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Low inflation was once welcomed by both policymakers and the public. However, Japan's experience during the 1990s changed the consensus of economists and central banks around the world regarding prices. Facing deflation and the zero-interest bound at the same time, the Bank of Japan had difficulty conducting an effective monetary policy, making Japan's stagnation unusually prolonged. The too-low inflation that concerns central banks today translates into the "Phillips curve puzzle." In the United States and Japan, in the course of the recovery from the Great Recession after the 2008 Global Financial Crisis, the unemployment rate had steadily declined to a level commonly regarded as lower than the natural rate or NAIRU. However, inflation remained low. In this paper, we consider a minimal model of the dual labor market to jointly investigate how the different factors affecting the structural evolution of the labor market have contributed to the observed flattening of the Phillips curve. We find that the level of bargaining power of workers, elasticity of the supply of labor to wage in the secondary market, and composition of the workforce are the main factors jointly explaining the evidence for Japan., Supplementary Information: The online version contains supplementary material available at 10.1007/s00191-022-00781-8., (© The Author(s) 2022, corrected publication 2022.)

Introduction: A postoperative clinically relevant pancreatic fistula can cause severe sequelae. We aimed to describe our minimally invasive procedure (rendezvous technique) for the treatment of a pancreatic fistula resulting from pancreaticojejunal anastomosis dehiscence involving a dislodged main pancreatic duct tube., Methods: In our rendezvous technique, a guidewire is advanced into the jejunal lumen from the access site of the drainage tube and is caught by a snare catheter, which is used to replace the dislodged main pancreatic duct tube. Then, the guidewire is passed from the access site of the drainage tube to the site of the dislodged main pancreatic duct tube. A sheath is inserted along the route of the dislodged main pancreatic duct tube and is placed across the pancreaticojejunal anastomosis over the guidewire. Another guidewire is advanced into the main pancreatic duct via the sheath, and a new main pancreatic duct tube is inserted into the main pancreatic duct over the second wire. This technique was performed in two patients with a pancreatic fistula., Results: Our rendezvous technique was successfully performed in a 73-year-old man with an intractable clinically relevant pancreatic fistula and large discharge from the drain and a 74-year-old woman with a pancreatic fistula and fluid collection between the elevated jejunum and remnant pancreas. Discharge from the drain and fluid collection decreased after the procedure., Conclusion: Our rendezvous technique is an effective minimally invasive approach for a pancreatic fistula resulting from pancreaticojejunal anastomosis dehiscence.

Background: Few studies have described the characteristics and prognostic factors of elderly patients with osteosarcoma. We retrospectively investigated clinico-pathological features and prognostic factors in osteosarcoma patients > 40 years old., Methods: Patients with high-grade osteosarcoma > 40 years old who were treated at our institutions from 2000 to 2016 were recruited for this study. Information on patient, tumour, and treatment-related factors was collected and statistically analyzed. The median follow-up was 26.5 months (range, 5-139 months) for all patients., Results: Fifty patients (30 males and 20 females) were included. The median age at diagnosis was 59.5 years (range, 41-81 years). The primary lesions were found in the limbs in 32 patients, trunk in 12, and craniofacial bones in six. Primary and secondary osteosarcoma occurred in 41 and 9 patients, respectively. Eight patients exhibited initial distant metastasis. Definitive surgery and chemotherapy were performed in 39 patients each. The rate of good responders after neoadjuvant chemotherapy was 38%. The five year overall survival (OS) rates for all patients and those without distant metastasis at diagnosis were 44.5% and 51.1%, respectively. Multivariate analysis showed that definitive surgery was the only significant prognostic factor in non-metastatic patients. The five year OS and disease-free survival (DFS) rates for non-metastatic patients who received definitive surgery were 64.3% and 60%, respectively. Among these patients, neoadjuvant and/or adjuvant chemotherapy significantly improved both OS and DFS., Conclusions: Complete surgical resection and intensive chemotherapy should be performed for osteosarcoma patients > 40 years old despite distinct clinicopathological characteristics from those of younger patients.

This study revealed the distinguished changes of preferential orientation of collagen and apatite and Young's modulus in two different types of osteoporotic bones compared with the normal bone. Little is known about the bone material properties of osteoporotic bones; therefore, we aimed to assess material properties in osteoporotic bones. 66 female Sprague-Dawley rats were used. We analyzed the volumetric bone mineral density, collagen/apatite orientation, and Young's modulus of fifth lumbar vertebral cortex for osteoporotic rats caused by ovariectomy (OVX), administration of low calcium and phosphate content (LCaP) diet, and their combination (OVX + LCaP), as well as sham-operated control. Osteocyte conditions were assessed by hematoxylin and eosin and immunohistochemical (matrix extracellular phosphoglycoprotein (MEPE) and dentin matrix protein 1 (DMP1)) staining. All osteoporotic animals showed bone loss compared with the sham-operated control. OVX improved craniocaudal Young's modulus by enhancing collagen/apatite orientation along the craniocaudal axis, likely in response to the elevated stress due to osteoporotic bone loss. Conversely, LCaP-fed animals showed either significant bone loss or degraded collagen/apatite orientation and Young's modulus. Osteocytes in LCaP and OVX + LCaP groups showed atypical appearance and MEPE- and DMP1-negative phenotype, whereas those in the OVX group showed similarity with osteocytes in the control group. This suggests that osteocytes are possibly involved in the osteoporotic changes in collagen/apatite orientation and Young's modulus. This study is the first to demonstrate that osteoporosis changes collagen/apatite orientation and Young's modulus in an opposite manner depending on the cause of osteoporosis in spite of common bone loss.

Purpose: This study aimed to compare clinical results and to restore radiographic parameters of corrective osteotomy for malunited distal radius fracture using a volar locking plate with a dorsal plate., Methods: We retrospectively studied 28 consecutive patients with symptomatic malunited distal radius fractures followed up for more than 12 months who underwent corrective osteotomy with a dorsal buttress plate (n = 9) or a volar locking plate (n = 19). Volar tilt (VT), radial inclination (RI), and ulnar variance (UV) were radiographically evaluated. Clinical examination parameters included pain, wrist and forearm ranges of motion (ROM), grip strength, and Mayo Modified Wrist Score (MMWS)., Results: The volar group had a significantly greater VT undercorrection for - 9.4° than did the dorsal group for - 1.2° (p < 0.001). Major complications requiring plate removal occurred in six of nine patients in the dorsal group and two of 19 patients in the volar group. The complication ratio was significantly greater in the dorsal group than in the volar group (p < 0.05). Improvements in forearm and wrist ROM, grip strength, and MMWS did not differ significantly between groups., Conclusions: Opening wedge osteotomy of the radius using a volar locking plate is preferable to dorsal buttress fixation in terms of surgical and technical demands and frequency of complications, but VT correction is insufficient. Surgeons should be aware of the mismatch between the plate and the volar surface of the malunited distal radius.

