Cross talk between hedgehog and epithelial-mesenchymal transition pathways in gastric pit cells and in diffuse-type gastric cancers.

We previously reported hedgehog (Hh) signal activation in the mucus-secreting pit cell of the stomach and in diffuse-type gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is known to be involved in tumour malignancy. However, little is known about whether and how both signallings cooperatively act in diffuse-type GC. By microarray and reverse transcription-PCR, we investigated the expression of those Hh and EMT signalling molecules in pit cells and in diffuse-type GCs. How both signallings act cooperatively in those cells was also investigated by the treatment of an Hh-signal inhibitor and siRNAs of Hh and EMT transcriptional key regulator genes on a mouse primary culture and on human GC cell lines. Pit cells and diffuse-type GCs co-expressed many Hh and EMT signalling genes. Mesenchymal-related genes (WNT5A, CDH2, PDGFRB, EDNRA, ROBO1, ROR2, and MEF2C) were found to be activated by an EMT regulator, SIP1/ZFHX1B/ZEB2, which was a target of a primary transcriptional regulator GLI1 in Hh signal. Furthermore, we identified two cancer-specific Hh targets, ELK1 and MSX2, which have an essential role in GC cell growth. These findings suggest that the gastric pit cell exhibits mesenchymal-like gene expression, and that diffuse-type GC maintains expression through the Hh-EMT pathway. Our proposed extensive Hh-EMT signal pathway has the potential to an understanding of diffuse-type GC and to the development of new drugs.

Hearing preservation and intraoperative auditory brainstem response and cochlear nerve compound action potential monitoring in the removal of small acoustic neurinoma via the retrosigmoid approach.

OBJECTIVE: Hearing preservation is the main focus of small acoustic neurinoma (AN) removal. Refinement of intraoperative auditory monitoring may improve postoperative hearing. We have introduced a newly designed intracranial electrode enabling continuous monitoring of the cochlear nerve compound action potential (CNAP). We performed simultaneous monitoring of the auditory brainstem response (ABR) and CNAP during retrosigmoid small AN removal, and clarified the surgical outcome and the usefulness of CNAP monitoring. METHODS: Twenty-two consecutive patients with a small AN underwent retrosigmoid tumour removal with attempting hearing preservation. ABR and CNAP were simultaneously monitored during tumour removal. RESULTS: AN was totally removed in all patients without facial palsy. Preservation rate of useful and serviceable hearing was 82% and 91%, respectively. During microsurgical tumour removal, various surgical equipments and procedures intensified artefacts of ABR, and reliable ABR monitoring with distinct wave V was obtained in 9/22 patients. Unaffected by artefacts, reliable CNAP monitoring was obtained more frequently (in 20/22 patients) than ABR (p = 0.0005). CNAP on completion of tumour removal predicted hearing preservation with no false positive or negative (100% sensitivity and 100% specificity). CNAP changed dynamically and stepwise with surgical manipulations. CONCLUSION: The retrosigmoid approach using auditory monitoring for a small AN can accomplish total tumour removal with an excellent hearing preservation rate. CNAP provides reliable auditory monitoring more frequently than ABR, reflects the intraoperative auditory function almost in real-time, predicts postoperative hearing with excellent sensitivity and specificity, and is more useful for monitoring in the removal of small AN with hearing preservation.

GASDERMIN, suppressed frequently in gastric cancer, is a target of LMO1 in TGF-beta-dependent apoptotic signalling.

Defining apoptosis-regulatory cascades of the epithelium is important for understanding carcinogenesis, since cancer cells are considered to arise as a result of the collapse of the cascades. We previously reported that a novel gene GASDERMIN (GSDM) is expressed in the stomach but suppressed in gastric cancer cell lines. Furthermore, in this study, we demonstrated that GSDM is expressed in the mucus-secreting pit cells of the gastric epithelium and frequently silenced in primary gastric cancers. We found that GSDM has a highly apoptotic activity and its expression is regulated by a transcription factor LIM domain only 1 (LMO1) through a sequence to which Runt-related transcription factor 3 (RUNX3) binds, in a GSDM promoter region. We observed coexpression of GSDM with LMO1, RUNX3 and type II transforming growth factor-beta receptor (TGF-betaRII) in the pit cells, and found that TGF-beta upregulates the LMO1- and GSDM-expression in the gastric epithelial cell line and induces apoptosis, which was confirmed by the finding that the apoptosis induction is inhibited by suppression of each LMO1-, RUNX3- and GSDM expression, respectively. The present data suggest that TGF-beta, LMO1, possibly RUNX3, and GSDM form a regulatory pathway for directing the pit cells to apoptosis.

