Avinash Mohan

Enlargement of a vestibular schwannoma after stereotactic radiotherapy.

Summary. Background: Radiosurgery has been increasingly advocated as a primary treatment for vestibular schwannoma (VS), and recently fractionation of the dose has been proposed as a method to decrease the risk of radiation injury when treating larger tumors. Method: The authors describe a 48-year-old woman who presented with right-sided hearing loss and new-onset tinnitus, with a progressive decrease in facial sensation. The diagnosis of a large right cerebellopontine angle VS was made on magnetic resonance imaging (MRI). The patient was treated with a course of fractionated stereotactic radiotherapy (SRT) (5 treatments of 4 Gy to the 90% isodose line over a 3-week period). Findings: Six months after the initiation of therapy, her symptoms increased, and a repeat MRI scan demonstrated that her tumor had increased in size, producing significant brainstem compression. She then underwent complete surgical resection of the tumor, with resolution of her symptoms. Interpretation: Stereotactic radiosurgery has been effective in controlling small VSs with low complication rates. Larger tumors pose a risk for increasing in size and producing symptoms from mass effect with SRT. There are at present limited data demonstrating safety and efficacy of fractionated SRT for the treatment of larger tumors.

Hemorrhagic Ganglioglioma of the Posterior Fossa: Case Report

Gangliogliomas are rare tumors of the central nervous system that are usually found in the supratentorial compartment, although cases throughout the nervous system have been described. They are generally low-grade malignancies that are amenable to cure by surgical resection. Most manifest as seizures, though, based on location, they can present with focal neurological deficits. We present here a rare case of an infratentorial ganglioglioma presenting with hemorrhage. To our knowledge this is the only reported case of a hemorrhagic ganglioglioma and, as such, we examine its possible prognosis.

Knife wound to the posterior fossa in a child

BackgroundKnife wounds to the posterior fossa are a rare occurrence, especially in children. We report an 8-year-old girl who sustained a penetrating knife injury through the occipital bone into the posterior fossa. On presentation, the large knife blade was firmly embedded in her head.MethodsRadiographic evaluation was limited to plain X-rays because of the large size and sharpness of the embedded blade. Innovative positioning was used during intubation and then the patient was positioned semi-prone on the operating room table. The blade was surgically removed and the dura was closed.ConclusionsAtypical penetrating cranial injuries in children may require the treatment team to take a creative approach to the evaluation and repair of the lesion in order to maximize patient safety and minimize the risk of neurological injury.

Obstructive hydrocephalus due to a third ventricular neuroepithelial cyst

Cysts occupying the third ventricle are rare lesions and may appear as an unusual cause of obstructive hydrocephalus. Various types of lesions occur in this location, and they generally have an arachnoidal, endodermal, or neuroepithelial origin. The authors present a case of acute hydrocephalus following minor trauma in a child due to cerebrospinal fluid outflow obstruction by a third ventricular cyst. Definitive diagnosis of this cystic lesion was possible only with contrast ventriculography and not routine computed tomography or magnetic resonance imaging. The investigation, treatment, and pathological findings are discussed.

A Novel Approach Using Electromagnetic Neuronavigation and a Flexible Neuroendoscope for Placement of Ommaya Reservoirs.

OBJECTIVE Placement of intraventricular catheters in oncology patients can be associated with morbidity given their small to slit-like ventricles and underlying hematologic disorders. We studied the accuracy of placing Ommaya reservoirs using neuronavigation and a flexible neuroendoscope to verify catheter positioning. METHODS Ommaya reservoirs placed in 25 oncology patients between 2013 and 2015 were retrospectively reviewed. Twenty-five ventricular catheters were placed using the AxiEM stealth frameless neuronavigation system and a flexible neuroendoscope. Postoperative catheter accuracy, operative complications, and postoperative complications were assessed. We discuss surgical protocol and technical nuances. RESULTS All ventricular catheters were successfully placed into the ipsilateral (84%) or contralateral (16%) foramen of Monro. A single ventricular catheter pass was needed to cannulate the ventricle in 96% of patients. The mean accuracy was 4.09 ± 3.47 mm from the target, the ipsilateral foramen of Monro. One patient had a catheter tract hemorrhage seen on postoperative imaging related to thrombocytopenia. No postoperative neurologic deficits were seen. CONCLUSIONS A combined neuronavigation and neuroendoscopic approach improved catheter tip accuracy compared with accuracy rates described in the literature using other techniques. This approach can be adapted toward routine clinical practice of placing ventricular shunt catheters and Ommaya reservoirs.

