Goals: Sarcomatous degeneration of giant cell tumours (GCT) occurs rarely. It occurs in less than 1% of the cases, and most of them are GCT previously treated with radiotherapy. The goal of this presentation is to review the CGT cases treated at our unit that have evolved towards malignization. Methods: Retrospective study of 96 GCT treated at our Hospital between 1983 and 2005. 5 presented sarcomatous degeneration in their evolution. These were the cases of 3 men and 2 women with a mean age of malignization of 42 years (32 years – 54 years). The median follow-up period was 155 months (5 months – 209 months). 3 cases affected the distal femur, one case affected distal radius and one case affected proximal humerus, with a slight tendency to the right hemibody. The primary treatment for GCT in these patients was curettage and bone graft. Only one case had received previous radiotherapy. In the same period of time we had two cases of lung dissemination of CGT with typical histology, without previous malignization of tumour. Results: Malignization takes place, on average, at the 1.8th recurrence (1.3). Histologically, we find 3 osteosarcomas and 2 indifferentiated tumours. Three patients developed distant dissemination; 2 patients died due to lung metastases, with a mean time between the first surgery and the sarcomatous degeneration of 90 months (40 monts – 183 months) and a mean time between malignization and mestastases of 22.3 months (9 months – 34 months) The treatment, once the malignization was diagnosed, consisted in wide resection and substitution with mega-arthroplasty in cases of distal femur and osteoarticular graft at the shoulder. 2 cases required amputation of the affected limb due to irresecable recurrence in soft tissues. Conclusions: There is no predictive criteria of which type of primary typical CGT will evolve into sarcoma. The malignization always has as a result high grade sarcomas, with a high tendency to hematogenous dissemination. When lung metastases appear the survival prognosis is a number of months. We must suspect malignization of a benign CGT when one of the relapses shows a very rapid growth with radiologic aggressive characteristics; in these cases we prefer wide resection of the tumour instead of curettage and thus we prevent the possible sarcomatous degeneration

Aims. We performed a systematic literature review to define features of patients, treatment, and biological behaviour of multicentric giant cell tumour (GCT) of bone. Methods. The search terms used in combination were “multicentric”, “giant cell tumour”, and “bone”. Exclusion criteria were: reports lacking data, with only an abstract; papers not reporting data on multicentric GCT; and papers on multicentric GCT associated with other diseases. Additionally, we report three patients treated under our care. Results. A total of 52 papers reporting on 104 patients were included in the analysis, with our addition of three patients. Multicentric GCT affected predominantly young people at a mean age of 22 years (10 to 62), manifesting commonly as metachronous tumours. The mean interval between the first and subsequent lesions was seven years (six months to 27 years). Synchronous lesions were observed in one-third of the patients. Surgery was curettage in 63% of cases (163 lesions); resections or amputation were less frequent. Systemic treatments were used in 10% (n = 14) of patients. Local recurrence and distant metastases were common. Conclusion. Multicentric GCT is rare, biologically aggressive, and its course is unpredictable. Patients with GCT should be followed indefinitely, and referred promptly if new symptoms, particularly pain, emerge. Denosumab can have an important role in the treatment. Cite this article: Bone Joint J 2022;104-B(12):1352–1361

We investigated whether the presence of a pathological fracture increased the risk of local recurrence in patients with a giant cell tumour (GCT) of bone. We also assessed if curettage is still an appropriate form of treatment in the presence of a pathological fracture. We conducted a comprehensive review and meta-analysis of papers which reported outcomes in patients with a GCT with and without a pathological fracture at presentation. We computed the odds ratio (OR) of local recurrence in those with and without a pathological fracture. . We selected 19 eligible papers for final analysis. This included 3215 patients, of whom 580 (18.0%) had a pathological fracture. The pooled OR for local recurrence between patients with and without a pathological fracture was 1.05 (95% confidence interval (CI) 0.66 to 1.67, p = 0.854). Amongst the subgroup of patients who were treated with curettage, the pooled OR for local recurrence was 1.23 (95% CI 0.75 to 2.01, p = 0.417). . A post hoc sample size calculation showed adequate power for both comparisons. . There is no difference in local recurrence rates between patients who have a GCT of bone with and without a pathological fracture at the time of presentation. The presence of a pathological fracture should not preclude the decision to perform curettage as carefully selected patients who undergo curettage can have similar outcomes in terms of local recurrence to those without such a fracture. Cite this article: Bone Joint J 2015;97-B:1566–71

