Intercalary Resection of the Tibia for Primary Bone Tumors: Are Vascularized Fibula Autografts With or Without Allografts a Durable Reconstruction?

BACKGROUND: Reconstruction with vascularized fibula grafts (VFG) after intercalary resection of sarcoma may offer longevity by providing early graft-host union and fracture healing. The ability of the fibula to hypertrophy under mechanical stress, as well as vascularized bone in the area, may also be advantageous, given that soft tissues may be compromised because of resection, chemotherapy, or radiation therapy. VFG with a massive allograft combines the primary mechanical stability of the graft with the biological potential of the vascularized fibula; however, complications and the durability of this combined reconstruction are not well described. QUESTIONS/PURPOSES: (1) What was the proportion of complications after reconstruction with VFG, with or without allografts? (2) What was the functional result after surgical treatment as assessed by the Musculoskeletal Tumor Society (MSTS) score? (3) What was the survivorship of these grafts free from revision and graft removal? METHODS: Between 1988 and 2021, 219 patients were treated at our institution for a primary malignant or aggressive benign bone tumor of the tibia with en bloc resection. Of those, 54% (119 of 219) had proximal tibial tumors with epiphyseal involvement and were treated with either intra-articular resection and reconstruction with an osteoarticular allograft, allograft-prosthesis composite (APC), or modular prosthesis according to age, diagnosis, and preoperative or postoperative radiotherapy. Nine percent (20) of patients had distal tibial tumors that were treated with intra-articular resection and reconstruction with ankle arthrodesis using allogenic or autologous grafts, and 0.5% (1 patient) underwent total tibial resection for extensive tumoral involvement of the tibia and reconstruction with an APC. Thirty-six percent (79) of patients had a metadiaphyseal bone tumor of the tibia and were treated with intercalary joint-sparing resection. We routinely use reconstruction with VFG after intercalary tibial resection for primary malignant or aggressive benign bone tumors in patients with long life expectancy and high functional demands and in whom at least 1 cm of residual bone stock of the proximal or distal epiphysis can be preserved. By contrast, we routinely use intercalary massive allograft reconstruction in short resections or in patients with metastatic disease who do not have long life expectancy. We avoid VFG in patients with tibial bone metastasis, patients older than 70 years, or primary bone tumors in patients who may undergo postoperative radiotherapy; in these patients, we use alternative reconstructive methods such as intercalary prostheses, plate and cement, or intramedullary nailing with cement augmentation. According to the above-mentioned indications, 6% (5 of 79) of patients underwent massive allograft reconstruction because they were young and had intercalary resections shorter than 7 cm or had metastatic disease at diagnosis without long life expectancy, whereas 94% (74) of patients underwent VFG reconstruction. The median age at operation was 16 years (range 5 to 68 years). The diagnosis was high-grade osteosarcoma in 22 patients, Ewing sarcoma in 19, adamantinoma in 16, low-grade osteosarcoma in five, fibrosarcoma in three, malignant fibrous histiocytoma and Grade 2 chondrosarcoma in two, and malignant myoepitelioma, angiosarcoma of bone, malignant peripheral nerve sheath tumor of bone, squamous cell carcinoma secondary to chronic osteomyelitis, and desmoplastic fibroma in one patient each. Median follow-up was 12.3 years (range 2 to 35 years). The median tibial resection length was 15 cm (range 7 to 27 cm), and the median fibular resection length was 18 cm (range 10 to 29 cm). VFG was used with a massive allograft in 55 patients, alone in 12 patients, and combined with