Biomedical subjects

Robert J Grimer

Publications and source records attributed to Robert J Grimer.

14 recordsLinked to original sources

PubMed2006

Size matters for sarcomas!

INTRODUCTION: By the time of diagnosis, sarcomas have frequently reached a large size and many patients have a long history of symptoms prior to diagnosis. The aim of this study was to assess whether size of tumour at presentation or duration of symptoms was a significant factor affecting outcome. PATIENTS AND METHODS: A prospective database recording patient, tumour, treatment and outcome factors was reviewed. A total of 1460 patients with newly diagnosed sarcomas and with > 3 years of follow-up were included for analysis. RESULTS: The mean size of sarcomas presenting to our unit was 10.7 cm at the time of diagnosis. Bone sarcomas averaged 11.3 cm with little variation by age or diagnosis, whilst subcutaneous soft tissue sarcomas averaged 10 cm. The incidence of metastases at diagnosis increased almost linearly with increasing size and the prognosis, even for patients without metastases at diagnosis became steadily worse with increasing size for all tumours, independent of other factors. Duration of symptoms did not correlate with size but patients with symptoms > 1 year had a slightly better prognosis than those with a shorter duration. CONCLUSIONS: The author makes a plea for greater awareness of potential malignancy in lumps and bumps, particularly those over the size of a golf ball (4.27 cm), making the point that the smaller the tumour at diagnosis the better the prognosis.

Adolescent↗

PubMed2006

Surgical options and outcomes in bone sarcoma.

Bone sarcomas are challenging to treat. The primary goal of treatment is local control of the disease while, if possible, achieving salvage of the limb and its function. There is no ideal method of reconstruction in limb-salvage surgery but the choice of the method of reconstruction should be individualized based upon many factors including the patient's age, the extent and location of the tumor, the wishes of the patient, and the availability of surgical facilities and expertise, as well as the cost of the procedure. In this review, the authors explore the advantages and disadvantages of the different methods of limb reconstruction. The surgical management of bone sarcomas is a real challenge to the orthopedic surgeon, owing to the diversity of sites in which tumors arise, combined with the extension of the tumor into adjacent soft tissues and their proximity, in many cases, to major neurovascular structures. There have been dramatic improvements in survival for patients with osteosarcoma and Ewing's sarcoma in the past 30 years owing to increasing effectiveness of chemotherapy. This, along with developments in imaging techniques (magnetic resonance imaging in particular) has led to earlier diagnosis and more accurate preoperative staging. Whilst traditional treatment for bone tumors used to be amputation, advances in surgical techniques have made limb-salvage procedures a valid alternative method of treatment to amputation in 80-85% of patients with primary bone sarcomas.

Amputation, Surgical↗

PubMed2005

Periosteal osteosarcoma--a European review of outcome.

Periosteal osteosarcoma is a rare primary malignant bone tumour. Treatment is by surgical excision, but controversy remains about the value of chemotherapy. The members of the European Musculo Skeletal Oncology Society (EMSOS) collaborated to produce a dataset of 119 patients. The predominant site for the tumour was the femur, followed by the tibia. All but 2 patients underwent surgery, with 9 requiring amputation and the others having limb salvage. A total of 81 patients had chemotherapy, of whom 50 had neoadjuvant chemotherapy. There was no standard chemotherapy regime, but all patients receiving chemotherapy were given doxorubicin combined with at least one other agent. The overall survival was 89% at 5 years and 83% at 10 years. Eight patients developed local recurrence, of whom 5 died. Survival was related to appearance of local recurrence (P < 0.0001) but no other single factor. The use of chemotherapy was not shown to be a prognostic factor, but was used in two-thirds of the patients in this study.

Adolescent↗

PubMed2005

Pre- and post-chemotherapy alkaline phosphatase levels as prognostic indicators in adults with localised osteosarcoma.

The prognostic value of alkaline phosphatase (AP) measured before and after chemotherapy, but before surgery was established in a retrospective survey of patients. The patients were 18 years or older, with non-metastatic high-grade osteosarcoma. Pre-chemotherapy AP was available in 89 cases, post-chemotherapy AP in 86 patients, and both in 71 cases. AP was classified as Normal (< 100% upper limit), High (100% < or = AP < 200%) or Very High (AP > or = 200%). Osteosarcoma subtype was predominantly conventional. No correlation was found between subtype and chemotherapy response, local recurrence or survival. Pre-chemotherapy AP was raised more in the osteoblastic subtype. Post-chemotherapy AP and normalisation were the same among different subtypes. AP was not correlated with local recurrence. Normal or High pre-chemotherapy AP correlated with better survival at 10 years (64% and 70%) than Very High pre-chemotherapy AP (37%, P = 0.005). Post-chemotherapy AP correlated with survival (68%, 39% and 25% in the Normal, High and Very High group, P = 0.0007) and response to chemotherapy (P = 0.049). A pre-chemotherapy AP above twice Normal correlated with worse survival. If AP decreased after chemotherapy, but was still raised, survival was better, but still worse than if AP normalised. A raised post-chemotherapy AP predicts poor chemotherapy response.

