Urothelial carcinoma of the upper urinary tract is uncommon and presents unique challenges for diagnosis and management. Nephroureterectomy has been the preferred management option, but it is associated with significant morbidity. Nephron-sparing treatments are a valuable alternative and provide similar efficacy in select cases. A PubMed literature review was performed in English language publications using the following search terms: urothelial carcinoma, upper tract, nephron-sparing, intraluminal and systemic therapy. Contemporary papers published within the last 10 years were primarily included. Where encountered, systematic reviews and meta-analyses were given priority, as were randomized controlled trials for newer treatments. Core guidelines were referenced and citations reviewed for inclusion. A summary of epidemiological data, clinical diagnosis, staging, and treatments focusing on nephron-sparing approaches to upper tract urothelial carcinoma (UTUC) are outlined. Nephron-sparing management strategies are viable options to consider in patients with favorable features of UTUC. Adjunctive therapies are being investigated but the data remains mixed. Protocol variability and dosage differences limit statistical interpretation. New mechanisms to improve treatment dwell times in the upper tracts are being designed with promising preliminary results. Studies investigating systemic therapies are ongoing but implications for nephron-sparing management are uncertain. Nephron-sparing management is an acceptable treatment modality best suited for favorable disease. More work is needed to determine if intraluminal and/or systemic therapies can further optimize treatment outcomes beyond resection alone.

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molecules may be a promising approach to reverse renal fibrosis. The goal of this study is to test the use of the cell-signaling chemokine CXCL12 in reversing renal fibrosis in a cat model of unilateral ischemia/reperfusion (I/R)-induced kidney fibrosis.METHODS: In this model, 30 adult female cats received an intra-renal injection of 100, 200, or 400 ng of recombinant human CXCL12, or sterile saline, into the I/R kidney 70 days post-injury, or were non-injured, non-injected controls (n[6/treatment condition). Kidney collagen content was quantified 4 months post CXCL12 or saline injection using Masson's Trichrome and Picrosirius Redstained renal collagen tissues. In additional pilot study, cats with I/R were assessed 30 minutes or 1 week post-CXCL12 injection for kidney expression of matrix metaloproteinase-1 (MMP-1), LOXL-2 (associated with collagen cross-linking) and CXCL12; using ELISA analysis of the I/R kidney.RESULTS: I/R increased the affected kidney collagen content, which both mid and high doses of CXCL12 restored to normal (p<.05 vs. untreated) (Figure 1). I/R increased collagen fiber width, which both mid and high doses of CXCL12 restored to normal (p<.001 vs. untreated) (Figure 1). Early changes in kidney (increased MMP-1) (increased CXCL12), and (decreased LOX-2) were not seen 4 months post CXCL12 injection.CONCLUSIONS: Local injection of recombinant CXCL12 reverses the formation of TIF in a dose dependent manner. Its early effects on molecules affecting collagen breakdown and cross-linking may alter collagen metabolism, resulting in reduced fibrosis. Additional mechanistic, long-term efficacy and safety studies are needed.

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