Prediction of intraoperative blood loss in pediatric posterior fossa tumors by neuroradiological evaluation: preliminary study.

BACKGROUND: Hemorrhage management is crucial for surgical resection of pediatric posterior-fossa tumors (PPFTs). Tumor volume and vascularity on preoperative magnetic resonance imaging (MRI) can help predict and control intraoperative blood loss (IBL). The present study aimed to assess the correlation between MRI features and IBL in PPFTs. METHODS: Eleven patients treated for PPFTs at our hospital using the transcerebellomedullary fissure approach were enrolled, including five (45.5%) males and six (54.5%) females, with a median age of 10 (range, 4-16) years. Nine patients with medulloblastoma, one with ependymoma, and one with atypical teratoid/rhabdoid tumor were included. Using susceptibility-weighted imaging-based intratumoral susceptibility signal (ITSS) grade as an index of tumor vascularity, we performed univariate analysis of the association of degree of vascularity (ITSS grade 0-2 vs. 3) and multivariate analysis of IBL. RESULTS: Univariate analysis showed that the high vascularity group (ITSS grade 3) had significantly larger tumor volume (p = 0.009) and higher IBL (p = 0.004). In multivariate analysis of age, tumor volume, ITSS grade, cerebral blood volume, and extent of resection, tumor volume was the only significant factor (p = 0.001); however, ITSS grade was also positively associated with IBL (p = 0.074). CONCLUSION: In this study, tumor volume and vascularity of PPFTs were strongly correlated, and tumor volume was the sole factor significantly associated with IBL. This study suggests that ITSS grade and tumor volume collaboratively influence IBL in surgical resection of PPFTs. IBL should be assessed based on MRI features, and suitable treatment strategies should be established.

Safety of a short-term infusion of fosnetupitant in patients with gastrointestinal and breast cancer: a prospective study.

BACKGROUND: Fosnetupitant, a neurokinin-1 receptor antagonist, is used to prevent chemotherapy-induced nausea and vomiting (CINV) in patients undergoing highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Previous phase III trials demonstrated the non-inferiority of its 30-minute infusion to fosaprepitant in efficacy and a favorable safety profile. METHODS: This was a single-arm, phase II study to investigate the safety of a 15-minute infusion of fosnetupitant in patients with gastrointestinal and breast cancer. Patients who had received their dose of fosnetupitant in a 30-minute infusion without developing an allergic reaction were eligible and received their next fosnetupitant dose for 15 minutes. The primary endpoint was the incidence of an allergic reaction during the first 15-minutes infusion, and the secondary endpoints were the incidence of injection site reaction (ISR), the incidence of a grade ≥ 3 treatment-related adverse event (TRAE) with fosnetupitant, and complete response (CR) rate. RESULTS: The study period was from February 17, 2023 to June 20, 2023. In an exploratory analysis, medical records from the end of the study period to December 31, 2023 were retrospectively evaluated to assess the time-saving effect and safety of the short-term infusion of fosnetupitant. Fifty-six patients with gastrointestinal and 14 patients with breast cancer were enrolled, one of whom with breast cancer did not receive study treatment at her own request. No allergic reactions occurred during the 15-minutes infusion. Furthermore, there were no allergic reactions across all 280 short-term injections (Table 1). Additionally, no ISR or grade 3 or higher TRAE were reported. The CR rate was 87.0%. CONCLUSION: Short-term infusion of fosnetupitant, administered over 15 minutes, was demonstrated to be safe and effective for patients receiving HEC or MEC (Japan Registry of Clinical Trials Trial ID: jRCT1041220144).

Neuroradiological, genetic and clinical characteristics of histone H3 K27-mutant diffuse midline gliomas in the Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network): multicenter retrospective cohort.