ATP-site binding inhibitor effectively targets mTORC1 and mTORC2 complexes in glioblastoma

The PI3K-AKT-mTOR signaling axis is central to the transformed phenotype of glioblastoma (GBM) cells, due to frequent loss of tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10). The mechanistic target of rapamycin (mTOR) kinase is present in two cellular multi-protein complexes, mTORC1 and mTORC2, which have distinct subunit composition, substrates and mechanisms of action. Targeting the mTOR protein is a promising strategy for GBM therapy. However, neither of these complexes is fully inhibited by the allosteric inhibitor of mTOR, rapamycin or its analogs. Herein, we provide evidence that the combined inhibition of mTORC1/2, using the ATP-competitive binding inhibitor PP242, would effectively suppress GBM growth and dissemination as compared to an allosteric binding inhibitor of mTOR. GBM cells treated with PP242 demonstrated significantly decreased activation of mTORC1 and mTORC2, as shown by reduced phosphorylation of their substrate levels, p70 S6K(Thr389) and AKT(Ser473), respectively, in a dose-dependent manner. Furthermore, insulin induced activation of these kinases was abrogated by pretreatment with PP242 as compared with rapamycin. Unlike rapamycin, PP242 modestly activates extracellular regulated kinase (ERK1/2), as shown by expression of pERK(Thr202/Tyr204). Cell proliferation and S-phase entry of GBM cells was significantly suppressed by PP242, which was more pronounced compared to rapamycin treatment. Lastly, PP242 significantly suppressed the migration of GBM cells, which was associated with a change in cellular behavior rather than cytoskeleton loss. In conclusion, these results underscore the potential therapeutic use of the PP242, a novel ATP-competitive binding inhibitor of mTORC1/2 kinase, in suppression of GBM growth and dissemination.

International teleconsultation on conjoined twins leading to a successful separation: a case report:

Conjoined twins are identical twins that have incompletely separated in utero. The prognosis for conjoined twins is poor and management in a skilled tertiary care centre is paramount for definitive care. We describe our experience with a telemedical consultation on conjoined twins in The Dominican Republic from our eHealth centre in Valhalla, NY. The patients were two month old, female, pygopagus conjoined twins. A multidisciplinary teleconference was initiated with the patients, their family, the referring paediatrician and our team. Based on this teleconsultation, the team felt as though the twins may be amenable to a surgical separation. They presented to our centre in Valhalla, NY, for a detailed physical examination and series of imaging studies. Soon after, the patients underwent a successful 21 h separation procedure and were discharged 12 weeks later. To our knowledge, this is one of the first reports of an international teleconsultation leading to a successful conjoined twin separation procedure.

Abstract 1670: Targeting PI3K/mTOR/MAPK pathway in inhibition of cell growth and dissemination of glioblastoma multiforme

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Activation of aberrant PI3K/AKT/mTOR (mammalian target of rapamycin) have been shown in tumorigenesis of glioblastoma multiforme (GBM), suggesting that inhibition of PI3K/mTOR may have therapeutic advantages. mTOR, which is deregulated in GBM, exists in two distinct mutiprotein complexes, mTORC1 and mTORC2, that regulates cell survival, growth, and motility. However, the inhibitors of mTOR, such as Rapamycin (RAPA) or its analogues that work via allosteric mechanism have provided limited clinical benefits to date. The aim of this study is to provide evidence that a combined inhibition of mTORC1/2 (via allosteric or ATP-competitive inhibition) with MAPK inhibitors would effectively suppress GBM growth and dissemination. We observed a significant number of GBM tumors showed increased expression of pAKTSer473 and pmTORSer2448, as assessed by immunohistochemistry. Inhibition of mTOR using RAPA suppressed pAKTSer473 levels. 12-O- Tetradecanoylphorbol-13-acetate (TPA) or insulin induced activation of pAKTSer473 was suppressed by pre-treatment with RAPA. Unlike this allosteric inhibitor of mTOR, ATP-competitive inhibitors of mTORC1/2, pp242, showed a complete suppression of pAKTSer473 in a dose-dependent manner. Also, pre-treatment with pp242 partially restored the insulin induced activation of pAKTSer473. The downstream substrate of mTORC1, p70S6KThr389 was noticeably suppressed by pp242 (2.2µM) and remained suppressed even after the treatment with TPA or insulin. Also, treatment with TPA or insulin significantly enhanced the activity of both p-p70S6K85and p-p70S6K70, which was completely abrogated by pretreatment with pp242, and partially by RAPA. Downstream from p70S6KThr389, S6 kinase (pS6KSer235/236 mTORC1 substrate), was suppressed in a dose dependent manner by pp242. We observed that PP242 completely inhibited the phosphorylation of a protein that controls protein synthesis, the mTORC1 substrate, eukaryotic initiation factor 4E binding protein-1 (4EBP1), whereas RAPA had partial effect. Analyses of extra-cellular signal regulated kinases (ERK1/2) showed that pp242 or RAPA suppressed the levels of pERK1/2Thr202/Tyr204. Significance of these altered signaling pathways by pp242 and RAPA correlated with cell proliferation and motility. Cell proliferation was suppressed by pp242 in a dose-dependent manner while RAPA also suppressed cell viability albeit was not as pronounced. Importantly, in the presence of MEK1/2 inhibitor, U0126, the pp242 noticeably suppressed cell growth as compared to RAPA. Moreover, the pp242 was effective in inhibiting the GBM cell migration. Taken together, these results suggest novel mTORC1/2/MAPK inhibitors suppress GBM growth and dissemination, which underscores the potential of a combined treatment strategy in GBM. . Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1670. doi:10.1158/1538-7445.AM2011-1670