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Kintomo Takakura

Publications and source records attributed to Kintomo Takakura.

17 recordsLinked to original sources

Does the prevalence of gsp mutations in GH-secreting pituitary adenomas differ geographically or racially? Prevalence of gsp mutations in Japanese patients revisited.

OBJECTIVE: The prevalence of gsp mutations in GH-secreting pituitary adenomas was thought to differ geographically or racially, given its exceptionally lower incidence among Japanese patients (4.4-9.3%) compared to other regions (30-50%). However, this notion is now being challenged after a recent paper reported a 53.3% incidence among Japanese with acromegaly. We have since re-evaluated the prevalence of gsp mutations on a larger scale. PATIENTS: One hundred Japanese acromegaly patients with surgically confirmed GH-secreting pituitary adenomas were enrolled. METHODS: mRNAs from primary cultured adenomas were used for reverse transcriptase-polymerase chain reaction and direct sequencing of the Gsalpha subunit. Patient data were reviewed from medical charts. RESULTS: There were 53 gsp mutations (53%), consisting of 42 Arg201Cys, one Arg201His, one Arg201Ser, 8 Gln227Leu, and one Gln227Arg mutation. Age at operation, sex ratio, basal serum GH and IGF-I levels were no different with or without the mutations. In contrast, patients responded differently to most dynamic tests with statistical significance: serum GH levels in gsp-positive patients had blunted response to GHRH, were well suppressed by bromocriptine, and had higher rates of paradoxical response to TRH. Notably, paradoxical response to LHRH was observed exclusively in gsp-negative patients. Octreotide suppressed GH levels strongly regardless of gsp status. These clinical characteristics are similar to those of Caucasian patients. CONCLUSION: We conclude that the prevalence of gsp mutations in Japanese acromegaly patients is comparable to those of other reports from various regions. Therefore, Japanese patients do not stand as an example for geographical or racial difference in the prevalence of gsp mutations in GH-secreting pituitary adenomas.

Acromegaly↗

Intelligent operating theater using intraoperative open-MRI.

Malignant brain tumors vary among patients and are characterized by their irregular shapes and infiltration. Localization of functional areas in the brain also differs among patients, and excess removal of tumor near eloquent areas may increase the risk of damage of function, such as motor paresis and speech disturbance. Recent progress in magnetic resonance (MR) imaging technology has enabled acquisition of intraoperative images and totally changed the neurosurgery of malignant brain tumors. Before, surgeons could merely speculate about the results of surgical manipulation and have no certainty about procedure outcomes until postoperative examination. Because intraoperative MR images allow visualization of the size of residual tumor(s) and the positional relationship between the tumor(s) and eloquent areas, surgeons are now able to achieve safe and reliable surgery. As an example, positional error on preoperative MR images caused by shifting of the brain (brain shift), a long-standing annoyance for surgeons, has been resolved using intraoperative MR images for surgical navigation, allowing precise resection. Two types of open-MR imaging scanner, a 0.2- or 0.3-tesla hamburger-type scanner with a horizontal gap and a 0.12- or 0.5-tesla double doughnut-type scanner with a vertical gap, are now available in the operating theater, and 1.5-tesla bore-type scanners are available. A 3.0-tesla bore-type scanner is planned. Intraoperative MR imaging includes diffusion-tensor and diffusion-weighted imaging, which allows visualization of nerve fibers in the white matter, especially the pyramidal tract. Such images are valuable aids in the precise resection of residual lesions of malignant brain tumors near eloquent areas without injuring motor function.

Brain Neoplasms↗

Long-term complications after gamma knife surgery for arteriovenous malformations.

