Prognostic survival biomarkers of tumor-fused dendritic cell vaccine therapy in patients with newly diagnosed glioblastoma.

Dendritic cell (DC)-based immunotherapy has been applied to glioblastoma (GBM); however, biomarkers informing response remain poorly understood. We conducted a phase I/IIa clinical trial investigating tumor-fused DC (TFDC) immunotherapy following temozolomide-based chemoradiotherapy in patients with newly diagnosed GBM and determined prognostic factors in patients receiving TFDC immunotherapy. Twenty-eight adult patients with GBM isocitrate dehydrogenase (IDH) wild-type (IDH-WT) were enrolled; 127 TFDC vaccine injections (4.5 ± 2.6 times/patient) were administered. Patients with GBM IDH-WT had a respectable 5-year survival rate (24%), verifying the clinical activity of TFDC immunotherapy, particularly against O6-methylguanine-DNA methyltransferase (MGMT) unmethylated GBM (5-year survival rate: 33%). To identify novel factors influencing overall survival (OS) in GBM IDH-WT treated with TFDC immunotherapy, clinical parameters were assessed and comprehensive molecular profiling involving transcriptome and exome analyses was performed. MGMT promoter methylation status, extent of tumor resection, and vaccine parameters (administration frequency, DC and tumor cell numbers, and fusion ratio) were not associated with survival following TFDC immunotherapy. Old age and pre- and post-operative Karnofsky performance status were significantly correlated with OS. Low HLA-A expression and lack of CCDC88A, KRT4, TACC2, and TONSL mutations in tumor cells were correlated with better prognosis. We validated the activity of TFDC immunotherapy against GBM IDH-WT, including chemoresistant, MGMT promoter unmethylated cases. The identification of molecular biomarkers predictive of TFDC immunotherapy efficacy in GBM IDH-WT will facilitate the design of and patient stratification in a phase-3 trial to maximize treatment benefits.

Pentapeptide IIAEK ameliorates cholesterol metabolism via the suppression of intestinal cholesterol absorption in mice.

Dietary protein-derived peptides are effective in improving dyslipidemia and hypercholesterolemia. We previously identified a novel cholesterol-lowering pentapeptide IIAEK from milk beta-lactoglobulin. However, it remains unclear whether IIAEK affects the micellar solubility of cholesterol and the bile acid-binding ability to lower cholesterol. Moreover, there is no direct evidence that IIAEK inhibits intestinal cholesterol absorption and affects hepatic cholesterol and fecal steroid excretion in vivo. Herein, we showed that IIAEK did not affect the micellar solubility of cholesterol and the bile acid-binding ability. However, we found that IIAEK decreased serum and liver cholesterol levels and increased fecal steroid excretion in mice. Interestingly, IIAEK markedly suppressed the intestinal absorption of [3H]-cholesterol in mice. In conclusion, we found that IIAEK ameliorated cholesterol metabolism by suppressing intestinal cholesterol absorption without affecting in vitro micellar solubility of cholesterol and the bile acid-binding ability in mice.

Protamine-derived peptide RPR (Arg-Pro-Arg) ameliorates oleic acid-induced lipogenesis via the PepT1 pathway in HepG2 cells.

The protamine-derived peptide arginine-proline-arginine (RPR) can ameliorate lifestyle-related diseases such as obesity and hypercholesterolemia. Thus, we hypothesized that the hypolipidemic activity of RPR could attenuate events leading to non-alcoholic fatty liver disease. Addition of 2 m m oleic acid (OA) to the culture medium induced fatty liver conditions in HepG2 cells. The OA + RPR group showed significantly decreased cellular or medium triglyceride (TG) level compared with the OA group. Stearoyl-CoA desaturase-1 (SCD1) or sterol regulatory element-binding protein 1 (SREBP1) protein level was significantly lower in the OA + RPR group than in the OA group. In the R + P + R amino acid mixture-treated group, the TG level was not significantly different from that in the OA-treated group. The OA + RP- or OA + PR-treated groups showed significantly decreased cellular TG level compared with the OA group. Moreover, the effect of RPR disappeared when the peptide transporter 1 (PepT1) was knocked down with a siRNA. Collectively, our results demonstrated that RPR effectively ameliorated hepatic steatosis in HepG2 cells via the PepT1 pathway.

Pulse-frequency-dependent resonance in a population of pyramidal neuron models.

