Research Items (81)
- May 2019
Background: Although multidisciplinary therapies have improved local control and overall survival in Ewing sarcoma (ES), the prognosis of pelvic lesions remains markedly worse than that of limb ES. Methods: We retrospectively evaluated the influence of the type of local treatment, margins, necrosis and sacrum involvement on overall survival (OS) and disease-free survival (DFS) in a series of 21 non-metastatic pelvic ES. Results: The average follow-up was 46.3 months (range 3-156). Only one patient had recurrence, at 11 months after surgery. Eight patients showed pulmonary metastasis and five showed bone metastases. Necrosis was the only significant prognostic factor for overall survival at 5 years (p=0.0132) and disease-free survival (p=0.0086). Overall survival at 5 years was 40.1%. Conclusion: Local control in pelvic Ewing sarcoma is comparable for patients treated with surgery (S), surgery plus radiotherapy (S/RT), or definitive radiotherapy (RT). The combination of surgery plus radiotherapy could be indicated in cases of large tumor, a poor necrosis response (< 90%), or an inadequate margin with involvement of the sacrum. A poor response to neoadjuvant therapy is a significant risk factor for both local control and overall survival.
Background Sarcomas that arise from the scapula or periscapular soft tissues often require a total scapulectomy. This often implies a large complex tissue defect that needs adequate reconstruction of both bone and soft tissue. Although various methods have been developed, no optimal procedure has emerged. Postoperative complications are common and functional recovery is not always satisfactory. This study aims to present a new surgical technique that combines a custom-made scapular prosthesis with a functional latissimus dorsi flap. Case presentation Two patients diagnosed with malignant tumour of the scapular region were surgically treated after proper multidisciplinary evaluation. The first patient underwent the procedure as a first surgery, the second as revision surgery. The new technique comprises three surgical stages: excisional surgery with soft tissue resection and scapulectomy, bone reconstruction with custom-made prosthesis, and soft tissue reconstruction using a latissimus dorsi rotational flap overturned on the prosthesis. The goal is to set up a new functional unit combining an anatomically shaped implant (manufactured using latest three-dimensional printing technology) and a muscular flap, and to maintain the neurovascular supply. The patients were followed up to evaluate functional outcome and complications. Both patients were alive with no evidence of disease. Functional results were satisfactory and the Musculoskeletal Tumor Society scores were 87% and 63%, respectively. No surgical complications such as implant breakage, joint collapse, wound dehiscence, or infection were observed. Conclusions This new technique upgrades the role of the latissimus dorsi flap to a functional tool in combination with an anatomical, three-dimensionally printed, custom-made prosthesis, and provides adequate well-vascularized and healthy tissue to maximize the likelihood of successful limb salvage.
- Dec 2018
Cryotherapy, also called Cryoablation (CA), is a technique that provides a local treatment to various pathological conditions. In Musculoskeletal tumours management, Cryoablation is well accepted and validated as a treatment in palliative cures for metastatic patients. Recently, CA has been proposed also as an alternative to radiofrequency ablation in osteoid osteoma and other benign tumour treatment with promising results. Cryotherapy with argon ice-balls as local adjuvant in open surgery is a tool that can provide enlargement of surgical margins if used properly. There is still not enough evidence supporting use of cryotherapy as local adjuvant in Musculoskeletal open surgery as the series cited above are very small and there is no comparative RCT between local adjuvant therapies including CA. One-hundred-and-eighty-three patients were treated with Cryoablation from 2000 and 2018 in the Musculoskeletal Tumours Surgery Unit of Careggi (Florence) and the University 2nd Clinic of Pisa. In our study group, 38 patients (26.6%) were affected by bone metastasis, 16 patients (11.1%) by aneurismal bone cysts or angiomas, 22 patients (15.4%) by low-grade malignant musculoskeletal tumours, 2 patients (1,4%) by fibromatosis, 63 patients (44.1%) by benign musculoskeletal tumours (principally Giant Cell Tumours-GCT) and 2 patients (1.4%) by Osteosarcomas. In 125 cases (87.4%), CA has been used as an adjuvant therapy, in 12 cases (8.4%) as a percutaneous ablation therapy and in 6 cases (4.2%) as adjuvant to remove tumoral lesions 'en bloc' or as a 'poor technique' for its sterilizing effect on previously resected bones. Mean follow-up was 10 years. Twenty-three patients (16%) were classified as Alive with Disease (AWD) due to local recurrence or tumour progression (14 metastases, 5 low-grade malignant bone tumours, 4 Giant Cell Tumours). Eight patients died due to the disease (6 metastases, 2 osteosarcomas), while 1 died from leukaemia. One-hundred-and-eleven patients (78%) were classified as Continues Disease Free (CDF). All patients reported decrease in pain-related symptoms after surgery and all surgeons reported better control of blood loss. Three cases (2%) of local skin necrosis or wound dehiscence were reported. No local recurrences were reported after fibromatosis ablation. Our results confirm that CA could be considered as a safe and effective technique to treat various conditions as adjuvant and palliative therapy. In particular, in open surgery, cryotherapy as an adjuvant treatment could lead to very low rates of recurrence in locally aggressive tumours like Giant Cell Tumours. These results could be generalized but a better understanding about indications and outcomes can be reached studying CA in specific populations with comparation to other adjuvant techniques.
- Nov 2018
Aim Liposarcoma (LPS) is rare tumor deriving from adipocytes. LPS is classified into histological subtypes: well-differentiated (WDLPS), dedifferentiated (DDLPS), myxoid (MLPS) and pleomorphic (PLPS). A tailored approach taking into account the specificity of disease subtype and age at presentation could be helpful in delineating therapeutic management of liposarcoma. In this paper, we report a retrospective series of a single-institution cohort of patients with LPS, undergoing surgery and radiotherapy and/or chemotherapy. The aim of this study is to evaluate whether clinical characteristics, tumor- and treatment-related features affect clinical outcome in patients treated with curative intent for non-metastatic liposarcoma. Methods Data of patients with locally advanced, non-metastatic liposarcoma treated between 1990 and 2015 were retrospectively reviewed. Data about patient, tumor and treatment features were collected. Two patients subgroups were identified according to age (cutoff: age < 65 years or > 65 years). Statistical analysis was performed to assess correlation between the above-cited variables and local recurrence-free survival (DFS-LR), distant metastasis-free survival, overall survival (OS) and disease-specific survival (DSS); moreover, differences in clinical outcome between the two age groups were identified. Results Data of 186 patients were collected. At diagnosis, 27.4% of patients were 65 years or older. At a median follow-up of 8.6 years (range 0.1–27.3 years), Kaplan–Meier (KM) survival analysis showed that LR, DM, OS and DSS were 75.5%, 76.6%, 48.1% and 72.1%, respectively. KM analysis showed that age > 65, DDLPS and lower limb localization were related to LR (p = 0.001, p = 0.0001 and p = 0.0001, respectively). Association between LR, age and DDLPS persisted both at univariate (p = 0.003 and p = 0.0001, respectively) and multivariate Cox regression (CR) analysis (p = 0.024 and p = 0.002). Age, tumor depth and grading influenced distant recurrence, both at KM (p = 0.023, p = 0.026 and p = 0.016) and univariate CR (p = 0.026, p = 0.042 and p = 0.012). Age and grading were confirmed at multivariate analysis (p = 0.009 and p = 0.017). Patients with WDLPS and wide excision had significantly better OS (p = 0.001 and p = 0.03, respectively), while histological G3 and age > 65 were related with worse OS (p = 0.008 and p = 0.0001, respectively). Age, DDLPS and grade were related to OS at univariate (p = 0.0001, p = 0.0001 and p = 0.03, respectively) and multivariate CR analysis (p = 0.031, p = 0.0001 and p = 0.001, respectively). However, analyzing the specific causes of death, female died less often for tumor-related causes, with a DSS of 91.0% compared to 57.4% of male counterpart (p = 0.005). At Kaplan–Meier analysis, postoperative radiotherapy resulted in a statistically significant better disease-specific survival than postoperative radiotherapy (82.9% vs. 46.2%, p = 0.045). High grade correlated with poorer disease-specific survival (59.3%) than intermediate and low grade (73.4% and 91.6%, respectively) (p = 0.008). Association between DSS, sex and grade persisted both at univariate (p = 0.008 and p = 0.022, respectively) and multivariate Cox regression (CR) analysis (p = 0.014 and p = 0.038). Histotype-driven schedules of treatment should be developed to take into account biological heterogeneity of this disease. Further studies are needed to stratify patients subgroup and develop tailored treatment strategies (i.e., altered fractionations and different chemotherapy regimens in aggressive subtypes), in particular more prospective trials are needed to develop treatment guidelines in elderly STS, taking into account the frailty and the peculiarity of this subgroup.
