Akira Matsuno

Analyses of the factors influencing bone graft infection after delayed cranioplasty

SummaryBackground. Several factors influencing bone graft infection after delayed cranioplasty are analyzed in order to reduce the occurrence of infection.Methods. For about 10 years, from March 1995 to February 2005, delayed cranioplasty was performed for 206 cases. The cases comprised 124 males and 82 females. Age distribution of the patients ranged from 6 months to 79 years old. The mean postoperative follow-up period was 1834 days. Autogenous bone, which was preserved in 100% ethanol at −20u2009°C and autoclaved before operation, was used in 54 patients. Polymethylmethacrylate (PMMA) was used in 55 patients. Custom-made PMMA was used in 3 patients. Custom-made titanium mesh was used in 77 patients. Custom-made ceramics (Alumina-ceramics 10 cases and hydroxyapatite 7 cases) was used in 17 patients.Findings. Autoclaved and autogenous bone graft and PMMA have a significantly high rate of graft infection. Titanium mesh has the significantly lowest rate of graft infection. Alumina-ceramic has a merit that it has sufficient strength, however the number of cases using custom-made ceramics including alumina-ceramic was relatively small, and thus we cannot find significant differences in infection rate compared with that of other materials. There was no statistically significant difference in the bone graft infection rate among four categories of preceding diseases; cerebrovascular diseases, head trauma, infectious diseases, and brain tumour.Conclusion. Autoclaved and autogenous bone grafts and PMMA have a significantly higher rate of graft infection. Titanium mesh has the significantly lowest rate of graft infection.

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

CONTEXTnTemozolomide (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).nnnOBJECTIVEnThe clinical and pathological characteristics of APAs and PCs treated with TMZ in Japan were surveyed and analyzed retrospectively.nnnDESIGNnMembers 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.nnnSUBJECTSnThree samples from 3 subjects with APA and 11 samples from 10 subjects with PC were available.nnnRESULTSnThe 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).nnnCONCLUSIONSnThis 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.

A mechanism of acquiring temozolomide resistance during transformation of atypical prolactinoma into prolactin-producing pituitary carcinoma: case report.

BACKGROUND AND IMPORTANCE:The case presented here describes the clinical evolution of a pituitary carcinoma from an atypical prolactinoma after temozolomide (TMZ) treatment. The mechanism of acquisition of TMZ resistance was analyzed. CLINICAL PRESENTATION:A 60-year-old woman with atypical prolactinoma had been treated for 7 years with multiple therapies, including dopamine agonists, surgical intervention (5 times), conventional radiotherapy, and radiosurgery. The patient deteriorated as a result of tumor enlargement. Ten cycles of TMZ therapy, 200 mg/m2 for 5 days every 4 weeks, improved the patients performance status and caused tumor shrinkage. Six months after discontinuation of TMZ, the tumor progressed into pituitary carcinoma with tumor regrowth and intraventricular dissemination. TMZ therapy was ineffective this time. A sixth surgery and salvage chemotherapy failed to improve the patients condition, and she died 9 years after the first diagnosis. Throughout the treatment course, O6-methyl-guanine-DNA methyltransferase (MGMT) was immunonegative in the tumor specimens, including the TMZ-refractory pituitary carcinoma. Mutation of p53 was identified in both the atypical prolactinoma and pituitary carcinoma. In contrast, major differences were noted for mismatch repair protein MSH6 immunostaining: Although MSH6 was diffusely immunopositive in the atypical adenoma, it became immunonegative when the tumor evolved into TMZ-refractory pituitary carcinoma. CONCLUSION:Loss of MSH6 occurred during the progression from an atypical prolactinoma to a pituitary carcinoma, which may have caused resistance to TMZ treatment. This case suggests that preserving MSH6 function is essential for responsiveness to TMZ treatment in MGMT-negative and p53-mutated atypical pituitary adenoma or pituitary carcinoma.

Three-dimensional Imaging of the Intracellular Localization of Growth Hormone and Prolactin and Their mRNA Using Nanocrystal (Quantum Dot) and Confocal Laser Scanning Microscopy Techniques:

Semiconductor nanocrystals (Quantum dots, Qdots) have recently been used in biological research, because they do not fade on exposure to light, and they enable us to obtain multicolor imaging because of a narrow emission peak that can be excited via a single wavelength of light. There have been no reports of simultaneous localization of mRNA and protein using Qdots. We successfully applied these advantages of Qdot and confocal laser scanning microscopy (CLSM) to three-dimensional images of the intracellular localization of growth hormone and prolactin and to their mRNA. In situ hybridization and immunohistochemistry using Qdots combined with CLSM can optimally illustrate the relationship between protein and mRNA simultaneously in three dimensions. Such an approach enables us to visualize functional images of proteins in relation with mRNA synthesis and localization.

SIRT1 regulates thyroid-stimulating hormone release by enhancing PIP5Kγ activity through deacetylation of specific lysine residues in mammals

Background SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there. Methodology/Principal Findings Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5K)γ was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5Kγ and enhanced PIP5Kγ enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kγ knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kγ, PI(4,5)P2, and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice. Conclusions/Significance Our findings indicated that the control of TSH release by the SIRT1-PIP5Kγ pathway is important for regulating the metabolism of the whole body.

