Cynthia M. Kelly

The use of a surgical grade calcium sulfate as a bone graft substitute: results of a multicenter trial.

In a prospective, nonrandomized, multicenter study, 109 patients with bone defects were treated with a surgical grade calcium sulfate preparation as a bone graft substitute. The calcium sulfate pellets were used in place of morselized cancellous bone graft for the treatment of patients with bone defects who usually would require grafting secondary to trauma, periprosthetic bone loss, tumor, or fusion. The calcium sulfate was used alone or mixed with other materials such as bone marrow aspirate, demineralized bone matrix, or autograft. The defects that were treated were contained and were not necessary for the stability of the bony structure. Radiographic and clinical data were collected at predetermined intervals for 12 months. At 6 months postoperatively, radiographic results for all patients showed that 99% of the calcium sulfate had been resorbed and 88% of the defect was filled with trabeculated bone. There were 13 complications; however, only four (3.6%) were attributable to the product. The results of a subgroup of 46 patients with benign bone lesions treated in the same manner are identical to the results of the overall study population. Surgical grade calcium sulfate pellets are considered a convenient, safe, and readily available bone graft substitute that yield consistent successful results.

Early multicenter experience with a noninvasive expandable prosthesis.

A noninvasive expandable prosthesis for skeletally immature children after limb salvage surgery has been developed. Between 1998 and 2001, 18 Phenix prostheses were implanted in 15 pediatric patients who had been diagnosed and treated for osteosarcoma about the knee. Of the 15 original prostheses, 10 were implanted at the time of primary tumor resection and five were revisions from an endoprosthetic modular knee system. Sixty expansions of the 18 prostheses were done, with all but two done as outpatient procedures. An average 8.5 mm was obtained per lengthening (range, 1–30 mm). The average followup was 21.5 months (range, 12–33 months) and the latest Musculoskeletal Tumor Society functional scores averaged 90%. Eight revisions were required for stem fracture or loosening. There was one amputation because of a postoperative arterial thrombosis. The principle of the Phenix prosthesis involves storage of energy in a spring compressed by a locking system. Lengthening is achieved via exposure to an electromagnetic field that allows controlled release of the spring. This is a unique expandable custom prosthesis that offers many benefits in maintaining limb length equality in growing patients. Although the early experience is promising, additional data are required regarding the long-term structural integrity of the prosthesis. We are optimistic that this technology will prove beneficial, not only for patients with malignant bone tumors but in applications requiring serial limb length equalizations or for spinal deformities.

Endoprosthetic reconstruction for malignant upper extremity tumors

Between December 1980 and December 1992, 59 patients underwent 60 reconstructions with endoprostheses after resection of malignant tumors in the upper extremity. There were 32 male patients and 27 female patients, with a mean age of 33 years (range, 3-83 years). The type of reconstruction was based on the location of the primary tumor site. The histologic diagnoses included osteosarcoma, chondrosarcoma, Ewings sarcoma, malignant fibrous histiocytoma, soft tissue sarcoma, and fibrosarcoma of bone. Most of the patients had Stage IIB disease (N = 38), as established by the Musculoskeletal Tumor Society classification. An additional six patients had metastatic tumors to the upper extremity. Twenty-seven of 59 patients died of disease progression. Two patients died of other causes (chronic leukemia, human immunodeficiency virus infection). The 30 survivors had a mean followup of 90 months (range, 60-170 months). The Musculoskeletal Tumor Society functional analysis for the patients with a minimum 2-year followup (N = 41) averaged 74%. Sixteen of the 59 (27%) patients had local complications. Problems related to mechanical failure and infection were managed successfully with second operation. Amputation was rare, occurring in three of 60 (5%) patients and was related only to local recurrence. Endoprosthetic reconstructions of the upper extremity after tumor resections have proven to be successful.

Superior survival in treatment of primary nonmetastatic pediatric osteosarcoma of the extremity.