Objective: To clarify the advantage of prone position over supine position in radiographically-demonstrating anterior knee laxity measurement for anterior cruciate ligament (ACL) injury, and to optimize the radiographic technique for the ACL-deficient knees in a clinical setting., Materials and Methods: Thirty-nine patients with unilateral ACL injury had consented to participate in this study. They were divided into two groups and subjected to the different radiographic evaluations: study 1 (20 patients); supine versus prone position with knee full-extended, and study 2 (19 patients); comparison of (1) prone position with knee full-extended (FPV), (2) prone position with knee flexed at 15° (AGV), and (3) supine position with calf put on a board at 15° of knee flexion (SGV). Lateral radiographs for both knees were taken and were measured the side-to-side difference of tibial position related to femur., Results: In study 1, the side-to-side difference was 2.8 ± 1.0 mm in supine position and 4.3 ± 2.1 mm in prone position, showing a statistically significant difference. In study 2, the side-to-side difference was 3.7 ± 2.4 mm in FPV, 4.6 ± 2.0 mm in AGV, and 4.2 ± 2.8 mm in SGV, while the difference in the latter two positions was larger than that in FPV., Conclusions: The anterior laxity in prone position is larger than that in supine position for ACL injury. Moreover, the gravity-assisted lateral radiograph in prone position with knee flexed at 15° could be one of the preferable radiographic techniques and could provide more information than the simple radiograph.

The partial physeal arrest of the distal radius could result in progressive deformities and functional problems of the wrist. Despite being the most preferred surgical intervention, physeal bar resection (Langenskiöld procedure) is technically demanding. This manuscript aims to illustrate the technical tricks and present an illustrative case of premature physeal arrest of the distal radius managed with a novel method for the Langenskiöld procedure, involving complete removal of the bar using a patient-specific guide in combination with an intramedullary endoscopy technique that facilitated direct observation.

Purpose: The Japan Clinical Oncology Group (JCOG) trial JCOG0505 demonstrated the statistically significant non-inferiority of paclitaxel plus carboplatin (TC) to paclitaxel plus cisplatin (TP) in terms of overall survival (OS) in metastatic or recurrent cervical cancer. In that trial, patients were randomly assigned, adjusting for institution and known prognostic factors. The objective of this ancillary study was to evaluate the appropriateness of the adjustment factors used to have randomly assigned treatments and to investigate new potentially useful prognostic factors of paclitaxel plus platinum for future randomized trials in metastatic or recurrent cervical cancer., Methods: The study subjects comprised 244 eligible patients in the JCOG0505 who were merged to have received either TC or TP. The effects of the following factors on OS were investigated using a Cox regression model taking into consideration the adjustment factors used in randomization in this trial (e.g., performance status [PS]) and other baseline factors, including platinum-free interval (PFI), pretreatment hemoglobin levels (PHLs), and pretreatment platelet counts (PPCs)., Results: The median follow-up was 17.6 months, and median OS was 18.0 months. The hazard ratio was 1.83 in patients with a PS of 1 or 2 (vs. 0; P = 0.0004; 95 % confidence interval [CI] 1.31-2.55), 2.92 in patients with a PFI of <6 months (vs. PFI of ≥12 months; P < 0.0001; 95 % CI 1.73-4.91), 2.09 in patients with a PFI of <12 months (vs. PFI of ≥12 months; P = 0.0034; 95 % CI 1.28-3.44), and 0.69 in patients with PHL higher than or equal to the median value (vs. less than the median; P = 0.016; 95 % CI 0.51-0.93). No significant differences were obtained for PPC or the other known factors., Conclusions: In addition to the known prognostic factor of PS, which was used as an adjusting factor, a PFI of <12 months and lower PHL were newly demonstrated to be associated with poor outcomes in patients with metastatic or recurrent cervical cancer. These new prognostic factors should be validated in future prospective trials., Clinical Trial Information: UMIN-CTR[ http://www.umin.ac.jp/ctr/ ] ID: C000000335.

Purpose: The aim of this study was to investigate the combination effects of pulsed HIFU (pHIFU) and phase-change nanodroplets (PCND) as a sensitizer on efficient induction of mechanical effects of pHIFU and chemically enhanced tumor growth inhibition for local anti-tumor therapy., Method: Changes in growth of colon 26 tumor tissue inoculated onto CDF1 mice were evaluated by the following treatments. (1) pHIFU exposure (1.1 MHz, 3.2 kW/cm(2), 300 cycles, and 50 ms interval) for 60 s, (2) PCND (1 %) injection, (3) adriamycin (4 mg/kg) injection, (4) pHIFU exposure after PCND injection, and (5) pHIFU exposure after PCND + adriamycin injection simultaneously., Results: Significant changes in tumor growth were observed in the group with combination of pHIFU and PCND, although single therapy did not show any significant difference. PCND enhanced mechanical tissue fractionation by pHIFU, which was detectable by Real-time tissue elastography. Moreover, the combination of pHIFU and PCND + Adriamycin suppressed the tumor growth for 2 weeks, and 3 of 4 mice did not show any sign of regrowth during the 30-day observation., Conclusion: The combination of pHIFU and PCND exerted a significant anti-tumor effect and may be a new candidate for treatment of locally advanced cancer.

Purpose: We evaluated the postnatal outcomes of patients with prenatally diagnosed agenesis of the corpus callosum (ACC), in conjunction with ventriculomegaly, as a tool for parental counseling., Materials and Methods: Through a retrospective review of maternal and infant records, we evaluated the postnatal outcomes of 21 patients with prenatally diagnosed ACC and fetal ventriculomegaly., Results: Ten of the 21 patients (48 %) were diagnosed with isolated ACC. Among these 10 patients, neurodevelopmental outcomes were normal in four, uncertain in one, and five demonstrated mild or moderate disabilities. The remaining 11 patients had ACC associated with either central nervous system (CNS) anomalies (7 of 11) or chromosomal abnormalities (4 of 11). The outcomes were estimated in nine of the 11 children; all nine had severe disabilities. The mortality rate of ACC, associated with other anomalies, was 29 % (2 of 7) in children with CNS anomalies and 75 % (3 of 4) for those with chromosomal abnormalities., Conclusion: If ACC with fetal ventriculomegaly is associated with other malformations, a poor outcome is highly likely. Although the outcome of isolated ACC with fetal ventriculomegaly was generally better, >50 % of the patients had mild or moderate neurodevelopmental disabilities. These findings provide useful information for parental counseling.