Gamma knife surgery for brain metastases: indications for and limitations of a local treatment protocol.

OBJECTIVE: The purpose of this retrospective study was to evaluate results of a local treatment protocol using gamma knife surgery (GKS) for brain metastases without upfront whole brain radiation therapy (WBRT). METHODS: Results for 521 consecutive patients satisfying the following 3 criteria were analysed: 1) a maximum of 3 tumours with a diameter of 25 mm or more; 2) no prior WBRT; 3) no surgically in accessible large (>30 mm) tumours. Large tumours were surgically removed and all smaller lesions were treated by GKS without up front WBRT. New lesions, detected with follow-up MRI, were appropriately treated with repeat GKS. Overall survival (OS), neurological survival (NS), qualitative survival (QS) and new lesion-free survival (NLFS) curves were calculated and the prognostic values of covariates were obtained. OS and NS were compared according to tumour number. RESULTS: In total, 1023 separate sessions were required to treat 4562 lesions. The primary organs were lung in 369 patients, gastro-intestinal tract in 70, breast in 33, urinary tract in 24, and others/unknown in 25. The median OS period was 9.0 months. On multivariate analysis, the significant prognostic factors for OS were found to be extracranial disease (risk factor: active), Karnofsky performance status (KPS) score (<70) and gender (male). NS and QS at one year were 85.6% and 73.0%, respectively. The only significantly poor prognostic factor for NS was carcinomatous meningitis. NLFS at 6 months was 68.9%. For both OS and NS, the differences between a few (10) tumours had a significantly poorer prognosis than those with

Cytosolic Ca2+ movements of endothelial cells exposed to reactive oxygen intermediates: role of hydroxyl radical-mediated redox alteration of cell-membrane Ca2+ channels.

1. The mode of action of reactive oxygen intermediates in cysosolic Ca2+ movements of cultured porcine aortic endothelial cells exposed to xanthine/xanthine oxidase (X/XO) was investigated. 2. Cytosolic Ca2+ movements provoked by X/XO consisted of an initial Ca2+ release from thapsigargin-sensitive intracellular Ca2+ stores and a sustained Ca2+ influx through cell-membrane Ca2+ channels. The Ca2+ movements from both sources were inhibited by catalase, cell-membrane permeable iron chelators (o-phenanthroline and deferoxamine), a *OH scavenger (5,5-dimethyl-1-pyrroline-N-oxide), or an anion channel blocker (disodium 4, 4'-diisothiocyano-2, 2'-stilbenedisulphonic acid), suggesting that *O2- influx through anion channels was responsible for the Ca2+ movements, in which *OH generation catalyzed by intracellular transition metals (i.e., Haber-Weiss cycle) was involved. 3. After an initial Ca2+ elevation provoked by X/XO, cytosolic Ca2+ concentration decreased to a level higher than basal levels. Removal of X/XO slightly enhanced the Ca2+ decrease. Extracellular addition of sulphydryl (SH)-reducing agents, dithiothreitol or glutathione, after the removal of X/XO accelerated the decrement. A Ca2+ channel blocker, Ni2+, abolished the sustained increase in Ca2+, suggesting that Ca2+ influx through cell-membrane Ca2+ channels was extracellularly regulated by the redox state of SH-groups. 4. The X/XO-provoked change in cellular respiration was inhibited by Ni2+ or dithiothreitol as well as inhibitors of Haber-Weiss cycle, suggesting that Ca2+ influx was responsible for *OH-mediated cytotoxicity. We concluded that intracellular *OH generation was involved in the Ca2+ movements in endothelial cells exposed to X/XO. Cytosolic Ca2+ elevation was partly responsible for the oxidants-mediated cytotoxicity.

