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.

Frontotemporal craniotomy with skin incision along the superior temporal line outside the hairline in bald male patients with temporal gliomas.

A head skin incision is inevitable in neurosurgical procedures and is usually concealed within the hairline. Androgenetic alopecia (AGA) is a progressive hair loss disorder or baldness highly prevalent in men. Therefore, if bald male patients require neurosurgical procedures, skin incisions cannot be concealed, but this subject is yet to be discussed in the literature. This study presents a frontotemporal craniotomy using a skin incision along the superior temporal line, ignoring the hairline in bald male patients. Thirty-three patients with temporal gliomas underwent surgical removal between 2015 and 2022. They were divided into three groups: bald male patients with skin incisions not concealed in the hairline (minimum group, n = 13), bald and non-bald male patients with skin incisions concealed in the hairline (male group, n = 11), and female patients with skin incisions concealed in the hairline (female group, n = 9). In the minimum group, patients had no complaints regarding the incision scar. Cosmetic outcome was excellent, and no cases showed surgical site infection or peripheral facial nerve palsy. Compared with the male and female groups, the minimum group had the shortest skin incision length; however, the craniotomy size and extent of resection were similar. Skin incision for frontotemporal craniotomy cannot be hidden in bald male patients, and the preferred location for the incision is unknown. The skin incision along the superior temporal line is a cosmetically favorable, feasible, and safe procedure.

Ribosomes and Ribosomal Proteins Promote Plasticity and Stemness Induction in Glioma Cells via Reprogramming.

Glioblastoma multiforme (GBM) is a lethal tumor that develops in the adult brain. Despite advances in therapeutic strategies related to surgical resection and chemo-radiotherapy, the overall survival of patients with GBM remains unsatisfactory. Genetic research on mutation, amplification, and deletion in GBM cells is important for understanding the biological aggressiveness, diagnosis, and prognosis of GBM. However, the efficacy of drugs targeting the genetic abnormalities in GBM cells is limited. Investigating special microenvironments that induce chemo-radioresistance in GBM cells is critical to improving the survival and quality of life of patients with GBM. GBM cells acquire and maintain stem-cell-like characteristics via their intrinsic potential and extrinsic factors from their special microenvironments. The acquisition of stem-cell-like phenotypes and aggressiveness may be referred to as a reprogramming of GBM cells. In addition to protein synthesis, deregulation of ribosome biogenesis is linked to several diseases including cancer. Ribosomal proteins possess both tumor-promotive and -suppressive functions as extra-ribosomal functions. Incorporation of ribosomes and overexpression of ribosomal protein S6 reprogram and induce stem-cell-like phenotypes in GBM cells. Herein, we review recent literature and our published data on the acquisition of aggressiveness by GBM and discuss therapeutic options through reprogramming.

Ribosomal proteins induce stem cell-like characteristics in glioma cells as an "extra-ribosomal function".

The characteristic features of plasticity and heterogeneity in glioblastoma (GB) cells cause therapeutic difficulties. GB cells are exposed to various stimuli from the tumor microenvironment and acquire the potential to resist chemoradiotherapy. To investigate how GB cells acquire stem cell-like phenotypes, we focused on ribosomal proteins, because ribosome incorporation has been reported to induce stem cell-like phenotypes in somatic cells. Furthermore, dysregulation of ribosome biogenesis has been reported in several types of cancer. We focused on ribosomal protein S6, which promotes sphere-forming ability and stem cell marker expression in GB cells. We expect that investigation of dysregulation of ribosome biogenesis and extra-ribosomal function in GB will provide new insights about the plasticity, heterogeneity, and therapeutic resistance of GB cells, which can potentially lead to revolutionary therapeutic strategies.

[A case of lymphomatosis cerebri rapidly confirmed by brain biopsy].

Lymphomatosis cerebri (LC) is a variant of primary central nervous system lymphoma, which demonstrates diffuse white matter infiltrates without showing definite enhanced mass lesions on MR scans. We present a case of seventy-one year-old immunocompetent male who manifested with progressive truncal ataxia and drowsiness. The MRI exhibited diffuse white matter lesions from brainstem to cerebral hemispheres with minimum enhanced lesions at the first presentation. Because the diagnosis of LC was suspected, we performed a brain biopsy from the enhanced lesion near the right thalamus, which revealed diffuse large B cell lymphoma. After he underwent methylprednisolone pulse therapy and methotrexate chemotherapy, he obtained remission. Making a diagnosis of LC is often difficult because image findings resemble those of inflammatory or autoimmune diseases. LC is an important differential diagnosis to be considered in patients presenting with diffuse white matter disease. Performing a brain biopsy at the early phase is essential for the correct diagnosis and the favorable prognosis.

[Hyponatremia caused by SIADH following endoscopic third ventriculostomy: a case report].

A 25-year-old man complained of disorientation and gait disturbance during the past 2 weeks. The patient had been treated for cerebellar astrocytoma by open surgery thrice, at ages 3, 5, and 11. Ventriculo-peritoneal shunt was performed for postoperative hydrocephalus at the age of 11. Magnetic resonance imaging(MRI)showed enlargement of both lateral ventricles, ballooning of the third ventricle, and obstruction of the aqueduct of Sylvius. The patient was diagnosed with recurrent hydrocephalus due to shunt malfunction, and treated by endoscopic third ventriculostomy(ETV)using a flexible endoscopic system. He was relieved of the symptoms immediately after surgery, and postoperative MRI showed reduced hydrocephalus. However, the symptoms reoccurred 6 days after surgery. Computed tomography did not show recurrence of hydrocephalus. Laboratory tests revealed hyponatremia(117mEq/L)and low serum osmolality(240mOsm/kg). The patient gained 2.4 kg over the preoperative body weight. The syndrome of inappropriate secretion of antidiuretic hormone(SIADH)was considered to be the cause of the hyponatremia, which was successfully treated with 3 days of fluid restriction. The patient was discharged 24 days after surgery. Hyponatremia is a relatively rare complication of ETV. When a patient shows recurrence of hydrocephalus-related symptoms during the early postoperative period after ETV, hyponatremia caused by SIADH should be considered.