We retrospectively compared the outcome after the treatment of giant cell tumours of bone either with curettage alone or with adjuvant cementation. Between 1975 and 2008, 330 patients with a giant cell tumour were treated primarily by intralesional curettage, with 84 (25%) receiving adjuvant bone cement in the cavity. The local recurrence rate for curettage alone was 29.7% (73 of 246) compared with 14.3% (12 of 84) for curettage and cementation (p = 0.001). On multivariate analysis both the stage of disease and use of cement were independent significant factors associated with local recurrence. The use of cement was associated with a higher risk of the subsequent need for joint replacement. In patients without local recurrence, 18.1% (13 of 72) of those with cement needed a subsequent joint replacement compared to 2.3% (4 of 173) of those without cement (p = 0.001). In patients who developed local recurrence, 75.0% (9 of 12) of those with previous cementation required a joint replacement, compared with 45.2% (33 of 73) of those without cement (p = 0.044).

Aims. Giant cell tumours (GCTs) of the proximal femur are rare, and there is no consensus about the best method of filling the defect left by curettage. In this study, we compared the outcome of using a fibular strut allograft and bone cement to reconstruct the bone defect after extended curettage of a GCT of the proximal femur. Methods. In a retrospective study, we reviewed 26 patients with a GCT of the proximal femur in whom the bone defect had been filled with either a fibular strut allograft (n = 12) or bone cement (n = 14). Their demographic details and oncological and nononcological complications were retrieved from their medical records. Limb function was assessed using the Musculoskeletal Tumor Society (MSTS) score. Results. Mean follow-up was 116 months (SD 59.2; 48 to 240) for the fibular strut allograft group and 113 months (SD 43.7; 60 to 192) for the bone cement group (p = 0.391). The rate of recurrence was not significantly different between the two groups (25% vs 21.4%). The rate of nononcological complications was 16.7% in the strut allograft group and 42.8% in the bone cement group. Degenerative joint disease was the most frequent nononcological complication in the cement group. The mean MSTS score of the patients was 92.4% (SD 11.5%; 73.3% to 100.0%) in the fibular strut allograft group and 74.2% (SD 10.5%; 66.7% to 96.7%) in the bone cement group (p < 0.001). Conclusion. Given the similar rate of recurrence and a lower rate of nononcological complications, fibular strut grafting could be recommended as a method of reconstructing the bone defect left by curettage of a GCT of the proximal femur. Cite this article: Bone Joint J 2022;104-B(2):297–301

Aims. There is a lack of evidence about the risk factors for local recurrence of a giant cell tumour (GCT) of the sacrum treated with nerve-sparing surgery, probably because of the rarity of the disease. This study aimed to answer two questions: first, what is the rate of local recurrence of sacral GCT treated with nerve-sparing surgery and second, what are the risk factors for its local recurrence?. Methods. A total of 114 patients with a sacral GCT who underwent nerve-sparing surgery at our hospital between July 2005 and August 2017 were reviewed. The rate of local recurrence was determined, and Kaplan-Meier survival analysis carried out to evaluate the mean recurrence-free survival. Possible risks factors including demographics, tumour characteristics, adjuvant therapy, operation, and laboratory indices were analyzed using univariate analysis. Variables with p < 0.100 in the univariate analysis were further considered in a multivariate Cox regression analysis to identify the risk factors. Results. The rate of local recurrence of sacral GCT treated with nerve-sparing surgery was 28.95% (33/114). Multivariate Cox regression analysis showed that large tumour size (> 8.80 cm) (hazard ratio (HR) 3.16; 95% confidence interval (CI) 1.27 to 7.87; p = 0.014), high neutrophil-to-lymphocyte ratio (NLR) (> 2.09) (HR 3.13; 95% CI 1.28 to 7.62; p = 0.012), involvement of a sacroiliac joint (HR 3.09; 95% CI 1.06 to 9.04; p = 0.039), and massive intraoperative blood loss (> 1,550 ml) (HR 2.47; 95% CI 1.14 to 5.36; p = 0.022) were independent risk factors for local recurrence. Conclusion. Patients with a sacral GCT who undergo nerve-sparing surgery have a local recurrence rate of 29%. Large tumour size, high NLR, involvement of a sacroiliac joint, and massive intraoperative blood loss are independent risk factors. Cite this article: Bone Joint J 2020;102-B(10):1392–1398