Stochastic resonance is known as a phenomenon whereby information transmission of weak signal or subthreshold stimuli can be enhanced by additive random noise with a suitable intensity. Another phenomenon induced by applying deterministic pulsatile electric stimuli with a pulse frequency, commonly used for deep brain stimulation (DBS), was also shown to improve signal-to-noise ratio in neuron models. The objective of this study was to test the hypothesis that pulsatile high-frequency stimulation could improve the detection of both sub- and suprathreshold synaptic stimuli by tuning the frequency of the stimulation in a population of pyramidal neuron models. Computer simulations showed that mutual information estimated from a population of neural spike trains displayed a typical resonance curve with a peak value of the pulse frequency at 80-120 Hz, similar to those utilized for DBS in clinical situations. It is concluded that a "pulse-frequency-dependent resonance" (PFDR) can enhance information transmission over a broad range of synaptically connected networks. Since the resonance frequency matches that used clinically, PFDR could contribute to the mechanism of the therapeutic effect of DBS.

Phase I/II trial of combination of temozolomide chemotherapy and immunotherapy with fusions of dendritic and glioma cells in patients with glioblastoma.

BACKGROUND: This trial was designed to evaluate the safety and clinical responses to a combination of temozolomide (TMZ) chemotherapy and immunotherapy with fusions of DCs and glioma cells in patients with glioblastoma (GBM). METHOD: GBM patients were assigned to two groups: a group of recurrent GBMs after failing TMZ-chemotherapy against the initially diagnosed glioma (Group-R) or a group of newly diagnosed GBMs (Group-N). Autologous cultured glioma cells obtained from surgical specimens were fused with autologous DCs using polyethylene glycol. The fusion cells (FC) were inoculated intradermally in the cervical region. Toxicity, progression-free survival (PFS), and overall survival (OS) of this trial were evaluated. Expressions of WT-1, gp-100, and MAGE-A3, recognized as chemoresistance-associated peptides (CAP), were confirmed by immunohistochemistry of paraffin-embedded tumor samples. Patient's PBMCs of pre- and post-vaccination were evaluated by tetramer and ELISPOT assays. RESULTS: FC-immunotherapy was well tolerated in all patients. Medians of PFS and OS of Group-R (n = 10) were 10.3 and 18.0 months, and those of Group-N (n = 22) were 18.3 and 30.5 months, respectively. Up-regulation and/or cytoplasmic accumulation of CAPs was observed in the recurrent tumors of Group-R patients compared with their initially excised tumors. Specific immune responses against CAPs were observed in the tetramer and ELISPOT assays. CONCLUSIONS: The combination of TMZ-treatment leading to up-regulation and/or cytoplasmic accumulation of CAPs, with FC-immunotherapy as a means of producing specific immunity against CAPs, may safely induce anti-tumor effects in patients with GBM.

Novel Enzyme Family Found in Filamentous Fungi Catalyzing trans-4-Hydroxylation of L-Pipecolic Acid.

Hydroxypipecolic acids are bioactive compounds widely distributed in nature and are valuable building blocks for the organic synthesis of pharmaceuticals. We have found a novel hydroxylating enzyme with activity toward L-pipecolic acid (L-Pip) in a filamentous fungus, Fusarium oxysporum c8D. The enzyme L-Pip trans-4-hydroxylase (Pip4H) of F. oxysporum (FoPip4H) belongs to the Fe(II)/α-ketoglutarate-dependent dioxygenase superfamily, catalyzes the regio- and stereoselective hydroxylation of L-Pip, and produces optically pure trans-4-hydroxy-L-pipecolic acid (trans-4-L-HyPip). Amino acid sequence analysis revealed several fungal enzymes homologous with FoPip4H, and five of these also had L-Pip trans-4-hydroxylation activity. In particular, the homologous Pip4H enzyme derived from Aspergillus nidulans FGSC A4 (AnPip4H) had a broader substrate specificity spectrum than other homologues and reacted with the L and D forms of various cyclic and aliphatic amino acids. Using FoPip4H as a biocatalyst, a system for the preparative-scale production of chiral trans-4-L-HyPip was successfully developed. Thus, we report a fungal family of L-Pip hydroxylases and the enzymatic preparation of trans-4-L-HyPip, a bioactive compound and a constituent of secondary metabolites with useful physiological activities.

Case of giant juvenile angiofibroma resected by external incision with temporary double balloon occlusion of the internal carotid artery by intraoperative endovascular treatment.

