Shiro Miyata

Survival benefit from boron neutron capture therapy for the newly diagnosed glioblastoma patients.

OBJECTIVE Since 2002-2007, we applied boron neutron capture therapy (BNCT) to >50 cases of malignant gliomas (MGs) with epithermal neutron irradiations. Recently, we showed the early radiographical improvement of malignant glioma patients by our modified BNCT, with simultaneous use of BPA (borono-phenylalanine) and BSH (sodium borocaptate). In this time, we focused on the survival benefit from BNCT for the newly diagnosed glioblastoma patients. METHODS BNCT group including 21 newly histological confirmed glioblastoma patients treated with surgical removal followed by BNCT in Osaka Medical College during 2002-2006 period. Ten patients were treated with BNCT only, and in the other 11 patients, 20-30 Gy fractionated external beam X-ray irradiation therapy (XRT) was performed after BNCT. No chemotherapy was administered until tumor progression was observed. RESULTS Treatments were well tolerated. Any kind of acute systemic or local severe toxicity were not demonstrated. Mean over all survival of the patients treated by BNCT was 20.7 and the median was 15.6 months with 2-years survival of 25%. Stratification by RPA criteria showed 6, 6, 8 and 1 patients, respectively, in classes III-VI. Three patients out of six in class III and one out of eight in class V are alive at the end point of this study. All the patients in classes IV and VI died. Median survival time for the BNCT group compared to the RTOG database was as follows: 20.6 months vs. 17.9 months for class III; 16.9 months vs. 11.1 months for class IV; 13.2 months vs. 8.9 months for class V. CONCLUSION The RTOG RPA prognostic criteria were helpful in establishing which class of glioma patients could potentially benefit from BNCT. BNCT showed a survival benefit in all of the RPA classes of the RTOG database not only for the good prognosis group.

Phase II clinical study of boron neutron capture therapy combined with X-ray radiotherapy/temozolomide in patients with newly diagnosed glioblastoma multiforme--study design and current status report.

Recently, we reported our clinical experiences of boron neutron capture therapy (BNCT) for the newly diagnosed glioblastoma. The major differences of our protocol from the other past studies were simultaneous use of both sodium borocapate and boronophenylalanine, and combination with fractionated X-ray irradiation. These results showed the efficacy of combination therapy with external beam X-ray irradiation and BNCT. For our future study, we planned the multi-centric phase II clinical study for newly diagnosed glioblastoma patients in Japan (OSAKA-TRIBRAIN0902, NCT00974987).

Computed Tomography Imaging of Transferrin Targeting Liposomes Encapsulating Both Boron and Iodine Contrast Agents by Convection-Enhanced Delivery to F98 Rat Glioma for Boron Neutron Capture Therapy

BACKGROUND:To achieve potent tumor-selective antitumor efficacy by boron neutron capture therapy (BNCT), it is important to have a significant differential uptake of 10B between tumor cells and normal cells. This should enable BNCT to reduce damage to normal tissues compared with other radiation therapies. OBJECTIVE:To augment the therapeutic efficacy of BNCT, we used transferrin-conjugated polyethylene glycol (PEG) (TF-PEG) liposome encapsulating sodium borocaptate and Iomeprol, an iodine contrast agent, with intratumoral convection-enhanced delivery (CED) in a rat glioma tumor model. METHODS:The in vitro 10B concentration of F98 rat glioma cells was determined by inductively coupled plasma atomic emission spectrometry after incubation with either TF-PEG or PEG liposomes. For in vivo biodistribution studies, 10B concentrations within blood, normal brain tissue, and intracerebrally transplanted F98 cells were measured with inductively coupled plasma-atomic emission spectrometry after CED of the compounds, and computed tomography was performed at selected time intervals. RESULTS:10B concentrations of F98 cultured glioma cells in vitro 6 hours after exposure to PEG and TF-PEG liposome were 16.1 and 51.9 ng10B/106 cells, respectively. 10B concentrations in F98 glioma tissue 24 hours after CED were 22.5 and 82.2 μg/g, by PEG and TF-PEG liposome, respectively, with lower 10B concentrations in blood and normal brain. Iomeprol provided vivid and stable enhanced computed tomography imaging of the transplanted tumor even 72 hours after CED by TF-PEG liposome. Conversely, tissue enhancement had already washed out at 24 hours after CED of the PEG liposomes. CONCLUSION:The combination of TF-PEG liposome encapsulating sodium borocaptate and Iomeprol and intratumoral CED enables not only a precise and potent targeting of boron delivery to the tumor tissue, but also the ability to follow the trace of boron delivery administered intratumorally by real-time computed tomography.