Concentrated growth factor (CGF) is an autologous leukocyte-rich and platelet-rich fibrin (L-PRF) biomaterial termed "second-generation platelet concentrate". CGF contains autologous osteoinductive platelet growth factors and an osteoconductive fibrin matrix. The purpose of this study was to assess the ability of CGF combined with bone marrow stromal cells (BMSCs) to heal critical-size rat calvaria defects in vivo and to modulate the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro. In the in-vivo study, the CGF group regenerated bone better than the control group, and combined therapy with CGF and BMSCs almost completely repaired critical-size bone defects within 12 weeks after surgery. In the in-vitro study, the CGF extract, at concentrations between 1 and 10%, promoted proliferation, osteogenic maturation, and mineralization of hTERT-E6/E7 human MSCs in a dose-dependent manner but had an inhibitory effect at higher concentrations. In conclusion, a CGF extract promoted the proliferation, osteogenic maturation, and mineralization of mesenchymal stem cells in vitro, and combination therapy with CGF and BMSCs resulted in excellent healing of critical-size bone defects in vivo.

The patient was a 13-year-old male with chief complaints of exertional chest pain and dyspnea. Cardiac murmur was suspected in a medical checkup at 1 month old, at which time he was diagnosed with subvalvular aortic stenosis. He had subsequently been under follow-up observation at a nearby hospital for subvalvular aortic stenosis. He was admitted to our department for surgery due to aggravation of symptoms that had occurred over the previous year. Transthoracic echocardiography after admission showed an abnormal structure in the subvalvular aortic area, and the maximum pressure gradient between the left ventricle and aortic valve was 84 mmHg. The preoperative valve area was 0.71 cm(2), as measured by the Doppler method. Measurement of valve area by the trace method was difficult. Transesophageal echocardiography (TEE) showed a septum-like structure extending from the ventricular septum in the subvalvular area. On 3D TEE, the valve areas in the systolic and diastolic phases were 0.86 and 0.49 cm(2), respectively. Postoperative echocardiography showed resection of the structure in the subvalvular area, and the postoperative course was favorable.

Objective: Quantitative knee cartilage T2 assessment on limited two-dimensional midsagittal or midcoronal planes may be insufficient to assess variations in normal cartilage composition. The purpose of this work was to reveal characteristic 3D distribution of T2 values in femoral cartilage in healthy volunteer knees., Materials and Methods: Sixteen volunteers were enrolled in this study. One knee joint in each volunteer was imaged using a 3D fast image employing steady-state acquisition cycled phases (FIESTA-C) sequence for modeling distal femoral morphology, as well as a sagittal T2 mapping of cartilage. 3D distribution of cartilage T2 values was generated for the femoral condyles. At each medial and lateral condyle, four regions of interest (ROI) were manually defined based on the cartilage covered by the 3D surface model of the medial and lateral menisci., Results: The 3D maps showed a relatively inhomogeneous distribution of cartilage T2 on the medial and lateral condyles. Cartilage T2 values in the internal half of the weight-bearing zone were significantly higher than those in all other zones on both lateral and medial condyles., Conclusions: Analysis of 3D distribution of femoral cartilage T2 may be valuable in determining the site-specific normal range of cartilage T2 in the healthy knee joint.

Purpose: The objective of this study was to evaluate the in vivo knee kinematics to assess the available functional motion of the characteristic mobile-bearing prosthesis design and to examine whether the artificial joint would work in vivo according to its design concept., Methods: We studied 14 knees (11 patients) implanted with the Vanguard RP Hi-Flex prosthesis. This prosthesis has a highly original form of post-cam called a PS saddle design with high compatibility, and with a rotating plate mobile-bearing mechanism. The cylinder-type post-cam is designed to enable contact in early flexion ranges, and to prevent paradoxical anterior femoral component movement. Each patient performed weight-bearing deep knee bending under fluoroscopic surveillance. Motion between each component including the polyethylene insert was analyzed using the 2D/3D registration technique., Results: The mean range of motion was 122.0°. The mean femoral component rotation for the tibial tray was 5.0°. No paradoxical anterior movement of the nearest point was confirmed between the femoral component and the tibial tray in the early flexion ranges. Initial contact of the post-cam was confirmed at a knee flexion angle of 33.8°. Subsequently, the wide contact of the post-cam was maintained until flexion reached 120° in all knees, but disengagement of the post-cam was observed in two knees when flexion was ≥130°., Conclusions: The results of this study demonstrated that the prosthesis design generally works in vivo as intended by its design concept. The present kinematic data may provide useful information for improvement of high-flex type prostheses.

Introduction: Acoustic radiation force (ARF) elastography is potentially useful for imaging the elasticity of human tissue. Because a "push wave" that is used to generate ARF is a long burst wave comparable to that used in regular clinical imaging, detailed investigation of its safety is required., Materials and Methods: We focus on the transient temperature rise in the far field, where the beam paths are overlapped. Soft tissue mimicking a phantom and bone samples were exposed to a 2-MHz plane wave for 20 s. The temperature rises in the far field were measured using a thermocouple. The temperature rises at 1 ms, the time required for the displacement measurement, were estimated by fitting the experimental results. The results showed that the thermosensitivity of the bone was 36 times higher than that of the phantom, and the use of a repeated push wave may have exceeded the allowable maximum temperature rise, 1°C, on the bone surface., Conclusion: In conclusion, the imaging area, including the path of the push wave, should be carefully checked and the time interval for consecutive use should be adjusted to prevent thermal risk on the surface of the bone.

Introduction: Joint space width (JSW) of hip joints on radiographs in normal population may vary by related factors, but previous investigations were insufficient due to limitations of sources of radiographs, inclusion of subjects with osteoarthritis, and manual measurement techniques. We investigated influential factors on JSW using semiautomatic computational software on pelvic radiographs in asymptomatic subjects without radiological osteoarthritic findings., Methods: Global and local JSW at the medial, middle, and lateral compartments, and the hip structural parameters were measured in asymptomatic, normal 150 cases (300 hips), using a customized computational software., Results: Reliability of measurement in global and local JSWs was high with intraobserver reproducibility (intraclass correlation coefficient) ranging from 0.957 to 0.993 and interobserver reproducibility ranging from 0.925 to 0.985. There were significant differences among three local JSWs, with the largest JSW at the lateral compartment. Global and medial local JSWs were significantly larger in the right hip, and global, medial and middle local JSWs were significantly smaller in women. Global and local JSWs were inversely correlated with CE angle and positively correlated with horizontal distance of the head center, but not correlated with body mass index in men and women. They were positively correlated with age and inversely correlated with vertical distance of the head center only in men., Conclusions: There were interindividual variations of JSW in normal population, depending on sites of the weight-bearing area, side, gender, age, and hip structural parameters. For accurate diagnosis and assessment of hip osteoarthritis, consideration of those influential factors other than degenerative change is important.

