Yoshikazu Ogawa

Logic design of Josephson network

New logic circuits are designed which employ as information bits the flux‐quantum vortices occurring in Josephson junctions of extended dimensions. It is shown that Josephson lines can be interconnected in certain direct ways so that complete logic capability can be achieved with networks of Josephson lines alone.

DNA Mismatch Repair Protein (MSH6) Correlated With the Responses of Atypical Pituitary Adenomas and Pituitary Carcinomas to Temozolomide: The National Cooperative Study by the Japan Society for Hypothalamic and Pituitary Tumors

CONTEXT Temozolomide (TMZ) is an alkylating agent and was a first-line chemotherapeutic agent for malignant gliomas. Recently, TMZ has been documented to be effective against atypical pituitary adenomas (APAs) and pituitary carcinomas (PCs). OBJECTIVE The clinical and pathological characteristics of APAs and PCs treated with TMZ in Japan were surveyed and analyzed retrospectively. DESIGN Members of the Japan Society of Hypothalamic and Pituitary Tumors were surveyed regarding the clinical characteristics of APAs and PCs treated with TMZ. Stored tumor samples were gathered from the responders and were assessed by the immunohistochemistry of Ki-67, O(6)-methyl-guanine-DNA methyltransferase, p53, MSH6, and anterior pituitary hormones. Responses to TMZ treatment were defined as complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD) according to RECIST (Response Evaluation Criteria in Solid Tumors) version 2.0. SUBJECTS Three samples from 3 subjects with APA and 11 samples from 10 subjects with PC were available. RESULTS The 13 subjects had APAs and PCs consisting of 5 prolactin-producing tumors, 5 ACTH-producing tumors, and 3 null cell adenomas. The clinical response to TMZ treatment was as follows: 4 cases of CR and PR (31%), 2 cases of SD (15%), 6 cases of recurrence after CR and PR (46%), and 1 case of PD (8%). However, considerable subjects had recurrent disease after a response to TMZ. The immunohistochemical findings of Ki-67, O(6)-methyl-guanine-DNA methyltransferase, and p53 did not show any significant correlation with the efficacy of TMZ. However, the immunopositivity of MSH6 was positively correlated with TMZ response (P = .015, Fishers exact test). CONCLUSIONS This study showed that preserving MSH6 function was contributory to the effectiveness of TMZ in malignant pituitary neoplasms. It is necessary to survey more cases and evaluate multifactor analyses.

Hemorrhagic onset of pilocytic astrocytoma and pilomyxoid astrocytoma

The incidence of hemorrhagic onset in pilocytic astrocytoma and pilomyxoid astrocytoma, and the clinical and histological characteristics, were compared to other types of neuroepithelial tumors or nonhemorrhagic pilocytic astrocytoma by retrospective review of 445 consecutive neuroepithelial tumors treated at our institute. Hemorrhagic onset was observed in 4 of 35 (11.4%) patients with pilocytic astrocytoma and pilomyxoid astrocytoma, with higher incidence than in glioblastoma (3.9%), anaplastic oligodendroglioma (7.7%), and anaplastic ependymoma (7.1%). The hemorrhagic onset occurred in 2 patients with sporadic pilocytic astrocytoma, 1 with pilocytic astrocytoma associated with neurofibromatosis type 1, and 1 with pilomyxoid astrocytoma. There was no correlation between hemorrhagic onset and clinical features, including age, sex, tumor location, proliferative activity, or microvascular proliferation. Hemorrhagic onset of pilocytic astrocytoma and pilomyxoid astrocytoma is not as uncommon as was previously thought, so pilocytic astrocytoma or pilomyxoid astrocytoma should be considered in the differential diagnosis of patients with brain tumors manifesting as hemorrhagic onset.

A partially ossified solid and cystic Rathke cleft cyst

A Rathke cleft cyst is considered to arise from the remnants of the Rathke pouch, and it consists of single cuboidal or columnar epithelium including cilia and goblet cells, which secrete mucus into the cyst. Magnetic resonance imaging characteristically shows a thin membranous cystic wall that enhances with Gd, and homogeneous intensity of the content suggesting fluid collection. Cases with an irregularly thickened and/or calcified cyst wall, presumably due to chronic inflammation of the wall, are rare. A 21-year-old woman presented with an extremely rare case of a solid and cystic Rathke cleft cyst with partial ossification, manifesting as bitemporal hemianopia. Magnetic resonance imaging showed a massive solid sellar lesion extending upward and compressing the optic chiasm and floor of the third ventricle. Transsphenoidal surgery was performed, resulting in total removal of the lesion and immediate recovery of visual function. Postoperative histological examination disclosed that the major part of the lesion consisted of various phases of clotting and granulation with significant fibrosis. Mature bone formation and abundant cholesterin clefts were also seen. Single cuboidal epithelium including goblet cells and cilia was found along this granulation, and the diagnosis was a Rathke cleft cyst. An ossified Rathke cleft cyst is extremely rare, and a solid Rathke cleft cyst has not before been reported. This case illustrates the extremely long and complex nature of this disease.