Adult↗

PubMed2005

TP53 mutations and outcome in osteosarcoma: a prospective, multicenter study.

PURPOSE: Mutations of the TP53 gene have been associated with resistance to chemotherapy as well as poor prognosis in many different malignancies. This is the first prospective study of the prognostic value of somatic TP53 mutations in patients with newly diagnosed extremity osteosarcoma. PATIENTS AND METHODS: One hundred ninety-six patients with high-grade, nonmetastatic osteosarcoma of the extremities were enrolled from seven tertiary care institutions and observed prospectively for tumor recurrence (median follow-up duration, 44 months). All patients received neoadjuvant or adjuvant chemotherapy and surgery. Tumors were analyzed for the presence of TP53 mutations by polymerase chain reaction single-strand conformation polymorphism analysis and direct DNA sequencing. The association of the status of the TP53 gene with the risk of systemic recurrence was examined using survival analyses with traditional and histologic markers as prognostic factors. RESULTS: Patient age was the only factor that varied with TP53 gene status (P = .05). No relationship was identified between TP53 status and systemic relapse (relative risk, 1.24; P = .41). Analyses based on missense or nonsense mutations gave similar results (P > .10). In multivariate analysis, large (> 9 cm) tumor size (relative risk, 1.9; P = .006) and poor histologic response (< or = 90% necrosis) to chemotherapy (relative risk, 2.14; P = .02) were the only significant independent predictors of systemic outcome. CONCLUSION: We found no evidence that TP53 mutations predict for development of metastases in patients with high-grade osteosarcoma. Identification of other genes that influence chemotherapy response and clinical outcome in osteosarcoma is needed to facilitate further improvements in patient outcomes.

Adolescent↗

PubMed2005

Management and outcome after local recurrence of osteosarcoma.

We report on the management and outcome of 96 patients who developed local recurrence (LR) after having definitive primary treatment with chemotherapy and surgery for non-metastatic osteosarcoma. LR developed at a median of 11 months from initial surgical treatment. 18% of patients had metastases prior to the diagnosis of LR and 23% were found to have metastases synchronously. The prognosis for this group with metastases was 14% survival at 2 years. In the 57 patients without metastases at the time of development of LR, survival was 51% at 2 years and 41% at 5 years. Treatment was by excision of the LR and radiotherapy or by amputation. The only significant prognostic factors identified were the presence of metastases at the time of development of LR (P < 0.0001) and small size of the LR. The role of adjuvant chemotherapy was unclear. Whilst every attempt should be made to avoid LR, patients who develop LR are curable, particularly if they do not have metastases at the time of diagnosis of the LR.

Adolescent↗

PubMed2005

Surgical options for children with osteosarcoma.

Osteosarcoma is the most common solid tumour of childhood. Chemotherapy has substantially improved survival, but surgical resection remains essential for cure. Limb-salvage surgery is now common and can be done for up to 85% of children with osteosarcoma. The main surgical challenge in children is how to reconstruct the limb after removal of the tumour. Knowledge of probable outcomes, risks, and benefits of each surgical option is essential for comparison of reconstruction with amputation, which is still the safest and most suitable option in some children.

Amputation, Surgical↗

PubMed2005

Clinical outcomes of deep atypical lipomas (well-differentiated lipoma-like liposarcomas) of the extremities.

AIM: Controversy exists with regard to the nomenclature, treatment and outcome of a group of well-differentiated lipomatous tumours sometimes labelled as atypical lipomas. The purpose of the present paper is to attempt to clarify these controversies by reporting our experience with this lesion. METHODS: The clinical features and follow up of 61 patients with the diagnosis of deep atypical lipoma and a minimum two-year follow up were examined. RESULTS: All patients were treated by marginal excision alone. A local recurrence was seen in five patients (8%). Three recurred once and two recurred twice. No patient had a metastasis or died as a result of the tumour. No lesion dedifferentiated. CONCLUSION: We believe the term atypical lipoma is appropriate for these tumours, as they appear not to have any metastatic potential, merely a propensity to recur locally. The chance of dedifferentiation is small and radiotherapy may play a role in its causation. We suggest that a simple marginal resection (shelling-out) is adequate treatment for these lesions. Radiotherapy should not be used.

Adolescent↗

PubMed2004

A gene expression signature associated with metastatic outcome in human leiomyosarcomas.

Metastasis is a major factor associated with poor prognosis in cancer, but little is known of its molecular mechanisms. Although the clinical behavior of soft tissue sarcomas is highly variable, few reliable determinants of outcome have been identified. New markers that predict clinical outcome, in particular the ability of primary tumors to develop metastatic tumors, are urgently needed. Here, we have chosen leiomyosarcoma as a model for examining the relationship between gene expression profile and the development of metastasis in soft tissue sarcomas. Using cDNA microarray, we have identified a gene expression signature associated with metastasis in sarcoma that allowed prediction of the future development of metastases of primary tumors (Kaplan-Meier analysis P = 0.001). Our finding may aid the tailoring of therapy for individual sarcoma patients, where the aggressiveness of treatment is affected by the predicted outcome of disease.

