Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Sonic Hedgehog (SHH) signaling drives a minority of MB, correlating with desmoplastic pathology and favorable outcome. The majority, however, arises independently of SHH and displays classic or large cell anaplastic (LCA) pathology and poor prognosis. To identify common signaling abnormalities, we profiled mRNA, demonstrating misexpression of MYCN in the majority of human MB and negligible expression in normal cerebella. We clarified a role in pathogenesis by targeting MYCN (and luciferase) to cerebella of transgenic mice. MYCN-driven MB showed either classic or LCA pathologies, with Shh signaling activated in~5% of tumors, demonstrating that MYCN can drive MB independently of Shh. MB arose at high penetrance, consistent with a role for MYCN in initiation. Tumor burden correlated with bioluminescence, with rare metastatic spread to the leptomeninges, suggesting roles for MYCN in both progression and metastasis. Transient pharmacological down-regulation of MYCN led to both clearance and senescence of tumor cells, and improved survival. Targeted expression of MYCN thus contributes to initiation, progression, and maintenance of MB, suggesting a central role for MYCN in pathogenesis.

Ultrasound-guided renal access for percutaneous nephrolithotomy (PCNL) is a safe, effective, and low-cost procedure commonly performed worldwide, but a technique underutilized by urologists in the United States. The purpose of this article is to familiarize the practicing urologist with methods for ultrasound guidance for percutaneous renal access. We discuss two alternative techniques for gaining renal access for PCNL under ultrasound guidance. We also describe a novel technique of using the puncture needle to reposition residual stone fragments to avoid additional tract dilation. With appropriate training, ultrasound-guided renal access for PCNL can lead to reduced radiation exposure, accurate renal access, and excellent stone-free success rates and clinical outcomes.

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OBJECTIVE To evaluate the impact of body mass index (BMI) on perioperative outcomes and radiation exposure for ultrasound (US)-guided percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS Data were prospectively collected for consecutive patients who underwent PCNL at the University of California, San Francisco, from July 2013 to November 2015. Patients were divided into 3 groups according to their BMI: <25 (normal weight), 25–29.9 (overweight), and >30 (obese) kg/m2. Perioperative outcomes were compared between patients who underwent US-guided vs fluoroscopy-guided PCNL. RESULTS One hundred thirty-five patients were enrolled; 93 cases were performed under US and 42 under fluoroscopic guidance. US successfully guided renal access in 76.9% of normal weight, 79.0% of overweight, and 45.7% of obese patients (P < .05). Mean fluoroscopic screening time and radiation exposure dose were reduced for US compared to fluoroscopy cases across all BMI categories (P < .05). As BMI increased, radiation exposure dose rose disproportionately faster compared to screening time (P < .001). No significant differences among the BMI groups were found with regard to complication rate, hospital stay, and stone-free status. CONCLUSION US-guided PCNL may be more difficult in obese patients, but with its use, the overweight and obese experience the largest absolute reduction in radiation exposure. Because these patients are inherently at greater risk for radiation exposure compared to normal weight patients, they may benefit the most from adoption of US for PCNL.

Purposes. To present our series of 38 prone percutaneous nephrolithotomy procedures performed with renal access and tract dilation purely under ultrasound guidance and describe the benefits and challenges accompanying this approach. Methods. Thirty-eight consecutive patients presenting for percutaneous nephrolithotomy for renal stone removal were included in this prospective cohort study. Ultrasonographic imaging in the prone position was used to obtain percutaneous renal access and guide tract dilation. Fluoroscopic screening was used only for nephrostomy tube placement. Preoperative, intraoperative, and postoperative procedural and patient data were collected for analysis. Results. Mean age of patients was 52.7 ± 17.2 years. Forty-five percent of patients were male with mean BMI of 26.1 ± 7.3 and mean stone size of 27.2 ± 17.6 millimeters. Renal puncture was performed successfully with ultrasonographic guidance in all cases with mean puncture time of 135.4 ± 132.5 seconds. Mean dilation time was 11.5 ± 3.8 min and mean stone fragmentation time was 37.5 ± 29.0 min. Mean total operative time was 129.3 ± 41.1. No patients experienced any significant immediate postoperative complication. All patients were rendered stone-free and no additional secondary procedures were required. Conclusions. Ultrasound guidance for renal access and tract dilation in prone percutaneous nephrolithotomy is a feasible and effective technique. It can be performed safely with significantly reduced fluoroscopic radiation exposure to the patient, surgeon, and intraoperative personnel.