Epigenetic regulation of interleukin-8, an inflammatory chemokine, in osteoarthritis.

OBJECTIVE: To determine whether altered IL8 methylation status is associated with increased expression of IL8 in human osteoarthritic (OA) chondrocytes. METHODS: IL8 expression levels and the percentage CpG methylation in human chondrocytes were quantified by qRT-PCR and pyrosequencing in OA patients and in non-OA osteoporotic controls. The effect of CpG methylation on IL8 promoter activity was determined using a CpG-free vector; co-transfections with expression vectors encoding nuclear factor-kappa B (NF-κB), AP-1 and C/EBP were subsequently undertaken to analyse for IL8 promoter activity in response to changes in methylation status. RESULTS: IL8 expression in OA patients was 37-fold higher than in osteoporotic controls. Three CpG sites in the IL8 promoter were significantly demethylated in OA patients. Multiple regression analysis revealed that the degree of methylation of the CpG site located at -116-bp was the strongest predictor of IL8 expression. In vitro DNA methylation was noted to decrease IL8 promoter basal activity. Furthermore, NF-κB, AP-1 and C/EBP strongly enhanced IL8 promoter activity whilst DNA methylation inhibited the effects of these three transcription factors. CONCLUSIONS: The present study demonstrates the key role of DNA methylation status on the expression of IL8 in human chondrocytes. We demonstrate a quantitative relationship between percentage methylation and gene expression within clinical samples. These studies provide direct evidence linking the activation of IL8, DNA demethylation and the induction of the OA process with important therapeutic implications therein for patients with this debilitating disease.

Influence of intramedullary stress on cervical spondylotic myelopathy.

STUDY DESIGN: A cross-sectional analysis. OBJECTIVE: To examine whether intramedullary stress is related to the appearance of symptoms in cervical spondylotic myelopathy (CSM). SETTING: Japan. METHODS: Thirty-three consecutive patients with CSM and 30 consecutive patients without CSM were enrolled. A total of 99 disc levels from C3 to C6 in 33 patients with CSM were divided into two groups: 33 disc levels with high signal intensity (HSI) on T2-weighted magnetic resonance image (HSI group) and 66 disc levels without HSI (Non-HSI group). Ninety disc levels from C3 to C6 in patients without CSM were set up in a control group. Intramedullary stress value at each level was analyzed using the finite element method. Stress was compared among the three groups. A cutoff value of stress to present HSI was investigated from receiver operator characteristics (ROC) curve. RESULTS: In all the patients with CSM, the disc level with HSI presented the highest stress among the three disc levels evaluated. The stress was 3.16 ± 0.86 kPa (mean ± s.d.) in the HSI group, 1.81 ± 0.72 kPa in the Non-HSI group and 1.01 ± 0.37 kPa in the control group. The stress differed significantly among the three groups (P<0.0001). The qualified cutoff value derived from the ROC curve was 2.30 kPa (sensitivity 78.8%, specificity 91.9%). None of the disc levels in the control group exceeded 2.30 kPa. CONCLUSION: HSI was strongly associated with intramedullary stress. Threshold of intramedullary stress to present HSI that related closely to the symptoms of myelopathy was revealed.

Coexistence of fibrotic and chondrogenic process in the capsule of idiopathic frozen shoulders.

OBJECTIVE: To analyze changes in the capsule from idiopathic frozen shoulders and clarify their etiology. MATERIALS AND METHODS: Samples (the rotator interval capsule, middle glenohumeral ligament (MGHL), and inferior glenohumeral ligament (IGHL)) were collected from 12 idiopathic frozen shoulders with severe stiffness and 18 shoulders with rotator cuff tears as a control. The number of cells was counted and the tissue elasticity of the samples was calculated by scanning acoustic microscopy (SAM). The amount of glycosaminoglycan content was assessed by alcian blue staining. Gene and protein expressions related to fibrosis, inflammation, and chondrogenesis were analyzed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Furthermore, the total genes of the two groups were compared by DNA microarray analysis. RESULTS: The number of cells was significantly higher and the capsular tissue was significantly stiffer in idiopathic frozen shoulders compared with shoulders with rotator cuff tears. Staining intensity of alcian blue was significantly stronger in idiopathic frozen shoulders. Gene expressions related to fibrosis, inflammation, and chondrogenesis were significantly higher in idiopathic frozen shoulders compared with shoulders with rotator cuff tears assessed by both qPCR and DNA microarray analysis. CONCLUSION: In addition to fibrosis and inflammation, which used to be considered the main pathology of frozen shoulders, chondrogenesis is likely to have a critical role in pathogenesis of idiopathic frozen shoulders.

