Endoscopic transsphenoidal surgery using pedicle vascularized nasoseptal flap for cholesterol granuloma in petrous apex: A technical note

Background Compared with surgical resection, endoscopic transsphenoidal surgery (TSS) for cholesterol granuloma (CG) in the petrous apex (PA) is associated with local recurrence due to obstruction of the drainage route. We present a detailed procedure of an endoscopic TSS using pedicle vascularized nasoseptal flap (PVNF). Methods A 40-year-old woman with a history of repeated surgery for left tympanitis was referred to our institution. Neurological examination revealed severe hearing loss in the left ear. Radiologic examination presented a round mass in the left PA and significant fluid collection in the mastoid air cells of the left temporal bone. CG was strongly suspected, and endoscopic TSS using PVNF was performed. Prior to endoscopic drainage, a PVNF was harvested from the mucosa of the ipsilateral nasal septum, with an attempt to preserve the sphenopalatine artery in the flap. Following this, puncture and adequate irrigation of the lesion was performed by endoscopic TSS, with neuro-navigation system assistance; the apex of PVNF was then placed into the lesion to prevent the obstruction of the drainage route. An absorbable polyglycolic acid sheet and fibrin glue were applied on the flap to prevent spontaneous deviation from the lesion. Results The patient was discharged without any further neurological complications. Eight-month postoperative computed tomography images showed no recurrence; the drainage route was patent and the fluid collection in the left mastoid air cells was resolved. Moreover, hearing loss was improved. Conclusions Endoscopic TSS using PVNF may be one of available surgical options for PACG

Reversal of cancer gene expression identifies repurposed drugs for diffuse intrinsic pontine glioma

Diffuse intrinsic pontine glioma (DIPG) is an aggressive incurable brainstem tumor that targets young children. Complete resection is not possible, and chemotherapy and radiotherapy are currently only palliative. This study aimed to identify potential therapeutic agents using a computational pipeline to perform an in silico screen for novel drugs. We then tested the identified drugs against a panel of patient-derived DIPG cell lines. Using a systematic computational approach with publicly available databases of gene signature in DIPG patients and cancer cell lines treated with a library of clinically available drugs, we identified drug hits with the ability to reverse a DIPG gene signature to one that matches normal tissue background. The biological and molecular effects of drug treatment was analyzed by cell viability assay and RNA sequence. In vivo DIPG mouse model survival studies were also conducted. As a result, two of three identified drugs showed potency against the DIPG cell lines Triptolide and mycophenolate mofetil (MMF) demonstrated significant inhibition of cell viability in DIPG cell lines. Guanosine rescued reduced cell viability induced by MMF. In vivo, MMF treatment significantly inhibited tumor growth in subcutaneous xenograft mice models. In conclusion, we identified clinically available drugs with the ability to reverse DIPG gene signatures and anti-DIPG activity in vitro and in vivo. This novel approach can repurpose drugs and significantly decrease the cost and time normally required in drug discovery

Distinct TERT promoter C228T and C250T mutations in a patient with an oligodendroglioma : A case report

The majority of oligodendroglial tumors harbor mutations in the telomerase reverse transcriptase (TERT) gene (TERT) promoter and the isocitrate dehydrogenase 1/2 (IDH1/2) gene (IDH1/2), as well as 1p/19q codeletion. Generally, TERT promoter mutations, C250T and C228T, are mutually exclusive. We present a case of oligodendroglioma harboring both C250T and C228T mutations in TERT promoter. A 38-year-old man presented with grand mal seizures and underwent a resection surgery for a left frontal lobe tumor. He was pathologically diagnosed as having oligodendroglioma and was carefully observed. At 48 years of age, he underwent another resection surgery due to tumor regrowth, with the pathological diagnosis of anaplastic oligodendroglioma. Genetic analysis of the initial tumor specimen revealed IDH1 R132H mutation and both C250T and C228T mutations in TERT promoter. Using mutation-specific primers, two mutations were considered to be distributed in different alleles. In the tumor specimen obtained during the second surgery, IDH1 R132H mutation was detected to be similar to that of the initial specimen; however, only C228T mutation was detected in TERT promoter. The 1p/19q codeletion was detected in both the initial and recurrent tumor specimens. According to the sequencing data from the two tumor specimens, although TERT promoter mutation has been considered to be an early genetic event in the tumorigenesis of oligodendroglial tumors, it is likely that the C250T and C228T mutations in TERT promoter are subclonally distributed in the same tumor specimen of the present case

Simplified Dural Reconstruction Procedure Using Biocompatible Polyglycolic Acid Felt with Autologous Abdominal Fat Grafts after a Transpetrosal Approach