allogenic cortical bone struts in seven patients. We used VFG combined with a massive allograft in patients undergoing juxta-articular, joint-sparing resections that left less than 3 cm of residual epiphyseal bone, for intra-epiphyseal resections, or for long intercalary resections wherein the allograft can provide better mechanical stability. In these clinical situations, the combination of a VFG and massive allograft allows more stable fixation and better tendinous reattachment of the patellar tendon. VFG was used with cortical bone struts in distal tibia intercalary resections where the narrow diameter of the allograft did not allow concentric assembling with the fibula. Finally, VFG alone was often used after mid- or distal tibia intercalary resection in patients with critical soft tissue conditions because of previous surgery, in whom the combination with massive allograft would result in a bulkier reconstruction. We ascertained complications and MSTS scores by chart review, and survivorship free from revision and graft removal was calculated using the Kaplan-Meier estimator. In our study, however, the occurrence of death as a competing event was observed in a relatively low proportion of patients, and only occurred after the primary event of interest had already occurred. Considering the nature of our data, we did not consider death after the primary event of interest as a competing event. RESULTS: In all, 49% (36 of 74) of patients experienced complications and underwent operative treatment. There were 45 complications in 36 patients. There was one instance of footdrop secondary to common peroneal nerve palsy, four wound problems, one acute vein thrombosis of the VFG pedicle and one necrosis of the skin island, two episodes of implant-related pain, 10 nonunions, six fractures, six deep infections, nine local recurrences, one Achilles tendon retraction, one varus deformity of the proximal tibia with postoperative tibial apophysis detachment, one knee osteoarthritis, and one hypometria. The median MSTS score was 30 (range 23 to 30); the MSTS score was assessed only in patients in whom the VFG was retained at the final clinical visit, although if we had considered those who had an amputation, the overall score would be lower. Revision-free survival of the reconstructions was 58% (95% confidence interval 47% to 70%) at 5 years, 52% (95% CI 41% to 65%) at 10 and 15 years, and 49% (95% CI 38% to 63%) at 20 and 30 years. Eight patients underwent VFG removal because of complications, with an overall reconstruction survival of 91% (95% CI 84% to 98%) at 5 years and 89% (95% CI 82% to 97%) at 10 to 30 years. CONCLUSION: VFG, alone or combined with an allograft, could be considered in reconstructing a lower extremity after intercalary resections of the tibia for primary bone tumors, and it avoids the use of a large endoprosthesis. However, this procedure was associated with frequent, often severe complications during the first postoperative years and complication-free survival of 58% at 5 years. Nearly 10% of patients ultimately had an amputation. For patients whose reconstruction succeeded, the technique provides a durable reconstruction with good MSTS scores, and we believe it is useful for active patients with long life expectancy. Fractures, frequently observed in the first 5 years postoperatively, might be reduced using long-spanning plate fixation, and that appeared to be the case in our study. Nonbridging fixation can be an option in intraepiphyseal resection when a spanning plate cannot be used or in pediatric patients to enhance fibula hypertrophy and remodeling. We did not directly compare VFG with or without allografts to other reconstruction options, so the decision to use this approach should be made thoughtfully and only after considering the potential serious risks. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Surgical treatment for pelvic bone metastatic disease from renal cell carcinoma.