Clinical significance of intramedullary Gd-DTPA enhancement in cervical myelopathy.

STUDY DESIGN: Prospective multicenter study. OBJECTIVE: To clarify the significance of intramedullary Gd-DTPA enhancement in cervical myelopathy, the prevalence, morphologic features, clinical relevance and postoperative change were investigated. SETTING: Four hospitals in Japan. METHODS: A total of 683 patients with cervical myelopathy who underwent decompressive surgery were consecutively examined. T1, 2 and Gd-DTPA-enhanced MRI were taken before surgery. Fifty consecutive cases without intramedullary enhancement were allocated in the non-enhancement group. The following variables were investigated: prevalence of the enhancement, the morphologic feature, the relationship between the enhancement and T2 high-intensity areas, the change of the Japanese Orthopedic Association (JOA) score for cervical myelopathy and the change of the enhancement after surgery. RESULTS: Intramedullary enhancement was observed in 50 cases (7.3%). The enhancements were observed between the most severely compressed disc and the cranial half of the lower vertebral body. On axial images, they were observed at the posterior or posterolateral periphery of the spinal cord. Enhancement areas were observed within T2 high-intensity areas and smaller than them. The preoperative JOA score was 9.8+/-2.8 points in the enhancement group and 9.8+/-3.3 points in the non-enhancement group (NS). The postoperative JOA score was 12.7+/-2.9 points in the enhancement group and 14.2+/-2.4 in the non-enhancement group (P=0.006). Intramedullary enhancement disappeared in 60% of the patients 1 year after surgery. CONCLUSION: Intramedullary enhancement indicated not the severity of preoperative symptoms, but a sign of a worse prognosis.

Degenerative rotator cuff tear, repair or not repair? A review of current evidence.

INTRODUCTION: We review the literature and highlight the important factors to consider when counselling patients with non-traumatic rotator cuff tears on which route to take. Factors include the clinical outcomes of surgical and non-surgical routes, tendon healing rates with surgery (radiological outcome) and natural history of the tears if treated non-operatively. METHODS: A PRISMA-compliant search was carried out, including the online databases PubMed and Embase™ from 1960 to the end of June 2018. FINDINGS: A total of 49 of the 743 (579 PubMed and 164 Embase™) results yielded by the preliminary search were included in the review. There is no doubt that the non-surgical route with an appropriate physiotherapy programme has a role in the management of degenerative rotator cuff tears. This is especially the case in patients with significant risk factors for surgery, those who do not wish to go through a surgical treatment and those with small, partial and irreparable tears. However, rotator cuff repair has a good clinical outcome with significant improvements in pain, range of motion, strength, quality of life and sleep patterns.

Bioactive TiNbSn alloy prepared by anodization in sulfuric acid electrolytes.

The bioactivity of anodized near-ß TiNbSn alloy with low Young's modulus prepared in sulfuric acid electrolytes was examined to explore the osseointegration mechanism with a focus on the role of anodic oxide. Hydroxyapatite (HA) precipitated on the surface of anodic oxide following immersion in Hank's solution, and precipitation accelerated with increase in the sulfuric acid concentration of the electrolyte. HA is formed on the surface of as-anodized oxide without subsequent annealing or hot water (HW) treatment. This outcome differs from that of a previous study using anodized TiNbSn alloy prepared in acetic acid electrolytes requiring for subsequent HW treatment. It was found that the oxide anodized in sulfuric acid electrolyte contains a large amount of internal pores and is highly crystallized thick TiO2, whereas the same prepared in the acetic acid electrolyte is low crystalline thin TiO2 containing a small amount of pores. The present anodized TiNbSn alloy is preferred for maintaining the low Young's modulus of the alloy and eliminating the subsequent treatment to increase the Young's modulus. A model to rationalize the bioactivity of the present anodic oxide is proposed based on the series of studies. It is concluded that the sulfuric acid electrolyte is favorable for both HA formation and low Young's modulus, and the bioactivity is attributed to the anodic TiO2 that facilitates incorporation of bone ingredients.

