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1.  PET/CT and MRI of intra-osseous haemangioma of the tibia 
The British Journal of Radiology  2012;85(1012):e094-e098.
Intra-osseous haemangioma is a rare, benign neoplasm that usually involves the vertebrae and craniofacial bones. Furthermore, its occurrence in the long bones is extremely rare. We report the findings of fluorine-18-fludeoxyglucose (18F-FDG) positron emission tomography (PET)/CT and MRI in a patient with intra-osseous haemangioma in the proximal tibia, who was initially misdiagnosed as having a malignancy based on 18F-FDG PET/CT. 18F-FDG PET/CT showed a well-marginated osteolytic lesion with abnormal FDG uptake. The mass demonstrated low signal intensity on T1 weighted MRI. On T2 weighted images, the lesion appeared as a cluster of high signal intensity lobules and showed strong enhancement on contrast-enhanced T1 weighted images. Surgical curettage was performed and histopathological examination of the excised tissue confirmed a cavernous haemangioma.
PMCID: PMC3486666  PMID: 22457416
2.  Suitability of imaging methods (X-ray, CT, MRI) in the diagnostics of Ewing’s sarcoma in children – analysis of own material 
Polish Journal of Radiology  2010;75(1):18-28.
Ewing sarcoma is a malignant, small round cell bone tumor, presenting predominantly in children and adolescents. Ewing sarcoma may develop in every bone; diaphyses of long bones, ribs and flat bones are the main locations. Local and systemic clinical symptoms are nonspecific - pain, swelling, fever or ill-being.
The aim of the study was to assess the role of radiography, computed tomography and magnetic resonance imaging in the analysis of bone lesions in children and young adults with Ewing sarcoma.
Twenty-seven patients, aged between 1 year and 10 months, and 17 years and 2 months, with histologically verified Ewing sarcoma of the bone, referred to the Radiological Department of University Hospital No 6., John Paul II Upper Silesian Centre for Child Health Katowice, in the period from 1996 to 2007, were included in the study.Plain radiography was performed in every child, CT in 20 and MRI in 12 individuals. Tumour location, extension of the tumour, soft tissue mass, and periosteal reaction were taken into consideration in the evaluation of the lesion. In some cases, pathological features of the MRI and CT were compared. The prevalence of some radiological features was compared to the literature data.
The most common site of tumor was: ribs (6 children), femoral bone (6 children), pelvis (4 children) and tibia (3 children). In 2 children, a primary tumor was diagnosed in the spine (multifocal in 1 child).
X-rays revealed: periosteal reaction in 17 children (63%), soft tissue involvement in 19 children (70%), permeative component in 16 children (59%), and sclerotic component in 5 children (19%). In 10 children (37%), periosteal reaction was not detected. The examination revealed: soft tissue calcifications in 7 cases (26%), a well-delineated focus of destruction within bones in 3 children (11%), cortical thickening in 4 children (15%), cortical destruction in 4 children (15%), saucerisation in 3 children (11%), bone expansion in 3 children (11%), pathological fracture in 2 children (7%), cystic component in 1 child (4%), and vertebra plana in 1 child (4%).Reaction of tumors after i.v. contrast administration, shown on CT, was visible in 16 children – it was useful for a better description of the tumor and extension of the mass within the soft tissue. All MRI examinations (12 children) showed a heterogenous mass with ill-defined borders and a violated cortex. Low signal intensity of the tumor in a T1-weighted image and high signal intensity in a T2-weighted image was shown as well.
Heterogenous enhancement of signal intensity on T1-weighted images could be observed after i.v. contrast administration.
MRI examinations showed: tumor in an adjacent soft tissue in 11 children, and involvement of the epiphyseal plate or of the joint cavity in 6 children.
X-ray and MRI are essential in diagnostics. CT examination is more useful to estimate periosteal reactions and destruction of bone and marrow cavity, especially in flat bones. However, to recognise a malignancy, it is necessary to perform a histopathological examination. In doubtful cases, the examination has to be verified as well.
PMCID: PMC3389856  PMID: 22802757
Ewing sarcoma; bone tumour; children; X-rays; CT; MRI
3.  Diagnostic efficacy of gadoxetic acid-enhanced MRI for the detection and characterisation of liver metastases: comparison with multidetector-row CT 
The British Journal of Radiology  2012;85(1013):539-547.
We compared the diagnostic performance of gadoxetic acid-enhanced MRI and 16-slice multidetector CT (MDCT) with respect to their abilities to detect hepatic metastases and differentiate hepatic metastases from hepatic cysts and haemangiomas.
67 patients with 110 liver metastases (size 0.3–2.5 cm), 33 haemangiomas (size 0.5–1.5 cm) and 17 cysts (size 0.3–1.0 cm) underwent 4-phase MDCT and gadoxetic acid-enhanced MRI, including early dynamic phases, post-contrast T2 weighted turbo spin echo sequences and 20 min hepatocyte-selective phases. Two observers independently analysed each image in random order. Sensitivity and diagnostic accuracy for lesion detection and differentiation for MDCT and gadoxetic acid-enhanced MRI were calculated using receiver operating characteristic analysis.
For both observers, the Az values of gadoxetic acid-enhanced MRI (mean, 0.982 and 0.981) were significantly higher than the Az values of MDCT (mean, 0.839 and 0.892) (p<0.05) for the detection of metastases and for the differentiation of metastases from haemangiomas and cysts. Sensitivities of gadoxetic acid-enhanced MRI with regard to the detection and characterisation of liver metastases (mean, 96.9% and 96.0%) were significantly higher than those of MDCT (mean, 78.7% and 75.0%) (p<0.05).
Gadoxetic acid-enhanced MRI showed higher diagnostic accuracy and sensitivity than did MDCT for the detection of hepatic metastases and for the differentiation between hepatic metastases and hepatic haemangiomas or cysts.
PMCID: PMC3479888  PMID: 22556405
4.  Hepatic haemangiomas: possible association with female sex hormones 
Gut  2004;53(9):1352-1355.
Background and aims: The association of hepatic haemangiomas with female sex hormones is not entirely clear. We prospectively evaluated the impact of female sex hormones on the natural history of liver haemangiomas.
Methods: We followed 94 women with 181 haemangiomas diagnosed by ultrasound for a period of1–17 years (mean 7.3 (5.5) years). The location, number, size, and ultrasonographic pattern of the lesions were evaluated. Patients were also evaluated by questionnaire for gynaecological and reproductive history. We compared the change in number and size of haemangiomas in patients who received or did not receive exogenous hormonal treatment.
Results: Age at first period was inversely associated with the size of haemangiomas (r = 0.181, p = 0.015) while age at menopause was positively correlated with the number of haemangiomas detected at first ultrasound (r = 0.542, p<0.0001). During follow up, no change in the ultrasonographic pattern or number of haemangiomas was observed. An increase in the size of the lesions was demonstrated in 5/22 (22.7%) hormone therapy exposed patients compared with 7/72 (9.7%) controls. Three variables (ultrasonographic pattern, number of haemangiomas, and hormone therapy) predicted whether or not a given haemangioma would increase in size. A hypoechoic pattern increased the risk of progression while a hyperechoic pattern decreases that risk (p = 0.003). The number of haemangiomas was inversely associated with the likelihood of progression (p = 0.006) and hormone therapy increased the risk of haemangioma enlargement (p = 0.05).
Conclusions: Hepatic haemangiomas seem to be influenced by both endogenous and exogenous female sex hormones although significant enlargement occurs only in a minority of patients. Consequently, routine liver ultrasound follow up in women with hepatic haemangiomas receiving hormone therapy appears appropriate.
