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Biomedical subjects

D C Mangham

Publications and source records attributed to D C Mangham.

At least 37 records · Page 2Linked to original sources

Metal-containing lymph nodes following prosthetic replacement of osseous malignancy: potential role of MR imaging in characterisation.

The identification of regional lymphadenopathy in patients with bone malignancy treated by excision and insertion of a prosthesis usually indicates metastatic disease. We present two cases in which the lymphadenopathy was due to an uncommon but well-recognized foreign body reaction. This is secondary to the lymphatic uptake of metal debris shed by the prosthesis. In one case the metal within the excised lymph node could be demonstrated on in vitro MR imaging and in retrospect on the original in vivo scans. This condition should be considered when undertaking an MR examination in patients with bone malignancy treated by prosthetic replacement in whom there is a clinical suspicion of metastatic spread to the regional lymph nodes.

Adolescent↗

MR imaging of brown tumour with fluid-fluid levels: a report of three cases.

Fluid-fluid levels on CT and MR imaging are a typical feature of aneurysmal bone cysts but have also been reported in many other osseous lesions containing haemorrhage. We report fluid-fluid levels in four brown tumour in three patients with primary hyperparathyroidism in which the initial radiological diagnosis was thought to be a bone tumour. To the authors' knowledge, this is the first time that association has been reported in the international literature.

Adult↗

Chordoma periphericum: a case report.

The authors describe a tumor that had the histologic and ultrastructural features and immunohistochemical profile of an axial chordoma, but arose in the distal ulna. A skeletal survey failed to show any other site of involvement. The tumor was resected, and the patient remains free of disease 2 1/2 years later. Rare tumors with the histologic features of chordoma have been reported in appendicular locations. Chordoma periphericum, a tumor that has the potential to metastasize, needs to be distinguished from parachordoma because no classic parachordoma has been reported to disseminate.

Adult↗

Solitary fibrous tumour of the thyroid gland.

Solitary fibrous tumours of the thyroid gland are rare; only five cases have been reported in the literature. Clinically, they present as a long-standing firm mass in the thyroid. Histologically, they show a range of appearances including so-called 'patternless growth pattern', spindle-cell morphology, alternating hypo- and hyper-cellular areas, keloid-like hyalinization and a prominent haemangiopericytoma - like architecture. The behaviour of extrathoracic solitary fibrous tumours is unpredictable and requires careful, long-term follow-up.

Humans↗

Synovial sarcoma arising in association with a popliteal cyst.

Synovial sarcoma is a relatively common soft tissue sarcoma particularly in the adolescent and young adult. We report an unusual case of a synovial sarcoma arising within a popliteal cyst in a 13-year-old female presenting with bilateral popliteal cysts. MR imaging demonstrated the cyst with evidence of subacute haemorrhage and a discrete nodule of tumour.

Adolescent↗

CD44 isoform expression in synovial sarcoma correlates with epitheliogenesis but not prognosis.

AIMS: We immunohistochemically determined the expression of CD44 standard and splice variant isoforms in a series of synovial sarcomas and sought correlations with histological subtype and clinical parameters including outcome. METHODS AND RESULTS: From 39 patients, a total of 56 formalin-fixed and paraffin-embedded tumour samples (including initial, recurrent and metastatic tumours) were used to immunohistochemically evaluate the expression of epitopes encoded by CD44s and the CD44 splice variants CD44v3-v10. Significance of proposed prognostic indicators was evaluated in relation to the survival, time to local recurrence and time to metastases using log-rank analysis. Sixty-four percent of synovial sarcomas expressed CD44s and 46% expressed CD44v3-v10 (var). Synovial sarcomas with epithelial or epithelioid areas preferentially expressed CD44s in these areas when compared with the spindle cell element. There were no correlations with clinical parameters or outcome. CONCLUSION: The expression of CD44 was not found to correlate with survival, local recurrence or metastatic ability. In synovial sarcoma, CD44 and variant isoform expression appears to be associated with the degree of epithelial differentiation. CD44 expression in synovial sarcoma shows interesting similarities to CD44 expression in embryological epitheliogenesis.

Cell Differentiation↗

MICA-a highly sensitive and avidin-free immunohistochemical detection system.