BACKGROUND: Dural reconstruction after transpetrosal approaches is complicated because complete primary closure of presigmoid dura mater is difficult to achieve. To address this problem, we use biocompatible polyglycolic acid (PGA) felt (Durawave) to reconstruct dural defects. To evaluate the use of PGA felt in dural reconstruction, we compared these results with those after conventional duraplasty using autologous fascia grafts. METHODS: We retrospectively surveyed all cases involving a transpetrosal approach reported since 2013. In the conventional procedure, autologous fascia was fixed over the dural defect using stay sutures; any remaining dead space was obliterated by placing abdominal fat grafts. Since April 2017, we have used PGA felt instead of fascia. RESULTS: Of the 37 cases identified, 27 were reconstructed according to the conventional procedure, and the remaining 10 cases were reconstructed using PGA felt. Among the 27 conventional cases, 8 involved cerebrospinal fluid (CSF)-related complications, including 3 cases of rhinorrhea and 5 cases of subcutaneous fluid collection, and 2 cases (7%) required repair surgery. Of the 10 cases involving PGA felt, 1 case (10%) involved subcutaneous fluid collection and required repair surgery, and whereas the remaining 9 cases had no evidence of CSF leakage. In addition, the median dural reconstruction time using PGA felt was 9 minutes, significantly shorter than that when autologous fascia was used (median, 44 minutes). CONCLUSIONS: Using PGA felt for presigmoid dura simplifies dural reconstruction because it obviates the need to suture in a deep field. PGA felt has the potential to prevent CSF-related complications after transpetrosal approaches

Reliability of the Size Evaluation Method for Meningiomas : Maximum Diameter, ABC/2 Formula, and Planimetry Method

Background: To evaluate the accuracy of tumor size by maximum diameter, ABC/2 formula, and planimetry method using thick-slice and thin-slice magnetic resonance imaging (MRI). Methods: Maximum diameter and tumor volume calculated using ABC/2 formula (V1) and planimetry method with thick-slice MRI (V2) and thin-slice MRI (V3) were examined in 83 meningiomas. Form factor (FF) analysis was performed to assess irregularity of the tumor. V3 values were considered as real tumor volumes. The accuracy of V1 and V2 was evaluated using ratio and difference from V3. Meningiomas were categorized by tumor locations: skull base (anterior, middle, and posterior) and non-skull base (calvaria and other sites). Results: Correlation between maximum diameter and V3 was statistically significant (r = 0.91), but the error was significant in tumors with longer maximum diameters. Correlation between V1 and V3 was significant (r = 0.97). However, V1 tended to be larger in middle skull base meningiomas or in tumors with low FF values (R2 = 0.21). V2 represented relatively accurate volumes in both groups except in the case of small meningiomas. When tumors were demonstrated within 3 fractions on thick-slice MRI, the ratio of V2 to V3 showed significant variability. Conclusions: Using the ABC/2 formula, the volume of meningiomas in the middle skull base or meningiomas with low FF value might be calculated larger than the real tumor volume. The planimetry method with thick-slice MRI demonstrated relatively accurate volumes if the tumor was fractionated in >4 slices

Endoscopic transsphenoidal surgery using pedicle vascularized nasoseptal flap for cholesterol granuloma in petrous apex : A technical note

Background: Compared with surgical resection, endoscopic transsphenoidal surgery (TSS) for cholesterol granuloma (CG) in the petrous apex (PA) is associated with local recurrence due to obstruction of the drainage route. We present a detailed procedure of an endoscopic TSS using pedicle vascularized nasoseptal flap (PVNF). Methods: A 40-year-old woman with a history of repeated surgery for left tympanitis was referred to our institution. Neurological examination revealed severe hearing loss in the left ear. Radiologic examination presented a round mass in the left PA and significant fluid collection in the mastoid air cells of the left temporal bone. CG was strongly suspected, and endoscopic TSS using PVNF was performed. Prior to endoscopic drainage, a PVNF was harvested from the mucosa of the ipsilateral nasal septum, with an attempt to preserve the sphenopalatine artery in the flap. Following this, puncture and adequate irrigation of the lesion was performed by endoscopic TSS, with neuro-navigation system assistance; the apex of PVNF was then placed into the lesion to prevent the obstruction of the drainage route. An absorbable polyglycolic acid sheet and fibrin glue were applied on the flap to prevent spontaneous deviation from the lesion. Results: The patient was discharged without any further neurological complications. Eight month postoperative computed tomography images showed no recurrence; the drainage route was patent and the fluid collection in the left mastoid air cells was resolved. Moreover, hearing loss was improved. Conclusions: Endoscopic TSS using PVNF may be one of available surgical options for PACG