Gene Expression Profiling↗

PubMed2004

Change in histological grade in locally recurrent soft tissue sarcomas.

Histological examination of locally recurrent soft tissue sarcomas usually reveals an appearance similar to that of the original tumour. Occasionally, however, recurrent sarcomas appear more or less malignant histologically than the initial lesion. The goals of this paper were to identify the frequency with which this phenomenon occurs, factors that predict for a change in grade and to determine if this change is associated with a different prognosis from other patients with local recurrence. From a large sarcoma database, 124 patients with local recurrence were identified. These patients were distributed into groups who had no change in histological grade, increased histological grade or decreased histological grade on local recurrence. Increased grade occurred approximately 20% of the time, whereas decreased grade occurred in 7% of cases. A histological diagnosis of myxofibrosarcoma was predictive of an increase in histological grade on local recurrence. An increase in histological grade with local recurrence was not associated with a poorer survival.

Adult↗

PubMed2004

Possible metastasis of osteosarcoma to a remote biopsy site: a case report.

In a patient who presented with an osteosarcoma of the proximal humerus, systemic staging revealed a lesion in the contralateral humerus, which was shown to be an enchondroma after open biopsy. The patient had a local recurrence develop, which necessitated forequarter amputation. Shortly thereafter, the patient had pain develop at the contralateral biopsy site, and examinations and repeat biopsy revealed metastatic osteosarcoma. We think it is likely that surgical trauma contributed to the development of this unusual metastasis. In this clinical situation, consideration should be given to doing the biopsy and definitive resection on separate occasions.

Adult↗

PubMed2002

The SYT-SSX1 fusion type of synovial sarcoma is associated with increased expression of cyclin A and D1. A link between t(X;18)(p11.2; q11.2) and the cell cycle machinery.

A recent large multi-centre study convincingly confirmed previous observations that the SYT-SSX1 fusion type, compared to SYT-SSX2, of synovial sarcoma is associated with a worse clinical outcome. Apart from the clinical impact, this fact also suggests (1) that the SYT-SSX fusion gene may influence molecular mechanisms involved in tumour growth and progression; and (2) that the SYT-SSX1 fusion type has a stronger influence on these mechanisms than SYT-SSX2. The nature of the underlying mechanisms is, however, still unknown. In this study we made use of the SYT-SSX1 vs SYT-SSX2 concept to investigate whether major, tumour relevant, and growth regulatory proteins (e.g. cyclins and cyclin-dependent kinases) may be involved. Using Western blotting analysis on 74 fresh, fusion variant-typed, tumour samples from localized synovial sarcoma, we found a significant correlation between SYT-SSX1 and high expression of cyclin A (P=0.003) and D1 (P=0.025). Our data suggest that SYT-SSX may influence the cell cycle machinery, and that the more aggressive phenotype of the SYT-SSX1 variant is due to an accelerated tumour cell proliferation.

Cell Cycle↗

PubMed2002

Two-stage revision for infected endoprostheses used in tumor surgery.

Thirty-four patients with infected massive endoprostheses had two-stage revision procedures to cure the infection and retain a useful functioning limb. An antibiotic impregnated cement spacer constructed with two cement gun liners and a Kuntscher nail provided temporary stability and also allowed a high dose of local antibiotic concentration. In three patients the infection never was controlled, and one of these patients had a successful second revision surgery. Six other patients had reinfection varying from 14 to 92 months after surgery. Risk factors for reinfection were previous radiotherapy and any additional operative intervention. The overall success rate for controlling infection was 91% at 1 year and 74% at 5 years. Six patients required amputation. The mean functional outcome for the retained limbs using the Musculoskeletal Tumor Society scoring system was 77%. Two-stage revisions seem almost as effective at controlling infection in massive endoprostheses as in conventional joint replacements, particularly if additional surgical interventions can be avoided.

Adolescent↗

PubMedDate not supplied

Pigmented villonodular synovitis of the foot and ankle: a 12-year experience from a tertiary orthopedic Oncology Unit.

Pigmented villonodular synovitis is a synovial proliferative process. In the majority of cases, it is monoarticular; however, in the foot and ankle, it can affect more than 1 joint. It may be a challenge to diagnose and treat successfully. Nine patients with foot and ankle pigmented villonodular synovitis synovial disease were reviewed from a tertiary Oncology Unit during a 12-year period. Seven of the patients had ankle involvement and 2 had foot involvement; all of the patients were women. The mean follow-up time was 3.4 years. Seven patients had localized disease and 2 had diffuse disease. All of the patients with localized disease had wide surgical excision and none had recurrence. Both patients with diffuse disease had multiple recurrences after attempted total synovectomy and adjuvant radiotherapy. A review of the diagnosis, imaging strategies, and treatment options is provided.

Adolescent↗