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.

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.

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

MRI of ectopic posterior pituitary bright spot with large adenomas: appearances and relationship to transient postoperative diabetes insipidus.

MRI of large pituitary adenomas has revealed that a posterior pituitary bright spot (PPBS), comprising ADH-containing neurosecretory granules, is commonly ectopic before surgery and attached to the tip of the pituitary stalk late after surgery. Although the PPBS indicates functional integrity of the posterior lobe, transient diabetes insipidus (DI), caused by deficiency of ADH, is frequent early after surgery. We attempted to clarify how the shape, signal intensity and site of the PPBS before surgery are related to transient DI in the early postoperative period. We carried out MRI on 15 patients with a large adenoma and an ectopic PPBS before surgery and then within 1 week (early), 1-2 months (intermediate) and 6 or more months (late) after the operation. There were nine who had transient DI, which subsided by the intermediate study; none had permanent DI. Regardless of transient DI, the PPBS was visible, and its signal intensity was similar, on all postoperative studies. Although 11 did not change in shape, four showed a remarkable change from a flat shape before surgery to a rounded one postoperatively. On the intermediate MRI, the PPBS had descended to the level of the diaphragma as mass effect disappeared.

Temporal parenteral nutrition in children causing t1 shortening in the anterior pituitary gland and globus pallidus.

Patients receiving long-term parenteral nutrition (PN) with trace elements (TE) may exhibit T (1) shortening in the anterior pituitary gland and basal ganglia. The purposes of this study were to clarify at what time or from what site the signal change begins in children. Retrospective analysis of magnetic resonance imaging results was performed for 10 pediatric patients aged from 1 to 16 years receiving temporal PN, eight of which received PN with TE for less than two months, and 13 patients with headache or seizures as age-matched controls. Axial and sagittal T (1)-weighted images were obtained to analyze the T (1) shortening in the anterior pituitary gland and globus pallidus. All eight patients receiving PN with TE exhibited T (1) shortening in the anterior pituitary gland (six patients) and/or globus pallidus (five patients). No T (1) shortening was observed in the other two patients without TE, or the 13 age-matched controls. Therefore, the signal change may be associated with TE administration, and begins markedly earlier than previously reported. We discussed the possibility that manganese (Mn) caused the signal change, and proposed that the administration of a lower dose of Mn is recommended, even in the case of temporal PN, to prevent possible Mn toxicity toward both the brain and liver.

Criteria for early detection of temporal hemianopia in asymptomatic pituitary tumor.

PURPOSE: To determine new criteria for early detection of temporal hemianopia in patients with asymptomatic pituitary tumor. METHODS: Fifteen patients without visual symptoms had pituitary tumor and subtle defects or normal visual fields by Goldmann perimetry. Twelve patients with visual symptoms had pituitary adenoma and visual field defects detected by Goldmann perimetry. All were examined by automated perimetry. The relationship between the tumor and the optic chiasm was graded by magnetic resonance imaging (MRI) on a scale of 0-4. Grade number increased with extent of compression. Temporal hemianopia observed by automated perimetry was estimated from normal data (52 normal fields). Vertical step was determined from the number of adjacent pairs along the midline; sensitivity was lower in the temporal field than in the nasal field. Temporal depression was calculated by the quadrant sum of sensitivity. RESULTS: All patients with symptomatic pituitary adenoma had vertical step and temporal depression in the upper field. Nine of 15 patients without visual symptoms had vertical step or temporal depression. Of nine patients with temporal hemianopia, two of four patients had grade 1 compression, three of five had grade 2, and four of four had grade 3. CONCLUSIONS: New criteria by automated perimetry could detect temporal hemianopia in patients with asymptomatic pituitary tumor.

Demonstration of the optic pathway in large pituitary adenoma on heavily T2 weighted MR images.

The objective of the investigation was to understand preoperatively the detailed anatomical relationship of large pituitary adenomas to surrounding structures, using the heavily T2-weighted reversed (T2R) MR images. This study consisted of 28 patients with pituitary adenoma, presenting with visual disturbance. The MRI scanner used was a Gyroscan ACSNT 1.5T and the slice thickness of the image was 3 mm with 0.5 mm interslice gap. The relation of pituitary adenoma to optic pathway and to the degree of visual field defect was assessed. Relations of the optic chiasm to adenoma were classified into three types: anterior, superior and posterior. The optic chiasm was directly visualized and identifiable in all patients studied. It was located anterior in four cases, superior in 22 and posterior in two in relation to the adenoma. Its location was further confirmed by the anatomical delineation of surrounding structures such as anterior commissure and lamina terminalis. Optic nerve or tract was unidentifiable in one case, for each category. Detectability of each optic component was higher on T2R images than on conventional T1-weighted images. The adenoma extended into and in front of the third ventricle in anterior and posterior types, respectively. The anterior communicating artery complex and the optic pathway were relocated together in anterior and superior types, and were separated in the posterior type. In a case of the posterior type, the complex was sectioned to obtain a wider surgical field during anterior interhemispheric approach. While degrees of visual field defect were proportional to tumour size in the superior type, they were unrelated in the anterior and posterior types. On choosing a transcranial approach, the transcallosal route is unsuitable for an adenoma of posterior type, which extends in front of the third ventricle. This preoperative MRI information makes it possible to visualize directly the optic pathway even in huge adenomas, and is useful in predicting surgical anatomy and selecting a proper surgical approach.

