A comparative study of apoptosis and proliferation in germinoma and glioblastoma.

Intracranial germinoma has a relatively good prognosis when treated with radiotherapy and chemotherapy, whereas glioblastoma has a poor prognosis irrespective of these treatments. Cell proliferation and cell death are opposing processes in tumor growth, with tumor progression reflecting the balance between proliferating and apoptotic cells. We investigated cell proliferation and cell death using MIB-1 staining and nick-end labeling in 13 germinomas in comparison with 11 glioblastomas. Expression of BAX and Bcl-2, which regulate apoptosis, were studied by immunohistochemistry. Although germinomas showed strong MIB-1 immunostaining similar to that seen in glioblastomas, germinomas included significantly more apoptotic cells. The ratio of apoptotic ratio to MIB-1 labeling index for germinomas was 72.9 +/- 36.9 (mean +/- SD), a higher, statistically significant ratio as compared with glioblastomas (14.5 +/- 11.2; P < 0.01). Furthermore, germinomas showed greater expression of BAX than did glioblastomas, while the expression of Bcl-2 was weak in both tumor types. A comparison of these apoptotic-related proteins showed that immunoreactivity for BAX was relatively higher in germinomas than in glioblastomas (P < 0.01), corresponding well to numerous apoptotic cells identified in germinoma tissues. These findings may account for the prognostic difference between germinoma and glioblastoma in the face of a similar proliferation potential according to MIB-1 immunostaining. The balance between cell proliferation and death should be considered when predicting outcomes in patients with intracranial tumors.

Efficacy of single-bolus vs. frequent low-dose treatment with nitrosourea in experimental gliomas.

BACKGROUND: Malignant glioma remains a fatal disease. Continuous or frequent low-dose (FLD) chemotherapy with nitrosoureas reportedly causes fewer side-effects than single-bolus therapy without decreasing the antitumour effects. MATERIALS AND METHODS: To study the effect of FLD treatment with nimustine (ACNU) in rats with glioma, we intracerebrally inoculated with C6 glioma cells. We began the ACNU treatment 5 or 8 days later (total dose, 25 or 40 mg/kg) i.p. as either one bolus or smaller doses spread over 5 days week. RESULTS: At a total dose of 25 mg/kg beginning at day 8, survival duration did not differ between untreated controls and the FLD group, while the bolus significantly prolonged survival; the FLD group showed some improvement beyond control survival at 40 mg/kg (each p <0.001). Beginning treatment after 5 rather than 8 days prolonged survival somewhat further. CONCLUSION: FLD treatment with ACNU is less effective against experimental glioma in rats than bolus treatment.

Fluid loading in rats increases serum brain natriuretic peptide concentration.

Hyponatremia after subarachnoid hemorrhage has been linked to high plasma concentration of atrial natriuretic peptide and brain natriuretic peptide. Volume expansion therapy to prevent symptomatic vasospasm, such as intensive hypertensive and hypervoremic therapy, may alter systemic concentration of these peptides. We therefore examine brain natriuretic peptide secretion in rats in response to acute volume expansion, infusing to 10 ml of saline over 1 h. In the 10 ml group, brain natriuretic peptide concentrations showed a significant increase from pre-infusion concentrations 1 h after initiation of infusion, but had begun to fall 1 h later. We suspect that high plasma concentration of brain natriuretic peptide after subarachnoid hemorrhage is partly caused by hypervoremic therapy.

High incidence of hyponatremia in patients with ruptured anterior communicating artery aneurysms.

We studied the incidence and timing of hyponatremia (Na < 135 mEq l-1) after subarachnoid hemorrhage (SAH) with special reference to ruptured anterior communicating artery (A-com) aneurysms. Hunt and Kosnik (HK) grading, symptomatic vasospasm in A-com aneurysm, and hydrocephalus were analyzed for connections to hyponatremia in 55 patients with ruptured A-com aneurysms, 65 with ruptured internal cerebral artery (ICA) aneurysms, and 49 with ruptured middle cerebral artery (MCA) aneurysms. Hyponatremia occurred in 28 (51%) of 55 patients with A-com aneurysms and in nine (18%) of 49 patients with MCA aneurysms. Severe hyponatremia (Na < 130 mEq l-1) occurred in 16 patients (29%) in the A-com group, four patients (6%) in the ICA group, and three patients (6%) in the MCA group. The A-com aneurysm group had a significantly higher incidence of mild hyponatremia (p < 0.01) and severe hyponatremia (p < 0.001) than other groups. Among A-com cases, hyponatremia occurred significantly more often in HK grade III and IV cases (p < 0.05), in cases with vasospasm (p < 0.001), and in cases with hydrocephalus (p < 0.01). Respective days of onset for symptomatic vasospasm and for hyponatremia were day 7.6 +/- 4.4 and day 10.6 +/- 5.8 following SAH, representing a 3-day delay for hyponatremia (p < 0.05). In most patients hyponatremia resolved within 28 days following SAH. Hyponatremia occurred more often with A-com aneurysms, possibly because of vasospasm around the A-com or hydrocephalus causing hypothalamic dysfunction. Since hypervolemic therapy can cause hyponatremia, particularly careful observation is required during such therapy in patients with A-com aneurysm.