Effect of pituitary microsurgery on acromegaly complicated nephrotic syndrome with focal segmental glomerulosclerosis: report of a rare clinical case.

A case of nephrotic syndrome complicated by acromegaly is presented. The first renal biopsy specimen showed minor glomerular abnormalities with glomerular hypertrophy, corresponding with minimal change nephrotic syndrome. Corticosteroid therapy led to a partial remission, followed by frequent relapses after reduction of the drug. A diagnosis of atypical focal segmental glomerulosclerosis (FSGS) was made based on the second renal biopsy results 6 months after the first. We combined steroid therapy with the administration of an anticoagulant, cytotoxic agents, angiotensin-converting enzyme inhibitor, and low-density lipoprotein adsorption. Except for the angiotensin-converting enzyme inhibitor, these medications were not effective in terms of allowing a reduction in the high dosage of steroid, which in turn threatened progressive osteoporosis and lumbar vertebrae fracture. Administering the steroid at a moderate dosage, treatment was focused on the complicating acromegaly from pituitary microadenoma. Subcutaneous injections of octreotide acetate, a somatostatin analogue, reduced proteinuria and increased urine volume. Subsequent transsphenoidal microsurgery of the adenoma resulted in the normalization of the elevated creatinine clearance and the further reduction in steroid dosage while maintaining a remission state. This is the first reported clinical case with acromegaly followed by FSGS, and it is suggested that hypersecretion of growth hormone participates in the development and progression of glomerular disease.

Glucose loading during primary culture has opposite effects on the viability of hepatocytes exposed to potassium cyanide and to iodoacetic acid.

Whether or not to apply nutritional pretreatment and how to do so are controversial issues with respect to the liver about to undergo aggressive intervention. We studied the effects of glucose loading on the viability of hepatocytes that were subsequently exposed to the inhibitors of carbohydrate metabolism, potassium cyanide (KCN) and iodoacetic acid (IAA). After rat hepatocytes were cultured for 24 hours in Leibovitz's L-15 medium containing 0, 10, 20, and 30 mmol/L glucose, the medium was replaced with modified Hanks-HEPES buffer with or without 2.5 mmol/L KCN or 0.5 mmol/L IAA. Lactate dehydrogenase (LDH) activity, lactate concentration, and pH of the supernatant were measured after 0, 2, 4, and 6 hours of exposure to KCN and after 0, 20, 40, and 60 minutes of exposure to IAA. Glycogen and adenosine triphosphate (ATP) contents in the hepatocytes were measured simultaneously. Hepatocytes cultured with various concentrations of glucose for 24 hours stored levels of glycogen in proportion to the glucose concentration in the culture medium without any significant difference in viability. The hepatocytes cultured with higher glucose concentrations maintained a higher ATP content and released less LDH and more lactate, and the pH decreased in the supernatant during exposure to KCN. Conversely, hepatocytes cultured with lower glucose concentrations maintained a higher ATP content and released less LDH during exposure to IAA. In conclusion, prior glucose loading appears to be beneficial for hepatocytes if oxidative phosphorylation is to be inhibited, whereas withholding glucose appears to be beneficial if glycolysis is to be inhibited.

Serological diagnosis of equine influenza using the hemagglutinin protein produced in a baculovirus expression system.

The hemagglutinin (HA) protein of an equine influenza strain, A/equine/La Plata/1/93 (LP/93), was produced using a baculovirus expression system. Silkworm larvae inoculated with recombinant baculovirus expressed high quantities of the HA protein which was then purified to greater than 95% purity by fetuin-affinity chromatography. Purified HA protein was used subsequently in an ELISA for detection of antibodies in horse sera. Two hundred serum samples from vaccinated racehorses were reacted on ELISA plates coated with 40.0 ng/ml of purified HA protein. Subsequent optical density (OD) levels revealed titers which correlated highly with respective hemagglutinin inhibition (HI) antibody titers which ranged from <1:8 to 1:256 (correlation coefficient among them was 0.850). ELISA OD levels and HI titers increased at 5 and 7 days post-inoculation, respectively, in a horse inoculated intranasally with LP/93. Respective antibody levels were observed to change in an essentially parallel manner during a period of 1 month. Similarly, ELISA OD levels correlated with HI titers in horses during a period of 6 weeks following intramuscular inoculation with inactivated single-strain vaccines containing LP/93, A/equine/Kentucky/1/81 (H3N8) or A/equine/Rome/5/91 (H3N8). A similar pattern was also observed in eight horses throughout a 10-week period following inoculation with a commercially available inactivated trivalent vaccine containing A/equine/Newmarket/1/77(H7N7), A/equine/Kentucky/81 and LP/93. From these results, it is suggested that this ELISA system could be used for disease diagnosis and surveillance of HI antibody titers among vaccinated horses.

