Spinal Dissemination of Pineal Parenchymal Tumors of Intermediate Differentiation Over 10 Years After Initial Treatment: A Case Report.

Pineal parenchymal tumors (PPTs) are rare, accounting for less than 0.3% of all primary central nervous system (CNS) tumors. Pineal parenchymal tumors of intermediate differentiation (PPTID) (WHO grade 2 or 3) show an intermediate prognosis between pineocytoma and pineoblastoma. The clinical course is unknown, and the optimal treatment for PPTID, especially for recurrence, has not been determined. We report a case of PPTID with spinal dissemination over 10 years after treatment and survival for four years. A 56-year-old woman presented with headaches and diplopia. Computerized tomography (CT) and magnetic resonance imaging (MRI) revealed a pineal mass, but leptomeningeal dissemination was not identified on whole-spine MRI. Microsurgical gross total tumor resection (GTR) was performed, and the pathological diagnosis was PPTID (grade 3). In addition, a later study found it to harbor a KBTBD4 mutation. She underwent whole-brain radiation therapy with a focal boost. The patient was unable to continue chemotherapy for severe myelosuppression after the first course of treatment. Eleven years after the surgery, she was unable to walk, and a whole-spine MRI revealed multiple masses at C3-4, T4, and cauda equina. Fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed accumulations of the same lesions. No recurrence was observed in the brain. A biopsy of the caudal portion was performed, and the histopathological findings were the same as those of the initial surgery. Spinal dissemination was refractory to chemotherapy but responded to whole spine radiotherapy with focal boost, and she remained tumor-free for four years. We considered good local control with a combination of GTR and subsequent radiation therapy to contribute to long-term survival. The timing of spinal radiation administration is controversial because of the tendency for late cerebrospinal dissemination. The importance of long-term follow-up of the spine and head is emphasized. In PPTID cases with good local control, withholding spinal radiation until spinal dissemination occurs may become a long-term treatment plan.

Surgical safety criteria for burr hole surgery with urokinase in patients with acute subdural hematoma: Retrospective comparison between burr hole surgery and craniotomy.

BACKGROUND: Acute subdural hematoma (ASDH) is a common disease and craniotomy is the first choice for removing hematoma. However, patients for whom craniotomy or general anesthesia is contraindicated are increasing due to population aging. In our department, we perform burr hole surgery under local anesthesia with urokinase administration for such patients. We compared the patient background and outcomes between burr hole surgery and craniotomy to investigate the surgical safety criteria for burr hole surgery. METHODS: We reviewed 24 patients who underwent burr hole surgery and 33 patients who underwent craniotomy between January 2010 and April 2020 retrospectively. RESULTS: The median age of the burr hole surgery group was older (P = 0.01) and they had multiple pre-existing conditions. Compared with the craniotomy group, neurological deficits and CT findings were minor in the burr hole surgery group, whereas the maximum hematoma thickness was not significantly different. The hematoma was excreted after a total of 54,000 IU of urokinase was administered for a median of 3 days. The Glasgow Coma Scale score improved in all patients in the burr hole surgery group and there were no deaths. Age, especially over 65 y.o., (OR 1.16, 95% CI 1.04-1.30) and the absence of basal cistern disappearance (OR 0.04, 95% CI 0.004-0.39) were significant factors. CONCLUSION: Burr hole surgery was performed safely in all patients based on the age, especially older than 65 y.o., and the absence of basal cistern disappearance. ASDH in the elderly is increasing and less invasive burr hole surgery with urokinase is suitable for the super-aging society.

Regulation of proliferation and functioning of transplanted cells by using herpes simplex virus thymidine kinase gene in mice.

Though cell transplantation is becoming an attractive therapeutic method, uncontrolled cell proliferation or overexpression of cellular functions could cause adverse effects. These unfavorable outcomes could be avoided by regulating the proliferation or functioning of transplanted cells. In this study, we used a combination of the herpes simplex virus thymidine kinase (HSVtk) gene, a suicide gene, and ganciclovir (GCV) to control the proliferation and functioning of insulin-secreting cells after transplantation in diabetic mice. Mouse pancreatic ß cell line MIN6 cells were selected as insulin-secreting cells for transfection with the HSVtk gene to obtain MIN6/HSVtk cells. Proliferation of MIN6/HSVtk cells was suppressed by GCV in a concentration-dependent manner; 0.25 µg/mL GCV maintained a constant number of MIN6/HSVtk cells for at least 16 days. MIN6 or MIN6/HSVtk cells were then transplanted to streptozotocin-induced diabetic mice. Mice transplanted with MIN6 cells exhibited hypoglycemia irrespective of GCV administration. In contrast, normal (around 150 mg/dL) blood glucose levels were maintained in mice transplanted with MIN6/HSVtk cells by a daily administration of 50 mg/kg of GCV. These results indicate that controlling the proliferation and functioning of HSVtk gene-expressing cells by GCV could greatly improve the usefulness and safety of cell-based therapy.

Bitterness evaluation of intact and crushed Vesicare orally disintegrating tablets using taste sensors.

OBJECTIVE: Vesicare tablets, whose main component is solifenacin succinate, are known to be extremely bitter. The purpose of this study was to evaluate the effect of crushing on the bitterness of the Vesicare orally disintegrating tablets (ODTs). METHOD: Vesicare ODTs and conventional Vesicare tablets (CTs) were crushed either heavily or lightly. The bitterness scores and release rates of sample solutions obtained 5, 10, 30, 60, 90 or 120 s after placing a crushed CT or ODT containing 5 mg solifenacin in 40 ml of water were predicted using two taste sensors (SA402B and a-ASTREE) and HPLC, respectively. The particle size and the surfaces of the crushed tablets were observed microscopically. KEY FINDINGS: The predicted bitterness scores and the drug release rates of CTs were high, irrespective of the degree of crushing. The lightly crushed ODT was predicted to be less bitter than the heavily crushed ODT. In lightly crushed ODTs, spherical particles were observed, about 200 mm in diameter. CONCLUSIONS: The degree of crushing was a critical factor in determining the expression of bitterness by crushed ODTs. When intact tablets of Vesicare must be crushed to adjust the dosage, it is strongly recommended that ODTs be crushed gently.