INTRODUCTION: Pelvic bone metastases from renal cell carcinoma (RCC) are challenging due to their destructive pattern, poor response to radiotherapy and hypervascularity. The purpose of our study was to review a series of patients undergoing surgical treatment with the aim to investigate: 1) survival; 2) local disease control; and 3) complications. METHODS: A series of 16 patients was reviewed. A curettage procedure was performed on 12 patients. In eight the lesion involved the acetabulum; a cemented hip arthroplasty with cage was performed in seven; a flail hip in one. Four patients received a resection; in two cases with acetabular involvement, reconstruction was performed with a custom-made prosthesis and with an allograft and prosthesis. RESULTS: Disease-specific survival accounted for 70% at 3 years and 41% at 5 years. Only one local tumor progression after curettage occurred. Revision surgery (flail hip) was necessary for deep infection of the custom-made prosthesis. CONCLUSION: A prolonged survival in patients affected by bone metastatic disease from RCC can justify also major surgical procedures. Due to a low local progression rate after intralesional procedures, curettage, cement and a total hip arthroplasty with cage, when feasible, should be considered as an alternative to more demanding surgeries like resections and reconstructions. LEVEL OF EVIDENCE (OXFORD): Level 4.

Are Vascularized Fibula Autografts a Long-lasting Reconstruction After Intercalary Resection of the Humerus for Primary Bone Tumors?

BACKGROUND: A vascularized fibula graft (VFG) is the vascular autograft most frequently used to restore large segmental long bone defects, particularly in the upper limb. Because the use of a vascularized fibula involves an operation in an uninvolved extremity with potential morbidity, it is important to document that this type of reconstruction is successful in restoring function to the humerus. However, the long-term results of VFG after intercalary resection of the humeral diaphysis for bone tumors are still unknown. QUESTIONS/PURPOSES: (1) What was the complication rate of reconstruction? (2) What was the functional result after surgical treatment, as assessed by the Musculoskeletal Tumor Society (MSTS) score, the American Shoulder and Elbow Society (ASES) score, and Constant score? (3) What was the survivorship of these grafts free from revision and graft removal at 5, 10, and 15 years? METHODS: Between 1987 and 2021, 127 patients were treated at our institution with en bloc resection for a primary malignant or an aggressive benign bone tumor of the humerus; we excluded patients treated with extra-articular resection or amputation. Of those, 14% (18 of 127) were treated with intercalary resection of the humeral diaphysis for primary bone tumors and reconstruction with VFG, with or without a bulk allograft, and were analyzed in this retrospective study. Generally, our indications for reconstruction with VFG are intercalary resection of the humerus for primary malignant or aggressive benign bone tumors in patients with long life expectancy and high functional demands, in whom adequate bone stock of the proximal and distal epiphysis can be preserved. In 13 patients, VFG was used alone, whereas in five patients, a massive allograft was used. Our policy was to use VFG combined with a massive allograft in patients undergoing juxta-articular joint-sparing resections in which proximal osteotomy was performed close to the anatomic neck of the humerus to obtain more stable fixation and better tendinous reattachment of the rotator cuff and deltoid. All 18 patients who were treated with a VFG were available for follow-up at a minimum of 2 years (median follow-up 176 months, range 26 to 275 months), and although three have not been seen in the past 5 years and are not known to have died, they had 172, 163, and 236 months of follow-up, and were included. The median age at surgery was 25 years (range 2 to 63 years), the median humeral resection length was 15 cm (range 8 to 21 cm), and the median fibular length was 16 cm (range 12 to 23 cm). Complications and functional scores were ascertained by chart review that was performed by an individual not involved in patient care. Functional results were assessed with the MSTS score (range 0 to 30), the ASES score (range 0 to 100), and the Constant score (range 0% to 100%). Survivorship was estimated using a Kaplan-Meier survivorship estimator, which was suitable because there were few deaths in this series. RESULTS: Seven patients underwent a revision procedure (one radial nerve transient palsy because of screw impingement, four nonunions in three patients with one humeral head avascular necrosis, treatment for screw-related pain in one patient, and two VFG fractures), and one patient underwent VFG removal. Donor site complications were observed in four patients (one ankle valgus deformity and three claw toes-the first toe in two patients and the other toes in the third). At the final clinical control, at a median follow-up of 176 months (range 26 to 275 months), the median MSTS score was 30 of 30 (range 28 to 30), the median ASES score was 98.3 (range 93 to 100), and the median Constant score was 93.5% (range 79% to 100%). Revision-free survival was 71% (95% CI 53% to 96%) at 5 years and 57% (95% CI 37% to 88%) at 10 and 15 years; VFG removal-free survival was 94% (95% CI 83% to 100%) at 5, 10, and 15 years. CONCLUSION: VFG appears to be an effective reconstructive option after humeral intercalary resection for primary bone tumors. These are complex procedures and should be performed by an experienced team of surgeons who recognize that complications may occur frequently in the first years after the procedure. The frequency of mechanical complications observed in the first 5 years postoperatively may be lessened by using long spanning-plate fixation, and if successful, this reconstruction provides a long-term, durable reconstruction with excellent functional results. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Salvage of limb salvage in oncological reconstructions of the lower limb with megaprosthesis: how much to push the boundaries?

