Clinical Features and Surgical Outcomes of Osteochondroma of the Spine.

Introduction: Spinal osteochondroma is rare. The purpose of this study is to examine the clinical characteristics and surgical treatment outcomes of 11 patients with spinal osteochondroma. Materials and methods: The study included 11 patients with spinal osteochondroma. In these patients, we examined the onset level, onset site, initial symptoms, surgical procedure, outcomes and complications. Results: Of the 11 patients, 9 presented with solitary tumours, and 2 had multiple. The mean post-operative observation period was six years and two months. The onset level was the cervical spine in eight patients, thoracic in two, and lumbar in one. The most common onset site was the posterior elements. The initial presentation was myelopathy in seven patients, radiculopathy in two, neck pain in one and feeling of mass in one. All patients underwent excision of the tumour, and depending on the tumour onset site, additional posterior or anterior decompression with or without fusion was performed. There was no recurrence in all patients. Intra-operative complications included dura tear and oesophageal injury in one patient with cervical onset, while post-operative complications included C5 palsy in one patient. Conclusions: In this study, surgical excision for osteochondroma of the spine were excellent with no recurrence of the tumour.

Dental caries experience, rather than toothbrushing, influences the incidence of dental caries in young Japanese adults.

A dose-response relationship between toothbrushing frequency and the incidence of dental caries has not been confirmed. Furthermore, no longitudinal study about this relationship has considered dental caries experience at baseline, which is an important factor influencing the frequency of future caries. OBJECTIVE: To elucidate the association between the incidence of dental caries and toothbrushing frequency after adjusting for dental caries experience at baseline in a Japanese population. BASIC RESEARCH DESIGN: The 92 recruits of the Japan Maritime Self-Defense Force in Kure, Japan, in 2011 were followed up for 3 years. They underwent oral examination at the annual checkups and answered questions about toothbrushing frequency. MAIN OUTCOME MEASURES: The multiple logistic regression analysis was used to analyze the incidence of dental caries and to identify independent effects of toothbrushing frequency and dental caries experience at baseline. Furthermore, the relative importance of the incidence of dental caries was investigated among other independent variables using the partial adjusted R² score. RESULTS: Logistic regression analysis showed that toothbrushing frequency alone did not influence the increment in decayed, missing, and filled teeth (DMFT). However, DMFT at baseline alone was associated with the increment in DMFT (crude odds ratio, OR, 1.20, 95% confidence interval, CI, 1.08,1.33). In the fully adjusted model, only DMFT at baseline was associated with the increment in DMFT (adjusted OR 1.23, 95%CI 1.09,1.38). CONCLUSION: After three years, the incidence of dental caries in young adult Japanese males was influenced by DMFT at baseline, rather than toothbrushing frequency.

Project for the development of the linac based NCT facility in University of Tsukuba.

A project team headed by University of Tsukuba launched the development of a new accelerator based BNCT facility. In the project, we have adopted Radio-Frequency Quadrupole (RFQ)+Drift Tube Linac (DTL) type linac as proton accelerators. Proton energy generated from the linac was set to 8MeV and average current was 10mA. The linac tube has been constructed by Mitsubishi Heavy Industry Co. For neutron generator device, beryllium is selected as neutron target material; high intensity neutrons are generated by the reaction with beryllium and the 80kW proton beam. Our team chose beryllium as the neutron target material. At present beryllium target system is being designed with Monte-Carlo estimations and heat analysis with ANSYS. The neutron generator consists of moderator, collimator and shielding. It is being designed together with the beryllium target system. We also acquired a building in Tokai village; the building has been renovated for use as BNCT treatment facility. It is noteworthy that the linac tube had been installed in the facility in September 2012. In BNCT procedure, several medical devices are required for BNCT treatment such as treatment planning system, patient positioning device and radiation monitors. Thus these are being developed together with the linac based neutron source. For treatment planning system, we are now developing a new multi-modal Monte-Carlo treatment planning system based on JCDS. The system allows us to perform dose estimation for BNCT as well as particle radiotherapy and X-ray therapy. And the patient positioning device can navigate a patient to irradiation position quickly and properly. Furthermore the device is able to monitor movement of the patient׳s position during irradiation.

