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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Anti-Obesity and Hypocholesterolemic Actions of Protamine-Derived Peptide RPR (Arg-Pro-Arg) and Protamine in High-Fat Diet-Induced C57BL/6J Mice.

Dietary protamine can ameliorate hyperlipidemia; however, the protamine-derived active peptide and its hypolipidemic mechanism of action are unclear. Here, we report the discovery of a novel anti-obesity and hypocholesterolemic peptide, RPR (Arg-Pro-Arg), derived from protamine in mice fed a high-fat diet for 50 days. Serum cholesterol levels were significantly lower in the protamine and RPR groups than in the control group. White adipose tissue weight was significantly decreased in the protamine and RPR groups. The fecal excretion of cholesterol and bile acid was significantly higher in the protamine and RPR groups than in the control group. We also observed a significant decrease in the expression of hepatic SCD1, SREBP1, and adipocyte FAS mRNA, and significantly increased expression of hepatic PPARα and adipocyte PPARγ1 mRNA in the protamine group. These findings demonstrate that the anti-obesity effects of protamine are linked to the upregulation of adipocyte PPARγ1 and hepatic PPARα and the downregulation of hepatic SCD1 via SREBP1 and adipocyte FAS. RPR derived from protamine has a crucial role in the anti-obesity action of protamine by evaluating the effective dose of adipose tissue weight loss.

Visualization of extracranial-intracranial bypass in moyamoya patients using intraoperative three-dimensional digital subtraction angiography with intravenous contrast injection and robotic C-arm: patient series.

BACKGROUND: The authors describe a noninvasive intraoperative imaging strategy of three-dimensional (3D) digital subtraction angiography (DSA) with intravenous (IV) contrast injection, using indocyanine green (ICG) as a test bolus, during extracranial-intracranial (EC-IC) bypass surgery for moyamoya disease. OBSERVATIONS: Four patients underwent EC-IC bypass surgery in a hybrid operating room. During the surgery, bypass patency was verified using ICG videoangiography and Doppler ultrasonography. After skin closure, the patients under anesthesia underwent IV 3D-DSA with a robotic C-arm in which the scan delay time for the 3D-DSA scan was estimated from the arrival time of ICG during the ICG videoangiography. One day after the surgery, the patients underwent magnetic resonance angiography (MRA). The IV 3D-DSA images were retrospectively compared with those obtained with other modalities. Good bypass patency was confirmed on IV 3D-DSA, ICG videoangiography, Doppler ultrasonography, and postoperative MRA in all cases. The delay time determined using ICG videoangiography as a test bolus resulted in IV 3D-DSA with adequate image quality, allowing assessment of the spatial relationships between the vessels and anastomoses from all directions. LESSONS: To evaluate bypass patency and anatomical relationships immediately after EC-IC bypass surgery, IV 3D-DSA may be a useful modality. ICG videoangiography can be used to determine the scan delay time.

Advanced Endoscopic Endonasal Approach to the Pterygopalatine Fossa and Orbit: The Endoscopic Tri-port Approach.

Objective The pterygopalatine fossa (PPF) is a narrow space situated posterior to the maxillary sinus. While external approaches have been used to treat tumors of the PPF, recent endoscopic approaches have become favored as an alternative; we developed an endoscopic tri-port approach, which provides wide surgical corridor with minimal invasion, for PPF. This report aims to introduce and verify the new approach. Design Case series. Setting A tertiary referral hospital. Participants We reviewed 11 patients with PPF or orbital tumors who were treated with the endoscopic tri-port approach. Main Outcome Measures Accessing tri-port approach's effects and limitations. Results When the tumor was located in the PPF or orbit without intracranial invasion, en bloc resection was achieved in six patients. With the exception of one patient, the nasal septum was preserved if not used for skull base reconstruction. If not invaded by a tumor or necessary for reconstruction, the inferior and middle turbinates were preserved. Conclusion The endoscopic tri-port approach provides an excellent surgical view and wide corridor and not requires an external approach, including a gingival incision.

Differentiating between glioblastomas with and without isocitrate dehydrogenase gene mutation by findings on conventional magnetic resonance images.

Various studies using advanced techniques have estimated the isocitrate dehydrogenase (IDH) gene mutation status in glioblastoma (GBM) from preoperative images. However, it is important to be able to predict mutation status using conventional MRI, which is more widely used in clinical practice. In this study, we examined the features of GBM with and without IDH gene mutation on conventional MRI. Twenty-three patients with GBM in whom IDH gene mutation status had been pathologically and molecularly confirmed in tumor specimens were included. The cases were divided into an IDH-wildtype group (n = 17) and an IDH-mutant group (n = 6). We retrospectively compared the following imaging parameters between the two groups: tumor location (superficial or deep), borders on T2-weighted images (regular or irregular), borders of enhancing lesions (regular or irregular), number of lesions showing contrast enhancement (solitary or multiple), presence or absence of intralesional bleeding, and presence or absence of a low-grade glioma in the background around the enhancing lesion. IDH-wildtype tumors were significantly more likely to be superficial than were IDH-mutant tumors (p < 0.05). Enhancing lesions in the IDH-wildtype group were less likely to have an irregular border (p = 0.059). Low-grade glioma was a background lesion in 5 patients (83.3%) in the IDH-mutant group and 9 (52.9%) in the IDH-wildtype group. The IDH mutation status is likely to be wildtype in patients with superficial GBM in which the enhancing lesion has a regular border and when low-grade glioma is not found as a background lesion on MRI.

A Compendium of Modern Minimally Invasive Intracerebral Hemorrhage Evacuation Techniques.

BACKGROUND: Minimally invasive intracerebral hemorrhage (ICH) evacuation has gained popularity with success in early-phase clinical trials. This procedure, however, is performed in very different ways around the world. OBJECTIVE: To provide a technical description of these strategies that facilitates comparison and aids decisions in which surgery to perform, and to inform further improvements in minimally invasive ICH evacuation. METHODS: Major authors of clinical trials evaluating each of the main techniques were contacted and asked to supply a case example and technical description of their respective surgeries. RESULTS: Five major techniques are presented including stereotactic thrombolysis, craniopuncture, endoscopic, endoscope-assisted, and endoport-mediated. Techniques differ in numerous ways including the size of the cranial access, the size of the access corridor through the brain to the hematoma, and the evacuation strategy. Regarding cranial access, a burr hole is created in stereotactic thrombolysis and craniopuncture, a small craniectomy in endoscopic, and a small craniotomy in the other 2. Access corridors through the parenchyma range from 3 mm in craniopuncture to 13.5 mm in the endoport-mediated evacuation. Regarding evacuation strategies, stereotactic thrombolysis and craniopuncture rely on passive drainage from a catheter placed during surgery that remains in place for multiple days, while the other 3 techniques rely on active evacuation with suction and bipolar cautery. CONCLUSION: Future comparative clinical trials may identify the advantageous components of each strategy and contribute to improved outcomes in this patient population.