Biomedical subjects
Publications and source records attributed to M Kochi.
We report two cases with subarachnoid dissemination of medulloblastoma depicted clearly by Gadolinium-DTPA enhanced MRI. We also demonstrate the superiority of Gadolinium-DTPA enhanced MRI over nonenhanced MRI, CT, myelography and postmyelographic CT for diagnosing subarachnoid dissemination and for monitoring the response to therapy.
Two patients with metastatic angiosarcoma of the brain are described. In one, a 17-year-old man, the tumor was located at the pineal region and exhibited significant vascularity. It was sensitive to radiation therapy and disappeared after radiation of 50 Gy; however, it recurred after 1 year and a new lesion was found in the liver. The other patient is a 31-year-old woman who experienced sudden onset of headache. Computed tomography scan revealed three separate masses in the brain. One tumor was surgically removed. The other two were sensitive to radiation therapy and disappeared after radiation of 40 Gy. A new lesion was found in the femur 16 months after the operation. Brain metastasis from angiosarcoma is exceedingly rare. Both patients developed symptoms with intracranial hemorrhage. The diagnosis of the metastatic lesions preceded diagnosis of the primary lesion by 12 and 16 months, respectively. Ulex europaeus 1 lectin and factor VIII were very useful in establishing the diagnosis of angiosarcoma.
UFT was orally administered at a dose of 600 mg/day as a preoperative chemotherapy for a 44-year old male with colon cancer. On the seventh day of the administration, severe anal bleeding occurred, and an emergent colectomy was performed. The macroscopic findings of the resected tumor were different from the first endoscopic picture, and the histopathological findings showed the significant effects of preoperative chemotherapy.
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A 54-year-old woman with cerebellar metastasis from ovarian adenocarcinoma was reported. Two years before admission, she underwent 7 courses of CAP therapy (cisplatin, adriamycin, cyclophosphamide) for ovarian cancer. On admission, no extracranial tumor was noticed. After the removal of a cerebellar tumor, she was treated by combination chemotherapy with cisplatin and etoposide. Her serum level of CA-125, which was still high after surgery, decreased to the normal level following chemotherapy. Chemotherapy was repeated six times, and no recurrence was noticed 1 year after surgery. Combination chemotherapy with cisplatin and etoposide was considered effective in the treatment of intracranial metastasis from ovarian cancer.
To test the feasibility of intrathecal perfusion of ACNU (3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitro sou rea hydrochloride) in the treatment of subarachnoid dissemination of malignant glioma, the neurotoxicity and pharmacokinetics of ACNU were studied in dogs. ACNU [1-2 mg dissolved in 10-20 ml of lactated Ringer's solution or artificial cerebrospinal fluid (CSF)] was administered via the right lateral ventricle by constant drip infusion and CSF was drained by lumbar puncture. The infusion time was from 15 to 71 min. For the control, a bolus injection was given. No neurological and systemic symptoms were noted after perfusion. Histological examination of the brain and spinal cord revealed only mild denudation of ependyma in the wall of the ventricles in a dog treated three times with 2 mg ACNU (perfusion twice, bolus injection once) and in 2 dogs perfused with 1 mg ACNU once a week for 10 weeks. ACNU was not detected in lumbar CSF after bolus injection into the lateral ventricle. When 1 mg of ACNU, dissolved in 10 ml of artificial CSF, was perfused for a duration of 22 to 31 min, it started to appear in the lumbar CSF 10 to 15 min after the start of perfusion, reaching a maximum concentration of 13.88 to 22.31 micrograms/ml. The area under the drug concentration-time curve was 344 to 706 micrograms x min/ml; the half-time was 15.5 to 19.5 min. The distribution volume was 30.6 to 54.1 ml. These findings suggest the feasibility of intrathecal perfusion of ACNU in the treatment of patients with subarachnoid dissemination of glioma.
We present six patients with intracranial nongerminomatous germ cell tumors that produced alpha-fetoprotein (AFP). Their ages ranged from 8 to 20 years (average, 11.5 years old); two were male and four were female. Four of the tumors originated in the pineal region and two in the suprachiasmatic region. One patient treated with only radiation therapy died within 3 months of admission as a result of intraperitoneal metastasis via a ventriculoperitoneal shunt. Another patient, treated with radiation therapy and intrathecal administration of neocarzinostatin, died after 12 months because of tumor progression and subarachnoid dissemination. Two patients who received radiation and combination therapy with cisplatin, vinblastine, and bleomycin died after 13 and 25 months. The remaining two patients treated with radiation therapy and adjuvant chemotherapy (cisplatin and etoposide) are now alive without recurrence after 16 and 19 months from admission. Adjuvant chemotherapy with cisplatin and etoposide appears to be efficacious in the treatment of intracranial nongerminomatous germ cell tumor.