OBJECT: The authors analyzed of the long-term complications that occur 2 or more years after gamma knife surgery (GKS) for intracranial arteriovenous malformations (AVMs). METHODS: Patients with previously untreated intracranial AVMs that were managed by GKS and followed for at least 2 years after treatment were selected for analysis (237 cases). Complete AVM obliteration was attained in 130 cases (54.9%), and incomplete obliteration in 107 cases (45.1%). Long-term complications were observed in 22 patients (9.3%). These complications included hemorrhage (eight cases), delayed cyst formation (eight cases), increase of seizure frequency (four cases), and middle cerebral artery stenosis and increased white matter signal intensity on T2-weighted magnetic resonance imaging (one case of each). The long-term complications were associated with larger nidus volume (p < 0.001) and a lobar location of the AVM (p < 0.01). Delayed hemorrhage was associated only with incomplete obliteration of the nidus (p < 0.05). Partial obliteration conveyed no benefit. Delayed cyst formation was associated with a higher maximal GKS dose (p < 0.001), larger nidus volume (p < 0.001), complete nidus obliteration (p < 0.01), and a lobar location of the AVM (p < 0.05). CONCLUSIONS: Incomplete obliteration of the nidus is the most important factor associated with delayed hemorrhagic complications. Partial obliteration does not seem to reduce the risk of hemorrhage. Complete obliteration can be complicated by delayed cyst formation, especially if high maximal treatment doses have been administered.

Adolescent↗

Gamma knife surgery of the pituitary: new treatment for thalamic pain syndrome.

OBJECT: Although reports in the literature indicate that thalamic pain syndrome can be controlled with chemical hypophysectomy, this procedure is associated with transient diabetes insipidus. It was considered reasonable to attempt gamma knife surgery (GKS) to the pituitary gland to control thalamic pain. METHODS: Inclusion criteria in this study were poststroke thalamic pain, failure of all other treatments, intolerance to general anesthetic, and the main complaint of pain and not numbness. Seventeen patients met these criteria and were treated with GKS to the pituitary. The target was the pituitary gland together with the border between the pituitary stalk and the gland. The maximum dose was 140 to 180 Gy. All patients were followed for more than 3 months. CONCLUSIONS: An initial significant pain reduction was observed in 13 (76.5%) of 17 patients. Some patients experienced pain reduction within 48 hours of treatment. Persistent pain relief for more than 1 year was observed in five (38.5%) of 13 patients. Rapid recurrence of pain in fewer than 3 months was observed in four (30.8%) of 13 patients. The only complication was transient diabetes insipidus in one patient. It would seem that GKS of the pituitary might have a role to play in thalamic pain arising after a stroke.

Aged↗

Gamma knife surgery for choroidal neovascularization in age-related macular degeneration. Technical note.

The authors conducted a study to determine a way of overcoming the poor-quality demonstration of choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) on conventional magnetic resonance (MR) imaging studies. The poor MR imaging demonstration of CNV in patients with AMD makes the use of gamma knife surgery more difficult. This difficulty, however, can be overcome by use of a modified time-of-flight MR imaging,sequence with Gd enhancement and coronal reconstruction.

Age Factors↗

Proton MRS of the peritumoral brain.

Long-echo (TR: 2000 ms, TE: 136 ms) proton MRS of the cerebral tissue in the vicinity to intracranial lesion was done in 15 patients, mainly with parenchymal brain tumors. Significant decrease of N-acetylaspartate (NAA) (P<0.001) and more frequent presence of lactate (P<0.01) comparing with distant normal white matter were found in the perilesional brain tissue. The level of NAA in the perilesional brain tissue had negative associations with presence of lactate in the lesion (P<0.05), excess of lactate in the lesion compared to perilesional brain (P<0.01), grade of the perilesional edema (P<0.01) and patient's age (P<0.05). Multivariate analysis disclosed that identification of lactate in the lesion is associated with lower relative NAA content in the perilesional brain tissue, independently on the presence or absence of any other factor, including brain edema (P<0.001). In patients with lobar lesions who had at least one epileptic seizure during course of their disease the relative NAA content in the perilesional brain was significantly lower, comparing with those who were seizure-free (P<0.05). Therefore, lactate diffused from the tumor, or other metabolites secreted by lactate-producing neoplasm, should be considered as important contributors to the neuronal dysfunction in the surrounding brain. Decrease of NAA in the vicinity to intracranial lesions may reflect neuronal alteration responsible for associated epilepsy.

