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.

A Case of Multifocal Ectopic Germinoma Manifesting with Medial Longitudinal Fasciculus Syndrome.

Introduction: Intracranial germinomas mainly arise in the pineal gland or neurohypophyseal region. The basal ganglia have been reported as the site of occurrence for ectopic germinomas, whereas other sites have been rarely described. We experienced a case of multifocal ectopic germinoma that arose in the septum pellucidum and the dorsal brain stem, not including the pineal gland, neurohypophysis, and basal ganglia of ectopic germinoma in a pregnant woman. Case Presentation: The patient initially presented to our institution with complaints of diplopia in the past 14 weeks of gestation, and imaging later revealed two intracranial neoplastic lesions, with one lesion involving the septum pellucidum and the other involving the dorsal brainstem. Both tumors were partially excised via a transcortical approach. Based on the results of pathology and immunohistochemistry, the patient was diagnosed with germinoma, and the intraoperative spinal fluid cytology was class V in Papanicolaou classification. The patient received three courses of ifosfamide, carboplatin, and etoposide together with whole-brain irradiation, which resulted in complete elimination of the tumors. No evidence of recurrence was identified after 18 months. Conclusion: The results illustrated the need to consider germinoma in the differential diagnosis if the lesions involve midline structures such as the septum pellucidum or dorsal brainstem. Given the rarity of germinoma arising outside the pineal gland and neurohypophyseal region, these findings provide key insights into the diagnosis and treatment of this disease.

Two Cases of Atypical Teratoid/Rhabdoid Tumor in the Spinal Cord: Loss of SMARCB1 in a Child and Loss of SMARCA4 in an Adult.

We compare two cases of primary spinal atypical teratoid/rhabdoid tumor (AT/RT), which rarely occurs in adults marked by SMARCA4 inactivation, and SMARCB1 inactivation for pediatric cases. AT/RT represents a highly malignant neoplasm comprising poorly differentiated constituents and rhabdoid cells, with SMARCB1(INI1) or infrequently SMARCA4 (BRG1) inactivation. These tumors are predominantly found in children but are rare in adults. While AT/RT can arise anywhere in the central nervous system, spinal cord localization is comparatively scarce. Despite mutation or loss of SMARCB1 at the 22q11.2 locus serving as the genetic hallmark of AT/RTs, infrequent cases of SMARCA4 inactivation with intact SMARCB1 protein expression are significant. We present each case of primary spinal tumors in a child and an adult, showing loss of the SMARCB1 and SMARCA4 proteins, respectively. Both tumors met the AT/RT diagnostic criteria. The histopathology demonstrated the presence of rhabdoid cells in both cases. Diagnosing primary spinal AT/RT with SMARCB1 protein loss remains a challenge. Nevertheless, the presence of SMARCB1 positivity alone must be noted to be insufficient to exclude the possibility of AT/RT diagnosis. In cases in which the diagnosis of AT/RT is highly suspected clinically, additional testing is warranted, including SMARCA4 analysis.

Dexamethasone-sparing on days 2-4 with combined palonosetron, neurokinin-1 receptor antagonist, and olanzapine in cisplatin: a randomized phase III trial (SPARED Trial).

BACKGROUND: This study evaluated the non-inferiority of dexamethasone (DEX) on day 1, with sparing on days 2-4 in cisplatin-based chemotherapy. METHODS: Patients with malignant solid tumors who were treated with cisplatin (≥50 mg/m²) were randomly assigned (1:1) to receive either DEX on days 1-4 (Arm D4) or DEX on day 1 (Arm D1) plus palonosetron, NK-1 RA, and olanzapine (5 mg). The primary endpoint was complete response (CR) during the delayed (24-120 h) phase. The non-inferiority margin was set at -15%. RESULTS: A total of 281 patients were enrolled, 278 of whom were randomly assigned to Arm D4 (n = 139) or Arm D1 (n = 139). In 274 patients were included in the efficacy analysis, the rates of delayed CR in Arms D4 and D1 were 79.7% and 75.0%, respectively (risk difference -4.1%; 95% CI -14.1%-6.0%, P = 0.023). However, patients in Arm D1 had significantly lower total control rates during the delayed and overall phases, and more frequent nausea and appetite loss. There were no significant between-arm differences in the quality of life. CONCLUSION: DEX-sparing is an alternative option for patients receiving cisplatin; however, this revised administration schedule should be applied on an individual basis after a comprehensive evaluation. CLINICAL TRIALS REGISTRY NUMBER: UMIN000032269.