Maxadilan specifically interacts with PAC1 receptor, which is a dominant form of PACAP/VIP family receptors in cultured rat cortical neurons.

Maxadilan is a potent vasodilator peptide isolated from salivary gland extracts of the hematophagous sand fly. Recently, the possibility was demonstrated that maxadilan binds to PAC1 receptor (PACAP, pituitary adenylate cyclase activating polypeptide type I receptor) in mammals. In the present study, we demonstrated that: (1) maxadilan specifically binds to PAC1 receptor and stimulates cyclic AMP accumulation in a dose-dependent manner in CHO cells stably expressing PAC1 receptor, not VIP (vasoactive intestinal polypeptide) receptors; that (2) the deleted peptide (amino acid #24-42) of maxadilan (termed max.d.4) also specifically binds to PAC1 receptor although max.d.4 inhibits cyclic AMP accumulation stimulated by both maxadilan and PACAP; and that (3) max.d.4 completely blocks the cyclic AMP accumulation induced by VIP in cultured rat cortical neurons. The expression of specific PACAP receptors in cultured rat cortical neurons was further investigated by the reverse transcription-polymerase chain reaction technique, which showed the presence of mRNA coding for PAC1 receptor among PACAP/VIP family receptors. These data indicate that maxadilan and max.d.4 represent important tools for clarifying the physiological role of PAC1 receptor, and that PAC1 receptor plays an important role in the regulation of the functions induced by PACAP in rat cultured cortical neurons.

Heavily T2-weighted MR imaging of white matter tracts in the hypothalamus: normal and pathologic demonstrations.

BACKGROUND AND PURPOSE: The MR appearance of white matter tracts in the hypothalamus and the role of the hypothalamus as a memory mechanism have not been sufficiently described in clinical settings. Heavily T2-weighted black-and-white reversed (T2R) images were assessed to reveal their visualization and clinical significance. METHODS: One hundred healthy subjects and three patients with hypothalamic lesions underwent fast spin-echo MR imaging to reveal the postcommissural fornix (PF) and mammillothalamic tract (MT). RESULTS: The PF was identifiable in axial and/or coronal sections in all healthy subjects. No remarkable asymmetry of its size or course was evident. Both anteroposterior and vertical dimensions ranged from 10.5 to 14 mm. The MT was visible in one or two axial sections above the mammillary body in 64% of healthy subjects and in a coronal section in 36%. Two patients with glioblastoma multiforme and lacunar infarct at the hypothalamus presented with anterograde amnesia; T2R imaging revealed involvement of both the PF and MT. The third patient had a suprasellar craniopharyngioma with PF injury sparing the MT resulting from surgical manipulation and was free of memory deficit. Anterograde amnesia was evident only when both the PF and MT were injured. CONCLUSION: T2R images have made a high rate of detection of the PF and MT possible and could provide a more detailed correlation of hypothalamic neuroanatomy and memory mechanism in clinical settings.

Microsurgical anatomy and clinical significance of the anterior communicating artery and its perforating branches.