The relationship between the glenoid track and the range of shoulder motion: A cadaver study.

INTRODUCTION: The concept of the glenoid track has been proposed to evaluate the risk of dislocation. The glenoid track width was demonstrated to be 84% of the glenoid width in cadaveric shoulders and 83% in live shoulders. HYPOTHESIS: The glenoid track width seems to be affected by the range of motion. PURPOSE: The purpose of this study was to determine the relationship between the glenoid track and the range of shoulder motion. METHODS: Ten fresh-frozen cadaveric shoulders were used. The specimen was fixed to a shoulder-positioning device. The anterior rim of the glenoid was marked on the humeral head using a Kirschner wire with the arm in 60° of abduction. This marking was repeated with the arm in (1) horizontal flexion/extension and (2) internal/external rotations (0° to max). The distances from the Kirschner wire markings to the footprint of the rotator cuff tendon were measured. RESULTS: The greater the angle of the horizontal extension or external rotation, the smaller the glenoid track width, whereas the greater the angle of the horizontal flexion or internal rotation, the greater the glenoid track width. There was a negative relationship between them. The horizontal flexion/extension motion was demonstrated to affect the glenoid track width more than the internal/external rotation motion. CONCLUSION: The glenoid track width decreased with the increase of horizontal extension. We should consider the range of horizontal extension angle when applying the glenoid track concept in clinical practice. TYPE OF STUDY: Laboratory study.

'On-track' and 'off-track' shoulder lesions.

Shoulder stability depends on the position of the arm as well as activities of the muscles around the shoulder. The capsulo-ligamentous structures are the main stabilisers with the arm at the end-range of movement, whereas negative intra-articular pressure and concavity-compression effect are the main stabilisers with the arm in the mid-range of movement.There are two types of glenoid bone loss: fragment type and erosion type. A bone loss of the humeral head, known as a Hill-Sachs lesion (HSL), is a compression fracture of the humeral head caused by the anterior rim of the glenoid when the humeral head is dislocated anteriorly in front of the glenoid. Four out of five patients with anterior instability have both Hill-Sachs and glenoid bone lesions, which is called a 'bipolar lesion'.With the arm moving along the posterior end-range of movement, or with the arm in various degrees of abduction, maximum external rotation and maximum horizontal extension, the glenoid moves along the posterior articular margin of the humeral head. This contact zone of the glenoid with the humeral head is called the 'glenoid track'.A HSL, which stays on the glenoid track (on-track lesion), cannot engage with the glenoid and cannot cause dislocation. On the other hand, a HSL, which is out of the glenoid track (off-track lesion), has a risk of engagement and dislocation. Clinical validation studies show that the 'on-track/off-track' concept is able to predict reliably the risk of a HSL being engaged with the glenoid. For off-track lesions, either remplissage or Latarjet procedure is indicated, depending upon the glenoid defect size and the risk of recurrence. Cite this article: EFORT Open Rev 2017;2:343-351.

Dedifferentiated chondrosarcoma with telangiectatic osteosarcoma-like features.

A 35-year-old Japanese man was admitted to the National Cancer Center, Tokyo, Japan, in December 2000, with a 2-month history of pain around the left thigh. Radiographs showed a poorly demarcated osteolytic lesion with focal mineralisation and endosteal scalloping in the left proximal femur. Biopsy showed a proliferation of highly anaplastic cells without any cartilaginous component. A wide excision of the left proximal femur with a replacement by endoprosthesis was carried out in February 2001 after treatment with methotrexate and 20 Gy radiation therapy. Pathological examination of the surgical specimen showed a focus of low-grade chondrosarcoma and the coexistence of telangiectatic osteosarcoma-like features. The patient was diagnosed with dedifferentiated chondrosarcoma with telangiectatic osteosarcoma-like features. Lung metastasis appeared in July 2001 despite an adjuvant chemotherapy including methotrexate, cis-platinum and doxorubicin. The latest follow-up study in June 2004 showed multiple lung metastases. Establishing a definitive diagnosis of dedifferentiated chondrosarcoma may be difficult with limited small biopsy specimens. Dedifferentiated chondrosarcoma should be included in the differential diagnosis of osteolytic tumours with focal calcification and endosteal scalloping even if an extraosseous tumour component is not identified.