Benign aggressive tumors are common and can be debilitating for patients especially if they are in peri-articular regions or cause pathological fracture as is common for giant cell tumor of bone (GCT). Although GCT rarely metastasize, the literature reports many series with high rates of local recurrence, and evidence about which risk factors influence recurrence is lacking. This study aims to evaluate the recurrence rate and identify local recurrence risk factors by reviewing patient data from a single high-volume orthopedic oncology center. A retrospective analysis of all patients treated for GCT at a tertiary orthopedic oncology center was conducted. In total 413 patients were treated for GCT between 1989 and 2017. Multiple patient and tumour characteristics were analysed to determine if they influenced local recurrence including: age, gender, anatomical site, Campanacci stage, soft tissue extension, presence of metastasis, pathologic fractures, and prior local recurrence. Additional variables that were analysed included type of treatment (en bloc resection or aggressive intralesional curettage) and use of local adjuvants. The main outcome parameters were local recurrence- free survival, metastasis-free survival and complications. Patients treated with Denosumab were excluded from analysis given its recently documented association with high rates of local recurrence. “There were 63/413 local recurrences (15.3%) at a mean follow-up of 30.5 months. The metastatic rate was 2.2% at a mean 50.6 months follow-up and did not vary based on type of treatment. Overall complication rate of 14.3% was not related to treatment modality. Local recurrence was higher (p=0.019) following curettage (55/310; 17.7%) compared to resection (8/103; 7.8%) however, joint salvage was possible in 87% of patients (270/310) in the curettage group. Use of adjuvant therapy including liquid nitrogen, peroxide, phenol, water versus none did not show any effect on local recurrence rates (p= 0.104). Pathological fracture did not affect local recurrence rates regardless of treatment modality (p= 0.260). Local recurrence at presentation was present in 16.3% (58/356) patients and did not show any significance for further local recurrence (p= 0.396). Gender was not associated with local recurrence (p=0.508) but younger patient age, below 20 years (p = 0.047) or below 30 years (p = 0.015) was associated with higher local recurrence rates. GCT in distal radius demonstrated the highest rate of local recurrence at 31.6% compared to other sites, although this was not significant (p=0.098). In addition, Campanacci stage and soft tissue extension were not risk factors for recurrence. The overall GCT local recurrence rate was 15.3%, but varied based on the type of resection: 17.7% following joint sparing curettage compared to 7.8% following resection. Local recurrence was also higher with younger patient age (30 years or less) and in distal radius lesions. In addition, neither Campanacci stage, soft tissue extension or presence of a pathologic fracture affected local recurrence. Most patients with GCT can undergo successful curettage and joint sparing, while only a minority require resection +/− prosthetic reconstruction. Even in the presence of soft tissue extension or a pathologic fracture, most joints can be salvaged with curettage

Various chemicals are commonly used as adjuvant treatment to surgery for giant-cell tumour (GCT) of bone. The comparative effect of these solutions on the cells of GCT is not known. In this study we evaluated the cytotoxic effect of sterile water, 95% ethanol, 5% phenol, 3% hydrogen peroxide (H. 2. O. 2. ) and 50% zinc chloride (ZnCI. 2. ) on GCT monolayer tumour cultures which were established from six patients. The DNA content, the metabolic activity and the viability of the cultured samples of tumour cells were assessed at various times up to 120 hours after their exposure to these solutions. Equal cytotoxicity to the GCT monolayer culture was observed for 95% ethanol, 5% phenol, 3% H. 2. O. 2. and 50% ZnCI. 2. The treated samples showed significant reductions in DNA content and metabolic activity 24 hours after treatment and this was sustained for up to 120 hours. The samples treated with sterile water showed an initial decline in DNA content and viability 24 hours after treatment, but the surviving cells were viable and had proliferated. No multinucleated cell formation was seen in these cultures. These results suggest that the use of chemical adjuvants other than water could help improve local control in the treatment of GCT of bone

