Are Complications Associated With the Repiphysis(®) Expandable Distal Femoral Prosthesis Acceptable for Its Continued Use?

BACKGROUND: Reconstruction of the distal femur after resection for malignant bone tumors in skeletally immature children is challenging. The use of megaprostheses has become increasingly popular in this patient group since the introduction of custom-made, expandable devices that do not require surgery for lengthening, such as the Repiphysis(®) Limb Salvage System. Early reports on the device were positive but more recently, a high complication rate and associated bone loss have been reported. QUESTIONS/PURPOSES: We asked: (1) what are the clinical outcomes using the Musculoskeletal Tumor Society (MSTS) scoring system after 5-year minimum followup in patients treated with this prosthesis at one center; (2) what are the problems and complications associated with the lengthening procedures of this implant; and (3) what are the specific concerns associated with revision of this implant? METHODS: At our institute, between 2002 and 2007, the Repiphysis(®) expandable prosthesis was implanted in 15 children (mean age, 8 years; range, 6-11 years) after distal femoral resection for malignant bone tumors. During this time, the general indication for use of this implant was resection of the distal femur for localized malignant bone tumors in pediatric patients. Alternative techniques used for this indication were modular prosthetic reconstruction, massive (osteoarticular or intercalary) allograft reconstruction, or rotationplasty. Age and tumor extension were the main factors to decide on the surgical indication. Of the 15 patients who had this prosthesis implanted during reconstruction surgery, five died with the implant in situ or underwent amputation before 5 years followup and the remaining 10 were evaluated at a minimum of 5 years (mean, 104 months; range, 78-140 months). No patients were lost to followup. These 10 patients were long-term survivors and underwent the lengthening program. They were included in our study analysis. The first seven lengthening procedures were attempted in an outpatient setting; however, owing to pain and burning sensations experienced by the patients, the procedures failed to achieve the desired lengthening. Therefore, other procedures were performed with the patients under general anesthesia. We reviewed clinical data at index surgery for all 15 patients. We further analyzed the lengthening procedures, implant survival, radiographic and functional results, for the 10 long-term survivors. Functional results were assessed according to the MSTS scoring system. Complications were classified according to the International Society of Limb Salvage (ISOLS) classification system. RESULTS: Nine of the 10 survivors underwent revision of the implant for mechanical failure. They had a mean MSTS score of 64% (range, 47%-87%) before revision surgery. At final followup the 10 long-term surviving patients had an average MSTS score of 81% (range, 53%-97%). In total, we obtained an average lengthening of 39 mm per patient (range, 17-67 mm). Exact expansion of the implant was unpredictable and difficult to control. Nine of 10 of the long-term surviving patients underwent revision surgery of the prosthesis-eight for implant breakage and one for stem loosening. At revision surgery, six patients had another type of expandable prosthesis implanted and three had an adult-type megaprosthesis implanted. In five cases, segmental bone grafts were used during revision surgery to compensate for loss of bone stock. CONCLUSIONS: We could not comfortably expand the Repiphysis(®) prosthesis in an outpatient setting because of pain experienced by the patients during the lengthening procedures. Furthermore, use of the prosthesis was associated with frequent failures related to implant breakage and stem loosening. Revisions of these procedures were complex and difficult. We no longer use this prosthesis and caution others against the use of this particular prosthesis design. LEVEL OF EVIDENCE: Level IV, therapeutic study

NYESO-1/LAGE-1s and PRAME Are Targets for Antigen Specific T Cells in Chondrosarcoma following Treatment with 5-Aza-2-Deoxycitabine

