Genomic landscape of glioblastoma without IDH somatic mutation in 42 cases: a comprehensive analysis using RNA sequencing data.

PURPOSE: Glioblastoma is a malignant brain tumor with a poor prognosis. Genetic mutations associated with this disease are complex are not fully understood and require further elucidation for the development of new treatments. The purpose of this study was to comprehensively analyze genetic mutations in glioblastomas and evaluate the usefulness of RNA sequencing. PATIENTS AND METHODS: We analyzed 42 glioblastoma specimens that were resected in routine clinical practice and found wild-type variants of the IDH1 and IDH2 genes. RNA was extracted from frozen specimens and sequenced, and genetic analyses were performed using the CLC Genomics Workbench. RESULTS: The most common genetic alterations in the 42 glioblastoma specimens were TP53 mutation (28.6%), EGFR splicing variant (16.7%), EGFR mutation (9.5%), and FGFR3 fusion (9.5%). Novel genetic mutations were detected in 8 patients (19%). In 12 cases (28.6%), driver gene mutations were not detected, suggesting an association with PPP1R14A overexpression. Our findings suggest the transcription factors SOX10 and NKX6-2 are potential markers in glioblastoma. CONCLUSION: RNA sequencing is a promising approach for genotyping glioblastomas because it provides comprehensive information on gene expression and is relatively cost-effective.

Analysis of False-negative Findings of the Incomparable Accuracy and Swiftness of Flow Cytometric Diagnosis of Primary Central Nervous System Lymphoma.

Primary central nervous system lymphoma (PCNSL), a relatively rare brain tumor, bears a dire prognosis. On occasion, the rapid progression of the tumor makes immediate diagnosis and initiation of therapy imperative. To achieve swift diagnosis, we adopt flow cytometry (FCM) in addition to conventional histopathology. This study aimed to reveal the utility of FCM diagnosis for PCNSL and the cause of false-negative results of FCM diagnosis. We investigated 33 patients with suspected PCNSL on neuroradiological findings and received both FCM and histological diagnosis. The patients' electronic medical records were investigated, and histological findings, results of FCM, and other clinical data were evaluated. Overall, 27 patients (14 males and 13 females) were diagnosed with PCNSL by histological confirmation. The median age at diagnosis was 68 years. FCM analysis showed lymphoma pattern in 24 cases; however, FCM results did not show lymphoma pattern (sensitivity: 88.9%, specificity: 100%) in the other three lymphoma cases (FCM discordant: FCM-D) and six nonlymphomatous tumor cases. Analysis of FCM-D cases showed the infiltration of T lymphocytes or astrocytes into the tumor tissue, indicating tumor microenvironmental reaction; it is assumed that these reactions deceived FCM diagnosis. The survival of FCM-D patients was superior to FCM concordant counterpart, although the difference was not significant (p = 0.459). The diagnosis of PCNSL by FCM is rapid and highly reliable. Some FCM-D cases are PCNSLs with strong tumor microenvironmental reactions.

Strategy of carotid artery stenting as first-line treatment and carotid endarterectomy for carotid artery stenosis: A single-center experience.

Background: The main surgical options for stenosis of the carotid artery are carotid endarterectomy (CEA) and carotid artery stenting (CAS). The number of CAS procedures performed in Japan greatly exceeds that of CEA procedures. In this study, we used data from a single center to examine CAS and CEA for carotid artery stenosis. Methods: The subjects were patients with carotid artery stenosis who underwent CAS or CEA between January 2012 and May 2020. CAS was the first-choice treatment. CEA was used in cases with vulnerable plaques, a relatively low risk of general anesthesia, and no anatomical features disadvantageous for endarterectomy. Results: A total of 140 cases (102 CAS and 38 CEA) were examined. There were more elderly patients in the CAS group. The CEA group had a higher rate of vulnerable plaques and only one case with an unfavorable anatomy for CEA. Major adverse events (stroke) occurred in two CAS cases. In multivariate logistic analysis, postoperative ischemic lesions were independently associated with age (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.01-1.26, P = 0.026) and vulnerable plaque (OR = 5.54, 95% CI: 1.48-20.70, P = 0.011) in the CAS group, but not in the CEA group. Conclusion: The results reflect the treatment algorithm at our hospital, indicating that triage is accurate. Thus, it is beneficial to assign cases based primarily on plaque vulnerability and anatomical risk for CEA, and to not hesitate to perform CEA simply because of old age. CAS as first-line treatment and CEA are effective and safe, which reflect the treatment situation in Japan.