Rathke's cleft cysts with significant squamous metaplasia--high risk of postoperative deterioration and close origins to craniopharyngioma.

BackgroundRathke’s cleft cyst (RCC) with significant squamous and/or stratified epithelium including smooth transition from single cuboidal to squamous epithelium (tRCC) is rare and possibly represents an intermediate form to craniopharyngioma.MethodsTwelve patients with histologically confirmed tRCC were retrospectively investigated from a series of 167 cases of RCC and 96 cases of craniopharyngiomas. Clinical data were reviewed, and immunohistochemistry findings for cytokeratins and β-catenin were examined.ResultsAll lesions were located in the sella turcica with marked extension to suprasellar cistern. Six of the 12 patients had suffered postoperative re-enlargement, and three of these six patients required more than two additional operations and irradiation. CAM5.2 was positive in the glandular epithelium in all tRCCs and focally positive in the squamous epithelium of all these tRCCs. 34βE12 was positive in the squamous epithelium in all tRCCs and focally positive in the glandular epithelium in all but one tRCC. The findings of cytokeratin expression of tRCCs were very similar to those of craniopharyngioma. β-Catenin showed nuclear translocation in five cases. All patients with nuclear translocation of β-catenin suffered postoperative re-enlargement.ConclusionstRCC carries an extremely high risk of re-enlargement. Cytokeratin expression resembles that in craniopharyngioma, which might indicate a very close origin of these pathologies. Nuclear translocation of β-catenin may be related to the aggressive clinical course.

Outcome and mid-term prognosis after maximum and radical removal of craniopharyngiomas with the priority to the extended transsphenoidal approach—A single center experience

OBJECTIVE The transsphenoidal approach has been increasingly used for the surgical treatment of craniopharyngiomas with/without sellar enlargement. However, the optimum indications for the extended transsphenoidal approach with opening of the posterior ethmoidal sinus in addition to opening of the sellar floor are still controversial. METHODS Forty-two patients with craniopharyngiomas treated by the extended transsphenoidal approach were retrospectively studied from a series of 993 cases of pituitary surgeries between April 2004 and September 2013. Removal rate, visual function, endocrinological changes, and mid-term prognosis were investigated. RESULTS Gross total removal was achieved in 31 of 42 patients (73.8%) overall, in 24 of 27 patients (88.9%) undergoing initial treatment, and in 7 of 15 patients (46.7%) undergoing re-treatment after previous transcranial tumor removal and/or radiation therapy. The major cause of abandonment of surgery in the re-treatment group was tight adhesion and/or encasement of the perforating arteries. The rate of total removal showed a significant difference between initial treatment and re-treatment groups (logrank test, p<0.001). Only one patient suffered tumor recurrence after total removal, but the others remained disease-free during the follow-up period. Postoperative visual acuity was improved in 20 of 40 patients evaluated, remained steady in 20, and deteriorated in none, indicating good ophthalmological outcomes in all 40 patients. The pituitary stalk was intentionally sectioned in 18 of 42 patients, and 9 of the 18 patients could discontinue usage of antidiuretic hormone in the follow-up period. All patients were discharged without neurological deficits, except for two patients with preoperative dysfunction of the mammillary bodies, and all maintained independence in daily life with hormonal supplementation. No other complications including cerebrospinal fluid leakage were experienced in the follow-up period. CONCLUSIONS Maximum and radical removal through the extended transsphenoidal approach achieved high rate of total removal and good visual outcomes. However, re-treatment still presents challenges.

Autoimmune hypophysitis presenting with intracranial multi-organ involvement: three case reports and review of the literature

BackgroundAutoimmune hypophysitis very rarely spreads to nearby organs outside the pituitary tissue, for unknown reasons, with only 5 reported cases of hypophysitis spreading over the cavernous sinus.Case presentationThree patients presented with cases of non-infectious hypophysitis spreading outside the pituitary tissue over the cavernous sinus. All three cases were diagnosed with histological confirmation by transsphenoidal surgery, and the patients showed remarkable improvement with postoperative pulse dose steroid therapy, including disappearance of abnormal signal intensities in the bilateral hypothalami on magnetic resonance imaging, resolution of severe stenosis of the internal carotid artery, and normalization of swollen pituitary tissues. Two of 3 cases fulfilled the histological criteria of immunoglobulin G4-related disease, although none of the patients had high serum immunoglobulin G4 level.ConclusionThe true implications of such unusual spreading of hypophysitis to nearby organs are not fully understood, but the mechanism of occurrence might vary according to the timing of inflammation in this unusual mode of spreading. Pulse dose steroid therapy achieved remarkably good outcomes even in the patient with progressive severe stenosis of the internal carotid artery and rapid visual deterioration.