Chondrosarcoma has no proven systemic option in the metastatic setting. The development of a non-cross-resistant strategy, such as cellular immunotherapy using antigen-specific T cells would be highly desirable. NY-ESO-1 and PRAME are members of the Cancer Testis Antigen (CTA) family that have been identified as promising targets for T cell therapy. LAGE-1 is a cancer testis antigen 90% homologous to NY-ESO-1, sharing the 157-165 A*0201 NY-ESO-1 epitope with its transcript variant, LAGE-1s. A number of CTA's have been induced using 5-Aza-2-Deoxycitabine (5-Aza-dC) in other cancers. We sought to evaluate the feasibility of targeting chondrosarcoma tumors using NY-ESO-1/LAGE-1s and PRAME specific T cells using 5-Aza-dC to induce antigen expression.We used 11 flash frozen tumors from the University of Washington tumor bank to test for the expression of NY-ESO-1, PRAME, LAGE-1s and LAGE-1L in chondrosarcoma tumors. Using four chondrosarcoma cell lines we tested the expression of these CTA's with and without 5-Aza-dC treatments. Finally, using NY-ESO-1/LAGE-1s and PRAME specific effectors that we generated from sarcoma patients, we evaluated the ability of these T cells to lyse A*0201 expressing chondrosarcoma cell lines in vitro both with and without 5-Aza-dC treatment.A minority (36%) of chondrosarcoma tumors expressed either NY-ESO-1 or LAGE-1s at >10% of our reference value and none expressed PRAME at that level. However, in all four of the chondrosarcoma cell lines tested, NY-ESO-1 and PRAME expression could be induced following treatment with 5-Aza-dC including in cell lines where expression was absent or barely detectable. Furthermore, NY-ESO-1/LAGE-1s and PRAME specific CD8+ effector T cells were able to specifically recognize and lyse A*0201 expressing chondrosarcoma cell lines following 5-Aza-dC treatment.These data suggest that adoptive immunotherapy in combination with 5-Aza-dC may be a potential strategy to treat unresectable or metastatic chondrosarcoma patients where no proven systemic therapies exist

Treatment of chronic osteomyelitis with antibiotic-loaded bone void filler systems: an experience with hydroxyapatites calcium-sulfate biomaterials

This is a retrospective study that aims to quantify the problem of chronic osteomyelitis in one of the largest Italian orthopedic centers. Furthermore this study is focused on evaluation of efficacy of bone void filler systems with particular attention to a subgroup of patients treated with PerOssal\uae. Ninety-seven patients were included in this study between 2008 and 2013 with a minimum follow up of 24 months. A subgroup of 52 patients was treated with curettage plus PerOssal\uae, another group was treated with curettage only or curettage with other bone void filler systems. Overall we obtained a cure rate of 80,4%, whereas 19,6% had recurrent infection. Looking at the subgroup treated with PerOssal\uae we found a healing rate of 86,5%, which was significantly higher compared to the other groups. Of the patients with recurrence of infection, those treated with PerOssal\uae recurred 106 days later than the other patients

Chondrosarcomas revisited.

Chondrosarcomas are malignant bone tumors with pure hyaline cartilage differentiation; myxoid changes, calcification, or ossification may be present. Several subtypes of chondrosarcomas exist. Behavior patterns vary, ranging from slow-growing nonmetastasizing lesions to aggressive metastasizing sarcomas. Symptoms are usually mild, with duration ranging from several months to years, and usually consist of persistent, dull, aching pain or palpable masses. Radiographic findings include bone expansion with cortical thickening, radiolucent areas with variably distributed punctate or ring-like matrix calcifications, cortical erosion or destruction, endosteal scalloping, and scant or absent periosteal reaction; extension into the soft tissue may be present. Histological differential diagnosis from benign cartilaginous lesions can be achieved by increased cellularity, enlarged plump nuclei, binucleated cells, hyperchromatic nuclear pleomorphism, and permeation of cortical or medullary bone. Atypia is usually mild to moderate; necrosis and mitoses can be seen, particularly in high-grade lesions. Adequate surgery is the mainstay of treatment. High-grade and pelvic chondrosarcomas are best managed with wide resection. Because of the low metastatic potential and low local recurrence rate noted with intralesional surgery, low-grade chondrosarcomas can be treated with curettage (with or without treatment of the defect cavity) with a local adjuvant, such as phenol or cryotherapy. Adjuvant chemotherapy may be considered for mesenchymal and dedifferentiated chondrosarcomas. Radiation therapy can be considered after incomplete resection or if resection is not feasible or would cause unacceptable morbidity

Chondrosarcomas revisited.