Genetic Alteration May Proceed with a Histological Change in Glioblastoma: A Report from Initially Diagnosed as Nontumor Lesion Cases.

Despite recent signs of progress in diagnostic radiology, it is quite rare that a glioblastoma (GBM) is detected asymptomatically. We describe two patients with asymptomatic nonenhancing GBMs that were not diagnosed with neoplasia at first. The patients had brain scans as medical checkups, and incidentally lesions were detected. In both cases, surgical specimens histopathologically showed no evidence of neoplasia, whereas molecular genetic findings were isocitrate dehydrogenase (IDH)-wildtype, O6-methylguanine-DNA methyltransferase promoter (pMGMT) unmethylated, and telomerase reverse transcriptase (TERT) promoter mutated, which matched to GBM. One patient was observed without adjuvant therapy and the tumor recurred 7 months later. Reoperation was performed, and histopathologically GBM was confirmed with the same molecular diagnosis as the first surgical specimen. Another patient was carefully observed, and chemoradiotherapy was begun 6 months after the operation following the extension of the lesion. Eventually, because of disease progression, both patients deceased. We postulate that in each case, the tumor was not lower-grade glioma but corresponded to the early growth phase of GBM cells. Thus far, cases of malignant transformation from lower-grade glioma or asymptomatic GBM with typical histologic features are reported. Nevertheless, to the best of our knowledge, no such case of nonenhancing, nonhistologically confirmed GBM was reported. We conjecture these cases shed light on the yet unknown natural history of GBM. GBM can take the form of radiological nonenhancing and histological nonneoplastic fashion before typical morphology. Molecular genetic analysis can diagnose atypical preceding GBM, and we recommend early surgical removal and adjuvant treatment.

Klebsiella invasive liver abscess syndrome presenting with a central nervous system manifestation secondary to latent cholecystitis: a case report.

BACKGROUND: Brain abscess is a life-threatening event. Moreover, when Klebsiella pneumoniae is the cause, rapid diagnosis and appropriate treatment are required. Klebsiella invasive liver abscess syndrome, a bloodstream metastatic infection of potentially aggressive nature, has been recognized to cause infection in the central nervous system, and concern for Klebsiella liver abscess syndrome is increasing globally. CASE PRESENTATION: A 73-year-old Japanese woman was admitted to the institution complaining of aggravated dysarthria and weakness in the right upper extremities with onset 5 days earlier. Magnetic resonance imaging revealed a brain abscess in the left basal ganglia, and abdominal computed tomography revealed a liver abscess in liver segment 7. The patient's dysarthria symptoms became increasingly worse over the next few days, so surgical drainage via frontotemporal craniotomy was performed on admission day 3, and subsequent culture from the brain abscess showed growth of Klebsiella pneumoniae. On admission day 9, percutaneous transhepatic drainage of the liver segment 7 abscess was undertaken. The pus culture also showed growth of Klebsiella pneumoniae, thus associating the liver abscess with the brain abscess. Following long-term conservative treatment with antibiotics and abscess drainage, the liver abscess disappeared. However, the patient continuously presented with right upper quadrant pain, and abdominal computed tomography showed swelling of the gallbladder. Consequently, percutaneous transhepatic gallbladder drainage was initially administered, and the bile culture was also positive for Klebsiella pneumoniae. For radical treatment, a laparoscopic cholecystectomy was performed on admission day 99. The postoperative period was complicated by an intraabdominal abscess; however, conservative therapy was successful. She was subsequently discharged, and 12-month follow-up revealed no further sequelae. CONCLUSIONS: We describe a rare case of Klebsiella liver abscess syndrome, which first presented with a central nervous system manifestation. Our patient was successfully treated via an early surgical intervention and subsequent antibiotic therapy. Although surgical drainage remains the cornerstone treatment for brain abscess, when a brain abscess is found, and there is a high index of suspicion for the existence of a liver abscess, Klebsiella liver abscess syndrome should be considered as a possible diagnosis.