Purpose Adjuvant radiotherapy is the standard postoperative treatment after conservative surgery in high risk soft tissue sarcoma. The role of adjuvant chemotherapy is still debated. Therefore, a matched cohort analysis was performed in high risk soft tissue patients to analyse differences in terms of clinical outcome and toxicity between patients treated with concomitant radio-chemotherapy (RTCT) and radiotherapy (RT) alone. Materials and Methods For each patient in RT group was selected a patient in the RTCT group matching for age, T stage and grading. Acute and late toxicity were recorded, overall survival, recurrence free survival and distant metastases free survival were analysed and compared between the two groups. Results Ninety patients were selected, half of patients underwent radio-chemotherapy and half received radiotherapy alone. During the treatment Grade 3 dermatitis was recorded in 15 (16.7%) patients, 6 (6.7%) patients associated chemotherapy and during follow up 12 (13.3%) patients developed grade 2 late fibrosis, 3 (3.3%) joint stiffness and 1 (1.1%) patient experienced a bone fracture. There were no differences in the rate of acute and late toxicity between RTCT and RT alone group. Nineteen (21.1%) patients developed local recurrence, overall 5-year local relapse free survival was 83%. There were no differences between the two groups. 29 patients developed distant metastases, 14 (15.6%) patients in the RTCT group and 15 (16.7%) patients in the RT group. The 5-year distant metastases free survival was 67%. Age > 65 years was the only independent factor affecting distant recurrence (HR = 5.7, 95% CI 2.7–11.9; p = 0.001). At the time of analysis 15 (16.7%) patients were dead, 6 (6.7%) patients in the RTCT group and 9 (10%) patients in the RT group. 5-years overall survival was: 88%. At multivariate analysis age > 65 years was an independent prognostic factor of overall survival (HR = 3.7, 95% CI 1.2–12.1, p = 0.037). Conclusions Prospective randomized studies with large size population and with subgroup analysis for histological subtypes are necessary to clarify the role of adjuvant chemotherapy in soft tissue sarcoma patients. Tailored treatment has to be considered in elderly soft tissue patients to guarantee a better outcome in this high risk and fragile population.
Study design: Retrospective case series. Objective: To report the outcome of a series of patients with sacral chordoma who were surgically treated at a single center. Summary: Chordomas are low-grade malignant tumors that arise from remnants of the notochord. They are most often found in the sacrum, spine and skull-base. These tumors have a slow clinical evolution and may eventually metastasize, even after adequate treatment. Rarely, they can dedifferentiate into high-grade sarcomas. Traditionally, chordomas were considered to be resistant to chemotherapy and standard radiation therapy. However, recently, adrotherapy has been shown to be effective for local and systemic control of the disease. In this study, clinical outcomes and local and systemic recurrence were reviewed to identify prognostic factors for local and systemic control. Methods: Thirty-three patients with sacral chordoma (19 males, 14 females; median age 61 y, range 43-80) who were surgically treated at our institution between 1994 and 2015 were reviewed. In 24 patients, resection was performed above S2. No patients received pre-operative radiotherapy (RT). Three cases received RT (carbon ion therapy) as treatment for local recurrence. Wide (R0) surgical margins were achieved in 17 patients, marginal (R1) margins in 14 patients and intralesional (R2) margins in 2 patients. Results: At a median follow-up of 53 months (range 0-198), 19 patients were continuously disease-free, 6 were disease-free after local recurrence (5) or metastases (1), 3 were alive with disease (2 local recurrence and 1 metastasis), 4 were dead of disease (1 patient died intraoperatively) and 1 was dead of another cause. Local recurrence was observed in 9 cases (27%); all 9 were treated surgically and 3 received carbon ion therapy after surgical intralesional excision. Overall survival at 10 years was 86.6%. Local recurrence-free survival at 10 years was 51%. A statistical analysis confirmed the importance of negative surgical margins (R0) to achieve local control of the disease (p = 0.0007). High resections (above S2) were associated with lower survival and higher risk of local recurrence. Conclusion: Surgical en bloc resection is the primary treatment for sacral chordoma. Carbon ion therapy is used when it is difficult to obtain wide surgical margins. Due to morbidity and the disabling sequelae of surgery, adrotherapy may be considered an alternative to high (above S2-S3) sacral chordoma resections.
- Aug 2018
Soft tissue sarcomas (STS) are aggressive tumors with a poor prognosis. Poly(ADP-ribose) polymerase (PARP)-1 inhibitors (PARPi) enhance the cytotoxic effects of radiation. In this study, we evaluated the effect of PARPi on survival and DNA damage of irradiated STS cells. For clonogenic assays, STS cell lines were irradiated with or without olaparib, iniparib or veliparib pretreatment. The effect of PARP inhibition on γ-H2AX and Rad51 foci formation, on PARP-1, phospho-ERK and cleaved caspase-3 protein expression and on cell cycle progression was evaluated on irradiated rhabdomyosarcoma cells pretreated with olaparib. The results from this work showed that PARPi induced significant radiosensitization in STS cells. Rhabdomyosarcoma cells showed the highest increase in radiosensitivity, with a radiosensitization enhancement ratio at 50% survival (ER50) of 3.41 with veliparib. All PARPi exerted a synergistic effect when combined with radiation. Fibrosarcoma cells showed an ER50 of 2.29 with olaparib. Leiomyosarcoma and liposarcoma cells showed their highest ER50 with veliparib (1.71 and 1.84, respectively). In rhabdomyosarcoma, olaparib enhanced the formation of radiation-induced γ-H2AX/Rad51 foci and PARP-1 cleavage, induced slightly increased expression of cleaved caspase-3 and reduced phospho-ERK expression. Moreover, the combination of olaparib and radiation resulted in a significantly enhanced cell cycle arrest in the G2/M phase compared to the two treatments alone. In conclusion, we have shown that PARPi are potent radiosensitizers of human STS cells. These results support the pursuit of further investigations into the effects of PARPi combined with radiation on STS.
One of the most frequent outcomes after resection of bone tumors in children is a limb-length discrepancy. An intramedullary nail is a valid method for lengthening the limb. We report our experience with four cases of limb-length discrepancy in the lower limbs several years after the primary treatment of bone tumor resection and subsequent reconstruction. Two femoral PRECICE® nails (NuVasive, Inc., San Diego, CA) were introduced retrograde and two were introduced in an anterograde manner. All four cases healed and showed a reduction of the limb-length discrepancy, early loading, and complete bone osteogenesis. In one case, a reduction of the joint ROM recovered after release of the iliotibial band and a quadriceps release according to Judet's arthrolysis.
Background and objectives: Liposarcoma (LPS) is a malignant mesenchymal tumor and the most common soft tissue sarcoma. Four different subtypes are described: well differentiated (WD) LPS or atypical lipomatous tumor (ALT), dedifferentiated (DD) LPS, myxoid LPS, and pleomorphic LPS (PLS). The objective of the study was to investigate prognostic factors and clinical outcome of liposarcoma. Methods: We retrospectively examined the clinico-pathological features of a series of 307 patients affected by Liposarcoma at a mean follow-up of 69 months (range 6-257). ALT/WD LPS were analyzed separately. The influence of site, size, type of presentation, grading, histotype and local recurrence on local and systemic control and survival was assessed. Results: The statistical analysis indicated that only surgical margins represented a significant prognostic factor for local recurrence in ALT/WD LPS (P = 0.0007) and other subtypes of LPS (P = 0.0055). In myxoid, PLS and DD LPS, significant prognostic factors for metastasis free survival (MFS) were surgical margins (P = 0.0009), size of the tumor (P = 0.0358), histology (P = 0.0117) and local recurrence (P = 0.0015). In multivariate analysis, surgical margins (0.0180), size (0.0432) and local recurrence (0.0288) correlated independently with MFS. Margins (P = 0.0315), local recurrence (P = 0.0482) and metastases (P < 0.0001) were prognostic factors for overall survival (OS). Conclusion: Marginal surgery can be an accepted treatment for ALT/WD LPS. In other liposarcoma subtypes (Myxoid, DD, PLS) wide or radical surgery is recommended as the margins significantly influence local recurrence-free survival (LRFS), metastasis-free survival (MFS) and overall survival (OS). Local recurrence and metastases were significant prognostic factors for OS.
- Jun 2018
Due to advances in neoadjuvant therapies and preoperative imaging modalities, joint-sparing resections have become appealing in bone tumor surgery. However, the intercalary reconstruction of metadiaphyseal bone defects of the femur and the tibia after juxta-articular tumor resection remains challenging. Both biological and prosthetic reconstructions have been used for joint-sparing resections, but little is known about the long-term outcome of these procedures. The authors reviewed a consecutive series of 64 patients treated with joint-sparing intercalary resection and reconstruction with bone grafts. Inclusion criteria were an osteotomy line within 5 cm from the knee and ankle joint surface and an osteotomy line proximal to 1 cm below the lesser trochanter at the hip level. Intra-epiphyseal resection was performed in 25 patients (39%)and intercalary resection was performed in 39 (61%). Reconstruction included 49 allograft + vascularized fibular graft (VFG), 10 allografts, and 5 VFG + structural allogenic grafts. At a mean follow-up of 117 months (range 12-305), 51 patients (80%) were continuously disease-free, and 6 showed no evidence of disease after treatment of local recurrence or metastatic lesion. One patient was alive with lung metastases at 26 months of follow-up and six patients died of disease. In the entire series of 64 patients, 26 had a non-oncological complication that required surgical revision (40.6%). Overall survival (OS) of reconstruction was 92% at 5 years and 90% at 10 and 15 years. Limb salvage survival (LSS) was 94% at 5, 10 and 15 years. Twenty-two fractures occurred in 17 patients (26.5%). There were a total of nine non-unions (14%). Six patients (9.3%) presented early wound dehiscence (average 1.8 months, range 0-6). A deep infection occurred in 3 cases (4.7 %). In 12 patients treated with VGF reconstruction (12/54:22%), a donor-site complication was observed. The overall Musculoskeletal Tumor Society (MSTS) functional score in 54 evaluable patients, who were alive with reconstruction in situ, was 27 points (range 18-30). Biologic intercalary reconstructions with bone grafts resulted in effective joint-sparing resections of the lower limb, allowing joint preservation in all but one case who required a total knee replacement for varus osteoarthritis. Despite the high rate of complications requiring surgical revision, at 15 years, overall survival of the reconstruction was 90% and limb salvage survival was 94%. In our experience, revision-free survival was better with VFG reconstruction than with allograft alone and the combination of VFG and allogenic graft seems to favor spontaneous fracture-healing and to decrease the non-union rate.
