Targeting the Axl and mTOR Pathway Synergizes Immunotherapy and Chemotherapy to Butylidenephthalide in a Recurrent GBM.

Background: The role of inherent tumor heterogeneity and an immunosuppressive microenvironment in therapeutic resistance has been determined to be of importance for the better management of glioblastoma multiforme (GBM). Some studies have suggested that combined drugs with divergent mechanisms may be promising in treating recurrent GBM. Methods: Intracranial sustained (Z)-n-butylidenephthalide [(Z)-BP] delivery through Cerebraca Wafers (CWs) to eliminate unresectable brain tumors was combined with the administration of temozolomide (TMZ), pembrolizumab, and cytokine-induced killer (CIK) cells for treating a patient with recurrent glioblastoma. Neurological adverse events and wound healing delay were monitored for estimating tolerance and efficacy. Response Assessment in Neuro-Oncology criteria were applied to evaluate progression-free survival (PFS); further, the molecular characteristics of GBM tissues were analyzed, and the underlying mechanism was investigated using primary culture. Results: Intracerebral (Z)-BP in residual tumors could not only inhibit cancer stem cells but also increase interferon gamma levels in serum, which then led to the regression of GBM and an immune-responsive microenvironment. Targeting receptor tyrosine kinases, including Axl and epidermal growth factor receptor (EGFR), and inhibiting the mechanistic target of rapamycin (mTOR) through (Z)-BP were determined to synergize CIK cells in the presence of pembrolizumab and TMZ in recurrent GBM. Therefore, this well-tolerated regimen could simultaneously block multiple cancer pathways, which allowed extended PFS and improved quality of life for 22 months. Conclusion: Given the several unique functions of (Z)-BP, greater sensitivity of chemotherapy and the synergism of pembrolizumab and CIK cells could have affected the excellent prognosis seen in this patient with recurrent GBM.

Treating intracranial dural arteriovenous fistulas with gamma knife radiosurgery: A single-center experience.

OBJECTIVE: We evaluated the effectiveness and safety of gamma knife radiosurgery (GKRS) for the treatment of intracranial dural arteriovenous fistulas (dural AVFs) over the past 10 years. MATERIALS AND METHODS: The records of 21 patients diagnosed with dural AVFs between 2004 and 2014 and treated with GKRS were reviewed retrospectively. Complete obliteration (CO) was defined as total symptom relief plus confirmation through magnetic resonance imaging or conventional angiography. RESULTS: The median follow-up was 70.5 months (range 3-136 months). Five patients underwent embolization (2 after GKRS). One patient underwent GKRS twice. The CO rate was 47%, and partial to CO rate was 88%. The complete symptom resolution rate was 77%, and all patients achieved partial to complete symptom resolution. The CO rates for Borden Type I and Type II/III dural AVFs were 66.7% and 25% (P = 0.153), respectively, and complete symptom-free rates were 76.9% and 75.0% (P = 1.000%), respectively. The median duration between initial GKRS and complete symptom resolution was 14.3 months. The median treatment to image-free durations for Borden Type I and Type II/III dural AVFs were 25.9 and 60.4 months (P = 0.028), respectively, and treatment to symptom-free durations were 10.6 and 36.7 months (P = 0.103), respectively. One patient had a recurrent hemorrhage. Two patients experienced brain edema after stereotactic radiosurgery and one patient experienced cystic formation after GKRS. The morbidity rate was 19% (four patients) and there was no mortality. CONCLUSION: Treatment with GKRS for dural AVFs offers a favorable rate of obliteration. Patients with dural AVFs that are refractory or not amenable to endovascular or surgical therapy may be safely and effectively treated using GKRS.

Effect of an Anterior Cingulotomy on Pain, Cognition, and Sensory Pathways.

BACKGROUND: Anterior cingulotomy (AC) was originally used to treat patients with a psychiatric disorder, but it is also useful for treating patients with chronic intractable pain. We reviewed 24 patients at our hospital who underwent AC for chronic intractable pain to determine whether surgery influenced patient cognition and the pain circuit. METHODS: A visual analog scale (VAS) was used to evaluate patients' pain scale preoperatively, at 1 month and 3-6 months postoperatively, and at the final follow-up. Mini-Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI) were used to evaluate postoperative cognitive function. The latencies of peaks P20 and P37 of the somatosensory evoked potential (SSEP) conductive time were used to evaluate the intactness of the thalamocortical tract after AC. RESULTS: The median preoperative VAS score was 8, MMSE score was 27, and CASI score was 86.8. Six patients underwent a reoperation because of recurrent pain. Pain was significantly reduced after AC, and the median VAS score at the last follow-up was 5. There was no significant pain improvement in patients who underwent a reoperation. There were no significant changes in MMSE and CASI scores or SSEP after cingulotomy. There were no operation-related complications in the patients. CONCLUSIONS: A stereotactic AC was safe and effective in resolving chronic refractory pain. It did not affect patient cognition or the sensory conductive pathway. However, patients who had recurrent intractable pain after a cingulotomy did not respond well to the reoperation.