Resolving obstructive hydrocephalus from AVM.

Obstructive hydrocephalus with deterioration of consciousness from a ruptured arteriovenous malformation (AVM) requires urgent decompression, but also vigilance during the preoperative stage in case of rare spontaneous resolution.

Mobile intracranial oily substances from a ruptured teratoma.

A patient with a ruptured intracranial teratoma is presented. The distinctive imaging and neuroendoscopic findings of mobile fatty or oily globules in the subarachnoid or ventricular space are described. Fat suppression magnetic resonance imaging (MRI) and MRI performed with the patient prone was helpful in distinguishing tumour tissue from floating oil.

[T-cell lymphoproliferative disorder involving the central nervous system in two cases].

Lymphoproliferative disorder (LPD) sometimes occurs in immunosuppressive patients. B-cell proliferation is predominantly seen in patients with LPD and T-cell proliferation is rare. We here report two patients with T-cell LPD involving the central nervous system (CNS). A 7-year-old boy developed increased intracranial pressure and computed tomography showed a ring-enhanced mass lesion in the right frontal lobe. A 10-year-old boy developed gait disturbance and magnetic resonance imaging showed a non-enhanced lesion in the left parietal lobe. Radiological findings could not differentiate CNS-LPD from other intracranial diseases. Only histologic examination could diagnose LPD in both cases, and Epstein-Barr virus associated RNA was found in the infiltrated T-cell of the latter case. Although chemotherapy with antitumor agents was effective for remission of LPD in both cases, both patients died 3 years after their operations. As CNS-LPD shows rapid progression and frequently results in fatality, this disease requires immediate histologic diagnosis followed by extensive chemotherapy.

[A case showing effective radiotherapy for a radiation-induced glioblastoma].

Radiation-induced glioblastoma is usually resistant to all treatments. We report a case with radiation-induced glioblastoma, in which radiotherapy was remarkably effective. A 14-year-old female with a history of acute lymphoblastic leukemia, at the age of 7, underwent 15 Gy of radiotherapy to the whole brain. She was admitted to our department due to the development of headache and nausea. Magnetic resonance imaging showed an irregularly enhanced mass in the left frontal lobe. Partial removal of the mass was performed and histological examination showed it to be glioblastoma with a high MIB-1 index. The patient underwent 40 Gy of local radiotherapy and chemotherapy with ACNU and Interferon-beta for 2 years. The residual tumor disappeared after the radiotherapy, and her status is still "complete remission", 29 months after the onset.

[Acute hepatitis B virus after chemotherapy for a case with germinoma].

A 28-year old man with HCG-producing germinoma had undergone chemotherapy and radiotherapy. On admission for the fifth session of maintenance chemotherapy, he was found to be positive for hepatitis B (HB)s antigen, but negative for HBs antibody. HBs antigen had been negative during previous admissions. Since liver function was normal, the patient underwent chemotherapy. During myelosuppression after chemotherapy, liver dysfunction developed and acute HB was diagnosed. He fortunately showed seroconversion 2 months after onset. Serum immunological examinations are required for patients receiving chemotherapy.

[Influence of scalp shaving on prevention of postoperative intracranial infection].

Shaving of the whole scalp is ordinarily performed prior to neurosurgical operation. Although it is performed in order to prevent postoperative intracranial infection, there has been no apparent basis for this practice published in previous reports. We examined whether shaving the whole scalp reduced the rate of postoperative infection or not. We divided 274 cases, who received their first intracranial operation in the last 2 years, into two groups; a whole shaving group and a partial shaving group. We compared the rate of postoperative intracranial infection between the two groups according to age, diagnosis, operation, operation time and placement of drainage. Overall, 12 cases out of 274 (4.38%) had postoperative intracranial infection. The long operation time and the long term placement of drainage mechanism increased the postoperative intracranial infection rate. There was no postoperative intracranial infection in 74 patients who received burr-hole/twist-drill operation. As for craniotomy/craniectomy operations, 7 cases out of 83 (8.4%) in the partial scalp-shaving group whole scalp shaving group and 5 cases out of 117 (4.2%) had postoperative intracranial infections. Thus, there was no significant difference in the rate of postoperative intracranial infection between the two groups, if anything, the whole scalp shaving group tended to show a higher rate. According to these results, partial scalp shaving did not increase the rate of postoperative intracranial infection. Considering that patients who have lost their hair find it embarrassing to return to society, it is well to know that the whole scalp shaving is not absolutely necessary for all first craniotomy.

[A penetrating cranio-facial injury due to a nail-gun accident].