Aims. To investigate the benefits of denosumab in combination with nerve-sparing surgery for treatment of sacral giant cell tumours (GCTs). Methods. This is a retrospective cohort study of patients with GCT who presented between January 2011 and July 2017. Intralesional curettage was performed and patients treated from 2015 to 2017 also received denosumab therapy. The patients were divided into three groups: Cohort 1: control group (n = 36); cohort 2: adjuvant denosumab group (n = 9); and cohort 3: neo- and adjuvant-denosumab group (n = 17). Results. There were 68 patients within the study period. Six patients were lost to follow-up. The mean follow-up was 47.7 months (SD 23.2). Preoperative denosumab was found to reduce intraoperative haemorrhage and was associated with shorter operating time for tumour volume > 200 cm. 3. A total of 17 patients (27.4%) developed local recurrence. The locoregional control rate was 77.8% (7/9) and 87.5% (14/16) respectively for cohorts 2 and 3, in comparison to 66.7% (24/36) of the control group. The recurrence-free survival (RFS) rate was significantly higher for adjuvant denosumab group versus those without adjuvant denosumab during the first two years: 100% vs 83.8% at one year and 95.0% vs 70.3% at two years. No significant difference was found for the three-year RFS rate. Conclusion. Preoperative denosumab therapy was found to reduce intraoperative haemorrhage and was associated with shorter operating times. Adjuvant denosumab was useful to prevent early recurrence during the first two years after surgery. Cite this article: Bone Joint J 2020;102-B(2):177–185

AIM. To present our experience in patients treated under primary diagnosis giant cell tumor of bone at Department Orthopaedic Surgery Zagreb University School of Medicine in a 15-year period from 1995 to 2009. METHODS. We performed a retrospective study of all patients treated in our Department because of giant cell tumor of bone (GCT) from 1995 to 2009. The mean age of our patients was 29,9 years (range: 14 to 70 years). Sex distribution showed prevalence in female (F:M=23:12=66%:34%). All together, 39 patients were operated under primary diagnosis of GCT. Four patients were lost in follow-up. In total, 35 patients were included in study. Diagnosis of GCT was made according to clinical, imaging and histological findings, and distributed by Campanacci's classification. RESULTS. Not including diagnostic biopsy, 84 operations were performed on 35 patients. Fourteen patients (40%) had GCT grade 1, fourteen (40%) had GCT grade 2, and seven (20%) had GCT grade 3. From the first symptoms to diagnosis there was an average duration of 7 months (range: 0 to 24 months), where the main symptoms were pain and swelling of affected bone and/or joint. GCT was localized in distal femur (n=12, 34%), proximal tibia (n=10, 29%), distal tibia (n=4, 11%), distal radius (n=3, 9%), and other locations (n=6, 17%). Patients with less aggressive GCT (grades 1 and 2) were treated with marginal excision: excochleation and reconstruction with bone transplant (n=12, 34%). In patients with locally more aggressive tumor (grades 2 and 3), “en bloc” resection and reconstruction with tumor endoprosthesis or bone transplant was performed (n=22, 63%). Due to localization of tumor, one patient was treated with radiation (3%). Complications were recorded in 12 patients (34%), and are shown as total number and percentage of all complications. Complications were the most common in knee region, proximal tibia (n=4, 33%) and distal femur (n=3, 25%). Also, the complications occured more frequently after “en bloc” resection (n=7, 58%). GCT classified as gradus 2 had most complications (n=5, 42%) till GCT classified as gradus 3 had least (n=3, 25% of complications, 9% of all). We recorded and treated local recurrence of tumor (n=6, 50%), infection (n=2, 17%), and mehanical complications of endoprosthesis (n=2, 17%). Due to local recurrences, in 2 patients underlying osteosarcoma was revealed, and they were treated with amputation. CONCLUSION. Each patient with GCT should be treated individually. Regardless non-malignant attribute, local behaviour of tumor determines treatment approach according to treatment principles of malignant tumor of bone. Number of complications in our patients is relatively high, recorded in one third of our patients, which matches the literature in announced studies

