Shigeki Kubo

Diagnosis and treatment of patients with meningeal carcinomatosis

SummaryThe records of thirty-four patients with meningeal carcinomatosis treated at our hospital between 1984 and 1990 were reviewed. The sources, histologies, metastatic lesions outside the central nervous system, the history of the treatment of primary lesions and intraparenchymal of metastatic brain tumors and the period from the diagnosis of primary lesions and the treatment of intraparenchymal metastatic brain tumors to the diagnosis of meningeal carcinomatosis were investigated. Meningeal carcinomatosis was diagnosed and by neurological signs, CSF cytology, CT scan and MRI.Each patient was given a 5 mg single dose of methotrexate (MTX) alone or combined with 20 mg cytosine arabinoside (Ara-C) adminstered by intrathecal injection via an Ommaya reservoir and standard lumbar puncture with or without radiotherapy. Following intrathecal chemotherapy 22 of 29 patients showed symptomatic improvement of meningeal irritation and in 10 of 29 patients with cranial nerve impairment amelioration of symptoms was also observed. Moreover, CSF cytology became negative in 10 of 29 patients after a full course of intrathecal chemotherapy. Neurotoxicity Leukoencephalopathy, a neurotoxic effect of intrathecal chemotherapy was not observed in any of the patients. From these results, MTX in small doses is recommended for intrathecal chemotherapy of meningeal carcinomatosis to prevent neurotoxicity.

Comparative Immunohistochemical Study of Insulin-like Growth Factor II and Insulin-like Growth Factor ReceptorType 1 in Pediatric Brain Tumors

Insulin-like growth factor (IGF)-II is an important growth factor in development of the central nervous system. The purpose of this study was to evaluate expression of IGF-II and IGF receptor type 1 (IGFR1) in various pediatric brain tumors. Immunohistochemistry for IGF-II and IGFR1 was performed on 15 choroid plexus papillomas (CPPs) including 1 atypical CPP, 2 choroid plexus carcinomas (CPCs), 5 anaplastic ependymomas, 7 nonanaplastic ependymomas (simply referred to as “ependymoma”), 5 medulloblastomas, 1 cerebral neuroblastoma, and 1 atypical teratoid/rhabdoid tumor (ATRT) along with 10 non-neoplastic choroid plexus and 3 non-neoplastic ependymal linings. All non-neoplastic choroid plexus, CPPs, CPCs, anaplastic ependymomas, ATRT, 71% of ependymomas, and 67% of non-neoplastic ependymal linings showed cytoplasmic positivity for IGF-II, whereas all medulloblastomas and the cerebral neuroblastoma were negative for IGF-II. In addition to cytoplasmic positivity for IGFR1, membranous positivity was observed in 73% of CPPs, both CPCs, the ATRT, 22% of non-neoplastic choroid plexus, 80% of anaplastic ependymomas, and 29% of ependymomas, but not in any medulloblastoma, cerebral neuroblastoma, or non-neoplastic ependymal lining. IGF-II and IGFR1 may play roles in the pathogeneses of CPP, CPC, anaplastic ependymoma, ependymoma, and ATRT. Immunohistochemical testing for IGF-II and IGFR1 may be useful in differentiating ATRT, CPC, and anaplastic ependymoma from medulloblastoma and cerebral neuroblastoma.

Selective intra-arterial chemotherapy with a combination of etoposide and cisplatin for malignant gliomas: Preliminary report

We administered selective intra-arterial chemotherapy consisting of a combination of etoposide and cisplatin to 20 patients with malignant glioma (seven with recurrent and six with enlarged tumors after initial treatment, and seven newly diagnosed patients). Evaluation of efficacy was based on computed tomographic and magnetic resonance imaging findings. In the process of establishing a safe technique for superselective intra-arterial chemotherapy, we encountered cerebrovascular accidents in two patients (after etoposide in one and after etoposide plus cisplatin in the other). In these two cases, 100 mg/m2 of etoposide and 100 mg/m2 of cisplatin were delivered via the horizontal segment of the middle cerebral artery (M1) or the tip of the basilar artery, with the infusion time reduced to 20 minutes. Thereafter, the etoposide was diluted, and the doses of both drugs were reduced to 80 or 50 mg/m2, and finally to 60 mg/m2, and both were infused over 60 minutes. In addition, for prevention of local spasm, papaverine hydrochloride and nicardipine were given via the same catheter at 5-minute intervals during administration of etoposide and cisplatin. No complications developed in the later cases. Thereafter, selective intra-arterial infusion of etoposide and cisplatin into the anterior cerebral artery, middle cerebral artery, posterior cerebral artery, or the basilar artery for malignant gliomas in the basal ganglia, internal capsule, and brainstem--a procedure generally considered risky in terms of potential complications--was performed safely, with tolerable side effects. Computed tomography and magnetic resonance imaging indicated improvement in 13 patients, including four whose tumors completely disappeared. This method of intra-arterial chemotherapy may be useful as an adjuvant treatment for malignant glioma.