We report the first case of a juvenile nasal angiofibroma (JNA) fed by multiple arteries from the internal carotid artery (ICA), removed without complications by temporarily blocking the ICA with two balloons. An early adolescent with JNA underwent preoperative embolisation of feeding arteries arising from the external carotid artery (ECA) (University of Pittsburgh Medical Centre classification IV). Endoscopic resection was attempted once but discontinued due to massive bleeding (7000 mL). 17 months later, the JNA had grown to fill both nasal cavities. Repeated preoperative embolisation of the feeders from the ECA was performed, followed by surgery combined with endoscopic and external incision. Intraoperatively, two balloons were inserted into the right ICA, which were inflated at the proximal and distal sites of the feeder vessels to cut-off blood flow to the tumour. The tumour was almost completely resected with 6270 mL of blood loss and no postoperative neurological deterioration.

MMP2 and MMP9 are associated with the pathogenesis of recurrent pregnancy loss through protein expression rather than genetic polymorphism.

Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins and are important for placenta formation during early pregnancy. Recurrent pregnancy loss (RPL) is associated with abnormalities in endometrial extracellular matrix remodeling. This study aimed to elucidate the roles of MMP2 and MMP9 in RPL pathogenesis. In total, 295 women with a history of RPL and 101 controls were included in this genetic study. Genotype analysis was performed using polymerase chain reaction (PCR) restriction fragment length polymorphisms. For proteolytic analysis, decidua and villi were collected from 10 RPL-miscarried women with normal fetal chromosomes (NC) and 19 women with fetal chromosome aberrations (AC). The expression of MMP2 and MMP9 in the decidua and villi was measured by IHC and ELISA. All samples were collected after obtaining informed consent. There were no statistically significant differences in MMP2-735 C/T and MMP9-1562 C/T frequencies between women with RPL and the controls. There was no significant difference in MMP2 expression levels in the villi; however, MMP9 expression was significantly higher in normal fetal chromosomes. In the decidua, the expression of MMP2 in the NC group was significantly lower, and MMP9 in the NC group was significantly higher than in the AC group. Although no differences in MMP2-735 C/T and MMP9-1562 C/T gene polymorphisms were observed in the present study, it is suggested that differences at the protein level are involved in the pathogenesis of RPL since MMP expression is not only regulated by genes but also by local inflammation and various inductive signals.

Reduction of Tumor Biomarkers from very High to Normal and Extensive Metastatic Lesions to Undetectability in a Patient With Stage IV HER2-positive Breast Cancer Treated With Low-dose Trastuzumab Deruxtecan in Combination With Oral Recombinant Methioninase and a Low-methionine Diet.

BACKGROUND/AIM: Breast cancer is the most common and the deadliest cancer among women in the world. Treatment options for HER2-positive metastatic breast cancer patients are limited. Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate (ADC), has recently been introduced as second-line chemotherapy for HER2-positive metastatic breast cancer. The aim of the present study was to evaluate the efficacy of methionine restriction with oral recombinant methioninase (o-rMETase) and a low-methionine diet combined with T-DXd, on a patient with HER2-positive recurrent stage IV breast cancer. CASE REPORT: A 66-year-old female was diagnosed with HER2-positive metastatic breast cancer. Computed tomography (CT) indicated peritoneal dissemination, thickening of the sigmoid colon and splenic flexure and widespread bone metastases. The patient was previously treated with fulvestrant, trastuzumab, pertuzumab, paclitaxel and capecitabine which were ineffective. T-DXd was administered as a second-line chemotherapy. Since the patient experienced strong side effects, the dose of T-Dxd was decreased. The patient began methionine restriction using o-rMETase and a low-methionine diet along with T-DXd. After the start of the combined treatment, CA15-3 and CA27.29, tumor markers for breast cancer, decreased rapidly from a very high level. The levels of both tumor markers are currently normal. Additionally, peritoneal-dissemination nodules, ascites and the thickness of the sigmoid colon and splenic flexure are no longer detected on CT. The patient maintains a high performance status, without severe side effects of the combination treatment. CONCLUSION: Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with T-DXd as second-line chemotherapy, was highly effective in a patient with HER2-positive stage IV breast cancer.

Extensive Shrinkage and Long-term Stable Disease in a Teenage Female Patient With High-grade Glioma Treated With Temozolomide and Radiation in Combination With Oral Recombinant Methioninase and a Low-methionine Diet.

