Gamma knife radiosurgery as primary management for intracranial meningioma identified as growing on serial imaging.

Gamma knife radiosurgery (GKRS) has emerged as a highly effective therapeutic modality for the management of intracranial meningiomas. However, the role of GKRS in treating growing meningiomas detected during active surveillance remains unclear. This study seeks to investigate the long-term outcomes of GKRS treatment for growing meningiomas. A retrospective analysis was conducted on patients who underwent GKRS as the primary treatment for growing meningiomas between 2004 and 2021. Growing meningiomas were defined as those exhibiting a > 10% increase in tumor volume (TV) compared to the previous imaging. Fifty-nine patients who received GKRS as their initial treatment were included, with a minimum follow-up period of 12 months. Comprehensive clinical, radiological, and procedural data were analyzed. Serial TV assessments were performed for all tumors before and after GKRS. Tumor progression and regression were defined as a > 10% increase or decrease in TV, respectively, compared to the pretreatment image. At a median follow-up of 41 months (range 15-197 months), TV was unchanged in 16 patients (27.1%), decreased in 41 patients (69.5%), and increased in 2 patients (3.4%). Multivariate analysis revealed that both TV (cm3) (hazard ratio [HR], 1.107; 95% confidence interval [CI], 1.002-1.222; P = .045) and volume growing rate (%/yr) (HR, 1.013; 95% CI, 1.000-1.025; P = .04) significantly correlated with tumor progression. Eleven patients (18.6%) experienced new or worsening symptoms. In multivariate analysis, factor predicting new or worsening neurological function was preexisting calcification (HR, 5.297; 95% CI, 1.328-21.124; P = .018). GKRS demonstrates a promising level of tumor control with minimal risk of neurological deterioration when applied to growing meningiomas. These findings provide compelling support for considering GKRS as a valuable therapeutic option following an initial period of active surveillance for these tumors.

Central Nervous System Dissemination of Solitary Sporadic Supratentorial Hemangioblastoma: A Case Report and Literature Review.

We report a patient with whole neuroaxis dissemination of a sporadic supratentorial hemangioblastoma (HB) for more than 15 years. A 68-year-old female patient presented with severe radiating pain in the right leg. Gadolinium-enhanced lumbar spine MRI showed an intradural mass (2.5 cm in diameter) at the L4 level. The patient had been severely disabled for 22 years after a previous intraventricular brain tumor resection. At that time, the diagnosis was angioblastic meningioma, which was thought to be incorrect. At 14 years after the brain surgery, gamma knife radiosurgery was performed three times for newly developed or recurred supratentorial and infratentorial tumors in the cerebrospinal fluid pathway. The patient underwent lumbar spinal surgery, and a gross total removal of the mass was performed, which confirmed the histopathological diagnosis of HB. We reexamined the old histopathological specimen of the intraventricular tumor from 20 years ago and changed the diagnosis from angioblastic meningioma to supratentorial HB. Six months after spinal surgery, the patient underwent a second spinal surgery and brain surgery, and the histopathological diagnosis was HB following both surgeries, which was the same following the first spinal surgery. Here, we report a sporadic supratentorial HB patient who showed cranial and spinal disseminations for more than two decades along with a literature review.

Leksell Frame-Based Stereotactic Biopsy for Infratentorial Tumor : Practical Tips and Considerations.

The Leksell frame-based transcerebellar approach was proposed with the arc support frame attached upside down to the Z coordinate. This study presented practical tips and considerations for obtaining adequate tissue samples for deep-seated cerebellar lesions or lower brainstem lesions specifically those accessible via the cerebellar peduncle. For practical insights, the Leksell coordinate frame G was fixed to prevent the anterior screw implantation within the temporalis muscle, to avoid interference with the magnetic resonance (MR)-adapter, and taking into account the magnetic field of MR in close proximity to the tentorium. After mounting of indicator box, the MR imaging evaluation should cover both the indicator box and the infratentorial region that deviated from it. The coordinates [X, Y, Za, Arc0, Ringa0] obtained from Leksell SurgiPlan® software (Elekta, Stockholm, Sweden) with arc 00 located on the patient's right side were converted to [X, Y, Zb=360-Za, Arc0, Ringb0=Ringa0-1800]. The operation was performed in the prone position under general anesthesia in four patients with deep cerebellar (n=3) and brainstem (n=1) tumors. The biopsy results showed two cases of diffuse large B-cell lymphoma, one metastatic braintumor and one glioblastoma. One patient required frame repositioning as a complication. Drawing upon the methodology outlined in existing literature, we anticipate that imparting supplementary expertise could render the stereotactic biopsy of infratentorial tumors more consistent and manageable for the practitioner, thereby facilitating adequate tissue samples and minimizing patient complications.