Giant cell tumours (GCTs) of the small bones of the hands and feet are rare. Small case series have been published but there is no consensus about ideal treatment. We performed a systematic review, initially screening 775 titles, and included 12 papers comprising 91 patients with GCT of the small bones of the hands and feet. The rate of recurrence across these publications was found to be 72% (18 of 25) in those treated with isolated curettage, 13% (2 of 15) in those treated with curettage plus adjuvants, 15% (6 of 41) in those treated by resection and 10% (1 of 10) in those treated by amputation. We then retrospectively analysed 30 patients treated for GCT of the small bones of the hands and feet between 1987 and 2010 in five specialised centres. The primary treatment was curettage in six, curettage with adjuvants (phenol or liquid nitrogen with or without polymethylmethacrylate (PMMA)) in 18 and resection in six. We evaluated the rate of complications and recurrence as well as the factors that influenced their functional outcome. At a mean follow-up of 7.9 years (2 to 26) the rate of recurrence was 50% (n = 3) in those patients treated with isolated curettage, 22% (n = 4) in those treated with curettage plus adjuvants and 17% (n = 1) in those treated with resection (p = 0.404). The only complication was pain in one patient, which resolved after surgical removal of remnants of PMMA. We could not identify any individual factors associated with a higher rate of complications or recurrence. The mean post-operative Musculoskeletal Tumor Society scores were slightly higher after intra-lesional treatment including isolated curettage and curettage plus adjuvants (29 (20 to 30)) compared with resection (25 (15 to 30)) (p = 0.091). Repeated curettage with adjuvants eventually resulted in the cure for all patients and is therefore a reasonable treatment for both primary and recurrent GCT of the small bones of the hands and feet. Cite this article: Bone Joint J 2013;95-B:838–45

Giant cell tumours (GCT) of the synovium and tendon sheath can be classified into two forms: localised (giant cell tumour of the tendon sheath, or nodular tenosynovitis) and diffuse (diffuse-type giant cell tumour or pigmented villonodular synovitis). The former principally affects the small joints. It presents as a solitary slow-growing tumour with a characteristic appearance on MRI and is treated by surgical excision. There is a significant risk of multiple recurrences with aggressive diffuse disease. A multidisciplinary approach with dedicated MRI, histological assessment and planned surgery with either adjuvant radiotherapy or systemic targeted therapy is required to improve outcomes in recurrent and refractory diffuse-type GCT. Although arthroscopic synovectomy through several portals has been advocated as an alternative to arthrotomy, there is a significant risk of inadequate excision and recurrence, particularly in the posterior compartment of the knee. For local disease partial arthroscopic synovectomy may be sufficient, at the risk of recurrence. For both local and diffuse intra-articular disease open surgery is advised for recurrent disease. Marginal excision with focal disease will suffice, not dissimilar to the treatment of GCT of tendon sheath. For recurrent and extra-articular soft-tissue disease adjuvant therapy, including intra-articular radioactive colloid or moderate-dose external beam radiotherapy, should be considered

Aims. Local recurrence remains a challenging and common problem following curettage and joint-sparing surgery for giant cell tumour of bone (GCTB). We previously reported a 15% local recurrence rate at a median follow-up of 30 months in 20 patients with high-risk GCTB treated with neoadjuvant Denosumab. The aim of this study was to determine if this initial favourable outcome following the use of Denosumab was maintained with longer follow-up. Methods. Patients with GCTB of the limb considered high-risk for unsuccessful joint salvage, due to minimal periarticular and subchondral bone, large soft tissue mass, or pathological fracture, were treated with Denosumab followed by extended intralesional curettage with the goal of preserving the joint surface. Patients were followed for local recurrence, metastasis, and secondary sarcoma. Results. A total of 25 patients with a mean age of 33.8 years (18 to 67) with high-risk GCTB received median six cycles of Denosumab before surgery. Tumours occurred most commonly around the knee (17/25, 68%). The median follow-up was 57 months (interquartile range (IQR) 13 to 88). The joint was salvaged in 23 patients (92%). Two required knee arthroplasty due to intra-articular fracture and arthritis. Local recurrence developed in 11 patients (44%) at a mean of 32.5 months (3 to 75) following surgery, of whom four underwent repeat curettage and joint salvage. One patient developed secondary osteosarcoma and another benign GCT lung metastases. Conclusion. The use of Denosumab for joint salvage was associated with a higher than expected rate of local recurrence at 44%. Neoadjuvant Denosumab for joint-sparing procedures should be considered with caution in light of these results. Cite this article: Bone Joint J 2021;103-B(1):184–191