Purpose: The purpose of this study was to assess accurately the three-dimensional movements of the scapula and humerus relative to the thorax during internal/external rotation motion with abduction of the shoulder joint., Methods: Ten right shoulders of ten healthy volunteers were examined using a wide-gantry open magnetic resonance imaging (MRI) system. MRI was performed every 30° from 90° external rotation to 90° internal rotation of the shoulder joint., Results: The contribution ratio of the scapulothoracic joint was 12.5% about the long axis of the humerus during internal/external rotation motion. With arm position changes from 90° external rotation to 60° internal rotation, most movement was performed by the glenohumeral joint. Conversely, at internal rotation of ≥60°, the scapula began to markedly tilt in the anterior direction. At 90° internal rotation, the scapula was significantly tilted anteriorly (p < 0.05) when compared with the other positions., Conclusions: We clarified the existence of a specific scapulohumeral motion pattern, whereby the glenohumeral joint moves with internal rotation and the scapulothoracic joint moves with anterior tilt together with internal rotation motion of the shoulder joint.

The Dual Bearing Knee (DBK) prosthesis is a new concept which has a mobile-bearing insert. In May 2001, the posterior femoral condyle design of the DBK was changed to become smaller and there was a posterior shift in the base of the insert dish (Hi-Flex). Between 1998 and 2004, 371 DBKs (112 Hi-Flex and 220 Standard) were performed by one surgical team. There was a significant difference in postoperative flexion angle between the Hi-Flex and Standard DBKs (117.0° and 111.3°; p = 0.001). The delta flexion angle in the Hi-Flex (-2.4°) was significantly increased compared with that in the Standard DBK (-9.6°) (p = 0.001). In the Hi-Flex DBK, the postoperative flexion angle (5.7°) and the delta flexion angle (7.2°) were significantly larger than for the Standard DBK (p < 0.001). These results suggest that the flexion is greater for a design with smaller posterior condyle prosthesis and with a posterior shift in the base of the insert dish in CR mobile-bearing TKA.

Kaposiform hemangioendothelioma (KHE) is a rare tumor that occurs nearly exclusively during infancy and childhood. It has features common to both capillary hemangioma and Kaposi sarcoma and for that reason many terms have been used for these tumors including "Kaposi-like infantile hemangioendothelioma" and "hemangioma with Kaposi sarcoma-like features." KHE typically presents as an ill-defined, red to purple, indurated plaque and is often complicated by the Kasabach-Merritt phenomenon (KMP), a condition of severe thrombocytopenia and consumptive coagulopathy. Knowledge of the radiological findings of this uncommon tumor might be helpful for diagnosis. We present the MRI features of a case of KHE with neither typical skin lesions nor the Kasabach-Merritt phenomenon.

Higher complication rates and lower survivorship are still seen for total elbow arthroplasties compared to total knee and hip arthroplasties. This is partly due to polyethylene wear of the articular surface induced by excessive articular contact stress during elbow motion. The aim of this study was to dynamically evaluate in vivo three-dimensional elbow motion after total elbow arthroplasty. Twelve patients (15 elbows) who underwent operation with the Osaka University Model Total Elbow System were analysed using X-ray fluoroscopic imaging and a two-dimensional/three-dimensional registration technique, which could accurately estimate the three-dimensional spatial position of components. Valgus/varus angle and rotation between humeral and ulnar components showed wide variations among patients. Elbows with valgus angle and internal rotation >10 degrees could induce edge-loading of the articular surface. Component alignment, articular configuration, and soft-tissue balance can affect the kinematics of total elbow arthroplasty.

Introduction: Osseous defects in nonunited open fracture of the lower limbs are difficult to treat. Autogenous bone grafting is a promising treatment options, but a finite amount of autogenous bone graft is available from each individual and donor site morbidity remains a problem. These limitations have prompted the development and use of synthetic biomaterials such as hydroxyapatite (HA) ceramics. However, little information is available regarding the challenging cases such as nonunited open fractures The purpose of the present study is to evaluate the outcomes associated with the treatment of osseous defects in nonunited open fracture using novel HA ceramics., Methods: Twelve bones (4 femora and 8 tibias) in 11 patients (10 men and 1 woman), with an average age of 49.1 (range 19-71) years, with nonunited osseous defects after open fracture were treated by the grafting of HA ceramics alone or with autogenous iliac bone followed by internal or external fixation., Results: The patients were followed for an average of 25.2 months in average (range 10.3 -58.1 months). Finally, 11 of 12 fractures united clinically and radiographically, while one fracture required a second procedure for additional autogenous iliac bone grafting. The average time to union from the index surgery was 5.6 months (median 5.3 months, range 2.3-11 months.). Radiographs showed good incorporation of grafted HA into the host bone in most of the united cases. As a complication, transient wound drainage was found in two cases., Conclusion: The current protocol using the HA ceramics appears to be safe and efficacious for the treatment of osseous defects after the open fractures.

Growth arrest following physeal injury may result in severe limb deformity. We report a case of complex wrist deformity caused by injury to the distal radial physis resulting in radial shortening and abnormal inclination of the radial articular surface, which was successfully treated by gradual correction after computer simulation. The simulation enabled us to develop an appropriate operative plan by accurately calculating the axis of the three-dimensional (3D) deformity using computer bone models. In the simulative surgery with a full-size stereolithography bone model, an Ilizarov external fixator was applied to the radius such that its two hinges were located on the virtual axis of the deformity, which was reproduced in the actual surgery. This technique of 3D computer simulation is a useful alternative to plan accurate correction of complex limb deformities following growth arrest.

Introduction: Surgical results of correction of three-dimensional deformities with shortening of lower limbs by simple two-ring system of Taylor Spatial Frame have been reported. The deformities were caused by various kinds of skeletal disorders., Methods: Ten cases were successfully corrected using distraction osteogenesis, being one case showed recurrence of deformity due to the nature of the disease., Results: The ranges of corrected deformities were 5 degrees-55 degrees in coronal angulation, 2 degrees-47 degrees in sagittal angulation, and 5 degrees-40 degrees in rotational deformities. Amount of lengthening ranged from 1.2 to 6.0 cm. Pin-site infection occurred in five cases, being no other complications. External fixation index was longer in a group of rotational correction over 10 degrees., Conclusion: The current report seems the first series of cases with four-dimensional deformities treated by distraction osteogenesis by TSF and may help to determine the indication of use of TSF in case of treatment of patients suffering from deformities in the lower limbs.

