Katsumi Harimaya

Changes in knee alignment after total knee arthroplasty.

Changes in limb alignment after total knee arthroplasty were evaluated in 20 knees replaced with the Miller Galante knee system. The mean follow-up period was 87.4 months. Seventeen of the 20 knees were in the varus position on the initial postoperative radiographs, but the alignment significantly changed to become even more aligned toward varus during the follow-up period. The thickness of the ultra-high-molecular-weight polyethylene (UHMWPE) also decreased significantly in the medial femorotibial joint. The wear of the UHMWPE possibly changed the alignment, and the postoperative alignment had a positive correlation with the wear rate. The components should be implanted so that the mechanical axis intersects the center of the components to prevent worsening of alignment as well as to minimize any such wear.

Small GTP‐binding Protein, Rho, Both Increased and Decreased Cellular Motility, Activation of Matrix Metalloproteinase 2 and Invasion of Human Osteosarcoma Cells

Rho, a member of the small GTP‐binding proteins, and one of its downstream effectors ROCK (Rho‐associated coiled‐coil forming protein kinase) play an important role in the invasion of tumor cells. Lysophosphatidic acid (LPA) activates Rho and ROCK and promotes the organization of stress fibers and focal adhesions. However, the effect of LPA on tumor cell invasion is still controversial. In the present study, human osteosarcoma cells treated with a high concentration of LPA (high LPA) showed considerable formation of stress fibers and focal adhesions compared to the cells treated with a low concentration of LPA (low LPA). C3 (inhibitor of Rho) or Y27632 (an inhibitor of ROCK) inhibited the effects of LPA, indicating that LPA activates the Rho‐ROCK pathway in the cells. In addition, Rho activation assay showed that the activation level of Rho can be altered by changing the concentration of LPA. Low LPA stimulated the motility and invasion of the cells, while high LPA reduced both. The disruption of extracellular matrix (ECM) by matrix metalloproteinase 2 (MMP2) is also critical for tumor cell invasion. MMP2 is activated by membranous type‐1 MMP (MT1‐MMP) and type‐2 tissue inhibitor of MMP (TIMP2). High LPA suppressed the activation of MMP2 through down‐regulation of MT1‐MMP and TIMP2. C3 and Y27632 reversed the suppression of the activation of MMP2 and expression of MT1‐MMP and TIMP2, suggesting the involvement of the Rho‐ROCK pathway in ECM degradation. Tyrosine phosphorylation of focal adhesion kinase (FAK) was also required for the invasion of tumor cells to occur. Low LPA enhanced the tyrosine phosphorylation of FAK whereas high LPA reduced it. In conclusion, we suggest that Rho has a dual effect on the invasion of osteosarcoma cells by modulating the motility, the ability to degrade ECM and tyrosine phosphorylation of FAK.

Primitive neuroectodermal tumor and extraskeletal Ewing sarcoma arising primarily around the spinal column: report of four cases and a review of the literature.

Study Design. Report of four cases and a review of the literature. Objectives. To study the clinical features and prognosis of primitive neuroectodermal tumor or extraskeletal Ewing sarcoma arising around the spinal column. Summary of Background Data. Primitive neuroectodermal tumor or extraskeletal Ewing sarcoma that originates around the spinal column is very rare, and its prognosis is very poor. Methods. Four patients were diagnosed and underwent treatment. Results. Although all the patients received high-dose chemotherapy with or without radiotherapy after surgery, three patients died of the disease. Only one patient who received en bloc resection of the tumor combined with multiagent chemotherapy followed by high-dose chemotherapy with peripheral blood stem cell transplantation remains alive and continues to be disease free. Conclusion. The prognosis of the patients with primitive neuroectodermal tumor or extraskeletal Ewing sarcoma around the spinal column is very poor. Multiagent chemotherapy combined with en bloc resection and radiation therapy is the preferred treatment for patients with primitive neuroectodermal tumor or extraskeletal Ewing sarcoma around the spinal column.

Expression and Prognostic Significance ofO6-Methylguanine-DNA Methyltransferase in Hepatocellular, Gastric, and Breast Cancers

AbstractBackground:O6-Methylguanine-DNA methyltransferase MGMT is an enzyme that repairs O6-methylguanine, a promutagenic DNA base damaged by endogenous and environmental alkylating agents. There are few reports that describe whether or not abnormal MGMT expression correlates with the prognosis in human solid cancers. Methods: The expression of MGMT was immunohistochemically evaluated in 60, 62, 105, and 46 paraffin-embedded samples from patients with curatively resected hepatocellular, gastric, colorectal, and breast cancers, respectively. Results: The expression of MGMT was a positive predictive factor for overall survival in hepatocellular P = .005 and gastric cancers P < .001 and for relapse-free survival in breast cancers P < .001. MGMT-positive gastric tumors n = 42 were correlated with the absence of serosal invasion P = .045, lymph node metastasis P = .006, intestinal type P = .018, and low pathological tumor, node, metastasis stage P < .001. All breast tumors that recurred locally after operation were MGMT negative P = .004. The clinicopathologic characteristics of colorectal cancers with respect to MGMT expression did not significantly differ. Conclusions: The expression of MGMT is a predictive prognostic marker in patients with hepatocellular, gastric, and breast cancers. These findings may help to establish therapeutic strategies for patients with these types of solid cancer.

