Clinical and molecular features of patients with IDH1 wild-type primary glioblastoma presenting unexpected short-term survival after gross total resection.

BACKGROUND: This study investigated the factors influencing short-term survivors (STS) after gross total resection (GTR) in patients with IDH1 wild-type primary glioblastoma. METHODS: We analyzed five independent cohorts who underwent GTR, including 83 patients from Kitasato University (K-cohort), and four validation cohorts of 148 patients from co-investigators (V-cohort), 66 patients from the Kansai Molecular Diagnosis Network for the Central Nervous System tumors, 109 patients from the Cancer Genome Atlas, and 40 patients from the Glioma Longitudinal AnalySiS. The study defined STS as those who had an overall survival ≤ 12 months after GTR with subsequent radiation therapy, and concurrent and adjuvant temozolomide (TMZ). RESULTS: The study included 446 patients with glioblastoma. All cohorts experienced unexpected STS after GTR, with a range of 15.0-23.9% of the cases. Molecular profiling revealed no significant difference in major genetic alterations between the STS and non-STS groups, including MGMT, TERT, EGFR, PTEN, and CDKN2A. Clinically, the STS group had a higher incidence of non-local recurrence early in their treatment course, with 60.0% of non-local recurrence in the K-cohort and 43.5% in the V-cohort. CONCLUSIONS: The study revealed that unexpected STS after GTR in patients with glioblastoma is not uncommon and such tumors tend to present early non-local recurrence. Interestingly, we did not find any significant genetic alterations in the STS group, indicating that such major alterations are characteristics of GB rather than being reliable predictors for recurrence patterns or development of unexpected STS.

Histological analysis of neuronal changes in the olfactory cortex during pregnancy.

Fluctuations in olfactory sensitivity are widely known to occur during pregnancy and may be responsible for hyperemesis gravidarum. These changes are thought to be caused by structural and functional alterations in neurons in response to marked changes of the hormonal milieu. In this study, we examined changes in neurons in the olfactory cortex during pregnancy and after delivery in rats. Dendritic spine densities were measured in the piriform cortex (PIR) and posterolateral cortical amygdala (COApl), which are involved in olfaction. The results showed increased numbers of dendritic spines in the PIR in mid-pregnancy and in the COApl during early and late pregnancy, but not in the motor area of the cerebral cortex, indicating a correlation with changes in olfactory sensitivity during pregnancy. Immunohistochemical analysis of expression of ovarian hormone receptors in these brain regions revealed a decrease in the number of estrogen receptor α-positive cells during pregnancy in the PIR and during pregnancy and the postpartum period in the COApl. Regarding pregnancy-related peptide hormones, oxytocin receptors were expressed in the PIR and COApl, while prolactin receptors were not found in these regions. Accordingly, oxytocin-containing neurites were distributed in both regions. These results suggest that the balance of these hormonal signals has an effect on olfactory sensitivity in pregnant females.

Free Flap Survival with External Jugular Vein as a Detour Due to Internal Jugular Vein Thrombosis.

In head and neck reconstructions, venous anastomosis of the free flap to the internal jugular vein system is a common procedure. However, in some cases, postoperative complications such as internal jugular vein thrombosis can occur. In this report, we present a case where postoperative internal jugular vein thrombosis was identified after venous anastomosis of the free flap to the internal jugular vein system. In this case, preserving the external jugular vein allowed for retrograde flow of venous blood in the internal jugular vein to enter the external jugular vein, serving as an alternative drainage pathway. This finding highlights the potential benefits of preserving the external jugular vein in head and neck surgery involving free flap venous anastomosis to mitigate the adverse effects of internal jugular vein thrombosis. Further investigations are warranted to better understand the underlying mechanisms and optimize surgical approaches for improved patient outcomes.

Effect of newly developed scissors-attached micro-forceps on the recipient clamp time and occurrence of anastomotic site infarction after bypass surgery for moyamoya disease.