MICA is an acronym for mirror image complementary antibodies. The MICA system is a novel, avidin-free immunohistochemical detection system that provides a significant increase in sensitivity compared to traditional immunodetection systems. The principle of the system is the alternate and sequential application of mutually attractive polyclonal antibodies to form a large complex of antibodies which can cross-link tissue-bound primary antibodies. Peroxidase conjugated to the constituent antibodies permits signal generation. The formed peroxidase-containing complex is very stable and, by cross-linking tissue-bound primary antibodies, possesses high avidity for the target antigens, thereby producing high immunohistochemical sensitivity.

Animals↗

Experience in the treatment of dedifferentiated chondrosarcoma.

Dedifferentiated chondrosarcoma is a rare, highly malignant variant of chondrosarcoma in which a high-grade spindle-cell sarcoma coexists with a lower-grade chondroid tumour. We have reviewed our experience with this neoplasm in 22 patients, all of whom were treated using modern oncological principles of planned resection and chemotherapy. Despite this the median survival was under nine months and only 18% were alive at five years. Those patients who received chemotherapy, and in whom wide margins of excision were achieved at operation, did best. It is essential to have an accurate preoperative diagnosis in order to plan treatment which may offer a better prospect of cure.

Adolescent↗

Telomerase activity in soft-tissue and bone sarcomas.

The telomerase enzyme is a reverse transcriptase capable of replacing the telomeric DNA sequences that are lost at each cell division. Telomerase activation permits extended cell proliferation beyond normal senescence checkpoints, and accordingly, telomerase activity has been detected in a wide range of malignant cells and tissues but is absent in terminally differentiated somatic cells. To date, the majority of cancer-related telomerase analyses have been performed on carcinomas that originate from epithelial cells, and few reports have included tumors originating from nonepithelial cells. In this study, we used the PCR-based telomeric repeat amplification protocol (TRAP) to assay telomerase activity in nuclear protein extracts obtained from a range of malignant and benign connective tissue lesions. In total, 62 histologically diagnosed specimens were analyzed including 37 sarcomas, 7 benign mesenchymal tumors, 12 normal tissue samples, and 6 carcinoma metastases obtained from bone. Thirty (81%) of the 37 primary sarcoma samples contained telomerase activity, and four of the six carcinoma metastases were also positive. Conversely, telomerase activity was detectable in only one of seven benign lesions and in none of the 12 normal connective tissue controls. Tumors of connective tissue origin can sometimes be difficult to categorize and to evaluate microscopically with regard to clinical management. As is the case in carcinomas, the presence of telomerase activity appears to be indicative of malignancy in mesenchymal tumor biopsy material and therefore may be useful as an adjunct to the pathologist in the assessment of borderline cases.

Adolescent↗

Parosteal osteosarcoma of a metatarsal with intramedullary invasion.

A 70-year-old man presented with increasing swelling of 2 years' duration, on the dorsal aspect of the forefoot. Imaging studies revealed a heavily calcified surface lesion of bone with early invasion of the underlying second metatarsal. Both imaging findings and the subsequent resection histology were consistent with a parosteal osteosarcoma, which is particularly rare at this site and at this age. The differential diagnosis of a mineralizing surface lesion of bone arising in the foot is discussed.

Aged↗

SAPHO syndrome: 20-year follow-up.

Considerable attention has been paid in the past 10 years to the radiological spectrum of disease entities belonging to the SAPHO syndrome. We report an unusual case presenting with an extra-axial (femoral) lesion, prior to description of this syndrome, which was radiologically and histologically mistaken for a parosteal osteosarcoma. Nineteen years later, a further lesion developed in the scapula together with the typical sternoclavicular manifestations, at which stage the correct diagnosis of SAPHO syndrome was established.

Acquired Hyperostosis Syndrome↗

Overexpression of p53 protein in primary Ewing's sarcoma of bone: relationship to tumour stage, response and prognosis.

Biopsy tissues of 52 patients with Ewing's sarcoma of bone treated between 1983 and 1993 were examined immuno-histochemically to determine the significance of p53 protein in diagnosis and prognosis of Ewing's sarcoma. Mean age at diagnosis was 17 years (range 6-36) and minimum follow-up was 30 months. The tumours were located in the extremities and central bones in 35 and 17 patients respectively. Metastases were present in seven patients at diagnosis. Treatment consisted of chemotherapy, surgery and/or radiotherapy in all the patients. Overexpression of p53 protein was demonstrated in seven patients (14%). There was no relationship between expression of p53 and site of tumours. Patients who overexpressed p53 protein appeared to have more advanced diseases at diagnosis and poorer response to chemotherapy than those without p53 overexpression. The 5-year relapse-free survival and overall survival in patients without metastases at the time of diagnosis were 66% and 71%, respectively, in p53 protein-negative patients compared with 20% relapse-free and overall survival in those with p53 protein overexpression (P= 0.01). The poorer prognosis in p53 protein-positive patients was independent of site, local treatment or necrosis of the tumours (P < 0.05). Over-expression of p53 protein is an independent poor prognostic factor in Ewing's sarcoma of bone.