Etiology and revision surgical strategies in failed lumbosacral fixation of adult spinal deformity constructs.

Study Design. Retrospective case analysis. Objective. The purpose of this study was to evaluate the etiology and salvage strategies of failed lumbosacral fixation in adult spinal deformity patients. Summary of Background Data. When extending a long spinal deformity fusion to the sacrum, the lumbosacral junction is a common site for implant problems and pseudarthrosis. Methods. Clinical and radiographic results of 33 patients (26 women/seven men; average age, 53.5 years; range, 21–73) diagnosed and treated for lumbosacral fixation failure between 1995 and 2007 were reviewed. Twenty-one of the 33 patients underwent revision surgery at one institution for these failures and were followed postoperatively for more than 2 years (average, 50.7 months). Results. Twenty-nine of these 33 patients had two sacral screws, two patients one sacral screw, and two patients none. Bicortical sacral screws were placed in 18 patients, only 12 had distal fixation to the sacral screws (bilateral iliac screws, n = 9; others, n = 3). Seventeen of 19 patients without distal fixation to the sacral screws had screw loosening/pullout at L5 or S1. Anteriorly at L5–S1: 4/6 bone grafts collapsed, 5 of 15 intervertebral discs without anterior column support collapsed, and two of 12 titanium cages subsided into the endplates. Rod breakage between L5 and S1 (n = 9) was seen only in patients with distal fixation to the sacral screws. Nineteen of 21 revision patients received two bicortical sacral screws, whereas 20 received distal fixation to the sacral screws consisting of bilateral iliac screws in 16. Nineteen patients received anterior column support at L5–S1. Fifteen of 21 revision patients achieved solid fusion at ultimate follow-up; however, six had additional rod breakage or dislodgement at the lumbosacral junction. Conclusion. With long fusions to the sacrum in the treatment of spinal deformity, the use of bilateral S1 screws alone may allow for screw loosening/pullout and/or L5–S1 cage/graft collapse/subsidence. Adding bilateral iliac screws and an anterior structural cage/graft at L5–S1 will protect the S1 screws, but may still allow L5–S1 rod breakage/dislodgement because of lumbosacral pseudarthrosis. Revision surgery in these patients remains a challenge.

Pigmented villonodular synovitis with chondroid metaplasia, resembling chondroblastoma of the bone : a report of three cases

We herein describe three cases of pigmented villonodular synovitis with chondroid metaplasia. Two cases involved the temporomandibular joint, whereas the remaining one case occurred in the hip joint. Histologically, the tumors showed a villous pattern and were mainly composed of histiocyte-like cells and scattered osteoclast-like multinucleated giant cells, accompanied by chondroid areas with occasional lace-like calcification. These features resembled those of chondroblastoma of the bone, with the exception of the villous pattern. The histiocyte-like cells showed positive immunoreactivity for CD68, whereas they were negative for S-100 protein. Some of the previously reported cases of chondroblastoma in the temporal bone may have actually been cases of pigmented villonodular synovitis with chondroid metaplasia. When histologically chondroblastoma-like lesions involve the temporal bone or temporomandibular joint, the possibility of pigmented villonodular synovitis with chondroid metaplasia should also be considered, in addition to chondroblastoma of the bone. The correlation between this lesion and synovial chondromatosis remains uncertain.

Fluid Shear Stress Increases Interleukin‐11 Expression in Human Osteoblast‐like Cells: Its Role in Osteoclast Induction

It is unclear how mechanical stress influences bone cells. Mechanical stress causes fluid shear stress (FSS) in the bone. Osteoblast lineage cells are thought to sense FSS and regulate bone remodeling. We therefore investigated the effects of FSS on human osteoblast‐like osteosarcoma cells: SaOS‐2 cells in vitro. The conditioned medium of the SaOS‐2 cells after 24 h of FSS (24 h‐FSS CM) showed such osteoclastic phenotype inductions as significantly increasing the number of tartrate‐resistant acid phosphatase (TRAP) positive multinuclear cells in rat bone marrow cells and TRAP‐positive cells in human preosteoclastic cells: FLG 29.1 cells. An enzyme‐linked immunosorbent assay showed interleukin‐11 (IL‐11) protein to increase 7‐fold in the 24 h‐FSS CM. A Northern analysis showed that IL‐11 mRNA increased 4‐fold in the SaOS‐2 cells after 6 h‐FSS; however, no IL‐6 mRNA expression was detected. Furthermore, the anti‐human IL‐11 antibody significantly neutralized the osteoclastic phenotype induction of the 24 h‐FSS CM. The IL‐11 mRNA up‐regulation in SaOS‐2 cells by the 6 h‐FSS was not inhibited by the anti‐human transforming growth factor‐β1 antibody, but it was significantly inhibited by indomethacin. An enzymeimmunoassay showed prostaglandin E2 to increase 7‐fold in the 1 h‐FSS CM. These findings thus suggest that FSS induces osteoblasts to produce IL‐11 (mediated by prostaglandins) and thus stimulates bone remodeling.