Background. Authors analyzed retrospectively 98 Atypical Lipomatous Tumor (ALT) treated at a single institution, 96% of which was localized to the extremities and 4% to the trunk, assessing MRI, surgical treatment, local recurrence, follow-up and de-differentiation ability. Methods. Authors used MRI in order to identify ALT size, site, the presence of septa and contrast enhancement. Surgical margins were divided at final histology in wide/radical, marginal and intralesional. Results. The most common localization was the lower limb (84% of cases), 52% of cases showed size larger than 10 cm; 80% of cases were deep-seated. MRI revealed thick septa in 83% and contrast enhancement in 78% of the cases. Eleven local recurrences of the disease (11%) were observed, with only surgical margins representing a significant prognostic factor on local recurrence (p = 0.0007). No de-differentiation was reported nor metastatic spread. Conclusions. The slow growth and the dedifferentiation ability in ALT needs a long follow-up. MRI with contrast is the imaging method of choice. The optimal treatment is wide/radical resection.
- Apr 2018
Introduction: This retrospective study analyzes the safety and feasibility of concurrent chemoradiotherapy (CRT) in adjuvant treatment of soft tissue sarcoma (STS). Methods: A total of 158 patients with STS were retrospectively analyzed. Anthracycline-based computed tomography was performed in high-risk patients. Acute radiotherapy toxicity and chemotherapy-related toxicity were assessed according to the Common Terminology Criteria for Adverse Events 4.0; late radiotherapy toxicity was recorded according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Results: Fifty-four (34.2%) patients received CRT. Mean follow up was 5.4 years (range .2-21.1 years). Local DFS-recurrence-free survival, distant DFS-relapse-free survival, and overall survival were 79.1%, 76.4%, and 64.6%, respectively, at last follow-up. Leukopenia occurred in 11.4% of patients. Skin acute toxicity developed in 60.1% of patients and determined interruption of radiotherapy treatment in 19 (12%) patients. Nineteen patients (12%) experienced moderate fibrosis (grade 2). Mild and moderate joint stiffness was recorded in 16 (10.1%) patients. Size ≥5 cm was the only predictor of local recurrence at multivariate analysis (hazard ratio [HR] 9.65, 95% confidence interval [CI] 1.28-72.83, p = .028). Age and stage resulted as independent distant relapse predictors (HR 4.77, 95% CI 1.81-12.58, p = .002 and HR 4.83, CI 1.41-16.57, p = .012, respectively). At Cox regression univariate analysis, Karnofsky Performance Status, size, and stage were significant survival predictors (HR 2.23, 95% CI 1.02-4.87, p = .045; HR 2.88, 95% CI 1.10-7.52, p = .031; HR 2.59, 95% CI 1.11-6.04, p = .028). Conclusions: Concurrent CRT is a well-tolerated treatment option with no additional toxicity compared to exclusive radiotherapy or sequential CRT.
Background: Poly(ADP-ribose) polymerases (PARP) are a large family of enzymes involved in several cellular processes, including DNA single-strand break repair via the base-excision repair pathway. PARP inhibitors exert antitumor activity by both catalytic PARP inhibition and PARP-DNA trapping, moreover PARP inhibition represents a potential synthetic lethal approach against cancers with specific DNA-repair defects. Soft tissue sarcoma (STSs) are a heterogeneous group of mesenchymal tumors with locally destructive growth, high risk of recurrence and distant metastasis. Objectives: The purpuse of this review is to provide an overview of the main preclinical and clinical data on use of PARPi in STSs and of effect and safety of combination of PARPi with irradiation. Results: Due to numerous genomic alterations in STSs, the DNA damage response pathway can offer an interesting target for biologic therapy. Preclinical and clinical studies showed promising results, with the most robust evidences of PARPi efficacy obtained on Ewing sarcoma bearing EWS-FLI1 or EWS-ERG genomic fusions. The activity of PARP inhibitors resulted potentiated by chemotherapy and radiation. Although mechanisms of synergisms are not completely known, combination of radiation therapy and PARP inhibitors exerts antitumor effect by accumulation of unrepaired DNA damage, arrest in G2/M, activity both on oxic and hypoxic cells, reoxygenation by effect on vessels and promotion of senescence. Early trials have shown a good tolerance profile. Conclusions: The use of PARP inhibitors in advanced stage STSs, alone or combined in multimodal treatments, is of great interest and warrants further investigations.
Aims: After intercalary resection of a bone tumour from the femur, reconstruction with a vascularized fibular graft (VFG) and massive allograft is considered a reliable method of treatment. However, little is known about the long-term outcome of this procedure. The aims of this study were to determine whether the morbidity of this procedure was comparable to that of other reconstructive techniques, if it was possible to achieve a satisfactory functional result, and whether biological reconstruction with a VFG and massive allograft could achieve a durable, long-lasting reconstruction. Patients and methods: A total of 23 patients with a mean age of 16 years (five to 40) who had undergone resection of an intercalary bone tumour of the femur and reconstruction with a VFG and allograft were reviewed clinically and radiologically. The mean follow-up was 141 months (24 to 313). The mean length of the fibular graft was 18 cm (12 to 29). Full weight-bearing without a brace was allowed after a mean of 13 months (seven to 26). Results: At final follow-up, the mean Musculoskeletal Tumor Society Score of 22 evaluable patients was 94% (73 to 100). Eight major complications, five fractures (21.7%), and three nonunions (13%) were seen in seven patients (30.4%). Revision-free survival was 72.3% at five, ten, and 15 years, with fracture and nonunion needing surgery as failure endpoints. Overall survival, with removal of allograft or amputation as failure endpoints, was 94.4% at five, ten, and 15 years. Discussion: There were no complications needing surgical revision after five years had elapsed from surgery, suggesting that the mechanical strength of the implant improves with time, thereby decreasing the risk of complications. In young patients with an intercalary bone tumour of the femur, combining a VFG and massive allograft may result in a reconstruction that lasts a lifetime. Cite this article: Bone Joint J 2018;100-B:378-86.
- Feb 2018
Background: Denosumab is a monoclonal RANKL antibody, which was originally introduced for the treatment of osteoporosis and bone metastases from solid tumors, but more recently has been used for treatment of giant cell tumor of bone (GCTB). In GCTB, denosumab has been used as a single agent in patients with inoperable tumors; it also has been used before surgery in some patients with the aim to downstage the tumor to facilitate a joint-preserving procedure (curettage) rather than a resection. However, few studies are available evaluating the benefits and risks of denosumab for the latter indication. Questions/purposes: (1) Does preoperative treatment with denosumab reduce the risk of local recurrence in patients treated for GCTB? (2) Are there adverse effects of short-term denosumab use before surgery and, if so, what are they? Methods: All patients with a diagnosis of GCTB surgically treated at our institution from June 2009 to June 2016 with curettage and cryotherapy were retrospectively evaluated to compare patients treated with curettage alone versus patients treated with curettage after preoperative therapy with denosumab. During that period, we treated 97 patients for GCTB; 30 patients were excluded because they received a resection; 34 patients were excluded because they received curettage without cryotherapy. Of the remaining 33 patients, four were excluded because they received denosumab only after surgery, one because she received zoledronic acid, one because she received a curettage after her refusal of a resection that was the advised procedure, two because they were lost to followup early, and four because they were treated for recurrence rather than a new diagnosis of GCTB. The remaining 21 patients were included. Twelve lesions had been treated with surgery after denosumab and nine with surgery alone. During the study period, we preferentially used denosumab for the more aggressive-looking lesions. After curettage, cryotherapy of the residual bone walls was performed with argon cryoprobes to -150° C after pouring gel into the cavity, and we then used cement (17 patients) or morcellized allograft (four patients). Tumors were Campanacci Grade 3 in eight of 12 patients in the denosumab group and in two of nine patients in the surgery-only group (p = 0.08), but the extent of epiphyseal juxtaarticular bone involvement was not different between the groups with the numbers available. Median followup was 39 months (range, 14-55 months) in the denosumab group and 27 months (range, 18-92 months) in the surgery-only group. We used chart review to record the proportion of patients in each treatment group who had a local recurrence and to tally adverse events. Results: With the numbers available, there was no difference in the proportion of patients experiencing a recurrence (five of 12 in the denosumab group and one of nine in the surgery-only group; p = 0.18). We found no adverse effects associated with denosumab either during or after treatment; specifically, we found no alterations in electrolyte levels, blood count, or liver and renal function parameters. In this small series, no patient has developed osteonecrosis of the jaw. Conclusions: In this small series, use of denosumab before surgery for GCTB appeared to allow the reforming of a bone peripheral rim around the tumor, perhaps facilitating curettage rather than osteoarticular resection in some patients. However, we did not observe a decrease in the risk of local recurrence with the use of denosumab, suggesting that it may not decrease the aggressiveness of the disease; according to our preliminary results, we cannot exclude that the rate of local recurrence could be even higher after curettage in denosumab-treated patients than in nontreated patients, and until or unless larger studies demonstrate such a reduction, primary intralesional surgery without denosumab seems more prudent when curettage is feasible at presentation. We did not observe any adverse effects with denosumab, but we caution readers that this study was underpowered to detect even relatively common complications and relatively large differences in the risk of local recurrence. Future studies should evaluate denosumab prospectively; given the relative rarity of this tumor, we suspect multicenter studies are needed to achieve this. Level of evidence: Level III, therapeutic study.
