Perioperative, functional, and oncologic outcomes of partial adrenalectomy for multiple ipsilateral pheochromocytomas.

OBJECTIVE: Managing patients with multiple adrenal masses is technically challenging. We present our experience with minimally invasive partial adrenalectomy (PA) performed for synchronous multiple ipsilateral pheochromocytomas in a single setting. MATERIALS AND METHODS: We reviewed records of patients undergoing PA for pheochromocytoma at the National Cancer Institute between 1994 and 2010. Patients were included if multiple tumors were excised from the ipsilateral adrenal gland in the same operative setting. Perioperative, functional, and oncologic outcomes of PA for multiple pheochromocytomas are shown. RESULTS: Of 121 partial adrenalectomies performed, 10 procedures performed in eight patients for synchronous multiple ipsilateral pheochromocytomas were identified. All eight patients were symptomatic at presentation. The mean patient age was 30.6 years, median follow up was 12 months. The average surgical time was 228 minutes, average blood loss of 125 mL, and average number of tumors removed was 2.6 per adrenal. In total, 26 tumors were removed, 24 were pathologically confirmed pheochromocytomas, while two were adrenal cortical hyperplasia. After surgery, all patients had resolution of their symptoms, one patient required steroid replacement postoperatively. On postoperative imaging, one patient had evidence of ipsilateral adrenal nodule at the prior resection site 2 months postoperatively, which was consistent with incomplete resection. CONCLUSIONS: Minimally invasive surgical resection of synchronous multiple pheochromocytomas is feasible with acceptable perioperative, functional, and short-term oncologic outcomes.

Outcomes of patients with surgically treated bilateral renal masses and a minimum of 10 years of followup.

PURPOSE: Nephron sparing surgery has been advocated for patients with bilateral renal masses but long-term functional and oncological outcomes are lacking. We report the outcomes of patients with bilateral renal masses and a minimum 10-year followup. MATERIALS AND METHODS: Patients with bilateral renal masses evaluated at our institution who were treated with initial surgery at least 10 years ago and underwent interventions on each renal unit were included in the analysis. Collected data included demographics, hereditary diagnosis, number of renal interventions, renal function and mortality status. Overall and renal cell carcinoma specific survival was assessed. Comparisons were made of renal function and overall survival between groups with 2 renal units and a surgically solitary kidney. RESULTS: A total of 128 patients met study inclusion criteria. Median followup in our cohort was 16 years (mean 17, range 10 to 49). The median number of surgical interventions was 3 (range 2 to 10). Of the patients 87 (68%) required repeat interventions on the ipsilateral renal unit at last followup with a median of 6.2 years (range 0.7 to 21) between interventions. Overall and renal cell cancer specific survival was 88% and 97%, respectively. Six patients (4.7%) ultimately underwent bilateral nephrectomy. Although renal function was better preserved in patients with 2 kidneys (70 vs 53 ml/minute/1.73 m(2), p = 0.0002), there was no difference in overall survival between those with bilateral kidneys or a surgically solitary kidney. CONCLUSIONS: At a minimum 10-year followup after initial surgery, nephron sparing surgery allowed for excellent oncological and functional outcomes. Despite the need for repeat surgical interventions, nephron sparing surgery enabled dialysis to be avoided in more than 95% of patients.

EGFR signaling through an Akt-SREBP-1-dependent, rapamycin-resistant pathway sensitizes glioblastomas to antilipogenic therapy.

Glioblastoma, the most common malignant brain tumor, is among the most lethal and difficult cancers to treat. Although epidermal growth factor receptor (EGFR) mutations are frequent in glioblastoma, their clinical relevance is poorly understood. Studies of tumors from patients treated with the EGFR inhibitor lapatinib revealed that EGFR induces the cleavage and nuclear translocation of the master transcriptional regulator of fatty acid synthesis, sterol regulatory element-binding protein 1 (SREBP-1). This response was mediated by Akt; however, clinical data from rapamycin-treated patients showed that SREBP-1 activation was independent of the mammalian target of rapamycin complex 1, possibly explaining rapamycin's poor efficacy in the treatment of such tumors. Glioblastomas without constitutively active EGFR signaling were resistant to inhibition of fatty acid synthesis, whereas introduction of a constitutively active mutant form of EGFR, EGFRvIII, sensitized tumor xenografts in mice to cell death, which was augmented by the hydroxymethylglutaryl coenzyme A reductase inhibitor atorvastatin. These results identify a previously undescribed EGFR-mediated prosurvival metabolic pathway and suggest new therapeutic approaches to treating EGFR-activated glioblastomas.