Primary diffuse large B-cell lymphomas of central nervous system exhibit remarkably high prevalence of oncogenic MYD88 and CD79B mutations

Abstract MYD88 and CD79B mutations that activate nuclear factor (NF)-κB signaling are prevalent in subsets of diffuse large B-cell lymphoma (DLBCL). We examined the prevalence of somatic mutations in the Toll/interleukin-1 receptor (TIR) domain of MYD88 and the tyrosine-based activation motif (ITAM) domain of CD79A/B in 18 primary central nervous system (CNS) DLBCLs, and their immunoprofile. MYD88 mutation was found in 17 cases (94.4%), all of which were L265P substitutions. CD79B mutation was found in 11 cases (61.1%), 10 (55.6%) of which were Y196C/D/H substitutions. Mutation of CD79A was completely absent. Immunohistochemically, all the tumors were CD3−/CD5−/CD20+/CD79a+/ GCET1−/BCL6+/MUM1+. Three (16.7%) cases were CD10+, but the majority (15 cases, 83.3%) were CD10−. Overall, all cases harbored either MYD88L265P or CD79BY196C/D/H, or both, irrespective of their immunoprofile. Our results suggest that CNS DLBCL is a group of tumors harboring a characteristic mutation profile which triggers NF-κB signaling in the immune-privileged site.

A simple and consistent technique for ventricular catheter insertion using a tripod.

OBJECTIVEnFor long-term preservation of ventriculo-peritoneal (VP) shunt function, it is essential to place the ventricular catheter tip above the foramen of Monro. But the free-hand technique for ventricular catheter passage is not consistent.nnnMETHODSnSupposing that a convex of skull matches to a sphere, in which the foramen of Monro is the center, a perpendicular direction from the surface of the sphere to inside always directs toward the center. The authors identified the range of skull where corresponded to the sphere by magnetic resonance imaging assessment and utilized tripod to achieve exactly perpendicular insertion of ventricular catheter. And an optimal length of catheter insertion was investigated by navigation system.nnnRESULTSnThe anterior-posterior range of the spherical portion was from coronal suture to 20mm anterior, and the lateral range of it was between 15 and 35mm lateral from sagittal suture. The optimal catheter length for insertion was between 55 and 58mm from the brain surface. Ideal placement of a ventricular catheter tip was achieved in more than 90% of cases (31/34) with this technique.nnnCONCLUSIONnTripod-guided ventricular catheter insertion is a simple and reliable method for VP shunt at any angle of head-rotation.

Specific gene suppression using antisense strategy for growth suppression of glioma

Antisense strategy using synthetic oligodeoxynucleotides has been applied to the suppression of specific gene expression, the modulation of various gene expression, and its biological activity. Antisense strategy is applicable for the growth suppression of glioma cells. Several genes, including transforming growth factor-α, basic fibroblast growth factor, fibroblast growth factor receptor 1, vascular endothelial growth factor, telomerase, topoisomerase II α-subunit, protein kinase C-α, and microtubule-associated protein 1A, have been targeted by antisense strategy in glioma cells. These antisense strategies provide a potential novel antitumor therapy for gliomas.

Tumefactive multiple sclerosis requiring emergent biopsy and histological investigation to confirm the diagnosis: a case report

IntroductionTumefactive multiple sclerosis is a demyelinating disease that demonstrates tumor-like features on magnetic resonance imaging. Although diagnostic challenges without biopsy have been tried by employing radiological studies and cerebrospinal fluid examinations, histological investigation is still necessary for certain diagnosis in some complicated cases.Case presentationA 37-year-old Asian man complaining of mild left leg motor weakness visited our clinic. Magnetic resonance imaging demonstrated high-signal lesions in bilateral occipital forceps majors, the left caudate head, and the left semicentral ovale on fluid-attenuated inversion recovery and T2-weighted imaging, and these lesions were enhanced by gadolinium-dimeglumin. Tumefactive multiple sclerosis was suspected because the enhancement indistinctly extended along the corpus callosum on magnetic resonance imaging and scintigraphy showed a low malignancy of the lesions. But oligoclonal bands were not detected in cerebrospinal fluid. In a few days, his symptoms fulminantly deteriorated with mental confusion and left hemiparesis, and steroid pulse therapy was performed. In spite of the treatment, follow-up magnetic resonance imaging showed enlargement of the lesions. Therefore, emergent biopsy was performed and finally led to the diagnosis of demyelinating disease. The enhanced lesion on magnetic resonance imaging disappeared after one month of prednisolone treatment, but mild disorientation and left hemiparesis remained as sequelae.ConclusionsFulminant aggravation of the disease can cause irreversible neurological deficits. Thus, an early decision to perform a biopsy is necessary for exact diagnosis and appropriate treatment if radiological studies and cerebrospinal fluid examinations cannot rule out the possibility of brain tumors.

Molecular status of pituitary carcinoma and atypical adenoma that contributes the effectiveness of temozolomide

There have been several reports of temozolomide (TMZ) treatment of pituitary carcinomas and atypical adenomas. O6-methyl-guanine-DNA methyltransferase is not the sole molecule determining the sensitivity to TMZ in pituitary carcinomas and atypical adenomas. The Japan Society of Hypothalamic and Pituitary Tumors study suggests that MSH6, one of mismatch repair pathway enzyme, fulfills a contributory role to the efficacy of TMZ treatment for pituitary carcinomas and atypical adenomas. The preserved MSH6 function might be essential for the responsiveness to TMZ treatment in pituitary carcinomas and atypical adenomas.