Introduction: This study aimed to examine the effect of newly developed scissors-attached micro-forceps in superficial temporal artery-to-middle cerebral artery (STA-MCA) anastomosis for moyamoya disease (MMD). Materials and methods: Of 179 consecutive STA-MCA anastomoses on 95 hemispheres of 71 MMD patients at the University of Fukui Hospital between 2009 and 2023, 49 anastomoses on 26 hemispheres of 21 patients were enrolled in this retrospective cohort clinical trial intraoperative indocyanine green video-angiography did not demonstrate bypass patency in three anastomoses in two patients who were excluded. Twenty-one anastomosis in 19 hemispheres of 16 patients were performed using the conventional micro-forceps (conventional group, CG), and 25 anastomoses in 22 hemispheres of 19 patients were performed using scissors-attached micro-forceps (scissors group, SG). A small infarction near the anastomotic site detected using postoperative diffusion-weighted imaging was defined as anastomotic site infarction (ASI). Factors affecting the occurrence of ASI were examined by univariate, logistic regression, and receiver operating curve (ROC) analysis. Results: There were no significant differences in clinical parameters such as age, sex, number of sacrificed branches, number of sacrificed large branches, and number of sutures between the CG and SG. However, the clamp time and occurrence of ASI were significantly lower in the SG than in the CG. Logistic regression analysis revealed that the clamp time was the only significant factor predicting the occurrence of ASI. A receiver operating curve analysis also revealed that the clamp time significantly predicted the occurrence of ASI (area under the curve, 0.875; cutoff value, 33.2 min). Conclusion: The newly developed scissors-attached micro-forceps could significantly reduce the clamp time and occurrence of ASI in STA-MCA anastomosis for MMD.

Usefulness of Serum Soluble Interleukin-2 Receptor Levels for Differentiating between PCNSL and SCNSL.

Serum soluble interleukin-2 receptor (sIL-2R) is a practical tumor marker that is elevated in hematogenous tumors. The purpose of this study was to determine the usefulness of serum sIL-2R for differentiating among malignant brain tumors, including primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL). This study retrospectively investigated the sIL-2R levels in 130 patients with various types of malignant brain tumors, including PCNSL patients (n = 48) and SCNSL (n = 8); metastatic brain tumors (MTs, n = 16); and glioblastoma (GBM, n = 58). The median sIL-2R level (U/mL) of the PCNSL, SCNSL, MTs, and GBM groups were 489.7, 1024.8, 413.3, and 332.7 respectively. The sIL-2R level was significantly higher in the SCNSL group than in the PCNSL or other groups. The area under the ROC curve generated from the sIL-2R level was 0.826 (sensitivity: 0.875, specificity: 0.667, cutoff value: 521 U/mL) for differentiating SCNSL from PCNSL and 0.685 (sensitivity: 0.667, specificity: 0.707, cutoff value: 342 U/mL) for differentiating PCNSL from GBM. Measurement of sIL-2R level was convenient and useful to differentiate between SCNSL and PCSNL, both of which demand different treatment strategies.

CEP-1347 Targets MDM4 Protein Expression to Activate p53 and Inhibit the Growth of Glioma Cells.

BACKGROUND/AIM: The development of pharmacological inhibitors targeting negative regulators of p53, such as murine double minute (MDM) 2 and, more recently, MDM4, has been actively pursued as a potential strategy to treat cancers with wild-type p53. We previously showed that CEP-1347, a small molecule kinase inhibitor originally developed for the treatment of Parkinson's disease, suppressed MDM4 expression and activated wild-type p53 in retinoblastoma cells. However, it remains unknown whether CEP-1347 acts as an MDM4 inhibitor and as such activates p53 in other types of human cancer cells. MATERIALS AND METHODS: The effects of CEP-1347 and MDM4 knockdown on the mRNA and protein expression of components of the p53 pathway, including MDM4, in human glioma cell lines with and without p53 mutation were examined by RT-PCR and western blot analyses. Trypan blue dye exclusion was used to examine the effect of CEP-1347 on cell growth. RESULTS: CEP-1347 decreased the expression of MDM4, increase that of p53, and activated the p53 pathway in glioma cells with wild-type p53. Knockdown-mediated inhibition of MDM4 expression in a glioma cell line with wild-type p53 that overexpresses MDM4 resulted in increased p53 expression and activation of the p53 pathway. CEP-1347 preferentially inhibited the growth of glioma cells with wild-type p53 without showing toxicity to normal cells at clinically relevant concentrations. CONCLUSION: Our findings suggest CEP-1347 is a novel inhibitor of MDM4 protein expression and as such activates p53 to inhibit the growth of cancer cells with wild-type p53, including retinoblastoma and glioblastoma.