HSV-NIS, an oncolytic herpes simplex virus type 1 encoding human sodium iodide symporter for preclinical prostate cancer radiovirotherapy.

Several clinical trials have shown that oncolytic herpes simplex virus type 1 (oHSV-1) can be safely administered to patients. However, virus replication in tumor tissue has generally not been monitored in these oHSV clinical trials, and the data suggest that its oncolytic potency needs to be improved. To facilitate noninvasive monitoring of the in vivo spread of an oHSV and to increase its antitumor efficacy, the gene coding for human sodium iodide symporter (NIS) was incorporated into a recombinant oHSV genome and the corresponding virus (oHSV-NIS) rescued in our laboratory. Our data demonstrate that a human prostate cancer cell line, LNCap, efficiently concentrates radioactive iodine after the cells have been infected in vitro or in vivo. In vivo replication of oHSV-NIS in tumors was noninvasively monitored by computed tomography/single-photon emission computed tomography imaging of the biodistribution of pertechnetate and was confirmed. LNCap xenografts in nude mice were eradicated by intratumoral administration of oHSV-NIS. Systemic administration of oHSV-NIS prolonged the survival of tumor-bearing mice, and the therapeutic effect was further enhanced by administration of (131)I after the intratumoral spread of the virus had peaked. oHSV-NIS has the potential to substantially enhance the outcomes of standard therapy for patients with prostate cancer.

Video-assisted thoracic surgery for lung cancer in hemodialysis patients.

INTRODUCTION: In recent years, the number of hemodialysis patients has been continuously increasing. At the same time, the use of video-assisted thoracic surgery (VATS) for lung cancer has also increased. However, reports of the outcome of VATS in hemodialysis patients are still quite rare. METHODS: From 1995 to 2011, 14 patients with non-small cell lung cancer who were also receiving hemodialysis underwent lung resection by open thoracotomy or VATS at our institution. These patients were divided into two groups as follows: open (five men and four women, mean age: 68.7 years) and (2) VATS (three men and two women, mean age: 64.0 years). We compared the clinical outcomes of these two groups. RESULTS: Lobectomy was performed in eight patients in the open group, including one patient who also underwent a pneumonectomy, and in four patients in the VATS group, including one who also underwent a wedge resection. There were no significant difference between the groups' operation times, intraoperative blood loss, length of postoperative chest drainage, and length of postoperative hospitalization. There were no hospital deaths in either group. The 5-year survival rate was 42.9% in the open group and 37.5% in the VATS group. This difference was not significant (P=0.73). CONCLUSION: VATS lung resection for lung cancer patients on hemodialysis is considered an acceptable treatment modality, though the long-term survival rate of such patients is relatively low, which can be attributed to the diseases underlying the need for hemodialysis.

Posterior/anterior combined surgery for thoracolumbar burst fractures--posterior instrumentation with pedicle screws and laminar hooks, anterior decompression and strut grafting.