OBJECTIVE: Precise identification of the anomalous anterior communicating artery (ACoA) or the perforating branches of the ACoA is usually difficult on preoperative angiograms because of the vascular complexity around the ACoA and its small-caliber branches. The purpose of this study was to review the microsurgical anatomy of the ACoA and its branches to show their importance for the interhemispheric trans-lamina terminalis approach and ACoA aneurysmal surgery. METHODS: In 30 cadaver brains, the ACoA and its branches were examined under magnification using a surgical microscope. RESULTS: The ACoA was evident in all specimens and had variations consisting of plexiform (33%), dimple (33%), fenestration (21%), duplication (18%), string (18%), fusion (12%), median artery of the corpus callosum (6%), and azygous anterior cerebral artery (3%). The perforating branches were also observed in all cadaver brains. They were classified into subcallosal, hypothalamic, and chiasmatic branches according to their vascular territories. The subcallosal branch, usually single and the largest, supplied the bilateral subcallosal areas, branching off to the hypothalamic area. The hypothalamic branches, multiple and of small caliber, terminated in the hypothalamic area. CONCLUSION: The incidence of anomalous ACoA was higher than has been previously reported, and any segment of the anomalous ACoA may have perforating branches regardless of diameter. Among the three branches, the subcallosal branch is the most important because it feeds bilateral subcallosal areas branching to the hypothalamic area.

Dissecting aneurysms of the intracranial vertebral artery.

Among 86 patients with aneurysms arising from the vertebral artery or its branches, 24 had dissecting aneurysms. The patients with dissecting aneurysms were characteristically relatively young males. Twenty-one patients presented with subarachnoid hemorrhage (SAH) and three with ischemia. Severe headache or neck pain occurred in all three patients with ischemia. Five of the 21 patients with SAH and all three patients with ischemia experienced recurrent episodes. Angiography typically showed fusiform dilatation and proximal and/or distal narrowing of the affected artery. The difficulty of diagnosing this disorder is pointed out. Surgery was performed in 19 patients, the most common technique being clip-occlusion of the proximal vertebral artery. There were no postoperative deaths or rebleeding; a lateral medullary syndrome developed in three patients. The observation at surgery of intramural clot with characteristic discoloration was limited to the cases operated on within 36 days after the ictus. After this period, the aneurysm was whitish gray in color and had become firm. Of 36 other cases of vertebral dissecting aneurysm reported in the literature, 20 were operated on. The indications for surgery are discussed.

Microsurgical anatomy of the upper basilar artery and the posterior circle of Willis.

The microvascular anatomy of the posterior part of the circle of Willis, important in surgery of pituitary tumors and basilar aneurysms, was defined in 50 cadaver brains. Significant findings were as follows: 1) Anomalies of the posterior half of the circle of Willis were found in 46% of cases. 2) Hypoplastic P-1 (posterior cerebral segment) and posterior communicating segments gave origin to the same number and size of perforating arteries, having the same termination as normal-sized segments. Thus hypoplastic segments should be handled with care and divided to aid in exposure of the basilar bifurcation only after careful consideration. 3) An average of four perforating branches arose from P-1; most from the superior and posterior sufaces. No branches arose from the anterior surface of the basilar bifurcation. The most proximal P-1 branch originated 2 to 3 mm distal to the basilar bifurcation. It was most commonly a thalamoperforating artery. The largest P-1 branch was usually a thalamoperforating or a posterior choroidal artery. 4) An average of seven branches emerged from the superior and lateral surfaces of the posterior communicating artery. The anterior half was a richer source of perforators than the posterior half. The largest communicating branch in 80% of specimens supplied the premamillary area. 5) The anterior choroidal artery originated from the carotid artery on both sides in all cases. A double anterior choroidal artery was present in 4% of cases.

Long-term natural history of hemorrhagic moyamoya disease in 42 patients.