Schlieren Phenomenon for Identification of Lymphorrhea Point.

Surgical invasion of the lymphatic system can lead to lymphorrhea. Lymphorrhea is first treated conservatively, but is often refractory and subsequently treated surgically. In surgery, it is difficult to identify the lymphatic leak points visually. In this study, we observed the schlieren phenomenon based on the difference in the refractive index between glucose solution and lymph fluid, and were able to easily identify the site of the lymphatic leakage in real time and treat lymphorrhea.

Functional Outcomes of Microsurgical Resection for Cavernous Malformations of the Brainstem.

Long-term functional outcomes of microsurgical resection for cavernous malformations of the brainstem (CMB) have been largely unknown. Favorable outcomes after CMB surgery might be related to the achievement of complete resection and mRS at 1 month after the surgery. Preoperative sensory, cerebellar, trigeminal nerve, and lower cranial nerve symptoms tended to improve after surgery.We evaluated 25 consecutive patients with CMB surgically treated at our center between 2006 and 2021. The subjects included 11 men and 14 women, with ages ranging from 13 to 61 years (mean ± SD = 37 ± 12 years). Modified Rankin Scale (mRS) scores and neurological symptoms of the patients were evaluated before surgery, 1 month after surgery, and at the final follow-up at the outpatient clinic. The mean number of previous hemorrhages was 7 ± 1.0 and the mean lesion size was 21 ± 8 mm. The mRS scores on admission and at the final follow-up were 2.9 points and 1.7 points, respectively. The mRS scores at the final follow-up were significantly improved compared to those on admission. There was no statistical difference between the preoperative mRS and mRS at 1 month after the operation. Multivariable analysis indicated that mRS scores at 1 month after surgery were the most significant predictive factors for favorable outcomes. Complete resection was achieved in 24 of 33 operations. Incomplete resection was significantly related to the frequency of subsequent recurrent hemorrhage and high mRS scores at the final follow-up. Preoperative sensory, cerebellar, trigeminal nerve, and lower cranial nerve symptoms improved significantly after surgery.

Incisional Hernia Repaired Using Thigh Muscle Fascia After Kidney Transplantation: A Case Report.

BACKGROUND: Although monofilament mesh-based repair is a safe and effective procedure for incisional hernia (IH) in organ transplant patients, there is no definite evidence of IH treatment for patients with graft rejection and enhanced immunosuppressive therapy. We report a successful case of large IH repair using an autologous thigh muscle fascia sheet in a kidney transplant patient. CASE PRESENTATION: A 69-year-old man had IH from the incision of kidney transplantation, which was performed 6 years ago. He had a large right lower abdominal distension hanging down to the inguinal portion. A computed tomography scan revealed a large IH with a maximum abdominal defect diameter of 15 cm. The hernia sac contained the intestine, colon, and transplanted kidney, which had pulled out along with the retroperitoneum and protruded into the abdominal wall. He had chronic active acute antibody-mediated rejection, which required frequent steroid pulse therapy and additional or adjusted immunosuppressive drugs. After total circumferential exposure of the hernia sac and abdominal fascia, the abdominal wall defect was closed using a horizontal mattress suture. The sutured line was covered with a thigh muscle fascia sheet harvested from the patient's right femur and attached to the closed fascia. He was discharged on postoperative day 13 without any complications, and no IH recurrence was observed 10 months after surgery. CONCLUSIONS: Hernia repair using autologous tissue could be a treatment option for post-transplant IH with a higher risk of infection.

