A comparison of cytoreductive and non-cytoreductive management strategies for nephron-sparing approaches to tumours in solitary kidneys.

INTRODUCTION: Tumours in a solitary kidney pose challenges in management. Metastatic tumours and those in difficult locations complicate treatment further. The advent of immunotherapy has shed new light on the management of such tumours. We present a series of three cases treated with nephron-sparing surgery following neoadjuvant immunotherapy and compare the outcomes with patients who underwent robotic partial nephrectomy in a solitary kidney. METHODS: We present the outcomes of three patients with solitary kidney tumours who underwent delayed nephron-sparing surgery following good response to immunotherapy. All patients had solitary kidney following a previous nephrectomy, two of which were nonmetastatic but, due to size/location, not amenable to primary treatment; the third patient had metastatic disease and responded to immunotherapy. Two patients underwent robotic partial nephrectomy and one opted for cryotherapy. We compared the preoperative, intraoperative and postoperative parameters of the two patients who underwent robotic cytoreductive partial with patients who underwent robotic partial nephrectomy in a solitary kidney. RESULTS: Out of 231 partial nephrectomy patients in our centre, 2 underwent cytoreductive partial nephrectomy and 5 underwent solitary partial nephrectomy. There was no statistically significant difference in the patient demographics in the two groups. Patients in both groups had comparable operative time, warm ischaemia time, blood loss and length of stay. Two of the five patients in the non-cytoreductive robotic partial nephrectomy had Clavien Dindo 1 complications compared with one patient in the robotic cytoreductive partial nephrectomy group. This was not statically significant. CONCLUSION: Neoadjuvant immunotherapy can play a valuable role in shrinking renal tumours in solitary kidneys to facilitate robotic partial nephrectomies. There were no significant differences in the intra- and postoperative parameters in patients who underwent cytoreductive partial nephrectomy when compared with patients undergoing robotic solitary partial nephrectomy.

Notch signaling is not essential in sonic hedgehog-activated medulloblastoma.

Dysregulated signal transduction through the notch pathway has been noted in human and mouse medulloblastoma studies. Gamma secretase inhibitors (GSIs) impair notch signaling by preventing the cleavage of transmembrane notch proteins into their active intracellular domain fragments. Previous studies have shown that GSI treatment caused apoptosis and impaired medulloblastoma cell engraftment in xenograft systems. In this study, we used in vivo genetic and pharmacologic approaches to quantify the contribution of notch signaling to sonic hedgehog (shh)-activated mouse medulloblastoma models. In contrast to prior in vitro studies, pharmacologic inhibition of notch pathways did not reduce the efficiency of medulloblastoma xenotransplantation nor did systemic therapy impact tumor size, proliferation, or apoptosis in genetically engineered mouse medulloblastoma models. The incidence and pathology of medulloblastomas driven by the SmoA1 transgene was unchanged by the bi-allelic absence of Notch1, Notch2, or Hes5 genes. These data show that notch signaling is not essential for the initiation, engraftment, or maintenance of sonic hedgehog pathway-driven medulloblastomas.

Comparison of methods to identify significant proteinuria in pregnancy in the outpatient setting.

The efficacy of the albumin/creatinine ratio (ACR) measurement in detection of significant proteinuria when performed in a high-risk antenatal clinic was compared with automated dipstick, protein/creatinine ratio (PCR), and 24-hour urine protein measurements. Both the ACR (DCA 2000) and PCR were strongly predictive for the presence or absence of significant proteinuria, with positive likelihood ratios (LRs) of 27.4 and 31.6 and negative LRs of 0.0 and 0.1, respectively. Both the ACR (DCA 2000) and PCR are effective tests for both identifying and excluding significant proteinuria in the outpatient setting. The ACR (DCA 2000) has the advantage of providing an immediate result.