Stereotactic radiosurgery/radiotherapy for pituitary adenomas: a review of recent literature

The recent clinical results are reviewed of stereotactic radiosurgery/radiotherapy for the treatment of pituitary adenomas. The outcomes of pituitary adenomas treated by stereotactic radiosurgery/radiotherapy with gamma knife, CyberKnife, or linear accelerator (LINAC) radiosurgery were evaluated from articles published after 2004. Each study was evaluated for the number of patients, radiosurgical parameter (marginal dose), length of follow up, tumor growth control, rate of hormonal normalization in secretary adenomas, and adverse events. After gamma knife radiosurgery, the tumor reduction rates varied from 42.3% to 89% in non-secreting adenomas. However, the tumor control rates in non-secreting adenomas were more than 90% in most studies. In growth hormone-secreting adenomas, the rates of insulin-like growth factor-1 normalization ranged from 36.9% to 82%. In adrenocorticotropin-secreting adenomas, the rates for 24-hour urine free cortisol normalization ranged from 27.9% to 54%. In prolactin-secreting adenomas, the prolactin normalization ranged from 17.4% to 50%. New hormonal deficits ranged from 0% to 34%. New visual deficits were relatively low. The number of patients treated with CyberKnife and LINAC radiosurgery/radiotherapy was small and follow-up periods were relatively short compared to those with gamma knife treatment, but the clinical outcomes after these therapies were similar to those after gamma knife therapy. Image-guided stereotactic radiosurgery/radiotherapy with the gamma knife, CyberKnife, or LINAC system is effective and safe against pituitary adenomas. Careful long-term follow up of the patients is necessary because of long-term anti-tumor effects and delayed adverse events.     

A case of Baraitser–Winter syndrome with unusual brain MRI findings: Pachygyria,subcortical-band heterotopia,and periventricular heterotopia

Baraitser–Winter syndrome (BaWS) is characterized by iris coloboma, ptosis, hypertelorism, and mental retardation; it is a rare multiple congenital anomaly or a mental-retardation syndrome of unknown etiology. Patients suffering from this syndrome have been also found to show brain anomalies such as pachygyria, subcortical-band heterotopia (SBH), and hippocampal malformations; therefore, these anomalies have been included in the phenotypic spectrum of this syndrome. We report the case of a Japanese boy suffering from BaWS; the patient’s brain magnetic resonance imaging scan revealed pachygyria, SBH, and periventricular heterotopia. However, the results of the genome-wide array comparative genomic hybridization did not reveal any chromosomal rearrangements.     

Angioimmunoblastic T-cell lymphoma and membranous nephropathy: a still unreported association

A 21-year-old man with lymphadenopathy and Coombs-positive hemolytic anemia had been treated with steroid maintenance therapy. He developed nephrotic syndrome with size increase of lymphadenopathy. Lymph node examination disclosed angioimmunoblastic T-cell lymphoma (AITL). Light microscopy of a renal biopsy specimen showed typical features of membranous nephropathy (MN), such as bubbling appearance and spike formation. Immunofluorescence studies revealed no significant deposition of immunoglobulins. Electron microscopy showed sparse degenerative materials on the epithelial side of the glomerular basement membranes, with intervening spikes. These unique histological findings suggested secondary MN. High-dose steroid therapy followed by six courses of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) therapy improved his symptoms. One-year follow-up revealed the patient in good health without any signs of relapse. Glomerular manifestations have rarely been reported in association with AITL. To our knowledge, this is the first reported case of nephrotic syndrome due to MN associated with AITL.     

Association between 5-hydroxytryptamine 2A receptor gene polymorphism and postoperative analgesic requirements after major abdominal surgery

Although the serotonin (5-hydroxytryptamine (5-HT)) 2A receptor has been reported to be associated with pain, no relationship has been found between single nucleotide polymorphisms in the 5-HT2A receptor gene and analgesic requirements. To clarify the mechanism of individual differences in analgesic requirements, we investigated the relationship between the 5-HT2A 102T/C gene polymorphism and analgesic requirements in 135 patients who underwent major open abdominal surgery and were managed with continuous epidural analgesia with opioids after surgery. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. We found that the 102T/C polymorphism had significant main effects with regard to analgesic requirements. In addition, significant interaction effects were found between the 102T/C polymorphism and sex in terms of analgesic requirements. Among female subjects, patients with the T/T genotype of the 102T/C polymorphism had more analgesic requirements than those with the other genotypes. This finding suggests that the linkage disequilibrium block, which includes the 102T/C polymorphism of the 5-HT2A receptor gene, is involved in individual differences in analgesic requirements in women.     

Immunization in familial amyloidotic polyneuropathy: counteracting deposition by immunization with a Y78F TTR mutant

The mechanism of amyloid formation in familial amyloidotic polyneuropathy (FAP), a hereditary disorder associated with mutant transthyretin (TTR), is still unknown. It is generally believed that altered conformations exposing cryptic regions are intermediary steps in this mechanism. A TTR mutant--Y78F (transthyretin mutant with phenylalanine replacing tyrosine at position 78)--designed to destabilize the native structure has been shown to expose a cryptic epitope recognized by a monoclonal antibody that reacts only with highly amyloidogenic mutants presenting the amyloid fold or with amyloid fibrils. To test whether TTR deposition in FAP can be counteracted by antibodies for cryptic epitopes, we immunized with TTR Y78F, transgenic mice carrying the most common FAP-associated TTR mutant--V30M (transthyretin mutant with methionine replacing valine at position 30)--at selected ages that present normally with either nonfibrillar or TTR amyloid deposition. Compared to age-matched control nonimmunized mice, Y78F-immunized mice had a significant reduction in TTR deposition usually found in this strain, in particular in stomach and intestine; by contrast, animals immunized with V30M did not show differences in deposition in comparison with nonimmunized mice. Immunohistochemical analyses of tissues revealed that immunization with Y78F lead to infiltration by lymphocytes and macrophages at common deposition sites, but not in tissues such as liver, choroid plexus, and Langerhans islets, in which TTR is produced. These results suggest that Y78F induced production of an antibody that reacts specifically with deposits and leads to an immune response effective in removing/preventing TTR deposition. Therefore, TTR immunization with selected TTR mutants has potential application in immune therapy for FAP.