Marc H. Isler

Giant cell tumor of long bone: a Canadian Sarcoma Group study.

A multicentric retrospective study of giant cell tumor of bone was conducted among Canadian surgeons. The hypothesis was that no differences would be found in health status, function, or recurrence rate irrespective to the nature of filling material or adjuvant used in patients treated with curettage. One hundred eighty-six cases were collected. There were 96 females and 90 males. The mean age of the patients was 36 years (range, 14–72 years), the minimum followup was 24 months, and the median followup was 60 months. Sixty-two percent of the tumors involved the knee region. One hundred fifty-eight were primary tumors and 28 were recurrences. Campanacci grading was as follows: Grade 1, seven patients; Grade 2, 100 patients; Grade 3, 76 patients; and unknown in three patients. Fifty-six patients had a pathologic fracture. Resection was done in 38 patients and 148 patients had curettage. The latter was supplemented with high speed burring in 135 patients, cement in 64 patients, various combinations of autograft or allograft bone in 61 patients, phenol in 37 patients, and liquid nitrogen in 10 patients. Structural allografts were used in 25 patients. The overall recurrence rate was 17%, 18% after curettage, and 16% after resection. Patients with primary tumors treated with curettage had a 10% recurrence rate. For recurrent lesions treated by curettage, the recurrence rate was 35%. The nature of the filling material used or the type of adjuvant method used or any combination of both failed to show any statistical impact on the recurrence risk. The results from the Musculoskeletal Tumor Society rating from 1987 were significantly lower in patients who sustained a displaced fracture. Results from the bodily pain section of the Short Form-36 also were found to be lower when a pathologic fracture was present. Results from the Musculoskeletal Tumor Society Rating 1987, the Short Form-36, and the Toronto Extremity Salvage Score did not show differences when either cement or bone graft were used after curettage.

Outcome after pelvic sarcoma resection reconstructed with saddle prosthesis.

We retrospectively reviewed 27 patients who had saddle prosthetic reconstruction for pelvic sarcoma from 1991 to 2001 with a mean followup of 45 months. Functional outcome was assessed with Musculoskeletal Tumor Society Scores of 1987 and 1993 and the Toronto Extremity Salvage score. Survival, recurrences, and complications were recorded. Seven (26%) patients had Type II (periacetabular) pelvic resection and 20 had Types II and III (periacetabular and pubis) pelvic resection. Eleven patients had chemotherapy treatment. None received radiation therapy. At final followup 14 patients were free of disease, 11 patients died, and two patients were alive with disease. The survival rate was 60%. Twenty-two percent had local recurrence, and 22% had metastasis. The mean Musculoskeletal Tumor Society Score 93 score in 17 patients was 50.8% ± 21.7%, the mean Musculoskeletal Tumor Society Score 87 score was 15.3 ± 6.1, and the mean Toronto Extremity Salvage score was 64.4% ± 17.2%. Infection occurred in 10 patients; six were deep infections. There were five nerve palsies. Heterotopic ossification occurred in 10 patients, fracture occurred in six patients, and dislocation occurred in six patients. Limb shortening was progressive until it stabilized at 12 months, and ultimately ranged between 1 and 6 cm. Five patients were retired, five had full-time employment, and six were disabled. Reconstruction with the saddle prosthesis after resection for pelvic sarcoma is associated with substantial morbidity. However, the functional results seem to confer an advantage when compared with the considerable disability incurred after hemipelvectomy. Level of Evidence: Therapeutic study, Level IV-1 (case series without control group). See the Guidelines for Authors for a complete description of levels of evidence.

Endothelin-1 (ET-1) promotes MMP-2 and MMP-9 induction involving the transcription factor NF-κB in human osteosarcoma

In the present study, we have investigated the effect of (i) ET-1 (endothelin-1) and its precursor, big ET-1, on MMP (matrix metalloproteinase)-2 and MMP-9 synthesis and activity in osteosarcoma tissue, and (ii) ET-1 receptor antagonists on cell invasion. Using Western blotting, zymography, RT-PCR (reverse transcription-PCR), immunohistochemistry, immunofluorescence and Northern blotting, we have shown that ET-1 and ET-1 receptors (ET(A) and ET(B)) were expressed in these cells. Additionally, we have demonstrated that ET-1 markedly induced the synthesis and activity of MMP-2, which was significantly increased when compared with MMP-9. Furthermore, inhibition of NF-kappaB (nuclear factor kappaB) activation blocked MMP-2 production and activity, indicating the involvement of NF-kappaB, a ubiquitous transcription factor playing a central role in the differentiation, proliferation and malignant transformation. Since ET-1 acts as an autocrine mediator through gelatinase induction and because inhibition of ET(A) receptor is beneficial for reducing both basal and ET-1-induced osteosarcoma cell invasion, targeting this receptor could be an attractive therapeutic alternative for the successful treatment of osteosarcoma.

Pathologic fractures in children.