The use of intraoperative near-infrared indocyanine green videoangiography in the microscopic resection of hemangioblastomas

BackgroundThe authors assessed the usefulness of intraoperative near-infrared indocyanine green videoangiography (ICG-VA) in the microscopic resection of hemangioblastomas.MethodsFrom January 2009 to February 2012, nine consecutive patients (seven men, two women) who underwent surgery for hemangioblastomas using intraoperative ICG-VA were included in this study. Surgery was performed on four cystic cerebellar lesions with mural nodules, two solid tumors (one in the cerebellar hemisphere and one in the medulla oblongata), one spinal tumor and multiple tumors in two patients with von Hippel-Lindau disease. Of the nine patients, three were treated for recurrent tumor. The ICG-induced fluorescence images of hemangioblastomas with variable presentation were evaluated.ResultsAll tumors could be completely removed en bloc. Blood flow in the tumor and tumor-related vessels at the brain surface were clearly detected by ICG-VA in all cases, except one recurrent tumor where postoperative adhesive scar tissue obstructed ICG-induced fluorescence resulting in poor delineation of the blood flow patterns and tumor margins. ICG-VA was also helpful for detecting the multiple small mural nodules within the cyst or the tumors buried under thin gliotic neural tissue despite reduced fluorescence.ConclusionIntraoperative ICG-VA is a safe and easy modality for confirming the vascular flow patterns in hemangioblastomas. In addition, ICG-VA provided useful information for intracystic small lesions or lesions concealed under thin brain tissue in order to accomplish total resection of these tumors.

Surgical Treatment of 127 Paraclinoid Aneurysms with Multifarious Strategy: Factors Related with Outcome.

BACKGROUND Few reports have been published discussing surgical outcomes of paraclinoid aneurysms using multifarious treatments such as high-flow bypass. MATERIAL AND METHODS We retrospectively analyzed findings from 127 consecutive patients (19 males, mean age at surgery: 56.8 years, range: 19-81 years) at our hospital. The size of aneurysms ranged from 2.7-43.2 mm (mean: 6.9 mm). Extradural anterior clinoidectomy was used to clip small aneurysms. As large or giant aneurysms required a longer temporal occlusion period and often could not undergo simple clipping, high-flow bypass with anterior clinoidectomy or cervical internal carotid ligation was performed to reduce aneurysm blood flow and induce thrombosis. We reviewed a postoperative modified Rankin Scale (mRS), radiographic outcomes, cerebral infarction, and visual disturbance. In addition, we analyzed factors relating to the outcomes and complications, with focus on the aneurysm size, location, and type of surgical treatment. RESULTS Good outcomes were achieved in all patients, as follows: mRS 0:100, mRS 1:16, mRS 2:11, and mRS 3-6:0. Among the 127 patients, complete exclusion of aneurysm was achieved in 119 cases (93.7%). Postoperative morbidity included ischemic lesions in 11 (8.6%) and visual disturbance in 24 (18.8%). Significant statistical differences were observed between ischemic complication and aneurysm size and location (P = 0.0001) and surgical treatment (P < 0.0001). CONCLUSION Surgical treatment of unruptured paraclinoid aneurysm has high efficacy with good outcomes and a high rate of complete exclusion. However, the rate of visual disturbance is relatively high. Careful surgical techniques and intraoperative monitoring are therefore required.

Risk factors for neurological worsening and symptomatic watershed infarction in internal carotid artery aneurysm treated by extracranial-intracranial bypass using radial artery graft.