Clinical Significance of Stiffness during Endoscopic Surgery for Intracerebral Hemorrhage: A Retrospective Study.

Studies regarding hematoma stiffness and removal difficulty are scarce. This study explored the association between hematoma stiffness and surgical results of endoscopic hematoma removal for intracerebral hemorrhage. It also aimed to clarify factors associated with hematoma stiffness. We classified intracerebral hematoma as either soft or firm stiffness by retrospectively evaluating operative videos by two neurosurgeons. The interobserver reliability of the classification was assessed by calculating the κ values. We investigated the relationship between hematoma stiffness and surgical results. Favorable hematoma removal (FHR) was defined as a residual hematoma volume of ≤15 mL or removal rate of ≥70%. Furthermore, we compared the background characteristics, imaging findings, and laboratory data between the two groups. Forty patients were included in this study. The mean baseline hematoma volume was 69.9 mL (range, 41.3-97.6 mL). FHR was accomplished in 35 cases (87.5%). Thirty-four patients (85%) were in the soft hematoma group (group S). Six patients (15%) were in the firm hematoma group (group F). Classification of hematoma stiffness demonstrated an excellent degree of interobserver agreement (κ score = 0.91). Patients in group S had a high FHR rate (p = 0.018) and short endoscopic procedure times (p = 0.00034). The island sign was present in group S (p = 0.030). Patients in group F had significantly high fibrinogen levels (p = 0.049) and low serum total calcium (p = 0.032), hemoglobin (p = 0.041), and hematocrit (p = 0.011) levels. Hematoma stiffness during endoscopic surgery for intracerebral hemorrhage correlates with surgical results, including the endoscopic procedure time and accomplishing rate of FHR.

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.

Assessing floor contamination by antineoplastic agents in a Japanese medical institution specializing in cancer treatment.

INTRODUCTION: This study investigated the extent of contamination with antineoplastic agents on floor surfaces of the ward and the outpatient chemotherapy center of a Japanese cancer center to evaluate healthcare workers' risk of occupational exposure to antineoplastic agents outside of the designated drug preparation areas. METHODS: In this study conducted at Aichi Cancer Center, the amount of fluorouracil detected on various floor surfaces was measured using liquid chromatography-tandem quadrupole mass spectrometry. Areas around the toilets were cleaned with a surfactant two or three times a day, whereas other floor surfaces were cleaned only with dry and wet mops. RESULTS: Fluorouracil was detected on all surveyed floor surfaces, with particularly high amounts detected around the toilet areas in the ward. Additionally, areas with more human traffic tended to have higher fluorouracil contamination. CONCLUSIONS: This survey suggested that antineoplastic agent contamination occurring through patient excretions might spread throughout the hospital with human traffic. Therefore, controlling the spread of antineoplastic agent contamination in hospitals should include the review of measures to mitigate contamination around toilets and to implement effective cleaning methods for floor surfaces.

Biopsy-proven Primary CNS Lymphoma in the Medulla Oblongata Presenting as Anorexia.

Eating disorders caused by brain tumors are infrequently seen. Recent studies revealed that a neurocircuit from the nucleus tractus solitarius of the medulla oblongata to the hypothalamus participates in the control of appetite. Among brain tumors, those located in the brain stem, especially a solitary one in the medulla oblongata, are rare. Tumors in the brainstem are generally considered gliomas, and with the difficulty in reaching the lesion, treatment without histological confirmation is often performed. However, there are a few reported cases of medulla oblongata tumors other than gliomas. We describe a case of a 56-year-old man who presented with persistent anorexia. Magnetic resonance images revealed a solitary tumor in the medulla oblongata. After several examinations, craniotomy for the biopsy of the tumor using the cerebellomedullary fissure approach was carried out and primary central nervous system lymphoma (PCNSL) was histologically proven. The patient was treated with effective adjuvant therapy and was discharged home after he recovered from the symptoms. No tumor recurrence was recognized 24 months after surgery. A PCNSL arising only from the medulla oblongata is very rare, and anorexia can be an initial symptom of a tumor in the medulla oblongata. Surgical intervention is safely achieved and is a key to a better clinical outcome.

Acute epidural vertex hematoma with good hemostasis using delayed surgery after monitoring of coagulation and fibrinolytic parameters: A case report.