Background: A protocol to treat osteosarcoma of the extremity was developed at two local institutions.Methods: The study involved a dose-intensified neoadjuvant protocol of intravenous doxorubicin and intra-arterial cisplatin administered repetitively until maximum angiographic response was noted. Definitive surgery was delayed until ≥90% reduction in tumor neovascularity was documented. Prospective assessment of serial arteriograms was highly accurate (94%) in predicting histological response and assisted in surgical planning. After resection, if patients were determined to be good responders (≥90% tumor necrosis), they underwent a 4-month postoperative course with the same agents. Poor responders (<90% necrosis) were treated with alternative agents for 12 months from diagnosis. Forty-seven assessable patients with primary, high-grade, nonmetastatic osteosarcoma of the extremity were included in this analysis. The median age was 15 years (range, 7–21 years).Results: Patients underwent an average of four preoperative intra-arterial courses. Forty-three patients underwent limb-preservation procedures, and 41 had >90% tumor necrosis. With an average follow-up of 92 months (range, 20–178 months), 39 patients were continuously disease free, 3 died of disease, 1 died of other causes, and 4 have no evidence of disease 11 to 51 months after relapse (all pulmonary metastases). There were no local recurrences. Kaplan-Meier analysis demonstrated a 10-year overall survival of 92% and an event-free survival of 84%.Conclusions: This study demonstrates excellent survival with a dose-intensified neoadjuvant protocol. Future endeavors should involve a multi-institutional randomized study comparing this approach with another multiagent intravenous neoadjuvant protocol.

Treatment of benign bone lesions with an injectable calcium sulfate-based bone graft substitute.

The treatment of benign bone lesions can be challenging due to the limited quantity of autogenous graft available for harvest and grafting of the defect. The use of an injectable calcium bone graft substitute, Minimally-Invasive Injectable Graft (MIIG) (Wright Medical Technology, Inc, Arlington, Tenn), material for treatment of these bone lesions is advantageous. Calcium sulfate has a long-standing history in the treatment of bone voids secondary to trauma, infection, or neoplastic processes. Minimally-Invasive Injectable Graft injectable calcium sulfate graft may be injected into surgically created osseous defects or bone defects secondary to traumatic injury. After hardening, the paste acts as a temporary intraosseous support through which internal fixation may be placed. Fifteen patients with benign space-occupying lesions were treated with curettage and grafting with an injectable, surgical-grade, calcium sulfate bone graft substitute. Bone healing was assessed postoperatively and defined as resorption of the bone graft substitute material and replacement with new bone formation. The grafted defects in 14 of the 15 patients showed complete incorporation of the graft material at an average of 8 weeks. One patient required incision and drainage for a deep infection 5 weeks postoperatively. The average follow-up was 6 months (range: 3-15 months), and Musculoskeletal Tumor Society functional outcome scores averaged 83%. This injectable, minimally invasive graft material is easy to use, provides a temporary structural support when grafting bone defects, and results in predictable rapid bone healing.

The Effect of AlloMatrix Injectable Putty on the Outcome of Long Bone Applications

Long bone defects due to nonunion or surgical excision of benign bone tumors result in areas that require rapid regeneration of local bone. This clinical and radiographic article details the results of a commercially prepared allograft demineralized bone matrix in patients with long bone voids or gaps. Of the 76 patients included for study, 41 (54%) patients were undergoing surgical intervention for removal of benign tumors or space-occupying lesions and 35 (46%) patients had long bone nonunions. AlloMatrix Injectable Putty (Wright Medical Technology, Inc, Arlington, Tenn) was used alone in 74 (97%) patients and in combination with bone marrow aspirate in two (3%) patients with tibial nonunion. Adjunctive strut allografts were used in three patients with humeral nonunion. The average time to follow-up for the combined population was 7 months (nonunion group 6 months; benign tumor group 7 months). At the most recent follow-up, radiographic evidence of the average percent of bone healing was 85.1% for the nonunion patient group and 93% for the benign tumor patient group. From this study, AlloMatrix Injectable Putty used as a bone void filler in long bone nonunions and benign tumors shows results equal to those historically reported for autograft and other materials.