Increased Facet Fluid Predicts Dynamic Changes in the Dural Sac Size on Axial-Loaded MRI in Patients with Lumbar Spinal Canal Stenosis.

BACKGROUND AND PURPOSE: Axial-loaded MR imaging, which simulates the spinal canal in a standing position, demonstrates reductions of the dural sac cross-sectional area in patients with lumbar spinal canal stenosis. However, there has been no useful conventional MR imaging finding for predicting a reduction in the dural sac cross-sectional area on axial-loaded MR imaging. Previous studies have shown that increased facet fluid is associated with the spinal instability detected during positional changes. The purpose of this study was to analyze the correlations between facet fluid and dynamic changes in the dural sac cross-sectional area on axial-loaded MR imaging. MATERIALS AND METHODS: In 93 patients with lumbar spinal canal stenosis, the dural sac cross-sectional area was measured by using axial images of conventional and axial-loaded MR imaging. Changes in the dural sac cross-sectional area induced by axial loading were calculated. The correlation between the facet fluid width measured on conventional MR imaging and the change in dural sac cross-sectional area was analyzed. The change in the dural sac cross-sectional area was compared between the intervertebral levels with and without the facet fluid width that was over the cutoff value determined in this study. RESULTS: The dural sac cross-sectional area was significantly smaller on axial-loaded MR imaging than on conventional MR imaging. The facet fluid width significantly correlated with the change in the dural sac cross-sectional area (r = 0.73, P < .001). The change in the dural sac cross-sectional area at the intervertebral level with the facet fluid width over the cutoff value was significantly greater than that at the other level. CONCLUSIONS: The increased facet fluid on conventional MR imaging is highly predictive of the dynamic reduction of dural sac cross-sectional area detected on axial-loaded MR imaging in the clinical assessment of lumbar spinal canal stenosis.

Comparative study of treatment for distal radius fractures with two different palmar locking plates.

Few randomized trials have shown how the placement of a palmar locking plate affects outcomes. The purpose of this study was to compare clinical and radiological outcomes of fixation using locking plates with different concepts for placement relative to the watershed line in a prospective randomized trial. Sixty-four patients with a displaced distal radius fracture were divided into two groups according to the plates used for fixation: distal-type (AcuLoc(TM), Group A) and proximal-type (VariAx(TM), Group V). Wrist function including the range of motion and grip strength was compared at 1, 2, 3 and 6 months postoperatively. Loss of reduction was assessed radiologically. Both groups demonstrated overall satisfactory function at 6 months with no significant difference found between the groups. Minimal loss of reduction was demonstrated in both groups. Internal fixation using the palmar locking plates with two different placements provided satisfactory outcomes at 6-month follow-up, but our results indicate that plates placed distal to the watershed line may delay recovery of wrist motion.

Outcome of Bankart repair in contact versus non-contact athletes.

BACKGROUND: The clinical results of arthroscopic Bankart repair for contact athletes varies according to published reports. The purposes of this study were to analyze the clinical outcome of open or arthroscopic Bankart repair and to investigate the results in contact and non-contact athletes. HYPOTHESIS: Clinical outcome of arthroscopic Bankart repair is similar to that of open procedure. PATIENTS AND METHODS: One hundred patients with recurrent anterior shoulder dislocation without a large bony defect were retrospectively reviewed. Fifty-one contact and 49 non-contact athletes were found with a mean follow-up of 17 months. Forty-nine shoulders underwent arthroscopic Bankart repairs; 51 shoulders had open Bankart repairs. RESULTS: In non-contact athletes, there was a 5% (1/22 cases) recurrence rate in the open group and 4% (1/27 cases) in the arthroscopic group. In contrast, in contact athletes, there was a 10% (3/29 cases) recurrence rate in the open group and 14% (3/22 cases) in the arthroscopic group. There was no significant difference in the recurrence rate between contact and non-contact athletes, although contact athletes showed two to three times a higher recurrence rate than that of non-contact athletes. The Rowe score and Constant score showed no significant difference between the two procedures and between the contact and non-contact athletes. The rate of the complete return to sports showed no significant difference between contact and non-contact athletes. CONCLUSION: The recurrence rate of Bankart repair in the contact athletes was 2 times higher in the open group and 3 times higher in the arthroscopic group than in the non-contact athletes. Clinical outcome of arthroscopic Bankart repair was similar to that of open procedure.

