Bcl-2 is a key regulator for the retinoic acid-induced apoptotic cell death in neuroblastoma.

Retinoic acid (RA) has been shown to induce neuronal differentiation and/or apoptosis, and is widely used as a chemotherapeutic agent for treating the patients with neuroblastoma. However, the therapeutic effect of RA is still limited. To unveil the molecular mechanism(s) inducing differentiation and apoptosis in neuroblastoma cells, we compared CHP134 and NB-39-nu cell lines, in which all-trans-RA (ATRA) induces apoptosis, with LA-N-5 and RTBM1 cell lines, in which it induces neuronal differentiation. Here, we found that Bcl-2 was strongly downregulated in CHP134 and NB-39-nu cells, whereas it was abundantly expressed in LA-N-5 and RTBM1 cells. ATRA-mediated apoptosis in CHP134 and NB-39-nu cells was associated with a significant activation of caspase-9 and caspase-3 as well as cytoplasmic release of cytochrome c from mitochondria in a p53-independent manner. Enforced expression of Bcl-2 significantly inhibited ATRA-mediated apoptosis in CHP134 cells. In addition, treatment of RTBM1 cells with a Bcl-2 inhibitor, HA14-1, enhanced apoptotic response induced by ATRA. Of note, two out of 10 sporadic neuroblastomas expressed bcl-2 at undetectable levels and underwent cell death in response to ATRA in primary cultures. Thus, our present results suggest that overexpression of Bcl-2 is one of the key mechanisms to give neuroblastoma cells the resistance against ATRA-mediated apoptosis. This may provide a new therapeutic strategy against the ATRA-resistant and aggressive neuroblastomas by combining treatment with ATRA and a Bcl-2 inhibitor.

[Aneurysms of the distal posterior inferior cerebellar artery; the report of 10 cases].

Non mycotic and non traumatic distal posterior inferior cerebellar artery (PICA) aneurysms are rare, but eleven aneurysms in ten cases were reported. They all originated from subarachnoid hemorrhage due to rupture of these aneurysms. The patients in these cases were all admitted within 5 days after the onset. The neurological state of four cases on admission was grade 4 or 5 in Hunt and Kosnik's grading system. Two patients of grade 5 died within 24 hours after the onset. The CT scan on admission revealed heavy subarachnoid hemorrhage mainly in the posterior fossa. In severe cases, ventricle hematoma, cerebellar hematoma and/or subdural hematoma were evident in the posterior fossa. The locations of these eleven aneurysms were as follows: On the bifurcation of the Telovelotonsillar segment in six cases. In the cortical segment in three cases. In the anterior medullary and tonsillomedullary segment in one case. Six saccular aneurysms were situated on bifurcations of parent arteries but three saccular aneurysms did not arise from bifurcations. Two of them were not from turning points of the arteries. One fusiform aneurysm situated on the bifurcation of telovelotonsillar segment was excised, and histologically shown to be a dissecting aneurysm with hypoplasia of elastic lamina and tunica media in the parent artery. Three cases were associated with small AVM located on the superior surface of the cerebellar vermis and fed mainly by the superior cerebellar artery (SCA) in two cases, and by SCA and PICA in one case. In these cases the hemodynamic stress on PICA did not seem to increase so remarkably.(ABSTRACT TRUNCATED AT 250 WORDS)

[Encapsulated chronic intracerebral hematoma caused by venous angioma of the basal ganglia: a case report].

