Citations

Purpose Molecular and clinical observations suggest a role of sex steroid hormones in the occurrence of meningioma. However, there is limited and often conflicting data on the use of hormone replacement therapy (HRT) as a possible risk factor for meningioma. The goal of this study was to investigate whether there is an association between a diagnosis of meningioma and either current or past HRT use in women. Methods We retrospectively reviewed records in the Mayo Clinic Jacksonville electronic patient database between 1993 and 2003 to identify women with a diagnosis of either symptomatic or incidentally discovered, clinically silent meningioma. Records were also searched to identify women with a documented history of either current or past HRT use. Results Of the 355,318 women, ages 26 to 86, evaluated for any medical issue, 18,037 (5%) were documented as current or past HRT users. A total of 1,390 women with a history of symptomatic or incidentally discovered meningiomas were identified, 156 (11%) of whom were either current or past HRT users. A logistic regression analysis, adjusted for age, demonstrated a positive association between a diagnosis of meningioma and HRT use, with an odds ratio of 2.2 (95% CI, 1.9 to 2.6; P < .0001). The frequency of meningioma in women with either current or past HRT use was 865 in 100,000, whereas the frequency of meningioma in women without the history of HRT use was 366 in 100,000. Conclusion The study provides evidence of a positive association between HRT use and diagnosis of meningioma, and therefore, HRT use may be a risk factor for meningioma.

Purpose In the phase III study AVF2107g, bevacizumab (BV) demonstrated a survival benefit when added to irinotecan, fluorouracil, and leucovorin (IFL) in first-line metastatic colorectal cancer (mCRC). In a parallel phase III study, Intergroup N9741, oxaliplatin plus fluorouracil and leucovorin (FOLFOX) also demonstrated a survival benefit compared with IFL. As these two superior therapies have differing mechanisms of action, we explored whether the improved survival associated with the superior therapy was dependent on tumor response. Patients and Methods For these retrospective, exploratory analyses, patients were defined as responders or nonresponders by whether complete or partial response was achieved with first-line therapy. Results Compared with IFL alone, BV plus IFL and FOLFOX each demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) regardless of objective tumor response. BV-treated nonresponders had a hazard ratio (HR) of 0.63 (P = .0001) for PFS and 0.76 (P = .0188) for OS compared with IFL-treated nonresponders. FOLFOX-treated nonresponders had an HR of 0.75 (P = .0029) for PFS and 0.74 (P = .0030) for OS compared with IFL-treated nonresponders. Conclusion In both AVF2107g and N9741, objective response did not predict the magnitude of PFS or OS benefit from the superior therapy; nonresponders, despite a poorer prognosis than responders, achieved extended PFS and OS from BV plus IFL or FOLFOX compared with IFL. On the basis of these data, tumor response in metastatic colorectal cancer is not a necessary factor for a therapy to provide benefit to an individual patient.

In this issue of Blood, Ruggeri and colleagues highlight the high risk of vascular events in patients with essential thrombocythemia and polycythemia vera undergoing operative procedures even with current “optimal” surgical prophylaxis.

Between 1986 and 2005, 22 patients (mean age, 14.7 years; range, 3-21) with renal hypertension underwent renal artery revascularization for 28 lesions, 23 with open repair (OR) and 5 with percutaneous transluminal renal angioplasty (PTRA). Thirty-day morbidity was 17% (4/23). Hypertension was cured in 13 (57%), improved in 8 (38%), and unchanged in 1 (5%). Renal function worsened in 1. At a mean follow-up of 4.9 years, 1-year patency rate was 94% and maintained for 5 years. Hypertension at 1 year was cured in 6 of 14 patients (43%; OR, 4; PTRA, 2) and improved in 8 (57%; OR, 7; PTRA, 1); hypertension at 5 years was cured in 50% and improved in 50%. Renal function remained unchanged in all patients who were followed. The authors conclude that both OR and PTRA benefit pediatric patients. PTRA for selected patients may be promising as a first line treatment or as a bridge to definitive OR in children with small arteries.

AbstractBackground: Newborn screening for maple syrup urine disease (MSUD) relies on finding increased concentrations of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine by tandem mass spectrometry (MS/MS). d-Alloisoleucine (allo-Ile) is the only pathognomonic marker of MSUD, but it cannot be identified by existing screening methods because it is not differentiated from isobaric amino acids. Furthermore, newborns receiving total parenteral nutrition often have increased concentrations of BCAAs. To improve the specificity of newborn screening for MSUD and to reduce the number of diet-related false-positive results, we developed a LC-MS/MS method for quantifying allo-Ile.Methods: Allo-Ile and other BCAAs were extracted from a 3/16-inch dried blood spot punch with methanol/H2O, dried under nitrogen, and reconstituted into mobile phase. Quantitative LC-MS/MS analysis of allo-Ile, its isomers, and isotopically labeled internal standards was achieved within 15 min. To determine a reference interval for BCAAs including allo-Ile, we analyzed 541 dried blood spots. We also measured allo-Ile in blinded samples from 16 MSUD patients and 21 controls and compared results to an HPLC method.Results: Intra- and interassay imprecision (mean CVs) for allo-Ile, leucine, isoleucine, and valine ranged from 1.8% to 7.4%, and recovery ranged from 91% to 129%. All 16 MSUD patients were correctly identified.Conclusions: The LC-MS/MS method can reliably measure allo-Ile in dried blood spots for the diagnosis of MSUD. Applied to newborn screening as a second-tier test, it will reduce false-positive results, which produce family anxiety and increase follow-up costs. The assay also appears suitable for use in monitoring treatment of MSUD patients.