A surgical case of pediatric spinal medulloepithelioma.

Embryonal tumor with multilayered rosettes (ETMR), C19MC-altered was introduced to the World Health Organization classification of central nervous system tumors in 2016. It is characterized by amplification or fusion of the chromosome 19 microRNA cluster (C19MC) locus at 19q13.42. Medulloepithelioma also an ETMR but lacks C19MC alteration. We report a rare case of spinal medulloepithelioma in a 2-year-old boy and review the literature.

Necessity for craniospinal irradiation of germinoma with positive cytology without spinal lesion on MR imaging-A controversy.

BACKGROUND: Cerebrospinal fluid (CSF) cytology and spinal MR imaging are routinely performed for staging before treatment of intracranial germinoma. However, the interpretation of the results of CSF cytology poses 2 unresolved clinical questions: (1) Does positive CSF cytology correlate with the presence of spinal lesion before treatment? and (2) Is craniospinal irradiation (CSI) necessary for patients with positive CSF cytology in the absence of spinal lesion? METHODS: Multicenter retrospective analyses were performed based on a questionnaire on clinical features, spinal MR imaging finding, results of CSF cytology, treatments, and outcomes which was sent to 86 neurosurgical and 35 pediatrics departments in Japan. Pretreatment frequencies of spinal lesion on MR imaging were compared between the patients with positive and negative cytology. Progression-free survival (PFS) rates were compared between patients with positive CSF cytology without spinal lesion on MR imaging treated with CSI and with whole brain or whole ventricular irradiation (non-CSI). RESULTS: A total of 92 germinoma patients from 45 institutes were evaluated by both CSF cytology and spinal MR images, but 26 patients were excluded because of tumor markers, the timing of CSF sampling or incomplete estimation of spinal lesion. Of the remaining 66 germinoma patients, spinal lesions were equally identified in patients with negative CSF cytology and positive cytology (4.9% and 8.0%, respectively). Eleven patients treated with non-CSI had excellent PFS comparable to 11 patients treated with CSI. CONCLUSION: CSI is unnecessary for germinoma patients with positive CSF cytology without spinal lesions on MR imaging.

Healing Effect of Subcutaneous Administration of Granulocyte Colony-Stimulating Factor on Acute Rotator Cuff Injury in a Rat Model.

Granulocyte colony-stimulating factor (G-CSF) is a cytokine that mobilizes bone marrow-derived cells (BMDCs) to peripheral blood and has been clinically used to treat neutropenia. Previously, we reported that BMDCs migrated into the rotator cuff repair site via peripheral blood in the healing process. However, techniques to accelerate the healing process using the peripheral blood pathway have not been established. We evaluated whether G-CSF has a noteworthy effect on improving rotator cuff healing by enhancing the influx of BMDCs into the peripheral blood. We used Sprague-Dawley rats and chimeric rats, selectively expressing green fluorescent protein (GFP) in BMDCs. Their bilateral supraspinatus tendons were resected and sutured to the greater tuberosity of the humerus using the Masson-Allen technique, and G-CSF was subcutaneously injected for 5 days after surgery. Several GFP-positive cells were observed around the enthesis in the G-CSF-treated group compared with that in the Control group. Histological analysis revealed that the tendon-to-bone maturing scores and the Safranin O-stained cartilaginous areas were significantly higher in G-CSF-injected rats than in the control rats at weeks 4 and 8 after surgery. Consistently, the ultimate force to failure in the G-CSF-treated group significantly increased compared with the Control group at weeks 4 and 8 after surgery. These results suggest that BMDCs mobilized into the peripheral blood after G-CSF administration migrated to the rotator cuff repair area and effectively enhanced rotator cuff healing by promoting tenocyte and cartilage matrix production. In conclusion, the BMDC mobilization technique by G-CSF treatment via peripheral blood will provide a potential therapeutic approach for rotator cuff healing with clinically relevant applications. Impact statement As the retear rate following rotator cuff repair is high, new methods to aid its healing are required. Granulocyte colony-stimulating factor (G-CSF) has been used clinically and may represent a novel approach to treating rotator cuff tear. Herein, using a rat model, we elucidate the kinetics of bone marrow-derived mesenchymal stem cells at the repair site following G-CSF administration and describe the underlying mechanism by which G-CSF can help promote the repair of the rotator cuff.

