Citations

Abstract Motivation: Using stable isotopes in global proteome scans, labeled molecules from one sample are pooled with unlabeled molecules from another sample and subsequently subjected to mass-spectral analysis. Stable-isotope methodologies make use of the fact that identical molecules of different stable-isotope compositions are differentiated in a mass spectrometer and are represented in a mass spectrum as distinct isotopic clusters with a known mass shift. We describe two multivariable linear regression models for 16O/18O stable-isotope labeled data that jointly model pairs of resolved isotopic clusters from the same peptide and quantify the abundance present in each of the two biological samples while concurrently accounting for peptide-specific incorporation rates of the heavy isotope. The abundance measure for each peptide from the two biological samples is then used in down-stream statistical analyses, e.g. differential expression analysis. Because the multivariable regression models are able to correct for the abundance of the labeled peptide that appear as an unlabeled peptide due to the inability to exchange the natural C-terminal oxygen for the heavy isotope, they are particularly advantageous for a two-step digestion/labeling procedure. We discuss how estimates from the regression model are used to quantify the variability of the estimated abundance measures for the paired samples. Although discussed in the context of 16O/18O stable-isotope labeled data, the multivariable regression models are generalizable to other stable-isotope labeled technologies. Contact: eckel@mayo.edu

OBJECTIVE. The aim of this study was to review our institutional experience managing pheochromocytomas and paragangliomas in children.METHODS. A retrospective chart review of the Mayo Clinic database from 1975 to 2005 identified 30 patients <18 years of age with histologically confirmed pheochromocytoma or paraganglioma.RESULTS. There were 12 patients with pheochromocytomas and 18 with paragangliomas. The most common presenting symptoms were hypertension (64%), palpitation (53%), headache (47%), and mass-related effects (30%). Nine patients (30%) had a genetic mutation or documented family history of pheochromocytoma or paraganglioma. Fourteen patients (47%) had malignant disease, whereas 16 (53%) had benign disease. Logistic analysis showed that statistically significant risk factors for malignancy were (1) paraganglioma, (2) apparently sporadic, as opposed to familial, pheochromocytoma or paraganglioma, and (3) tumor size of >6 cm. Surgical resection was performed for 28 patients (93%), with perioperative mortality and major morbidity rates of 0% and 10%, respectively. Resection achieved symptomatic relief for 25 patients (83%). All patients with benign disease appeared cured after resection. For patients with malignant disease, the 5- and 10-year disease-specific survival rates were 78% and 31%, respectively, and the mean survival time was 157 ± 32 months.CONCLUSIONS. The incidence of malignant pheochromocytoma/paraganglioma was high in children (47%), particularly those with apparently sporadic disease, paraganglioma, and tumor diameters of >6 cm. Patients with a known genetic mutation or familial pheochromocytoma/paraganglioma were more likely to achieve resection with negative microscopic margins and had improved disease-specific mortality rates. Surgical resection remains the treatment of choice for pheochromocytoma and paraganglioma.

Purpose Preoperative therapy for localized gastric cancer has considerable appeal. We hypothesized that, in a cooperative group setting, preoperative chemoradiotherapy would induce a 20% pathologic complete response (pathCR) rate. Combined-modality therapy quality, survival, and safety were secondary end points. Patients and Methods Patients with localized gastric adenocarcinoma were eligible. A negative laparoscopic evaluation was required. Patients received two cycles of induction fluorouracil, leucovorin, and cisplatin followed by concurrent radiation and chemotherapy (infusional fluorouracil and weekly paclitaxel). Resection was attempted 5 to 6 weeks after chemoradiotherapy was completed. Quality of therapy was assessed with other end points. Results Twenty institutions participated. Forty-nine patients were entered and 43 were assessable (12% stage IB; 37% stage II; and 52% stage III). The pathCR and R0 resection rates were 26% and 77%, respectively. At 1 year, more patients with pathCR (82%) are living than those with less than pathCR (69%). Grade 4 toxicity occurred in 21% of patients. Chemotherapy, radiotherapy, and surgery per protocol (including acceptable variations) occurred in 98%, 44%, and 63% of patients, respectively. A D2 dissection was performed in 50% of patients. Of 18 major radiotherapy variations, 17 were due to the lack of inclusion of the L3-4 vertebral interphase as prespecified. Conclusion For localized gastric cancer, preoperative chemoradiotherapy strategy achieved a pathCR rate of more than 20% in a cooperative group setting. The quality of surgery improved (50% with D2 dissection) possibly because surgery was part of this trial. With some refinements, this preoperative chemoradiotherapy strategy is poised for a randomized comparison with postoperative adjuvant chemoradiotherapy in patients with gastric cancer.