BACKGROUND/AIM: Gliomas are the most common and recalcitrant malignant primary brain tumors. All cancer types are addicted to methionine, which is a fundamental and general hallmark of cancer known as the Hoffman effect. Particularly glioma cells exhibit methionine addiction. Because of methionine addiction, [11C]-methionine positron emission tomography (MET-PET) is widely used for glioma imaging in clinical practice, which can monitor the extent of methionine addiction. Methionine restriction including recombinant methioninase (rMETase) and a low-methionine diet, has shown high efficacy in preclinical models of gliomas, especially in combination with chemotherapy. The aim of the present study was to determine the efficacy of methionine restriction with oral rMETase (o-rMETase) and a low-methionine diet, combined with radiation and temozolomide (TMZ), on a teenage female patient with high-grade glioma. CASE REPORT: A 16-year-old girl was diagnosed with high-grade glioma. Magnetic resonance imaging (MRI) showed a left temporal-lobe tumor with compression to the left lateral ventricle and narrowing of sulci in the left temporal lobe. After the start of methionine restriction with o-rMETase and a low-methionine diet, along with TMZ combined with radiotherapy, the tumor size shrunk at least 60%, with improvement in the left lateral ventricle and sulci. The patient's condition remains stable for 19 months without severe adverse effects. CONCLUSION: Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with radiation and TMZ as first-line chemotherapy, were highly effective in a patient with high-grade glioma.

The Combination of Methionine Restriction and Docetaxel Synergistically Arrests Androgen-independent Prostate Cancer But Not Normal Cells.

Background/Aim: Androgen-independent prostate cancer (AIPC) is resistant to androgen-depletion therapy and is a recalcitrant disease. Docetaxel is the first-line treatment for AIPC, but has limited efficacy and severe side-effects. All cancers are methionine-addicted, which is termed the Hoffman effect. Recombinant methioninase (rMETase) targets methionine addiction. The purpose of the present study was to determine if the combination of docetaxel and rMETase is effective for AIPC. Materials and Methods: The half-maximal inhibitory concentrations (IC50) of docetaxel and rMETase alone were determined for the human AIPC cell line PC-3 and Hs27 normal human fibroblasts in vitro. The synergistic efficacy for PC-3 and Hs27 using the combination of docetaxel and rMETase at their IC50s for PC-3 was determined. Results: The IC50 of docetaxel for PC-3 and for Hs27 was 0.72 nM and 0.94 nM, respectively. The IC50 of rMETase for PC-3 and for Hs27 was 0.67 U/ml and 0.76 U/ml, respectively. The combination of docetaxel and rMETase was synergistic for PC-3 but not Hs27 cells. Conclusion: The combination of a relatively low concentration of docetaxel and rMETase was synergistic and effective for AIPC. The present results also suggest that the effective concentration of docetaxel can be reduced by using rMETase, which may reduce toxicity. The present results also suggest the future clinical potential of the combination of docetaxel and rMETase for AIPC.

Targeting Methionine Addiction Combined With Low-dose Irinotecan Arrested Colon Cancer in Contrast to High-dose Irinotecan Alone, Which Was Ineffective, in a Nude-mouse Model.

BACKGROUND/AIM: Colorectal cancer (CRC) is the third-leading cause of death in the world. Although the prognosis has improved due to improvement of chemotherapy, metastatic CRC is still a recalcitrant disease, with a 5-year survival of only 13%. Irinotecan (IRN) is used as first-line chemotherapy for patients with unresectable CRC. However, there are severe side effects, such as neutropenia and diarrhea, which are dose-limiting. We have previously shown that methionine restriction (MR), effected by recombinant methioninase (rMETase), lowered the effective dose of IRN of colon-cancer cells in vitro. The aim of the present study was to evaluate the efficacy of the combination of low-dose IRN and MR on colon-cancer in nude mice. MATERIALS AND METHODS: HCT-116 colon-cancer cells were cultured and subcutaneously injected into the flank of nude mice. After the tumor size reached approximately 100 mm3, 18 mice were randomized into three groups; Group 1: untreated control on a normal diet; Group 2: high-dose IRN on a normal diet (2 mg/kg, i.p.); Group 3: low-dose IRN (1 mg/kg i.p.) on MR effected by a methionine-depleted diet. RESULTS: There was no significant difference between the control mice and the mice treated with high-dose IRN, without MR. However, low-dose IRN combined with MR was significantly more effective than the control and arrested colon-cancer growth (p=0.03). Body weight loss was reversible in the mice treated by low-dose IRN combined with MR. CONCLUSION: The combination of low-dose IRN and MR acted synergistically in arresting HCT-116 colon-cancer grown in nude mice. The present study indicates the MR has the potential to reduce the effective dose of IRN in the clinic.