Estrogens influence female itch sensitivity via the spinal gastrin-releasing peptide receptor neurons.

There are sex differences in somatosensory sensitivity. Circulating estrogens appear to have a pronociceptive effect that explains why females are reported to be more sensitive to pain than males. Although itch symptoms develop during pregnancy in many women, the underlying mechanism of female-specific pruritus is unknown. Here, we demonstrate that estradiol, but not progesterone, enhances histamine-evoked scratching behavior indicative of itch in female rats. Estradiol increased the expression of the spinal itch mediator, gastrin-releasing peptide (GRP), and increased the histamine-evoked activity of itch-processing neurons that express the GRP receptor (GRPR) in the spinal dorsal horn. The enhancement of itch behavior by estradiol was suppressed by intrathecal administration of a GRPR blocker. In vivo electrophysiological analysis showed that estradiol increased the histamine-evoked firing frequency and prolonged the response of spinal GRP-sensitive neurons in female rats. On the other hand, estradiol did not affect the threshold of noxious thermal pain and decreased touch sensitivity, indicating that estradiol separately affects itch, pain, and touch modalities. Thus, estrogens selectively enhance histamine-evoked itch in females via the spinal GRP/GRPR system. This may explain why itch sensation varies with estrogen levels and provides a basis for treating itch in females by targeting GRPR.

Subcellular dynamics of estrogen-related receptors involved in transrepression through interactions with scaffold attachment factor B1.

Estrogen-related receptor (ERR), a member of the nuclear receptor superfamily, consists of three subtypes (α, ß, γ) and has strong homology with estrogen receptor. No endogenous ligands have been identified for ERRs, but they play key roles in metabolic, hormonal, and developmental processes as transcription factors without ligand binding. Although subnuclear dynamics are essential for nuclear events including nuclear receptor-mediated transcriptional regulation, the dynamics of ERRs are poorly understood. Here, we report that ERRs show subcellular kinetic changes in response to diethylstilbestrol (DES), a synthetic estrogen that represses the transactivity of all three ERR subtypes, using live-cell imaging with fluorescent protein labeling. Upon DES treatment, all ERR subtypes formed discrete clusters in the nucleus, with ERRγ also displaying nuclear export. Fluorescence recovery after photobleaching analyses revealed significant reductions in the intranuclear mobility of DES-bound ERRα and ERRß, and a slight reduction in the intranuclear mobility of DES-bound ERRγ. After DES treatment, colocalization of all ERR subtypes with scaffold attachment factor B1 (SAFB1), a nuclear matrix-associated protein, was observed in dot-like subnuclear clusters, suggesting interactions of the ERRs with the nuclear matrix. Consistently, co-immunoprecipitation analyses confirmed enhanced interactions between ERRs and SAFB1 in the presence of DES. SAFB1 was clarified to repress the transactivity of all ERR subtypes through the ERR-response element. These results demonstrate ligand-dependent cluster formation of ERRs in the nucleus that is closely associated with SAFB1-mediated transrepression. Taken together, the present findings provide a new understanding of the pathophysiology regulated by ERR/SAFB1 signaling pathways and their subcellular dynamics.

Hepatocyte growth factor regulates HIF-1α-induced nucleus pulposus cell proliferation through MAPK-, PI3K/Akt-, and STAT3-mediated signaling.