PMCID: PMC1774167  PMID: 15306599
hepatic haemangioma; hormones; oestrogens
5.  Prospective two year follow up study comparing novel and conventional imaging procedures in patients with arthritic finger joints 
Annals of the Rheumatic Diseases  2002;61(10):895-904.
Objective: To carry out a prospective two year follow up study comparing conventional radiography, three-phase bone scintigraphy, ultrasonography (US), and three dimensional (3D) magnetic resonance imaging (MRI) with precontrast and dynamic postcontrast examination in detecting early arthritis. The aim of the follow up study was to monitor the course of erosions during treatment with disease modifying antirheumatic drugs by different modalities and to determine whether the radiographically occult changes like erosive bone lesions of the finger joints detected by MRI and US in the initial study would show up on conventional radiographs two years later. Additionally, to study the course of soft tissue lesions depicted in the initial study in comparison with the clinical findings.
Methods: The metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints (14 joints) of the clinically more severely affected hand (soft tissue swelling and joint tenderness) as determined in the initial study of 49 patients with various forms of arthritis were examined twice. The patients had initially been divided into two groups. The follow up group I included 28 subjects (392 joints) without radiographic signs of destructive arthritis (Larsen grades 0–1) of the investigated hand and wrist, and group II (control group) included 21 patients (294 joints) with radiographs showing erosions (Larsen grade 2) of the investigated hand or wrist, or both, at the initial examination.
Results: (1) Radiography at the two year follow up detected only two erosions (two patients) in group I and 10 (nine patients) additional erosions in group II. Initial MRI had already detected both erosions in group I and seven (seven patients) of the 10 erosions in group II. Initial US had depicted one erosion in group I and four of the 10 erosions in group II. (2) In contrast with conventional radiography, 3D MRI and US demonstrated an increase in erosions in comparison with the initial investigation. (3) The abnormal findings detected by scintigraphy were decreased at the two year follow up. (4) Both groups showed a marked clinical improvement of synovitis and tenosynovitis, as also shown by MRI and US. (5) There was a striking discrepancy between the decrease in the soft tissue lesions as demonstrated by clinical findings, MRI, and US, and the significant increase in erosive bone lesions, which were primarily evident at MRI and US.
Conclusions: Despite clinical improvement and a regression of inflammatory soft tissue lesions, erosive bone lesions were increased at the two year follow up, which were more pronounced with 3D MRI and less pronounced with US. The results of our study suggest that owing to the inadequate depiction of erosions and soft tissue lesions, conventional radiography alone has limitations in the intermediate term follow up of treatment. US has a high sensitivity for depicting inflammatory soft tissue lesions, but dynamic 3D MRI is more sensitive in differentiating minute erosions.
PMCID: PMC1753903  PMID: 12228160
6.  Focal hepatic lesions in Gd-EOB-DTPA enhanced MRI: the atlas 
Insights into Imaging  2012;3(5):451-474.
This article reviews the different technical aspects and pitfalls of gadolinium (Gd)-ethoxibenzyl (EOB)-diethylenetriamine pentaacetic acid (DTPA) and the advantages of the hepatocellular phase (HCP) and defines its specific imaging features of liver lesions.
Gd-EOB-DTPA is a contrast agent with combined properties of a conventional non-specific extracellular and a hepatocyte-specific contrast agent. Benign cirrhosis-associated nodules are characterised by isointensity in dynamic imaging and the HCP. Hepatocellular carcinomas (HCCs) usually show hyperenhancement in the arterial phase, with washout in the portal vein pressure (PVP) and hypointensity in the HCP. Among other characteristic findings, we have the mosaic pattern, a capsule, the “nodule-in-nodule” appearance and the satellite nodules. The fibrolamellar HCC is a large enhancing heterogeneous lesion, on a non-cirrhotic liver, with a hypointense scar in every sequence. THIDs (transient hepatic intensity differences) are perfusional alterations, characterised by hyperintensity in the arterial phase, with no alterations in the rest of the sequences including the HCP. Adenoma and focal nodular hyperplasia (FNH) are lesions, occurring more frequently in young women, with brisk arterial enhancement, differentiated by the scar and the uptake of Gd-EOB-DTPA in the HCP. Focal eosinophilic infiltration is a difficult diagnosis, with characteristics such as a non-spherical shape and irregular borders suggesting it. Besides these lesions, in which Gd-EOB-DTPA has a clear advantage, there are a few where the specificities of this agent can be troublesome: haemangiomas, focal fat/sparing, foreign body reaction, cholangiocarcinoma and metastases.
Gd-EOB-DTPA is comparable to extracellular agents, and uptake by functioning hepatocytes in the delayed phase provides additional information that further improves detection and characterisation of many hepatic lesions.
Main Messages
• Gd-EOB-DTPA offers advantages for the imaging of many liver lesions including HCC, fibrolamellar HCC, FNH and adenoma.
• The properties of Gd-EOB-DTPA can pose problems when dealing with haemangiomas, cholangiocarcinoma and metastases among others.
• The uptake of Gd-EOB-DTPA by functioning hepatocytes in the delayed phase provides additional information that further improves detection and characterisation of many hepatic lesions.
PMCID: PMC3443279  PMID: 22700119
Magnetic resonance; MR; Gd-EOB-DTPA; Liver
7.  Solitary fibrous tumors of the soft tissues: imaging features with histopathologic correlations 
To describe the imaging features of soft tissue solitary fibrous tumors, with histopathological correlations and clinical outcome.
Material and methods
Twenty-seven patients with histologically proven SFTs were retrospectively evaluated. Imaging studies included six radiographs, five U/S studies, eighteen CT scans, fourteen MRI exams, and one angiography.
On CT scans, two lesions were isodense and five were mildly hypodense compared to muscle while 11 lesions appeared heterogeneous-mixed of iso and hypodense areas. Heterogeneous enhancement was depicted in 13 lesions and four lesions enhanced homogeneously. Six lesions were partially calcified. On T1W MR images, seven lesions were isointense and one was slightly hyperintense relative to adjacent muscles while five lesions appeared heterogeneous-mixed of iso and hypointense areas. T2W images showed high SI in two cases and heterogeneous-mixed in seven cases. Enhancement was heterogeneous in six and homogeneous in four lesions. Patchy unenhanced areas (on CT and T1W MR images) along with patchy areas of low to markedly high SI on T2W images were depicted in 19 lesions. The enhanced portions correlated to areas of increased vascularity and cellularity. The four clinically more aggressive lesions could not be predicted on imaging.
Typical soft tissue SFTs are deep masses made of isodense and isointense areas relative to adjacent muscles mixed with hypodense and hypointense areas on unenhanced CT and MR T1W respectively. Variable enhancement patterns and mixed to high signal intensities on MRT2W are attributed to tumor’s cellularity, vascularity, collagen distribution and/or degeneration. Heterogeneity of SFTs affects imaging features on MRI and CT modalities. The biological behavior of soft tissue SFTs can not be predicted based solely either on histopathologic or imaging evaluation.
PMCID: PMC3637805  PMID: 23351922
Solitary fibrous tumor; Magnetic resonance imaging; Soft tissue tumor; Computed tomography; Soft tissue tumor
8.  Spinal intradural capillary haemangioma: a review 
European Spine Journal  2001;10(6):464-472.
