levoleucovorin and Atrophy

The purpose of this study was to investigate the incidence, origin, and clinical significance of liver atrophy during chemotherapy for colorectal cancer.. This study included 103 patients who underwent chemotherapy before resection for colorectal liver metastases (training set) and 171 patients who underwent adjuvant or first-line chemotherapy without liver resection (validation set). A greater than 10% decrease (atrophy) or increase (hypertrophy) of the liver volume from the baseline was defined as a significant change.. In the training set, the numbers of patients who developed atrophy, no change of volume, and hypertrophy of the liver after chemotherapy were 15 (14.6%), 73 (70.9%), and 15 (14.6%), respectively. Liver atrophy was associated with impaired hepatic function, and the postoperative morbidity rate and refractory ascites/pleural effusion were higher in the patients with liver atrophy than those without (60.0% vs. 31.8%, P = 0.045 and 46.7% vs. 8.0%, P < 0.001, respectively). Histopathological examination revealed a strong association between sinusoidal injury and liver atrophy (P < 0.001). The cumulative incidence of liver atrophy increased with increasing duration of chemotherapy, whereas the incidence of liver atrophy was less frequent in patients who had received bevacizumab than those who had not in both the training set (odds ratio [OR], 0.13; P = 0.001) and the validation set (OR, 0.31; P = 0.007).. Liver atrophy is associated with impaired hepatic functional reserve and observed at an increasing frequency as the duration of chemotherapy increases with frequent histopathological evidence of sinusoidal injury in the liver. Bevacizumab may protect against the development of liver atrophy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Atrophy; Bevacizumab; Chemical and Drug Induced Liver Injury; Colorectal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Postoperative Complications; Prognosis; Retrospective Studies; Survival Rate

Folinic acid-responsive seizures (FARS) are a rare treatable cause of neonatal epilepsy. They have characteristic peaks on CSF monoamine metabolite analysis, and have mutations in the ALDH7A1 gene, characteristically found in pyridoxine-dependent epilepsy. There are case reports of patients presenting with seizures at a later age, and with folate deficiency due to different mechanisms with variable response to folinic acid supplementation. Here, we report 2 siblings who presented with global developmental delay and intractable seizures who responded clinically to folinic acid therapy. Their work-up included metabolic and genetic testing. The DNA sequencing was carried out for the ALDH7A1 gene, and the folate receptor 1 (FOLR1) gene. They had very low 5-methyltetrahydrofolate (5-MTHF) in CSF with no systemic folate deficiency and no characteristic peaks on neurotransmitter metabolite chromatogram. A novel mutation in the FOLR1 gene was found. The mutation in this gene is shown to affect CSF folate transport leading to cerebral folate deficiency. The response to treatment with folinic acid was dramatic with improvement in social interaction, mobility, and complete seizure control. We should consider the possibility of this treatable condition in appropriate clinical circumstances early, as diagnosis with favorable outcome depends on the specialized tests.

Topics: Atrophy; Brain; Brain Diseases, Metabolic, Inborn; Child Development Disorders, Pervasive; Child, Preschool; Consanguinity; Developmental Disabilities; Early Diagnosis; Electroencephalography; Epilepsies, Myoclonic; Female; Folate Receptor 1; Folic Acid Deficiency; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Mutation, Missense; Point Mutation; Pyridoxine; Siblings; Tetrahydrofolates

Topics: Antiparkinson Agents; Atrophy; Basal Ganglia; Brain Diseases, Metabolic; Carbidopa; Cerebellum; Demyelinating Diseases; Dystonia; Female; Folic Acid Deficiency; Humans; Leucovorin; Levodopa; Male; Syndrome; Tetrahydrofolates; Treatment Outcome; Vitamin B Complex