Objective: In order to clarify the increased 2-deoxy-2-fluoro-(18)F-D: -glucopyranose ((18)F-FDG) accumulation in schwannoma by positron emission tomography (PET) analysis, immunohistochemical analysis for the factors involved in glucose transportation and vascular formation was performed., Materials and Methods: Twenty-six patients with schwannoma (13 men and 13 women) with ages ranging from 27 to 75 years, who received whole body (18)F-FDG PET scan, were enrolled for the present study. The retention index (RI) was calculated by dividing the increase in the standardized uptake value (SUVmax) at the delayed scan by the SUVmax in the early scan. SUVmax and RI were compared with the histologic variables, including the expression of glucose transporters 1 and 3, hexokinase II, vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), and microvascular density shown by CD31 immunohistochemistry., Results: Mean SUVmax values in the early and delayed scans were 2.64 +/- 1.47 and 2.71 +/- 1.57 (mean +/- SD), respectively. RI was -2.5 +/- 21 (percentage). SUVmax showed a positive correlation with the tumor size (tumor size <5 cm, 2.06 +/- 0.72; >5 cm, 3.95 +/- 1.89; p < 0.05) and the microvascular density (negative density, 2.16 +/- 1.12; positive density, 3.56 +/- 1.67; p < 0.05). RI correlated with VEGF/VPF expression in the tumors (negative expression, -11 +/- 6.1; positive expression, 13 +/- 8.1; p < 0.05). Other factors showed no correlation with SUVmax or RI., Conclusions: Microvascular density and vascular permeability of the tumor are suggested to affect the enhanced (18)F-FDG accumulation in schwannoma.

Introduction: Patients undergoing total hip arthroplasty (THA) exhibit changes in the alignment of lower extremities following the procedure, and these changes may exert effects on other joints over the long-term. Therefore, we investigated the course of knee osteoarthritis in patients undergoing long-term follow up after THA, in addition to the relationship between the course of knee osteoarthritis and alignment of lower extremities., Materials and Methods: We retrospectively performed radiographic evaluation of the course of knee osteoarthritis (OA) after THA. Thirty patients undergoing successful unilateral THA were followed for a minimum of 10 years., Results: Eleven (33%) subjects showed progression of medial tibiofemoral OA on the non-THA side, while only three (10%) showed progression on the THA side, and this difference was significant (P = 0.033). In addition, the mechanical axes on the THA side passed through more lateral regions of the tibial plateau than those on the non-THA side (P = 0.044)., Conclusion: Medial tibiofemoral OA on the THA side was less likely to deteriorate than on the non-THA side. The reduced vulnerability to OA progression on the THA side may be due to the lower offset and resultant lateral shift in mechanical axes.

In revision surgery with proximal femoral bone loss, progressive bone atrophy due to stress shielding remains a concern. We compared 2-year radiological results between two types of cementless long titanium stems with different configurations and surface coatings. Of 17 hips implanted with a wholly hydroxyapatite-coated stem, 12 (71%) exhibited stress shielding of the second degree or higher according to Engh's criteria, and the mean relative bone mass index decreased from 22.1% pre-operatively to 14.6% at 2 years post-operatively. In 23 hips implanted with a sand-blasted, conically shaped stem, no hip showed stress shielding of the second degree or higher. The mean relative bone mass index increased from 21.6% to 31.4%. These results indicate that the configuration and surface coating of the stem have a significant influence on proximal bone remodelling after revision surgery.

Growth arrest in the epiphyseal plate during childhood often causes both periarticular deformities and limb length discrepancy, leading to compartmental osteoarthrosis and gait disturbance or spinal disorders, respectively. Distraction osteogenesis using external fixators with hinge systems appears to be useful for the simultaneous correction of deformity and shortening. In this paper, we evaluated cases of lower limbs with periarticular deformities and limb length discrepancy after epiphyseal plate injury that has been treated by distraction osteogenesis using external fixators. This is the first report regarding the outcomes of distraction osteogenesis for a group of patients having deformity and limb length discrepancy due to traumatic arrest of the physis. Successful outcomes may promise the use of this method as the first choice for the treatment of growth disorders after the arrest of the epiphyseal plate in the lower limbs. However, treatment under 20 years of age may provide a better outcome with a lower incidence of complications.

Introduction: Preoperative femoral templating for total hip arthroplasty (THA) has been performed by antero-posterior radiographs of both hips which should be taken with the femur rotated internally to reduce the effect of femoral anteversion. However, there is no criterion to evaluate the optimal rotated radiograph. Here, we quantitatively investigated 50 femora whether the thickness of the lesser trochanter (TLT) was useful when evaluating the femoral rotation, and assessed the effect of prosthetic templating on the inappropriate rotated radiographs., Materials and Methods: We assessed 50 femora of 46 consecutive osteoarthritic patients using "synthetic X-ray" based on computer tomography (CT) images, which can be displayed as virtual plain radiographs with any magnification and any projected direction such as plain radiographs. We made four femoral radiograph groups of different rotation prepared (neutral, 15 degrees, 30 degrees, and 45 degrees external rotation), and measured the TLT. We also templated femoral stem on the different rotated synthetic X-ray of each patient, and investigated the effect of inappropriate rotated radiograph by the measurement of the position and the size of the stem., Results: Seventy-four percent of the neutral rotational group had less than 5 mm of the TLT. While 30 degrees and 45 degrees external rotation group had few cases with less than 5 mm of the TLT. Compared to the neutral group, smaller stem size was selected in more than 80% cases of 30 degrees and 45 degrees external rotational group, and the stem position in these two groups was more than 5 mm proximally., Conclusion: We suggest that when templating femoral stem, this criterion "the TLT is less than 5 mm" reduces some risks by inappropriate rotated radiograph.

Pycnodysostosis is a rare hereditary disease, characterized by systemic bone sclerosis. The most important orthopedic problem in this condition is the recurrent pathological fracture of long bones. In this paper, the surgical results for fractures of six limbs (three femurs and three tibias) in five cases of pycnodysostosis are reported. Five limbs achieved fracture union and union is developing in one tibia after intramedullary nail (IM) nailing or Ilizarov external fixation (IEF), although fracture line tends to persist for longer periods of time. One femoral fracture was treated by IM nailing, and one femoral and one tibial fracture were treated by IEF leading to final bone union. One femoral and one tibial fracture were initially treated by IEF, and were treated by IM nailing after re-fracture. One tibial fracture was initially treated by IEF leading to a failure of union, and was converted to IM nailing. All cases are able to walk; one case requires a single crutch. Infection was noted in two limbs after IM nailing following IEF. Fixation with IM nail was effective in preventing re-fracture as well as in alignment correction. Although the surgical technique is more difficult, IM nailing in the initial surgery may be a better choice for achieving successful union while reducing the risk of re-fracture or infection.

We report a rare case of chondroblastoma arising from the ischium which showed an increased (18)F-FDG uptake. Chondroblastoma is an uncommon lesion and usually involves the epiphysis of long bones. However, in this case, the tumor appeared as a well-defined osteolytic lesion in the ischium on radiographs. MR imaging demonstrated two components in the tumor: a solid one and a multilobular cystic component. (18)F-FDG PET imaging revealed an increased uptake in the ischium. The (18)F-FDG uptake resembled the results observed in malignant bone tumors. A histological diagnosis of chondroblastoma was obtained from tissue of an open biopsy. An immunohistochemical analysis demonstrated weak expression of both Glut-1 and HK-II. These findings suggest that Glut-1 and HK-II expression are not strongly related to FDG uptake in chondroblastoma.

