Atsushi Tsugu

Impact of the Combination of 5-Aminolevulinic Acid-Induced Fluorescence with Intraoperative Magnetic Resonance Imaging-Guided Surgery for Glioma

OBJECTIVE To compare intraoperative magnetic resonance imaging (MRI)-guided resection with resection guided by 5-aminolevulinic acid (5-ALA)-induced fluorescence in patients with gliomas and to evaluate the impact of intraoperative MRI in glioma surgery. METHODS From January 2005 to February 2009, 33 patients with gliomas (6 with World Health Organization [WHO] grade II, 7 with WHO grade III, 20 with WHO grade IV) who underwent craniotomy with neuronavigation and received 5-ALA by the same neurosurgeon were investigated retrospectively. In 19 patients, operations were performed using a combination of 5-ALA with intraoperative 1.5-T MRI. All patients were subjected to postoperative 1.5-T MRI to confirm the extent of resection. RESULTS Of 33 patients with gliomas, 21 (4 with WHO grade III and 17 with WHO grade IV) were 5-ALA-induced fluorescence-positive (5-ALA (+)). Surgery with intraoperative MRI was performed in 10 of the 21 patients, and the average resection rate was 92.6%. The average resection rate of patients who underwent surgery without intraoperative MRI was 91.8%. 5-ALA-induced fluorescence was not detected in 12 patients (6 with WHO grade II, 3 with WHO grade III, and 3 with WHO grade IV) with gliomas. Surgery with intraoperative MRI was performed in 9 of 12 patients, and the average resection rate was 89.2%. The average resection rate of patients who underwent surgery without intraoperative MRI was 68.7%. Intraoperative MRI-guided tumor resection resulted in a better resection rate in patients with 5-ALA-induced fluorescence-negative (5-ALA (-)) gliomas than in patients with 5-ALA (+) gliomas (20.5% vs 0.8%). CONCLUSIONS Intraoperative MRI-guided resection is a powerful tool to treat 5-ALA (-) gliomas (mostly low grade), and 5-ALA is useful for high-grade gliomas. The combination of intraoperative MRI and 5-ALA has a synergistic effect in glioma surgery. Additionally, precise tumor grading in preoperative imaging studies can be difficult. Surgery for gliomas should be performed using both 5-ALA-induced fluorescence and intraoperative MRI-guided resection.

Ultrastructural localization of P-glycoprotein on capillary endothelial cells in human gliomas.

The P-glycoprotein (P-Gp) encoded by the human multidrug-resistance gene MDR1 has been suggested to play certain roles in the blood-brain barrier (BBB). However, the detailed mechanism of the activity of P-Gp in multidrug-resistance (MDR) remains unclear in human glioma. We examined the localization of P-Gp in human glioma by immunohistochemical (IHC) and immunoelectron microscopic (IEM) methods with anti P-Gp monoclonal antibodies (C219, MRK16). We also examined MDR1 expression in primary glioma and xenografts by reverse transcription-polymerase chain reaction (RT-PCR) with human MDR1-specific primers. The IHC study showed no P-Gp expression on tumour cells but it was present on capillary endothelial cells and IEM analysis showed definitive localization on their luminal surface. MDR1 gene expression was detected in eight primary glioma and three normal brain specimens by RT-PCR, but not in glioma xenografts. The lack of MDR1 expression in these cells appears to be a consequence of the replacement of the original human stroma, including blood vessels, by murine stroma in glioma xenografts. The unique distribution of P-Gp on the capillary blood vessels was confirmed in human glioma by the results of immunohistochemical and molecular biological studies.

Murine P-glycoprotein on stromal vessels mediates multidrug resistance in intracerebral human glioma xenografts.