Shifting of dural arteriovenous malformation from the cavernous sinus to the sigmoid sinus to the transverse sinus after transvenous embolization. A case of left spontaneous carotid-cavernous sinus fistula.

The angiographic features of left spontaneous carotid-cavernous sinus fistula and multiple dural arteriovenous malformations that developed after transvenous embolization are described. A dural arteriovenous malformation involving the left sigmoid sinus was demonstrated, along with a marked decrease in size of the left carotid-cavernous sinus fistula and the disappearance of venous drainage from the left cavernous to the right cavernous sinus after embolization with spring coils via the left superior ophthalmic vein. The dural arteriovenous malformation of the left sigmoid sinus subsequently extended to the transverse sinus after partial embolization of the sigmoid sinus. Finally, a dural arteriovenous malformation involving the left transverse sinus developed, with the disappearance of the arteriovenous malformation affecting the sigmoid sinus and left carotid-cavernous sinus fistula following complete embolization of the sigmoid sinus via the left transverse sinus.

Headache associated with postpartum cerebral angiopathy: monitoring with transcranial color-coded sonography.

We report a case of postpartum cerebral angiopathy with headache; a rare entity that affects women within the early postpartum period. Cerebral angiography revealed multiple segmental narrowings of major cerebral arteries. The patient was monitored with transcranial color‐coded sonography of the middle cerebral artery. Abnormally increased flow velocity within the middle cerebral artery decreased following initiation of steroid therapy, and the patients headache improved dramatically.

Difference in CDDP penetration into CSF between selective intraarterial chemotherapy in patients with malignant glioma and intravenous or intracarotid administration in patients with metastatic brain tumor

Abstract Platinum (Pt) levels in plasma and cerebrospinal fluid (CSF) in patients with malignant glioma were determined after initiation of selective intraarterial chemotherapy with a combination of VP-16 (etoposide) and CDDP (cisplatin), and were compared with the CSF Pt levels in patients with metastatic brain tumors after intravenous or intracarotid administration of VP-16 and CDDP. CSF Pt levels were also compared for various administration routes, doses, CSF sampling routes and blood–CSF barriers in metastatic brain tumor. Changes in the blood-CSF barrier to CDDP during treatment in a patient with meningeal lymphoma and in a patient recovering from surgical removal of a metastatic brain tumor were also examined by periodic administration of CDDP. All CSF samples were taken through Ommaya reservoirs placed in the anterior horn of the lateral ventricle or the postoperative cavity. The mean peak CSF/plasma total Pt ratio (T/T ratio) and the mean CSF total Pt/plasma ultrafiltrable Pt ratio (T/U ratio) were highest (15.0% and 24.4%, respectively) following selective intraarterial infusion of CDDP in patients with malignant glioma, followed by intravenous infusion in meningeal carcinomatosis (11.5% and 18.9%), intracarotid administration (5.4% and 8.7%) and intravenous infusion (60 mg/m2 2.5% and 100 mg/m2 2.9%; and 60 mg/m2 3.5% and 100 mg/m2 7.7%) in patients with the solid type of metastatic brain tumor. In CSF obtained from the postoperative cavity in cases of metastatic brain tumor, T/T and T/U ratios were extremely high (40.9% and 62.4%). However, the CSF Pt level even after selective intraarterial administration of CDDP in malignant glioma was 0.51–1.64 μg/ml total Pt and 0.43–1.08 μg/ml ultrafiltrable Pt. Even the CSF level obtained from the postoperative cavity was 1.0–4.7 μg/ml total Pt. These low levels of total and ultrafiltrable Pt are considered not to be cytotoxic to disseminated cells in the CSF space and to normal brain cells. As for changes in the blood–CSF barrier, repeated administration of CDDP showed that the rate of entry of Pt into the CSF decreased in parallel with improvements apparent on CT scans in the patient with meningeal lymphoma, and also showed that the blood–CSF barrier to Pt was gradually repaired after the metastatic brain tumor had been removed.

Systemic multiple aneurysms of the extracranial internal carotid artery, intracranial vertebral artery, and visceral arteries: case report.

A rare case of systemic multiple aneurysms located in the extracranial internal carotid artery, intracranial vertebral artery, and intraperitonial arteries is described. A 56-year-old woman was referred to our hospital with suspected rupture of an aneurysm of the right extracranial internal carotid artery. Digital subtraction angiography demonstrated a giant aneurysm in the right extracranial internal carotid artery and an aneurysm of fusiform type of the left intracranial vertebral artery. The extracranial carotid artery aneurysm was successfully resected, with end-to-end anastomosis of the internal carotid artery, preserving the cranial nerves. Five days later, an aneurysm of the left hepatic artery ruptured unexpectedly and was treated with emergency surgery. Other aneurysms in the liver and spleen were identified on postoperative celiac angiography. The patient subsequently underwent an operation for a left intracranial vertebral artery aneurysm by proximal clipping.

Repair of intractable cerebrospinal fluid rhinorrhea with mucosal flaps and recombinant human basic fibroblast growth factor: technical case report.