Long-term effects of withdrawal of bisphosphonate incadronate disodium (YM175) on bone mineral density, mass, structure, and turnover in the lumbar vertebrae of ovariectomized rats.

This study was designed to evaluate the long-term effects of incadronate disodium (YM175) after its withdrawal on cancellous bone mass in ovariectomized (OVX) rats. Thirteen-week-old female SD rats were randomized into four groups: sham-operated, OVX, low-YM, and high-YM (0.01 mg/kg or 0.1 mg/kg subcutaneously [sc], three times a week after OVX) groups. After 4 weeks of treatment with vehicle or YM175, rats from each group were killed at time points of 0 (baseline), 3, 6, 9, and 12 months after withdrawal of the agent. Bone mineral density (BMD) of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry (DXA). Bone volume (BV/TV), trabecular number and trabecular separation (Tb.N and Tb.Sp), eroded surface (ES/BS), osteoclast number and osteoclast surface (N.Oc/BS and Oc.S/BS), osteoid surface (OS/BS), and bone formation rate (BFR/BS) were measured as histomorphometric parameters of the fifth lumbar vertebra. BMD, BV/TV, Tb.N, and Tb.Sp in YM175-treated groups were maintained at the same level as in the sham group until 12 months after withdrawal in the high-YM group and until 3 months after withdrawal in the low-YM group. YM175 decreased both bone formative and resorptive parameters in histomorphometry. Serum bone-specific alkaline phosphatase (ALP) and urinary deoxypyridinoline at both doses of YM175 also showed a suppressive effect of this agent on bone turnover. These results indicate that YM175, after withdrawal, still maintains bone volume dose dependently by depressing bone resorption and formation in OVX rats. Intermittent YM175 treatment with a long interval may be sufficient to maintain the bone volume and structure in OVX rats.

Effects of combined treatment of insulin and human parathyroid hormone(1-34) on cancellous bone mass and structure in streptozotocin-induced diabetic rats.

The purpose of this study was to test the hypothesis that combined treatment with insulin and human parathyroid hormone (hPTH) is more effective than treatment with insulin or hPTH alone in improving cancellous bone mass, connectivity, and strength in insulin-dependent diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) in 7-month-old female Wistar rats. The diabetic rats received insulin, hPTH, insulin and hPTH, or hPTH vehicle for 4 weeks, starting 8 weeks after STZ injection. They were compared with baseline controls and normal controls that received STZ alone and STZ vehicle alone, respectively. The rats' proximal right tibias were processed to serve as undecalcified Villanueva-stained bone sections for histomorphometry. Changes in trabecular connectivity were determined through node-strut analysis. The decreased cancellous bone volume (BV/TV) and bone formation in diabetic rats improved in all the drug-treated groups compared with baseline controls. Furthermore, recovery of BV/TV was greater in rats that received the combination of insulin and hPTH than in those that received insulin or hPTH alone. In node-strut analysis, the node-related parameter (N.Nd/TV) significantly increased in rats that received the combination of insulin and hPTH, but did not increase in those that received insulin or hPTH alone. In addition to these results, the combination treatment significantly increased bone mineral density of the femur and bone strength in the femoral metaphysis compared with treatment with insulin or hPTH alone. These results indicate that the doses of insulin and hPTH employed in the combination treatment were more effective in improving not only bone mass but also trabecular connectivity and bone strength than treatment with insulin or hPTH alone in insulin-dependent diabetic rats.

Stronger back muscles reduce the incidence of vertebral fractures: a prospective 10 year follow-up of postmenopausal women.