Capillary haemangioma is a benign tumour frequently encountered in the skin and other soft tissues. Histologically, these vascular lesions are characterised by nodules of capillary-sized vessels lined by flattened endothelium, each of which is subserved by a feeding vessel. Capillary haemangioma of the central and peripheral nervous system is extremely rare. Less than 20 of these lesions have been described as occurring within the confines of the spinal dura mater, in close relation to the conus medullaris and nerve roots of the cauda equina. The presenting symptoms are similar to those of more common intradural tumours at the conus-cauda region. Magnetic resonance imaging is the imaging modality of choice, and homogeneous enhancement following administration of Gd-DTPA is a useful clue to the diagnosis. Complete resection is the treatment of choice, and during surgery the vascular tumour is usually found encapsulated and sharply bordered from the surrounding parenchyma of the spinal cord and affected nerve roots. In the present account we give an overview of the clinical features, neuroradiological findings, therapeutic options and histopathological differential diagnostic aspects of spinal intradural capillary haemangioma. In general, vascular lesions of this entity are preoperatively misdiagnosed as neoplasms, and a higher level of clinical and radiological suspicion may avoid surgical overtreatment of these benign tumours.
PMCID: PMC3611536  PMID: 11806386
Capillary haemangioma Spinal cord Vascular malformation Spinal surgery Review
9.  Intramuscular cavernous haemangioma of the triceps 
Haemangiomas are one of the most common soft tissue tumours comprising 7% of all benign tumours. Vascular malformations are often confused with haemangiomas. The etiology is unknown. They are common in infancy and childhood and females are more commonly affected. These tumours may be superficial or deep, and deeply seated lesions, are difficult to diagnose clinically and hence require radiographic assessment. Deep-seated haemangiomas are usually intramuscular, although intra-articular synovial haemangiomas also occur. The commonest anatomic site is the lower limb.
Despite their vascular origin, haemangiomas do not metastasize or undergo malignant transformation. Many treatment modalities for the symptomatic haemangioma are available but surgical excision is the preferred treatment. We present an unusual case of a dumb-bell intramuscular haemangioma involving the triceps and extending into the cubital tunnel of the elbow, distinguish between haemangiomas and vascular malformations and emphasize the importance of surgical technique in ensuring ulnar nerve safety.
PMCID: PMC3199638  PMID: 22096691
Cavernous haemangioma; Haemangioma; Triceps; Intramuscular haemangioma
10.  Cross-sectional imaging of metal-on-metal hip arthroplasties 
Acta Orthopaedica  2014;85(6):577-584.
Background and purpose —
Metal artifact reduction sequence (MARS) MRI is widely advocated for surveillance of metal-on-metal hip arthroplasties (MOM-HAs). However, its use is limited by susceptibility artifact at the prosthesis-bone interface, local availability, patient compliance, and cost (Hayter et al. 2011a). We wanted to determine whether CT is a suitable substitute for MARS MRI in evaluation of the painful MOM-HA.
Patients and methods —
50 MOM-HA patients (30 female) with unexplained painful prostheses underwent MARS MRI and CT imaging. 2 observers who were blind regarding the clinical data objectively reported the following outcomes: soft tissue lesions (pseudotumors), muscle atrophy, and acetabular and femoral osteolysis. Diagnostic test characteristics were calculated.
Results —
Pseudotumor was diagnosed in 25 of 50 hips by MARS MRI and in 11 of 50 by CT. Pseudotumors were classified as type 1 (n = 2), type 2A (n = 17), type 2B (n = 4), and type 3 (n = 2) by MARS MRI. CT did not permit pseudotumor classification. The sensitivity of CT for diagnosis of pseudotumor was 44% (95% CI: 25–65). CT had “slight” agreement with MARS MRI for quantification of muscle atrophy (κ = 0.23, CI: 0.16–0.29; p < 0.01). Osteolysis was identified in 15 of 50 patients by CT. 4 of these lesions were identified by MARS MRI.
Interpretation —
CT was found to be superior to MRI for detection of osteolysis adjacent to MOM-HA, and should be incorporated into diagnostic algorithms. CT was unable to classify and failed to detect many pseudotumors, and it was unreliable for assessment of muscle atrophy. Where MARS MRI is contraindicated or unavailable, CT would be an unsuitable substitute and other modalities such as ultrasound should be considered
PMCID: PMC4259024  PMID: 25267500
11.  Osteogenic Protein-1 for Long Bone Nonunion 
Executive Summary
To assess the efficacy of osteogenic protein-1 (OP-1) for long bone nonunion.
Clinical Need
Although most fractures heal within a normal period, about 5% to 10% do not heal and are classified as delayed or nonunion fractures. Nonunion and segmental bone loss after fracture, reconstructive surgery, or lesion excision can present complex orthopedic problems, and the multiple surgical procedures often needed are associated with patient morbidity and reduced quality of life.
Many factors contribute to the pathogenesis of a delayed union or nonunion fractures, including deficiencies of calcium, vitamin D, or vitamin C, and side effects of medications such as anticoagulants, steroids, some anti-inflammatory drugs, and radiation. It has been shown that smoking interferes with bone repair in several ways.
Incidence of Nonunion and Delayed Union Cases
An estimated 5% to 10% of fractures do not heal properly and go on to delayed union or nonunion. If this overall estimate of incidence were applied to the Ontario population1, the estimated number of delayed union or nonunion in the province would be between 3,863 and 7,725.
Treatment of Nonunion Cases
The treatment of nonunion cases is a challenge to orthopedic surgeons. However, the basic principle behind treatment is to provide both mechanical and biological support to the nonunion site.
Fracture stabilization and immobilization is frequently used with the other treatment modalities that provide biological support to the fractured bone. Biological support includes materials that could be served as a source of osteogenic cells (osteogenesis), a stimulator of mesenchymal cells (osteoinduction), or a scaffold-like structure (osteoconduction).
The capacity to heal a fracture is a latent potential of the stromal stem cells, which synthesize new bone. This process has been defined as osteogenesis. Activation of the stem cells to initiate osteogenic response and to differentiate into bone-forming osteoblasts is called osteoinduction. These 2 properties accelerate the rate of fracture healing or reactivate the ineffective healing process. Osteoconduction occurs when passive structures facilitate the migration of osteoprogenitor cells, the perivascular tissue, and capillaries into these structures.
Bone Grafts and Bone Graft Substitutes
Bone graft and bone graft substitutes have one or more of the following components:
Undifferentiated stem cells
Growth factors
Structural lattice
Undifferentiated stem cells are unspecialized, multipotential cells that can differentiate into a variety of specialized cells. They can also replicate themselves. The role of stem cells is to maintain and repair the tissue in which they are residing. A single stem cell can generate all cell types of that tissue. Bone marrow is a source of at least 2 kinds of stem cells. Hematopoietic stem cells that form all types of blood cells, and bone marrow stromal stem cells that have osteogenic properties and can generate bone, cartilage, and fibrous tissue.
Bone marrow has been used to stimulate bone formation in bone defects and cases of nonunion fractures. Bone marrow can be aspirated from the iliac crest and injected percutaneously with fluoroscopic guidance into the site of the nonunion fracture. The effectiveness of this technique depends on the number and activity of stem cells in the aspirated bone marrow. It may be possible to increase the proliferation and speed differentiation of stem cells by exposing them to growth factor or by combining them with collagen.
Many growth factors and cytokines induced in response to injury are believed to have a considerable role in the process of repair. Of the many bone growth factors studied, bone morphogenetics (BMPs) have generated the greatest attention because of their osteoinductive potential. The BMPs that have been most widely studied for their ability to induce bone regeneration in humans include BMP-2 and BMP-7 (osteogenic protein). Human osteogenic protein-1 (OP-1) has been cloned and produced with recombinant technology and is free from the risk of infection or allergic reaction.