We studied the feasibility of intrathecal ACNU perfusion therapy against subarachnoid dissemination of malignant glioma. Intrathecal perfusion was performed in adult dogs by constant drip administration of 1 to 2 mg ACNU dissolved in 10 to 20 ml of lactate Ringer solution into the lateral ventricle and cerebrospinal fluid drainage through the lumbar puncture. The perfusion time was changed from 15 to 71 min. A bolus injection of 2 mg ACNU was also tested in one dog. No neurological symptom was noted during and after perfusion, and histological examination reveal only a minimum denudation of ependyma in a small area. Concentration of ACNU in CSF and serum were measured by HPLC (high-performance liquid chromatography). ACNU was detected in lumbar CSF only by perfusion, not by bolus injection, and the maximum concentrations were 6.26 to 25.76 micrograms/ml. The elimination phase of ACNU in lumbar CSF followed linear kinetics and the half-time was 18 min on average. AUCs (area under the drug concentration-time curve) were 346 to 896 micrograms.min/ml and they were the equivalent of in vitro cell kills in excess of 3 logs for rat 9L gliosarcoma and human glioma 126 cells. Serum concentration was 0.10 micrograms/ml in maximum. These findings suggest the feasibility of intrathecal ACNU perfusion therapy against subarachnoid dissemination of malignant glioma and warrant further studies.
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A new morpholino anthracycline derivative, MX2, has a potent antitumor activity similar to adriamycin. Because of high lipid solubility of MX2 (log P = 2.84, pH 7.4), the compound can cross the blood-brain barrier easier than adriamycin. In this study we tested the anti-tumor activity of MX2 against human glioma in vitro and in vivo. MX2 showed a marked cytocidal effect against U105MG, U251MG, U373MG and KMG4 cells when more than 30 ng/ml was added in the medium. Although the sensitivity against MX2 differed depending on the cell lines, the cytocidal effect of MX2 was similar to adriamycin. The colony formation of KMG4 cells was markedly inhibited by MX2 dose-dependently. The growth of KMG4 cells inoculated subcutaneously into nude mice was inhibited by the intraperitoneal administration of MX2 4 or 1.3 mg/kg. These results suggest that MX2 seemed to be useful in the treatment of malignant glioma.
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Occlusion of the intracranial portion of the internal carotid artery were encountered in two cases with suprasellar tumours, who had received irradiation therapy previously and shown excellent clinical improvement postoperatively. Clinical features and the angiographic characteristics were analysed in these two cases and the results were compared with reports in the literature. The occlusive effect of radiation on the arterial wall was conceived as the cause of carotid obstruction. In order to avoid this side effect of radiation therapy, especially for brain tumours of low malignancy in childhood, careful estimation of the radiation dose should be required and cerebral angiographic follow-up during and after the treatment with radiation is indicated, particularly when the patient develops cerebral transient ischaemic symptoms.
Benzaldehyde, in the form of 4,6-benzylidene-alpha-D-glucose (BG), was given iv at a daily dose of 720-1800 mg/m2 to 65 patients with inoperable carcinoma in the advanced stages. The overall objective response rate was 55%; seven patients achieved complete response, 29 achieved partial response, 24 remained stable, and five showed progressive disease. Response was seen in various cell types. Prolongation of survival was apparent for the patients. Toxic reactions were not observed during long-term injection with BG.
Ninety patients with inoperable carcinoma in the terminal stages and 12 patients in serious condition with other tumor types were given benzaldehyde in the form of beta-cyclodextrin benzaldehyde inclusion compound (CDBA) orally or rectally at a daily dose of 10 mg/kg divided in four doses. Toxic effects, including hematologic or biochemical disturbances, were not seen during long-term successive administration of CDBA. Fifty-seven of the patients treated were evaluable; 19 patients responded completely and ten patients responded partially (greater than 50% regression). For all responding patients longer response durations were associated with longer CDBA treatment periods. Treatment of squamous cell carcinoma induced the cancer cells to change into a conglomeration of pearls (the well-known product of differentiation) which consisted of keratinized normal squamous cells.
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The toxicity and therapeutic effect of the ventriculolumber perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl-1-1(2-chloroethyl)-1-nitros our ea hydrochloride (ACNU) against subarachnoid dissemination of gliomas were studied. Twenty-one patients (6 patients with anaplastic glioma, 7 with glioblastoma and 8 with medulloblastoma or PNET) received ventriculolumber perfusion of ACNU when they were diagnosed as having subarachnoid dissemination. The course of perfusion and cumulative dose of ACNU was 10 times and 95 mg on average, respectively. Most of the patients received systemic chemotherapy in combination with perfusion therapy and some patients with radiotherapy. Response rate was 17% and median survival time after the diagnosis of dissemination was 12 months for anaplastic gliomas, 29% and 12 months for glioblastoma, and 88% and over 25 months for medulloblastoma and PNET. The ventriculolumber perfusion of ACNU was performed for prophylactic purpose in 7 patients with high risk at the early postoperative period in combination with conventional adjuvant therapy. The course of perfusion and cumulative dose of ACNU was 2.3 times and 21 mg on average, respectively. One patient developed subarachnoid dissemination and died 22 months after surgery. Other 6 patients survived without dissemination on median over 29 months after surgery. Side effects encountered were headache in 4 patients, nausea and vomiting in 5, a convulsion in 2, right facial weakness in 1, fecal incontinence in 3 and meningitis in 2. They were all temporary except for facial weakness occurred in one patient. These data suggest that the ventriculolumber perfusion of ACNU is a safe and useful in the treatment and prophylaxis against the subarachnoid dissemination of gliomas.