Neurofibromatosis type 1 (NF1) patients are prone to the development of malignant tumors, the most common being Malignant Peripheral Nerve Sheath Tumor (MPNST). NF1-MPNST patients have an overall poor survival due to systemic metastasis. Currently, the management of MPNSTs includes surgery and radiation; however, conventional chemotherapy is not very effective, underscoring the need for effective biologically-targeted therapies. Recently, the NF1 gene product, neurofibromin, was shown to negatively regulate the phosphoinositide-3-kinase (PI3K)/Protein Kinase-B (Akt)/mammalian Target Of Rapamycin (mTOR) pathway, with loss of neurofibromin expression in established human MPNST cell lines associated with high levels of mTOR activity. We developed and characterized a human NF1-MPNST explant grown subcutaneously in NOD-SCID mice, to evaluate the effect of the mTOR inhibitor rapamycin. We demonstrate that rapamycin significantly inhibited human NF1-MPNST mTOR pathway activation and explant growth in vivo at doses as low as 1.0 mg/kg/ day, without systemic toxicities. While rapamycin was effective at reducing NF1-MPNST proliferation and angiogenesis, with decreased CyclinD1 and VEGF respectively, there was no increase in tumor apoptosis. Rapamycin effectively decreased activation of S6 downstream of mTOR, but there was accompanied increased Akt activation. This study demonstrates the therapeutic potential and limitations of rapamycin in NF1-associated, and likely sporadic, MPNSTs.Malignant Peripheral Nerve Sheath Tumors (MPNST) have an incidence of 0.001% in the general population, however, as many as 5-10% of individuals with the inherited cancer syndrome, neurofibromatosis type 1 (NF1) will develop an MPNST in their lifetime. In adults with NF1, MPNSTs are the most common malignancy and the major source of morbidity.1 The poor survival associated with NF1-associated MPNST (NF1-MPNST) reflects the earlier age of onset, multiple MPNSTs, and their overall resistance to conventional chemo-and radiation treatment. Unfortunately, pre-or postoperative adjuvant chemotherapy is not effective 2 and the five year survival after MPNST diagnosis is $20% for individuals with NF1.3 In addition, these tumors have a high propensity to metastasize to bone and lung, even after surgical excision and local radiation therapy. 4 As such, there is a recognized need for effective targeted biological therapies for NF1-MPNSTs.With the identification of the NF1 protein (neurofibromin), it became possible to consider treatments that reverse the biochemical abnormalities resulting from loss of neurofibromin function in NF1-MPNST. Neurofibromin functions in part as a Ras GTPase Activating Protein (Ras-GAP) by accelerating the conversion of active, GTP-bound p21-Ras to inactive, GDP-bound Ras and reducing p21-Ras stimulation of cell growth. We and others have previously shown that p21-ras-GTP levels are elevated in human NF1-MPNST tumors. 5,6 However, biological therapies targeting p21-Ras activation, such as farnesyltransferase inhibitors (FTIs), ...
A 57-year-oldpatient diagnosed witha right glomus jugularae was referred to the ENT unit TH/Anuradhapura for further management. Multidisciplinary discussion and multi-modality imaging confirmed the diagnosis to be a jugular schwannoma. The Patient underwenttumour excision via a combined petro-occipital trans-sigmoidal approach withclose perioperative monitoring and post-operative rehabilitation.This article discusses the importance of a detailed history, examination and multimodality imaging for correct diagnosis of jugular foramen lesions which governs the selection of the surgical approach.
A 49-year-old female with grade 3 tracheal stenosis underwent Coblator assisted recanalization and mytomycin-C application. Montgomery T-Tube was used to stent the lumen and she was successfully decanulated after one year. We believe that use of Coblator, mytomycin-C and T-tube resulted in successful outcome.