Early rebleeding of a foramen magnum dural arteriovenous fistula: A case report and review of the literature.

Foramen magnum dural arteriovenous fistula (FM-DAVF) is a subset of craniocervical junction arteriovenous fistulas. We report a rare case of FM-DAVF with early rebleeding and review the literature. A 50-year-old man experienced 3 episodes of intracranial bleeding from a vessel malformation in the acute stage. We identified an FM-DAVF, supplied by multiple feeding arteries (eg, left ascending pharyngeal artery) that drained into the straight sinus and left superior petrosal sinus. The draining vein had venous varices. We performed transarterial feeder embolization and surgical disconnection of the DAVF. Early rebleeding of FM-DAVF is rare. High-risk patients require risk assessment and appropriate treatment as soon as possible in the acute stage.

Aplastic or Twig-Like Middle Cerebral Artery Presenting with Intracerebral Hemorrhage During Pregnancy: Report of Two Cases.

BACKGROUND: An aplastic or twig-like middle cerebral artery (Ap/T-MCA) is a rare congenital anomaly that can present with both ischemic and hemorrhagic stroke. The etiology of this pathology has remained unclear. Here, we report 2 cases of intracerebral hemorrhage (ICH) owing to an Ap/T-MCA in pregnant patients. CASE DESCRIPTION: In both patients, cerebral angiography revealed a steno-occlusive lesion and an abnormal arterial network on the unilateral middle cerebral artery. One patient was treated conservatively for a putaminal hemorrhage, and a cesarean section was performed uneventfully 6 months after onset of the ICH. The other patient underwent a craniotomy for evacuation of the lobar hemorrhage. Subsequently, a cesarean section was performed uneventfully. Both patients gradually recovered without significant disabilities. CONCLUSIONS: An Ap/T-MCA is a rare congenital anomaly and is a potential cause of ICH for pregnant patients. A cesarean section is a useful option for pregnant patients with this condition.

[Two Cases of Difficult-to-Treat Acute Epidural Hematoma and a Review of Decompressive Craniectomy with Hematoma Evacuation].

INTRODUCTION: Decompressive craniectomy(DC)with craniotomy for acute epidural hematoma(AEDH)removal is controversial. Here, we summarized two difficult AEDH cases where DC was performed. CASE 1:A 26-year-old man sustained a head injury in a bicycle accident, with a Japan Coma Scale(JCS)score of 200, right pupil mydriasis, and a left decerebrate posture on admission. Computed tomography(CT)revealed right AEDH with a midline shift. Craniotomy was performed without DC. Postoperatively, his consciousness level and anisocoria improved(JCS score, 30). Furthermore, no cerebral infarction was observed on CT at 9 h after surgery;however, at 48 h after surgery, a cerebral infarction with a mild midline shift was evident in the right hemisphere. His consciousness level deteriorated(JCS score, 100), and we initiated glyceol infusion. Worsening of the midline shift was apparent on CT 100 h after surgery;thus, DC was immediately performed. CASE 2:A 15-year-old boy was injured in a fall. On admission, his JCS score was 10. Immediately afterward, he showed neurological deterioration(JCS score, 200), right pupil mydriasis, and a left decorticate posture. CT revealed right AEDH with a midline shift;thus, craniotomy was performed with DC. On hospitalization day 10, he had orthostatic headache and a JCS score of 1. CT revealed paradoxical midline shift to the opposite side of craniotomy, and syndrome of the trephined was considered. He was placed in the Trendelenburg position until cranioplasty was performed on hospitalization day 18. CONCLUSION: Patients with AEDH presenting severe consciousness issues should undergo hematoma removal. Although DC is controversial, surgeons should administer intensive and prompt treatment according to the circumstance and should consider DC for appropriate AEDH cases.