INTRODUCTION: Megaprosthesis represent the most commonly used limb salvage method after musculoskeletal tumor resections. Nevertheless, they are burdened by high complication rate, requiring several surgical revisions and eventually limb amputation. The aims of this study were to evaluate the effect of rescuing the limb with subsequent revisions on complication rates (a), incidence of amputations (b), and whether complications reduce functional outcome after the first surgical revision (c). MATERIALS AND METHODS: We retrospectively reviewed 444 lower limb megaprosthesis implanted for primary musculoskeletal tumors or metastatic lesions, from February 2000 to November 2017. 59 patients received at least one revision megaprosthesis surgery. MSTS score was used to assess final functional results. Complication-revision-amputation free survival rates were calculated both at 5 and 10 years of follow-up. RESULTS: Complication free survival, revision free survival and amputation free survival at 10 years were 47% and 53%, 61% and 67%, 90% and 86% among all 444 patients and the group of 59 revised patients, respectively. The incidence of further complications after the first complication was 26% in the group treated with no subsequent revision surgeries and 51% in the group with at least one revision surgery. We found a trend of inverse linear relationship between the number of complications needing subsequent revision surgeries and the final MSTS. CONCLUSION: The number of further revision surgeries after limb salvage with megaprosthesis increases the incidence of complications. Repeated surgical revisions, in particular after infection, increase the amputation rate. The most frequent causes of failure were structural failures and infections. MSTS score was superior for patients undergoing limb salvage than amputees. However, MSTS progressively decreased with multiple revisions becoming inferior to the functional score of an amputated patient.

Growth arrest-specific 5 lncRNA as a valuable biomarker of chemoresistance in osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumour in children and teenagers, and it is characterised by drug resistance and high metastatic potential. Increasing studies have highlighted the critical roles of long noncoding RNAs (lncRNAs) as oncogenes or tumour suppressors as well as new biomarkers and therapeutic targets in osteosarcoma. The growth arrest-specific 5 (GAS5) lncRNA can function as a tumour suppressor in several cancers. The present study aimed to validate GAS5 and other chemoresistance-associated lncRNAs as biomarkers in a cohort of primary osteosarcoma samples, to obtain predictive information on resistance or sensitivity to treatment. The GAS5 and a panel of lncRNAs related to chemoresistance [SNGH1, FOXD2-AS1, deleted in lymphocytic leukemia (DLEU2) and LINC00963] were evaluated in a cohort of osteosarcoma patients enrolled at the Careggi University Hospital. Total RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue sections and the expression levels of the lncRNAs were quantified by qPCR. A bioinformatic analysis on deposited RNA-seq data was performed to validate the qPCR results. Clustering analysis shows that GAS5 could be linked to the expression of isoforms 02 and 04 of the lncRNA DLEU2, whereas the DLEU2 isoform 08 is linked to the lncRNA LINC00963. We found that GAS5 is significantly increased in patients with a good prognosis and is expressed differently between chemosensitive and chemoresistant osteosarcoma patients. However, the results obtained are not concordant with the in-silico analysis performed on the TARGET osteosarcoma dataset. In the future, we would enlarge the case series, including different disease settings.

Alteration of the Nucleotide Excision Repair (NER) Pathway in Soft Tissue Sarcoma.