A case is reported of venous angioma at the right basal ganglia simulating the encapsulated chronic intracerebral hematoma. A 29-year-old man was admitted to our hospital on July 14, 1988 with a two-month history of headache. Neurological examination revealed left homonymous lower quadrantic anopsia. CT scans showed a mosaic high density lesion at the right basal ganglia with extensive adjacent edema. MRI revealed that the high density lesion on CT scans was the combination of a reticulated core of mixed signal intensity with a surrounding rim of decreased signal intensity. The lesion was accompanied with extensive edema. Followed up CT scans showed the transformation of the lesion and ring-shaped enhancement. A right frontotemporal craniotomy was performed on August 9, 1988. After thorough dissection of the sylvian fissure and small corticotomy to the insula, a tough capsule was seen. There was blood in various stages of organization in the capsule. A histological examination gave a diagnosis of venous angioma in the membrane similar to the outer membrane of chronic subdural hematomas. Postoperatively, the patient showed slight left motor weakness, but it gradually improved and he was discharged on foot, on October 19, 1988. There have been a lot of reports about angiographically occult intracranial vascular malformation (AOIVM). But AOIVM at the basal ganglia is rare, and to our knowledge, only 8 cases have been reported. In our case, the presence of adjacent extensive edema, and ring-shaped enhancement on CT scans confused the preoperative diagnosis. Those findings might have been caused by encapsulation. By using CT scans and MRI, a complete and accurate diagnosis was impossible.(ABSTRACT TRUNCATED AT 250 WORDS)

Results of stereotactic aspiration in 175 cases of putaminal hemorrhage.

Believing that improved therapeutic results in cases of intracerebral hematoma might be obtained by minimal invasion of the brain, we used computed tomographic-guided stereotactic aspiration in 175 of 241 patients with putaminal hemorrhage. These patients, who were treated 6 or more hours after onset, had hematomas larger than 8 ml and were unable to raise an arm and/or leg on the affected side. Craniotomy was performed in 15 other patients, most of whom were brought to the hospital with large hematomas within 6 hours of onset. The remaining patients either had mild deficits of consciousness (33 patients) or severe deficits and/or were elderly (18 patients) and were treated conservatively. Thirteen patients (7.4%) showed rebleeding after stereotactic aspiration (6 instances of major and 7 instances of minor rebleeding). Craniotomy and removal of the hematoma were required in three of these patients. Aspiration should be avoided in patients who have a tendency for bleeding, even if mild, because rebleeding occurred in 6 of 23 such patients (26%) in these study. The consciousness level improved in 66 patients (38%), was unchanged in 103 patients (59%), and was worse in 6 patients (3%) 1 week postoperatively. Motor function of the arm improved in 55 patients (31%) and was worse in 23 patients (14%). Six months after surgery, the results for the 175 patients who underwent stereotactic aspiration were: 19% excellent, 32% good, 35% fair, 7% poor, 6% dead, and 1% unknown. For the entire series of 241 patients, the results were: 24% excellent, 26% good, 31% fair, 7% poor, 11% dead, and 1% unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental retrograde adriamycin trigeminal sensory ganglionectomy.

Direct destruction of the sensory ganglion or its root, by either surgical transection or injection of phenol, has been employed as preferred treatment for a variety of neuralgic pain syndromes. In this report, the suicide axoplasmic transport of adriamycin is described as a novel approach to sensory ganglionectomy. When injected into a branch of the trigeminal nerve in the cat, adriamycin was swiftly transported by way of retrograde axoplasmic flow to the sensory neurons parental to the injected nerve, where adriamycin-specific autofluorescence was observed. Trigeminal sensory evoked potentials became unobtainable 24 to 48 hours after injection of adriamycin in concentrations of 1% to 10%. The sensory neurons underwent subacute degeneration within a week due to the delayed action of adriamycin, and consequently the primary afferents degenerated in a restricted projection field of the brain-stem trigeminal sensory nuclei. These results indicate that retrograde axoplasmic transport of adriamycin is a unique approach to noninvasive sensory ganglionectomy with strict, albeit simple, safe targeting of sensory neurons and little likelihood of regeneration.

Intracerebral hemorrhage from a metastatic brain tumor. Importance of differential diagnosis preceding stereotaxic hematoma aspiration.

Three cases of sudden intracerebral hemorrhage, which were diagnosed as hemorrhage from metastatic brain tumors following stereotaxic aspiration of a hematoma, are reported. Two cases had subcortical hemorrhage and one had cerebellar hemorrhage. Neither contrast-enhanced computed tomography scans nor angiograms revealed any findings other than those indicating the hematoma in all three cases. However, retrospective study of the anamnesis showed very mild symptoms due to metastasis to the brain or spinal cord in one case each. In cases of intracerebral hematoma located at atypical sites, extreme care is required for the differential diagnosis.