Adult↗

Analysis of nidus obliteration rates after gamma knife surgery for arteriovenous malformations based on long-term follow-up data: the University of Tokyo experience.

OBJECT: A large number of clinical studies have been made on treatment outcomes of radiosurgery for arteriovenous malformations (AVMs), but the reported obliteration rates following this treatment vary significantly, perhaps reflecting the different methods and timings of the imaging studies used. METHODS: The authors retrospectively analyzed their experience with gamma knife surgery in 400 patients with AVMs (follow-up period 1-135 months, median 65 months), with special reference to the imaging modality used in each case. The calculated obliteration rates varied from 68.2 to 92%, depending on imaging modality and timing of evaluation. When only unquestionable imaging data such as demonstrations of a residual nidus on computerized tomography (CT) or magnetic resonance (MR) images or findings on angiograms were used in the calculation, the obliteration rates were 72% at 3 years and 87.3% at 5 years. Factors leading to a better obliteration rate were previous hemorrhage (p = 0.0084), smaller nidus (p = 0.0023), and higher radiation dose to the lesion's margin (p = 0.0495), as determined in a multivariate analysis. Factors leading to an earlier obliteration of the nidus were male sex (p = 0.0001), previous hemorrhage (p = 0.0039), smaller nidus diameter (p = 0.0006), and dose planning using angiography alone (p = 0.0201). CONCLUSIONS: After the introduction of CT and MR images into dose planning, the conformity and selectivity of dosimetry improved remarkably, although the latency intervals until obliteration were prolonged. Imaging outcomes for AVMs should be evaluated using data provided by longer follow-up periods. The timing of additional treatments for residual AVMs should be decided cautiously, considering the size of the AVM, the patient age and sex, and the history of hemorrhage before radiosurgery.

Adolescent↗

[Intraoperative MRI and updated navigation].

Although advanced preoperative imaging has been developed recent years, intraoperative imaging and monitoring are limited. We have developed an operating system to obtain objective and visible information for advanced neurosurgery. Intraoperative MRI and updated navigation are powerful tools to navigate surgeons to the residual lesions. This system has contributed to the improvement of the resection rate and the safety in the cases of gliomas and pituitary tumors.

Adult↗

[Robotic surgery in neurosurgical field].

Computer-aided surgery commenced in the late 1980s when computer was clinically used for diagnosis and surgical planning. Since then the computer has been used in a surgical navigation system. In the early 1990s a robotic surgery using intelligent manipulator as surgeon's new hands took place. Nowadays intraoperative diagnostic imaging as surgeon's new eyes has become ubiquitous Diagnosis, surgical planning, and navigation are required to be real-timely performed intraoperatively. The time has really come to concurrently diagnose and treat, in which technology visualizing intraoperative medical information and minimally invasive surgery are fused. For that it is necessary to develop a system that real-timely updates information for decision making, and at the same time to present the timely, optimum treatment to be done according to the results of instant evaluation of ongoing treatment. To realize and support above system it is essential to combine a sensor which can precisely distinguishes a focal area from a normal tissue intraoperatively, and a manipulator which participates the treatment. In addition, the manipulator should be accurately controlled using a computer (computer-aided manipulation) according to the surgical plan made by a method aided by a computer (computer-aided design) based on intraoperatively acquired information. It is about to change quality of life to quality of treatment.

Humans↗

Role of pituitary radiosurgery for the management of intractable pain and potential future applications.

