Norihiko Saito

Comparison of metastatic brain tumour models using three different methods: the morphological role of the pia mater

As methods of cancer diagnosis and treatment progress, interest in metastatic brain tumours continues to increase. There are many studies using various methods of animal model and we considered that each model reflects different pathological processes because of the unique composition of the brain. We prepared metastatic brain tumour models using three different methods. In this study, we attempted to elucidate the roles of the pia mater in brain metastasis. The metastatic foci showed an angiocentric pattern, forming collars of neoplastic cells, and were designated ‘perivascular proliferations’. Furthermore, we observed neoplastic cells that infiltrated the brain parenchyma, the border of which had become indistinct. These were labelled ‘invasive proliferations’. The internal carotid artery injection model reflects haematogenous metastasis. In this model, both perivascular and invasive proliferations were observed. The intrathecal injection model reflects leptomeningeal carcinomatosis. In this model, metastasis to the meninges was observed. In the stereotactic injection model, the tumour proliferation at the injection site and the infiltration into the brain parenchyma were observed. The pia‐glial membrane serves as a scaffold when neoplastic cells spread to the perivascular space forming angiocentric pattern. The pia‐glial membrane is found between the brain parenchyma and blood vessels. Blood vessels penetrate the brain through tunnels known as perivascular spaces that are covered by pia mater. Three different methods which we prepared reflect three different pathological processes. Our findings suggest that the pia mater is a critical factor in brain metastasis.

Intra-arterial Administration of Fasudil Hydrochloride for Vasospasm Following Subarachnoid Haemorrhage: Experience of 90 Cases

BACKGROUND we investigated the clinical efficacy of intra-arterial administration of fasudil hydrochloride for cerebral vasospasm. METHOD we reviewed 90 cases treated with intra-arterial administration of fasudil hydrochloride between August 1998 and April 2009 and investigated the clinical efficacy for cerebral vasospasm. FINDINGS angiographic improvement of vasospasm was noted in all procedures. Eight had ischemic lesion on CT at discharge in Group A, which included 39 patients who presented angiographic and symptomatic vasospasm. However, 4 (50%) of these eight were recovered with a condition of GR. No patients showed ischemic lesion on CT in Group B, which included 51 patients who presented angiographic vasospasm without symptoms. Two (3.3%) of 59 patients who presented angiographic vasospasm without symptoms at the initial follow-up angiography had ischemic lesion on CT at discharge. The 1-year follow-up showed 78.9% of GR. No patient showed any adverse effects resulting from intra-arterial administration of fasudil hydrochloride. CONCLUSION intra-arterial administration of fasudil hydrochloride was an effective and safe management technique for vasospasm.

Dynamics of global gene expression changes during brain metastasis formation

As methods of cancer diagnosis and treatment improve, interest in metastatic brain tumors continues to increase. In the present study, we attempted to characterize genetically the dynamic changes occurring during brain metastasis formation by DNA microarray, and attempted to compare these findings with histological observations. Lewis lung carcinoma cells were injected into C57BL/6Ncrj mice carotid arteries. The mice were sacrificed at days 1–9 after injection. We performed histological observation and genome‐wide expression profiling using a DNA microarray. In histological observation, tumor cells were observed in capillary vessels at day 1 after injection. At day 3, the tumor cells had begun to proliferate. At day 6, the metastatic foci showed “perivascular proliferations”. Next, we performed a pairwise comparison of gene expression microarray data from day 1 to day 9 after injection. The first major change occurred between Phase Two and Phase Three. When hierarchical clustering was performed between different samples using the 867 genes, they could be classified into identical clusters for days 1 and 2, identical clusters for day 3 to day 5, and identical clusters for day 6 to day 9. For time course analysis, we extracted 623 genes by the pairwise comparison. By using the quality threshold (QT) nonhierarchical clustering method, we identified 37 expression patterns. These patterns can be separated into eight clusters by using the k‐means method. The microarray results reported here strongly suggest that a large number of genes exhibit a spike pattern, which is tantamount to phase‐specific expression.