Evaluation of Fine Feeding System and Angioarchitecture of Giant Pituitary Adenoma—Implications for Establishment of Surgical Strategy

BACKGROUND Giant pituitary adenomas carry higher surgical risks despite recent advances in microsurgical and/or endoscopic surgery, and postoperative acute catastrophic changes without major vessel disturbance are still extremely difficult to predict, may manifest as postoperative pituitary apoplexy, and are associated with poor outcomes. METHODS Eight males and 4 females aged 31-72 years (mean 50.7 years) with giant pituitary adenomas underwent preoperative investigation of fine angioarchitecture using C-arm cone-beam computed tomography with a flat-panel detector. Angiographical findings were used to decide the surgical routes and compared with clinical outcome. RESULTS Feeding arteries were verified in 10 of 12 patients, whereas no feeding arteries were evident in 2 patients. The patients were divided into the faint tumor staining group and the significant staining group, which was reconfirmed by region of interest analysis. The former group had faint supply from the ipsilateral superior hypophyseal arteries and meningohypophyseal trunk, and the latter group had significant supply from the meningohypophyseal and inferolateral trunks, which passed centrifugally from the inferoposterior pole of the tumor. All patients were treated through the extended transsphenoidal approach. Intraoperative bleeding was significantly greater in the latter group (P = 0.013). All patients had improvement of neurologic deficit and were released from the intensive care unit within a few days. CONCLUSIONS Major blood supply of giant pituitary adenomas originates from branches of the infraclinoidal portion of the internal carotid artery, different from the normal anterior pituitary gland. Surgical route should depend on not only tumor shape and extension but also feeding systems.

Ischemic pituitary adenoma apoplexy—Clinical appearance and prognosis after surgical intervention

BACKGROUND Several retrospective investigations have recommended more passive surgical indications for intratumoral hemorrhage of pituitary adenomas due to probable spontaneous resolution. However, no definitive analyses have compared pituitary adenomas with hemorrhagic apoplexy and intratumoral hemorrhage without evident apoplectic symptoms or pituitary adenoma infarction. METHODS This study retrospectively identified 43 patients with symptomatic pituitary apoplexy among 1067 patients with pituitary adenomas initially treated by surgery at a single institute between April 2005 and May 2015, with 27 cases of hemorrhagic (2.53%) and 16 cases of ischemic apoplexy (1.50%). The inclusion criteria involved evident and sudden onset of symptoms and simultaneous histological confirmation as hemorrhagic or ischemic pituitary apoplexy. Diagnostic differentiation with magnetic resonance (MR) imaging was performed to examine the agreement between MR imaging and histological findings, and the clinical appearance and mid-term prognosis were compared for ischemic pituitary apoplexy and hemorrhagic apoplexy. RESULTS Diagnostic matching with MR imaging could be performed in 41 of 43 patients (25 with hemorrhagic and 16 with ischemic apoplexy). Agreement with the histological finding was found in 32 of 41 patients overall (78%), 23 of 25 patients with hemorrhagic apoplexy (92%), and 9 of 16 patients with ischemic apoplexy (56%). The main reason for diagnostic discrepancy was thought to be the difficulty in identifying ischemic lesion. All patients in the ischemic group suffered progression of symptoms from initial onset including various cranial nerve palsies, aseptic meningitis, and decreased level of consciousness, whereas the hemorrhagic group suffered progression in 4 of 27 patients. Ischemic group showed a statistically stronger tendency to disease progression than the hemorrhagic group (P<0.001). Endocrinological examinations showed 4 patients required no hormone supplement therapies but the other 11 patients had persistent hypopituitarism and required hormone supplementation in the ischemic group, whereas 2 of 25 patients required hormone supplementation in the hemorrhagic group. Endocrinological recovery showed a significant difference between the ischemic group and hemorrhagic group (P<0.01). CONCLUSIONS Ischemic pituitary adenoma apoplexy has a more severe clinical course than hemorrhagic apoplexy. Development of preoperative diagnostic technology to differentiate ischemic from hemorrhagic apoplexy is required to improve the low rate of agreement between the histological and MR imaging findings in patients with ischemic apoplexy.

Mechanics of the injected pulsejet into gelatin gel and evaluation of the effect by puncture and crack generation and growth

Recently, fluid jets have become widely used in medical devices and have been created and evaluated in clinical environments. Such devices are classified into two broad groups; those adopting continuous jets and those adopting discrete (or pulsed) jets. We developed a discrete jet device for brain cancer treatment, called a laser-induced liquid jet (LILJ) system. Although several studies have evaluated the availability and described the treatment mechanisms of fluid jet devices, the mechanisms of the fluid and injected material remain under-investigated. In this paper, we report the mechanism of frequent pulsejet injections into a viscoelastic biological material; namely, simulated gelatin brain tissue. The mechanism is evaluated by the injection depth, an easily measured parameter. To explain the injection mechanism, we propose that the pulsejet is pressured by forces introduced by resistance on the side surface of the hole and the reaction force proportionate to the injection depth. The pulsejet generated and propagated cracks in the gelatin, and the resistance eventually fractured the side surface of the hole. We evaluated the proposed model by measuring the behavior of pulsejets injected into gelatin by the LILJ. From the results, the following conclusions were obtained. First, the proposed model accurately describes the behavior of the injected pulsejet. Second, whether the hole or crack growth largely increases the final injection depth can be evaluated from differences in the decay constant. Finally, crack growth increases the final injection depth when the number of the injected pulsejets is greater than the inverse of the decay constant.