Clinical responses to anticancer therapies in advanced soft tissue sarcoma (STS) are unluckily restricted to a small subgroup of patients. Much of the inter-individual variability in treatment efficacy is as result of polymorphisms in genes encoding proteins involved in drug pharmacokinetics and pharmacodynamics. The nucleotide excision repair (NER) system is the main defense mechanism for repairing DNA damage caused by carcinogens and chemotherapy drugs. Single nucleotide polymorphisms (SNPs) of NER pathway key genes, altering mRNA expression or protein activity, can be significantly associated with response to chemotherapy, toxicities, tumor relapse or risk of developing cancer. In the present study, in a cohort of STS patients, we performed DNA extraction and genotyping by SNP assay, RNA extraction and quantitative real-time reverse transcription PCR (qPCR), a molecular dynamics simulation in order to characterize the NER pathway in STS. We observed a severe deregulation of the NER pathway and we describe for the first time the effect of SNP rs1047768 in the ERCC5 structure, suggesting a role in modulating single-stranded DNA (ssDNA) binding. Our results evidenced, for the first time, the correlation between a specific genotype profile of ERCC genes and proficiency of the NER pathway in STS.

Extra-abdominal desmoid tumor fibromatosis: a multicenter EMSOS study.

BACKGROUND: Extra-abdominal desmoid tumor fibromatosis (DTF) is a rare, locally aggressive soft tissue tumour. The best treatment modality for this patient cohort is still object of debate. QUESTIONS/PURPOSE: This paper aimed to (1) to compare the outcomes of DTF after different treatment modalities, (2) to assess prognostic factors for recurrence following surgical excision, and (3) to assess prognostic factors for progression during observation. METHODS: This was a retrospective multicenter study under the patronage of the European Musculoskeletal Oncology Society (EMSOS). All seven centres involved were tertiary referral centres for soft tissue tumours. Baseline demographic data was collected for all patients as well as data on the diagnosis, tumour characteristics, clinical features, treatment modalities and whether they had any predisposing factors for DTF. RESULTS: Three hundred eighty-eight patients (240 female, 140 male) with a mean age of 37.6 (±18.8 SD, range: 3-85) were included in the study. Two hundred fifty-seven patients (66%) underwent surgical excision of ADF, 70 patients (18%) were observed without therapy, the residual patients had different conservative treatments. There were no significant differences in terms of tumour recurrence or progression between the different treatment groups. After surgical excision, younger age, recurrent disease and larger tumour size were risk factors for recurrence, while tumours around the shoulder girdle and painful lesions were at risk of progression in the observational group. CONCLUSION: Local recurrence rate after surgery was similar to progression rates under observation. Hence, observation in DTF seems to be justified, considering surgery in case of dimensional progression in 2 consecutive controls (3 and 6 months) and in painful lesions, with particular attention to lesions around the shoulder girdle.

Antibacterial hydrogel coating in joint mega-prosthesis: results of a comparative series.

PURPOSE: Joint mega-prosthesis after bone tumors, severe trauma or infection is associated with high rates of post-surgical septic complications. A fast-resorbable antibacterial hydrogel coating (DAC®, Defensive Antibacterial Coating) has previously been shown to be able to significantly reduce surgical site infection in various clinical settings. Aim of the present study was to evaluate the safety and efficacy of the DAC hydrogel coating to prevent early periprosthetic joint infection after joint mega-prosthesis. METHODS: In this three-centers, case-control study, 43 patients, treated with an antibacterial hydrogel coated mega-prosthesis for oncological (N = 39) or non-oncological conditions (N = 4), were retrospectively compared with 43 matched controls, treated with mega-implants without the coating. Clinical, laboratory and radiographic examinations were performed to evaluate the occurrence of post-surgical infection, complications and adverse events. RESULTS: At a mean follow-up of 2 years, no evidence of infection or adverse events were observed in the DAC-treated group, compared to six cases of post-surgical infection in the control group. CONCLUSION: This matched case-control study shows that a fast-resorbable, antibiotic-loaded coating can be safely used to protect joint mega-prosthesis, providing a reduction of early surgical site infections with no side effects. Larger prospective trials with longer follow-ups are warranted to confirm this report. TRIAL REGISTRATION: RS1229/19 (Regina Elena National Cancer Institute Experimental Registry Number).