The long-term protective effect of stronger back muscles on the spine was determined in 50 healthy white postmenopausal women, aged 58-75 years, 8 years after they had completed a 2 year randomized, controlled trial. Twenty-seven subjects had performed progressive, resistive back-strengthening exercises for 2 years and 23 had served as controls. Bone mineral density, spine radiographs, back extensor strength, biochemical marker values, and level of physical activity were obtained for all subjects at baseline, 2 years, and 10 years. Mean back extensor strength (BES) in the back-exercise (BE) group was 39.4 kg at baseline, 66.8 kg at 2 years (after 2 years of prescribed exercises), and 32.9 kg at 10 years (8 years after cessation of the prescribed exercises). Mean BES in the control (C) group was 36.9 kg at baseline, 49.0 kg at 2 years, and 26.9 kg at 10 years. The difference between the two groups was still statistically significant at 10 year follow-up (p = 0.001). The difference in bone mineral density, which was not significant between the two groups at baseline and 2 year follow-up, was significant at 10 year follow-up (p = 0.0004). The incidence of vertebral compression fracture was 14 fractures in 322 vertebral bodies examined (4.3%) in the C group and 6 fractures in 378 vertebral bodies examined (1.6%) in the BE group (chi-square test, p = 0.0290). The relative risk for compression fracture was 2.7 times greater in the C group than in the BE group. To our knowledge, this is the first study reported in the literature demonstrating the long-term effect of strong back muscles on the reduction of vertebral fractures in estrogen-deficient women.

Effect of back-strengthening exercise on posture in healthy women 49 to 65 years of age.

OBJECTIVE: To evaluate the effect of back-strengthening exercise on posture in 60 healthy estrogen-deficient women. DESIGN: The 60 study subjects were randomly assigned to either an exercise or a control group, and various factors were assessed at time of enrollment in the study and at 2-year follow-up. MATERIAL AND METHODS: The 32 women in the exercise group were instructed in progressive back-strengthening exercises, whereas the 28 women in the control group had no exercise prescription and were asked to continue their usual physical and dietary activities. At baseline and 2-year follow-up examinations, back extensor strength was measured with a strain-gauge dynamometer, and lateral roentgenograms of the thoracic and lumbar areas of the spine were obtained to measure the angles of thoracic kyphosis, lumbar lordosis, and sacral inclination. The changes in radiographic measurements and back extensor strength were analyzed statistically. RESULTS: Back extensor strength increased significantly in both the exercise and the control groups, but no radiographic measurements were significantly different between these groups. The significant increase in back extensor strength in both groups of healthy women suggested that the original grouping did not accurately reflect the amount of exercise. Thus, the 60 subjects were reclassified for comparison on the basis of increase in back extensor strength--27 with more than or equal to the mean increase of 21.1 kg and 33 with less than 21.1 kg. Furthermore, each of these groups of subjects was subdivided on the basis of degree of thoracic kyphosis. Among the subjects with substantial thoracic kyphosis, those with a significant increase in back extensor strength had a significant decrease in thoracic kyphosis (-2.8 +/- 4.2 degrees; P = 0.041), whereas those with a small increase in strength had a nonsignificant increase in thoracic kyphosis (1.8 +/- 5.3 degrees). The increase in back extensor strength did not seem to affect mild degrees of kyphosis. CONCLUSION: Increasing the back extensor strength in healthy estrogen-deficient women helps decrease thoracic kyphosis.

Superior-inferior stability of the shoulder: role of the coracohumeral ligament and the rotator interval capsule.

OBJECTIVE: To study the superior-inferior stabilizing functions of the coracohumeral ligament (CHL) and the rotator interval capsule (RIC) with use of a material testing machine. MATERIAL AND METHODS: The axial translations of the humerus with the superior-inferior translation force of 30 N applied were recorded under the following joint capsule conditions: (1) intact, (2) vented, (3) the CHL sectioned, and (4) the RIC incised in six cadaver shoulders. The order of sectioning was changed for conditions 3 and 4 in six other cadaver shoulders. RESULTS: With the arm in internal and neutral rotations, venting the capsule significantly increased the superior-inferior translation, which was unaffected by further sectioning of the CHL and the RIC. With the arm in external rotation, only the CHL contributed significantly to inferior stability, whereas both this ligament and the RIC contributed to superior stability to a lesser degree. CONCLUSION: The CHL is a stabilizer in superior inferior directions with the arm in external rotation, and the intra-articular pressure that is maintained by the intact RIC is a stabilizer in superior-inferior directions with the arm in internal and neutral rotations. These findings may provide a scientific background to support closure of the interval space to stabilize the shoulder and may explain part of the superior instability observed in shoulders with rotator cuff tears.