Potential role of the anterior spinal artery in preventing propagation of thrombus in a therapeutically occluded vertebral artery: angiographic studies before and after endovascular treatment.

Therapeutic occlusion of the vertebral artery (VA) is one of the treatments for unclippable aneurysms and other lesions, although controversy still surrounds the appropriate site for occlusion to attain selective thrombosis of the lesion while avoiding ischaemic complications. The lower two-thirds of the lateral medulla are supplied by perforating branches of both the VA and the posterior inferior cerebellar artery (PICA). However, in patients without a PICA or in whom the origin of the PICA is low (at or below the foramen magnum), the VA is usually the only source of perforating vessels. We retrospectively studied the results of VA occlusion on such anatomically high-risk patients, and propose a safer procedure. Five high-risk patients underwent therapeutic occlusion of the VA for dissecting aneurysms or arteriovenous fistula. A lateral medullary syndrome developed due to propagation of thrombus after the procedure in two patients in whom angiography did not demonstrate the anterior spinal artery (ASA) within the stump of the VA. Ischaemic signs did not develop in the other three patients, in whom the ASA was visible, and retrograde flow was observed proximal to the origin of the ASA. This suggests that the ASA may play a role in preventing propagation of thrombus in the VA distal to the site of occlusion and supply blood to its perforating arteries in high-risk patients. Angiographic assessment of the ASA may be useful for predicting the likelihood of the lateral medullary syndrome developing with therapeutic occlusion of the VA in patients without a PICA or with one whose origin is low.

Heavily T2 weighted MR images of anterior optic pathways in patients with sellar and parasellar tumours - prediction of surgical anatomy.

OBJECTIVE: Location of anterior optic pathways in sellar and parasellar tumours was preoperatively evaluated, by use of heavily T2 weighted MR images. METHODS: Heavily T2 and conventional T1 weighted images were studied in 20 patients with sellar and parasellar tumours who underwent craniotomy. Pathology revealed pituitary adenoma in 5 patients, craniopharyngioma in 8 and parasellar meningioma in 7. Maximum sizes ranged from 15 mm to 58 mm. Sequence parameters of TR/TE for heavily T2 weighted and T1 weighted images were 5800/220 msec and 600/20 msec, respectively, and slice thickness was 3 mm for both. RESULTS: The anterior optic pathway was detected in 95% on heavily T2 weighted images and 50% on T1 weighted images. All preoperative heavily T2 weighted images were compatible with operative findings. The optic chiasms were most commonly supero-posterior in pituitary adenomas, anterior (prefixed) in craniopharyngiomas and posterior in meningiomas. The optic nerves were commonly located superior or lateral to the tumours. However, parasellar meningiomas, off the midline, revealed the optic nerves in various locations, depending on the tumour origin. In such tumours, heavily T2 weighted images provided surgical information on the width of the working space through prechiasmal and/or optico-carotid spaces in the pterional approach. Spatial relation of the tumours to the lamina terminalis, anterior commissure and anterior communicating artery complex was clearly shown in craniopharyngioma patients, who underwent the anterior interhemispheric approach. CONCLUSION: Heavily T2 weighted MR images are useful in determining the location of optic pathways and surgical approach and in individual prediction of the anatomy for even large sellar and parasellar tumours.

Long-term Karnofsky performance status and neurological outcome in patients with neurohypophyseal germinomas.

Long-term posttreatment Karnofsky Performance Status (KPS) and neurological status of 16 patients with neurohypophyseal (NH) germinomas were retrospectively analysed, in order to deduce the best treatment modality to achieve a good outcome. The average age at treatment was 15.5 years (rouge 6-26) and they were followed up for 107.3 months (26-209). The KPS averaged 81.5 (0-100). Three patients were below 60 in the KPS. The first one had hemiparesis due to a delayed cerebrovascular accident (CVA), and the second became indifferent and inactive with recent memory loss. The third died from marginal recurrence of tumour and subsequent systemic metastasis. The low scores were all more or less attributable to complications related to irradiation: delayed CVA, diffuse cortical atrophy and inappropriate selection of irradiation field, respectively. The second case had the tumour origin at the hypothalamus, which indicates intraparenchymal tumour location as another factor to worsen the quality of life (QOL). Visual field and acuity, and EOM impairment were observed in eight and five patients, respectively. It improved in all patients but one. The visual and EOM dysfunction recovered satisfactorily and was not a disabling factor. The intraparenchymal lesion resulting in hemiparesis and higher cortical dysfunction due to either irradiation-related complications or tumour invasion is a major determining factor of lower KPS. Irradiation related complications are considered to be avoidable by reducing radiation dosage with appropriate chemotherapy and/or proper selection of irradiation field. Patients with smaller tumour size of less than 20 mm had higher KPS. Accordingly, repeated studies of tumour markers and neuroimages are required in patients with idiopathic diabetes insipidis, in order to detect the tumour, if present, at the small-sized and early stage.

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.