OBJECT The revascularization technique, including bypass created using the external carotid artery (ECA), radial artery (RA), and M2 portion of middle cerebral artery (MCA), has remained indispensable for treatment of complex aneurysms. To date, it remains unknown whether diameters of the RA, superficial temporal artery (STA), and C2 portion of the internal carotid artery (ICA) and intraoperative MCA blood pressure have influences on the outcome and the symptomatic watershed infarction (WI). The aim of the present study was to evaluate the factors for the symptomatic WI and neurological worsening in patients treated by ECA-RA-M2 bypass for complex ICA aneurysm with therapeutic ICA occlusion. METHODS The authors measured the sizes of vessels (RA, C2, M2, and STA) and intraoperative MCA blood pressure (initial, after ICA occlusion, and after releasing the RA graft bypass) in 37 patients. Symptomatic WI was defined as presence of the following: postoperative new neurological deficits, WI on postoperative diffusion-weighted imaging, and ipsilateral cerebral blood flow reduction on SPECT. Neurological worsening was defined as the increase in 1 or more modified Rankin Scale scores. First, the authors performed receiver operating characteristic curve analysis for continuous variables and the binary end point of the symptomatic WI. The clinical, radiological, and physiological characteristics of patients with and without the symptomatic WI were compared using the log-rank test. Then, the authors compared the variables between patients with and without neurological worsening at discharge and at the 12-month follow-up examination or last hospital visit. RESULTS Symptomatic WI was observed in 2 (5.4%) patients. The mean MCA pressure after releasing the RA graft (< 55 mm Hg; p = 0.017), mean (MCA pressure after releasing the RA graft)/(initial MCA pressure) (< 0.70 mm Hg; p = 0.032), and mean cross-sectional area ratio ([RA/C2 diameter](2) < 0.40 mm [p < 0.0001] and [STA/C2 diameter](2) < 0.044 mm [p < 0.0001]) were related to the symptomatic WI. All preoperatively independent patients remained independent (modified Rankin Scale score < 3). After adjusting for age and sex, left operative side (p = 0.0090 and 0.038) and perforating artery ischemia (p = 0.0050 and 0.022) were related to neurological worsening at discharge (11 [29%] patients) and at the 12-month follow-up or last hospital visit (8 [22%] patients). CONCLUSIONS Results of the present study showed that the vessel diameter and intraoperative MCA pressure had impacts on the symptomatic WI and that operative side and perforating artery ischemia were related to neurological worsening in patients with complex ICA aneurysms treated by ECA-RA-M2 bypass.

Reconstruction of intracranial vertebral artery with radial artery and occipital artery grafts for fusiform intracranial vertebral aneurysm not amenable to endovascular treatment: technical note

BackgroundSymptomatic fusiform intracranial vertebral artery aneurysms pose a formidable treatment challenge when not amenable to endovascular treatment. In this paper, we illustrate the microsurgical management of such an aneurysm.MethodsTo prevent neurological deterioration, anatomical reconstruction preserving all vessels including posterior inferior cerebellar artery and perforators is essential. In this case illustration, the occipital artery was used as a donor to a perforator originating from the aneurysmal segment. This bypass was performed in an end-to-side fashion. Subsequently, the aneurysmal component of the vertebral artery was resected and an end-to-side (V4 to V3) bypass was performed using a radial artery graft.ResultsThe patient achieved complete resection of the aneurysm preserving normal anatomy of the posterior circulation without any ischemic complications.ConclusionsComplex cerebral artery bypass techniques are essential in the armamentarium of cerebrovascular for the treatment of complex lesions not amenable to endovascular therapy.

Retrograde Suction Decompression for Clip Occlusion of Internal Carotid Artery Communicating Segment Aneurysms