Analysis of distress in patients undergoing radical prostatectomy: A multicenter prospective study.

PURPOSE: To analyze the degree of psychological distress experienced pre- and postoperatively in patients who underwent radical prostatectomy after being diagnosed with prostate cancer. MATERIALS AND METHODS: Patients diagnosed with prostate cancer who underwent radical prostatectomy without history of psychiatric disorders were included in this study. The degree of psychological distress was evaluated using hospital anxiety and depression scale (HADS) and distress thermometer (DT) questionnaires preoperatively and at 1, 3, 6, and 12 months postoperatively. RESULTS: Distress was high preoperatively and decreased over the entire period. In addition, HADS-anxiety and HADS-depression scores showed an improved severity, shifting from an abnormal state to a borderline state in some patients. However, the DT score, including emotional problems, spiritual concerns, physical problems, family problems, and practical problems, was slightly higher at 1 month postoperatively compared to preoperatively. Furthermore, even at 12 months postoperatively, about one fifth of patients surveyed had a DT score of 4 or higher, requiring psychiatric intervention. CONCLUSIONS: Before and after radical prostatectomy, a significant number of patients complained of distress such as anxiety, depression, and insomnia, and they needed help from a specialist because of psychological distress even 12 months postoperatively. Therefore, a close evaluation of the patient's psychological distress and supportive treatment are needed during the entire pre- and postoperative period.

Oncological Outcomes in Men with Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide with versus without Confirmatory Bone Scan.

PURPOSE: In men with metastatic castration-resistant prostate cancer (mCRPC), new bone lesions are sometimes not properly categorized through a confirmatory bone scan, and clinical significance of the test itself remains unclear. This study aimed to demonstrate the performance rate of confirmatory bone scans in a real-world setting and their prognostic impact in enzalutamide-treated mCRPC. MATERIALS AND METHODS: Patients who received oral enzalutamide for mCRPC during 2014-2017 at 14 tertiary centers in Korea were included. Patients lacking imaging assessment data or insufficient drug exposure were excluded. The primary outcome was overall survival (OS). Secondary outcomes included performance rate of confirmatory bone scans in a real-world setting. Kaplan-Meier analysis and multivariate Cox regression analysis were performed. RESULTS: Overall, 520 patients with mCRPC were enrolled (240 [26.2%] chemotherapy-naïve and 280 [53.2%] after chemotherapy). Among 352 responders, 92 patients (26.1%) showed new bone lesions in their early bone scan. Confirmatory bone scan was performed in 41 patients (44.6%), and it was associated with prolonged OS in the entire population (median, 30.9 vs. 19.7 months; p < 0.001), as well as in the chemotherapy-naïve (median, 47.2 vs. 20.5 months; p=0.011) and post-chemotherapy sub-groups (median, 25.5 vs. 18.0 months; p=0.006). Multivariate Cox regression showed that confirmatory bone scan performance was an independent prognostic factor for OS (hazard ratio 0.35, 95% confidence interval, 0.18 to 0.69; p=0.002). CONCLUSION: Confirmatory bone scan performance was associated with prolonged OS. Thus, the premature discontinuation of enzalutamide without confirmatory bone scans should be discouraged.

Two-Day Fraction Gamma Knife Radiosurgery for Large Brain Metastasis.

