Ventricular opening and cerebrospinal fluid circulation accelerate the biodegradation process of carmustine wafers suggesting their immunomodulation potential in the human brain.

PURPOSE: Opening the ventricular system during glioblastoma surgery is often necessary, but the consequent effect on the tumor microenvironment of glioblastoma remains unknown. Implantation of carmustine wafer enables direct drug delivery to the tumor site; however, the exact mechanism of the wafer's biodegradation process is unclear, and the available data is limited to in vivo non-human mammalian studies. We hypothesized that the ventricular opening affects the degradation process of the wafer and the glioblastoma tumor microenvironment. METHODS: This study included 30 glioblastoma patients. 21 patients underwent carmustine wafer implantation during initial surgery. All patients underwent repeated surgical resection upon recurrence, allowing for pathological comparison of changes associated with wafer implantation. Immunohistochemical analyses were performed using CD68, TMEM119, CD163, IBA1, BIN1, and CD31 antibodies to highlight microglia, macrophages, and tumor vascularity, and the quantitative scoring results were correlated with clinical, molecular, and surgical variables, including the effect of the ventricular opening. RESULTS: The carmustine wafer implanted group presented significantly less TMEM119-positive microglia within the tumor (P = 0.0002). Simple and multiple regression analyses revealed that the decrease in TMEM119-positive microglia was correlated with longer intervals between surgeries and opened ventricular systems. No correlation was observed between age, methylated O6-methylguanine DNA methyltransferase promoter expression, and the extent of surgical resection. CONCLUSIONS: Our study findings strongly suggest that biomaterials may possess immunomodulation capacity, which is significantly impacted by the ventricular opening procedure. Furthermore, our data highlights the pathophysiological effects of the ventricular opening within the surrounding human brain, especially after the wafer implantation.

Development of a novel fungicide, tolprocarb.

Tolprocarb developed by Mitsui Chemicals Agro, Inc. (Tokyo, Japan) was discovered as a new oomycete fungicide. However, its antifungal spectrum and action mechanisms against fungi are completely different from those of the original compound, iprovalicarb. Tolprocarb has a potent and highly controlled effect on a rice blast fungus Magnaporthe grisea, and its mode of action was revealed to be the inhibition of polyketide synthase in the melanin biosynthesis pathway. In addition, tolprocarb induced systemic acquired resistance in Arabidopsis thaliana and rice (Oryza sativa L.). Owing to these double modes of action, tolprocarb can effectively control not only rice blast but also bacterial diseases, and has a low risk of developing fungicide-resistant isolates. Tolprocarb also provides long-term residual activity. A meta-analysis was performed in order to demonstrate tolprocarb's superior control against panicle blast in paddy fields. In addition, tolprocarb did not show cross-resistance against the fungi that are resistant to dehydratase inhibitor in melanin biosynthesis (Melanin Biosynthesis Inhibitor-Dehydratase; MBI-D) or respiratory complex III: cytochrome bc 1 at Quinone outside site inhibitor (Quinone outside Inhibitor; QoI). Owing to its stable effects, tolprocarb appears to be a suitable choice for practical use against fungi in the rice production field.

Clinicopathological features of human brainstem gliomas.

We describe the clinicopathological features of 25 brainstem gliomas (BSGs). Twenty BSGs located in the pons and were all in children. Four BSGs located in the medulla oblongata were in 2 children and 2 adults. One (in a child) was located in the midbrain. Radiological findings on MR images were low-intensity on T1 weighted images and high-intensity on T2 weighted images. Mean survival when pontine glioma was treated by radiotherapy and/or use of temozolomide was 14 months, although 4 patients (3 cervicomedullary types and one focal type arising from midbrain) are alive. Follow up was from 5 months to 6 years. Histopathological features of 10 cases of the diffuse type were: 4 grade II astrocytomas, 4 grade III astrocytomas, and 2 glioblastomas. MIB-1 index was from 0.8 to 38 %. P53 was positive for 80 % of 15 tumors and there were no negative results. MGMT was positive in 60 % of 15 tumors and negative in 12.4 %. IDH1 was negative in 61.6 %. There was no positive result for IDH1 in this study. Thus, our histopathological results were indicative of high p53 immunoreactivity and no IDH1 immunoreactivity related to secondary malignant change.

Granulofilamentous meningioma.