STUDY DESIGN: A prospective clinical study. OBJECTIVE: The purpose of this study was to evaluate prospectively a large group of patients with thoracolumbar burst fractures who were treated with a posterior/anterior combined procedure and to report on the surgical outcomes, complications and radiographic results. METHODS: A total of 100 consecutive patients were surgically managed with posterior instrumentation, anterior decompression and anterior strut grafting. There were 71 males and 29 females; the mean age was 36 years. Patients with osteoporotic delayed vertebral body collapse were excluded. The mean follow-up period was 30 months. Surgical outcomes such as operative time, blood loss and sagittal alignment were investigated. A neurological assessment was performed by a rating system based on the American Spine Injury Association impairment scale. An interbody fusion was judged using plain X-ray and computed tomographic scans. RESULTS: The mean operative time was 256 min and the mean operative bleeding was 985 ml. Most of the patients were ambulatory within 3 days after surgery. Of the 76 patients with neurological injury, 54 (71.1%) recovered function following surgery. The mean local kyphosis angle was 12.2° kyphotic preoperatively and 0.8° lordotic at the final observation. The mean correction angle was 15.7° and correction loss was 2.6°. No instrumentation failure was observed and the postoperative fusion rate was 99%. CONCLUSIONS: Posterior/anterior combined surgery with posterior pedicle screws and hooks fixation, and reconstruction by simultaneous strut grafting and anterior decompression, achieved short segment fixation and can be a useful option for surgically treating thoracolumbar burst fractures.

Mutation screening of the CARD15 gene in sarcoidosis.

CARD15 was first identified as a susceptibility gene for Crohn's disease. More recently, CARD15 mutations were shown to be associated with the pediatric granulomatous inflammatory diseases, Blau syndrome and early-onset sarcoidosis (EOS). The aim of the present study was to evaluate whether CARD15 variants also play a role in patients with ordinary sarcoidosis other than EOS. We enrolled 135 Japanese sarcoidosis patients with uveitis as well as 95 healthy individuals and performed mutation analysis by direct sequencing of CARD15 exon 4. Direct DNA sequencing in the sarcoidosis patients showed eight CARD15 variants, including five novel mutations (13402C>T, 13543C>T, 13775C>A, 13937G>A, and 14079C>T). Compared with healthy individuals, CARD15 mutations are not common in the Japanese patients with sarcoidosis. Based on the results, we examined the clinical manifestations in patients with sarcoidosis according to their CARD15 mutations. Sarcoidosis patients with these mutations have no specific clinical features with regard to course of the disease or disease severity. Our results indicate that in general, CARD15 mutations may not contribute to the risk of sarcoidosis.

A dose-escalation study of rituximab for treatment of systemic lupus erythematosus and Evans' syndrome: immunological analysis of B cells, T cells and cytokines.

OBJECTIVE: Accumulating evidence suggests that B-cell depletion therapy by rituximab may be effective for autoimmune disorders. However, an optimal dose of rituximab and a mechanism of its action remain to be established. We performed a dose-escalation study for treatment of Japanese patients with autoimmune diseases including eight with SLE and one with Evans' syndrome. METHODS: Rituximab was infused intravenously, weekly 4 times in a dose-escalating fashion at three different doses of 100, 250 or 375 mg/m(2) to three patients each. Immunological parameters were monitored at certain points until 12 months after the treatment. RESULTS: Rituximab was well tolerated and safe in these patients. Seven out of eight SLE patients and one with Evans' syndrome clinically responded completely or partially to the treatment. Four patients achieved long-term remission (18-30 months) without any additional treatment. In these patients, a significant decrease in circulating B cells continued for 6 months after the treatment. The mean fluorescence intensities of CD19, CD21, CD40 and BR3 on the residual B cells as well as the percentage of CD69+ CD4+ T cells decreased significantly. Serum TNF-alpha levels decreased significantly on day 2. The Th1/Th2 balance of CD4+ T cells gradually shifted towards a Th1 type by 6 months. CONCLUSION: In addition to B-cell depletion, modification of B-cell and T-cell phenotypes as well as cytokine profiles may be involved in the action of rituximab.

Increased serum levels of circulating CD40 ligand in patients with bullous pemphigoid: preliminary results.