Upfront Gamma Knife Surgery for Giant Central Neurocytoma.

BACKGROUND: In this report, we present the results of using upfront Gamma Knife surgery (GKS) in the management of giant central neurocytoma (CNC) (volume >50 mL) without the initial removal of the tumor mass. CASE DESCRIPTIONS: Two patients underwent GKS for histologically proven CNC. Clinical and imaging studies were performed to evaluate the response to treatment. GKS involved delivery doses of 12 or 13 Gy to the tumor margin at the isodose line of 50%. Tumor response to GKS appeared as early as 4-6 months after GKS, at which point a dramatic reduction in volume was observed. No adverse effects of radiation or new neurologic deficits were observed in either of the cases. In case 1, we observed a reduction in tumor volume from 69 to 20 mL at 6 months and a further reduction to 10.3 mL at 86 months. In case 2, we observed a reduction in tumor volume from 62 to 31 mL at 4 months with a further reduction to 22.5 mL at 30 months. The female patient (case 1) showed mild weakness in the right lower limb after the minimal surgical removal of tumor using the cortical approach. No additional neurologic deficits were observed after GKS. The young male patient (case 2) presented a complete recovery without any signs of headache at 3 months after GKS. CONCLUSIONS: Based on this initial experience, it appears that GKS is an effective treatment for CNC and may be used for upfront management in cases of indolent clinical symptoms, even when the tumor is very large.

Prognostic factors of paranasal sinusitis with intracranial invasion: A 14-year review of cases at Hualien Buddhist Tzu Chi Hospital.

Intracranial invasion of paranasal sinusitis is an emergency condition that requires surgical and medical intervention in order to avoid further deterioration. We surveyed patients at the Buddhist Tzu Chi Hospital (Hualien, Taiwan) who had paranasal sinusitis with intracranial invasion. A total of 505 patients with paranasal sinusitis were surveyed at Hualien Buddhist Tzu Chi Hospital over a 14-year period (2000-2013). Data on clinical presentations, microbiology, host factors, postinterventional morbidity, and postinterventional mortality are presented. Of the 505 patients, nine had intracranial invasions (incidence rate, 1.8%). The mortality rate was high among these patients (44.4%, 4/9). Among the various risk factors identified, diabetes had the greatest influence (66.7%, 6/9), which in combination with an immunocompromised condition and cirrhosis is indicative of a poor prognosis.

Xylitol production from rice straw hemicellulose hydrolyzate by polyacrylic hydrogel thin films with immobilized Candida subtropicalis WF79.

Xylose from rice straw hemicellulose hydrolysate was fermented for xylitol production using Candida subtropicalis WF79 cells immobilized in polyacrylic hydrogel thin films of 200 mum thickness. Cell immobilization was conducted by first suspending the yeast cells in a mixture of 2-hydroxyethyl methacrylate (HEMA, hydrophilic monomer), polyethylene glycol diacrylate (PEG-DA, crosslinking agent), and benzoin isopropyl ether (photoinitiator). The mixture was then allowed to form polyacrylic hydrogel thin films, between two pieces of glass sheets, by UV-initiated photopolymerization. The hemicellulose of rice straw was hydrolyzed using dilute sulfuric acid at 126 degrees C. The hydrolysate was neutralized with calcium hydroxide. After separating the solid residues and calcium sulfate precipitates by filtration, the hydrolysate was treated with charcoal to partially remove potential inhibitory substances, followed by vacuum concentration to obtain solutions of desired xylose concentrations for yeast fermentation. The thin films with immobilized yeast cells were submerged in the xylose solution from rice straw hydrolysate for fermentation in an Erlenmeyer flask. The maximum yield was 0.73 g of xylitol per gram of xylose consumed. In the 52.5-day long durability test, after 40 d of repeated batchwise operation, the fermentation activities of the cell immobilized in thin films began to decline to a yield of 0.57 g/g at the end.