[CT-guided stereotaxic implantation of the Ommaya reservoir for cystic brain tumors].

We report the use of CT-guided stereotaxic system to implant Ommaya reservoir in 26 patients with cystic brain tumors consisting of 16 gliomas, 3 craniopharyngiomas, 3 metastatic brain tumors and 5 other and unknown pathologies, on the way of their biopsy. The entire procedure was carried out in the CT room using Leksell's CT stereotaxic system. In 24 cases with supratentorial tumors, it was at the option of the operator to take any approach such as frontal, posterior temporal and parietal approaches. Especially in 3 cases of craniopharyngioma, we inserted the tube into their cyst directly so that the ventricle should not be open to the cyst. Also in cases of a pontine glioma and a C-P angle metastatic tumor, we used retromastoid approach to the posterior fossa by making patient's heads turned about 30 to 40 degrees to contralateral side of the approach, with slight flexion of the neck. Minimal bleeding occurred during operation in one case, however, it showed no clinical symptoms. Advantages of this method are as follows: Operative invasion is minimal; The surgeon can check the course of the cannula and position of the tip of Ommaya tube even at operation, and can modify it, if necessary.

[CT-guided stereotaxic biopsy in 104 cases of brain tumor].

Biopsy of suspected brain tumor was performed on 104 cases using Leksell's CT-guided stereotaxic system. The entire operation was performed in the CT room. A Backlund's spiral biopsy needle was advanced to the target point in a stepwise fashion and two to nine tissue samples were obtained from one to three biopsy tracks. Tissue sampling was impossible in two cases because the tumors were too hard for biopsy needle to advance. Also, sampling was sometimes difficult in the case of soft and necrotic tumor, cystic tumor, already treated (irradiated) tumor and the lesion including old blood clot. After the biopsy, minimal bleeding occurred in nine cases, however, stopped within 10 minutes by controlling the blood pressure. A minimum sized hematoma was visible on the postoperative CT in four cases. Postoperative neurological deterioration was seen in two cases. One case was transient and the other seemed to be in his natural course. Anyway, there were neither cases of operative mortality nor severely complicated cases in these series. Useful pathological diagnosis was possible in 83 cases (80%). Accurate diagnosis was not possible in the remaining 21 cases, however, their histological datum such as necrosis, blood clot, and so on were very useful to estimate the lesions. In summary, accurate diagnosis rate of CT-guided stereotaxic needle biopsy was 80%. However, it appeared to be a safe and useful procedure in the diagnosis of intracranial mass lesions.

Experiences with CT-guided stereotaxic biopsies in 121 cases.

Needle biopsy using a CT-guided stereotaxic technique was performed in 121 cases of suspected brain tumour. Using this technique, it is possible to perform biopsies safely and accurately on even small and deep-seated lesions with a minimum of surgical intervention. However, accurate diagnoses are sometimes not possible when only a small number of viable cells are obtained, such as in lesions containing old haematoma, cystic tumours, previously treated tumours or tumours which are either too hard or too soft. We were able to make accurate diagnoses in 98 of our 121 cases (81%). The accuracy of diagnosis is somewhat hampered by the small volume of sample material obtained using this biopsy technique, and this fact should be kept in mind when evaluating the histological material.

[A case of prolactinoma in close association with Rathke's cleft cyst].

We report a case of Rathke's cleft cyst in pituitary tumor. A 31-year-old woman admitted to our hospital complained of visual disturbance, headache, amenorrhea and galactorrhea. Serum prolactin level was 3,060 ng/ml. By means of CT scan and MRI, we found suprasellar-extending tumor to have cystic component in the center of the tumor. Transsphenoidal surgery revealed grayish jelly-like content in the cyst. Histologically tumor cells were composed of chromophobic, basophilic and eosinophilic cells. The cyst wall in the pituitary adenoma was composed of ciliated or non-ciliated columnar epithelium intermingled with goblet cells, being similar to Rathke's cleft cyst. Except for the cells of the cyst wall, most of the tumor cells were immunoreactive for prolactin. As for intermediate filament, tumor cells in both solid and cystic portions showed positive immunoreactivity for cytokeratin and GFAP, and not for vimentin and neurofilament. These results suggest that the nature of the intracytoplasmic filament in the pituitary tumor with Rathke's cleft cyst may be not only keratin but also GFAP.