OBJECT: The purpose of this study was to delineate the long-term natural history of hemorrhagic moyamoya disease (MMD). METHODS: A retrospective review was conducted among 42 patients suffering from hemorrhagic MMD who had been treated conservatively without bypass surgery. The group included four patients who had undergone indirect bypass surgery after an episode of rebleeding. The follow-up period averaged 80.6 months. The clinical features of the first bleeding episode and repeated bleeding episodes were analyzed to determine the risk factors of rebleeding and poor outcome. Intraventricular hemorrhage with or without intracerebral hemorrhage was a dominant finding on computerized tomography scans during the first bleeding episode in 29 cases (69%). During the follow-up period, 14 patients experienced a second episode of bleeding, which occurred 10 years or longer after the original hemorrhage in five cases (35.7%). The annual rebleeding rate was 7.09%/person/year. The second bleeding episode was characterized by a change in which hemisphere bleeding occurred in three cases (21.4%) and by the type of bleeding in seven cases (50%). After rebleeding the rate of good recovery fell from 45.5% to 21.4% and the mortality rate rose from 6.8% to 28.6%. Rebleeding and patient age were statistically significant risk factors of poor outcome. All four patients in whom there was indirect revascularization after the second bleeding episode experienced a repeated bleeding episode within 8 years. CONCLUSIONS: The occurrence of rebleeding a long time after the first hemorrhagic episode was not uncommon. Furthermore, the change in which hemisphere and the type of bleeding that occurred after the first episode suggested the difficulty encountered in the prevention of repeated hemorrhage.

Gamma knife treatment for multiple metastatic brain tumors compared with whole-brain radiation therapy.

OBJECT: The purpose of this retrospective study was to compare the effectiveness of gamma knife radiosurgery (GKS) for multiple cerebral metastases with that of whole-brain radiation therapy (WBRT). METHODS: Ninety-six consecutive patients with cerebral metastases from nonsmall cell lung cancer were treated between 1990 and 1999. The entry criteria were the presence of between one and 10 multiple brain lesions at initial diagnosis, no surgically inaccessible tumors with more than a 30-mm diameter, no carcinomatous meningitis, and more than 2 months of life expectancy. The patients were divided into two groups: the GKS group (62 patients) and the WBRT group (34 patients). In the GKS group, large lesions (> 30 mm) were removed surgically and all other small lesions (< or = 30 mm) were treated by GKS. New distant lesions were treated by repeated GKS without prophylactic WBRT. In the WBRT group, the patients were treated by the traditional combined therapy of WBRT and surgery. In both groups, chemotherapy was administered according to the primary physician's protocol. The two groups did not differ in terms of age, sex, initial Karnofsky Performance Scale (KPS) score, type, lesion number, and size of lesion, systemic control, and chemotherapy. Neurological survival and qualitative survival of the GKS group were longer than those of the WBRT group. In multivariate analysis, significant poor prognostic factors were systemically uncontrolled patients, WBRT group, and poor initial KPS score. CONCLUSIONS: Gamma knife radiosurgery without prophylactic WBRT could be a primary choice of treatment for patients with as many as 10 cerebral metastases from nonsmall cell cancer.

Topographical analysis of proliferating cells in meningiomas. Regional heterogeneity of the ability of tumors to proliferate.

Regional heterogeneity of the ability of tumors to proliferate has been pointed out, but its topographical analysis has not been studied in detail. To evaluate the distribution of highly proliferating cells in totally resected meningiomas, seven cases (including one recurrent case) were investigated in this study. Immunostaining of PCNA was performed on the sections crossing the equator of the tumors. These sections were divided into multi-squares with sides of 500 micrometers. The proliferating potential was determined as the PCNA positive cell count in each square. By painting those squares in eight kinds of color corresponding to the value of the PCNA positive cell count, maps of proliferative ability were made. To predict the localization of proliferating cells, we studied these maps in relation to the following: MR image, calcification, distance from the dural attachment and distance from the tumor capsule. Maps of the PCNA positive cell count showed the intra-tumoral heterogeneity of proliferative ability in all cases. Most of the cases showed homogeneous enhancement on MRIs and these images could not be a predicting factor of the highly proliferating area. There was no significant relationship between the calcification and the PCNA positive cell count. Although the proliferating ability was not correlated with the distance from the dural attachment, inner regions distant from the capsule showed higher proliferative ability in all cases. From these results, one should be aware that the information from the samples of meningiomas do not reflect the proliferating ability of the whole tumor.

Glucose and methionine uptake and proliferative activity in meningiomas.