BACKGROUND: Autoimmune bullous diseases are characterized by autoantibodies against specific adhesion molecules of the skin and/or mucous membrane. While these autoantibodies are known to play a primary role in the disease manifestation, it remains unknown how disease-specific autoreactive B cells and autoantibodies are induced. Recent studies have indicated the importance of the CD40 and CD40 ligand (CD40L) receptor-ligand pair in the immunopathogenesis of autoimmune diseases. CD40L circulates in soluble form, and some reports suggest that serum soluble CD40L (sCD40L) levels are increased in various autoimmune diseases. OBJECTIVES: To determine serum sCD40L levels in patients with pemphigus vulgaris (PV) and bullous pemphigoid (BP), and to determine their correlation with clinical findings and laboratory findings. PATIENTS AND METHODS: Sera from 10 PV patients, 35 BP patients and 12 normal controls were subjected to ELISA assays to measure serum levels of sCD40L, anti-desmoglein-3 antibody and anti-BP180 antibody. RESULTS AND CONCLUSIONS: Circulating sCD40L levels were significantly elevated in BP patients, but not in PV patients. Serum sCD40L levels increased in the early stage of disease onset and recurrence in BP patients. In conclusion, circulating sCD40L levels may be a useful marker for early activation of autoimmune diathesis and, furthermore, an effective therapeutic target in patients with BP.

Serum chemokine profile in patients with bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune inflammatory disease causing blister formation at the dermoepidermal junction. Cutaneous infiltration of activated CD4+ T cells and eosinophils is an early event in blister formation during the disease process, suggesting that the trafficking of circulating leucocytes through the sites of inflammation is crucial in the pathogenesis of the disease. While the accumulated evidence suggests that some cytokines are involved in the pathogenesis, there have been few reports about serum chemokine profiles in patients with BP. OBJECTIVES: To determine serum profiles of various chemokines and their clinical association in patients with BP. METHODS: Concentrations of 10 chemokines - interferon (IFN)-gamma-inducible protein-10 (IP-10), monokine induced by IFN-gamma (MIG), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, RANTES, eotaxin, monocyte chemoattractant protein (MCP)-1, MCP-2, MCP-3 and growth-regulated oncogene-alpha- were measured in serum samples from 38 patients with BP, 16 with pemphigus vulgaris (PV) and 17 normal controls using a sandwich immunoassay-based multiplex protein array system. RESULTS: While there was no significant increase in any serum chemokine levels in patients with PV, serum levels of IP-10 and MCP-1 were significantly increased in patients with BP compared with healthy controls. Furthermore, serum levels of IP-10, MIG, MCP-1 and eotaxin in patients with BP increased significantly with disease severity as determined by the area affected. CONCLUSIONS: These observations suggest that an elaborately orchestrated network of chemokines, especially MCP-1 and IP-10, contributes to the pathomechanism of BP.

Increased serum levels of a proliferation-inducing ligand in patients with bullous pemphigoid.

BACKGROUND: B cells have been demonstrated to have critical roles in developing autoimmune bullous diseases. Recently identified tumor necrosis factor-like molecules, B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) are essential molecules for B cell development, survival, and proliferation. Although the functions of APRIL have not been fully evaluated, recent studies suggest that circulating levels of APRIL are increased in various autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. OBJECTIVES: To determine serum APRIL levels in patients with pemphigus vulgaris (PV) and bullous pemphigoid (BP), and compare those with clinical findings and laboratory findings. PATIENTS/METHODS: Sera from 15 PV patients, 43 BP patients, and 15 normal controls were subjected to ELISA assays to measure serum APRIL, BAFF, Dsg3, and BP180 levels. RESULTS AND CONCLUSIONS: Circulating APRIL levels were significantly elevated in BP patients but not in PV patients, and correlated with serum BAFF levels. Our study revealed that serum APRIL levels tended to be increased in the quite early stage of disease. In conclusion, circulating APRIL levels may be a useful marker for early activation of autoimmune diathesis, and furthermore, an effective therapeutic target molecule in patients with BP.

Interventional navigation for abdominal therapy based on simultaneous use of MRI and ultrasound.