Purpose: Tubercular prosthetic joint infection (TB-PJI) is an uncommon complication. Lack of evidence of systemic tuberculosis and clinical suspicion could bring a delay in the time of the diagnosis. The aims of this study are to underline the importance of awareness and suspicion of mycobacterial infection in the differential diagnosis in PJI and to evaluate the appropriateness of different therapeutic options. Methods: Case report and literature review. Results: We report two cases of TB-PJI after total knee arthroplasty in Caucasian patients without prior history of tubercular disease or exposure. In both cases, the diagnosis was obtained years after the onset of symptoms. Despite that, both patients improved during antitubercular treatment (a four-drug regimen consisting of rifampicin, isoniazid, ethambutol, and pyrazinamide for 2 months, followed by rifampicin and isoniazid). Moreover, after an 18-month course of treatment, there was no need for surgical therapy. The result of the literature review allows us to identify 64 cases of TB-PJI. Many differences in both medical and surgical management have been found, among those reviewed cases. Conclusions: Considering our experience and the literature review, we recommend considering a conservative approach (debridement and adequate antituberculous chemotherapy) as a suitable and safe option.
Treatment of bone metastases is often palliative, aiming at pain control and stabilization or prevention of pathological fractures. However, a complete resection with healing purposes can be performed in selected cases. The aim of our work was to evaluate the survival of megaprostheses used for reconstruction after bone metastases. Between January 2001 and March 2015, we implanted 169 Megasystem-C® (Waldemar LINK® GmbH & Co. KG, Hamburg, Germany) after bone metastasis resection. Patients, 95 females and 74 males, were operated at an average age of 61 (12-87) years for proximal femoral resection in 135 (79.9%) cases, distal femur in 24 (14.2%), proximal tibia in 6 (3.6%), total femur in 3 (1.8%) and intercalary femur in 1 (0.6%). Mostly, breast cancer metastases (30.8%), kidney (17.8%) and lung (14.2%) were treated. At an average follow-up of 21 (1-150) months, we found a 99.4% overall limb salvage and a 96.1% overall survival rate at 1 year, 92.8% at 2 years, and 86.8% at 5 and 10 years. We found 9 (5.3%) mobilization cases of the proximal femoral implant, 3 needed surgical reduction; 2 (1.2%) cases of aseptic loosening of the prosthetic stem; 2 (1.2%) periprotetic infection cases, one requiring a 2-stage revision. Few literature studies have evaluated the survival of megaprosthetic implant in the treatment of bone metastases. Our data show how in this specific context the rate of complications is significantly lower than expected in general orthopedic orthopedic surgery. The use of modular prostheses is a valid reconstructive strategy after bone metastasis resection in selected patients. The rate of short-term complications is exceptionally low; further studies will have to confirm this in the longer term.
The use of modular endoprostheses is a viable option to manage both tumor resection and severe bone loss due to nonneoplastic conditions such as fracture sequelae, failed osteoarticular grafts, arthroplasty revisions, and periprosthetic fractures. We sought to investigate both midterm complications and failures occurred in 87 patients who underwent a megaprosthetic reconstruction in a nonneoplastic setting. After a mean follow-up of 58 (1–167) months, overall failure-free survival was 91.5% at 1 year, 80% at 2 years, 71.6% at 5 years, and 69.1% at 5 and 10 years. There was no significant difference in the survival rate according to the diagnosis at the index procedure ( p=0.921 ), nor to the reconstruction site ( p=0.402 ). The use of megaprostheses in a postneoplastic setting did not affect survival rate in comparison with endoprosthetic reconstruction of pure nonneoplastic conditions ( p=0.851 ). Perimegaprosthetic infection was the leading complication, occurring in 10 (11.5%) patients and implying a megaprosthetic revision in all but one case. Physicians should consider these results when discussing with patients desired outcomes of endoprosthetic reconstructions of a nonneoplastic disease.
Background The RANK ligand inhibitor denosumab is being investigated for treatment of giant cell tumor of bone, but the available data in the literature remains sparse and controversial. This study analyzes the results of combining denosumab with surgical treatment and highlights possible changes for the oncologic surgeon in daily practice. MethodsA total of 91 patients were treated surgically for giant cell tumor of bone between 2010 and 2014 in an institution, whereas 25 patients of the total additionally received denosumab and were part of this study. The average age of the patients was 35 years. Eleven patients received denosumab pre- and postoperatively, whereas with 14 patients, the denosumab treatment was applied either before (7 patients) or after (7 patients) the surgery. The average preoperative therapy duration was 3.9 months and the postoperative therapy 6 months by default. ResultsSixteen patients presented a large tumor extension necessitating a resection of the involved bone or joint. In 10 of these patients, the indication for a resection procedure was abandoned due to the preoperative denosumab treatment and a curettage was performed. In the remaining six cases, the surgical indication was not changed despite the denosumab treatment, and two of them needed a joint replacement after the tumor resection. Also with patients treated with curettage, denosumab seems to facilitate the procedure as a new peripheral bone rim around the tumor was built, though a histologic analysis reveals viable tumor cells persisting in the denosumab-induced bone formation.After an average follow-up of 23 months, one histologically proven local recurrence occurred, necessitating a second curettage. A second patient showed a lesion in the postoperative imaging highly suspicious for local relapse which remained stable under further denosumab treatment. No adverse effect of the denosumab medication was observed in this study. Conclusions Denosumab can be a help to the oncologic surgeon by reconstituting a peripheral rim and switching the stage from aggressive to active or latent disease. But as tumor cells remain in the new-formed bone, the surgical technique of curettage has to be changed from gentle to more aggressive to avoid higher local recurrence rates.
Introduction: Infection in megaprostheses remains an unsolved problem, with a rate of occurrence ranging from 5% to 12%. Silver coating of medical devices has recently been proposed to reduce infection rate because of the antibacterial effect of silver. This innovation could be particularly interesting for megaprostheses, but few data have been reported in the literature. Materials and methods: From June 2010 to August 2014 a modified MegaC System megaprosthesis with an innovative peripheral silver-added layer of titanium alloy ('Porag') was implanted in 33 patients after previous infection (21 patients) or at high risk for infection because of local or general conditions (12 patients). Previous infection followed megaprosthesis or standard arthroplasty procedures in 14 patients and trauma surgery in seven patients. A proximal femur replacement was performed in 13 patients, distal femur replacement in 13, total femur in one, and knee arthrodesis in six. Clinical results and levels of silver in blood, urine and wound drains were examined. Results: Minimum follow-up of the patients was one year (average 25.9 months). There was no infection during the first two years after surgery in the 12 patients who received a silver-coated megaprosthesis and had no previous history of infection. An infection developed in one patient at 25 months after surgery following two further surgical procedures. Infection recurred at seven months and 24 months in two out of the 21 patients (9.5%) who had received the implant because of previous septic complications. There was no clinical evidence of argyria, and no local or systemic side effects related to silver were detected. Mean levels of silver ranging from 0.41 to 5.33μg/L in blood and from 0.28 to 0.86μg/L in urine were detected at 24h to 36 months after surgery. Conclusions: Silver-coated megaprostheses showed promising results in this series in terms of prevention of infection in a high-risk group of patients, many of whom had a history of infection. No side-effects were detected. The circulating silver levels confirm both the persistence of silver-coating activity after three years and the safety of silver-coated implants. Longer follow-up and larger series are needed.
Background: Reconstruction of large bone defects around the elbow joint is surgically demanding due to sparse soft tissue coverage, complex biomechanics and the close proximity to neurovascular structures. Modular megaprostheses are established reconstruction tools for the elbow, but only small case series have been reported in the literature. Methods: Thirty-six patients who underwent reconstruction of the elbow joint with a modular megaprosthesis were reviewed retrospectively. In 31 patients (86.1%), elbow replacement was performed after resection of a bone tumour, whereas five non-oncological patients (13.9%) underwent surgery because of a previous failed elbow reconstruction. Functional outcome, rate of complications and oncological results were considered as primary endpoints. Results: The mean follow-up was 25 months. The average achieved Mayo Elbow Performance Score (MEPS) was 77.08 (range 40-95) and the average Musculoskeletal Tumor Society (MSTS) score was 22.9 (range 8-30). Six complications (16.7%) were observed: two radial palsies, one temporary radial nerve dysfunction, one ulnar palsy, one disassembling of the articular prosthesis component and one deep infection necessitating the only implant removal. The overall 5-year survival rate of the patients was poor (25.1%) because of rapid systemic progression of the oncological disease in patients with metastatic lesion. However, the 5-year survival rate of the implant was very satisfactory (93%). Conclusions: Modular megaprosthesis is a reliable and effective reconstruction tool in large bone defects around the elbow joint. The complication rates are lower than seen in osteoarticular allografts and allograft-prosthesis composites while the functional outcome is equal. In palliative situations with metastatic disease involving the elbow, modular megaprosthesis enables rapid recovery and pain relief and preserves elbow function.