Fractures through bone tumors are often difficult to treat. We reviewed our combined experience with this problem in children, as well as the existing literature, to formulate management guidelines. For this study, prospective databases (1987 to 2002) from three referral centers were screened for pathologic fractures occurring under the age of 14 years. One hundred five patients presented with fracture through unicameral bone cyst, nonossifying fibroma, fibrous dysplasia, aneurysmal bone cyst and osteosarcoma. Seventeen patients were excluded. The most common primary locations were the proximal humerus and proximal femur. Pathologic fracture through nonossifying fibroma had the best outcome; union occurred with nonsurgical treatment in all cases. Unicameral bone cyst required surgical treatment to avoid persistence of the cyst and refracture. However fracture healing was predictable without surgical treatment. Proximal femoral lesions tended to heal in malunion if not fixed surgically. Aneurysmal bone cyst required surgical treatment for the lesion to heal and to allow the fracture to heal as well. Percutaneous sclerotherapy may be the treatment of choice for many of these lesions. Fibrous dysplasia allows fracture healing with nonoperative therapy. Progressive deformity requires followup and surgical correction. Malignant lesions presenting a pathologic fracture are best managed by initial nonoperative therapy during investigation and neoadjuvant therapy when possible, followed by definitive treatment.

Cemented rotating hinge endoprosthesis for limb salvage of distal femur tumors.

We retrospectively ascertained the outcomes and complications with a cemented rotating hinge implant. Implant failure was defined as amputation of the affected limb and revision of part or all of the components. We included 77 consecutive distal femoral replacements performed between 1989 and 2004. The mean age was 42 years (range, 12-87 years) and the mean length of followup was 52 months (range, 1.5-157 months). Five-year implant survival was 84% and 10-year survival was 79%. There were 67 bone sarcomas, two soft tissue sarcomas and eight metastatic carcinomas. At followup, 54 patients had no evidence of disease, 16 were alive with disease, and seven were dead from disease. Six patients had deep infection, two of which required amputations. There were five local recurrences; three needed amputation and two soft-tissue excisions only. Three patients sustained a tibial bearing fracture and one required replacement of loose bumper. No revision was performed for stem loosening, stem fracture, or bushing wear. Musculoskeletal Tumor Society 1987 scores averaged 30 and Toronto Extremity Salvage Scores averaged 77.6 at latest followup. Cemented endopros- thesis is a reliable procedure after resection of the distal femur for tumors.Level of evidence: Therapeutic study, level IV (case series). See Guidelines for Authors for a complete description of levels of evidence.

Function and health status in surgically treated bone metastases.

In a prospective study, we evaluated if surgery substantially improved functional and quality of life outcomes in patients with nonspinal bone metastases. Sixty-seven patients were followed up prospectively. The Short Form-36, the Musculoskeletal Tumor Society 1987 form, the Musculoskeletal Tumor Society 1993 form, and the Toronto Extremity Salvage Score were administered preoperatively and 6 weeks and 3 months postoperatively. Fifty percent of the patients had pathologic fractures. Intramedullary nailing was done in 36 patients, prosthetic replacement was done in 24 patients, and plating was done in five patients. The average postoperative survival was 8 months. At 6 weeks, 13 patients had died and seven were lost to followup. Twenty-one percent of patients had complications, although only 4.5% needed additional surgery. The patients’ Musculoskeletal Tumor Society 1987 form, Musculoskeletal Tumor Society 1993 form, and Toronto Extremity Salvage Score scores improved at 6 weeks and 3 months postoperatively. There were no improvements in the Short Form-36 mental and physical summary scales of the patients. The number of patients using pain medication did not decrease. Patients had functional improvements after surgical treatment of bone metastases, even patients with a limited life expectancy. Future prospective studies should anticipate a high rate of attrition with this population from death and loss to followup. Level of Evidence: Prognostic study, Level I (high quality prospective study—all patients were enrolled at the same point in their disease with ≥ 80% followup of enrolled patients). See the Guidelines for Authors for a complete description of levels of evidence.

Experience with cemented large segment endoprostheses for tumors.

Published reports dealing with tumor prosthesis have yet to establish a clear advantage of using either cemented or cementless implants. We examined the outcome and complications with modular cemented implants in 135 patients identified from our database to strengthen the argument for routine use of cemented constructs. The minimum followup was 1.4 months (mean, 57 months; median, 47 months; range, 1.4-157 months). The majority of patients (104) had sarcoma. The complications included: 11 infections, three of which underwent amputation and one a stem revision; eight local recurrences, five of which underwent amputation; three hip dislocations; and three incidents of shoulder instability. One periprosthetic femur fracture was stabilized operatively. There was no aseptic loosening or stem fracture. The 5-year survival rates for distal femoral and proximal humeral replacements were 84% and 70%; the 10-year survival rates were 79% and 59%. The 5-year survival rates for proximal femur and proximal tibia replacements were 78% and 37%. Average Musculoskeletal Tumor Society 1987 scores and Toronto Extremity Salvage Scores were 21.5 and 73% for proximal femur, 28.1 and 67% for distal femur, and 21 and 78% for proximal humerus. The survival of the endoprostheses related to site of bone resection. Cemented constructs of modern design in the context of tumor surgery provide good short-term results.Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Functional evaluation in distal femoral endoprosthetic replacement for bone sarcoma