Calcaneal reconstruction after total calcanectomy with iliac crest free flap.

INTRODUCTION: Calcaneal tumors being a rare occurrence, surgical options and outcomes are not well-known. Extensive defects following wide resection, especially in weight-bearing areas, still remain a challenge and different reconstructive techniques have been proposed. The aim of this report was to analyze the clinical and functional long-term outcomes of heel reconstruction using an iliac crest free flap. PATIENTS AND METHODS: Four patients who underwent calcaneal reconstruction between 1999 and 2012 were included. Two were females and mean age was 27 years, ranging 18-42 years. Each patient underwent total calcanectomy, for two osteoblastomas, one osteosarcoma, and one Ewing's sarcoma. An iliac crest flap was harvested and shaped to fit the residual space. After the articular cartilage at recipient site was debrided, the flap was fixed to the talus and the cuboid. RESULTS: The average size of the flaps was 2 x 7 x 5 cm. Postoperatively wound dehiscence, screw breaking, and graft fracture healed conservatively. All the arthrodesis healed successfully and no donor site complication occurred. At an average follow-up of 13 years (range 6-19 years) any patient claimed pain, evident limp or limitation of daily activities. Computerized pedobarographic examination and gait analysis revealed a satisfactory result and an acceptable weight-bearing area in the reconstructed limb in each patient. CONCLUSIONS: Calcaneal reconstruction with iliac crest free flap is likely to provide good chances of a long-lasting result, especially in young patients. Particularly, it provides the possibility to adequately shape the graft to fit the bone loss while using the crest as the weight-bearing surface.

Soft tissue sarcomas: new opportunity of treatment with PARP inhibitors?

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.

A matched cohort study of radio-chemotherapy versus radiotherapy alone in soft tissue sarcoma patients.

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.

Influence of age and subtype in outcome of operable liposarcoma.

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.

Latissimus dorsi rotational flap combined with a custom-made scapular prosthesis after oncological surgical resection: a report of two patients.

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.

Preoperative Denosumab With Curettage and Cryotherapy in Giant Cell Tumor of Bone: Is There an Increased Risk of Local Recurrence?

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.

Liposarcoma: Clinico-pathological analysis, prognostic factors and survival in a series of 307 patients treated at a single institution.

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.

Is an Intramedullary Nail a Valid Treatment for Limb-Length Discrepancy After Bone Tumor Resection? Case Descriptions.

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.

Surgical Treatment of Sacral Chordoma: En Bloc Resection with Negative Margins is a Determinant of the Long-Term Outcome.

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.

Biological Intercalary Reconstruction with Bone Grafts After Joint-Sparing Resection of the Lower Limb: Is this an Effective and Durable Solution for Joint Preservation?

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.

Giant schwannoma of the foot: a case report and literature review.

A schwannoma is a rare, benign tumor originating from Schwann cells of peripheral nerve sheath. It commonly occurs in subjects between 20 and 50 years of age, and its malignant transformation is exceptional. While schwannomas usually affect the head and neck region, localization in the lower extremity is exceptionally rare, and even fewer cases have described schwannomas occurring in the foot. We report a case of a giant schwannoma of the foot diagnosed in a 65-year-old woman. A giant schwannoma of the foot is an extremely rare soft tissue tumor. MRI may allow an earlier diagnosis and provide valuable information about the size and possible bone invasion. This case report noted that a complete excision of the schwannoma may prevent the risk of local recurrence, regardless of its size.

Soft tissue myxofibrosarcoma: A clinico-pathological analysis of a series of 75 patients with emphasis on the epithelioid variant.

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;114:50-55. © 2016 Wiley Periodicals, Inc.