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Bone & Joint Research
Vol. 10, Issue 9 | Pages 602 - 610
24 Sep 2021
Tsoi KM Gokgoz N Darville-O'Quinn P Prochazka P Malekoltojari A Griffin AM Ferguson PC Wunder JS Andrulis IL

Aims

Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients.

Methods

Matched tumour and blood were collected from 64 sarcoma patients (n = 70 samples) prior to resection of the primary tumour (n = 57) or disease recurrence (n = 7). DNA was isolated from plasma, quantified, and analyzed for cfDNA. A subset of cases (n = 6) underwent whole exome sequencing to identify tumour-specific alterations used to detect ctDNA using digital droplet polymerase chain reaction (ddPCR).


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 39 - 39
1 Mar 2010
Kulidjian A Deheshi B Ferguson PC Wunder JS Bell RS Griffin A
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Purpose: To review the oncologic outcomes following treatment of soft tissue sarcomas in the foot and ankle, and to determine the results of limb salvage surgery in this anatomically constrained area with often expected close pathologic margins.

Method: One hundred twenty-nine patients with soft tissue sarcomas of the foot were treated at our institution since 1986. Average age at presentations was 55 years old. Females and males were equally represented. Most common diagnosis was MFH in 31 patients, followed by leiomyosarcoma in 16 patients, synovial sarcoma in 13, and clear cell sarcoma in 6, the remainder being other soft tissue sarcomas. Most of sarcomas were intermediate or high grade. Our follow-up averaged 58 months.

Results: Limb salvage surgery was possible in 97 patients. Of those, negative margin excision was achieved in 75 patients, 18 patients had micro-positive margins, and 4 had grossly positive margins. Fifty-three patients in the limb salvage group required free tissue transfer for coverage. Of 97 limb salvage patients, 82 received radiation therapy, 5 patients received chemotherapy. Local recurrence occurred in 24 patients. Two of these were amenable to re-excision, the remaining required amputation. Thirty-two patents developed systemic disease. Average disease-free survival for patients with recurrent disease was 23 months. At last follow-up, 78 patients were alive with no evidence of disease and 24 were alive with disease. Seventeen patients died of disease, and the remainder of other causes.

Conclusion: In the setting of soft tissue sarcoma in foot and ankle, amputation rate is higher than in other anatomic areas. However, limb salvage surgery can be achieved with good oncological outcomes despite often unavoidable close margins. Soft tissue reconstructive procedures aid in achieving good surgical results while radiation therapy aids local control. Given these results, limb salvage in soft tissue tumors of foot and ankle should be the goal.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 38 - 38
1 Mar 2010
Ferguson PC Griffin A Deheshi B Wunder JS
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Purpose: Patients presenting with metastatic soft tissue sarcoma (STS) generally have a poor prognosis. The factors that determine ultimate outcome in this setting are poorly understood. The purpose of this study is to establish factors that affect outcomes in a group of patients with metastatic STS at initial presentation who underwent surgical resection of their primary tumour.

Method: A retrospective review of our institutional database from 1986 to present was carried out. We identified all patients with STS who, at presentation, had metastatic disease. Patients who did not undergo surgical resection of their primary tumour were excluded. Factors affecting overall survival were assessed using the methods of Kaplan and Meier and ANOVA.

Results: We identified 130 patients with metastatic STS (75 male, 55 female). Of these, 81 patients presented with pulmonary metastases, 20 with lymph node metastases, 13 with both lung and lymph node metastases, and in 16 patients initial resection was of a metastatic lesion. Currently only 17 patients (13%) are free of disease. Factors associated with improved survival were lymph node metastases as opposed to pulmonary metastates (p=0.0006), size less than 5 cm (p=0.02), low grade sarcoma (p=0.05) and 3 or fewer pulmonary metastases (p=0.04). Age, gender, histological subtype, anatomic location, use of chemotherapy, depth, bilaterality of pulmonary metastases and pulmonary metastasectomy had no effect on overall survival.

Conclusion: A small percentage of patients presenting with metastatic STS can be cured with aggressive surgical management. Patients with lymph node metastases, small tumours, low grade tumours and 3 or fewer lung metastases at presentation have a better outcome and longer life expectancy.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 64 - 64
1 Mar 2010
Gortzak Y Mahendra A Griffin AM Wunder JS Ferguson PC
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Objectives: A stable shoulder is essential for proper elbow and hand function after oncologic resection of the shoulder girdle. We describe a surgical technique for replacing the shoulder joint capsule using synthetic mesh after resections of the shoulder girdle that resulted in gross intraoperative instability of the shoulder joint.

