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Open access

Daisuke Sakai, Jordy Schol, Akihiko Hiyama, Hiroyuki Katoh, Masahiro Tanaka, Masato Sato, and Masahiko Watanabe

OBJECTIVE

The objectives of this study were to apply the simultaneous translation on two rods (ST2R) maneuver involving rods contoured with a convexity at the desired thoracic kyphosis (TK) apex level and to assess the effects on the ability to support triplanar deformity corrections, including TK apex improvement, in patients with hypokyphotic adolescent idiopathic scoliosis (AIS).

METHODS

Using retrospective analysis, the authors examined the digital records that included 2- to 4-week, 1-year, and 2-year postoperative radiographic follow-up data of female hypokyphotic (TK < 20°) AIS patients (Lenke type 1–3) treated with ST2R. The authors assessed the corrections of triplanar deformities by examining the main Cobb angle, TK, rib hump, apical vertebral rotation, Scoliosis Research Society 22-item questionnaire scores, and TK apex translocation. In order to better grasp the potential of ST2R, the outcomes were compared with those of a historical matched case-control cohort treated with a standard rod rotation (RR) maneuver.

RESULTS

Data were analyzed for 25 AIS patients treated with ST2R and 27 patients treated with RR. The ST2R group had significant improvements in the main Cobb angle and TK, reduction in the rib hump size at each time point, and a final correction rate of 72%. ST2R treatment significantly increased the kyphosis apex by an average of 2.2 levels. The correction rate was higher at each time point in the ST2R group than in the RR group. ST2R engendered favorable TK corrections, although the differences were nonsignificant, at 2 years compared with the RR group (p = 0.056). The TK apex location was significantly improved in the ST2R cohort (p < 0.001). At the 1-month follow-up, hypokyphosis was resolved in 92% of the ST2R cohort compared with 30% of the RR cohort.

CONCLUSIONS

Resolving hypokyphotic AIS remains challenging. The ST2R technique supported significant triplanar corrections, including TK apex translocation and restoration of hypokyphosis in most patients. Comparisons with the RR cohort require caution because of differences in the implant profile. However, ST2R significantly improved the coronal and sagittal corrections. It also allowed for distribution of correctional forces over two rod implants instead of one, which should decrease the risk of screw pullout and rod flattening. It is hoped that the description here of commercially available reducers used with the authors’ surgical technique will encourage other clinicians to consider using the ST2R technique.

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Masahiro Indo, Soichi Oya, Michihiro Tanaka, and Toru Matsui

Object

Surgery for aneurysms at the anterior wall of the internal carotid artery (ICA), which are also referred to as ICA anterior wall aneurysms, is often challenging. A treatment strategy needs to be determined according to the pathology of the aneurysm—namely, whether the aneurysm is a saccular aneurysm with firm neck walls that would tolerate clipping or coiling, a dissecting aneurysm, or a blood blister–like aneurysm. However, it is not always possible to properly evaluate the condition of the aneurysm before surgery solely based on angiographic findings.

Methods

The authors focused on the location of the ophthalmic artery (OA) in determining the pathology of ICA anterior wall aneurysms. Between January 2006 and December 2012, diagnostic cerebral angiography, for any reason, was performed on 1643 ICAs in 855 patients at Saitama Medical Center. The authors also investigated the relationship between the origin of the OA and the incidence of ICA anterior wall aneurysms. The pathogenesis was also evaluated for each aneurysm based on findings from both angiography and open surgery to identify any correlation between the location where the OA originated and the conditions of the aneurysm walls.

Results

Among 1643 ICAs, 31 arteries (1.89%) were accompanied by an anomalous origin of the OA, including 26 OAs originating from the C3 portion, 3 originating from the C4 portion, and 2 originating from the anterior cerebral artery. The incidence of an anomalous origin of the OA had no relationship to age, sex, or side. Internal carotid artery anterior wall aneurysms were observed in 16 (0.97%) of 1643 ICAs. Female patients had a significantly higher risk of having ICA anterior wall aneurysms (p = 0.026). The risk of ICA anterior wall aneurysm formation was approximately 50 times higher in patients with an anomalous origin of the OA (25.8% [8 of 31]) than in those with a normal OA (0.5% [8 of 1612], p < 0.0001). Based on angiographic classifications, saccular aneurysms were significantly more common in patients with an anomalous origin of the OA than in those with a normal OA (p = 0.041). Ten of 16 patients with ICA anterior wall aneurysms underwent craniotomies. Based on the intraoperative findings, all 6 aneurysms with normal OAs were dissecting or blood blister–like aneurysms, not saccular aneurysms.