Hereditary multiple exostoses (HME) is an inherited genetic condition characterized by the presence of multiple exostoses (osteochondromas). MHE is a relatively rare autosomal dominant disorder, mainly caused by loss of function mutations in two genes: exostosin-1 (EXT1) and exostosin-2 (EXT2). These genes are linked to heparan sulfate (HS) synthesis, but the specific molecular mechanism leading to the disruption of the cartilage structure and the consequent exostoses formation is still not resolved. The aim of this paper is to encounter the main aspects of HME reviewing the literature, in order to improve clinical features and evolution, and the metabolic-pathogenetic mechanisms underlying. Although MHE may be asymptomatic, a wide spectrum of clinical manifestations is found in paediatric patients with this disorder. Pain is experienced by the majority of patients, even restricted motion of the joint is often encountered. Sometimes exostoses can interfere with normal development of the growth plate, giving rise to limb deformities, low stature and scoliosis. Other many neurovascular and associated disorders can lead to surgery. The most feared complication is the malignant transformation of an existing osteochondroma into a secondary peripheral chondrosarcoma, during adulthood. The therapeutic approach to HME is substantially surgical, whereas the medical one is still at an experimental level. In conclusion, HME is a complex disease where the paediatrician, the geneticist and the orthopaedic surgeon play an interchangeable role in diagnosis, research and therapy. We are waiting for new studies able to explain better the role of HS in signal transduction, because it plays a role in other bone and cartilage diseases (in particular malignant degeneration) as well as in skeletal embryology. © Copyright 2016 CIC Edizioni Internazionali Unauthorized reproduction of this article is prohibited.
Background and objectives: The clinical course of soft tissue myxofibrosarcoma is characterized by a high incidence of recurrences and there is no agreement on how to identify patients at major risk. An epithelioid histological variant has been described, with a possible worse prognosis. We reviewed our series to identify prognostic factors and assess clinical significance of the epithelioid variant. Methods: We examined the clinico-pathological features of a series of 75 patients affected by soft tissue myxofibrosarcoma at a mean follow-up of 63 months (range 17-132). Results: Disease specific survival and local recurrence free survival were, respectively, 84.8% and 76.8% at 5 years. Seven patients (8.6%) presented with the epithelioid variant with a survival of 62.5%. High grade and epithelioid morphology were negative prognostic factors for patient survival, high grade, and inadequate surgical margins for local recurrence. Radiotherapy had a local protective effect in high grade tumors. Conclusions: Our experience confirms the difficulties in obtaining wide margins in myxofibrosarcoma and the high rate of recurrence. Local recurrences did not significantly affect survival and a limb-sparing approach can be chosen also in recurrences. Patients affected by the epithelioid variant showed a worse prognosis. Chemotherapy should be considered as adjuvant treatment in this subtype. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.
- Feb 2016
Background: Limb-sparing surgery in combination with radiation therapy is a well-established treatment for high-grade soft tissue sarcomas of the extremities. But selection of cases and optimal sequence of irradiation and surgery still remain controversial. Methods: 769 patients with a high-grade soft tissue sarcoma of the extremities, who underwent a limb-sparing surgery, were retrospectively reviewed. Group 1 (N = 89) was treated with neo-adjuvant radiation therapy, group 2 (N = 315) with adjuvant irradiation and group 3 (N = 365) with surgery alone. Results: After a mean follow up of 45 months 95 local recurrences occurred resulting in a local recurrence-free survival of 83.2% after 5 years and 75.9% after 10 years. Contaminated surgical margins (Odds ratio: 2.42) and previous inadequate surgeries (Odds ratio: 1.89) were identified as risk factors for failed local control. Neo-adjuvant radiation therapy provides the best local recurrence-free rate for 5 years (90.0%), whereas after 10 years (78.3%) adjuvant irradiation showed better local control. The metastatic-free rate was independent from achieved surgical margins (p = 0.179). Group 1 showed the highest rate of revision surgery (9.0%), followed by group 3 (5.5%) and group 2 (4.4%) (p = 0.085). However, the rate of irradiation-correlated side effects was higher in group 2 (15.2%) than in group 1 (11.2%) (p = 0.221). Conclusion: Surgery has to be effective for successful local control and remains the mainstay of the treatment in combination with neo-adjuvant as well as adjuvant irradiation. In really wide or even radical resections the benefit of radiation therapy can be discussed as the irradiation induced side effects are not negligible.
Osteoarticular allografts represent a reconstructive option after bone tumor resection around the knee in growing children. The major advantage is the chance to preserve the growth plate of the remaining bone, but the disadvantage is the high failure rate eventually requiring definitive prosthetic replacement at skeletal maturity. We retrospectively reviewed 22 patients who underwent osteoarticular allograft reconstructions of the distal femur (16) or proximal tibia (6). There were 12 females and 10 males with an average age at surgery of 11 years (7-15). The diagnosis was osteosarcoma in 19 cases and Ewing sarcoma in 3. All patients underwent pre- and post-operative chemotherapy. At an average follow-up of 103 months (12-167), 18 patients (82%) were alive and 4 had died (18%). We observed 10 allograft failures requiring prosthetic replacement, 6 in distal femur and 4 in proximal tibia reconstructions. At last follow-up 8 allografts (36%) were still in place. Overall allograft survival was 79.6% at five and 45.8% at ten years. In distal femur, allograft survival was 86.2% at five and 59.1% at ten years. In proximal tibia, allograft survival was 62.5% at 5 years and 31.2% at 67 months. Average limb shortening was 3 cm (0- 5) in 8 patients with the allograft still in situ and 2 cm (0-4) in 10 patients after prosthetic replacement. Average MSTS functional score of the whole series was 25 (83.7%). The MSTS score of patients after revision with prosthetic replacement was 24 (80%) while patients who still had the allograft retained had an average MSTS scores of 26.8 (89.3%). In conclusion, osteoarticular allograft reconstruction of the knee after bone tumor resection in pediatric age can be considered a temporary solution with the aim to limit limb length discrepancy before definitive prosthetic replacement after skeletal maturity.
Denosumab, a fully human monoclonal antibody directed against RANKL, has recently been introduced in the treatment strategy of giant cell tumour of bone (GCTB). Aim of this study was to investigate the phenotypical modifications induced by denosumab treatment in a series of 15 GCTB. The tumours were characterised for histone 3.3 mutations, and studied immunohistochemically for the modifications of RANKL, RANK, SATB2 and RUNX2 expression, as well as of tumour proliferative activity and angiogenesis. Nine of 11 tumours investigated presented a histone 3.3 mutation in H3F3A, and 2 of these for which the analysis was carried out in pretreatment and post-treatment specimens showed the same mutation in both. Denosumab induced the disappearance of osteoclast-like giant cells, leaving residual spindle neoplastic cells arranged in a storiform pattern, with deposition of trabecular collagen matrix and osteoid, which tended to maturation in the peripheral portions of the lesion. RANK and RANKL expression was variable, with no significant variation after treatment. Moreover, we did not observe any significant modification of the expression of the osteoblastic markers SATB2 and RUNX2. Denosumab treatment determined a significant reduction of the proliferative index and of tumour angiogenesis (p=0.001, Wilcoxon rank-sum test). These results indicate that denosumab induces a partial maturation towards the osteoblastic phenotype of the neoplastic cells of GCTB, with production of fibrous and osteoid matrix, but with minor immunophenotypical changes. Finally, we first report an antiangiogenic activity of denosumab in GCTB, possibly mediated by a RANKL-dependent pathway. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Human disorders of phosphate (Pi) handling and skeletal mineralization represent a group of rare bone diseases. One of these disease is tumoral calcinosis (TC). In this study, we present the case of a patient with TC with a new GALNT3 gene mutation. We also performed functional studies using an in vitro cellular model. Genomic DNA was extracted from peripheral blood collected from a teenage Caucasian girl affected by TC, and from her parents. A higher capability to form mineralization nodules in vitro was found in human preosteoblastic cells of mutant when compared to wild-type controls. We found a novel homozygous inactivating splice site mutation in intron I (c.516-2a>g). A higher capability to form mineralization nodules in vitro was found in the mutant cells in human preosteoblastic cells when compared to wild-type controls. Understanding the functional significance and molecular physiology of this novel mutation will help to define the role of FGF23 in the control of Pi homeostasis in normal and in pathological conditions.
- Jan 2015
Needle biopsy is the main standard method used for diagnosis of musculoskeletal tumors of the limbs and superficial trunk. Pain control during this procedure is through the use of Local Anaestetic (L.A.). In order to achieve a complete pain control in our cases, recently we started using diclofenac HPβCD 50 mg via s.c. preoperativly. We present the clinical results of a non-randomized study of two eterogeneous groups of patients: "Experimental" Group (1): diclofenac HPβCD 50 mg via s.c. one hour before surgical procedure, local anesthesia and ev. diclofenac HPβCD 50 mg via s.c. 12 hours postoperative; "Conventional" Group (2): local anesthesia and ev. postoperative tramadol 100 mg via oral for pain control. In October 2014, at the Department of Orthopedic Oncology and Reconstructive Surgery of Florence, 37 musculoskeletal biopsies for a bone or a soft tissue lesion were performed. Exclusion criteria for this study were: known allergies to lidocaine, diclofenac, tramadol; known gastric or duodenal ulcers; known gastrointestinal bleed or perforation; refusal of the patients to collaborate. For one or more of these reasons, 6 patients were excluded from this study. In the Group 1, 10 patients (59%) referred no pain during the surgical procedure (8/14 biopsies on soft tissue and 2/3 on bone). In 5 cases (29%) no exacerbation of previous chronic pain, and in 2 cases (12%) a progression of local pain after biopsy (average 1 points higher in the VAS). In Group 2, only 6 patients (42%) did not have any pain during the procedure, 4 (29%) no exacerbation of previous chronic pain and 4 (29%) a progression of local pain (average 2 points higher in the VAS). Despite similar results in both Groups, Group 1 seemed to have a mild better control of perioperative pain. The use of diclofenac HPβCD 50 mg preoperative seems to be a rational approach for minimizing perioperative pain and the preliminary data of our study seem encouraging. Obviously many bias are present in this study (small numbers of cases, heterogeneity of diseases, association with local anesthetic, non-randomized study, comparison between preoperative versus postoperative treatment) and this cannot absolutely be considerate as definitive conclusions.