Objective: We investigated how treating large brain metastasis (LBM) using two-day fraction gamma knife radiosurgery (GKRS) affects tumor control and patient survival. A prescription dose of 10.3 Gy was applied for two consecutive days, with a biologically effective dose (BED) equivalent to a tumor single-fraction dose of 16.05 Gy and a brain single-fraction dose of 15.12 Gy. Methods: Between November 2017 and December 2021, 42 patients (mean age: 68.3 years, range: 50-84 years, male: 29 [69.1%], female: 13 [30.9%]) with 44 tumors underwent two-day fraction GKRS to treat large volume brain metastasis. The main cancer types were non-small cell lung cancer (NSCLC, N=16), small cell lung cancer (SCLC, N=7), colorectal cancer (N=7), breast cancer (N=3), gastric cancer (N=2), and other cancers (N=7). Twenty-one (50.0%) patients had a single LBM, nineteen (46.3%) had a single LBM and other metastasi(e)s, and two had two (4.7%) large brain metastases. At the time of the two-day fraction GKRS, the tumors had a mean volume of 23.1 cc (range: 12.5-67.4). on each day, radiation was administered at a dose of 10.3 Gy, mainly using a 50% isodose-line. Results: We obtained clinical and magnetic resonance imaging (MRI) follow-up data for 34 patients (81%) with 35 tumors, who had undergone two-day fraction GKRS. These patients did not experience acute or late radiation-induced complications during follow-up. The median and mean progression-free survival (PFS) periods were 188 and 194 days, respectively. The local control rates at 6, 9, and 12 months were 77%, 40%, and 34%, respectively. The prognostic factors related to PFS were prior radiotherapy (P = 0.019) and lung cancer origin (P = 0.041). Other factors such as tumor volumes, each isodose volumes, and peri-GKRS systemic treatment were not significantly related to PFS. The overall survival period of the 44 patients following repeat SRS ranged from 15-878 days (median: 263±38 days, mean: 174±43) after the two-day fraction GKRS. Eight patients (18.2%) were still alive. Conclusion: Considering the unsatisfactory tumor control, a higher prescription dose should be needed in this procedure as a salvage management. Moreover, in the treatment for LBM with fractionated SRS, using different isodoses and prescription doses at the treatment planning for LBMs should be important. However, this report might be a basic reference with the same fraction number and prescription dose in the treatment for LBMs with frame-based SRS.

Strategy for dealing with unfamiliar and thick vessels during microvascular decompression: A first case report of hemifacial spasm caused by a persistent primitive trigeminal artery.

RATIONALE: A persistent primitive trigeminal artery (PPTA) is a rare embryonic cerebrovascular anomaly. Hemifacial spasm (HFS) refers to involuntary contractions of facial muscles caused by the compression of blood vessels against the root exit zone of the facial nerve. There have been no reported cases of PPTA causing neurovascular contact and HFS. Microvascular decompression surgery effectively treats HFS, but operating on strong PPTA vessels poses challenges. We aim to introduce a more efficient approach for overcomes these difficulties and facilitates surgery. PATIENT CONCERNS: A 44-year-old male patient without any underlying medical conditions presented to our hospital with involuntary movements of the left side of his face accompanied by numbness in the left maxilla (V2 area). DIAGNOSIS: Brain magnetic resonance imaging and magnetic resonance angiography showed that PPTA was in contact with the left facial nerve. INTERVENTIONS AND OUTCOMES: Following a retro-sigmoid craniotomy, we attempted to interpose the facial nerve and the PPTA as an offender vessel, but the decompression was not sufficient. However, after transposing the vessel using the proximal Teflon transposition with interposition technique, the strength of the involuntary movements was reduced. Following surgery, there was no more lateral spreading response, and the patient symptoms improved. LESSIONS: In cases where the vessel causing HFS is particularly strong and thick, the proximal Teflon transposition with interposition technique for transposition may be advantageous. This method could simplify and enhance the efficacy of microvascular decompression, without compromising the quality of surgical outcomes.

Effects of resection volume on postoperative micturition symptoms and retreatment after transurethral resection of the prostate.