The structural lattice is osteoconductive; it supports the ingrowth of developing capillaries and perivascular tissues. Three distinct groups of structural lattice have been identified: collagen, calcium sulphate, and calcium phosphate. These materials can be used to replace a lost segment of bone.
Grafts Used for Nonunion
Autologous bone graft is generally considered the gold standard and the best material for grafting because it contains several elements that are critical in promoting bone formation, including osteoprogenitor cells, the matrix, and bone morphogenetic proteins. The osteoconductive property of cancellous autograft is related to the porosity of bone. The highly porous, scaffold-like structure of the graft allows host osteoblasts and host osteoprogenitor cells to migrate easily into the area of the defect and to begin regeneration of bone. Sources of cancellous bone are the iliac crest, the distal femur, the greater trochanter, and the proximal tibia. However, harvesting the autologous bone graft is associated with postoperative pain at the donor site, potential injury to the surrounding arteries, nerves, and tissues, and the risk of infection. Thus the development of synthetic materials with osteoconductive and osteoinductive properties that can eliminate the need for harvesting has become a major goal of orthopedic research.
Allograft is the graft of tissue between individuals who are of the same species but are of a disparate genotype. Allograft has osteoconductive and limited osteoinductive properties. Demineralized bone matrix (DBM) is human cortical and cancellous allograft. These products are prepared by acid extraction of allograft bone, resulting in the loss of most of the mineralized component while collagen and noncollagenous proteins, including growth factors, are retained. Figures 1 to 5 demonstrate the osteogenic, osteoinduction, and osteoconduction properties of autologous bone graft, allograft, OP-1, bone graft substitutes, and bone marrow.
Autologous Bone Graft
Osteogenic Protein-1
Allograft bone and Demineralized Bone Matrix
Bone Graft Substitutes
Autologous Bone Marrow Graft
New Technology Being Reviewed: Osteogenic Protein-1
Health Canada issued a Class IV licence for OP-1 in June 2004 (licence number 36320). The manufacturer of OP-1 is Stryker Biotech (Hapkinton, MA).
The United States Food and Drug Administration (FDA) issued a humanitarian device exemption for the application of the OP-1 implant as an “alternative to autograft in recalcitrant long bone nonunions where use of autograft is unfeasible and alternative treatments have failed.” Regulatory agencies in Europe, Australia, and New Zealand have permitted the use of this implant in specific cases, such as in tibial nonunions, or in more general cases, such as in long bone nonunions.
According to the manufacturer, OP-1 is indicated for the treatment of long bone nonunions. It is contraindicated in the patient has a hypersensitivity to the active substance or collagen, and it should not be applied at the site of a resected tumour that is at or near the defect or fracture. Finally, it should not be used in patients who are skeletally immature (< 18 years of age), or if there is no radiological evidence of closure of epiphysis.
Review Strategy
To summarize the safety profile and effectiveness of OP-1 in the treatment of cases of long bone nonunion and bone defects
To compare the effectiveness and cost effectiveness of OP-1 in the treatment of long bone nonunions and bone defects with the alternative technologies, particularly the gold standard autologous bone graft.
Literature Search
International Network of Agencies for Health Technology Assessments (INAHTA), the Cochrane Database of Systematic Reviews and the CCTR (formerly Cochrane Controlled Trials Register) were searched for health technology assessments. MEDLINE, EMBASE, Medline In Process and Other Non-Indexed Citations were searched from January 1, 1996 to January 27, 2004 for studies on OP-1. The search was limited to English-language articles and human studies. The search yielded 47 citations. Three studies met inclusion criteria (2 RCTs and 1 Ontario-based study presented at an international conference.
Summary of Findings
Friedlaender et al. conducted a prospective, randomized, partially blinded clinical trial on the treatment tibial nonunions with OP-1. Tibial nonunions were chosen for this study because of their high frequency, challenging treatment requirements, and substantial morbidity. All of the nonunions were at least 9 months old and had shown no progress toward healing over the previous 3 months. The patients were randomized to receive either treatment with autologous bone grafting or treatment with OP-1 in a type-1 collagen carrier. Both groups received reduction and fixation with an intramedullary rod. Table 1 summarizes the clinical outcomes of this study.
Outcomes in a Randomized Clinical Trial on Tibial Nonunions: Osteogenic Protein-1 versus Autologous Bone Grafting
Clinical success was defined as full weight-bearing, loss of severe pain at the fracture site on weight-bearing, and no further surgical treatment to enhance fracture repair.
The results of this study demonstrated that recombinant OP-1 is associated with substantial clinical and radiographic success for the treatment of tibial nonunions when used with intramedullary rod fixation. No adverse event related to sensitization was reported. Five per cent of the patients in the OP-1 group had circulating antibodies against type 1 collagen. Only 10% of the patients had a low level of anti-OP-1 antibodies, and all effects were transient. Furthermore, the success rate with the OP-1 implant was comparable with those achieved with autograft at 9 and 24 months follow-up. Eighty-two per cent of patients were successful at 24 months follow-up in both groups.
Statistically significant increased blood loss in the group treated with the autograft was observed (P = .049). Patients treated with autograft had longer operation and hospitalization times. All patients in the autograft group had pain at the donor site after surgery, and more than 80% judged their postoperative pain as moderate or severe. At their 6-month visit, 20% of the patients in the autograft group had persistent pain, mild or moderate in nature, at the donor site. This number fell to 13% at 12 months.
All patients in each of the groups had at least 1 adverse event that wasn’t serious, such as fever, nausea and vomiting, leg edema, discomfort, and bruising at the operative site. The incidence of these events was similar in both groups. Serious adverse events were observed in 44% of both groups, none of which were considered related to the OP-1 implant or autograft.
On the basis of this data, the FDA issued a humanitarian device exemption for the application of OP-1 implant as an alternative to autograft in recalcitrant long bone nonunions when the use of autograft is unfeasible and alternative treatments have failed.
Study on Fibular Defects
Geesink et al. investigated the osteogenic activity of OP-1 by assessing its value in bridging fibular defects made at the time of tibial osteotomy for varus or valgus deformity of the knee. This study had 2 phases and included 12 patients in each phase. Each phase included 12 patients (6 in each group). Patients in the first phase received either DBM or were left untreated. Patients in the second phase received either OP-1 on collagen type-1 or collagen type-1 alone.
Radiological and Dual Energy X-ray Absorptiometry (DEXA) evaluation showed that in patients in whom the defect was left untreated, no formation of bone occurred. At 12 months follow-up, new bone formation with bridging occurred in 4 of the 6 patients in DMB group, and 5 of the 6 patients in OP-1 group. One patient in OP-1 group did not show any evidence of new bone formation at any point during the study.
Ontario Pilot Study
A prospective pilot study was conducted in Ontario, Canada to investigate the safety and efficacy of OP-1 for the treatment of recalcitrant long bone nonunions. The study looked at 15 patients with complex, recalcitrant, long bone nonunions whose previous treatment had failed. The investigators concluded that this bone graft substitute appears to be safe and effective in providing sufficient biological stimulation in difficult to treat nonunions. Results of a more complete study on 70 patients are ready for publication. According to the principal investigator, OP-1 was 90% effective in inducing bone formation and bone healing in this sample.