Methods: 68 patients who underwent shoulder girdle resection between 1989 and 2006 were identified in our prospective database. This report focuses on nine patients whose shoulder joint was reconstructed with synthetic mesh. All patients were followed on a 3 monthly basis. Shoulder joint instability was determined from clinical records, database and radiographs.

Results: Nine patients underwent shoulder joint reconstruction with synthetic mesh. One patient underwent a shoulder disarticulation within 30 days of the index surgery and was excluded from this rapport.

No dislocations were noted during follow-up (range 3–48 months). Radiographs revealed an average vertical displacement of the humeral head compared to its original position of 0.7 cm (range 0–1.7 cm). There were two surgical complications. In one patient the humeral prosthesis migrated proximally and eroded through the skin requiring additional surgery. In another case erosion of the distal clavicle was noted. This was biopsied and foreign body reaction identified.

Conclusions: Joint instability following major resections of the shoulder girdle is a source of morbidity and affects the function of the salvaged limb. Synthetic capsular reconstruction using Marlex mesh is a useful adjunct in patients where insufficient shoulder musculature and joint capsule remains after resection to allow for stable suspension of the upper limb.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 63 - 63
1 Mar 2010
Gortzak Y Mahendra A Griffin AM Lockwood G Wang Y Deheshi B Wunder JS Ferguson PC
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Objectives: To formulate a scoring system enabling decision making for prophylactic stabilization of the femur following surgical resection of a soft tissue sarcoma (STS) of the thigh.

Methods: A logistic regression model was developed using patient variables collected from a prospective database. The test group included 22 patients with radiation-related pathological femur fracture following surgery and radiation for a thigh STS. The control group of 79 patients had similar treatment but without a fracture. No patients received chemotherapy. Mean follow-up was 8.6 years. Variables examined were: Age (< 49, 50–70, > 70 years), gender, tumor size (0–7, 8–14, > 14 cm), radiation dose (low=5000 cGy, high> 6000 cGy), extent of periosteal stripping (< 10, 10–20, > 20 cm) and thigh compartment (posterior, adductor, anterior). A score was assigned to each variable category based on the coefficients obtained in the logistic regression model.

Results: Based on the regression model and an optimal cut-point, the ability to predict radiation associated fracture risk was 91% sensitive and 86% specific. The area under the Receiver Operating Characteristic (ROC) curve was 0.9, which supports this model as a very accurate predictor.

Conclusions: Radiation-related femur fractures following combined surgery and radiation treatment for STS are uncommon, but are difficult to manage and their non-union rate is extremely high. These results suggest that it is possible to predict radiation-associated pathological fracture risk with high sensitivity and specificity. This would allow identification of high risk patients and treatment with prophylactic IM nail stabilization. Presentation of this model as a clinical nomogram will facilitate its clinical use.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 64 - 64
1 Mar 2010
Mahendra A Griffin AM Yu C Gortzak Y Bell Ferguson PC Wunder JS Davis A
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Objectives: To investigate whether components of MSTS-87 (Pain, ROM, Strength, Stability, Deformity, Acceptance and Function) correlate with function as measured by TESS following endoprosthetic replacement (EPR) for patients with bone sarcoma.

Methods: 255 patients with extremity bone sarcoma treated by resection & EPR were identified from a prospective database. From this group we investigated 111 patients with primary bone sarcoma with > 2 years follow up, evaluated by both MSTS-87 & TESS, no local recurrence, metastasis or major complication for at least 2 years prior to the follow-up. Upper extremity patients were excluded due to small numbers. We examined the influence of patient demographics and tumour characteristics on functional outcome scores. Correlation between MSTS-87 & TESS was performed using linear regression analysis.

Results: Age, gender, tumour size, anatomical site, chemotherapy treatment and presence of pathological fracture did not significantly correlate with TESS. Linear regression analysis of MSTS-87 individual criteria and total score revealed that only pain, ROM and function helped explain the TESS score (p < 0.05) while strength, stability, deformity & acceptance had no significant effect on overall functional outcome.

Conclusions: Of the seven MSTS-87 variables, only pain, ROM and function significantly correlate with overall functional outcome as measured by TESS following EPR for bone sarcoma. This suggests that patients with decreased strength, stability, deformity and acceptance as defined by MSTS-87 scores, may still adapt well with good overall functional outcomes.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 38 - 38
1 Mar 2010
Gortzak Y Lockwood G Mahendra A Wang Y Griffin A Deheshi B Wunder JS Ferguson PC
Full Access

Purpose: To formulate a scoring system enabling decision making for prophylactic stabilization of the femur following surgical resection of a soft tissue sarcoma (STS) of the thigh.