- Jun 2014
Prosthetic replacement is the most commonly used option for reconstruction of osteoarticular bone loss resulting from bone neoplasm resection or prosthetic failure. Starting in late 2001, we began exclusively using a single system for large-segment osteoarticular reconstruction after tumor resection; to our knowledge, there are no published series from one center evaluating the use of this implant.
- Nov 2013
The aim of this study was to evaluate disease-free survival (DFS), overall survival and toxicity of patients who underwent preoperative therapy for soft tissue sarcoma. The data of 38 consecutive patients affected by soft tissue sarcoma were retrospectively analysed. Six (15.8 %) patients were treated only with neoadjuvant radiotherapy, and 32 (84.2 %) with neoadjuvant chemo-radiation therapy. Surgery was performed within 4-6 weeks after the completion of neoadjuvant treatment. Median follow-up was 4.9 years (range 1-13.7 years). All patients received preoperative external beam radiotherapy (RT). Most patients (84.2 %) underwent neoadjuvant chemotherapy treatment associated with radiotherapy. After neoadjuvant treatment, the majority of patients underwent wide excision (32 out of 38) and five patients had marginal surgery; only one patient underwent amputation. Local recurrence was observed in only two patients (5.2 %). Fourteen (36.8 %) patients experienced metastatic relapse. At the time of our analysis 13 patients (34.2 %) had died due to metastatic spread of the disease. In our series, DFS in relation to distant metastases (DM) showed a significant result for lower limb involvement (p = 0.038) and marginal excision (p = 0.024), both predictors of a worse DFS, histology was statistically significant although it was not possible to evaluate the risk for specific histology due to the small number of events in the different subtypes. The results obtained from our study are encouraging with regard to the feasibility and efficacy of preoperative RT in the treatment of soft tissue sarcoma in view of the results obtained in terms of local control, limb sparing and safety.
Background Diagnosis and treatment of low-grade chondrosarcoma remain controversial. We performed a review of a single-center series with the aims of assessing the oncologic outcome of these patients, verifying if intralesional curettage can be adequate treatment, and defining clinical criteria to support the surgeon and the oncologist in decision-making for surgery and subsequent follow-up. Materials and methods A retrospective review of 85 patients was performed (61 females and 24 males, age range 20–76 years). The site of the lesion was the femur in 35 cases, humerus in 33, tibia in 15, and fibula in 2. Sixty-four patients were treated by intralesional curettage. Twenty-one patients with aggressive radiological patterns were treated with wide resection. Results Mean follow-up was 67 months (range 24–206 months). Two patients developed local recurrence, both after intralesional curettage. The difference in incidence of recurrence was not statistically significant between the two groups. No distant metastases were observed. Postsurgical complications were significantly higher in the resection group. Conclusions Low-grade chondrosarcoma of the appendicular skeleton without aggressive radiological patterns can be treated with intralesional surgery with good oncological outcome and very low rate of postsurgical complications. Wide resection, following surgical principles of malignant bone tumors, should be considered only when aggressive biologic behavior is evident on imaging.
Purpose: The purpose of this report was to retrospectively review a series treated with pelvic tumour resection and massive allograft reconstruction, and determine survival of patients and implants, functional results and morbidity of surgical technique. Methods: From 1999, 33 patients underwent pelvic tumour resection and massive allograft reconstruction. The mean age was 40 years (range, 14-72) and 29 patients had a primary malignant tumour. The resection involved the acetabular area in all but three patients. Results: At a median follow-up of 33 months (range, two-143) four patients had local recurrence. The morbidity was high: five deep infections (15 %), requiring two allograft removal, six hip dislocations (18 %), eight sciatic nerve palsy (24 %), persistent in six cases, and two loosening of the acetabular component. Implant survival was 87.3 % at last follow up. The cumulative overall patient's survival was 41.5 % at five and ten years. The average MSTS functional score was 70 % (range, 54-100 %) when the acetabulum was preserved while it was 61 % (30-100 %) in patients with acetabular resection. Conclusion: In conclusion, pelvic allografts represent a valid option for reconstruction after resection of pelvic tumours but due to the associated morbidity, patients should be carefully selected.
We describe the clinicopathological, immunohistochemical, and molecular features of 3 primary juxtacortical myoepithelioma/mixed tumor of bone. The patients were 2 males (13 and 23 years of age) and a 15-year-old female. The juxtacortical lesions were all located in the femur, and were surgically removed, 2 with wide margins and one with marginal margins. This latter tumor recurred locally 18 months later. The 3 patients were free of disease at 6 to 17 months follow-up. Histologically, all lesions showed a prominent multinodular architecture, and were formed by epithelioid and stellate elements, organized in solid sheets, or embedded in myxoid or chondroid matrix. Areas of osteoid formation were also observed. One tumor had the appearance of classical mixed tumor, showing aspects of duct formation and focal squamous differentiation. Immunohistochemically, all cases were positive for cytokeratins, epithelial membrane antigen, and S100 protein. The expression of other myoepithelial markers, including p63, glial fibrillary acid protein and calponin was more limited. No rearrangement of Ewing sarcoma region 1 (EWSR1) and fused in sarcoma (FUS) genes was observed by fluorescent in situ hybridization. To our knowledge, this is the first report of primary myoepitheliomas of bone arising at juxtacortical sites. These lesions must be distinguished from other benign and malignant bone and cartilage-forming surface tumors, including periosteal chondroma and chondrosarcoma, juxtacortical chondromyxoid fibroma, and periosteal and paraosteal osteosarcoma. The clinicoradiologic presentation and their histological and immunohistochemical features are distinctive enough to allow the separation from these entities.
- Nov 2011
Bony non-union and muscle ischaemic contracture are the most frequent late complications of forearm replantation. We report our experience in a case of forearm replantation, where an early restoration of arterial inflow was achieved by the anastomosis of the anterior interosseus artery (A.I.A.) immediately after bone fixation. There was no complication in this case and the functional results were particularly encouraging. The biological and practical advantages of using the A.I.A. for vascular anastomosis are described and discussed.
- Oct 2011
Great advances in oncological orthopaedic surgery have been accomplished in recent years due to development of new prosthetic systems, improvement in the use of allografts, new microsurgical procedures. Often a combination of them (allograft + prosthesis or allograft + vascularized bone transplant) has been the key to obtain major improvement in results. Some of these advances are addressed on the basis of the experience of the Authors in the treatment of bone and soft tissue tumors. Mini-invasive techniques are also finding a place in the oncological practice and their role is going to grow, even if limited to specific issues. Recent development in technology and instruments for cryotherapy makes this technique a valuable aid for the surgeons in many oncological situations.
Intraarticular extension of a tumor requires a conventional extraarticular resection with en bloc removal of the entire knee, including extensor apparatus. Knee arthrodesis usually has been performed as a reconstruction. To avoid the functional loss derived from the resection of the extensor apparatus, a modified technique, saving the continuity of the extensor apparatus, has been proposed, but at the expense of achieving wide margins. In tumors involving the joint cavity, the entire joint complex including the distal femur, proximal tibia, the full extensor apparatus, and the whole inviolated joint capsule must be excised. We propose a novel reconstructive technique to restore knee function after a true extrarticular resection. The approach involves a true en bloc extraarticular resection of the whole knee, including the entire extensor apparatus. We performed the reconstruction with a femoral megaprosthesis combined with a tibial allograft-prosthetic composite with its whole extensor apparatus (quadriceps tendon, patella, patellar tendon, and proximal tibia below the anterior tuberosity). We retrospectively reviewed 14 patients (seven with bone and seven with soft tissue tumors) who underwent this procedure from 1996 to 2009. Clinical and radiographic evaluations were performed using the MSTS-ISOLS functional evaluation system. The minimum followup was 1 year (average, 4.5 years; range, 1-12 years). We achieved wide margins in 13 patients (two contaminated), and marginal in one. There were three local recurrences, all in the patients with marginal or contaminated resections. Active knee extension was obtained in all patients, with an extensor lag of 0° to 15° in primary procedures. MSTS-ISOLS scores ranged from 67% to 90%. No patients had neurovascular complications; two patients had deep infections. Combining a true knee extraarticular resection with an allograft-prosthetic composite including the whole extensor apparatus generally allows wide resection margins while providing a mobile knee with good extension in patients traditionally needing a knee arthrodesis. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
- Feb 2011
The aim of this study was to investigate the expression of cell cycle regulators p53, p16, cyclin-D1, and retinoblastoma (Rb) gene protein in leiomyosarcoma of the peripheral soft in order to identify expression profiles potentially useful for clinical prognostic purposes. A tissue microarray representing 70 localized leiomyosarcomas of the limbs and limb girdles was created with 3 representative cores from each tumor. Immunohistochemical staining was performed for p53, p16, cyclin-D1, and Rb using standard techniques. Staining was scored as either absent-low (<20% of neoplastic cells) or moderate-diffuse (≥20%). Outcome analysis was performed for local recurrence-free survival (LFS), metastatic disease-free survival (MDFS), and disease-specific survival (DSS). Kaplan-Meier analysis of survival revealed that no single alteration of the factors examined was associated with outcome, but tumors showing concomitant alteration of p16 and p53 were characterized by reduced MDFS and DSS (P = 0.01 and P < 0.001, respectively). In addition, patients who received adjuvant therapy consisting of radiotherapy alone or radiotherapy and chemotherapy had a better DSS than those receiving surgery alone or surgery and chemotherapy (P = 0.05). In multivariate analysis, altered p16/p53 remained the only parameter predictive of MDFS and DSS (P = 0.048, hazard ratio [HR] = 2.488, 95% confidence interval [95% CI] 1.006-5.116; P = 0.043, HR = 2.498, 95% CI 1.029-5.909, respectively). Accumulation of cell cycle alterations represents a prognostic indicator in localized soft tissue leiomyosarcoma, and in particular altered p16/p53 expression is associated with an unfavorable prognosis. This may help the clinical management of patients with leiomyosarcomas.