Alternative Technologies
The Medical Advisory Secretariat conducted a literature search from January 1, 2000 to February 28, 2005 to identify studies on nonunions/bone defects that had been treated with alternative technologies. A review of these studies showed that, in addition to the gold standard autologous bone marrow grafting, bone allografts, demineralized bone matrices, bone graft substitutes, and autologous bone marrow have been used for treatment of nonunions and bone defects. These studies were categorized according to the osteoinductive, osteoconductive, and osteogenesis properties of the technologies studied.
A review of these studies showed that bone allografts have been used mostly in various reconstruction procedures to restore the defect after excavating a bone lesion. Two studies investigated the effectiveness of DBM in healing fracture nonunions. Calcium phosphate and calcium sulphate have been used mostly for repair of bone defects.
Several investigators have looked at the use of autologous bone marrow for treatment of long bone nonunions. The results of these studies show that method of percutaneous bone marrow grafting is highly effective in the treatment of long bone nonunions. In a total of 301 fractures across all studies, 268 (89%) healed with a mean healing time of 2.5 to 8 months. This healing time as derived from these case series is less than the timing of the primary end point in Friedlaender’s study (9 months). Table 2 summarizes the results of these studies. Table 2 summarizes the results of these studies.
Studies that used Percutaneous Bone Marrow Grafting for Treatment of Nonunions
Economic Analysis
Based on annual estimated incidence of long-bone nonunion of 3,863 - 7,725, the annual hospitalization costs associated with this condition is between $21.2 and $42.3 million based on a unit cost of $5,477 per hospital separation. When utilized, the device, a single vial of OP-1, is approximately $5,000 and if adopted universally in Ontario, the total device costs would be in the range of $19.3 - $38.6 million annually. The physician fee for harvest, insertion of bone, or OP-1 is $193 and is $193 for autologous bone marrow transplantation. Total annual physician costs are expected to be in the range of from $0.7 million to $1.3 million per year. Expenditures associated with long-bone nonunion are unlikely to increase since incidence of long-bone nonunion is unlikely to change in the future. However, the rate of uptake of OP-1 could have a significant impact on costs if the uptake were large.
The use of OP-1 and autologous bone marrow transplantation may offset pain medication costs compared with those associated with autologous bone harvest given that the former procedures do not involve the pain associated with the bone harvest site. However, given that this pain is normally not permanent, the overall offset is likely to be small. There are likely to be smaller OHIP costs associated with OP-1 than bone-harvest procedures given that only 1, rather than 2, incisions are needed when comparing the former with the latter procedure. This offset could amount to between $0.3 million to $0.7 million annually.
No data on the cost-effectiveness of OP-1 is available.
PMCID: PMC3382627  PMID: 23074475
12.  Skeletal Muscle Haemangioma: A Cause for Chronic Pain about the Knee: A Case Report 
Case Reports in Orthopedics  2012;2012:452651.
Skeletal muscle haemangiomas are uncommon soft tissue tumors; more than 90% are misdiagnosed initially. They present as chronic pain and swelling in a muscle with or without a history of trauma. Plain X-rays, bone scans, computerized tomography (CT) studies, and angiography studies may not always be specific for this tumor. Diagnostic ultrasound is an appropriate initial imaging modality for suspected haemangioma, although magnetic resonance imaging is the investigation of choice. Many treatment modalities for the symptomatic haemangiomas are available of which surgical excision is the most preferred. We present an unusual case of pain, swelling, and restriction of movements in the right knee following an episode of trauma in a 12-year-old boy who was being followed for 1 year by a general practioner and later referred to us. The patient was diagnosed to have intramuscular cavernous haemangioma in the vastus medialis by us for which he was treated by surgical excision and followed for 1 year and found to have no recurrence. The clinical features, radiological picture, pathological histology, diagnostic tools, and treatment options have been discussed.
PMCID: PMC3504282  PMID: 23259123
13.  Postradiotherapeutic changes and their evolution in MRI in children with aggressive soft tissue tumors 
Polish Journal of Radiology  2010;75(3):7-16.
Magnetic resonance imaging is a commonly used method of monitoring of soft tissue tumours. The aim of the work was to describe precisely the typical changes within soft tissues and bones occurring after radiotherapy in children treated for sarcomas and other soft tissue tumours. With time, the changes undergo evolution and their characteristics and comparison with previous examinations help in a difficult differentiation between tumour lesions and posttherapeutic changes.
Fifteen children and young adolescents (9 boys and 6 girls) aged between 2 and 22 years (mean age of 13.4 years) with diagnosed aggressive soft tissue tumours, were treated with radiotherapy. There were 102 MRI examinations analysed in the period from February 2004 to February 2008. The examinations were performed with a 1.5T MRI scanner in the following sequences: SE T1, SE T1+fatsat, before and after gadolinium administration (Gd), FSE T2 and STIR in three planes, and, in some selected cases, a dynamic gadolinium-enhanced (DCE MRI) examination with FAME sequence.
Histopathological examinations showed: rhabdomyosarcoma (RMS) in 8 cases, synovial sarcoma – 3, agressive desmoid fibroma – 3, mesenchymoma mal. – 1. MRI examinations were performed at different postradiotherapeutic stages, several times in one patient (12 times at the most).
Every postirradiation stage revealed a typical picture of posttherapeutic changes. We distinguished four stages and described changes in different sequences within soft tissues and bones, as well as features of contrast enhancement and enhancement curves in a dynamic study. The stages included: I stage – early, up to 3 months after rth, II stage – chronic, from 3 months to 12 months after rth, with some differences between the following periods: • 3–9 months; 9–12 months; III stage – late, from 1 to 3 years after rth, IV stage – distant, more than 3 years after rth.
In the early stage, there were 2 cases with a suspicious, equivocal image of postradiotherapeutic changes. In the chronic stage, there was one recurrence and one case of increasing changes after the therapy. However, the changes resolved in subsequent examinations. In the distant stage, we found two cases of a local recurrence.
1. MRI is a method of choice in the monitoring of treatment of aggressive soft tissue tumours and in diagnosis of recurrence. 2. To interpret the examination results, it is very important to know the MRI characteristics of changes after radiotherapy and their evolution with time. 3. Interpretation of MRI images and differentiation between postradiotherapeutic and neoplastic changes is difficult, especially at an early postradiotherapeutic stage. 4. A dynamic MRI examination may be useful in the differentiation between postradiotherapeutic and neoplastic changes but it may be unreliable at an early postradiotherapeutic stage. 5. When interpreting the results, it is very important to compare the image with the previous ones. It is therefore indicated to carry out a baseline MRI in the early postradiotherapeutic stage, and then further follow-up images, at several-month intervals.
PMCID: PMC3389886  PMID: 22802785
soft tissue sarcomas; magnetic resonance imaging (MRI); radiotherapy (rth)
14.  Pitfalls in the diagnosis of paediatric tumours 
Cancer Imaging  2010;10(1A):S42.