Prognostic relevance of rosette-like features in osteosarcoma.

AIMS: To clarify the prognostic relevance of rosette-like features and other clinicopathological and immunohistochemical variables in patients with osteosarcoma. METHODS: Clinicopathological and immunohistochemical variables were analysed in 131 patients with non-metastatic high grade conventional osteosarcoma, with particular attention to the prognostic impact of rosette-like features. RESULTS: Rosette-like features were present in 18 (14%) cases. Rosette-like features were significantly associated with the osteoblastic subtype, numerous osteoclast-like giant cells, moderate pleomorphism, frequent haemangiopericytoma-like vascular patterns, epithelioid cytological features, positive immunoreactivity for epithelial membrane antigen and CD56, and negative staining for cytokeratin. In a multivariate analysis, rosette-like features (relative risk (RR), 3.8), a poor chemotherapy effect (RR, 2.9), and a tumour size of 10 cm or more (RR, 2.8) were identified as unfavourable prognostic factors. CONCLUSIONS: Rosette-like features can easily be identified from routine histological slides and the relative risk in patients with non-metastatic, conventional osteosarcoma is as high as other well known prognostic factors, including large size and poor chemotherapy effect.

Osteosarcoma with cytokeratin expression: a clinicopathological study of six cases with an emphasis on differential diagnosis from metastatic cancer.

AIMS: To clarify the clinicopathological profile of osteosarcomas showing an intensely positive immunoreaction for cytokeratin. METHODS: Clinicopathological and immunohistochemical features were analysed in 131 patients with non-metastatic, conventional osteosarcoma, treated in Akita University and National Cancer Centre in Tokyo between 1972 and 1999. RESULTS: Six patients (4.5%; mean age, 32 years; four men, two women) had osteosarcomas showing intense cytokeratin expression. Tumours were located on the long bones of the extremities in five patients and the ilium in one. Osteoid formations were found in biopsied specimens in all cases. Three tumours were classified as osteoblastic osteosarcoma, two as fibroblastic, and one as chondroblastic. In three tumours classified as the osteoblastic subtype, epithelioid features were prominent, and four tumours showed pronounced cellular pleomorphism. In contrast to the expression of cytokeratin, epithelial membrane antigen was negative in all cases. Surgery with a wide excisional margin was performed in six patients. Preoperative and postoperative chemotherapy was given to five of the six patients, but the effects of these agents were negligible. Three of the six patients developed lung metastases, whereas the other three patients have remained well with no evidence of local recurrence or distant metastasis. CONCLUSIONS: Osteosarcoma with intense immunoreaction for cytokeratin was rare. The clinicopathological features were similar to those of patients with conventional osteosarcoma, except for a higher age, chemotherapy resistance, histological epithelioid features, and pleomorphism. This study indicates that osteoid formation and negative expression of epithelial membrane antigen are key features in the differentiation from metastatic carcinoma.

Malrotation of the humeral component of the capitellocondylar total elbow replacement is not the sole cause of dislocation.

Malrotation of the humeral component of the capitellocondylar total elbow replacement is thought but not proved to be one of the major causes of postoperative dislocation. The purpose of this study was to quantitate the effect of malrotation of the humeral component on the kinematics and laxity of the capitellocondylar total elbow prosthesis. Eleven fresh previously frozen elbows were used. With the humeral component in optimal position, external rotation, or internal rotation, movements of the elbow with neutral, valgus, and varus loading were monitored with an electromagnetic tracking device. When the humeral component was positioned in external rotation, the ulna was more valgus and supinated than when the component was in optimal position, and when the component was in internal rotation the ulna was more valgus in extension and more supinated in flexion. Malrotation in external rotation decreased valgus-varus laxity, and malrotation in internal rotation increased rotational laxity. Only one elbow became dislocated, despite constant severe maltracking between the components in all of the specimens. We concluded that although malrotation of the humeral component influences the laxity and causes maltracking, it is not the primary cause of postoperative dislocation. The contribution of other factors should be investigated.