Regulatory T-cells (Tregs) are immunosuppressive T-cells, which arrest immune responses to ‘Self’ tissues. Some immunosuppressive Tregs that recognize seminal epitopes suppress immune responses to the proteins in semen, in both men and women. We postulated that GBMs express reproductive-associated proteins to manipulate reproductive Tregs and to gain immune privilege. We analyzed four GBM transcriptome databases representing ≈900 tumors for hypoxia-responsive Tregs, steroidogenic pathways, and sperm/testicular and placenta-specific genes, stratifying tumors by expression. In silico analysis suggested that the presence of reproductive-associated Tregs in GBM tumors was associated with worse patient outcomes. These tumors have an androgenic signature, express male-specific antigens, and attract reproductive-associated Related Orphan Receptor C (RORC)-Treg immunosuppressive cells. GBM patient sera were interrogated for the presence of anti-sperm/testicular antibodies, along with age-matched controls, utilizing monkey testicle sections. GBM patient serum contained anti-sperm/testicular antibodies at levels > six-fold that of controls. Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are associated with estrogenic tumors which appear to mimic placental tissue. We demonstrate that RORC-Tregs drive poor patient outcome, and Treg infiltration correlates strongly with androgen levels. Androgens support GBM expression of sperm/testicular proteins allowing Tregs from the patient’s reproductive system to infiltrate the tumor. In contrast, estrogen appears responsible for MDSC/TAM immunosuppression.
Background: Overdrainage after cerebrospinal fluid diversion remains a significant morbidity. The hydrostatic, gravitational force in the upright position can aggravate this. Siphon control (SC) mechanisms, as well as programmable and flow regulating devices, were developed to counteract this. However, limited studies have evaluated their safety and efficacy. In this study, direct comparisons of the complication rates between siphon control (SC) and non-SC (NSC), fixed versus programmable, and flow- versus pressure regulating valves are undertaken. Methods: A retrospective chart review was performed over all shunt implantations from January 2011 to December 2016 within the Houston Methodist Hospital system. Complication rates within 6 months of the operative date, including infection, subdural hematoma, malfunction, and any other shunt-related complication, were analyzed via Fisher’s exact test, with P < 0.05 regarded as significant. Subgroup analyses based on diagnoses – normal pressure hydrocephalus (HCP), pseudotumor cerebri, or other HCP – were also performed. Results: The overall shunt-related complication rate in this study was 19%. Overall rates of infection, shunt failure, and readmission within 180 days were 3%, 11%, and 34%, respectively. No difference was seen between SC and NSC groups in any complication rate overall or on subgroup analyses. When comparing fixed versus programmable and flow- versus pressure-regulating valves, the latter in each analysis had significantly lower malfunction and total complication rates. Conclusions: Programmable and pressure regulating devices may lead to lower shunt malfunction and total complication rates. Proper patient selection should guide valve choice. Future prospective studies may further elucidate the difference in complication rates between these various shunt designs.
Purpose Subependymal giant cell astrocytomas (SEGAs) are rare tumors typically found in tuberous sclerosis patients. They typically grow in the region of the foramen of Monro and can occlude it, leading to hydrocephalus. Currently, gross total resection is the standard of care, with low rates of recurrence but high rates of complication, especially with larger lesions. Laser interstitial thermal therapy (LITT) is a newly emerging treatment modality for a variety of pathologies. Here, we present a case series of SEGAs managed via LITT and endoscopic, stereotactic septostomy. Methods A retrospective chart review was performed to identify three cases in which SEGAs were treated via LITT and septostomy. Stereotactic ablation was performed via magnetic resonance (MR) thermometry with laser output set to 69% for 2.5 min, with post-ablation scans for visualization of treatment area.Results Average age at surgery was 8.2 years. Pre-operative tumor volumes were 0.43, 1.51, and 3.88 cm 3 . Post-operative tumor volumes were 0.25, 0.21, and 0.68 cm 3 . Mean tumor volume reduction was 70%. No complications occurred. Conclusion LITT with septostomy should be considered a viable primary or adjunct treatment modality for SEGAs.
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