Intervertebral discs are important for maintaining mobility and offer support to the body trunk. If these discs lose their biomechanical features, lower back pain can occur. We previously reported that hepatocyte growth factor (HGF) promotes cell proliferation and suppresses apoptosis, inflammation, and matrix degradation in nucleus pulposus (NP) cells. In the present study, we investigated the molecular mechanisms of how HGF promotes the proliferation of NP cells in hypoxic conditions. Hypoxic stimulation promoted modest cell proliferation, which was further upregulated by HGF. Expression of hypoxia-inducible factor (HIF-1α) protein, which contributes to the maintenance of homeostasis in NP cells, was also upregulated in hypoxia-treated cell groups; HGF further increased HIF-1α expression in NP cells. Additionally, knockdown of HIF-1α expression significantly reduced the proliferation of NP cells. An MAPK inhibitor inhibited the expression of HIF-1α and pERK, as well as cell proliferation in a dose-dependent manner. Similarly, inhibiting the PI3K/Akt and STAT3 pathways also decreased the expression of HIF-1α and cell proliferation. These results show that under hypoxic conditions, HGF promotes NP cell proliferation via HIF-1α-, MAPK-, PI3K/Akt-, and STAT3-mediated signaling which is involved in this pathway. The control of these signaling pathways may be a target for potential therapeutic strategies for the treatment of disc degeneration in hypoxic conditions.

Malignant Progression of an IDH Mutant Brainstem Glioma in Adult.

Brain stem gliomas (BSG) in adults are rare and less aggressive than those in children. However, the molecular profile of adult BSG cases has not been well characterized. We report a case of adult BSG with isocitrate dehydrogenase (IDH) mutation. A 43-year-old male was admitted to our hospital with diplopia and right-sided hypesthesia. An open biopsy led to the tumor being diagnosed as a diffuse astrocytoma. Immunohistochemically, the tumor was positive for IDH1 R132H, but negative for H3K27M. The patient received 54 Gy of local radiotherapy and adjuvant temozolomide, which resulted in the size of the lesion decreasing significantly. At 56 months after the initial diagnosis, the patient was referred to our hospital with a severe headache and ataxia. Magnetic resonance imaging (MRI) revealed a contrast-enhanced lesion in the brain stem, which extended into the left cerebellar hemisphere and brainstem. Partial tumor removal was performed, and a pathological examination revealed the features of glioblastoma. Immunohistochemically, the tumor was positive for IDH1 R132H and p53 and negative for ATRX. To the best of our knowledge, there are few reports about adult case of brain stem astrocytoma to be confirmed via histological and molecular examinations of the primary and recurrent tumor. We exhibit detailed pathological and molecular findings which resembles to IDH mutant supratentorial diffuse astrocytic tumors.

So-called bifocal tumors with diabetes insipidus and negative tumor markers: are they all germinoma?

BACKGROUND: The Delphi consensus statements on the management of germ cell tumors (GCTs) failed to reach agreements on the statement that the cases with (i) pineal and neurohypophyseal bifocal lesion, (ii) with diabetes insipidus, and (iii) with negative tumor markers can be diagnosed as germinoma without histological verification. To answer this, multicenter retrospective analysis was performed. METHODS: A questionnaire on clinical findings, histological diagnosis, and details of surgical procedures was sent to 86 neurosurgical and 35 pediatrics departments in Japan. RESULTS: Fifty-one institutes reported 132 cases that fulfilled the 3 criteria. Tissue sampling was performed in 91 cases from pineal (n = 44), neurohypophyseal (n = 32), both (n = 6), and distant (n = 9) lesions. Histological diagnosis was established in 89 cases: pure germinoma or germinoma with syncytiotrophoblastic giant cells in 82 (92.1%) cases, germinoma and mature teratoma in 2 cases, and granulomatous inflammation in 2 cases. Histological diagnosis was not established in 2 cases. Although no tumors other than GCTs were identified, 3 (3.4%) patients had non-germinomatous GCTs (NGGCTs). None of the patients developed permanent complications after endoscopic or stereotactic biopsy. Thirty-nine patients underwent simultaneous procedure for acute hydrocephalus without permanent complications, and hydrocephalus was controlled in 94.9% of them. CONCLUSION: All patients who fulfilled the 3 criteria had GCTs or granulomatous inflammation, but not other types of tumors. However, no fewer than 3.4% of the patients had NGGCTs. Considering the safety and the effects of simultaneous procedures for acute hydrocephalus, biopsy was recommended in such patients.