The most important factor in terms of differential diagnosis of a new mass lesion in children is the child’s age. In infancy, for example, congenital masses and many benign tumours are relatively common. As children grow older, the likely tumours vary with time. Some tumours, such as rhabdomyosarcomas, occur throughout childhood but most malignancies have relatively specific ages when their frequency is greatest. Those masses that manifest as a lump anywhere in the body, including the skull, should be evaluated first with ultrasound. Although benign lesions are often soft to palpation and malignant lesions firm, this is an unreliable clinical sign. Many lymphatic malformations come to attention as a result of an intra-lesional bleed which makes the mass tense and firm initially. Ultrasound can identify the cystic or solid nature of a mass lesion with relative ease. Vascularity can also be easily assessed, an important factor in evaluating proliferating haemangiomas, which manifest typically as fast-growing lumps in the first year of life. More complex mass lesions, or lesions with a deep extension, merit further cross-sectional imaging ideally with magnetic resonance (MR) imaging. If computed tomography (CT) is used, then only post contrast enhanced images are necessary as non-contrast images are usually uninterpretable (because of a lack of retroperitoneal or mediastinal fat in the abdomen and chest, respectively). Post contrast enhanced MR images are useful too in general, because enhanced sequences are necessary to fully evaluate lymphatic and vascular malformations, both of which can mimic malignant solid masses. Most solid tumours ultimately need biopsy confirmation, which is usually possible under ultrasound guidance. All tumours, with the exception of neuroblastoma, require chest CT for staging purposes. Sarcomas currently are also staged with radionuclide bone scans although there is a trend towards using more positron emission tomography (PET)/CT in patients with sarcomatous tumours. Neuroblastoma is staged via a combination of a meta-iodo-benzyl-guanidine scan plus bone marrow aspirates and trephine biopsies. Some imaging pitfalls such as foot vein contrast medium injection mimicking inferior vena cava thrombus, false-positive bone scans after bone biopsy, heavily calcified lesions mitigating against adequate ultrasound evaluation, and other examples will be illustrated via individual case presentations.
PMCID: PMC2967142
15.  Discovertebral (Andersson) lesions in severe ankylosing spondylitis: a study using MRI and conventional radiography 
Clinical Rheumatology  2010;29(12):1433-1438.
The objective of this study is to investigate the prevalence of Andersson lesions (AL) in ankylosing spondylitis (AS) patients who will start anti-tumor necrosis factor (TNF) treatment. Radiographs and magnetic resonance imaging (MRI) of the spine were performed before therapy with anti-TNF. ALs were defined as discovertebral endplate destructions on MRI, associated with bone marrow edema and fat replacement or sclerosis, a decreased signal on T1, enhancement after contrast administration (gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)), and increased signal on T2 and short tau inversion recovery (STIR). Additionally, conventional radiography showed a fracture line, irregular endplates, and increased sclerosis of adjacent vertebral bodies. Fifty-six AS patients were included, 68% males, mean age of 43 years, and mean disease duration of 11 years. The mean bath ankylosing spondylitis disease activity index was 6.4, and 24% of all patients had ankylosis. Only one patient showed a discovertebral abnormality with bone marrow edema of more than 50% of the vertebral bodies adjacent to the intervertebral disk of T7/T8 and T9/T10, a hypodense signal area on T1, and a high signal on STIR. Irregular endplates were depicted, and T1 after Gd-DTPA demonstrated high signal intensity around the disk margins. However, no fracture line was visible on conventional radiology, and therefore, this case was not considered to be an AL. No AL was detected in our AS patients, who were candidates for anti-TNF treatment. One patient showed a discovertebral abnormality on MRI, without a fracture line on conventional radiology. The relative small proportion of patients with a long-established disease might explain this finding for, particularly, an ankylosed spine is prone to develop an AL.
PMCID: PMC2970813  PMID: 20496041
Andersson lesion; Ankylosing spondylitis; anti-TNF; Discovertebral lesion; MR imaging
16.  Sphenoid sinus ectopic pituitary adenomas: CT and MRI findings 
The British Journal of Radiology  2010;83(987):218-224.
Ectopic pituitary adenomas (EPAs) are rare lesions. The purpose of this study was to describe the CT and MRI features of sphenoid sinus EPAs. Eight patients with histology-proven EPAs in the sphenoid sinus, all of whom underwent CT and MRI, were reviewed retrospectively. The following imaging features were analysed: (i) size, (ii) margin, (iii) CT attenuation characteristics and (iv) MRI signal intensity. In addition, the involvement of adjacent structures and the time–intensity curve (TIC) of dynamic contrast-enhanced (DCE) MRI were analysed. All EPAs had well-defined margins and showed no relationship to the intrasellar pituitary gland. The mean size was 28 mm (range, 20–46 mm). On non-enhanced CT, the lesions appeared isodense to grey matter in 7 (88%) patients and hypodense in 1 (12%) patient. Only two patients underwent post-contrast CT, and they showed moderate enhancement. On T1 weighted images, EPAs appeared isointense in 6 (75%) patients and hypointense in 2 (25%). On T2 weighted images, the lesions appeared hyperintense in 2 (25%) patients and isointense in 6 (75%). EPAs showed mild to moderate heterogeneous contrast enhancement and exhibited a cribriform-like appearance. Two patients underwent DCE MRI; the TIC showed a rapidly enhancing and slow washout pattern. The following features were also seen: an empty sella, bone changes and involvement of the cavernous sinus (5 patients; 62.5%). In conclusion, a high index of suspicion for EPA and a familiarity with the imaging findings may help to diagnose this rare entity accurately.
PMCID: PMC3473558  PMID: 19651706
17.  Perfusion and Diffusion Abnormalities of Multiple Sclerosis Lesions and Relevance of Classified Lesions to Disease Status 
Journal of neurology & neurophysiology  2014;2014(Suppl 12):12-.
Hemodynamic abnormality and disruption of white matter (WM) integrity are significant components in the pathophysiology of multiple sclerosis (MS) lesions. However, the roles of stratified lesions with distinct degrees of hemodynamic and structural injury in disease states remain to be explored. We tested the hypothesis that hemodynamic and structural impairment, as assessed by cerebral blood volume (CBV) and fractional anisotropy (FA), respectively, characterizes the extent of tissue injury, and the load of lesion with substantial tissue destruction would reflect the disease status and therefore, would be related to clinical disability.
Seven relapsing-remitting MS patients and seven healthy controls underwent perfusion, diffusion and conventional MRI scans. Based on T2-FLAIR and T1-weighted image, WM plaques were classified. After image coregistration, values of CBV and FA were estimated in three distinct lesion types (active, T1-hypointense and T1-isointense lesion) and compared with those obtained in WM from controls. A total of 1135 lesions were evaluated. Brain volumetric measurement and correlative analysis between brain atrophy, lesion volume and clinical disability were also performed.
Compared with normal WM, significantly reduced CBV and FA were present in the T1-hypointense lesion, while insignificant changes in both parameters were exhibited in the T1-isointense lesion. However, increased CBV but significantly decreased FA was detected in the active lesion. A close spatial relationship between active and T1-hypointense lesion was observed. Lesion load represented by T1-hypointense plus active lesion volume significantly correlated with brain atrophy, which, in turn, significantly correlated with the severity of clinical disability.
A distinct combination of CBV and FA characterizes the status of a specific lesion type. A severe structural impairment does not solely occur in the T1-hypointense lesion, but is also associated with the active lesion. The burden of the lesion with extensive structural damage provides an image index, indicative of disease status.
PMCID: PMC4309012  PMID: 25642354
Cerebral blood volume; Fractional anisotropy; Multiple sclerosis; Lesion load; Brain atrophy; Clinical disability; MRI
18.  Presumptive Intramuscular Hemangioma of the Masseter Muscle 
Patient: Male, 34
Final Diagnosis: Intramuscular hemangioma of the masseter muscle
Symptoms: Swelling over parotid region
Medication: —
Clinical Procedure: Clinical-Radiological work-up
Specialty: Radiology
Rare disease
Hemangioma is a benign vascular proliferation. Intramuscular hemangiomas are rare, accounting for less than 1% of all hemangiomas, and occur normally in the trunk and extremities. Approximately 10–20% of intramuscular hemangiomas are found in the head and neck region, most often in the masseter muscles. The typical clinical characteristic is a painful soft tissue mass without cutaneous changes. Currently, MRI is the standard imaging technique for diagnosing soft-tissue hemangioma. The optimal management is the surgical resection.