RATIONALE: Two or three decades ago, cancer pain was treated by surgical/chemical hypophysectomy. In one report, the control of central pain (thalamic pain syndrome) was also approached with chemical hypophysectomy. Although in most of the patients these treatments resulted in a decrease in severe pain, concomitantly severe adverse effects (panhypopituitarism, diabetes insipidus and visual dysfunction) occurred in most patients. This historical evidence prompted us to perform Gamma Knife surgery (GKS) for this kind of intractable severe pain using a high irradiation dose to the pituitary stalk/gland. In the majority of patients, marked pain relief was achieved, surprisingly without any of the complications mentioned above. MATERIALS AND METHODS: A prospective multicenter study was conducted to evaluate the efficacy and safety in patients treated in Prague, Hong Kong and Tokyo. Indications of this treatment were: (1) failure of other effective treatment approaches prior to GKS, (2) good general patient condition (Karnofsky performance status >40%), (3) response to morphine for pain control (cancer pain), and (4) no previous radiotherapy of brain metastases (GKS/conventional radiotherapy). Eight patients with severe cancer pain due to bone metastasis and 12 patients with post-stroke thalamic pain syndrome were treated with GKS. The target was the border between the pituitary stalk and gland. Maximum dose was 160 Gy for cancer pain and 140 Gy for central pain. Follow-up included 6 patients (>1 month) with cancer pain and 8 patients (> 6 months) with thalamic pain syndrome. RESULTS: All patients (6/6) with cancer pain experienced significant pain reduction, and 87.5% (7/8) of the patients with thalamic pain had initially significant pain reduction. In some patients, pain reduction was delayed for several hours. Pain relief was noted within 7 days (median 2 days). No recurrence was observed in the patients with cancer pain. However, in 71.4% (5/7) of the patients with thalamic pain syndrome, disease recurred during the 6-month follow-up. Up to now, other complications have not been observed. CONCLUSION: Our clinical study protocol is only preliminary. Further clinical results on the management of thalamic pain are required to develop this treatment protocol. However, efficacy and safety have been shown in all our cases. In our opinion, this treatment has a potential to control severe pain, and GKS will play an important role in the management of intractable pain.

Bone Neoplasms↗

Research progress in the last quarter of the 20th century at the University of Tokyo and Tokyo Women's Medical University.

Professor Keiji Sano described the history of neurosurgery in Japan until 1975. After World War II, not only neurosurgery but all fields of medicine were devastated in Japan. Professor Sano contributed greatly to the reform and modernization of neurosurgery during that very difficult era in Japan. He performed much research by himself and also as a leader of research groups on stereotactic and functional neurosurgery, cerebrovascular diseases, head injuries, and brain tumors. He organized the Fifth International Congress of Neurological Surgery in Tokyo in 1973. I succeeded in the chairmanship of the Department of Neurosurgery of the University of Tokyo in 1981. We have performed research on the treatment of brain tumors and cerebrovascular diseases. To obtain the best results for brain tumor treatment, we have introduced several new radiotherapeutic methods, such as the gamma knife, heavy-particle irradiation, and the photon radiosurgery system. To improve surgical treatment, we have energetically engaged in medical engineering research on computer-assisted surgical systems (intraoperative monitoring and navigation systems). We have also performed much research on chemotherapy and immunotherapy. In the field of cerebrovascular diseases, the main research projects have been focused on the mechanism and treatment of vasospasm and brain edema after subarachnoid hemorrhage. I summarize the results of our research performed in the Department of Neurosurgery of the University of Tokyo until 1992 and at Tokyo Women's Medical University after 1992, in the last quarter of the 20th century.

Biomedical Research↗

Effects of moderate hyperthermia on the rabbit sarcoma model.