- Jan 2011
Reconstructions of large lesions or defects often require a bone graft or a bone substitute to promote healing. In common practice the reconstruction of a bone defect is dependent on the site and size of the lesion: in long bones intercalary defects may be managed with Ilizarov technique of bone transport and distraction osteogenesis or the use of a free or pedicled vascularized bone graft, or with Masquelet technique. For cavitary defects the available surgical options include autograft, allograft or xenograft or the use of synthetic scaffolds to promote bone regeneration. In order to promote a faster bone healing tissue engineering proposed the application of enriched graft to fill bone defects. The employment of enriched bone graft has been our choice in the last years to fill contained defects following curettage of a pseudotumoral lesion of bone. We report our clinical experience in terms of safety and success of these procedures at a long-term follow up.
- Dec 2010
Several techniques have been described to reconstruct a mobile wrist joint after resection of the distal radius for tumour. We reviewed our experience of using an osteo-articular allograft to do this in 17 patients with a mean follow-up of 58.9 months (28 to 119). The mean range of movement at the wrist was 56° flexion, 58° extension, 84° supination and 80° pronation. The mean ISOLS-MSTS score was 86% (63% to 97%) and the mean patient-rated wrist evaluation score was 16.5 (3 to 34). There was no local recurrence or distant metastases. The procedure failed in one patient with a fracture of the graft and an arthrodesis was finally required. Union was achieved at the host-graft interface in all except two cases. No patient reported more than modest non-disabling pain and six reported no pain at all. Radiographs showed early degenerative changes at the radiocarpal joint in every patient. A functional pain-free wrist can be restored with an osteo-articular allograft after resection of the distal radius for bone tumour, thereby avoiding the donor site morbidity associated with an autograft. These results may deteriorate with time.
- Jun 2010
MRI is a unique imaging technique that allows direct visualization of bone marrow with high spatial resolution and is considered the best tool for local staging of bone tumors. Owing to its high natural contrast resolution, it can depict specific tissue components useful for tumor characterization. Moreover, there is great interest in MRI capability to assess post-chemotherapy changes in order to identify unresponsive tumors early in the course of therapy. To increase the accuracy in the assessment of tumor response to treatment, new and more sophisticated approaches using fast and ultrafast MRI are under evaluation. This article presents an overview of the state-of-the-art of MRI in staging bone lesions, discusses the role that this technique plays in tumor characterization and provides a quick look at future technological advancements.
We reviewed 25 patients who had undergone resection of a primary bone sarcoma which extended to within 5 cm of the knee with reconstruction by a combination of a free vascularised fibular graft and a massive allograft bone shell. The distal femur was affected in four patients and the proximal tibia in 21. Their mean age at the time of operation was 19.7 years (5 to 52) and the mean follow-up period 140 months (28 to 213). Three vascularised transfers failed. The mean time to union of the fibula was 5.6 months (3 to 10) and of the allograft 19.6 months (10 to 34). Full weight-bearing was allowed at a mean of 21.4 months (14 to 36). The mean functional score at final follow-up was 27.4 (18 to 30) using a modified 30-point Musculoskeletal Tumour Society rating system. The overall limb-salvage rate was 88%. The results of our study suggest that the combined use of a vascularised fibular graft and allograft is of value as a limb-salvage procedure for intercalary reconstruction after resection of bone tumours around the knee, especially in skeletally immature patients.
The concept of limb salvage led to increased demand for more complex and sophisticated reconstructive options to achieve better functional and cosmetic outcome. Reconstruction of the total or partial loss of quadriceps muscle after soft tissue sarcomas excision with free functioning latissimus dorsi muscle transfer had become more popular in the last years. Between November 1993 and October 2004, 11 patients with average age 45.5 years underwent excision of quadriceps muscle followed by simultaneous reconstruction with free functioning latissimus dorsi muscle. There were six men and five women. The tumors were high grade in 90.9% of patients and were >10 cm in 81.8% of patients. The tumor extension required the resection of the entire quadriceps in four cases, of three heads in six cases, of only two heads in one case. The average follow up was 69 months. The average time of recovery of the contractile activity of the muscle was 8.3 months after operation. The musculoskeletal tumor society rating score (MTSRS) scored excellent or good in 73% of patients. Three patients (27.3%) died of metastatic disease. Local recurrence occurred in one patient (9.1%). Limb salvage was achieved in all the patients (100%). This method of reconstruction is a reliable technique not only to fill the defect resulting from oncological resection but also to provide better function. Microsurgical reconstruction of soft tissue sarcoma helps to expand the indications of limb salvage by allowing better local control and achieving adequate function and coverage.
Reconstruction after excision of bone tumor of the proximal tibia is a challenging issue for the reconstructive surgeon. The combined use of a free fibular flap and allograft can provide a reliable reconstructive option in this location. This article describes the authors' long-term follow-up using this technique. Twenty-seven patients that had resection of proximal tibia bone tumors underwent reconstruction using this technique. Only 21 patients that had primary reconstruction were included in this study. All patients had their surgeries performed at least 24 months before the end of the study. The average age at time of operation was 18.1 years. The average follow-up time was 139.3 months. Limb salvage was 82.7%. The average length of the resected tibial segment was 15.3 cm and that of the residual proximal tibia remaining after resection was 2.7 cm. The average time of union of fibula was 5.4 months and for union of allograft was 19.1 months. Primary union of the allograft was achieved in 90.5% of cases. Full weight-bearing was achieved at an average of 21.6 months. Ten patients (47.6%) had 14 local complications. The (MTSRS) average score at final follow-up was 27.3. Local recurrences occurred in two patients (9.5%). Distant metastasis to the lung occurred in three patients (14.3%). One patient died of disease. This technique provides good long-term results in reconstruction of proximal tibia. The viability of the fibula is a cornerstone in both success of reconstruction as well as successful management of complications.
- Nov 2008
Treatment of distal tibial tumors is challenging due to the scarce soft tissue coverage of this area. Ankle arthrodesis has proven to be an effective treatment in primary and post-traumatic joint arthritis, but few papers have addressed the feasibility and techniques of ankle arthrodesis in tumor surgery after long bone resections. Resection of the distal tibia and reconstruction by ankle fusion using non-vascularized structural bone grafts was performed in 8 patients affected by malignant (5 patients) or aggressive benign (3 patients) tumors. Resection length of the tibia ranged from 5 to 21 cm. Bone defects were reconstructed with cortical structural autografts (from contralateral tibia) or allografts or both, plus autologous bone chips. Fixation was accomplished by antegrade nailing (6 cases) or plating (2~cases). All the arthrodesis successfully healed. At followup ranging from 23 to 113 months (average 53.5), all patients were alive. One local recurrence was observed with concomitant deep infection (a below-knee amputation was performed). Mean functional MSTS score of the seven available patients was 80.4% (range, 53 to 93). Resection of the distal tibia and arthrodesis of the ankle with non-vascularized structural bone grafts, combined with autologous bone chips, can be an effective procedure in bone tumor surgery with durable and satisfactory functional results. In shorter resections, autologous cortical structural grafts can be used; in longer resections, allograft structural bone grafts are needed.
Capillary hemangioblastoma (CHB) is a benign, highly vascularized tumor that generally occurs in the central nervous system either in the setting of von Hippel-Lindau (VHL) disease or, more often, as a solitary sporadic lesion that is increasingly recognized in extraneural sites. We present the case of a 72-year-old woman with low back pain and a well-demarcated lytic lesion of the sacrum, which at histological and ultrastructural examination was indistinguishable from central nervous system CHB. The patient had no signs of VHL disease and died of another cause with no evidence of disease 57 months after curettage of the lesion. To our knowledge, this is the second case of CHB reported to occur in bone.