Chondrosarcomas are malignant bone tumors with pure hyaline cartilage differentiation; myxoid changes, calcification, or ossification may be present. Several subtypes of chondrosarcomas exist. Behavior patterns vary, ranging from slow-growing nonmetastasizing lesions to aggressive metastasizing sarcomas. Symptoms are usually mild, with duration ranging from several months to years, and usually consist of persistent, dull, aching pain or palpable masses. Radiographic findings include bone expansion with cortical thickening, radiolucent areas with variably distributed punctate or ring-like matrix calcifications, cortical erosion or destruction, endosteal scalloping, and scant or absent periosteal reaction; extension into the soft tissue may be present. Histological differential diagnosis from benign cartilaginous lesions can be achieved by increased cellularity, enlarged plump nuclei, binucleated cells, hyperchromatic nuclear pleomorphism, and permeation of cortical or medullary bone. Atypia is usually mild to moderate; necrosis and mitoses can be seen, particularly in high-grade lesions. Adequate surgery is the mainstay of treatment. High-grade and pelvic chondrosarcomas are best managed with wide resection. Because of the low metastatic potential and low local recurrence rate noted with intralesional surgery, low-grade chondrosarcomas can be treated with curettage (with or without treatment of the defect cavity) with a local adjuvant, such as phenol or cryotherapy. Adjuvant chemotherapy may be considered for mesenchymal and dedifferentiated chondrosarcomas. Radiation therapy can be considered after incomplete resection or if resection is not feasible or would cause unacceptable morbidity

Synovial sarcoma: Retrospective analysis of 250 patients treated at a single institution

BACKGROUND: The optimal treatment for synovial sarcoma remains controversial. Treatment, outcome, and prognostic factors in patients treated in a single institution were examined. METHODS: Synovial sarcoma patients who underwent surgery at the Rizzoli Institute between 1976 and 2006 were identified and analyzed. RESULTS: Characteristics of the 250 patients (128 female; 122 male) included: median age, 37 years (range, 7-83 years); 177 (71%) with tumors in the lower extremity, 40 (16%) with tumors in the upper extremity, and 33 with tumors in the trunk (13%); primary lesion size >5 cm in 121 patients (55%); and 204 (82%) patients with localized disease and 46 (18%) with metastatic disease at the time of presentation. All patients with localized disease underwent surgery. Twenty-four percent of patients underwent amputation. Adequate surgical margins were achieved in 88% patients. In patients with localized disease, radiotherapy was administered to 103 (50%) patients, and chemotherapy to 98 (48%). With a median follow-up of 5.5 years (range, 1-30 years), the 5-year overall survival rate was 10% for patients with metastatic disease and 76% for patients with localized disease (P = .0001). The 5-year event-free survival was 58% in patients with localized disease. Multivariate analysis indicated that size, age, histologic subtype, and the use of radiotherapy were independent factors for event-free survival. CONCLUSIONS: In those patients with localized disease, a good rate of cure can be achieved. Age, size, histology, and use of radiotherapy influence prognosis, whereas to the authors' knowledge, the role of adjuvant chemotherapy remains unproven. \ua9 2009 American Cancer Society

Fibrosarcomatous changes and expression of CD34+ and apolipoprotein-D in dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is a relatively common soft-tissue tumor. A more aggressive appearing fibrosarcoma may arise in DFSP, changing its biological behavior. CD34 and apolipoprotein-D are highly expressed in DFSP, but their prognostic significance is uncertain. METHODS: DFSP and fibrosarcomatous-DFSP (FS-DFSP) patients referred to our institute between 1982 and 2009 were identified. Fibrosarcomatous changes, expression of CD34 and apolipoprotein-D were evaluated. RESULTS: 40 patients, (median age 43 years, 55% males) were identified. Tumor was located in the limbs in 60%, in the trunk in 40%. Thirty-seven patients had localized and 3 had metastatic disease. Thirteen (32%) patients were FS-DFSP. All but one underwent surgery with adequate surgical margins in 72%. 7 FS-DFSP received also radiotherapy (RT). Chemotherapy was administered to 3 patients with FS-DFSP. With a median follow-up of 49 months, the 5-OS was 90%. Local recurrence rate was 23%: 42% FS-DFSP, 15% DFSP. Metastases developed in three FS-DFSP patients. The 5-year EFS was 70% in localized patients. Histology (DFSP 75% vs. FS-DFSP 52%, p = 0.002), surgical margins (adequate 74% vs. inadequate 55%, p = 0.02), site (limb 47% vs. trunk 100%), CD34 expression (CD34 positive: 70% vs. CD34 negative: 33%, p = 0.05), and apolipoprotein-D expression (Apo-D positive: 73% vs. Apo-D negative: 33%, p = 0.02) influenced the 5-year EFS, whereas sex, use of RT or number of previous surgical treatments did not. CONCLUSIONS: Patients with DFSP have a high survival probability. Site, adequate surgical margins, presence of the fibrosarcomatous component, lack of CD34 expression and apolipoprotein-D influence outcome