BackgroundBased on the hypothesis that cancer cells may not be able to metabolize ketones as efficiently as normal brain cells, the ketogenic diet (KD) has been proposed as a complementary or alternative therapy for treatment of malignant gliomas.Case presentationWe report here our experience in treating two glioma patients with an IRB-approved energy-restricted ketogenic diet (ERKD) protocol as monotherapy and review the literature on KD therapy for human glioma patients. An ERKD protocol was used in this pilot clinical study. In addition to the two patients who enrolled in this study, we also reviewed findings from 30 other patients, including 5 patients from case reports, 19 patients from a clinical trial reported by Rieger and 6 patients described by Champ. A total of 32 glioma patients have been treated using several different KD protocols as adjunctive/complementary therapy. The two patients who enrolled in our ERKD pilot study were monitored with twice daily measurements of blood glucose and ketones and daily weights. However, both patients showed tumor progression while on the ERKD therapy. Immunohistochemistry reactions showed that their tumors had tissue expression of at least one of the two critical mitochondrial ketolytic enzymes (succinyl CoA: 3-oxoacid CoA transferase, beta-3-hydroxybutyrate dehydrogenase 1). The other 30 glioma patients in the literature were treated with several different KD protocols with varying responses. Prolonged remissions ranging from more than 5 years to 4 months were reported in the case reports. Only one of these patients was treated using KD as monotherapy. The best responses reported in the more recent patient series were stable disease for approximately 6 weeks. No major side effects due to KD have been reported in any of these patients.ConclusionsWe conclude that 1. KD is safe and without major side effects; 2. ketosis can be induced using customary foods; 3. treatment with KD may be effective in controlling the progression of some gliomas; and 4. further studies are needed to determine factors that influence the effectiveness of KD, whether as a monotherapy, or as adjunctive or supplemental therapy in treating glioma patients.Trial registrationClinicalTrials.gov# NCT01535911
A phase III multicenter study was conducted in 89 patients with known intracranial vascular lesions to evaluate an extracellular gadolinium contrast agent, gadoteridol, for intracranial magnetic resonance (MR) angiography. The pre- and postcontrast MR angiograms of 82 patients were evaluated by the unblinded investigators and by two blinded readers (A and B) for visualization of lesions; arterial and venous anatomy; extent, size, and number of lesions; and disease classification. The unblinded readers indicated that lesions were visualized better on postcontrast images in the following categories: venous anatomy, 87 (81%) of 107 lesions; arterial anatomy, 43 lesions (40%); and extent or size of lesions, 38 lesions (36%). In 29 (35%) of 82 patients, the unblinded readers determined that enhanced MR angiography provided more diagnostic information than unenhanced MR angiography. The blinded readers determined that enhanced MR angiography provided more information for visualization of vascular anatomy in more than 60% of cases. The additional information provided with gadoteridol would have changed the diagnosis in nine (8%) of 107 lesions seen by the unblinded readers, 11 (12%) of 90 lesions seen by reader A, and three (3%) of 93 lesions seen by reader B. The results confirm that the use of gadoteridol improves the visualization of intracranial vascular lesions with MR angiography. The authors conclude that development of new postprocessing algorithms will improve the utility of contrast-enhanced MR angiography.
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