Giant cell tumors of bone (GCTs) are locally aggressive tumors with recurrence potential that represent up to 10% of primary tumors of the bone. GCTs pathogenesis is driven by neoplastic mononuclear stromal cells that overexpress receptor activator of nuclear factor kappa-B/ligand (RANKL). Treatment with specific anti-RANKL antibody (denosumab) was recently introduced, used either as a neo-adjuvant in resectable tumors or as a stand-alone treatment in unresectable tumors. While denosumab has been increasingly used, a percentage of patients do not improve after treatment. Here, we aim to determine molecular and histological patterns that would help predicting GCTs response to denosumab to improve personalized treatment. Nine pre-treatment biopsies of patients with spinal GCT were collected at 2 centres. In 4 patients denosumab was used as a neo-adjuvant, 3 as a stand-alone and 2 received denosumab as adjuvant treatment. Clinical data was extracted retrospectively. Total mRNA was extracted by using a formalin-fixed paraffin-embedded extraction kit and we determined the transcript profile of 730 immune-oncology related genes by using the Pan Cancer Immune Profiling panel (Nanostring). The gene expression was compared between patients with good and poor response to Denosumab treatment by using the nSolver Analysis Software (Nanostring). Immunohistochemistry was performed in the tissue slides to characterize cell populations and immune response in CGTs. Two out of 9 patients showed poor clinical response with tumor progression and metastasis. Our analysis using unsupervised hierarchical clustering determined differences in gene expression between poor responders and good responders before denosumab treatment. Poor responding lesions are characterized by increased expression of inflammatory cytokines as IL8, IL1, interferon a and g, among a myriad of cytokines and chemokines (CCL25, IL5, IL26, IL25, IL13, CCL20, IL24, IL22, etc.), while good responders are characterized by elevated expression of platelets (CD31 and PECAM), coagulation (CD74, F13A1), and complement classic pathway (C1QB, C1R, C1QBP, C1S, C2) markers, together with extracellular matrix proteins (COL3A1, FN1,. Interestingly the T-cell response is also different between groups. Poor responding lesions have increased Th1 and Th2 component, but good responders have an increased Th17 component. Interestingly, the checkpoint inhibitor of the immune response PD1 (PDCD1) is increased ~10 fold in poor responders. This preliminary study using a novel experimental approach revealed differences in the immune response in GCTs associated with clinical response to denosumab. The increased activity of checkpoint inhibitor PD1 in poor responders to denosumab treatment may have implications for therapy, raising the potential to investigate immunotherapy as is currently used in other neoplasms. Further validation using a larger independent cohort will be required but these results could potentially identify the patients who would most benefit from denosumab therapy

The purpose of our study was to identify possible risk factors of patients with GCT of the long bones after curettage and packing the bone cavity with bone cement or bone allografts. We retrospectively reviewed the records of 249 patients with GCT of the limbs treated at Musculoskeletal Oncology Department of our institution between 1990 and 2013, confirmed histologically and recorded in the Bone Tumor Registry. We reviewed 219 cases located in the lower limb and 30 of the upper limb. This series includes 135 females and 114 males, with mean age 32 years (ranging 5 to 80 yrs). According to Campanacci's grading system, 190 cases were stage 2, 48 cases stage 3, and 11 cases stage 1. Treatment was curettage (intralesional surgery). Local adjuvants, such as phenol and cement, were used in 185 cases; whereas in the remaining 64 cases the residual cavity was filled with allografts or autografts only. Oncological outcome shows 203 patients alive and continuously disease-free (CDF), 41 patients NED1 after treatment of local recurrence (LR), 2 patients NED1 after treatment of lung metastases, 2 AWD with lung metastases. One patient died of unrelated causes (DOD). LR rate was 15.3% (38 pts). Lung metastases rate was 1.6% (4 pts). In patients treated by curettage and cement (185 cases) LR was 12% (22 pts). Conversely, in patients treated curettage and bone allografts it was higher (16/64 cases), with an incidence of 25% of cases (p=0.004). Oncological complications seemed to be related with site, more frequently occurring in the proximal femur (p=0.037). LR occurred only in stage 2 or 3 tumors without statistical significance (p>0.05). The mean interval between the first surgical treatment and LR was 22 months (range: 3–89 mos). However, in the multivariate analysis no significant statistical effect on local recurrence rate could be identified for gender, patient's age, Campanacci's grading, or cement vs allografts. The only independent risk factor related to the local recurrence was the site, with a statistical significance higher risk for patients with GCT of the proximal femur (p= 0.008). Our observation on the correlation of tumor location and risk of local recurrence is new. Therefore, special attention must be given to GCTs in the proximal femur. In fact, primary benign bone tumors in the proximal femur are difficult to treat due to the risk of secondary osteonecrosis of the femoral head or pathologic fracture. Numerous methods of reconstructions have been reported. Among these, total hip arthroplasty (THA) or bipolar hip arthroplasty (BHA) should be avoided when possible as more cases are observed in young patients. Therefore, we do not suggest different approach for the proximal femur. GCT in the proximal femur is much more difficult to treat than in other sites, but if curettage is feasible, the best way is to save the joint with a higher risk of local recurrence, knowing that the sacrifice of the hip articulation in case of recurrence is always possible with THA or BHA