Prophylactic Intra-arterial Administration of Fasudil Hydrochloride for Vasospasm Following Subarachnoid Haemorrhage

PURPOSE We evaluated patients treated with prophylactic intra-arterial administration of fasudil hydrochloride (IAF) after subarachnoid haemorrhage (SAH). MATERIALS AND METHODS Between August 1998 and December 2012, 92 patients with aneurysmal SAH were treated with IAF for angiographic vasospasm without ischemic symptoms after their follow-up angiography. Patients comprised 50 women and 42 men, aged 24-83 (mean 56.6) years. IAF consisted of 15 mg of fasudil hydrochloride dissolved in 20 ml physiological saline and injected through a catheter during approximately 15 min, after diagnostic angiography. The clinical outcome was evaluated using the Glasgow Outcome Scale (GOS) at discharge and ischemic lesions resulting from vasospasm were assessed on computed tomography (CT) scan at discharge. RESULTS Forty-eight patients underwent surgical clipping and 44 patients underwent endovascular coiling. Angiographic improvement was observed in all patients (100 %). At discharge, 76 (83.0 %) of 92 patients showed good recovery on GOS. Nine patients developed progression of delayed ischemic neurological deficits (DIND) and three of these patients had ischemic lesions on CT scans. No patient had any significant changes in vital signs or any other adverse effects resulting from IAF. CONCLUSION IAF therapy was safe and effective for patients with vasospasm following SAH. Prophylactic IAF therapy may prevent symptomatic vasospasm.

A Case of Concomitant Occurrence of Struma Ovarii and Malignant Transformation of Cystic Teratoma

A 77-year-old woman received a total abdominal hysterectomy and bilateral salpingo-oophorectomy because of a tumor in the left ovary. The surgical specimen measured 8.5 × 4.5 × 4.0 cm, and the solid lesion measured 4.0 × 3.5 × 3.5 cm. The solid lesion was diagnosed as struma ovarii. The cyst wall partially comprised squamous epithelium-like and ciliated columnar epithelium-like cells. The tumorous lesion of the cyst wall revealed a poorly differentiated adenocarcinoma. Immunohistochemically, the tumor cells were positive for cytokeratin7, and were negative for cytokeratin20 and thyroid transcription factor-1. The authors diagnosed that struma ovarii and other parats coexisted as a poorly differentiated adenocarcinoma that had arisen from a mature ovarian cystic teratoma. As for the identification of the origin of adenocarcinomas arising from mature ovarian cystic teratomas, more cases need to be identified and investigated.

Posttraumatic Cranial Cystic Fibrous Dysplasia

A 14-year-old was girl admitted to our hospital with a subcutaneous mass of the occipital head. The mass had grown for 6 years, after she had sustained a head injury at the age of 6, and was located directly under a previous wound. Skull X-ray Photograph (xp), computed tomography (CT), and magnetic resonance imaging (MRI) showed a bony defect and cystic changes in the skull corresponding to a subcutaneous mass. Bone scintigraphy revealed partial accumulation. The patient underwent total removal of the skull mass, and the diagnosis from the pathological findings of the cyst wall was fibrous dysplasia (FD). The radiographic findings for cystic cranial FD can be various. Progressive skull disease has been reported to be associated with head trauma, but the relationship between cranial FD and head trauma has not been previously reported. Previous studies have suggested that c-fos gene expression is a key mechanism in injury-induced FD.

Treatment of Moyamoya Syndrome Associated with Systemic Lupus Erythematosus and Hypothyroidism in an Adult by Encephaloduroarteriosynangiosis: A Case Report

A 54-year-old woman presented to our hospital with progressive motor weakness of the right arm. She had a medical history of systemic lupus erythematosus (SLE) and hypothyroidism. Magnetic resonance imaging indicated a watershed infarction of the left hemisphere. Cervical echogram indicated severe stenosis of the internal carotid artery (ICA) without wall thickening. Cerebral angiography indicated left ICA occlusion, development of unilateral moyamoya vessels, and leptomeningeal anastomosis. Encephaloduroarteriosynangiosis (EDAS) was performed after cerebral 99 mTechnetium-ethyl-cysteinate-dimer single-photon emission computed tomography indicated a decreased cerebral blood flow, diminished cerebrovascular perfusion reserve. Motor weakness finally disappeared 6 months after surgery. Moyamoya syndrome is a rare complication of both SLE and hypothyroidism, and the surgical indication remains controversial. By evaluating the decreased cerebral perfusion reserve capacity and the existence of leptomeningeal anastomosis, EDAS could be an efficient method for the treatment of moyamoya syndrome associated with SLE and hypothyroidism.

Automated voxel-based analysis of brain perfusion SPECT for vasospasm after subarachnoid haemorrhage

Background We evaluated regional cerebral blood flow (rCBF) during vasospasm after subarachnoid haemorrhage (SAH) using automated voxel-based analysis of brain perfusion single-photon emission computed tomography (SPECT).