[Intracranial malignant glioma presenting as subarachnoid hemorrhage].

Cerebral aneurysms are the predominant cause of spontaneous subarachnoid hemorrhage (SAH). However, if an aneurismal cause has been excluded, there remains but a short list of meningiomas or metastatic lesions as possible causes. This article details a case of neoplasm that presented exclusively with SAH. A 31-year-old male presented with a SAH with normal cerebral angiography. The initial magnetic resonance image (MRI) revealed a lesion in the left uncus thought to be recovering hemorrhage. Subsequent MRI, however revealed the mass to be expanding. A neuroendoscopical biopsy of the lesion established a diagnosis of glioblastoma. An affirmation is made that patients experiencing "angiographically-negative" SAH should undergo MRI, occasionally on a serial basis, to exclude other etiologies for hemorrhage, including neoplasma.

Real Stiffness and Vividness Reproduction of Anatomic Structures Into the 3-Dimensional Printed Models Contributes to Improved Simulation and Training in Skull Base Surgery.

BACKGROUND: Despite the advancement of 3-dimensional (3D) printing technology with medical application, its neurosurgical utility value has been limited to understanding the anatomy of bones, lesions, and their surroundings in the neurosurgical field. OBJECTIVE: To develop a 3D printed model simulating the surgical technique applied in skull base surgery (SBS), especially to reproduce visually the surgical field together with the mechanical properties of tissues as perceived by the surgeon through procedures performance on a model. METHODS: The Young modulus representing the degree of stiffness was measured for the tissues of anesthetized animals and printing materials. The stiffness and vividness of models were adjusted appropriately for each structure. Empty spaces were produced inside the models of brains, venous sinuses, and tumors. The 3D printed models were created in 7 cases of SBS planned patients and were used for surgical simulation. RESULTS: The Young modulus of pig's brain ranged from 5.56 to 11.01 kPa and goat's brain from 4.51 to 13.69 kPa, and the dura of pig and goat values were 14.00 and 24.62 kPa, respectively. Although the softest printing material had about 20 times of Young modulus compared with animal brain, the hollow structure of brain model gave a soft sensation resembling the real organ and was helpful for bridging the gap between Young moduli values. A dura/tentorium-containing model was practical to simulate the real maneuverability at surgery. CONCLUSION: The stiffness/vividness modulated 3D printed model provides an advanced realistic environment for training and simulation of a wide range of SBS procedures.

Rose polyphenols exert antiobesity effect in high-fat-induced obese mice by regulating lipogenic gene expression.

Obesity presents a major risk factor in the development of cardiovascular diseases. Recent reports indicate that many kinds of polyphenols have the potential to prevent metabolic diseases. We hypothesized that rose polyphenols (ROSE) have the effect of improvement in lipid metabolism. In this study, we investigated whether rose polyphenols affected lipid metabolism and exerted antiobesity. To clarify the mechanism, C57BL/6J mice were fed a high-fat diet containing 0.25% ROSE for 35 days. Compared with the control group, body weight gain and adipose tissue weight in the 0.25% ROSE group were significantly decreased. Serum cholesterol and hepatic triglyceride concentrations significantly decreased, whereas fecal triglyceride was significantly increased in the 0.25% ROSE group. Liver stearoyl-CoA desaturase 1 (Scd1), 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), and acyl-CoA:cholesterol acyltransferase 1 (Acat1) mRNA as well as protein stearoyl-CoA desaturase 1 concentrations were significantly lower in the 0.25% ROSE group than that in the control group. The mRNA and the protein concentrations of adipose triglyceride lipase, hormone-sensitive lipase, and peroxisomal acylcoenzyme A oxidase 1 in white adipose tissue were significantly higher in the 0.25% ROSE group than that in the control group. The components in rose polyphenols were quantified by liquid chromatography-tandem mass spectrometry, and we consider that ellagic acid plays an important role in an antiobesity effect because the ellagic acid content is the highest among polyphenols in rose polyphenols. In summary, rose polyphenols exhibit antiobesity effects by influencing lipid metabolism-related genes and proteins to promote lipolysis and suppress lipid synthesis.

Cervicovaginal microbiome in patients with recurrent pregnancy loss.