PURPOSE: Despite advances in technology, such as advent of laser enucleation and minimally invasive surgical therapies, transurethral resection of the prostate (TURP) remains the most widely performed surgical technique for benign prostatic hyperplasia (BPH). We evaluated resection volume (RV)-derived parameters and analyzed the effect of RV on post-TURP outcomes. METHODS: This observational study used data from patients who underwent TURP at two institutions between January 2011 and December 2021 Data from patients with previous BPH surgical treatment, incomplete data, and underlying disease affecting voiding function were excluded. The collected data included age, prostate-specific antigen, transrectal ultrasound (TRUS)- and uroflowmetry-derived parameters, RV, perioperative laboratory values, perioperative International Prostatic Symptom Score (IPSS), follow-up period, retreatment requirements and interval between the first TURP and retreatment. RESULTS: In 268 patients without prior BPH medication, there were no differences in prostate volume (PV), transitional zone volume (TZV), or RV according to IPSS. A total of 60 patients started retreatment, including medical or surgical treatment, within the follow-up period. There was a significant difference in RV/PV between the groups without and with retreatment respectively (0.56 and 0.37; p = 0.008). However, preoperative TRUS- and uroflowmetry-derived parameters did not differ between the two groups. Multiple linear regression analysis showed that RV (p = 0.003) and RV/TZV (p = 0.006) were significantly associated with differences in perioperative IPSS. In the multivariate logistic regression analysis, only RV/PV was correlated with retreatment (p = 0.010). CONCLUSION: Maximal TURP leads to improved postoperative outcomes and reduced retreatment rate, it may gradually become a requirement rather than an option.

Radiologic Follow-up of Ruptured Arachnoid Cysts With or Without Hemorrhage: Five Case Reports and a Review of the Literature.

Arachnoid cysts are usually asymptomatic and discovered incidentally. However, cysts may occasionally rupture because of minor head trauma. We describe the radiologic follow-up of 5 patients with ruptured arachnoid cysts featuring spontaneous resolution, subdural hygroma formation, and cystic and subdural hemorrhage. From January 2004 through July 2020, 5 patients (1.3%) with ruptured arachnoid cysts were evaluated out of 388 patients with arachnoid cysts encountered at our institution at that time. The 5 patients were all male, and they ranged in age from 6-17 years (median, 12 years). The median duration of radiologic follow-up was 3.5 years (range, 2.3-10.1 years). All of the ruptured arachnoid cysts were overlying the temporal lobe with Galassi type II. The median cyst diameter was 4.9 cm (range, 4.4-8.9 cm). Four patients had a history of recent minor head trauma. There were no particular neurologic symptoms in their past medical history in all patients. In the follow-up, two patients' cysts resolved spontaneously without hemorrhage. One patient's cyst resolved post-burr-hole drainage for chronic subdural hemorrhage. Another patient, whose cyst led to a hemorrhage and chronic subdural hemorrhage, recovered following a craniotomy, hematoma removal, and cyst fenestration. Another patient, presenting with hygroma, cystic hemorrhage, and chronic subdural hemorrhage, was treated with burr-hole drainage. Three patients recovered postoperatively. Arachnoid cysts rarely rupture, and surgical intervention is required for some cases associated with hemorrhage. Postoperatively, all patients had good outcomes without complications in this series.

Intracranial Efficacy of Systemic Therapy in Patients with Asymptomatic Brain Metastases from Lung Cancer.