This study aims to elucidate the clinical and molecular characteristics, treatment outcomes and prognostic factors of patients with histone H3 K27-mutant diffuse midline glioma. We retrospectively analyzed 93 patients with diffuse midline glioma (47 thalamus, 24 brainstem, 12 spinal cord and 10 other midline locations) treated at 24 affiliated hospitals in the Kansai Molecular Diagnosis Network for CNS Tumors. Considering the term "midline" areas, which had been confused in previous reports, we classified four midline locations based on previous reports and anatomical findings. Clinical and molecular characteristics of the study cohort included: age 4-78 years, female sex (41%), lower-grade histology (56%), preoperative Karnofsky performance status (KPS) scores ≥ 80 (49%), resection (36%), adjuvant radiation plus chemotherapy (83%), temozolomide therapy (76%), bevacizumab therapy (42%), HIST1H3B p.K27M mutation (2%), TERT promoter mutation (3%), MGMT promoter methylation (9%), BRAF p.V600E mutation (1%), FGFR1 mutation (14%) and EGFR mutation (3%). Median progression-free and overall survival time was 9.9 ± 1.0 (7.9-11.9, 95% CI) and 16.6 ± 1.4 (13.9-19.3, 95% CI) months, respectively. Female sex, preoperative KPS score ≥ 80, adjuvant radiation + temozolomide and radiation ≥ 50 Gy were associated with favorable prognosis. Female sex and preoperative KPS score ≥ 80 were identified as independent good prognostic factors. This study demonstrated the current state of clinical practice for patients with diffuse midline glioma and molecular analyses of diffuse midline glioma in real-world settings. Further investigation in a larger population would contribute to better understanding of the pathology of diffuse midline glioma.

Clinical features of pediatric patients with cerebral venous sinus thrombosis after isolated head trauma.

OBJECTIVE: An association between blunt head trauma and cerebral venous sinus thrombosis (CVST) has been recognized, but its symptoms are nonspecific and the duration of symptoms remains unclear. Anticoagulation therapy is not considered necessary in most cases of traumatic CVST; however, this is controversial. The aim of this study was to describe the clinical characteristics and outcomes of children with CVST after isolated head trauma. METHODS: The records of pediatric patients with isolated head trauma admitted for observation at 3 medical centers between January 2018 and May 2023 were reviewed retrospectively. CVST was diagnosed on MR venography (MRV). Clinical presentation, therapeutic management, and outcomes were evaluated in patients who had follow-up MRV. RESULTS: Of 260 pediatric patients with head trauma admitted to the 3 hospitals, 26 patients underwent MRV and 8 (30.8%) were diagnosed with CVST. One patient was treated with heparin, while the others received conservative treatment. All patients were discharged home asymptomatic. MRV performed during follow-up displayed complete recanalization in all cases, except for 1 case with partial recanalization. The median hospital stay was longer in patients with CVST than in those without CVST (9.5 vs 3.0 days, p = 0.001). CONCLUSIONS: The length of stay of pediatric patients with traumatic CVST was prolonged compared with those without CVST, but most patients had good outcomes with spontaneous recanalization following conservative treatment.

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.

Nation-wide survey of oral care practice in Japanese intensive care units: A descriptive study.

Oral care for critically ill patients helps provide comfort and prevent ventilator-associated pneumonia. However, a standardized protocol for oral care in intensive care units is currently unavailable. Thus, this study aimed to determine the overall oral care practices, including those for intubated patients, in Japanese intensive care units. We also discuss the differences in oral care methods between Japanese ICUs and ICUs in other countries. This study included all Japanese intensive care units meeting the authorities' standard set criteria, with a minimum of 0.5 nurses per patient at all times and admission of adult patients requiring mechanical ventilation. An online survey was used to collect data. Survey responses were obtained from one representative nurse per intensive care unit. Frequency analysis was performed, and the percentage of each response was calculated. A total of 609 hospitals and 717 intensive care units nationwide participated; among these, responses were collected from 247 intensive care units (34.4%). Of these, 215 (87.0%) and 32 (13.0%) reported standardized and non-standardized oral care, respectively. Subsequently, the data from 215 intensive care units that provided standardized oral care were analyzed in detail. The most common frequency of practicing oral care was three times a day (68.8%). Moreover, many intensive care units provided care at unequal intervals (79.5%), mainly in the morning, daytime, and evening. Regarding oral care methods, 96 (44.7%) respondents used only a toothbrush, while 116 (54.0%) used both a toothbrush and a non-brushing method. The findings of our study reveal current oral care practices in ICUs in Japan. In particular, most ICUs provide oral care three times a day at unequal intervals, and almost all use toothbrushes as a common tool for oral care. The results suggest that some oral care practices in Japanese ICUs differ from those in ICUs in other countries.