We report a case of a penetrating cranio-facial injury due to a nail-gun accident. An 18-year-old worker was admitted to our hospital as an emergency patient. He was working using a nail-gun when a nail ricocheted off a wall and pierced the right side of his face. Skull X-rays and a CT scan showed that a 9 cm nail had pierced his right frontal lobe through the right maxillary bone via the orbital space. The patient was alert without any neurologically abnormal findings. A small stab wound was recognized on his face. The nail was removed six hours after the injury through a sublabial approach and a fronto-temporal craniotomy. The nail was very tightly fixed in the maxillary bone and skull base bones, and a screw driver normally used in orthopedic surgery proved to be very useful for removing the nail. The patient returned home 14 days later without any neurological deficits. The technical problems associated with such a nail-gun injury in the face and skull are also discussed.

[Educational level of patients with germ cell tumor radiated in childhood].

In order to estimate the influence of radiotherapy on the intellectual development of children with brain tumor, we investigated the educational level of 21 patients with germ cell tumor who had undergone radiotherapy. They were divided into three groups in accordance with their age at the time of radiation; under school age group (under 6 years of age), elementary school age group (from 7 to 12 years of age), and junior high and high school age group (from 13 to 18 years of age). There were 2 cases in the under school age group, one of them graduated from high school and the other is presently a junior high school student. There were 5 cases in the elementary school age group. 3 of these graduated from university, 1 is presently a university student and 1 is a high school student. There were 14 cases in the junior high and high school age group. 2 of these are university students, 7 graduated from high school, 1 is presently a junior high school student, and 4 died because of tumor progression. The mean period of hospitalization of the patients who have been admitted to university was 63.0 days, and that of patients who have not been admitted university was 135 days. There is a statistical difference (p < 0.05). It could be concluded that the period of hospitalization rather than radiotherapy seemed to influence the educational status of children with brain tumor.

[A case of effective urgent irradiation therapy for metastatic spine tumor].

A 74-year-old man noticed weakness in bilateral lower limbs 2 months prior to admission. The weakness had rapidly progressed and he could not stand by himself on admission. All thoracic vertebral bodies showed mosaic pattern on T 2 weighted-image. At Th 10 and Th 11, two enhanced masses compressed spinal cord posteriorly. Basal-serum tumor markers, such as LDH, ALP, total-acid phosphatase and prostatic acid phosphatase were elevated, metastatic spine tumor from prostatic carcinoma was suspected. Biopsy specimen from its prostate revealed low differentiated adenocarcinoma. Because sphincter dysfunction progressed rapidly after admission, we started 3 Gy/day irradiation within 24 hr from its appearance targeting both Th 10 to L 1 vertebral bodies and the prostate in total 30 Gy. The clinical symptoms started to resolve immediately, and the disappearance completely within 7 months. This case illustrated that urgent irradiation was effective for broad metastatic spinal tumor with rapidly progressive neurological deficits.

[Relationship between cardiac natriuretic peptide (ANP/BNP) and fluid intake in patients with subarachnoid hemorrhage].

Several authors described elevated natriuretic peptides, atrial natriuretic peptide(ANP) and brain natriuretic peptide (BNP), in patients with subarachnoid hemorrhage(SAH), which were account for inappropriate antidiuretic hormone(SIADH) or cerebral salt wasting syndrome(CSW). Although the secretion of natriuretic peptide depends on the total blood volume, central venous pressure, and cardiac output volume, the volume of fluid intake in patients with SAH had not been taken in consideration in previous report. We here examined the relationship between fluid intake and the natriuretic peptides in two cases without cardiac failure. ANP elevated 2 or 3 days after SAH and remained in normal range for 2 weeks. BNP elevated when the volume of fluid intake was increased, and BNP did not elevate during the periods with lower fluid intake. Several authors proposed the possibility of iatrogenic factor in natriuresis after SAH and these results supported this opinion.

[Primary thalamic hemorrhage penetrating to the lateral ventricle in an infant with abnormal protein S(protein S-Tokushima)].

We experienced a 3 months infant with thalamic hemorrhage penetrating to lateral ventricle with abnormal Protein S. Although the coagulation factor and fibrinogenolysis factors were evaluated, there were no remarkable abnormal laboratory data except for slightly decline of Protein S. The DNA analysis was performed for Protein S, and a missense mutation(A to G transmission) was found, which was resulting in Lys-155 to Glu. The total Protein S antigen was normal level, but co-factor activity for activated Protein C was declined. That mutation is named Protein S-Tokushima, and the patient who has abnormal Protein S tends to suffer recurrent coagulopathy. In our patient, it was interesting that any thrombotic disease had not occurred, but cerebral hemorrhage had occurred.

Neuroendoscopic treatment of cystic craniopharyngioma in the third ventricle.

The third ventricle is a relatively uncommon location for craniopharyngiomas. Generally, craniotomy has been considered the procedure of choice in such cases. We describe a girl in whom a cystic third ventricular craniopharyngioma was successfully treated by evacuation of the cyst contents via a flexible neuroendoscope and precise placement of an Ommaya reservoir catheter within the tumor.