Background Zoledronic acid, a bisphosphonate, delays progression of bone metastases in adult malignancies. Bone is a common metastatic site of advanced neuroblastoma. We previously reported efficacy of zoledronic acid in a murine model of neuroblastoma bone invasion prompting this Phase I trial of zoledronic acid with cyclophosphamide in children with neuroblastoma and bone metastases. The primary objective was to determine recommended dosing of zoledronic acid for future trials. Procedure Escalating doses of intravenous zoledronic acid were given every 28 days with oral metronomic cyclophosphamide (25 mg/m2/day). Toxicity, response, zoledronic acid pharmacokinetics, bone turnover markers, serum IL-6, and sIL-6R were evaluated. Results Twenty-one patients, median age 7.5 (range 0.8 - 25.6) years were treated with 2 mg/m2 (n=4), 3 mg/m2 (n=3), or 4 mg/m2 (n=14) zoledronic acid. Fourteen patients were evaluable for dose escalation. A median of one (range 1-18) courses was given. Two dose limiting toxicities (Grade 3 hypophosphatemia) occurred at 4 mg/m2 zoledronic acid. Other Grade 3-4 toxicities included hypocalcemia (n=2), elevated transaminases (n=1), neutropenia (n=2), anemia (n=1), lymphopenia (n=1), and hypokalemia (n=1). Osteosclerosis contributed to fractures in one patient after 18 courses. Responses in evaluable patients included 1 partial response, 9 stable disease (median 4.5 courses, range 3-18), and 10 progressions. Zoledronic acid pharmacokinetics were similar to adults. Markers of osteoclast activity and serum IL-6 levels decreased with therapy. Conclusions Zoledronic acid with metronomic cyclophosphamide is well tolerated with clinical and biologic responses in recurrent/refractory neuroblastoma. The recommended dose of zoledronic acid is 4 mg/m2 every 28 days.

We present a patient with a history of end-stage renal disease, who developed skin lesions in the bilateral calves a month after the initiation of hemodialysis. The lesions were biopsied, and the histological findings were consistent with a diagnosis of calciphylaxis. The patient had a baseline pretreatment bone scan that showed extensive systemic disease. The patient died 20 days after the imaging study. A review of the literature on bone scans and calciphylaxis is presented.

Local evaluation of the primary tumor in patients with transitional cell carcinoma on PET is often limited by the obscuring effect of excreted FDG, but assessment of metabolic activity may still be possible through close correlation with CT images. PET/CT may also be helpful in the detection of disease outside the bladder at nodal or more distant sites and in the assessment of recurrent disease.

The impact of overnight intravenous lipid emulsion (ILE) infusion on upper gastrointestinal tract physiology was assessed in 10 healthy volunteers. No changes in lower esophageal sphincter pressure (before infusion: 28 +/- 4 mm Hg; after infusion 20.5 +/- 3; p:NS), plasma concentrations of gastrointestinal hormones (gastrin: preprandial before/after lipids: 14 +/- 2.1/13 +/- 1.4 pM; postprandial before/after lipids: 28 +/- 2.7/30 +/- 3.4 pM, CCK: preprandial before/after lipids: 69 +/- 10/64 +/- 10 pM; postprandial before/after lipids: 96 +/- 11/95 +/- 12 pM; neurotensin: levels less than 6 pM in all samples; somatostatin levels undetectable in all samples) nor on pathologic gastroesophageal reflux episodes (% of time of pH less than 4, before/after lipids: 0.6 +/- 0.4/0.15 +/- 0.09), were found (p = NS). In contrast, technetium gastric emptying studies showed a significant delay when comparing pre- and post-lipid infusion values (37 +/- 4/54 +/- 4%) (p greater than 0.005). The mechanism of this effect remains unexplained.

Background and Purpose From the literature the prevalence of FDG uptake in large artery atherosclerotic plaques shows great heterogeneity. We retrospectively reviewed 100 consecutive patients who underwent FDG-PET/CT imaging of their whole body, to evaluate FDG uptake in the arterial wall. Materials & Methods We retrospectively evaluated 100 whole-body PET-CT scans. The PET co-registered CT images were reviewed with for abnormal 18F-FDG uptake. The mean standard uptake value (SUV) was measured in regions of interest (ROIs). The prevalence of PET+ plaques was determined based on the qualitative PET review, used as the gold standard in a receiver-operating characteristic (ROC) curve analysis to determine an optimal threshold for the quantitative PET analysis. Results The qualitative, visual assessment demonstrated FDG uptake in the arterial walls of 26 patients. A total of 85 slices exhibited FDG uptake within the arterial wall of 37 artery locations. 11, 17 and 2 patients exhibited FDG uptake respectively within the wall of carotid arteries of the aorta, and of the iliac arteries. Only 4 of the 26 patients had positive FDG uptake in more than one artery location. In terms of quantitative analysis, a threshold of 2.8 SUV was associated with a negative predictive value of 99.4% and a positive predictive value of 100% to predict qualitative PET+ plaques. A threshold of 1.8 SUV was associated with a negative predictive value of 100% and a positive predictive value of 99.4%. Area under the ROC curve was 0.839. Conclusion The prevalence of PET uptake in arterial walls in a consecutive population of asymptomatic patients is low and usually confined to one type of artery and its clinical relevance in terms of vulnerability to ischemic events remains to be determined.