Interaction of reactive astrocytes with type I collagen induces astrocytic scar formation through the integrin–N-cadherin pathway after spinal cord injury

Central nervous system (CNS) injury transforms naive astrocytes into reactive astrocytes, which eventually become scar-forming astrocytes that can impair axonal regeneration and functional recovery. This sequential phenotypic change, known as reactive astrogliosis, has long been considered unidirectional and irreversible. However, we report here that reactive astrocytes isolated from injured spinal cord reverted in retrograde to naive astrocytes when transplanted into a naive spinal cord, whereas they formed astrocytic scars when transplanted into injured spinal cord, indicating the environment-dependent plasticity of reactive astrogliosis. We also found that type I collagen was highly expressed in the spinal cord during the scar-forming phase and induced astrocytic scar formation via the integrin–N-cadherin pathway. In a mouse model of spinal cord injury, pharmacological blockade of reactive astrocyte–type I collagen interaction prevented astrocytic scar formation, thereby leading to improved axonal regrowth and better functional outcomes. Our findings reveal environmental cues regulating astrocytic fate decisions, thereby providing a potential therapeutic target for CNS injury.

Neurological complications of cervical laminoplasty for patients with ossification of the posterior longitudinal ligament - A multi-institutional retrospective study

Study Design. Retrospective multi-institutional study. Objective. To investigate the incidence of neurological deficits after cervical laminoplasty for ossification of the posterior longitudinal ligament (OPLL). Summary of Background Data. According to analysis of long-term results, laminoplasty for cervical OPLL has been reported as a safe and effective alternative procedure with few complications. However, perioperative neurological complication rates of laminoplasty for cervical OPLL have not been well described. Methods. Subjects comprised 581 patients (458 men and 123 women; mean age: 62 ± 10 years; range: 30–86 years) who had undergone laminoplasty for cervical OPLL at 27 institutions between 2005 and 2008. Continuous-type OPLL was seen in 114, segmental-type in 146, mixed-type in 265, local-type in 24, and not judged in 32 patients. Postoperative neurological complications within 2 weeks after laminoplasty were analyzed in detail. Cobb angle between C2 and C7 (C2/C7 angle), maximal thickness, and occupying rate of OPLL were investigated. Pre- and postoperative magnetic resonance imaging was performed on patients with postoperative neurological complications. Results. Open-door laminoplasty was conducted in 237, double-door laminoplasty in 311, and other types of laminoplasty in 33 patients. Deterioration of lower-extremity function occurred after laminoplasty in 18 patients (3.1%). Causes of deterioration were epidural hematoma in 3, spinal cord herniation through injured dura mater in 1, incomplete laminoplasty due to vertebral artery injury while making a trough in 1, and unidentified in 13 patients. Prevalence of unsatisfactory recovery not reaching preoperative level by 6-month follow-up was 7/581 (1.2%). Mean occupying rate of OPLL for patients with deteriorated lower-extremity function was 51.2 ± 13.6% (range, 21.0%–73.3%), significantly higher than the 42.3 ± 13.0% for patients without deterioration. OPLL thickness was also higher in patients with deterioration (mean, 6.6 ± 2.2 mm) than in those without deterioration (mean, 5.7 ± 2.0 mm). No significant difference in C2/C7 lordotic angle was seen between groups. Conclusion. Although most neurological deterioration can be expected to recover to some extent, the frequency of short-term neurological complications was higher than the authors expected.

Clinical results of open synovectomy for treatment of diffuse pigmented villonodular synovitis of the knee: case series and review of literature.

PURPOSE The purpose of current study was to evaluate recurrence of diffuse pigmented villonodular synovitis (DPVNS), functional outcome, and osteoarthritic change of the knee. METHODS Seventeen cases in 17 patients who had DPVNS of the knee that had not been previously treated were reviewed to determine the outcomes of surgical treatment. There were 10 males and 7 females, and their average age was 33.2 years (SD 17.2) at the time of first operation. Magnetic resonance imaging (MRI) was performed preoperatively to estimate the extent of the lesion. All patients were operated with open synovectomy. The mean postoperative follow-up period was 65.4 months (range 10.2 to 145.8; SD 48.3). RESULTS Two of 17 patients had posterior extra-articular lesions and recurrence. Two knees slightly reduced range of motion (from 145 to 130, from 145 to 125) and four knees progressed osteoarthritic changes, but overall postoperative results were satisfactory. CONCLUSIONS Because DPVNS sometimes exists out of knee joint, we should adequately check the location of the lesions using preoperative MRI, and synovectomy should be performed throughout knee joint including extra-articular lesion, especially around ligaments, meniscus, and suprapatellar was completely resected.