Despite similar benign histological appearances, proliferative activity of meningiomas varies tumor to tumor, and even region to region in a tumor. To predict proliferative potential before surgery, we compared regional uptake of 2-[18F]fluoro-2-deoxyglucose ([18F]FDG) and L-[methyl-11C]methionine ([11C]MET) with histological indices of tumor proliferative activity in 17 specimens from six patients with meningioma obtained by PET guided stereotactic biopsies. Uptake of [11C]MET, an index of protein synthesis rate, significantly correlated not only with the count of nucleolar organizer regions (NORs), a histological index of protein synthesis, but also with Ki-67 index, a histological index of proliferative activity. On the other hand, [18F]FDG uptake showed no significant correlation with Ki-67 index or clinical malignancy. These results suggest that [11C]MET-PET is a useful tool for predicting tumor proliferative potential in meningiomas.

Evaluation of outcome and QOL in patients with craniofacial resection for malignant tumors involving the anterior skull base.

The purpose of this study was to retrospectively evaluate the effectiveness of anterior craniofacial resection in the treatment of nasal and paranasal malignant tumors involving anterior skull base. Between 1992 and 1998, 13 patients with nasal or paranasal malignant tumors underwent this surgical procedure. The site and time of metastasis or recurrence, and survival outcome were retrospectively surveyed. Current status of long-surviving patients and their subjective assessment of the surgical treatment were also evaluated through questionnaires. Median follow-up period was 52 months. Nine patients (69%) were alive with no evidence of disease. Of these patients, eight had survived for more than three years. Recurrence or metastasis occurred in four patients (31%). The mean time interval between surgery and recurrence or metastasis was 11 months. According to the results of questionnaires to long-surviving patients, 89% patients had some complaints. In particular, complaints of unsightly appearance were manifested by all these patients. When the patients themselves evaluated their current conditions resulting from this surgical treatment, 63% were dissatisfied. These results suggest that this surgical treatment is valid for selected patients in regard to survival outcome. When the effectiveness of this treatment is evaluated, however, psychological and functional issues should not be taken lightly.

Empty sella in children as a key for diagnosis.

We performed magnetic resonance imaging of the pituitary gland in 354 children who were under the care of our pediatric neurological outpatient department. Among them, an empty sella was recognized in 11 children, who all showed normal hormonal results. The frequency of an empty sella was significantly high in idiopathic intracranial hypertension (4/4; P<0.0001) and nevoid basal cell carcinoma syndrome (3/5; P<0.0001). The ratio of an empty sella in children, excluding patients with idiopathic intracranial hypertension and nevoid basal cell carcinoma syndrome, is estimated to be 4/345 (1.2%), which is markedly lower than that in adults. Magnetic resonance imaging of the pituitary gland in children could provide important clues for the diagnosis of idiopathic intracranial hypertension or nevoid basal cell carcinoma syndrome.

Hemorrhagic type moyamoya disease.

The clinical picture of hemorrhagic type Moyamoya disease was analyzed in 20 cases. Hematoma at the basal ganglia was noted in 40% of cases, intraventricular hemorrhage (IVH) in 30%, thalamic hemorrhage with ventricular rupture in 15% and subcortical hemorrhage in 5%. The location was undetermined in two cases (10%) due to bleeding in the pre-computed tomography (CT) era. The frequencies shown above were correlated well to previous reports. In magnetic resonance imaging (MRI) performed 1 year or more after IVH, the primary bleeding site was demonstrated at the lateral wall of lateral ventricle, in portion density weighted and T2 weighted images. MRI can detect the site of old bleeding points and its chronological change if the study is repeated. In a follow-up period of 6.2 years, 35% of the cases had rebleeding once or twice. The second bleeding occurred seven times and the third twice. IVH occurred five times and the most common, basal ganglia hematoma three times while thalamic hemorrhage once. As a result, the rate of good outcome was 60% after the first bleeding and 40% after rebleeding. The mortality rate was 5% after the first 25% after rebleedings. Factors related to rebleedings and their poorer outcome are sex (with women being more susceptible), massive ICH and early recurrence. Rebleeding worsened the outcome. Therefore, prevention of rebleeding is important. From a therapeutic viewpoint, although a close relation between rebleeding and untreated hypertension could not be established, blood pressure control is critical at the both acute and chronic stages. Bypass surgery for bleeding type of Moyamoya disease seems to be less promising than ischemic type, even though a definite answer may not be obtained from our small number of cases.