We reported a rare revision case necessitated by massive metallosis of a metal head due to a fragmented ceramic screw which had been extraarticularily used in the primary THA here and reviewed previous literature about metallosis of metal heads associated with ceramic materials. The ceramic screw had been used for the fixation of a bone graft and reattachment of the greater trochanter in the primary THA. Scanning electron microscope analysis revealed large alumina ceramic particles embedded on the bearing surface of the polyethylene. It has previously been pointed out that metallosis of an inner head occurred in bipolar case due to a fracture of the ceramic screws in contact with a proximally migrated outer head. However, this case showed that if a ceramic screw fragmented even though it was used outside of the hip joint, the fragments could migrate into bearing surface and cause serious metallosis of the metal head. Thus, we recommend that surgeons should pay special attention to the radiographic signs of ceramic failure or metallosis such as a change of the metal head contour, if an aseptic loosening or severe osteolysis is observed in a THA in which ceramic materials were used near the hip joint. And, when a surgical revision is planned, the surgeon should be prepared to exchange with a new ceramic head.

A case of deformity and shortening after post-traumatic growth arrest treated using the Taylor Spatial Frame (Smith & Nephew, Tennessee, USA) is presented. This is the first report showing the application of the frame for post-traumatic deformity in the distal femur, and successful outcomes promise utilization of the frame even for correction of severe deformity in the distal femur.

Split-hand/split-foot malformation (SHFM) is a congenital limb malformation characterized by a median cleft of hand and/or foot due to the absence of central rays. Five loci for syndromic and non-syndromic SHFM, termed SHFM1-5, have been mapped to date. Recently, a 0.5 Mb tandem genomic duplication was found at chromosome 10q24 in SHFM3 families. To refine the minimum duplicated region and to further characterize the SHFM3 locus, we screened 28 non-syndromic SHFM families for tandem genomic duplication of 10q24 by Southern blot and sequence analysis of the dactylin gene. Of 28 families, only two showed genomic rearrangements. Representative patients from the two families exhibit typical SHFM, with symmetrically affected hands and feet. One patient is a familial case with a 511,661 bp tandem duplication, whereas the second is a sporadic case arising from a de novo, 447,338 bp duplication of maternal origin. The smaller duplication in the second patient contained the LBX1, BTRC, POLL, and DPCD genes and a disrupted extra copy of the dactylin gene, and was nearly identical to the smallest known duplicated region of SHFM3. Our results indicate that genomic rearrangement of SHFM3 is rare among non-syndromic SHFM patients and emphasize the importance of screening for genomic rearrangements even in sporadic cases of SHFM.

Objective: Extraskeletal mesenchymal chondrosarcoma (EMC) is a rare soft-tissue tumor that most arises in young adults. Because of its rarity, few imaging studies have been reported to date. The purpose of this study was to elucidate the imaging features of this tumor., Design: We conducted a multi-institutional study in cooperation with five referral cancer centers in Japan. Imaging findings of ten new EMC cases, including conventional radiography, computed tomography (CT), and magnetic resonance imaging (MRI), performed at each institute, were reviewed along with clinical features., Patients: Ten patients with EMC, who had been treated at each hospital from 1990 to 2001, participated in this study., Results and Conclusions: Soft-tissue masses with well-demarcated, dense and granular calcification were most frequently observed on plain radiographs and CT scans. T2-weighted MR images most clearly depicted a two-component structure composed of calcified and uncalcified areas, and enhanced MRI showed inhomogeneous enhancement in both areas. Although the sensitivity and specificity of these findings are unknown, they might be characteristic and have diagnostic value for this rare tumor.

Chronic expanding hematoma is a rare presentation of a hematoma characterized by a persistent increase in size for more than a month after the initial hemorrhage. We present a 65-year-old man with a chronic expanding hematoma in his ilium who was receiving anticoagulant treatment. The patient had a delayed manifestation of a femoral neuropathy with massive bone destruction. 2-Deoxy-[18F]fluoro-D: -glucose (FDG) positron emission tomography (PET) imaging revealed an increased uptake in the rim of the mass in images acquired 1 h after FDG injection. FDG-PET scans were performed using a dedicated PET scanner (HeadtomeV/SET2400 W, Shimadzu, Kyoto, Japan), and the PET data for the most metabolically active region of interest (ROI) were analyzed. The maximum standardized uptake value (SUVmax) was set to a cut-off point of 3.0 to distinguish between benign and malignant lesions. The SUVmax of the patient's lesion was 3.10, suggesting a malignant lesion. The characteristics of FDG-PET images of chronic expanding hematomas, including the uptake of FDG in the peripheral rim of the mass as a result of inflammation, should be recognized as a potential interpretive pitfall in mimicking a sarcoma.

The purpose of this study was to compare mid-term results of mobile-bearing and fixed-bearing in bilateral total knee arthroplasty (TKA). Twenty-two patients underwent bilateral TKA with a mobile-bearing prosthesis (Rotaglide, Corin, UK) on one side and a fixed-bearing prosthesis (NexGen-CR, Zimmer, USA) on the other. There were 21 female patients, and in 18 patients, the diagnosis was rheumatoid arthritis. The average age was 59.6 (35-78) years. In all procedures, the posterior cruciate ligament was retained and patella re-surfaced. The average follow-up in the mobile-bearing group was 98 (79-107) months and 96 (79-107) months in the fixed-bearing group. At the final follow-up, the knee score was 91.8 points and 91.1 points, respectively, and the function score 65.5 points. The range of motion was similar in the two groups (1.1-106.9 degrees; 0.4-106.9 degrees). Five patients favoured the fixed-bearing prosthesis, but 16 found no difference. In patients with bilateral TKA, there was no difference in the short-term result between mobile-bearing and fixed-bearing prostheses.

We developed neural tube-like structures accompanying neural crest-like cells by treating embryonic stem (ES) cells with retinoic acid. The structures contained pseudostratified Nestin+Vimentin+ neuroepithelial cells surrounded by Masson staining+ basement membrane. betaIIItubulin+Synaptophysin+ mature neurons and glial fibrillary acidic protein (GFAP)+ glial cells dispersed outside of the membrane. Addition of Noggin to the culture induced prominent proliferation of the neuroepithelial cells, leading to epithelial hyperstratification of the structures. mRNAs of transcription factors essential for forebrain development such as Emx1/2 and Pax6 were specifically expressed and Islet1+Lim1/2- motoneurons appeared by the addition of Noggin. In contrast, basic fibroblast growth factor (bFGF) promoted enlargement of central lumen and elongation of the structures. mRNAs of caudal markers, Gbx2, Cdx2 and Hoxb4/9 were expressed and Lim1/2+ spinal motoneurons appeared by the addition of bFGF. Addition of BMP-4 similarly brought about mild enlargement of central lumen of the structures. Interestingly, the addition of BMP-4 induced Slug+ neural crest-like cells surrounding the tube-like structures. mRNAs of Snail and dHand, other markers for neural crest cells, were also expressed by the addition of BMP-4. These results suggest that Noggin lead the neural-tube like structures to forebrain fate, whereas bFGF was involved in the caudalization. BMP-4 was implicated in emergence of the neural crest-like cells. Differentiation of ES cells by the present methods may mimic neurulation and subsequent neural development of early embryos, and elucidates the opposite effects of Noggin and bFGF for the neural tube development.