[Results of supratentorial low-grade astrocytoma--effects of combined radiochemotherapy].

The retrospective analysis of 53 cases with supratentorial low-grade (grade 1 or 2 due to WHO grading) astrocytomas included the years 1965-84. The 5-year and 10-year survival rates were 61.9% and 52.1%, respectively. The recurrence of tumors occurred in 15 cases (28.3%), almost within 3 years after the initial treatment, and early recurrent cases indicated poor results. Among them, 6 cases were noticed increasing malignancy of histological findings. According to our investigations, the factors which influence to the survival rate were age of patients, duration of symptoms before treatment, presence of neurological deficits and degree of surgical removal of tumor. The patients with good prognosis were under 20-year old, over 6 months of duration, with no neurological signs and with total or subtotal removal. But, 5-year survival rate was not so improved by postoperative radiation therapy. Analysis on the effects of chemotherapy for low-grade astrocytoma was little reported. We treated 26 patients with RAFP therapy (Radiation + ACNU + FT-207 + PSK). Only 2 cases out of 26 showed the recurrence till now. The rate of reduction of their tumors was 46.2% by CT scan. So, it was considered that RAFP therapy was effective for supratentorial low-grade astrocytoma.

[Results of combined radiochemotherapy of intracranial ependymoma].

Thirty patients with intracranial ependymoma were treated in our clinic from 1965 through 1984. They were 13 children and 17 adults. As for the location of tumor, 9 were in the lateral ventricle, 8 in the cerebral hemisphere, 12 in the fourth ventricle and one in the third ventricle. Histologically, 18 were benign and 12 were anaplastic. The clinical course was analyzed in 24 cases. Out of the 24 cases, surgical treatment with postoperative radiation therapy was done in 16 cases, surgical treatment with postoperative radiochemotherapy in 6, and radiochemotherapy alone in two. Five-year survival rate of patients treated by surgery with radiation therapy and with radiochemotherapy was 35.7% and 66.7%, respectively. Patients treated by surgery not only with radiation therapy but also with chemotherapy took a better outcome. Recurrence was observed in 9 cases. Four cases of the 9 were benign ependymoma. The recurrence was observed within 3 years after the initial treatment in all cases. Even if histologically benign, the recurrence occurred in a relatively high rate as reported in the past literature. It should, therefore, be stressed that the initial treatment is important not only for a malignant ependymoma but also for a benign one, and the postoperative radiochemotherapy is useful for the improvement of the results.

[Results in oligodendroglioma: postoperative radiotherapy combined with chemotherapy].

The retrospective analysis of 39 cases of supratentorial oligodendroglioma included the years 1965 - 84. The 5-year and 10-year survival rates were 73.1% and 32.2%, respectively. Although oligodendrogliomas were benign tumor, the 10-year survival rate was not good. Recurrence of tumor appeared in 9 cases and some cases were noticed about 10 years after the treatment. So, long term follow-up is important for oligodendrogliomas. Our treatment for oligodendrogliomas was surgical removal and postoperative radiochemotherapy (radiation + ACNU + FT-207 + PSK) for several years. The previous cases who had only subtotal removal of tumor showed short survival time. On the other hand, the cases treated with postoperative radiotherapy or radiochemotherapy showed relatively good results.

A case of cebocephaly-holoprosencephaly with an aberrant adenohypophysis.

An autopsy case of cebocephaly-holoprosencephaly at 27 weeks' gestation is reported. Chromosome analysis revealed a 46, XX,-7, +der(7), t(7;13) (q32;q34) pat karyotype. Pathological examination disclosed a hypoplastic aberrant adenohypophysis, in which immunohistochemical localization of four anterior pituitary hormones (ACTH, GH, PRL, TSH-beta) was demonstrated. Malformation of the pituitary gland in holoprosencephaly can include ectopic adenohypophysis as well as pituitary dysgenesis, so a careful search for adenohypophysis should be made in future cases for a better understanding of endocrine dysgenesis associated with holoprosencephaly.