A method of induction of moderate hyperthermia with a plate heater and a direct current energy source was investigated in the VX-2 rabbit sarcoma model. The theoretical distribution of temperature in the rabbit brain was calculated under various heating conditions. The calculated temperatures coincided well with the temperatures of moderate hyperthermia measured by a thermocouple to a depth of 7 mm under the heater. Moderate hyperthermia was induced in the VX-2 sarcoma. Hyperthermia at 40 degrees C for 20 minutes caused no changes in the lesion. Hyperthermia at 45 degrees C for 20 minutes destroyed the lesion partially to a maximum depth of 3 mm. Hyperthermia at 50 degrees C for 20 minutes caused greater destruction, but also caused edema in the lesion and the surrounding normal brain. Hyperthermia at 55 degrees C for 20 minutes caused severe damage in both the lesion and the surrounding normal brain. Comparison of the actual destruction by hyperthermia and the theoretical temperature distribution indicated that hyperthermia at 43 degrees C for 20 minutes was effective against brain tumor, and destruction reached at least 3 mm from the heater.

Animals↗

NeuRobot: telecontrolled micromanipulator system for minimally invasive microneurosurgery-preliminary results.

OBJECTIVE: Microneurosurgery can be performed less invasively with the recent advances in neuronavigation and neuroendoscopy. For even less invasive microneurosurgery, we have developed a telecontrolled micromanipulator system. METHODS: The NeuRobot telecontrolled micromanipulator system was developed. With the use of this system, surgical simulations were performed with a human cadaveric head. RESULTS: The system consists of four main parts, i.e., a micromanipulator (slave manipulator), a manipulator-supporting device, an operation-input device (master manipulator), and a three-dimensional display monitor. Three 1-mm forceps and a three-dimensional endoscope, which could be remotely controlled with three degrees of freedom (rotation, neck swinging, and forward/backward motion), were installed in the slave manipulator. All surgical procedures were accurately performed with this system. CONCLUSION: The use of telecontrolled manipulator systems in neurosurgery is very promising, and we are convinced that this system will facilitate more accurate, less invasive microneurosurgery. The details of the NeuRobot system and preliminary results are presented.

Cadaver↗

[Monoclonal immunotherapy with human monoclonal antibody(CLN-IgG) in glioma patients].

It is well recognized that malignant gliomas escape an immune response by hiding behind the blood-brain barrier and by producing proteins that suppress systemic immunity. However, if gliomas can be made to be more immunogenic or if a tumor vaccine can be produced, then access to all tumor cells including those that infiltrate into the brain can be achieved through the patient's immune response. Several strategies have been investigated for immunotherapy. Laboratory studies and animal models have shown that these immune cells will attack the tumor cell, reduce the size of implanted tumors, and that the immune memory is sufficient to suppress tumor growth when the animal is rechallenges with a tumor implant. Since the development of hybridoma technology, monoclonal antibodies against human cancer cells have been produced and antigens have been identified. Hagiwara reported the production of a human monoclonal antibody, CLN-IgG, made by fusing UC 729-6, human lymphoblastoid B-cell line, with lymphocytes obtained from a patient with the cervical carcinoma. It has been reported that CLN-IgG recognized the antigen expressed in various histological types of human cancers including malignant gliomas. The effect of human monoclonal antibody(CLN-IgG) on malignant brain tumors was evaluated in patients with malignant glioma. Early phase II study was concluded that this specific immunotherapy with CLN-IgG is safe and effective therapy in patients with malignant glioma. We treated 10 cases of malignant gliomas with CLN-IgG. All patients had received radiotherapy and chemotherapy before this immunotherapy using the human monoclonal antibody. The human monoclonal antibody(CLN-IgG) was administered intravenously once or twice/week during 24 weeks. Six cases of glioblastoma, 1 medulloblastoma and 3 cases of potine glioma histologically unverified, were treated. Five cases of 6 glioblastomas died 4 to 12 months after this treatment, 3 cases of pontine glioma showed good responses, 2 cases showed marked decrease of tumor size and 1 case showed no regrowth of tumor on MRI imaging. For the above reasons, Human monoclonal antibody(CLN-IgG) might be useful as an immunotherapy of malignant gliomas.

Animals↗