The main principle of bone tissue engineering strategy is to use an osteoconductive porous scaffold in combination with osteoinductive molecules or osteogenic cells. The requirements for a scaffold in bone regeneration are: (1) biocompatibility, (2) osteoconductivity, (3) interconnected porous structure, (4) appropriate mechanical strength, and (5) biodegradability. We recently developed a fully interconnected porous hydroxyapatite (IP-CHA) by adopting the "form-gel" technique. IP-CHA has a three-dimensional structure with spherical pores of uniform size that are interconnected by window-like holes; the material also demonstrated adequate compression strength. In animal experiments, IP-CHA showed superior osteoconduction, with the majority of pores filled with newly formed bone. The interconnected porous structure facilitates bone tissue engineering by allowing the introduction of bone cells, osteotropic agents, or vasculature into the pores. In this article, we review the accumulated data on bone tissue engineering using the novel scaffold, focusing especially on new techniques in combination with bone morphogenetic protein (BMP) or mesenchymal stem cells.

We present two cases of peripheral nerve schwannoma which showed an increased accumulation of 2-deoxy-[(18)F] fluoro-D-glucose (FDG) in the tumors on positron emission tomography (PET) imaging acquired at both 1 h (early phase) and 2 h (delayed phase) after FDG injection. FDG-PET scans were performed with a dedicated PET scanner (HeadtomeV/ SET2400 W, Shimadzu, Kyoto, Japan) and the PET data analyzed the most metabolically active region of interest (ROI). We set the maximum standardized uptake value (SUV max) with a cut-off point of 3.0 to distinguish benign and malignant lesions. Although the mechanism responsible for the increased FDG uptake in benign schwannomas remains unknown, we discuss our findings in the context of tumor cellularity and briefly review other studies on the subject.

We reviewed 21 patients with rheumatoid arthritis who had a total ankle replacement between 1984 and 2000. The average follow-up was 72 (15-169) months. Clinical results were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) score. At the latest review, three ankles had been revised. Two ankles were excellent, seven good, three fair, and 12 poor. Eleven patients with 13 ankles had residual pain, with radiographs showing a high incidence of radiolucent lines. Migration of the tibial component was seen in 13 ankles and collapse of talus in nine. Although clinical results were poor, patient satisfaction was not.

Objective: To characterize the radiological and clinicopathologic features of cystic synovial sarcoma., Design and Patients: Seven patients with primary cystic synovial sarcoma were evaluated. Computed tomography (CT) and magnetic resonance (MR) imaging were undertaken at the first presentation. The diagnosis of synovial sarcoma was made on the basis of histological examinations followed by molecular analysis. Radiological and clinicopathologic findings were reviewed., Results: CT showed well-defined soft tissue mass without cortical bone erosion and invasion. Calcification was seen at the periphery of the mass in three cases. T2-weighted MR images showed multilocular inhomogeneous intensity mass in all cases, five of which showed fluid-fluid levels. On gross appearance, old and/or fresh hematomas were detected in six cases. In the one remaining case, microscopic hemorrhage in the cystic lumen was proven. Four cases had poorly differentiated areas. In five cases prominent hemangiopericytomatous vasculature was observed. Histologic grade was intermediate in one tumor and high in six. One case had a history of misdiagnosis for tarsal tunnel syndrome, one for lymphadenopathy, two for sciatica and two for hematoma., Conclusion: All cystic synovial sarcomas demonstrated multilocularity with well-circumscribed walls and internal septae. Synovial sarcoma should be taken into consideration in patients with deeply situated multicystic mass with triple signal intensity on T2-weighted MR imaging.

Objective: In patients with non-traumatic osteonecrosis of the femoral head (ONFH), the shoulder is one of the major affected sites secondary to the proximal and distal femur in cases of multiple osteonecrosis. The present study attempted to investigate whether technetium bone scintigraphy is useful for screening of non-traumatic osteonecrosis of the shoulder (ONS)., Design and Patients: A total of 170 shoulder joints in 85 patients with ONFH were evaluated by bone scintigraphy and the findings compared with those of magnetic resonance imaging (MRI). The MR diagnosis was used as the gold standard., Results: Based on the diagnosis by MRI, ONS was detected in 43 shoulders of 27 patients (25%). All necrotic lesions were located in the humeral head. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value of bone scintigraphy for ONS detection were 65%, 81%, 77%, 54% and 87%, respectively. When the necrotic angle of the lesions on the mid-coronal MRI was more than 40 degrees, the sensitivity of bone scintigraphy for ONS detection increased to 88% (21/24 shoulders)., Conclusion: Bone scintigraphy may be useful for demonstrating medium or large ONS lesions on screening of patients with ONFH.

We report three cases of spinal osteoblastoma with ossification of the ligamentum flavum (OLF) adjacent to the tumor. The patients in this report, all young adults, had no symptoms except for back pain. Computed tomography (CT) demonstrated a typical radiolucent nidus in the spinal pedicle/lamina with a dense sclerotic rim. In addition, ectopic bone formation at the insertion point of the ligamentum flavum adjacent to the tumor was clearly illustrated. Magnetic resonance imaging (MRI) revealed the tumor and surrounding inflammatory responses, but OLF was not detected clearly. Histological examination revealed endochondral ossification of the ligamentum flavum that is quite unusual for normal young adults. Immunohistochemical assays in one case demonstrated that bone morphogenetic protein (BMP)-2/4 was expressed in the osteoblastic tumor cells. This case raises the possibility that BMPs secreted from the tumor cells triggered ectopic ossification in the spinal ligament.

Objective: To characterize the radiologic features of postradiation sarcomas arising in the pelvic bones following treatment for uterine cervical carcinoma., Design and Patients: Five patients who developed postradiation sarcomas in the pelvic bones following radiation therapy for carcinoma of the uterine cervix within the irradiated field were evaluated. Pelvic radiographs, computed tomography (CT) and magnetic resonance (MR) imaging were undertaken in all patients. Histologic confirmation of the tumor type was obtained., Results: Three patients whose tumors were characterized as an osteosarcoma, an angiosarcoma and a malignant fibrous histiocytoma (MFH) showed a large round or oval mass mainly in the sacroiliac joint which extended into the posterior gluteal soft tissues. In a fourth patient an osteosarcoma developed in the central ilium extending widely into the soft tissues both anteriorly and posteriorly, with calcified areas within the extraosseous mass. The fifth patient had a MFH which showed osteolytic destruction of the cortex of the acetabulum, and minimal soft tissue extension. There were no specific features or signal intensity changes on MR imaging to differentiate these cases from primary sarcomas., Conclusion: Postradiation sarcoma must be considered in patients with uterine carcinoma when a soft tissue mass is seen in the previously irradiated field, especially if the mass is posterior to the sacroiliac joint and the latent period is more than 5 years.

