (72%) and in each category (plant-based beef 109%, pork 128%, chicken 100%, and seafood 148%). Calcium content was higher (plant-based beef 317%, pork 144%, chicken 291%, and seafood 295%) compared with animal protein. Conclusions: Most plant-based meat products consist of protein sources that are, relative to animal protein sources, higher in oxalate, sodium, and calcium. Stone-forming patients should be counseled about the potential lithogenic risk of these processed products.

Background: Measuring quality of care indicators is important for clinicians and decision making in health care to improve patient outcomes. Objective: The primary objective was to identify quality of care indicators for patients with upper tract urothelial carcinoma (UTUC) and to validate these in an international cohort treated with radical nephroureterectomy (RNU). The secondary objective was to assess the factors associated with failure to validate the pentafecta. Design: We performed a retrospective multicenter study of patients treated with RNU for EAU high-risk (HR) UTUC. Outcome measurements and statistical analysis: Five quality indicators were consensually approved, including a negative surgical margin, a complete bladder-cuff resection, the absence of hematological complications, the absence of major complications, and the absence of a 12-month postoperative recurrence. After multiple imputations and propensity-score matching, log-rank tests and a Cox regression were used to assess the survival outcomes. Logistic regression analyses assessed predictors for pentafecta failure. Results: Among the 1718 included patients, 844 (49%) achieved the pentafecta. The median follow-up was 31 months. Patients who achieved the pentafecta had superior 5-year overall- (OS) and cancer-specific survival (CSS) compared to those who did not (68.7 vs. 50.1% and 79.8 vs. 62.7%, respectively, all p < 0.001). On multivariable analyses, achieving the pentafecta was associated with improved recurrence-free survival (RFS), CSS, and OS. No preoperative clinical factors predicted a failure to validate the pentafecta. Conclusions: Establishing quality indicators for UTUC may help define prognosis and improve patient care. We propose a pentafecta quality criteria in RNU patients. Approximately half of the patients evaluated herein reached this endpoint, which in turn was independently associated with survival outcomes. Extended validation is needed.

Background and objectives Urinary stone disease has been associated with inflammation, but the specific cell interactions that mediate events remain poorly defined. This study compared calcification and inflammatory cell patterns in kidney tissue from radical nephrectomy specimens of patients without and with a history of urinary stone disease. Design, setting, participants, & measurements Nontumor parenchyma of biobanked radical nephrectomy specimens from age- and sex-matched stone formers ( n =44) and nonstone formers ( n =82) were compared. Calcification was detected by Yasue staining and inflammatory cell populations by immunohistochemistry for CD68 (proinflammatory M1 macrophages), CD163 and CD206 (anti-inflammatory M2 macrophages), CD3 (T lymphocytes), and tryptase (mast cells). Calcifications and inflammatory cells were quantified in cortex and medulla using Image-Pro analysis software. Results Calcification in the medulla of stone formers was higher than in nonstone formers ( P <0.001). M1 macrophages in the cortex and medulla of stone formers were greater than in nonstone formers ( P <0.001), and greater in stone former medulla than stone former cortex ( P =0.02). There were no differences in age, sex, body mass index, tumor characteristics (size, stage, or thrombus), vascular disease status, or eGFR between the groups. M2 macrophages, T lymphocytes, and mast cells did not differ by stone former status. There was a correlation between M1 macrophages and calcification in the medulla of stone formers (rho=0.48; P =0.001) and between M2 macrophages and calcification in the medulla of nonstone formers (rho=0.35; P =0.001). T lymphocytes were correlated with calcification in the cortex of both nonstone formers (rho=0.27; P =0.01) and stone formers (rho=0.42; P =0.004), whereas mast cells and calcification were correlated only in the cortex of stone formers (rho=0.35; P =0.02). Conclusions Higher medullary calcification stimulated accumulation of proinflammatory rather than anti-inflammatory macrophages in stone formers.

Objective To report perioperative, renal functional and oncologic outcomes for patients undergoing partial or radical nephrectomy for cT2 renal masses. Methods Retrospective review of patients who underwent partial ( n = 72) or radical nephrectomy ( n = 379) for cT2 renal masses from 2000 to 2016. After propensity adjustment using inverse probability weighting, the following were compared by surgery (partial or radical nephrectomy): complications, renal function measured by estimated glomerular filtration rate as continuous and as <60 mL/min/1.73 m 2 at 1 and 3 years postoperatively and overall, metastases‐free survival and cancer‐specific survival in patients with renal cell carcinoma. Results After propensity adjustment, clinical and radiographic features were well‐balanced between groups. Overall and severe complications were more common for partial compared with radical nephrectomy, although not statistically significant (19 vs 13%, P = 0.14 and 4 vs 2%, P = 0.3, respectively). Estimated glomerular filtration rate change at 1 and 3 years was more pronounced in radical compared with partial nephrectomy (median −16 vs −5 and −14 vs −2, respectively, P < 0.001). A greater proportion of radical nephrectomy patients had an estimated glomerular filtration rate <60 at 1 and 3 years (55 vs 17% and 48 vs 17%, respectively, P < 0.01). In renal cell carcinoma patients, overall, metastases‐free and cancer‐specific survival were not significantly different between groups (median survivor follow up 7.1 years, interquartile range 3.6–11.4). Conclusions Partial nephrectomy appears to be a relatively safe and a potentially effective treatment for cT2 renal masses, conferring better renal functional preservation compared with radical nephrectomy. These data support continued use of partial nephrectomy for renal masses >7 cm in appropriately selected patients.