There has been controversy over whether to radiologically follow up or use local treatment for asymptomatic small-sized brain metastases from primary lung cancer. For brain tumors without local treatment, we evaluated potential factors related to the brain progression and whether systemic therapy controlled the tumor. We analyzed 96 patients with asymptomatic small-sized metastatic brain tumors from lung cancer. These underwent a radiologic follow-up every 2 or 3 months without local treatment of brain metastases. The pathologies of the tumors were adenocarcinoma (n = 74), squamous cell carcinoma (n = 11), and small cell carcinoma (n = 11). The primary lung cancer was treated with cytotoxic chemotherapy (n = 57) and targeted therapy (n = 39). Patients who received targeted therapy were divided into first generation (n = 23) and second or third generation (n = 16). The progression-free survival (PFS) of brain metastases and the overall survival (OS) of patients were analyzed depending on the age, tumor pathology, number, and location of brain metastases, the extent of other organ metastases, and chemotherapy regimens. The median PFS of brain metastases was 7.4 months (range, 1.1-48.3). Targeted therapy showed statistically significant PFS improvement compared to cytotoxic chemotherapy (p = 0.020). Especially, on univariate and multivariate analyses, the PFS in the second or third generation targeted therapy was more significantly improved compared to cytotoxic chemotherapy (hazard ratio 0.229; 95% confidence interval, 0.082-0.640; p = 0.005). The median OS of patients was 13.7 months (range, 2.0-65.0). Univariate and multivariate analyses revealed that the OS of patients was related to other organ metastases except for the brain (p = 0.010 and 0.020, respectively). Three out of 52 patients with brain recurrence showed leptomeningeal dissemination, while the recurrence patterns of brain metastases were mostly local and/or distant metastases (94.2%). Of the 52 patients who relapsed, 25 patients received local brain treatment. There was brain-related mortality in two patients (2.0%). The intracranial anti-tumor effect was superior to cytotoxic chemotherapy in the treatment of asymptomatic small-sized brain metastases with targeted therapy. Consequently, it becomes possible to determine the optimal timing for local brain treatment while conducting radiological follow-up for these tumors, which do not appear to increase brain-related mortality. Furthermore, this approach has the potential to reduce the number of cases requiring brain local treatment.

From the perspective of pseudo-progression rather than treatment failure, how long should we wait before considering treatment failure if large cystic enlargement occurs after Gamma Knife radiosurgery for vestibular schwannoma?: insight into pseudoprogression based on two case reports.

Gamma knife radiosurgery (GKRS) has been accepted as a safe and effective treatment for vestibular schwannoma (VS). However, during follow-up, tumor expansion induced by irradiation can occur, and diagnosis of failure in radiosurgery for VS is still controversial. Tumor expansion with cystic enlargement causes some confusion regarding whether further treatment should be performed. We analyzed more than 10 years of clinical findings and imaging of patients with VS with cystic enlargement after GKRS. A 49-year-old male with hearing impairment was treated with GKRS (12 Gy; isodose, 50%) for a left VS with a preoperative tumor volume of 0.8 cc. The tumor size increased with cystic changes from the third year after GKRS, reaching a volume of 10.8 cc at 5 years after GKRS. At the 6th year of follow-up, the tumor volume started to decrease, up to 0.3 cc by the 14th year of follow-up. A 52-year-old female with hearing impairment and left facial numbness was treated with GKRS for a left VS (13 Gy; isodose, 50%). The preoperative tumor volume was 6.3 cc, which started to increase with cystic enlargement from the first year after GKRS, and reaching 18.2 cc by 5 years after GKRS. The tumor maintained a cystic pattern with slight changes in size, but no other neurologic symptoms developed during the follow-up period. After 6 years of GKRS, tumor regression was observed, eventually reaching a volume of 3.2 cc by the 13th year of follow-up. In both cases, persistent cystic enlargement in VS was observed at 5 years after GKRS, after which the tumors began to stabilize. After more than 10 years of GKRS, the tumor volume was less than that before GKRS. Enlargement with large cystic formation in the first 3-5 years after GKRS has been considered as treatment failure. However, our cases show that further treatment for cystic enlargement should be deferred for at least 10 years, especially in patients without neurological deterioration, as inadequate surgery can be prevented within that period.

Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study).

