Congenital obstructive nephropathy is a common cause of chronic kidney disease and a leading indication for renal transplant in children. The cellular and molecular responses of the kidney to congenital obstruction are incompletely characterized. In this study, we evaluated global transcription in kidneys with graded hydronephrosis in the megabladder (mgb −/−) mouse to better understand the pathophysiology of congenital obstructive nephropathy. Three primary pathways associated with kidney remodeling/repair were induced in mgb −/− kidneys independent of the degree of hydronephrosis. These pathways included retinoid signaling, steroid hormone metabolism, and renal response to injury. Urothelial proliferation and the expression of genes with roles in the integrity and maintenance of the renal urothelium were selectively increased in mgb −/− kidneys. Ngal/Lcn2, a marker of acute kidney injury, was elevated in 36% of kidneys with higher grades of hydronephrosis. Evaluation of Ngalhigh versus Ngallow kidneys identified the expression of several novel candidate markers of renal injury. This study indicates that the development of progressive hydronephrosis in mgb −/− mice results in renal adaptation that includes significant changes in the morphology and potential functionality of the renal urothelium. These observations will permit the development of novel biomarkers and therapeutic approaches to progressive renal injury in the context of congenital obstruction.
BACKGROUND: Transurethral resection of bladder tumor (TURBT) is fundamental to the diagnosis and management of bladder cancer. The impact of tumor size on perioperative outcomes is seemingly intuitive albeit incompletely defined. OBJECTIVE: To compare outcomes following TURBT of small, medium, and large tumors to determine if larger tumors truly resulted in a greater degree of complications. METHODS: The National Surgical Quality Improvement Project (NSQIP) Participant Use File (PUF) was queried to extract all TURBT cases performed from 2011–2015. CPT codes 52234 (small), 52235 (medium), and 52240 (large) were used to stratify the data into three cohorts. Outcomes of interest included any complications, hospital length of stay (LOS), reoperation within 30-days, 30-day readmission, and mortality. RESULTS: 17,839 patients who underwent TURBT were included. 44% had small (n = 7,805), 35% had medium (n = 6,240), and 21% had large tumors (n = 3,794). Univariate analysis revealed significant differences in complications, length of stay, reoperation rate, readmission at 30-days, and mortality when stratifying TURBT by tumor size (p < 0.0001). In the multivariable regression model, medium and large tumors were associated with significantly greater odds of a postoperative complication (OR = 1.37 and 1.64; p < 0.0001), reoperation (OR = 1.33 and 1.52; p = 0.019 and p = 0.002), readmission at 30-days (OR = 1.27 and 1.56; p = 0.001 and p < 0.0001), and death (OR = 1.65 and 2.59; p = 0.015 and p < 0.0001) compared to smaller tumors. CONCLUSIONS: Larger tumor size (>5 cm) is associated with greater length of stay, reoperation, readmission, and death following TURBT. Patients should be counseled appropriately and likely warrant vigilant observation prior to and following hospital discharge.
Pathologic characteristics of extirpated renal cell carcinoma (RCC) specimens <7 cm were reviewed to get better information on technical nuances of renal mass biopsy (RMB). Specimens were stratified according to tumor stage, nuclear grade, size, histology, presence of lymphovascular invasion (LVI), necrosis, and sarcomatoid features. When considering pT1 (0–7 cm) tumors, pT1b (4–7 cm) RCC masses were more likely to have necrosis (43% vs 16%, P < 0.001), LVI (6% vs 2%, P = 0.024), high-grade nuclear elements (29% vs 17%, P < 0.001), and sarcomatoid features (2% vs 0%, P = 0.006) compared with pT1a (0–4 cm) tumors. Additionally, pT3a tumors were more highly associated with necrosis (P = 0.005), LVI, sarcomatoid features, and high-grade disease (P for all < 0.001) when compared to pT1 masses. For masses ≤ 4 cm, pT3a cancers were more likely to demonstrate necrosis (38% vs 16%, P < 0.001), LVI (22% vs 2%, P < 0.001), high-grade nuclear elements (45% vs 17%, P < 0.001), and sarcomatoid features (12% vs 0%, P < 0.001) compared to pT1a tumors. Similarly, for masses 4–7 cm, pathologic T3a tumors were significantly more likely to have sarcomatoid features (12% vs 2%, P = 0.006) and LVI (22% vs 6%, P = 0.003) compared to pT1b tumors. In summary, pT3a tumors and those RCC masses >4 cm exhibit considerable histologic heterogeneity and may harbor elements that are not easily appreciated with limited renal sampling. Therefore, if RMB is considered for renal masses greater than 4 cm or those that abut sinus fat, a multi-quadrant biopsy approach is necessary to ensure adequate sampling and characterization of the mass.
HR 0.41, CI 0.40 e 0.43 and HR 0.63, CI 0.59 e 0.68 respectively, p<0.001).CONCLUSIONS: Treatment at academic high volume facilities was associated with survival benefit in patients with mRCC. Patients treated at AC were more likely to receive CN and Immunotherapy.
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