Thirty-two polyethylene sockets and 22 femoral heads were retrieved because of aseptic loosening more than 9 years after total hip arthroplasty. The volumetric wear rates of the retrieved polyethylene sockets were significantly greater in those coupled with an alumina head (P < 0.05). The retrieved alumina heads showed significantly better surface roughness and roundness than heads of Co-Cr and of stainless steel (P < 0.05). However, no significant difference was found in polyethylene quality demonstrated as fusion defects among the three different groups. The present study suggests that maintaining better surface roughness and roundness of the femoral heads does not always result in an in vivo reduction of polyethylene wear.

In a prospective study of cementless total hip arthroplasty, 19 hips in 17 patients (Group A) were allowed full weight-bearing immediately after the operation while 18 hips in 16 patients (Group B) were first allowed weight-bearing after 6 weeks. Patients were matched for sex, age at surgery, height, weight, and follow-up period and there were no significant differences in hip scores between the two groups. Rehabilitation to gain walking ability with a cane lasted 5.8 days for Group A and 44.8 days for Group B (P = 0.0001). The hospital stay after surgery was 30.1 days for Group A and 46.7 days for Group B (P = 0.006). All patients showed bone ingrowth radiographically. There were no complications in either group.

Purpose: Osteosarcoma is a common malignant tumor. The first choice of treatment plan for osteosarcoma is chemotherapy. In particular, preoperative chemotherapy is most important in clinical treatment in orthopedics. In these chemotherapies, multiple anticancer drugs such as Adriamycin (ADM), CDDP, cyclophosphamide (CPM), methotrexate (MTX) and vincristine (VCR) are commonly used in combination. Recently, anticancer drugs have been shown to trigger apoptosis in various cancer cells. However, many studies on this topic have been examined using leukemia cell lines, and many kinds of cancer cells established from solid tumor are resistant to the induction of apoptosis by anticancer drugs. So in this study, we examined the effects of the anticancer drugs ADM, CDDP, CPM, MTX and VCR on osteosarcoma cells in vitro. We also examined the signaling pathways of each anticancer drug by studying the induction of apoptosis and activation of caspases in the osteosarcoma cells., Methods: We examined the effects of the anticancer drugs ADM, CDDP, CPM, MTX and VCR, which are used clinically for the treatment of osteosarcoma, on cells of the human osteosarcoma (HOS) cell line. The cytotoxic effects of the anticancer drugs were evaluated using the MTT assay. We used both flow cytometry and activation of caspases to confirm the induction of apoptosis in the HOS cells. To dissect the pathway of the caspase cascade in apoptosis in HOS cells, we used the tetrapeptides YVAD-CHO, DMQD-CHO, VEID-CHO and IETD-CHO, which selectively inhibit caspase-1, -3, -6 and -8, respectively., Results: ADM, CDDP, CPM and VCR, but not MTX, induced death of HOS cells in a dose-dependent manner. CDDP at 10 microM, CPM at 7.5 microM, ADM at 20 microM and VCR at 150 microM caused 80% cell death of HOS cells after 12 h. However, the percentages of apoptotic cells were 5.6% (medium alone), 75.9% (CDDP), 20.0% (CPM), 22.2% (ADM), 20.5% (VCR) and 13.1% (MTX). In addition, direct measurement of caspase-3 activity revealed that CDDP but not the other drugs activated caspase-3 in HOS cells. These analyses revealed that only CDDP induced apoptosis of HOS cells via activation of caspases. Furthermore, DMQD-CHO, VEID-CHO and IETD-CHO inhibited CDDP-induced apoptosis of HOS cells, suggesting that caspase-3, -6 and -8 are involved in the signaling pathway of CDDP-induced apoptosis. In contrast, none of the caspase inhibitors inhibited cell death induced by the other anticancer drugs., Conclusions: This study demonstrates that CDDP specifically induces apoptosis via activation of caspases and the other anticancer drugs induce death of HOS cells via different signaling pathways. It also demonstrates that caspase-8 is a key molecule in the earliest stage of the signaling pathway of CDDP-induced apoptosis of HOS cells, and caspase-3 works downstream of caspase-8.

Three cases of granular cell tumor (GCT) of the subcutis are presented. Computed tomography showed a mass isodense with muscle with an ill-defined margin. Magnetic resonance imaging showed a mass with inhomogeneous low signal intensity on both T1- and T2-weighted-images. Another characteristic feature of subcutaneous GCT is its attachment in part to muscle. Histological examination confirmed the diagnosis in all cases.

Purpose: Stress conditions, such as glucose starvation and hypoxia, that induce glucose-regulated proteins (GRPs) in cells, are seen in most solid tumors. These conditions have been shown to cause cellular resistance to multiple anticancer drugs, such as etoposide, doxorubicin, and camptothecin. We examined the effect of the GRP-inducing conditions on cellular sensitivity to cisplatin and carboplatin, which are widely used drugs against solid tumors., Methods: We generated the GRP-inducing culture conditions by exposing cells to 2-deoxyglucose (2DG), calcium ionophore A23187 and tunicamycin, and examined cellular sensitivity to cisplatin and carboplatin under these conditions. We next measured platinum accumulation and DNA-bound platinum in 2DG-stressed cells after cisplatin exposure., Results: The GRP-inducing stress conditions led to cellular sensitization to cisplatin and carboplatin. This sensitization was reversible, as the cellular sensitivity returned to normal levels 12 h after removal of 2DG. Platinum accumulation and DNA-bound platinum that were found immediately after exposure to cisplatin for 1 h were slightly increased in 2DG-stressed cells as compared with nonstressed cells. After a drug-free recovery incubation of 8 h, the DNA-bound platinum in the nonstressed cells was reduced by 33% while the amount in the 2DG-stressed cells was sustained at the initial levels., Conclusions: These results indicated that the decreased removal of platinum-DNA adducts was associated with increased sensitivity to cisplatin and carboplatin in the stressed cells. The sensitization of cancer cells under the GRP-inducing stress conditions would explain, in part, the clinical potency of platinum drugs against solid tumors.

Focal fibrocartilaginous dysplasia (FFCD) is a rare condition causing tibia vara in childhood. It is characterized by progressive tibia vara in young children with a characteristic radiographic lesion. This paper is thought to be the first to describe FFCD exhibiting florid periosteal reaction at the time of presentation with a subtle faint osteolytic lesion in the diametaphysis of the proximal tibia.