A 55-year old female was referred to the Department of Neurosurgery, Kitasato Hospital, because of a hearing impairment. Neuroimaging revealed a typical meningioma attached to the falx in the right frontal region. During surgery, an encapsulated, circumscribed, reddish-gray, slightly hard tumor attached to the falx was completely removed by an interhemispheric approach. On light microscopy, many of the tumor cells contained eosinophilic inclusions with single or multiple vacuoles that displaced the cytoplasm. The nuclei of the tumor cells were eccentric. There were no signs of malignancy in the specimen. Electron microscopy revealed that most of the eosinophilic inclusions were composed of filaments measuring 12 nm in diameter. There have been several reports of benign meningiomas with eosinophilic inclusions composed of intermediate filaments. The microscopic differences between these types of tumor and rhabdoid meningiomas are very subtle, and it is important the two types of tumors are not confused. Benign meningiomas with eosinophilic inclusions comprising intermediate filaments, for example the tumor described in this report, have been diagnosed as granulofilamentous meningiomas, which is a subtype of benign meningioma.

Utility of intraoperative fluorescent diagnosis of residual hemangioblastoma using 5-aminolevulinic acid.

Hemangioblastoma is a benign tumor of the cerebellum, and treatment involves surgical excision, both as the initial treatment and also in case of recurrence. Recurrence of hemangioblastoma can be local due to incomplete resection or can be distant and separate from the tumor resection region. Local recurrence can largely be avoided by verifying for any residual tumor intraoperatively before closure. In this study, we used intraoperative fluorescent diagnosis using 5-aminolevulinic acid (5-ALA) to verify the presence of a residual tumor during surgical resection. Nine patients with hemangioblastoma were given 1 g of 5-ALA orally before surgery, and a laser beam of 405 nm was focused on the tumor during resective surgery. Fluorescence of protoporphyrin IX (PPIX) was observed in the core of tumor in all the cases. Fluorescence of PPIX was observed in the peritumoral cyst wall in two patients after tumor resection, and in both of them fluorescent parts of PPIX were resected and histological examination showed tumor cells. Usually, there are no tumor cells in the peritumoral cyst of a hemangioblastoma, yet hemangioblastomas may sometimes recur from an unresected cyst wall. It is thus necessary to excise an infiltrating cyst of tumor cells to prevent recurrence. Intraoperative fluorescent diagnosis using 5-ALA is a useful method to discern whether tumor cells are present in the peritumoral cyst wall of a hemangioblastoma.

Depth-adjustable fixation of external ventricular drains to counteract obstruction in tight ventricles.

Tightness of the lateral ventricle may result in mechanical obstruction of an external ventricular drain (EVD). We propose a modified EVD fixation method that allows retraction of the EVD to reopen the drainage. We used this technique in patients requiring long-term EVD placement in the frontal horn who were expected to develop tightening of the ventricle. We placed a catheter fixation device consisting of a dialysis catheter with a catheter-holding wing and a fixture spring. The wing is placed on the EVD just distal to its exit and tied down, and the fixture spring is attached to the wing to secure the EVD. If EVD obstruction associated with tightening of the ventricle was suspected, we removed the spring and retracted the EVD to the depth required for cerebrospinal fluid drainage, then replaced the spring. Retraction by 5-12 mm (mean 8.7 mm) resulted in opening of 8 of the 10 obstructed EVD devices. We encountered no major procedure-related complications. This modified EVD fixation method facilitates depth adjustments for reopening the obstructed drain.

Preparation of eukaryotic mRNA having differently methylated adenosine at the 5'-terminus and the effect of the methyl group in translation.

Cap analogues having differently methylated adenosine at 2' and N6 position, m(7)G(5')pppApG which is existed in plant mRNA (plant type), m(7)G(5')pppAmpG (animal type), m(7)G(5')pppm(6)AmpG (mammalian type) and m(7)G(5')pppm(6)ApG (unnnatural type), were synthesized. In order to clarify the function of these methyl groups, luciferase mRNAs having differently methylated adenosine at the 5'-terminus, were successfully prepared by in vitro transcription using the synthesized cap anologues. As the preliminary results of in vitro translation with rabbit reticulocyte lysate and luciferase assay, luciferase mRNA having the mammalian type of cap structure, m(7)G(5')pppm(6)AmpG, was most efficiently translated. In the case of m(7)G(5')pppApG (plant type) efficiency of translation was lowest.

Change of patient position using a transportation board during lumboperitoneal shunting. Technical note.