Case Report:
We report a case of 34-year-old male patient consulted for a swelling of 1 year evolution, around the parotid region. On physical examination, a soft, well-contoured lesion of about 2 cm on its long axis was found. MRI showed a space-occupying lesion in the left masseter muscle, with intermediate signal intensity on T1-weighted images and hyperignal intensity on T2-weighted images, containing nodular hypointense foci corresponding to calcification. The presumptive diagnosis of an intramasseteric hemangioma with phlebolith was made based on these findings. The patient was informed about her condition, and treatment options were discussed; however, the patient elected to forgo treatment at that time.
The possibility of an IMH should be included in the differential diagnosis of any intra-masseteric lesion. The appropriate radiologic examinations especially MRI can enhance accurate preoperative diagnosis; the treatment of choice should be individualized in view of the clinical status of the patient.
PMCID: PMC4298281  PMID: 25590509
Diagnostic Imaging; Hemangioma; Magnetic Resonance Imaging
19.  Bizarre Parosteal Osteochondromatous Proliferation: Nora's Lesion 
Iranian Journal of Radiology  2011;8(2):119-125.
The purpose of this study was to review the imaging and anatomopathologic findings and to discuss the main differential diagnosis of bizarre parosteal osteochondromatous proliferation (BPOP) or Nora's lesion, a rare benign surface lesion of the bone. Histologically confirmed plain radiographs, ultrasound, CT and MRI images of four patients with BPOP were obtained and retrospectively reviewed. Three cases involving the hand and one involving the foot are reported. On plain radiographs, BPOP is a wellmarginated, calcified or ossified mass arising directly from the cortical surface of the underlying bone. Ultrasound images show a low echoic peripheral cap around the lesion. CT images show the wide base of the lesion. On MRI, BPOP was of a low signal on T1, enhancing following gadolinium administration. Underlying bone and adjacent surrounding soft tissues were normal.
PMCID: PMC3522321  PMID: 23329928
Parosteal Osteochondroma; Bone; Radiography; Ultrasound; CT; MRI
20.  Diffusion weighted MR imaging in the differential diagnosis of haemangiomas and metastases of the liver 
Radiology and Oncology  2010;44(1):24-29.
The purpose of the study was to evaluate the value of diffusion-weighted imaging in the differential diagnosis of haemangiomas from metastases of the liver.
Patients and methods.
We analyzed 69 lesions in 38 patients (33 haemangiomas; 36 metastases) in the retrospective study. Diffusion-weighted imaging was performed using a breath-hold single-shot echo-planar spin echo sequence with three b factors (0, 500 and 1000 sec/mm2), and apparent diffusion coefficients (ADCs) were calculated. For the quantitative evaluation, signal intensity of the lesions, lesion-to-liver signal intensity ratios, ADC of the lesions, and lesion-to-liver ADC ratios were compared between the groups. The statistical significance was determined by student’s-t test.
With the b factor 500 sec/mm2, no statistical significance was achieved (p>0.05). With the b factor of 1000 sec/mm2, both the signal intensity and lesion-to-liver signal intensity ratio of the metastases were significantly higher than those for haemangiomas (p<0.001). The cut-off value at 2.6 yielded a sensitivity of 86% and a specificity of 82% for the lesion-to-liver signal intensity ratio. The ADC, and lesion-to-liver ADC ratio of the metastases were significantly lower than those of haemangiomas (p<0.001). With cut-off value of 1.7, ADC ratio had a sensitivity of 88% and a specificity of 72% for ADC lesion/liver.
Diffusion-weighted imaging with high b value may help in the differential diagnosis of metastases from haemangiomas of the liver.
PMCID: PMC3423674  PMID: 22933887
liver; haemangioma; metastasis; magnetic resonance imaging; diffusion-weighted imaging, apparent diffusion coefficient
21.  An intradural cervical chordoma mimicking schwannoma 
Journal of Injury and Violence Research  2012;4(3 Suppl 1): Paper No. 83.
Chordoma is a relatively rare tumor originating from the embryonic remnants of the notochord. This is an aggressive, slow growing and invasive tumor. It occurs mostly at the two ends of neuroaxis which is more frequent in the sacrococcygeal region. Chordoma in vertebral column is very rare. This tumor is extradural in origin and compresses neural tissues and makes the patient symptomatic. This tumor found extremely rare in the spinal region as an intradural tumor.
The present study reports a rare case of intradural chordoma tumor as well as its clinical manifestations and treatment options.
The patient was a 50-year-old female presented with 9 months history of progressively worsening neck pain, cervical spine chordoma resembling neurinoma and right arm numbness. Physical examination showed no weakness in her limbs, but she had upward plantar reflex and mild hyperreflexia. In a magnetic resonance imaging (MRI) scan of the cervical spine there was an ill-defined enhancing mass in the posterior aspect of C2-C3 body caused cord compression more severe in right side as well as foraminal scalloping. The patient underwent surgery and after midline posterior cervical incision and paravertebral muscle stripping a laminectomy was performed from C1 through C4 using a high speed drill. Needle biopsy revealed chordoma on frozen section and all of accessible parts of tumor were excised. The gross and microscopic histopathological appearance was consistent with chordoma.
Chordomas are malignant tumors that arise from remains of embryonic notochord. These ectopic rests of notochord termed “ecchordosis physaliphora “can be found in approximately 2% of autopsies. These are aggressive, slow growing, locally invasive and destructive tumors those occur in the midline of neuroaxis. They generally thought to account for 2% to 4% of all primary bone neoplasms and 1% to 4% malignant bone neoplasms. They are the most frequent primary malignant spinal tumors after plasmacytomas. The incidence has been estimated to be 0.51 cases per million. The most common location is sacrococcygeal region followed by the clivus. These two locations account for approximately 90% of chordomas. Of the tumors that do not arise in the sacrum or clivus, half occur in the cervical region, with the remainder found in the lumbar or thoracic region, in descending order of frequency. Cervical spine chordomas account for 6% of all cases. Distal metastasis most often occurs in young patients, those with sacrococcygeal or vertebral tumors, and those with atypical histological features. These tumors usually spread to contiguous anatomical structures, but they may be found in distant sites (skin, musculoskeletal system, brain, and other internal organs). Seeding of the tumor has also been reported, and the likely mechanism seems to be tumor cell of contamination during the surgical procedures. The usual radiological findings in chordomas of spine are destructive or lytic lesions with occasional sclerotic changes. They tend to lie anterolateral, rather than dorsal towards the cord, and reportedly known to invade the dura. The midline location, destructive nature, soft tissue mass formation and calcification are the radiological hallmarks of chordomas. Computed Tomography (CT) scan is the best imaging modality to delineate areas of osteolytic, osteosclerotic, or mixed areas of bone destruction.Chordoma is usually known as a hypovascular tumor which grows in a lobulated manner. Septal enhancement which reflects a lobulated growth pattern is seen in both CT and MRI and even in gross examination. Other epidural tumors include neurinoma, neurofibroma, meningioma, neuroblastoma, hemangioma, lymphoma and metastases. Their differentiation from chordoma may be difficult due to the same enhancement pattern on CT and MRI.