Background: The appropriate timing and method of surgery for vertex epidural hematoma (VEDH) are uncertain due to the presentation and slow symptomatic exacerbation caused by bleeding from a venous origin involving the injured superior sagittal sinus (SSS). Coagulation and fibrinolytic disorders that occur after traumatic brain injury also worsen bleeding. For these reasons, it is challenging to decide the surgical procedure and timing of surgery. Case Description: A 24-year-old man involved a car accident and was transported to our emergency department. He was unconscious but not lethargic. Computed tomography showed VEDH overlying the SSS, and hematoma increased temporarily. Due to abnormal coagulation and fibrinolysis at admission, he underwent intentionally delayed surgery after control of coagulation and fibrinolysis. Bilateral parasagittal craniotomy was chosen to ensure hemostasis from the torn SSS. The patient improved without complications and was discharged with no neurological deficit. This case indicates that this surgical strategy is favorable for VEDH with slow symptomatic progression. Conclusion: VEDH is mostly caused by bleeding from the injured SSS secondary to diastatic fracture of sagittal suture. Intentionally delayed surgical intervention using bilateral parasagittal craniotomy after stabilization of coagulation and fibrinolysis is favorable for prevention of further hemorrhage and good hemostasis.

Effects of ABCB1 and ABCG2 Polymorphisms on the Pharmacokinetics of Abemaciclib Metabolites (M2, M20, M18).

BACKGROUND/AIM: Abemaciclib, an oral anticancer drug used in the treatment of breast cancer, is metabolised to its active forms - M2, M20 and M18; these forms have a potency similar to that of the parent drug. Abemaciclib and its active metabolites are reportedly transported by P-glycoprotein and breast cancer resistance protein (BCRP). We previously reported that the ABCB1 2677G>T/A homozygous type is associated with a higher abemaciclib concentration leading to treatment withdrawal and/or dose reduction. However, the pharmacokinetics of its metabolites have not been investigated. The purpose of the present study was to evaluate the effects of ABCB1 and ABCG2 polymorphisms on the pharmacokinetics of the abemaciclib metabolites M2, M20 and M18. PATIENTS AND METHODS: We evaluated 40 patients with breast cancer who received 150 mg abemaciclib twice per day for 2 weeks at the Aichi Cancer Center Hospital, Japan. Peak areas (arbitrary unit) of abemaciclib metabolites were measured using liquid chromatography tandem with mass spectrometry and compared between ABCB1 1236T>C, 2677G>T/A, 3435C>T and ABCG2 421C>A gene polymorphisms. RESULTS: For ABCB1 2677G>T/A polymorphisms, exposure doses for the abemaciclib metabolites M2 and M20 were higher in the homozygous (TT + AT) group than in the wild-type and heterozygous (GG + GA + GT) groups (p=0.09 and p=0.06, respectively). No significant association was observed between abemaciclib metabolites and ABCB1 1236T>C, ABCB1 3435C>T and ABCG2 421C>A polymorphisms. CONCLUSION: The ABCB1 2677G>T/A polymorphism may influence tolerance to abemaciclib in breast cancer patients by affecting the pharmacokinetics of the agent and its active metabolites.

Time-of-flight magnetic resonance angiography for detection of postoperative recurrence in patients with chronic subdural hematoma.

PURPOSE: Chronic subdural hematoma (CSDH) is associated with postoperative recurrence. Although various factors are involved in postoperative recurrence of CSDH, blood flow, especially in the middle meningeal artery (MMA), is considered to play an important role. We investigated whether the degree of signal intensity (SI) of the MMA on time-of-flight magnetic resonance angiography (TOF MRA) and various clinical factors are involved in recurrence of CSDH. METHODS: The maximum SI of both MMAs was measured on TOF MRA images within 1 month before or after the initial surgery. RESULTS: In total, 185 patients (20 with and 165 without recurrence of CSDH) were included in the analysis. The SI ratio and dementia were significant predictors of recurrence of CSDH (SI ratio: odds ratio [95% confidence interval (CI)] = 1.71 [1.32, 2.22], p < 0.0001; dementia: odds ratio [95% CI] = 7.41 [1.83, 30.1], p = 0.005). The estimated regression coefficients in the final model were 6.14 for the SI ratio and 1.28 for dementia. The risk score was derived according to these regression coefficients as follows: score = 5 × SI ratio + 1 (dementia: yes). With a score of 5, the predicted probability of recurrence was 2% [95% CI 0.7, 5.7], whereas with scores of 8 and 10, the probability was 43.3% [27.0, 61.1] and 89.5% [65.7, 97.5], respectively, which increased the risk of recurrence. CONCLUSION: Patients with an increased SI ratio of the affected MMA on TOF MRA who underwent surgery for CSDH were significantly more likely to experience recurrence.