There have been few studies concerning an association between unexplained recurrent pregnancy loss (RPL) and the microbiome. A recent study including 67 patients demonstrated that an increase in Ureaplasma species in the endometrium raised the risk of miscarriage with an euploid karyotype. While endometrial sampling is invasive, cervicovaginal sampling is not. We compared vaginal and cervical microbiomes with a 16 S ribosomal RNA sequence between 88 patients with unexplained RPL and 17 healthy women with no history of miscarriage. We prospectively assessed risk factors for maternal colonization at a subsequent miscarriage without an aneuploid karyotype in patients. Cervicovaginal bacteria were dominated by Lactobacillus iners, Gardnerella vaginalis, Atopobium vaginae and Bifidobacterium breve in Japanese population. The proportions of Delftia and unknown bacteria in the cervix were significantly higher in patients with RPL than in controls. Streptococcus, Microbacterium, Delftia, Anaerobacillus and Chloroplast in the cervix were significantly higher in patients with a history of chorioamnionitis compared to the controls. The abundance of Cutibacterium and Anaerobacillus in the cervix was significantly higher in patients who had subsequently miscarried compared to those who gave birth. The miscarriage rate in patients with higher proportions of both Cutibacterium and Anaerobacillus (66.7%, 2/3) was significantly greater than that of patients who lacked these bacteria (9.2%, 6/65, adjusted odds ratio 16.90, 95% confidence interval 1.27-225.47, p = 0.032). The presence of certain bacteria could be a predictor of subsequent miscarriage without an aneuploid karyotype. The cervicovaginal microbiome might be useful for investigating a possible cause of RPL.

Lynch syndrome-associated chordoma with high tumor mutational burden and significant response to immune checkpoint inhibitors.

Chordoma is a rare malignant bone tumor arising from notochordal tissue. Conventional treatments, such as radical resection and high-dose irradiation, frequently fail to control the tumor, resulting in recurrence and re-growth. In this study, genetic analysis of the tumor in a 72-year-old male patient with refractory conventional chordoma of the skull base revealed a high tumor mutational burden (TMB) and mutations in the MSH6 and MLH1 genes, which are found in Lynch syndrome. The patient and his family had a dense cancer history, and subsequent germline genetic testing revealed Lynch syndrome. This is the first report of a chordoma that has been genetically proven to be Lynch syndrome. Chordomas usually have low TMB; however, this is an unusual case, because the TMB was high, and immune checkpoint inhibitors effectively controlled the tumor. This case provides a basis for determining the indications for immunotherapy of chordoma based on the genetic analysis. Therefore, further extensive genetic analysis in the future will help to stratify the treatment of chordoma.

Fully-Endoscopic Resection of Deep-Seated Pilocytic Astrocytoma Under 5-Aminolevulinic Acid Fluorescence Guidance: A Technical Note.

AIM: To improve the extent and safety of resecting these deep-seated tumors, we report a novel procedure of minimally invasive endoscopic resection of deep-seated pilocytic astrocytomas under the guidance of 5-aminolevulinic acid (5-ALA) fluorescence undescribed until now. CASE DESCRIPTION: A 53-year-old male presented with a gradually progressing mild right hemiparesis. Imaging studies showed a solid tumor with degenerative cystic formation in the left basal ganglia. The tumor was removed endoscopically via right frontal small craniotomy. The tumor was positive for 5-ALA fluorescence and allowed better detection of the dissection margin of the solid tumor from the surrounding brain tissue. The histopathological diagnosis was pilocytic astrocytoma. No recurrence was observed on follow-up magnetic resonance imaging (MRI) 2 years after surgery, and the patient was fully independent after rehabilitation. CONCLUSION: This minimally invasive technique, enhanced by intraoperative fluorescence, might be a safe and feasible alternative to open surgery in the removal of deeply located gliomas.

Optimal Multiple-Layered Anterior Skull Base Reconstruction Using a 360° Suturing Technique.

BACKGROUND: Advances in technique and instrumentation have improved outcomes after resection of anterior skull base tumors. However, cerebrospinal fluid (CSF) leak occurs in 4%-20% of patients. To reduce the risk of CSF leak, we have developed a novel reconstruction technique that consists of a 4-layered graft with patchwork suturing and hard material. OBJECTIVE: To evaluate the effectiveness of this reconstruction technique when used for resection of anterior skull base tumors. METHODS: This case series included 59 patients with anterior skull base tumors in whom the 4-layered closure technique was used. The main outcome measures were complications, including CSF leak, meningitis, postoperative bleeding, and infection. RESULTS: There were no CSF leak cases or serious complications after closure of the anterior skull base using the 4-layered technique. CONCLUSION: Closure of the anterior skull base in 4 layers prevented CSF leak and was not associated with any serious complications. However, further studies in larger numbers of patients are needed to confirm our outcomes using this closure method.