A dumbbell-shaped chordoma is a rare pathogenic condition. The dumbbell shape is a characteristic finding of neurinomas in spine but in spinal neurinomas extention to transverse foramina has not yet been reported. Although our case mimicked a dumbbell shaped neurogenic tumor, its midline location and destructive pattern were characteristic feature indicating a clue to the diagnosis of chordoma that was already confirmed with histopathology.
This unusual behavior of tumor extension can be explained by the soft and gelatinous nature of the tumor enabling the mass to extend or creep into the existing adjacent anatomical structures.
Cervical Chordoma, Intradural, Computed tomography
PMCID: PMC3571609
22.  Radiographic characteristics of bone metastases from hepatocellular carcinoma 
Contemporary Oncology  2012;16(5):424-431.
Aim of the study
Different carcinomas have different characteristics, which may play a crucial role in diagnosis and treatment. Our study was aimed at understanding the development pattern of bone metastasis from hepatocellular carcinoma, based on its imaging characteristics, so as to provide a more targeted treatment.
Material and methods
Forty two patients (123 lesions) with hepatocellular carcinoma hospitalized from June 2006 to June 2011 underwent radiotherapy for bone metastasis in our department. Clinical and imaging data were analyzed retrospectively (based on CT imaging, also with reference to MRI, ECT, or PET-CT, etc.).
One hundred of 123 lesions were vertebral metastases; 23 were non-vertebral. The major form of bone destruction was osteolytic change. Metastasis in the vertebral body was found in 87.8%, and lesions were well distributed in various sections. Vertebral appendix metastasis accounted for 52%, where lesions could be independent of vertebral body metastasis. Formation of a soft tissue mass in bone metastasis was found in 68.6% of all patients. The center of the mass from a vertebral body metastasis was mostly located at the site of the lesion; masses from the vertebral appendix and the pelvis, on the other hand, often presented as a “peripheral mass”. Masses were not formed in lesions with pure osteoblastic changes.
The most common radiographic feature is an osteolytic lesion, either replaced by soft tissue mass, or invaded by soft tissue mass from the vicinity, which often cause compression syndrome. Vertebral appendix metastasis can exist independently from vertebral body metastasis, which should be paid more attention to avoid missed diagnosis.
PMCID: PMC3687457  PMID: 23788922
hepatocellular carcinoma; bone metastasis; vertebrae; spinal cord compression; computer assisted radiographic image interpretation
23.  Bone Metastasis from Primary Hepatocellular Carcinoma: Characteristics of Soft Tissue Formation 
To assess the characteristics of bone metastasis from hepatocellular carcinoma and the radiation field arrangement based on imaging studies.
Materials and Methods
Fifty-three patients (84 lesions) with bone metastasis from a primary hepatocellular carcinoma completed palliative radiation therapy. All patients underwent one of following imaging studies prior to the initiation of radiation therapy: a bone scan, computed tomography or magnetic resonance imaging. The median radiation dose was 30 Gy (7~40 Gy). We evaluated retrospectively the presence of soft tissue formation and the adjustment of the radiation field based on the imaging studies.
Soft tissue formation at the site of bony disease was identified from either a CT/MRI scan (41 lesions) or from a symptomatic palpable mass (5 lesions). The adjustment of the radiation field size based on a bone scan was necessary for 31 of 41 soft tissue forming lesions (75.6%), after a review of the CT/MRI scan. The median survival from the initial indication of a hepatoma diagnosis was 8 months (2 to 71 months), with a 2-year survival rate of 38.6%. The median survival from the detection of a bone metastasis was 5 months (1 to 38 months) and the 1-year overall survival rate was 8.7%.
It was again identified that bone metastasis from a primary hepatocellular carcinoma is accompanied by soft tissue formation. From this finding, an adjustment of the radiation field size based on imaging studies is required. It is advisable to obtain a CT or MRI scan of suspected bone metastasis for better tumor volume coverage prior to the initiation of radiation therapy.
PMCID: PMC2739323  PMID: 19746218
Bone metastasis; hepatocellular carcinoma; soft tissue formation; radiation therapy
24.  Giant Cavernous Haemangioma of the Wandering Spleen 
The Indian Journal of Surgery  2012;75(1):54-55.
Cavernous haemangioma is a rare disorder of the spleen with fewer than 100 cases reported [1]. Spleen may have an unusual degree of mobility and occupy an atypical location in less than 0.2 % of all the patients [2] Wandering spleen has been associated with incomplete fusion or even absence of gastrosplenic and lienorenal ligaments [3]. A 36-year-old woman presented with a six-month history of pain in the left hypochondrium and a massive splenomegaly. Ultrasonography, Doppler studies, and computed tomography were performed. Ultrasonography showed a large heterogeneous solid cystic mass, measuring 11.2 cm × 10.6 cm, located in the pelvis. Thin soft tissue connecting this mass to spleen noticed. Spleen was malrotated & in left lumbar fossa. Doppler studies shows prominent vessels at the periphery of the mass with high velocity external flow and scanty vascularity at the centre, probably suggesting haemangioma. Contrast-enhanced computed tomography (CECT) of the abdomen showed spleen in left lumbar region with a large heterogeneous, predominantly cystic mass lesion measuring 11.2 x 10.6 cm seen arising from diaphragmatic surface of lower pole of the spleen (Fig. 1), findings were suggestive of wandering spleen with a haemangioma or a hydatid cyst. The patient was explored by a left para-median incision under general anaesthesia. Peroperatively, there was a malrotated enlarged spleen with a large solid lesion confined to the lower half of the spleen (Fig. 2). Gastrosplenic ligament was not visualized. Total splenectomy was done after ligating the splenic artery as the main splenic artery was supplying the mass.
PMCID: PMC3585528  PMID: 24426387
Cavernous hemangioma; Wandering spleen; Splenectomy
25.  The role of magnetic resonance imaging in the evaluation of bone tumours and tumour-like lesions 
Insights into Imaging  2014;5(4):419-440.
Bone tumours and tumour-like lesions are frequently encountered by radiologists. Although radiographs are the primary screening technique, magnetic resonance imaging (MRI) can help narrow the differential or make a specific diagnosis when a lesion is indeterminate or shows signs of aggressiveness. MRI can extend the diagnostic evaluation by demonstrating several tissue components. Even when a specific diagnosis cannot be made, the differential diagnosis can be narrowed. MRI is superior to the other imaging modalities in detecting bone marrow lesions and tumoral tissue (faint lytic/sclerotic bone lesions can be difficult to visualise using only radiographs). Contrast-enhanced MRI can reveal the most vascularised parts of the tumour and MRI guidance makes it possible to avoid biopsing necrotic areas. MRI is very helpful in local staging and surgical planning by assessing the degree of intramedullary extension and invasion of the adjacent physeal plates, joints, muscle compartments and neurovascular bundles. It can be used in assessing response to neoadjuvant therapy and further restaging. The post-therapeutic follow-up should also be done using MRI. Despite the high quality of MRI, there are a few pitfalls and limitations of which one should be aware. Applications of MRI in bone tumours will probably continue to grow as new sequences are further studied.
Teaching Points
• When a lesion is indeterminate or shows signs of aggressiveness, MRI is indicated.
• When MRI does not lead to a diagnosis, biopsy is indicated.
• MRI is superior to the other imaging modalities in detecting bone marrow lesions.
• MRI is very helpful in local staging and surgical planning.
• MRI is used in assessing the response to neoadjuvant therapy, restaging and post-therapeutic follow-up.
PMCID: PMC4141345  PMID: 25005774
Magnetic resonance imaging; Bone neoplasms; Diagnosis; Neoplasm staging; Follow-up

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