Conclusions

There was a close relationship between the location of the OA origin and the predisposition to ICA anterior wall aneurysms. Developmental failure of the OA and subsequent weakness of the vessel wall might account for this phenomenon, as previously reported regarding other aneurysms related to the anomalous development of parent arteries. The data also appear to indicate that ICA anterior wall aneurysms in patients with an anomalous origin of the OA tend to be saccular aneurysms with normal neck walls. These findings provide critical information in determining therapeutic strategies for ICA anterior wall aneurysms.

Full access

Ryohei Otani, Akitake Mukasa, Masahiro Shin, Mayu Omata, Shunsaku Takayanagi, Shota Tanaka, Keisuke Ueki, and Nobuhito Saito

OBJECTIVE

Chordoma is a slow-growing but clinically malignant tumor, and the prognosis remains poor in many cases. There is a strong impetus to develop more effective targeted molecular therapies. On this basis, the authors investigated the potential of Brachyury, a transcription factor involved in notochord development, as a candidate molecular target for the treatment of chordoma.

METHODS

Brachyury gene copy number and expression levels were evaluated by quantitative polymerase chain reaction in 27 chordoma samples, and the transcriptomes of Brachyury high-expression tumors (n = 4) and Brachyury low-expression tumors (n = 4) were analyzed. A chordoma cell line (U-CH2) was used to investigate the signaling pathways that regulate Brachyury expression.

RESULTS

All chordoma specimens expressed Brachyury, and expression levels varied widely. Patients with higher Brachyury expression had significantly shorter progression-free survival (5 months, n = 11) than those with lower expression (13 months, n = 16) (p = 0.03). Somatic copy number gain was confirmed in 12 of 27 (44%) cases, and copy number was positively correlated with Brachyury expression (R = 0.61, p < 0.001). Expression of PI3K/Akt pathway genes was upregulated in Brachyury high-expression tumors, and suppression of PI3K signaling led to reduced Brachyury expression and inhibition of cell growth in the U-CH2 chordoma cell line.

CONCLUSIONS

Activation of the PI3K/Akt pathway and Brachyury copy number gain are strongly associated with Brachyury overexpression, which appears to be a key event in chordoma growth regulation. These findings suggest that targeting Brachyury and PI3K/Akt signaling may be an effective new approach for treating chordoma.

Restricted access

Kunio Yokoyama, Masahiro Kawanishi, Makoto Yamada, Hidekazu Tanaka, Yutaka Ito, and Toshihiko Kuroiwa

The authors report a rare case of iatrogenic spinal epidural hematoma associated with central venous catheter cannulation via the right internal jugular vein. This 59-year-old man was operated on for stomach cancer while under general anesthesia. A central venous line was inserted via the right internal jugular vein. The operation was completed uneventfully and postoperative fluid replacement was continued without interruption. On postoperative Day 2, marked swelling around the right side of his neck gradually worsened. Cervical CT demonstrated that the catheter tip of the central venous line had penetrated the jugular vein and entered the intervertebral foramen (C5–6), thereby reaching the spinal epidural space. The patient was immediately transported to the operating room and the catheter was carefully extracted under fluoroscopy. Several minutes after catheter removal, the patient complained of sudden severe back pain and over time developed mild paraparesis of both lower extremities. Urgent MR imaging of the spine revealed a large spinal epidural hematoma extending from C-1 to T-8 that was compressing the dorsal spinal cord. The patient underwent emergency surgical removal of the epidural hematoma as well as spinal cord decompression with a T1–4 laminectomy. After surgery, the patient showed full recovery of his lower-extremity motor function.

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Hua Zhong, Zhihong Zhou, Guo-Hua Lv, Jing Li, and Ming-Xiang Zou

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Yuta Fukushima, Soichi Oya, Hirofumi Nakatomi, Junji Shibahara, Shunya Hanakita, Shota Tanaka, Masahiro Shin, Kensuke Kawai, Masashi Fukayama, and Nobuhito Saito

Object

Meningiomas treated by subtotal or partial resection are associated with significantly shorter recurrence-free survival than those treated by gross-total resection. The Simpson grading system classifies incomplete resections into a single category, namely Simpson Grade IV, with wide variations in the volume and location of residual tumors, making it complicated to evaluate the achievement of surgical goals and predict the prognosis of these tumors. Authors of the present study investigated the factors related to necessity of retreatment and tried to identify any surgical nuances achievable with the aid of modern neurosurgical techniques for meningiomas treated using Simpson Grade IV resection.