belonged to the age group of 0 to 12 years. Of these, 52 patients presented with headache and 40 had vomiting. Blurring of vision was seen in 22 patients. Most common midline posterior fossa tumor was medulloblastoma. Postoperative hydrocephalus and seizures were seen in six patients. Out of 60 patients, 12 patients had poor outcome versus 48 patients with good outcome on the Karnofsky performance status.Conclusion: Midline posterior fossa tumors were more common in males. Symptoms of raised ICP and cerebellar symptoms were most common presentations. Headache and histopathology of tumor: high grade or low grade shows statistically significant correlation with outcome of patients as measured with the Karnofsky performance scoring. As our study was of small duration, long-term study can give better results Introduction: The advent of intraoperative magnetic resonance imaging (IOMRI) represents a substantial improvement in ensuring complete removal of intracranial lesions but poses specific challenges to the neurosurgical OT team. KeywordsMethodology/Description: This observational study was conducted to assess our learning curve of resource utilization and conduct of 3T-IOMRI at our hospital for the first month. Every time we performed an IOMRI, we collected data and noted mistakes and processes we could improve next time. Data collected included time required to move patients into the MRI room and back to OT, number of personnel required, changes made to our checklist, and standard operating procedures for equipment utilization and patient transfer. We also collected data regarding number of patients with residue who underwent resurgery, quality of scans, and surgeon satisfaction. patients allocated into three equal groups to receive either sevoflurane (n = 22), desflurane (n = 22), or propofol (n = 22). Standard anesthesia protocol was followed. Patients with preoperative MMSE ≤ 23 were excluded. Each patient was assessed thrice with battery of cognitive tests in preoperative period (baseline), after 72 hours (early POCD), after 3 months (delayed POCD) of surgery. Serum levels of IL-6, TNF-α, and S-100β were measured before surgery and 72 hours after surgery.Results: Mean score of various psychometric tests was improved slightly in early postoperative period which was not significant (p > 0.5). In delayed postoperative period, there was significant improvement in cognitive scores as compared with baseline (p < 0.5) in all the groups. There was nonsignificant change in the levels of biomarkers S-100β, TNF-α, and IL-6 between baseline and postoperative period in all the groups.Conclusion: In young patients, there is no effect of anesthesia on postoperative cognitive functions. As far as inflammatory markers are concerned, they do not relate to patient's cognitive status.Keywords: anesthesia, sevoflurane, desflurane Postoperative cognitive dysfunction in middle-aged patients.
Inclusion Criteria: Age between 18and 65 years. Patients undergoing clipping, coiling for anterior circulation aneurysm with WFNS grade III, IV, and V. ICU admission within 48 to 72 hours of surgery.Exclusion Criteria: Patient not giving consent. Contraindication for application of NIRS sensors (pneumocephalus). Data of rSO 2 , SjvO 2 , and CBFV were collected at the following time points-arrival in the ICU (baseline), second hourly daily during the ICU stay (up to 5 days) prior to and after intervention. The significant changes were recorded.Results: Injured side NIRS values were less compared with normal side. Injured side TCD values were always higher by > 25 cm/sec. The side-side differences existed for NIRS and TCD. The trend values were similar in all patients and consistent.Conclusion: Interhemispheric differences in rSO 2 and TCD could be considered as an early sign of VS-induced DCI rather than absolute threshold values. However, large studies are needed to test our observations. Introduction: Von Hippel-Lindau (VHL) disease is an inherited autosomal dominant disorder with predilection to develop characteristic tumors in the cerebellar hemispheres, retina, brain stem, and spinal cord with a prevalence of approximately 1/50,000. KeywordsMethodology/Description: A 29-year-old, 55-kg woman presented with tingling and numbness in all four limbs, difficulty in walking, constipation, and urge for micturition. MRI revealed multiple cystic enhancing lesions in cervical and dorsal cord with significant cord edema. Diagnosed with VHL disease, pancreatic cyst, and diabetes mellitus for past 5 years on treatment. Multiple hemangiomas in retina. Operated for right partial nephrectomy 5 years back. Patient had a Glasgow Coma Scale (GCS) of 15/15 preop. Power of 4/5 on right side, 5/5 on left side. Routine hematological, biochemical values, thyroxin, cortisol, chest X-ray, serum electrolytes, calcium and phosphorus levels, 12-lead electrocardiogram, and echocardiogram were normal. Patient was posted for cervical laminectomy and intramedullary cyst excision from C2 to C7 level. Routine monitors were attached, left radial artery was cannulated. Patient induced with inj. midazolam, fentanyl, propofol, and atracurium. Anesthesia maintained with oxygen-air mixture with sevoflurane (<0.5 MAC), dexmedetomidine, and propofol infusion. Intraop neuromonitoring-somatosensory evoked potential (SSEP), motor evoked potential (MEP), bispectral index, neuromuscular monitoring done. MEP-amplitude decreased < 50 intraoperatively with baseline values, while SSEP were maintained. Postoperatively, patient had right upper and lower limb power grade 0/5, which improved significantly by POD-3 to preop level 4/5. Patient was discharged on POD-8.Conclusion: There is very little literature available for anesthetic management in a VHL disease. Anesthetic management of VHL is by itself a challenge; this case was more challenging due to the presence of cervicodorsal and pancreatic cyst with multiple hemangiomas. The case was successfully managed b...
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