Adolescent↗

A novel immunohistochemical detection system using mirror image complementary antibodies (MICA).

AIMS: To describe and illustrate a novel and highly sensitive peroxidase-based immunohistochemical detection system which employs mutually attractive, mirror image complementary antibodies (MICA). METHODS AND RESULTS: To demonstrate the sensitivity of the MICA system alongside the avidin-biotin complex (ABC) method, we selected a range of mouse monoclonal and rabbit polyclonal primary antibodies against antigens that are generally regarded as relatively difficult or impossible to detect on formalin-fixed, paraffin-embedded lymphoid tissue. Compared with the ABC method, the MICA immunodetection method enabled us to dilute primary antibodies up to 200-fold with equivalent or superior immunostaining results and, usually, considerably shortened primary antibody incubation times. CONCLUSIONS: We have described and illustrated a novel immunohistochemical detection system and demonstrated greatly increased sensitivity over the commonly used ABC system. An additional advantage of the MICA system is that it is avidin-free and so avoids non-specific staining due to endogenous tissue biotin.

Animals↗

Tumour volume as a predictor of necrosis after chemotherapy in Ewing's sarcoma.

We studied the CT and MR scans, and the histology of 50 patients with primary Ewing's sarcoma of bone to determine the association between the change in tumour volume and necrosis after chemotherapy, and to ascertain their influence on prognosis. The mean age of the patients was 17 years. The limbs were involved in 40 and the axial bones in ten. The volume of the tumour at diagnosis varied from 31 to 1790 ml. There was a significant relationship between necrosis and the measured change in volume of the tumour after chemotherapy. Progression of the tumour despite chemotherapy was seen only in patients with necrosis of grades 4 to 6. Necrosis significantly influenced survival (p < 0.05), but the effect of change in volume was less significant. Change in volume of the tumour is a good predictor of necrosis induced by chemotherapy. Necrosis is a strong prognostic factor in Ewing's sarcoma.

Adolescent↗

Osteosarcoma of the pelvis.

Over a 25-year period we have treated 36 patients with osteosarcoma of the pelvis. Of the tumours, 24 (67%) were primary osteosarcomas and 12 (33%) arose either after irradiation or in association with Paget's disease. Six patients had a hindquarter amputation and 12 were treated by a limb-salvage procedure with intrapelvic excision. The five-year survival rate of all the patients with pelvic osteosarcoma was 18%, while for 17 treated by chemotherapy and surgery it was 41%. The prognosis for patients presenting with metastases or with secondary osteosarcoma was appalling and none survived after 29 months. No patient over the age of 50 years when seen initially survived for a year. Youth and a good response to chemotherapy along with complete surgical excision offer the best chance of cure.

Adolescent↗

Autologous bone grafting in staged scoliosis surgery. The patient as bone bank.

STUDY DESIGN: A prospective clinical study in which autologous rib graft, harvested during the thoracotomy in staged scoliosis correction, is stored within the patient for use during the second stage (posterior intrumentation and fusion). OBJECTIVE: To determine whether the bone stored by this technique is biologically viable and microbiologically safe. SUMMARY OF BACKGROUND DATA: To the authors' knowledge, this method of storage of bone has never been described previously. METHODS: During the first operation, the excised rib was divided into 3-5 cm fragments and stored in a sub-muscular plane adjacent to the posterior elements of the spine before closure. The graft was then retrieved at the second stage. Samples were sent for histologic and microbiologic examination before implantation. RESULTS: On histologic examination, more than 50% of the osteocytes retained their basophilic staining, indicating that they were viable. In addition, osteoclastic activity was notably absent. There was no significant bacterial contamination of the samples. Clinically, all patients achieved satisfactory bone fusion. CONCLUSION: Homeostatic equilibrium in humans provides the ideal environment in which bone graft can be stored. There is no increased risk of infection, and the osteogenic potential of the graft is retained.

Bone Transplantation↗