Lumboperitoneal shunt placement requires access to the lumbar theca in the lateral position, followed by subsequent laparotomy in the supine position. This position change and repeat draping are bothersome, especially in heavy patients, so we developed a method that facilitates changing the patient position while keeping the surgical drapes in place. An oblong plastic board covered with Teflon-coated glassfiber cloth and surrounded by a nylon-cloth sleeve is used. The sleeve can be easily moved over the board, so patients can be moved in the transverse direction with minimal pushing force. The patient is placed in the lateral position on the board on the operating table and draped from the back to the abdomen. After catheter insertion into the lumbar theca and introduction of a subcutaneous tunnel to the flank, the patient is pushed in the ventral direction, moved to the opposite edge of the operating table, and the position is changed from lateral to supine, leaving the original drape intact. Finally, a catheter is placed by laparotomy. We were able to change position easily in 20 patients weighing 47-85 kg (mean 69.6 kg). This technique reduces the labor required for position change and preserves sterility.

[Technique for embedding a titanium miniplate in the forehead that avoids objectionable bulges].

OBJECTIVE: As the fixation of cranial bone flaps with titanium miniplates may produce esthetically objectionable bulges especially on the forehead covered with thin scalp, we developed a technique that solves this problem. PATIENTS AND METHODS: The study material consisted of 19 consecutive sides treated by frontotemporal cranioplasty using free bone flaps and miniplate-fixation. A pit matching the width and depth of the miniplate was drilled on the outer table, the miniplate was embedded in the pit in the forehead and fixed with screws. RESULTS: Fixation of the bone flap was successful on 18 sides. In one instance the outer table lost the strength to sustain the screws due to excessively deep drilling. No esthetically objectionable bulges were noted even in patients with a thin scalp cover. CONCLUSIONS: This simple technique avoids the development of bulges and provides satisfactory cosmetic results. The key to this technique is preservation of the outer table at the bottom of the pit (more than 1 mm in thickness) to assure the stability of the fixation screws.

Cardboard dural retractor for drilling of the sphenoid wing in the pterional approach.

BACKGROUND: In the pterional approach, adequate removal of the sphenoid wing is essential. For safe drilling of the medial part, the dura beside the wing is usually retracted with a metal instrument and damage to the instrument may occur. We developed an alternative retraction method that uses a cardboard shield. METHODS: Before drilling the medial part of the sphenoid wing, a cardboard shield featuring a notch and a bend in its center is prepared. The notch is inserted between the wing to be drilled and the dura. RESULTS: The shield retracted the dura beside the wing effectively and provided sufficient space for the diamond drill bit. It held up to the drilling and protected the dura. CONCLUSION: This simple method provides a safe adequate operative field without involving additional instruments or expenditures.

Efficacy of a direct puncture approach for anterior circulation aneurysms using a newly developed guiding catheter - especially for geriatric patients.

BACKGROUND: Endovascular surgery is being increasingly used as an alternative to craniotomy clipping surgery, especially for aged patients and complicated cases. However, tortuous atherosclerotic arteries sometimes interfere with advancement of catheters so that direct puncture may be necessary. Short guiding catheters for use with this approach have been newly developed, as discussed in this article. METHODS: One hundred twenty three anterior circulation aneurysms in 121 patients were consecutively treated by endovascular coil embolization, of which 42 (34%) were older than 70 years. RESULTS: With 21 aneurysms, coil embolization via the transfemoral approach failed, but all could be successfully treated with the direct puncture approach with minor complications such as 1 transient ischemic attack and 1 nonsymptomatic minor leakage. In the aged patients, the direct puncture approach with short guiding catheter resulted in complete obliteration of aneurysms in 20 (71%) of 28 with follow-up angiography. CONCLUSION: Direct puncture using newly developed short guiding catheters is an alternative to femoral approaches for patients with anterior circulation aneurysm with tortuous arteries and obvious atherosclerotic change at bifurcations of the common carotid artery.

Development of multiple cerebral arteriovenous malformations documented in an adult by serial angiography. Case report.

A 50-year-old woman with a parietal intracerebral hematoma was initially treated by hematoma evacuation. Initial preoperative and follow-up angiograms obtained 6 months later demonstrated no pial arteriovenous malformations (AVMs). She suffered a subarachnoid hemorrhage 8 years later. Results of follow-up cerebral angiography revealed the development of previously undetected multiple cerebral AVMs. This appears to be the first reported case of the development of multiple cerebral AVMs in an adult, demonstrated on serial angiography.