The Value of Serial Arteriography in Osteosarcoma: Delivery of Chemotherapy, Determination of Therapy Duration, and Prediction of Necrosis

PURPOSE To investigate the value of serial arteriography to assess tumor response, predict necrosis, and individualize the duration of a combined intravenous (IV) and intraarterial (IA) neoadjuvant chemotherapy protocol in patients with biopsy-proven high-grade osteosarcoma or malignant fibrohistiocytoma of bone. MATERIALS AND METHODS Between July 1987 and March 2003, 109 patients completed a chemotherapy protocol of neoadjuvant IV doxorubicin and IA cisplatin. Patients were eligible regardless of age, disease stage, or disease site. A minimum of three IA cycles followed by definitive surgery was required for inclusion in the final analysis. IA dose and duration were increased for tumors larger than 10 cm. Initial arteriograms were scored as indicating mild, moderate, or marked tumor neovascularity (TNV). Subsequent arteriograms were prospectively compared with the baseline image for percent change in TNV. Treatment continued until a maximum of five cycles were administered or one of three criteria were met: (i) at least 90% decrease in TNV, (ii) plateau of effect, or (iii) no response. RESULTS Of 408 IA procedures, 42 patients underwent three cycles, 53 underwent four, and 14 required five cycles of neoadjuvant therapy. There was a 2.5% minor complication rate. Eighty-six percent of patients exhibited at least 90% decrease in TNV and 82% exhibited good histologic response (> or =90% tumor necrosis). Serial arteriography predicted a good histologic response with an accuracy of 90% and a sensitivity of 97%. CONCLUSIONS Serial arteriography was highly sensitive and accurately predicted good responses. This individually modified, dose-intensified neoadjuvant protocol yielded an excellent histologic response rate with minimal complications. Future endeavors should involve a multiinstitutional study of this unique approach.

Revision of the failed distal femoral replacement to allograft prosthetic composite

Orthopaedic oncologists often prefer a modular prosthetic cemented prosthesis for reconstruction after tumor excision in the distal femur. However, these frequently young patients face the prospect of either mechanical failure or loosening during their lifetime. Between 1993 and 2000, 41 patients (18 males, 23 females) with a malignancy of the distal femur had distal femoral replacement. Eight revisions and one amputation were required. Of these, four patients had revision to an allograft-prosthetic composite because of prosthetic fracture or loosening. These patients comprise the study population. Revisions were required at an average of 4 years after distal femoral replacement and the average age of the patients at revision was 17 years. The average time to achieve healing at the allograft-host junction was approximately 3 months and patients were fully weightbearing by that time. Followup from revision surgery to the last visit averaged 59 months, with average Musculoskeletal Tumor Society and Hospital for Special Surgery scores of 62% and 72%, respectively. There have been no mechanical problems, fractures, or osteolysis to signify loosening in the allograft or host bone. It is anticipated that this type of revision will survive longer than a conventional cemented revision and obviate the need for multiple reoperations in young patients who have difficulty with the biologic features of a cemented prosthesis construct.

Custom cross-pin fixation of 32 tumor endoprostheses stems.

The main cause of mechanical failure of primary and revision cemented tumor endoprosthetic stems is aseptic loosening. The placement of custom designed pins through the bone, the cement, and the stem can create a bone-cement-prosthesis composite that resists the rotatory stresses that lead to aseptic loosening. At risk situations include large primary reconstructions where the residual short metaphyseal articular segments lack sufficient length and cortical contact to provide lasting fixation, and revision prostheses that are to be recemented into straight diaphyseal segments that already have experienced aseptic loosening. Current modular tumor endoprosthetic systems have improved availability and allow for some intraoperative flexibility, but they do not provide solutions for these at risk scenarios. Additional customization is necessary. We report on the 16-year experience with 32 custom cross-pin stems at the University of California, Los Angeles (UCLA). Twenty of these patients have been followed up for more than 2 years. There were three mechanical failures, three patients were lost to followup, and five patients died of disease. There have been no cases of aseptic loosening in this series. Cross-pin fixation has been effective when used in carefully selected cases.