[A case of arachnoid cyst in the middle cranial fossa presenting with trigeminal neuralgia].

A 50-year-old man had been suffering from left trigeminal neuralgia for 30 years. CT scan revealed an arachnoid cyst occupying the anterior two-thirds of the left middle cranial fossa. Cerebral angiography showed elevation of the left middle cerebral artery and medial shift of the left posterior cerebral artery. Metrizamide CT showed that the cyst was not communicating with the subarachnoid space. Air CT revealed the root of the left trigeminal nerve in contact with the arachnoid cyst. The patient became completely free from the trigeminal neuralgia 6 months after cystoperitoneal shunt. This case seems to be a very rare case of trigeminal neuralgia caused by an arachnoid cyst.

Trigeminal neurinoma associated with suprasellar arachnoid cyst: case report.

The first case of trigeminal neurinoma associated with suprasellar arachnoid cyst is presented. Coexistence of these two lesions may be accidental, but it is also possible that the arachnoid cyst was secondary to the neurinoma.

[Trigeminal neurinoma associated with suprasellar arachnoid cyst].

A rare case of trigeminal neurinoma associated with suprasellar arachnoid cyst is reported. A 49-year-old female had been suffering from character change, memory disturbance and mild headache for three years prior to admission. On admission, there were bilateral choked disc and binasal lower quadrant anopsia. Visual acuity was 20/200 on the left side and 10/200 on the right side. Facial and auditory nerves were intact. Cerebellar sign was not present. In plain skull roentgenograms, there were destruction of the right apex of the pyramis. However, the internal auditory meatuses were normal. Computed tomography revealed a contrast enhanced mass at the right cerebellopontine angle and a large cystic lesion in the suprasellar region. The relation between both lesions was clearly demonstrated in the coronal computed tomography and the NMR imaging of the sagittal section. The patient was operated on through subtemporal approach. The well-defined yellowish tumor was totally removed and the cyst was opened. The tumor and the cyst were distinguished separately. Post-operative course was uneventful except for the right trigeminal palsy. Mental symptoms disappeared. The mechanism of the appearance of symptoms in the case is considered as follows. That is, the slowly expanding tumor progressively compressed the cyst and the cyst enlarged, then the various symptoms appeared. The possibility that the suprasellar arachnoid cyst was a secondary arachnoid cyst due to the trigeminal neurinoma is also discussed.

Aneurysmal bone cyst of the skull.

A case of a 48-year-old woman with aneurysmal bone cyst of the skull is reported. By using estrogen, which is one of the chemical embolizing agents, the abnormal vascular shadow disappeared and clinical symptoms were improved. The significance of selective external carotid angiography in the diagnosis of this lesion is discussed and the benefit of this therapeutic method is argued.

[CT-guided stereotaxic implantation of a deep brain electrode for the stimulation of the internal capsule--a case report].

A 47-year-old man was admitted to our clinic because of the pain of left extremities for four years. The patient developed dysesthesia, hyperpathia and spontaneous pain 2 months after the onset of cerebrovascular accident with left hemiparesis. Using Toshiba TCT-20A CT scanner and Leksell's CT-stereotaxic system, stimulation electrode (by Medtronic Co.) was implanted in the posterior limb of the internal capsule which was 25 mm lateral to the posterior commissure. Ventriculography was not necessary because the target point was directly measured from the axial CT and midsagittal reformatted CT based on 18 axial CT images (2 mm thick slices). Anterior commissure, pineal calcification, posterior commissure and Sylvian aqueduct were demonstrated on the midsagittal reformatted CT by this method. The pain was relieved by the ramped square pulse stimulation (2 V, 0.6 msec, 50 Hz) and receivor system was internalized. The patient was free from pain by 30 minutes-long stimulation four to six times a day. Precise electrode placement was possible by CT images alone using high resolution CT and CT-stereotaxic system. CT-guided stereotaxic technique seemed to have an advantages especially for the implantation of electrode in the posterior limb of the internal capsule. The reason is as follows: The target is just lateral to the posterior commissure which could be recognized easily on the midsagittal reformatted CT. The internal capsule is advantageously demonstrated on the axial CT.