Methods

This retrospective analysis included patients with WHO Grade I meningiomas treated using Simpson Grade IV resection as the initial therapy at the University of Tokyo Hospital between January 1995 and April 2010. Retreatment was defined as reresection or stereotactic radiosurgery due to postoperative tumor growth.

Results

A total of 38 patients were included in this study. Regrowth of residual tumor was observed in 22 patients with a mean follow-up period of 6.1 years. Retreatment was performed for 20 of these 22 tumors with regrowth. Risk factors related to significantly shorter retreatment-free survival were age younger than 50 years (p = 0.006), postresection tumor volume of 4 cm3 or more (p = 0.016), no dural detachment (p = 0.001), and skull base location (p = 0.016). Multivariate analysis revealed that no dural detachment (hazard ratio [HR] 6.42, 95% CI 1.41–45.0; p = 0.02) and skull base location (HR 11.6, 95% CI 2.18–218; p = 0.002) were independent risk factors for the necessity of early retreatment, whereas postresection tumor volume of 4 cm3 or more was not a statistically significant risk factor.

Conclusions

Compared with Simpson Grade I, II, and III resections, Simpson Grade IV resection includes highly heterogeneous tumors in terms of resection rate and location of the residual mass. Despite the difficulty in analyzing such diverse data, these results draw attention to the favorable effect of dural detachment (instead of maximizing the resection rate) on long-term tumor control. Surgical strategy with an emphasis on detaching the tumor from the affected dura might be another important option in resection of high-risk meningiomas not amenable to gross-total resection.

Free access

Satoshi Suehiro, Takanori Ohnishi, Daisuke Yamashita, Shohei Kohno, Akihiro Inoue, Masahiro Nishikawa, Shiro Ohue, Junya Tanaka, and Takeharu Kunieda

OBJECTIVE

High invasiveness of malignant gliomas frequently causes early local recurrence of the tumor, resulting in extremely poor outcome. To control such recurrence, novel therapies targeted toward infiltrating glioma cells around the tumor border are required. Here, the authors investigated the antitumor activity of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas to explore the possibility for clinical use of 5-ALA–mediated SDT (5-ALA-SDT).

METHODS

In vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells. Treatment-related apoptosis was analyzed using flow cytometry and TUNEL staining. Intracellular reactive oxygen species (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined by analysis of the effect of pretreatment with the radical scavenger edaravone. Effects of 5-ALA-SDT with high-intensity focused ultrasound (HIFU) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated.

RESULTS

The 5-ALA-SDT inhibited cell growth and changed cell morphology, inducing cell shrinkage, vacuolization, and swelling. Flow cytometric analysis and TUNEL staining indicated that 5-ALA-SDT induced apoptotic cell death in all gliomas. The 5-ALA-SDT generated significantly higher ROS than in the control group, and inhibition of ROS generation by edaravone completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. The proliferative activity of the entire tumor was markedly decreased. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact.

CONCLUSIONS

The 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field, whereas the surrounding brain tissue remained normal, resulting in longer survival of the HIFU-treated mice compared with that of untreated mice. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-specific therapy, not only for a tumor mass but also for infiltrating tumor cells in malignant gliomas.

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Takahide Nejo, Shota Tanaka, Masako Ikemura, Masashi Nomura, Shunsaku Takayanagi, Masahiro Shin, Tetsuo Ushiku, Junji Shibahara, Nobuhito Saito, and Akitake Mukasa

Maffucci syndrome (MS) and Ollier disease (OD) are nonhereditary congenital diseases characterized by multiple enchondromas and/or chondrosarcomas. Recent studies have implicated somatic mosaic mutations of isocitrate dehydrogenase 1 or 2 (IDH1/2) as contributing to the pathogenesis of MS and OD. Occasionally, patients with these disorders may also present with central nervous system (CNS) tumors; however, detailed genetic analyses are limited. In this article, the authors report on a male patient with MS, harboring three CNS tumors that share a common genetic alteration. Over a 9-year period, three separate tumor resections were conducted for sellar, intraparenchymal brainstem, and osseous clival tumors. The histopathological diagnoses were pituitary adenoma, diffuse astrocytoma, and chondrosarcoma, respectively. Sanger sequencing revealed a common IDH1 R132C mutation among all three CNS tumors but not in blood DNA. Administering chemotherapy (nimustine) and subsequent radiation therapy to the brainstem glioma and the residual lesion in the clivus have kept the patient progression free for 18 months. This is the first report demonstrating an IDH1 mutation shared among three different CNS tumors in a single patient with MS. The findings support the hypothesis that in MS and OD, a single common IDH1 mutation triggers tumorigenesis in cells of different origins and locations in a somatic mosaic fashion.