OBJECTIVE AND IMPORTANCE:Repair of a cerebrospinal fluid leak is not always easy, especially when a large fistula, with concomitant infection and injured mucosa, has developed from repeated transsphenoidal operations. We repaired such a sellar floor defect with mucosal flaps via the endonasal endoscopic approach and finally obliterated the fistula by promoting granulation-like tissue formation with recombinant human basic fibroblast growth factor (bFGF). CLINICAL PRESENTATION:A 27-year-old woman with intractable cerebrospinal fluid rhinorrhea was referred to our department after repeated operations for a relapsing Rathke’s cleft cyst. Endonasal endoscopic examination revealed a large bone defect on the sellar floor through which previously packed fat and fascia were exposed to the nasal cavity. INTERVENTION:Mucosal flaps were harvested endoscopically from the nasal septum and the superior and middle turbinates. These pedicled flaps were transposed to the sellar defect. The flaps survived but did not cover the whole area, resulting in gaps between the flaps through which cerebrospinal fluid still leaked. Recombinant bFGF was repeatedly applied endoscopically to the mucosal flaps. The flaps turned into granulation-like tissue, and complete mucosal covering was finally achieved. CONCLUSION:bFGF has a wide range of biological effects, including stimulation of fibroblast growth and promotion of angiogenesis. It accelerates wound healing and is used clinically to treat dermal ulcers. The method presented here to treat an intractable fistula with mucosal flap and recombinant bFGF may suggest a new clinical application of bFGF. This possibility should be examined in a large number of patients in the future.Accepted, August 15, 2004. OBJECTIVE AND IMPORTANCE: Repair of a cerebrospinal fluid leak is not always easy, especially when a large fistula, with concomitant infection and injured mucosa, has developed from repeated transsphenoidal operations. We repaired such a sellar floor defect with mucosal flaps via the endonasal endoscopic approach and finally obliterated the fistula by promoting granulation-like tissue formation with recombinant human basic fibroblast growth factor (bFGF). CLINICAL PRESENTATION: A 27-year-old woman with intractable cerebrospinal fluid rhinorrhea was referred to our department after repeated operations for a relapsing Rathke’s cleft cyst. Endonasal endoscopic examination revealed a large bone defect on the sellar floor through which previously packed fat and fascia were exposed to the nasal cavity. INTERVENTION: Mucosal flaps were harvested endoscopically from the nasal septum and the superior and middle turbinates. These pedicled flaps were transposed to the sellar defect. The flaps survived but did not cover the whole area, resulting in gaps between the flaps through which cerebrospinal fluid still leaked. Recombinant bFGF was repeatedly applied endoscopically to the mucosal flaps. The flaps turned into granulation-like tissue, and complete mucosal covering was finally achieved. CONCLUSION: bFGF has a wide range of biological effects, including stimulation of fibroblast growth and promotion of angiogenesis. It accelerates wound healing and is used clinically to treat dermal ulcers. The method presented here to treat an intractable fistula with mucosal flap and recombinant bFGF may suggest a new clinical application of bFGF. This possibility should be examined in a large number of patients in the future.

Cis-diamminedichloroplatinum (CDDP) therapy for brain metastasis of lung cancer

SummaryThe distribution of cis-diamminedichloroplatinum (CDDP) was studied in 23 patients undergoing surgical resection of brain tumors metastatic from lung cancer. CDDP (100mg/m2) was administered intravenously (IV) or intra-arterially (IA) at the time of surgery, and various fluids and tissues were sampled for measurement of drug concentration. Comparison of the two routes of administration disclosed that the plasma level was slightly lower after IA than after IV infusion, whereas there was no difference between the two routes in terms of drug diffusion into the brain tissue adjacent to the tumor. However, IA administration resulted in an intratumoral drug concentration twice as high as that achieved with IV infusion. The tumor:plasma and tumor: adjacent brain ratios of drug concentration after IA injection were also twice those measured after IV administration. The distribution pattern of CDDP is characteristic of water-soluble agents. All patients experienced tolerable nausea and vomiting. Creatinine clearance was moderately reduced in ten cases, but no serious renal toxicity was observed. Seizures occurred postoperatively in nine patients. Infrequent side effects were myelosupression, ototoxicity, and postoperative intracranial bleeding. All adverse effects disappeared with conservative treatment or no intervention.

Endoscopic cranioplasty with calcium phosphate cement for pterional bone defect after frontotemporal craniotomy: technical note.

OBJECTIVE Postoperative pterional depression is a minor but unpleasant sequela of frontotemporal craniotomy. We developed a simple method for repair of this condition with the use of an endoscope and calcium phosphate cement. METHODS The cranial defect was approached by means of endoscopic visualization through a small incision within the hairline. The defect was repaired with an injectable calcium phosphate cement. RESULTS The bone defect was easily accessed and readily repaired in all five patients. No adverse reactions to the implant were observed. Satisfactory cosmetic results were obtained in all patients treated with the use of this method. CONCLUSION This minimally invasive cranioplasty technique proved to be effective for the repair of the postoperative pterional defect.