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.

Derivation of Coagulation Phenotypes and the Association with Prognosis in Traumatic Brain Injury: A Cluster Analysis of Nationwide Multicenter Study.

BACKGROUND: The pathogenesis and pathophysiology of traumatic coagulopathy during traumatic brain injury is not well understood, and the appropriate treatment strategy for this condition has not been established. This study aimed to evaluate the coagulation phenotypes and their effect on prognosis in patients with isolated traumatic brain injury. METHODS: In this multicenter cohort study, we retrospectively analyzed data from the Japan Neurotrauma Data Bank. Adults with isolated traumatic brain injury (head abbreviated injury scale > 2; abbreviated injury scale of any other trauma < 3) who were registered in the Japan Neurotrauma Data Bank were included in this study. The primary outcome was the association of coagulation phenotypes with in-hospital mortality. Coagulation phenotypes were derived using k-means clustering with coagulation markers, including prothrombin time international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), fibrinogen (FBG), and D-dimer (DD) on arrival at the hospital. Multivariable logistic regression analyses were conducted to calculate the adjusted odds ratios of coagulation phenotypes with their 95% confidence intervals (CIs) for in-hospital mortality. RESULTS: In total, 556 patients were enrolled and five coagulation phenotypes were identified. The median (interquartile range) score for the Glasgow Coma Scale was 6 (4-9). Cluster A (n = 129) had the closest to normal coagulation values; cluster B (n = 323) had a mild high DD phenotype; cluster C (n = 30) had a prolonged PT-INR phenotype with a higher frequency of antithrombotic medication in elderly patients than in younger patients; cluster D (n = 45) had a low amount of FBG, high DD, and prolonged APTT phenotype with a high incidence of skull fracture; and cluster E (n = 29) had a low amount of FBG and extremely high DD phenotype with high energy trauma and a high incidence of skull fracture. In the multivariable logistic regression analysis, the association of clusters B, C, D, and E with in-hospital mortality yielded the corresponding adjusted odds ratios of 2.17 (95% CI 1.22-3.86), 2.61 (95% CI 1.01-6.72), 10.0 (95% CI 4.00-25.2), and 24.1 (95% CI 7.12-81.3), respectively, relative to cluster A. CONCLUSIONS: This multicenter, observational study identified five different coagulation phenotypes of traumatic brain injury and showed associations of these phenotypes with in-hospital mortality.

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.

Prevalence, Location, and Interference With Daily Life of Chronic Pain in Long-Term Survivors After Discharge From a Tertiary Emergency Center.

Background This study aimed to investigate the prevalence, location, and characteristics of new-onset chronic pain by using a new definition in long-term survivors after discharge from a tertiary emergency center. Materials and methods We conducted a single-center ambidirectional cohort study from January to May 2022. A survey of patients was conducted by postal mail two to 2.5 years after their discharge from a tertiary emergency center. We used the Brief Pain Inventory to investigate chronic pain parameters, and the painDETECT questionnaire to investigate neuropathic pain. Patient information during hospitalization was collected retrospectively from medical records. Results The survey was sent to 78 patients, 63 (81%) of whom responded and were included in the analysis. Nine of the 63 patients (14%) had new-onset chronic pain. Of these, six (67%) had chronic pain of moderate or severe intensity which interfered with daily life. The most frequent location of chronic pain was the foot/ankle (n=4, 44%). Neuropathic pain was present in four (44%) patients with new-onset chronic pain. Conclusion New-onset chronic pain may occur for up to two to 2.5 years after discharge from a tertiary emergency center, and this may interfere with daily life. Therefore, a follow-up system for chronic pain is warranted.

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.