Application of endoscopic ultrasonography to intraventricular lesions

Background: Anatomical landmarks such as choroid plexus and foramen of Monro are very important to undergo intraventricular surgery safely and effectually. These landmarks would be unclear in cases with a huge cyst or repeat surgery. We report the usability and precautions to apply a bronchoscope with an ultrasonic convex probe to intraventricular surgery. Methods: Two patients diagnosed with obstructive hydrocephalus, one with a large cyst and the other with recurrent craniopharyngioma in the third ventricle, were applied to the EBUS system. Results: In both patients, the EBUS system was applied safely, and lesions beyond the wall of ventricles or the cyst were visible. Color Doppler ultrasonography detected choroid plexus and internal cerebral veins. Furthermore, we performed real-time ultrasound-guided cyst puncture safely on the case with a large cyst. The most important precaution is that the curved portion of the EBUS system is too long to be bent within cerebral ventricles. Conclusions: The new EBUS system with an ultrasonic convex probe is a novel and effectual device to perform intraventricular surgery

Identification of PEPT2 as an important candidate molecule in 5-ALA-mediated fluorescence-guided surgery in WHO grade II/III gliomas

Purpose5-aminolevulinic acid (5-ALA) fluorescence-guided surgery (FGS) appears to be a promising treatment for glioma. However, 5-ALA-mediated fluorescence cannot always be detected in grade II/III gliomas. We hypothesized that gene expression patterns in the Protoporphyrin IX (PpIX) synthesis pathway may be associated with intraoperative fluorescence status of grade II/III gliomas, and then attempted to identify the key molecule of 5-ALA-mediated fluorescence.MethodsUsing 50 surgically obtained specimens, which were diagnosed as grade II and III gliomas, we analyzed gene expression within the PpIX synthesis pathway to identify candidate molecules according to intraoperative 5-ALA-mediated fluorescence status. The most likely candidate gene was selected and confirmed by protein expression analysis. To evaluate the biological function of the molecule in PpIX synthesis, functional analysis was performed using specific, small interference (si)RNA in the SW-1783human grade III glioma cell line.ResultsAmong the genes involved in the porphyrin synthesis pathway, the mRNA expression of Peptide transporter 2 (PEPT2) in FGS fluorescence-positive gliomas was significantly higher than that in fluorescence-negative gliomas. Protein expression of PEPT2 was also significantly higher in the fluorescence-positive gliomas, which was confirmed by western blot analysis and immunofluorescence analysis. The siRNA-mediated downregulation of the mRNA and protein expression of PEPT2 led to decreased PpIX fluorescence intensity, as confirmed by fluorescence spectrum analysis.ConclusionsThe results suggest PEPT2 is an important candidate molecule in 5-ALA-mediated FGS in grade II/III gliomas. As the overexpression of PEPT2 was associated with higher PpIX fluorescence intensity, PEPT2 may improve fluorescence-guided resection in grade II/III gliomas

Diencephalic pediatric low-grade glioma harboring the BRAF V600E mutation presenting with various morphologies in sequential biopsy specimens

A 5-year-old boy underwent biopsy of an intra-axial calcified tumor in the hypothalamus, which was incidentally found. Based on the presence of ganglion-like cells combined with glial cell element, the pathological diagnosis was ganglioglioma. Because the tumor grew gradually in size over the next 2 years, he underwent chemotherapy with temozolomide. However, at 8 years of age, the boy developed hydrocephalus and the cystic lesion had re-grown. Endoscopic cyst fenestration and tumor biopsy was performed, and pathological diagnosis was tentatively oligodendroglioma based on the presence of tumor cells with a perinuclear halo. At 10 years of age, hydrocephalus recurred and the cystic lesion had re-grown. A second round of endoscopic cyst fenestration and tumor biopsy led to a pathological diagnosis of pilocytic astrocytoma due to a biphasic appearance with areas of dense tumor cells and microcystic areas, tumor cells with eosinophilic processes, and the presence of an eosinophilic granular body. Genetic analysis of the first biopsy successfully identified the BRAF V600E mutation. Because pathological diagnosis of diencephalic low-grade glioma harboring BRAF V600E would be sometimes difficult due to pathological variations, pathological diagnosis should be performed under the consideration of molecular diagnosis of BRAF V600E for optimal diagnosis and treatment

Successful Removal of a Metastatic Gastrointestinal Stromal Tumor in the Craniovertebral Junction using an Occipital Artery to Posterior Inferior Cerebellar Artery Bypass

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms arising from the gastrointestinal tract. The authors present a case of the successful removal of a metastatic GIST in the craniovertebral junction, using an occipital artery to posterior inferior cerebellar artery (OA-PICA) bypass. The patient is a 54-year-old male who underwent his first surgery for a small-bowel tumor at the age of 45 and was diagnosed with GIST. Nine years after his primary diagnosis, the patient suffered from severe neck pain. MRI demonstrated a large demarcated mass adjacent to the right atlas. The right vertebral artery (VA), completely engulfed by the tumor, showed a narrowing and ended in the PICA. Poor collateral blood supply in the right PICA territory was presumed. To prevent ischemic complications, an OA-PICA bypass was performed prior to the tumor resection. After the OA-PICA bypass, the tumor associated with the right VA was successfully removed, and the patient was discharged without any neurological deficits