BACKGROUND Retrograde suction decompression (RSD) can achieve proximal parent vessel control, improve aneurysm neck visualization, and allow parent vessel reconstruction for direct clipping of internal carotid artery (ICA) aneurysms. The aim of the present study was to describe the technique and surgical results of RSD for direct clipping of ICA communicating segment (C1) aneurysms. METHODS The clinical data and treatment summaries of 20 patients who underwent RSD-assisted clipping of ICA C1 aneurysms were retrospectively reviewed. Pre- and postoperative three- or four-dimensional computed tomography angiograms, postoperative magnetic resonance images, surgical notes, operative complications, and outcomes were assessed. RESULTS All patients except one harbored unruptured C1 aneurysms. Extracranial-intracranial graft bypass using the radial artery was performed in five patients. Fifteen patients required temporary clipping of the posterior communicating artery for further reduction of blood back-flow into the aneurysm. All aneurysms were successfully clipped and postoperative three- or four-dimensional computed tomography angiography revealed no major branch occlusion or residual aneurysm. At the 6-month follow-up examination, 19 patients had a good outcome and 1 patient had poor outcome associated with anterior choroidal artery ischemia. No death had occurred at 6-month follow-up examination. CONCLUSIONS The RSD technique is a useful procedure to achieve proximal vascular control, to soften and shrinkage the aneurysm sac, and to provide a wide and clean operative field allowing safe clip placement. The RSD technique requires special attention to the relationship between the perforators and the aneurysm, and close cooperation between the surgeon and the assistant.

Surgical Microanatomy of the Posterior Condylar Emissary Vein and its Anatomical Variations for the Transcondylar Fossa Approach

BACKGROUND It is essential to identify and be aware of the anatomy of the posterior condylar emissary vein (PCEV) for achieving an adequate operative field for the transcondylar fossa approach (TCFA). OBJECTIVE To describe the variations in the drainage patterns of PCEVs and the technical issues encountered in such cases. METHODS This was a retrospective analysis of the anatomy of PCEVs in 104 sides in 52 cases treated by the TCFA. Preoperative findings of multidetector-row computed tomography (CT) and CT venography (CTV) were compared with the intraoperative findings. The drainage patterns were classified as 5 types: the sigmoid sinus (SS), jugular bulb (JB), occipital sinus (OS), anterior condylar emissary vein (ACEV), and marginal sinus (MS). RESULTS The SS, JB, ACEV, and OS types were observed in 33 (31.7%), 42 (40.3%), 8 (7.7%), and 1 (1.0%) side(s), respectively. One side (1.0%) each had combined drainage from MS and JB, and ACEV and JB, respectively. In 17 sides (16.3%), the PCEVs and posterior condylar canals could not be identified on CT and CTV. CONCLUSIONS Preoperative CT and CTV findings correlated well with the intraoperative findings. To make a sufficient operative field for TCFA, PCEVs should be appropriately dealt with based on the preoperative knowledge of their running course, pattern, and origin.

Open Surgery for Recurrent Intracranial Aneurysms: Techniques and Long-Term Outcomes

BACKGROUND After occlusion of an aneurysm, a patient may experience aneurysm regrowth at the same site or develop de novo aneurysms. We present our experience in microsurgery of recurrent aneurysms with analysis of long-term results. METHODS The senior authors (R. T. and H. K.) performed recurrent aneurysm clipping on 44 patients at Teishinkai Hospital and Asahikawa Red Cross Hospital in Sapporo, Japan. Operative techniques included clipping only, clipping and protective bypass, trapping of aneurysm with bypass, proximal occlusion, and bypass. Postoperative outcome was analyzed retrospectively using the modified Rankin Scale. RESULTS Our series included 10 men (23%) and 34 women (77%), with a mean patient age of 63 years (range, 7-82 years). Before primary treatment, 11 patients (25%) had a ruptured aneurysm, while 33 patients (75%) had an unruptured aneurysm. The mean follow-up time after primary surgery was 7.6 years (range, 0.8-25 years). At our department the treatment of recurrent aneurysm included the clipping in 19 patients (43%), clipping with bypass in 6 patients (14%), aneurysm trapping with bypass in 10 patients (23%), and proximal occlusion and bypass in 9 patients (20%). The mean follow-up time after surgical treatment of recurrent aneurysms stood at 3.5 years (range 0.1-9 years). Altogether, 37 patients (84%) experienced favorable outcomes at last follow-up examination (modified Rankin Scale scores 0 and 1). CONCLUSIONS Microsurgery of recurrent aneurysms may be performed safely and effectively, as shown by our study, in which 84% of patients experienced favorable results.