- Aug 2008
While combined treatment of high-grade soft tissue sarcoma with resection and radiotherapy has become an accepted standard, outlines of treatment algorithms remain a matter of debate. Our institutional practice foresees wide surgical resection with adjuvant brachytherapy and external beam radiation. It was the purpose of this study to determine long-term outcome, prognostic factors for local and systemic recurrence and morbidity in patients with high-grade soft tissue sarcomas of the extremities, who were subjected to this regimen. One hundred and twelve patients met the inclusion criteria (56 male, 56 female; median age, 50 years). Median follow-up was 75 months (min. 11 months). Overall survival rate was 77.5% and 71.1% at 5 and 7 years, respectively. Disease-free survival rate was 63.3% and 58.4% at 5 and 10 years, respectively. Local control was achieved in 91.5% and 87.0% at 5 and 10 years, respectively. Wide surgical margins were associated with a significantly better local control rate compared to marginal or intralesional margins. Tumor size did correlate with systemic but not local recurrence. Tumor site and histotype did not appear to have an impact on outcome. Chemotherapy did not show to have an impact on local or systemic control. Fourteen patients (12.5%) had local complications attributed to radiotherapy. Eleven patients developed wound-healing problems, which needed further surgery. Using our treatment algorithm for high-grade soft tissue sarcoma of the extremities, good local and systemic control can be achieved with a low complication rate.
Many percutaneous image-guided ablative techniques have been used in the treatment of cancer-related bone metastases. These techniques are rapidly becoming a focus in the palliative and curative treatment of patients with both benign and malignant forms of bone cancer. In this article we will review the principles of radiofrequency ablation and our experience with this technique, including its use in combination with surgery; we will also discuss other mini-invasive techniques such as cryoablation and osteoplasty in the treatment of bone metastases.
Treatment of pathological fractures or impending fractures should be based on a multidisciplinary approach. Surgical procedures have to be suited not only to local mechanical conditions but also to patient’s life expectancy and behaviour of the particular tumor in relation to adiuvant not surgical treatments. Indications of osteosynthesis versus resection-reconstruction, choice of fixation alone or after curettage, different fixation options in metastatic disease and technical tips are analyzed.
Metastatic bone disease requires a multidisciplinary approach and the goal of the purposed protocol of treatment is to integrate the role of different specialistic figures in the treatment program. The aims of treatment in appendicular skeletal metastases are to prevent and to cure pathologic fractures of long bones, to achieve pain control and to provide an adequate quality of life. The guide lines of protocol resulted helpful in defining when surgery was indicated and what kind of surgery had to be preferred for every single metastatic patient.
The most important factor to consider in decision making for treatment of patients with bone metastases from carcinoma is the expected survival. For this reason it seems important to identify reliable prognostic factors in patients with bone metastases from carcinoma in order to predict long survivors requiring a more aggressive and durable surgical treatment. The most significative prognostic factors resulted to be the type of primitive tumor, the presence of visceral metastases, the number of bone metastases and the performance status of the patient.
- Jun 2007
Limb salvage surgery of popliteal soft tissue sarcomas may be hampered due to the incomplete anatomical containment of this region and the vicinity of neurovascular structures. The scope of this study was to determine outcome and to define risk factors. 27 patients (53.3+/-15.8 y; 16/27 male) with popliteal soft tissue sarcomas were assessed. Mean follow-up was 40.9+/-33.8 months (48.5+/-36.7 months in surviving patients). 9/27 patients were included after prior treatment elsewhere (5 after intralesional resections and 4 local recurrences). The lesions were staged IB in 8/27 patients, IIB in 17/27 and III in 2/27. Immediate amputations were performed in 7/27 patients. 15/27 patients were subjected to radiation therapy (preoperative in 6/15 cases), 8/27 patients received chemotherapy (5/8 preoperatively). Overall survival and disease-free survival at 5 y was 63.0% and 59.5%. Local recurrence occurred in 2 patients. 8/27 patients developed metastatic disease after 28.9+/-9.8 months. Survival (p=0.397) and disease-free survival (p=0.113) did not differ in patients after amputations vs limb salvage. Application of radiation therapy was associated with a better survival (p=0.003). Complications related to the surgical intervention were recorded in 2/27 patients, complications related to radiation therapy occurred in 6/15 patients. Despite being extra-compartmental, popliteal sarcomas can be treated with a high rate of limb salvage while equal safety compared to amputations is maintained. Irradiation improved survival in our patient population. In cases with involvement of neurovascular structures, preoperative down-staging with radio or chemo-therapy may prevent amputation.
- Feb 2007
In 1988, the excellent results obtained with the use of vascularized fibular autograft as a salvage procedure in massive allograft failures caused by non-union or massive resorption prompted a trial of an original reconstructive technique for intercalary defects based on the primary combination of the two types of graft. The authors believe the excellent final results and the ability to avoid further salvage surgical procedures justify the primary application of this more complicated technique despite longer surgical times.
- Feb 2006
We assessed the occurrence of long-bone fracture and other side effects in a group of 214 consecutive patients who underwent radical excision for soft-tissue sarcoma of the limb followed by postoperative irradiation. Two hundred fourteen patients underwent postoperative irradiation after radical excision of soft-tissue sarcoma of the limb; 156 (73%) received postoperative brachytherapy (BRT) plus external-beam radiation therapy (EBRT), and 58 (27%) underwent postoperative EBRT only. All patients were followed-up for a median time of 4.5 years (range 3 months to 10 years). Seven patients developed bone fracture, which is considered severe morbidity; time between surgery and occurrence of fracture ranged between 10 and 72 months (average 31). Severe sclerosis with impairment of limb function was diagnosed in 5 and peripheral nerve damage in 3 patients. Wound complications were detected in 8 patients. In our series, no statistically significant correlation between bone fracture and clinical features or "technical" parameters was found, but all of the patients who experienced bone fracture (7 of 7) were postmenopausal women >55 years old.
- Jan 2005
The aims were to describe the clinico-pathological features of 65 patients affected by soft tissue pleomorphic sarcomas of the extremities, to evaluate their clinical outcome and to explore the prognostic impact of clinical and pathologic parameters, on disease-free and overall survival. Soft tissue pleomorphic sarcomas of the extremities were retrieved to be retrospectively re-evaluated in the current analysis. The following parameters were analysed: age, sex, site, size, stage, histotype, grade, surgical margins, therapy. Disease-free and overall survival rates were calculated according to the Kaplan-Meier method. A multivariate analysis was used to determine which variable had an independent effect on clinical outcome. Sixty-five patients with soft tissue pleomorphic sarcomas of the extremities were included in the study. Upon revision, there were 22 leiomyosarcomas, 13 myxofibrosarcomas, 9 liposarcomas, 10 pleomorphic MFH/undifferentiated high grade pleomorphic sarcomas, and 11 cases were other types of plemorphic sarcomas, including rhabdomyosarcoma (n=4), osteosarcoma (n=2), myofibrosarcoma (n=5). In the whole series, by multivariate analysis, stage was the only factor predictor of disease progression (p=0.001; RR 6.9; 95% CI 1.3-15.6). Considering only localized pleomorphic sarcomas the independent predictors of disease relapse were site (p=0.03; RR 3.6; 95% CI 1.0-12.4) and myogenic differentiation (p=0.04; RR 2.9; 95% CI 0.9-10.0), whereas myogenic differentiation resulted the only independent predictor of overall survival (p=0.03; RR 6.5; 95% CI 1.1-37.9). These results indicate that histopathological classification of soft tissue pleomorphic sarcomas is clinically relevant. In our experience, AJCC stage and myogenic differentiation are the factors which independently affect prognosis.
- Jun 2004
Soft tissue leiomyosarcomas (LMS) are rare tumours which are associated with a poor prognosis. The goals of the present study were to describe the clinico-pathological and prognostic features of 42 patients affected by soft tissue LMS of the extremities. The following clinical and pathological parameters were analysed: age, sex, site, size, depth, previous surgical procedures, stage, histological type, nuclear atypia, grade, mitotic activity, necrosis, surgical margins, therapy. Disease-free survival rates were calculated. The overall 2-year and 5-year disease free survival rates were 42.3% and 32.6%, respectively. By univariate analysis, tumour size (< or =10 cm vs. >10 cm; p = 0.01), average mitotic rate (< or =19/10 HPF vs. >19/10 HPF; p = 0.05), type of excision (wide vs. marginal or intralesional; p = 0.001) and adjuvant radiotherapy (none vs. brachytherapy+external beam radiotherapy vs. external beam radiotherapy; p = 0.02) were significantly correlated with disease progression. By multivariate analysis, the only factor that was found to be an independent predictor of disease relapse was type of excision (p = 0.001). Large tumour size and high mitotic rate resulted adverse prognostic factors. Adjuvant radiation therapy, in combination with wide surgical excision, allowed the best chance of cure.
- Jul 1996
Between 1989 and 1994 free gracilis muscle reinnervation was used to treat three patients severely affected with Volkmann's syndrome of the forearm. All three patients were males and they had supracondyloid fracture of the humerus, treated nonsurgically an average of 7.6 years previously. Mean age at the time of surgery was 19.3 years. The flap was transplanted in flexor function of the fingers in two of the patients, in extensor function of the wrist in one. Electromyography and successive clinical monitoring revealed an increase in contractile strength up to one year after surgery. In the first two cases final hold strength exceeded by more than 50% that of the contralateral limb, in the third case excursion of the wrist which could not be quantified, but which was useful for elementary activities was recovered. When myotendinous units for transplantation are not available, free gracilis muscle reinnervation constitutes a valid surgical solution in cases of severe Volkmann's syndrome of the forearm.