PURPOSE: Glioblastoma (GBM) has a poor prognosis after standard treatment. Recently, metformin has been shown to have an antitumor effect on glioma cells. We performed the first randomized prospective phase II clinical trial to investigate the clinical efficacy and safety of metformin in patients with recurrent or refractory GBM treated with low-dose temozolomide. METHODS: Included patients were randomly assigned to a control group [placebo plus low-dose temozolomide (50 mg/m2, daily)] or an experimental group [metformin (1000 mg, 1500 mg, and 2000 mg per day during the 1st, 2nd, and 3rd week until disease progression, respectively) plus low-dose temozolomide]. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), disease control rate, overall response rate, health-related quality of life, and safety. RESULTS: Among the 92 patients screened, 81 were randomly assigned to the control group (43 patients) or the experimental group (38 patients). Although the control group showed a longer median PFS, the difference between the two groups was not statistically significant (2.66 versus 2.3 months, p = 0.679). The median OS was 17.22 months (95% CI 12.19-21.68 months) in the experimental group and 7.69 months (95% CI 5.16-22.67 months) in the control group, showing no significant difference by the log-rank test (HR: 0.78; 95% CI 0.39-1.58; p = 0.473). The overall response rate and disease control rate were 9.3% and 46.5% in the control group and 5.3% and 47.4% in the experimental group, respectively. CONCLUSIONS: Although the metformin plus temozolomide regimen was well tolerated, it did not confer a clinical benefit in patients with recurrent or refractory GBM. Trial registration NCT03243851, registered August 4, 2017.

Efficacy of recombinant Bacillus Calmette-Guérin containing dltA in in vivo three-dimensional bio-printed bladder cancer-on-a-chip and ex vivo orthotopic mouse model.

PURPOSE: We investigated the efficacy and optimal dosage of recombinant Bacillus Calmette-Guérin-dltA (rBCG-dltA) in a high-throughput 3D bio-printed bladder cancer-on-a-chip (BCOC) and orthotopic bladder cancer mouse model. MATERIALS AND METHODS: We fabricated high-throughput BCOC with microfluidic systems, enabling efficient drug screening. The efficacy of rBCG-dltA was evaluated using BCOC by the cell viability assay, monocyte migration assay, and measuring cytokine levels. The anti-tumor effect was compared using the orthotopic bladder cancer mouse model. RESULTS: The cell proliferation rates of T24 and 253J bladder cancer cell lines (mean±standard error) were measured at three days after treatment. In T24 cell line, there was significantly decreased T24 cells compared to control at rBCG 1 multiplicity of infection (MOI) and 10 MOI (30 MOI: 63.1±6.4, 10 MOI: 47.4±5.2, 1 MOI: 50.5±7.5, control: 100.0±14.5, p<0.05). In 253J cell line, a statistically significant decrease in 253J cell count compared to control and mock BCG 30 MOI (30 MOI: 11.2±1.3, 10 MOI: 22.5±2.3, 1 MOI: 39.4±4.7, Mock: 54.9±10.8, control: 100.0±5.6, p<0.05). The migration rates of THP-1 cells showed increased patterns after rBCG-dltA treatment in BCOC. The concentration of tumor necrosis factor-α and interleukin-6 after rBCG-dltA 30 MOI treatment was higher than control in T24 and 253J cell line. CONCLUSIONS: In conclusion, rBCG-dltA has the potential to have better anti-tumor activity and immunomodulatory effects than BCG. Furthermore, high-throughput BCOCs have potential to reflect the bladder cancer microenvironment.

Kaposiform hemangioendothelioma of skull base with dura invasion in a pediatric patient: a case report.

Kaposiform hemangioendothelioma is an extremely rare vascular tumor which shows aggressive local growth. We present a case of rapid growing vascular skull tumor with dura invasion in a pediatric patient with neurofibromatosis type 1. A 14-year-old male complained of headache and dizziness for 1 month after minor head trauma. Brain magnetic resonance imaging (MRI) revealed a 5-cm-sized tumor in the left frontotemporal bone with internal hemorrhage and cystic changes. The gross total resection of tumor was done. At the 7-month follow-up, brain MRI revealed a recurrent skull tumor with intracranial dura mass. He underwent second surgery, and the pathologic diagnosis was suggestive of Kaposiform hemangioendothelioma. For this vascular proliferative tumor, mTOR inhibitor was treated for 6 months, and there was the recurred nodular-enhancing mass along the sphenoid ridge. After additional 2 months of medication, the following MRI revealed a decreased nodular-enhancing mass.