Human glioma usually shows intrinsic multidrug resistance because of the blood-brain barrier (BBB), in which membrane-associated P-glycoprotein (P-gp), encoded by the human multidrug resistance gene MDR1, plays a role. We studied drug sensitivity to vincristine (VCR), doxorubicin (DOX) and nimustine (ACNU) in both intracerebrally and subcutaneously xenotransplanted human glioma. We examined the levels of MDR1 and murine mdr3 gene expression in the xenografts by reverse transcriptase polymerase chain reaction and the localization of P-gp by immunohistochemistry. Six of seven subcutaneously transplanted xenografts (scX) were sensitive to the above three drugs. In contrast, all three intracerebrally transplanted human glioma xenografts (icX) were resistant to P-gp-mediated drugs VCR and DOX, but were sensitive to the non-P-gp-mediated drug ACNU. Neither icX nor scX showed any MDR1 expression. Intracerebrally transplanted human glioma xenografts showed an increased level of murine mdr3 gene expression, whereas scX showed only faint expression. The localization of P-gp was limited to the stromal vessels in icX by immunohistochemistry, whereas scX expressed no P-gp. Our findings suggest that the P-gp expressed on the stromal vessels in icX is a major contributing factor to multidrug resistance in human glioma in vivo.

Development of akinetic mutism and hyperphagia after left thalamic and right hypothalamic lesions

A case of childhood post-traumatic akinetic mutism is presented. The patient showed a hyperphagic condition while recovering from akinetic mutism. He had lesions in the left interlaminal nucleus of the thalamus, right globus pallidus, and right dorsomedial nucleus of the hypothalamus. Laboratory data indicated slightly disturbed hypothalamic functions. In general, akinetic mutism can be seen with bilateral destructive lesions, while hyperphagia may occur after destruction of dorsomedial hypothalamic nucleus, but it is very rare. This is the first reported case of akinetic mutism caused by a unilateral lesion.

Brain metastasis from large cell neuroendocrine carcinoma of the urinary bladder

Background In patients with urinary bladder cancer, brain metastases are quite rare and occur in only 1–7% of these patients. Of the urinary bladder cancers, large cell neuroendocrine carcinoma (LCNEC) is extremely rare; only 16 cases have been reported to date. In this report, a case of brain metastasis from LCNEC of the urinary bladder is described. Case Description A 74-year-old man was admitted with confusion and left-sided hemiparesis. Head magnetic resonance imaging demonstrated a ring-enhancing lesion in the right frontal lobe. Whole body computed tomography revealed a suspicious lesion in the urinary bladder. These findings were considered consistent with metastatic brain tumor. Craniotomy and tumor removal were performed. After craniotomy, the patient underwent cystoscopy and the bladder mass was biopsied. Histological and immunohistochemical examination of both the brain tumor and bladder mass revealed LCNEC. According to these findings, the patient was diagnosed with a brain metastasis from LCNEC of the urinary bladder. Conclusion To our knowledge, this is the first report of a patient with a brain metastasis from LCNEC of the urinary bladder.

Improving Patient Safety in the Intra-operative MRI Suite Using an On-Duty Safety Nurse, Safety Manual and Checklist

This paper describes the use of an on-duty safety nurse, a surgical safety manual and a checklist as an essential precursor to evaluating how these approaches affect surgical quality, communication in surgery crews and contribute to the safety of surgical care in the intra-operative magnetic resonance imaging (MRI) suite.

A Multimodal Diagnostic, Interventional, and Surgical Procedure Suite: The MRI/X-Ray/Operation Suite (MRXO)

Magnetic resonance imaging (MRI) provides images with high soft tissue contrast and can offer physiological information (e.g., temperature and blood and cerebrospinal fluid flow measurements) and chemical information (e.g., magnetic resonance spectroscopic imaging). In addition, MRI is a totally radiation-free imaging technique, unlike computed tomography (CT) and angiography. CT remains an excellent modality for diagnosis of bony structures and hemorrhagic lesions and also offers a short imaging time, making CT useful for beating and pulsatile organs. CT is a particularly powerful imaging tool in the field of emergency medicine. Angiography is a sophisticated tool for vascular imaging procedures. Angiography is currently the main imaging modality for endovascular interventions, allowing excellent catheter manipulation. In the field of surgery, many optical tracking and magnetic surgical navigation systems are available. In addition, ultrasonographic systems provide the surgeon with high-quality intraoperative images. Moreover, intraoperative CT and MRI have developed dramatically over the past 20 years. In the operating theater, surgeons must identify not only approaching angles, but also lesion remnants during surgical procedures. Complementary combination of these diagnostic modalities is useful to overcome their individual weaknesses, such as imaging speed, soft tissue resolution, radiation exposure, and multidimensional projection imaging. Simultaneous use of imaging equipment during surgery also promises favorable outcomes for patients.