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.

Revisiting the definition of glioma recurrence based on a phylogenetic investigation of primary and re-emerging tumor samples: a case report.

A recurrent tumor is defined as a re-emerging subclone originating from an ancestorial clone of the primary neoplasm. Hence, it should be distinguished from de novo tumor emerging from other clones. Herein, we describe an exceptional case in which the locally re-emerging glioma did not share genetic alterations of the primary tumor. While the initial tumor harbored mutations in IDH1 and TERT genes as well as 1p/19q codeletion, the re-emerging tumor did not present any of these genetic abnormalities. Variant calling for tumor samples using whole-genome sequencing revealed that 1696 mutations within the primary tumor faded in the re-emerging tumor, and that 4591 mutations were newly detected in the re-emerging tumor. These results suggested that the initial and re-emerging tumors did not share same clonal origins, although the second tumor appeared adjacent to the old surgical cavity 5 years after the initial surgery. We finally speculated that the re-emerging tumor could be a "de novo glioma" or "radiation-induced glioblastoma following treatment of a diffuse glioma." This case highlights the importance of molecular re-evaluation of clinically diagnosed "recurrent" glioma lesions.

Effects of ABCB1 and ABCG2 polymorphisms on the pharmacokinetics of abemaciclib.

PURPOSE: Adverse events after the use of the CDK4/6 inhibitor abemaciclib are dose-dependent. However, its pharmacokinetics varies among individuals. Abemaciclib is reportedly transported by P-glycoprotein and breast cancer resistance protein. Therefore, we evaluated whether ABCB1 and ABCG2 polymorphisms are pharmacokinetic predictive factors of abemaciclib. METHODS: A total of 45 patients with breast cancer taking abemaciclib (150 mg twice per day) for 2 weeks were evaluated to determine the associations among abemaciclib concentration; adverse events; and ABCB1 1236 T > C, 2677G > T/A, 3435C > T, and ABCG2 421C > A gene polymorphisms. RESULTS: The trough concentration of abemaciclib was significantly higher in the group with grade 2 or greater neutropenia and thrombocytopenia than in those with grades 0 or 1. For ABCB1 2677G > T/A polymorphisms, the concentration of abemaciclib tended to be higher in the homozygous group (TT + AT) than in the wild-type + heterozygous group (GG + GA + GT) (median [range], 222.8 [80.5-295.8] ng/mL vs. 113.5 [23.6-355.2] ng/mL, P = 0.09), Moreover, the ABCB1 2677G > T/A homozygous group had a higher tendency of abemaciclib withdrawal or dose reduction within 4 weeks than the wild-type + heterozygous group (odds ratio, 4.22; 95% confidence interval, 0.86-20.7; P = 0.08). No significant association was observed among abemaciclib concentration; adverse reactions; and ABCB1 1236 T > C, 3435C > T, and ABCG2 421C > A polymorphisms. CONCLUSION: ABCB1 2677G > T/A polymorphism might be a predictor of the pharmacokinetics and tolerability of abemaciclib.

Stat5b inhibition blocks proliferation and tumorigenicity of glioblastoma stem cells derived from a de novo murine brain cancer model.

Glioblastoma (GBM) is the most common and malignant type of brain cancer in adults with poor prognosis. GBM stem cells (GSCs) reside within niches in GBM tissues and contribute to recurrence and therapy resistance. Previous studies have shown that expression of leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), a Wnt pathway-related stem cell marker, correlates with a poor prognosis in GBM, and its knockdown in GSCs induces apoptosis accompanied with downregulation of signal transducer and activator of transcription 5b (Stat5b). Here, we show that Stat5b co-localizes with Lgr5 in hypoxia-inducible factor 2α (Hif2α)-positive regions in GBM tissues. Functional analyses using GSCs derived from a murine de novo GBM model induced by oncogenic genes transduction using the Sleeping-Beauty transposon system revealed that expression of Stat5b was induced by culturing under hypoxia together with Lgr5, repressed by Hif2α knockdown, and reduced by Lgr5 knockdown or a Wnt/ß-catenin signaling inhibitor ICG-001 treatment. Stat5b inhibition in the GSCs induced apoptosis and caused downregulation of Cyclin E2 resulted in blockade of entry into S-phase in the cell cycle. Disruption of Stat5b in an orthotopic transplantation model significantly prolongs event-free survival. These results suggest that Stat5b, regulated by hypoxia and the Wnt pathway, plays an important role in the maintenance and tumorigenicity of GSCs and may be a promising therapeutic molecular target to attack GSCs.