Distinct Specialized Center of Excellence, the Story of Hwasun Neurosurgery at Chonnam National University Hwasun Hospital.

The paper provides a comprehensive overview of the growth and development of Hwasun Neurosurgery at Chonnam National University Hwasun Hospital over the past 18 years. As the first brain tumor center in Korea when it was established in April 2004, Hwasun Neurosurgery has since become one of the leading institutions in brain tumor education and research in the country. Its impressive clinical and basic research capabilities, dedication to professional education, and numerous academic achievements have all contributed to its reputation as a top-tier institution. We hope this will become a useful guide for other brain tumor centers or educational institutions by sharing the story of Hwasun Neurosurgery.

Different Expression and Clinical Implications of Cancer-Associated Fibroblast (CAF) Markers in Brain Metastases.

Aims: This study assessed the expression and clinical relevance of cancer-asssociated fibroblast (CAF)-related biomarkers in brain metastasis (BM). Moreover, molecular characterization of patient-derived primary CAFs and normal fibroblasts (NFs) was performed. Methods: Sixty-eight patients with BM from various primary cancer types were selected. Immunohistochemistry (IHC) and immunofluorescence (IF) staining were performed to evaluate the expression of various CAF-related biomarkers. CAFs and NFs were isolated from fresh tissues. Results: Various CAF-related biomarkers were expressed in CAFs in BMs of different primary cancers. However, only PDGFR-ß, α-SMA, and collagen type I were associated with BM size. PDGFR-ß and α-SMA were associated with BM recurrence after resection. PDGFR-ß was associated with recurrence-free survival (RFS). Interestingly, high expression of PDGFR-ß and α-SMA was found in the patients with previous chemotherapy or radiotherapy for primary cancer. In primary cell culture, PDGFR-ß and α-SMA were expressed at higher levels in patient-derived CAFs than in NFs or cancer cells. The origins of CAF in BM were presumed to be pericytes of blood vessels, circulating endothelial progenitor cells, or transformed astrocytes of the peritumoral glial stroma. Conclusion: Our results suggest that high expression of CAF-related biomarkers, particularly PDGFR-ß and α-SMA, is associated with poor prognosis and recurrence in patients with BM. With the elucidation of the role and origins of CAF in the tumor microenvironment, CAF can be a new imperative target for BM immunotherapy.

Contralateral subfrontal approach for tuberculum sellae meningioma: techniques and clinical outcomes.

OBJECTIVE: Tuberculum sellae meningiomas (TSMs) present a burdensome surgical challenge because of their adjacency to vital neurovascular structures. The contralateral subfrontal approach provides an outstanding corridor for removing a TSM with an excellent visual outcome and limited complications. The authors present their long-term surgical experience in treating TSMs via the contralateral subfrontal approach and discuss patient selection, surgical techniques, and clinical outcomes. METHODS: Between 2005 and 2021, the authors used the contralateral subfrontal approach in 74 consecutive patients presenting with TSMs. The surgical decision-making process and surgical techniques are described, and the clinical outcomes were retrospectively analyzed. RESULTS: The mean patient age was 54.4 years, with a female predominance (n = 61, 82%). Preoperatively, 61 patients (82%) had vision symptoms and 73 (99%) had optic canal invasion by tumor. Gross-total resection was achieved in almost all patients (n = 70, 95%). The visual function improvement and stabilization rate was 91% (67/74). Eight patients (11%) showed a worsening of visual function on the less-compromised (approach-side) optic nerve. There was no occurrence of cerebrospinal fluid leakage. Four patients (5%) experienced recurrences after the initial operation (mean follow-up duration 63 months). There were no deaths in this study. CONCLUSIONS: The contralateral subfrontal approach provides a high chance of complete tumor removal and visual improvement with limited complications and recurrences, especially when the tumor is in a unilateral or midline location causing unilateral visual symptoms or bilateral asymmetrical visual symptoms, regardless of tumor size or encasement of major vessels. With the appropriate patient selection, surgical technique, and familiarity with surrounding neurovascular structures, this approach is reliable for TSM surgery.