A multicenter study of successfully treated patients (mean age, 36.7 years) with a minimum 1-year followup (average, 35.4 months) after distal femoral endoprosthetic replacement for bone sarcoma was done using the 1987 and 1993 versions of the Musculoskeletal Tumor Society, the Short Form-36, and the Toronto Extremity Salvage Score functional evaluation criteria. Fifty-six patients (28 women and 28 men) fulfilled the criteria. Thirty-one Kotz prostheses (fixed hinge, uncemented) and 25 Modular Replacement System Prostheses (rotating hinge, cemented) were used. Thirty-five patients walked without aids, 19 used a cane, and two used crutches or a walker. The Musculoskeletal Tumor Society 1987 mean score was 28.1. The Musculoskeletal Tumor Society 1993 mean score was 80.4. The Toronto Extremity Salvage Score mean was 81.6. The Short Form-36 Physical Component Score had a mean of 43.2 and Mental Component Score mean of 54.2. The two groups of implants were comparable, except for the length of bone resection. Multivariate regression analysis revealed that patient age, existence of a pathologic fracture, and type of prosthesis all significantly accounted for differences in functional outcome as measured by the Musculoskeletal Tumor Society 1993, the Toronto Extremity Salvage Score, and the Short Form-36 Physical Component Score scales. Although both implants provided satisfactory function, the Musculoskeletal Tumor Society 1993 and the Toronto Extremity Salvage Score results were significantly better with the Modular Replacement System prosthesis. The effect of possible differences among surgeons or institutions was not addressed.

Sciatic nerve resection in the thigh: A functional evaluation

Patients with a soft tissue malignancy involving the sciatic nerve who present with neurologic loss generally are advised to have an amputation. Twenty patients who underwent limb-sparing procedures with complete resection of the sciatic nerve as treatment for neurofibrosarcomas (12 patients), liposarcomas (four patients), malignant fibrous histiocytomas (two patients), recurrent desmoid tumor (one patient), and epithelioid hemangioendothelioma (one patient) were reviewed retrospectively. The mean age of these nine women and 11 men at the time of surgery was 51 years (range, 28–84 years). The right sciatic nerve was affected in 12 patients. These tumors were large and high grade. A mean of 22 cm of the nerve had to be resected (range, 8–42 cm). Ten patients received preoperative radiotherapy and 16 patients had intraoperative or postoperative radiotherapy. At a mean followup of 35 months (range, 7–97 months), 14 of the 20 patients were alive. Two patients had local recurrences develop (10%), whereas 12 patients had distant metastases. The function of the 10 patients as assessed by the Toronto Extremity Salvage Score averaged 74%. Most patients indicated that walking in the house is not difficult, but walking is compromised as soon as an effort is needed. Four patients walk without a cane, four needed one cane, and two needed two canes. The patients experienced stiffness, a sense of numbness, and premature fatigue. The use of analgesics was infrequent. Generally, patients rated themselves to be mildly to moderately disabled. From this small number of patients, it is shown that a tumor involving the sciatic nerve can be treated by limb-sparing surgery, including complete nerve resection, as an alternative to hip disarticulation or hindquarter amputation because the limb salvage option provides an acceptable functional outcome.

Iliosacral resection for primary bone tumors: is pelvic reconstruction necessary?

Iliosacral resection for primary bone tumors creates a large unstable pelvic ring defect, the treatment of which remains controversial. We did this study to determine if skeletal reconstruction of such defects is necessary. Sixteen patients whose data were collected prospectively had iliosacral resection with a minimum followup of 12 months. The surgical and functional results of patients who had skeletal reconstruction (n = 4) were compared with the results of patients who did not have iliosacral repair (n = 12) using a case-control design. Function was evaluated by assessing impairment using the Musculoskeletal Tumor Society 1987 and 1993 rating scales, and disability was measured using the Toronto Extremity Salvage Score. Although all four iliosacral arthrodeses initially healed, one allograft used for reconstruction fractured and another was removed because of progressive lumbosacral spinal instability. Patients treated without pelvic reconstruction had fewer operative complications. Although the Toronto Extremity Salvage Score and the Musculoskeletal Tumor Society 1987 and 1993 scores were similar for both patient groups, those patients who were treated without reconstruction were less likely to require the use of an ambulatory assistive device, less likely to require narcotics or have chronic pain, and more likely to return to work. These results suggest that reconstruction of the skeletal defect to restore pelvic stability after iliosacral resection is not mandatory. Level of Evidence: Therapeutic study, Level III-1 (case-control study). See the Guidelines for Authors for a complete description of levels of evidence.