Method: A logistic regression model was developed using patient variables collected from a prospective database. The test group included 22 patients with radiation-related pathological femur fracture following surgery and radiation for a thigh STS. The control group of 79 patients had similar treatment but without a fracture. No patients received chemotherapy. Mean follow-up was 8.6 years. Variables examined were: Age (70 years), gender, tumor size (0–7, 8–14, > 14 cm), radiation dose (low=5000 cGy, high> 6000 cGy), extent of periosteal stripping (20 cm) and thigh compartment (posterior, adductor, anterior). A score was assigned to each variable category based on the coefficients obtained in the logistic regression model.

Results: Based on the regression model and an optimal cut-point, the ability to predict radiation associated fracture risk was 91% sensitive and 86% specific. The area under the Receiver Operating Characteristic (ROC) curve was 0.9, which supports this model as a very accurate predictor.

Conclusion: Radiation-related femur fractures following combined surgery and radiation treatment for STS are uncommon, but are difficult to manage and their non-union rate is extremely high. These results suggest that it is possible to predict radiation-associated pathological fracture risk with high sensitivity and specificity. This would allow identification of high risk patients and treatment with prophylactic IM nail stabilization. Presentation of this model as a clinical nomogram will facilitate its clinical use.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 64 - 65
1 Mar 2010
Mahendra A Gortzak Y Griffin AM Wunder JS Ferguson PC
Full Access

Objectives: Well fixed, ingrown stems in patients with infected, uncemented knee tumor prostheses are difficult to remove. We have shown that it?s not necessary to remove them for infection control. We describe a technique for intraoperative fabrication of antibiotic-impregnated temporary cement prostheses using rush pin endoskeleton during first stage revision of infected, uncemented knee tumor prostheses.

Methods: We used this method in 7 patients with infected uncemented tumor prostheses around the knee. Two patients are awaiting second stage procedures. Surgery involved removing exchangeable components and retaining well-ingrown stemmed intramedullary components. Spacers were made of Rush pins that were bent and placed through hinge of retained component to allow knee movement. Antibiotic impregnated cement was placed around pins.

Results: This method allowed partial weight-bearing, knee movement, stability and pain control between first and second stages. In 4/5 patients infection was eradicated. Second-stage reimplantations were accomplished successfully in 3/5 patients with no obvious metal wear. Mean interval between the 2 stages was 12 weeks. One patient had residual infection requiring amputation and one patient did not agree to further surgery. Overall functional outcome following revision was TESS 82.3/100, MSTS93 73.3/100, MSTS87 23.3/35.

Conclusions: The technique allows maintenance of length, stability and knee joint movement, thus subsequent revision becomes technically simpler. Cement construct has large surface area to maximize antibiotic elution. This method has advantages of low cost, availability of numerous pin dimensions, which allows a custom component. Although there is no obvious wear, this remains a potential concern at articulation of rush rods and retained component.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 253 - 253
1 May 2009
Al Jahwari AS Ferguson PC Schemitsch E Wunder J Zdero R
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This study examines the biomechanical performance of five types of fixation techniques in a model of pathological fracture of the diaphyseal humerus.

In forty synthetic humeri, a hemi cylindrical defect centered in the middle third of the diaphysis was created. A transverse fracture was created through the centre of each defect. The bones were randomly assigned to five groups. Group A was fixed with standard ten hole DCP plates centered over the defect with five screws inserted on either end. In group B, the screw holes were injected with bone cement and then the screws and plate were reapplied while the cement was still soft. The defect was also filled with cement. Group C was fixed by injecting the cement into the entire intramedullary canal. The fracture was then reduced and the screws and plate were applied once the cement had hardened. In group D, the specimens were fixed with locked antegrade IM nail with one proximal and one distal interlocking screw. Group E was same as D except that the defect was filled with cement. Each specimen was tested in external rotation to failure by fracture.

There was no significant difference in torsional stiffness between groups B, C, and E (P> 0.16), whereas there were differences between all other groups using pairwise comparisons(p< 0.001). Groups B, C, and E were of highest stiffness followed by A and then D. Group C had the highest torque to failure, followed by groups A/B and then D/E. Total cumulative energy to failure for group C was statistically greater than each of B, D, and E (p< 0.005), but not different from A, though it approached significance (p=0.057).

This study demonstrates that, in a model of a fracture through a hemicylindrical defect in the middiaphysis of the humerus, fixation with a broad ten-hole dynamic compression plate after filling the entire medullary canal with cement is associated with the highest torque to failure and energy to failure with torsional forces. This fixation technique may best accomplish the clinical goal of maximal initial stability.