Obstructive Sleep Apnea and Its Influence on Intracranial Aneurysm.

Obstructive sleep apnea syndrome (OSAS) is associated with cerebrovascular disease, which can lead to life-threatening outcomes. The purpose of the study was to investigate the relationship between OSAS and comorbid intracranial aneurysms. We retrospectively reviewed 564 patients who underwent a polysomnography and brain magnetic resonance angiography as part of their health checkup. We calculated the prevalence of an intracranial aneurysm and OSAS in patients and measured the size of the intracranial aneurysm if present. The mean patient age was 55.6 ± 8.5 years, and 82.3% of them were men. The prevalence of an intracranial aneurysm in patients with OSAS was 12.1%, which is significantly higher than patients with non-OSAS (5.9%, p = 0.031). Patients with OSAS had a much higher prevalence of intracranial aneurysms, after adjusting all possible confounding factors such as age, sex, smoking status, alcohol drinking, and body mass index (odds ratio: 2.32; 95% confidence interval: 1.07-5.04). Additionally, the OSAS group had noticeably larger aneurysms compared with those of the non-OSAS group (3.2 ± 2.0 mm vs. 2.0 ± 0.4 mm, p = 0.013). We found a significant association between OSAS and intracranial aneurysms. OSAS could be another risk factor for the development of intracranial aneurysms.

The long multi-epitope peptide vaccine combined with adjuvants improved the therapeutic effects in a glioblastoma mouse model.

Emerging data have suggested that single short peptides have limited success as a cancer vaccine; however, extending the short peptides into longer multi-epitope peptides overcame the immune tolerance and induced an immune response. Moreover, the combination of adjuvants such as lenalidomide and anti-programmed cell death protein 1 (PD1) with a peptide vaccine showed potential vaccine effects in previous studies. Therefore, the effects of a long multi-epitope peptide vaccine in combination with lenalidomide and anti-PD1 were analyzed in this study. Long multi-epitope peptides from two MHCI peptides (BIRC597-104 and EphA2682-689) and the pan-human leukocyte antigen-DR isotype (HLA-DR) binding epitope (PADRE) were synthesized. The therapeutic effects of long multi-epitope peptides in combination with lenalidomide and anti-PD1 were confirmed in the murine GL261 intracranial glioma model. Immune cells' distribution and responses to the long multi-epitope peptides in combination with these adjuvants were also estimated in the spleens, lymph nodes, and tumor tissues. The difference between long multi-epitope peptides and a cocktail of multi-epitope peptides combined with lenalidomide and anti-PD1 was also clarified. As a result, long multi-epitope peptides combined with lenalidomide and anti-PD1 prolonged the survival of mice according to the suppression of tumor growth in an intracranial mouse model. While long multi-epitope peptides combined with these adjuvants enhanced the percentages of activated and memory effector CD8+ T cells, the increase in percentages of regulatory T cells (Tregs) was observed in a cocktail of multi-epitope peptides combined with lenalidomide and anti-PD1 group in the tumors. Long multi-epitope peptides combined with these adjuvants also enhanced the function of immune cells according to the enhanced pro-inflammatory cytokines and cytotoxicity against GL261 cells in ex vivo. In conclusion, long multi-epitope peptides composed of MHCI peptides, BIRC5 and EphA2, and the MHCII peptide, PADRE, in combination with lenalidomide and anti-PD1 has the potential to improve the therapeutic effects of a vaccine against GBM.

Meningioma With Partial and Spontaneous Regression of Peritumoral Edema on Long-Term Follow Up.

Spontaneous regression of meningioma is rarely observed. We report a one person of an incidentally diagnosed meningioma with a spontaneous regression. The 73-year-old female patient without symptoms showed the right sphenoid meningioma with peritumoral edema. The meningioma was incidentally diagnosed and followed up by MRI for 10 years. The tumor shrank with a decrease of edema on T2 MRI. The initial volume of 58.59 cm3, regressed to 37.16 cm3.