A tumefactive anti-MOG antibody associated disorder heralding central nervous system B-cell lymphoma: Case report on diagnostic challenge.

We present the case of a 52-year-old woman with right hemiparesis due to a mass lesion in the left parietal white matter and corpus callosum. The lesion was hyperintense on diffusion weighted image and homogenously enhanced with gadolinium on magnetic resonance imaging, and was radiologically indistinguishable with lymphoma. Following progressive aggravation of symptoms, craniotomy for biopsy of the lesion was performed, and it was revealed that the patient had anti-myelin oligodendrocyte glycoprotein-associated disease by histopathological and serological diagnosis. Initial treatment with steroid dramatically improved the symptoms, but they exacerbated again. Then, through cerebrospinal fluid examination, it was revealed that the patient had B-cell lymphoma.

A case of fibromuscular dysplasia related intracerebral hemorrhage without angiographically cerebral abnormal vessels.

BACKGROUND: Fibromuscular dysplasia (FMD) can cause cerebral aneurysms and dissection, which can lead to stroke. Angiographic findings are important in the diagnosis. We report a case of FMD in which the cause of hemorrhage could not be determined by angiography. CASE DESCRIPTION: A 73-year-old woman suffered from intracerebral hemorrhage (ICH) associated with FMD without abnormal angiography cerebral vessels. She presented with headache and nausea. Subsequent head-computed tomography-revealed ICH in the left frontal lobe, and contrast-enhanced magnetic resonance imaging revealed a gadolinium-enhancing lesion in the perihematoma area and in the genu of the corpus callosum. Although cerebral angiography revealed a string of beads appearance in the bilateral extracranial internal carotid arteries, no abnormality explaining the hemorrhage was identified. The hematoma was removed and the pathological diagnosis was FMD. In the pathological specimen, various patterns of vulnerable vessels, such as aneurysmal dilatation and obstruction, were observed, which could easily collapse and result in hemorrhage. In the case of ICH of unknown origin, microscopic vessel disruption due to FMD should also be considered. CONCLUSION: FMD can cause ICH in microscopic vascular lesions that are undetectable on angiography.

Maintenance of WT1 expression in tumor cells is associated with a good prognosis in malignant glioma patients treated with WT1 peptide vaccine immunotherapy.

We have previously revealed the overexpression of Wilms' tumor gene 1 (WT1) in malignant glioma and developed WT1 peptide vaccine cancer immunotherapy. A phase II clinical trial indicated the clinical efficacy of the WT1 peptide vaccine for recurrent malignant glioma. Here, we aimed to investigate the immunological microenvironment in glioma tissues before and after WT1 peptide vaccine treatment. Paired tissue samples were obtained from 20 malignant glioma patients who had received the WT1 peptide vaccine for > 3 months and experienced tumor progression, confirmed radiographically and/or clinically, during vaccination. We discovered that the expression of WT1 and HLA class I antigens in the tumor cells significantly decreased after vaccination. Maintenance of WT1 expression, which is the target molecule of immunotherapy, in tumor cells during the vaccination period was significantly associated with a longer progression-free and overall survival. A high expression of HLA class I antigens and low CD4+/CD8+ tumor-infiltrating lymphocytes (TIL) ratio in pre-vaccination specimens, were also associated with a good prognosis. No statistically significant difference existed in the number of infiltrating CD3+ or CD8+ T cells between the pre- and post-vaccination specimens, whereas the number of infiltrating CD4+ T cells significantly decreased in the post-vaccination specimens. This study provides insight into the mechanisms of intra-tumoral immune reaction/escape during WT1 peptide vaccine treatment and suggests potential clinical strategies for cancer immunotherapy.

Super-selective balloon test occlusion with electrophysiological monitoring to occlude angiographically invisible posterior communicating artery perforators with unruptured aneurysm.

Balloon test occlusion (BTO) can predict the ischemic complication risk associated with arterial occlusion. We present a case of an unruptured, broad-necked internal carotid artery-posterior communicating artery (PcomA) aneurysm that was successfully embolized after super-selective BTO of fetal PcomA with electrophysiological monitoring. The proximal portion of the PcomA was internally occluded without causing major neurological deficits, although we observed a small new infarction in the ipsilateral anterior thalamus postoperatively. We recognized small perforators arising from the proximal PcomA during a previous clipping surgery. Super-selective BTO with electrophysiological monitoring could be useful for functional preservation after infarction from angiographically invisible perforators.