An interventional navigation system designed for percutaneous abdominal therapies was proposed, and a pilot study was carried out to assess the proposed system. Integration of US to MRI-based segmentation and 3D display of tumours can help physicians deal with instabilities such as respiratory motion and soft tissue shift that are inherent in abdominal interventions. In addition to the 3D display of the needle and tumours, we adapted the system for the abdominal applications and incorporated a process to correct the mismatch in needle path between MRI and US. The preliminary results of phantom and animal experiments indicated that the proposed method could combine the advantages of both MRI and US. The time required to determine the optimal needle insertion path by using this system was significantly less than that required when either US or MRI guidance alone was employed. The developed system was applied in two patients who underwent PEIT therapy, and its clinical feasibility was partially confirmed.

Serum levels of BAFF are increased in bullous pemphigoid but not in pemphigus vulgaris.

BACKGROUND: BAFF [B-cell activating factor belonging to the tumour necrosis factor (TNF) family] is a member of the TNF superfamily that regulates B-lymphocyte proliferation and survival. It has been demonstrated that increased levels of soluble BAFF are associated with systemic autoimmunity in patients with systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome, and in animal models of spontaneous autoimmune diseases. However, the significance of circulating BAFF in autoimmune bullous diseases is unknown. OBJECTIVES: To examine whether BAFF levels are elevated in the autoimmune blistering diseases pemphigus vulgaris (PV) and bullous pemphigoid (BP). METHODS: We examined sera obtained from 21 patients with PV, 39 patients with BP and 22 healthy donors. We performed enzyme-linked immunosorbent assays for soluble BAFF and each disease-specific antibody: antidesmoglein-3 antibody for PV and anti-BP180 antibody for BP. RESULTS: Significant elevations of serum BAFF levels were found in the patients with BP, but not with PV. There was apparently no significant association between the serum BAFF levels and titres of anti-BP180 antibodies in the patients with BP. However, serum BAFF levels tended to be more elevated in patients with a shorter disease duration. There was a tendency that BAFF levels increased before the anti-BP180 antibody levels increased at the onset of BP and quickly decreased in response to treatment. CONCLUSIONS: BAFF may be a useful marker for early activation of an autoimmune diathesis and may play a critical role in triggering activation of self-antigen-driven autoreactive B cells in BP.

Prevention of abdominal aortic aneurysms by simultaneous inhibition of NFkappaB and ets using chimeric decoy oligonucleotides in a rabbit model.

Abdominal aortic aneurysm (AAA) is one of the major vascular diseases caused by atherosclerosis. Because treatment for AAA mainly consists of surgery to prevent deaths from AAA rupture and there is a conspicuous absence of alternative therapeutic strategies, the development of minimally invasive treatment is needed. To develop a novel therapeutic approach, we examined the simultaneous inhibition of the transcription factors NFkappaB and ets, which regulate inflammation and matrix degradation, in a rabbit AAA model. In this study, we employed chimeric decoy oligodeoxynucleotides (ODN), containing the consensus sequences of both the NFkappaB- and ets-binding sites, to inhibit both the transcription factors simultaneously. Using a delivery sheet, we examined the inhibitory effect of chimeric decoy ODN on aortic dilatation. Ultrasound and angiographic analysis demonstrated that treatment with chimeric decoy ODN significantly prevented the progression of elastase-induced aortic dilatation. The inhibitory effect of chimeric decoy ODN on aortic dilatation was also confirmed by histological studies. Treatment with chimeric decoy ODN reduced the activities of matrix metalloproteinase (MMP)-2 and MMP-9 and markedly inhibited the proteolysis of elastin as compared to scrambled decoy ODN. Interestingly, treatment with chimeric decoy ODN also suppressed VCAM-1 and MCP-1 gene expression, leading to inhibition of macrophage infiltration in the adventitia and media. The present study in a rabbit model provides a novel strategy to treat AAA by the simultaneous inhibition of both NFkappaB and ets using chimeric decoy ODN. Further modification of chimeric decoy ODN would be useful to treat AAA as a decoy-based therapy.