TERT promoter mutation associated with multifocal phenotype and poor prognosis in patients with IDH wild-type glioblastoma.

BACKGROUND: Although mutations in the promoter region of the telomerase reverse transcriptase (TERTp) gene are the most common alterations in glioblastoma (GBM), their clinical significance remains unclear. Therefore, we investigated the impact of TERTp status on patient outcome and clinicopathological features in patients with GBM over a long period of follow-up. METHODS: We retrospectively analyzed 153 cases of GBM. Six patients with isocitrate dehydrogenase 1 (IDH1) or H3F3A gene mutations were excluded from this study. Among the 147 cases of IDH wild-type GBM, 92 (62.6%) had the TERTp mutation. Clinical, immunohistochemical, and genetic factors (BRAF, TP53 gene mutation, CD133, ATRX expression, O 6-methylguanine-DNA methyltransferase [MGMT] promoter methylation) and copy number alterations (CNAs) were investigated. RESULTS: GBM patients with the TERTp mutation were older at first diagnosis versus those with TERTp wild type (66.0 vs. 60.0 years, respectively, P = .034), and had shorter progression-free survival (7 vs. 10 months, respectively, P = .015) and overall survival (16 vs. 24 months, respectively, P = .017). Notably, magnetic resonance imaging performed showed that TERTp-mutant GBM was strongly associated with multifocal/distant lesions (P = .004). According to the CNA analysis, TERTp mutations were positively correlated with EGFR amp/gain, CDKN2A deletion, and PTEN deletion; however, these mutations were negatively correlated with PDGFR amp/gain, CDK4 gain, and TP53 deletion. CONCLUSIONS: TERTp mutations were strongly correlated with multifocal/distant lesions and poor prognosis in patients with IDH wild-type GBM. Less aggressive GBM with TERTp wild type may be a distinct clinical and molecular subtype of IDH wild-type GBM.

TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations.

TERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90-100%) were associated with favorable prognosis (p < 0.05). A multivariable Cox regression model revealed that TERT promoter mutation had a significantly favorable prognostic impact (hazard ratio = 0.421, p = 0.049), while 1p/19q codeletion did not have a significant impact (hazard ratio = 0.648, p = 0.349). Analyses incorporating patient clinical and genetic information were further conducted to identify subgroups showing the favorable prognostic impact of TERT promoter mutation. Among the grade II-III glioma patients with a KPS score of 90 or 100, those with IDH-TERT co-mutation and intact 1p/19q (n = 17) showed significantly longer survival than those with IDH mutation, wild-type TERT, and intact 1p/19q (n = 185) (5-year overall survival, 94% and 77%, respectively; p = 0.032). Our results demonstrate that TERT promoter mutation predicts favorable prognosis independent of 1p/19q codeletion in IDH-mutated gliomas. Combined with its adverse effect on survival among IDH-wild glioma cases, the bivalent prognostic impact of TERT promoter mutation may help further refine the molecular diagnosis and prognostication of diffuse gliomas.

[Optic Neuropathy Secondary to Compression by the Internal Carotid Artery Concomitant with an Inflammatory Granuloma:A Case Report].

A 77-year-old man presented with a 6-month history of progressive right optic neuropathy secondary to compression by the ipsilateral internal carotid artery(ICA). We performed anterior clinoidectomy and optic canal unroofing. Subsequently, we wrapped the ICA with a polytetrafluoroethylene tape, pulled the vessel laterally, and sutured the tape to the dura mater at the anterior skull base for optimal decompression. An inflammatory mass lesion was observed around the ICA, which led to further compression of the optic nerve. Histopathological examination of the resected specimen showed an inflammatory granuloma. The patient's visual field deficit showed partial improvement postoperatively. Transposition using a tape might be an effective surgical alternative for compressive optic neuropathy.