Introduction: Giant cell tumor (GCT) is a benign but locally aggressive tumor that primarily affects the epiphyses of long bones of young adults. Pulmonary metastases in giant cell tumor are rare. We report our experience of treating pulmonary metastatic GCT of bone over the last 24 years between 1984–2007. Methods: A retrospective review of patients’ records and oncology database of patients with metastatic GCT. Results: We had 471 patients with GCT of bone out of which 7 patients developed pulmonary metastases (1.48%). Six patients following diagnosis and initial treatment and one with pulmonary metastases present at the diagnosis. There were 4 males and 3 females aged between 23 to 40 years (median, 27 years). All patients had GCT around the knee (distal femur/proximal tibia). All patients eventually required Endoprosthetic Replacement apart from one who was treated with curettage only. The time of pulmonary metastases from initial diagnosis was 16–92 months (median, 44.6 months). All patients who developed metastases in the postoperative period had thoracotomy for excision of the pulmonary metastases. Two patients received chemotherapy for control of the local recurrence. At an average follow up of 151 months (27–304 months), all patients were alive. Discussion: Pulmonary metastases have been reported as 1% to 9% in GCT. Because of its rarity, very little is known about the long-term outcome and the best treatment for the pulmonary lesions. The mortality rates recorded for patients with pulmonary metastatic GCT range from 0% to 37%. In our series the mortality rate was 0% and metastases 1.48%. It seems that surgical resection of pulmonary metastases gave excellent rate of survival

Giant cell tumour of bone (GCT) is a primary osteolytic neoplasm, histopathologically characterized by osteoclast-like giant cells and clinically characterized by local bone destruction and high recurrence rates. There is a need to identify risk factors for recurrence. In order to reduce the recurrence rate we initiated an international, multicenter, randomised phase II trial with adjuvantzoledronic acid as compared to standard care for high risk GCT patients. One hundred and sixteen GCT patients, treated at the LUMC from 1971 to 2006, with a minimal follow-up of a year, were retrospectively analysed for the following risk factors for local recurrence: GCT grade III and tumour involvement into soft tissue caused by ingrowth or fracture. Resection was used as treatment in 21 patients (group A), intralesional surgery with cement or adjuvant in 24 (group B) and intralesional surgery with cementation and adjuvant in 71 patients (group C). GCT recurred in 5% (1/21) in group A. Risk factors were found in 90% of patients without recurrence (18/20). Group B shows a recurrence of 25% (6/24). Risk factors were found in 83% (5/6) of recurring GCTs, compared with 28% in patients without recurrence. In group C, a recurrence rate of 23% (16/71) was found. Risk factors were present in 94% (15/16) of recurrences, compared to 36% (20/55) in patients without recurrence. Soft tissue involvement and GCT grade 3 and up are risk factors for recurrence in GCT. Recurrence rates are lowest when resection is used. Risk factors may influence the choice of treatment. High risk patients may benefit from resection or systemic treatment with adjuvant therapy

To present the oncological outcome of eleven patients with stage-3 GCT of bone. Thirty-nine cases of GCT who were treated the past nine years at our department were reviewed. Five tumors were classified as stage I, twenty-three tumors as stage II and eleven as stage III tumors. In stage I or II tumors we proceeded to an intraoperative biopsy (frozen biosy).In cases where the intraoperative pathological findings confirmed our diagnosis of GCT we proceeded to operative management. In cases where the intraoperative pathologist’s findings were not clear as well as in cases of stage III tumors we performed only a traditional open biopsy proceeding surgery in a second stage. In stage III tumors we aimed wide margins. Ten of these patients underwent wide surgical excision and limb salvage, while in one patient curettage with cementation was the treatment of choice in order to obtain a fair functional outcome. With a minimum follow up of 3 years, we had no case of local recurrence in cases treated with wide excision and limb salvage. One stage III GCT treated with curettage recurred. Two stage III tumors metastized to the lung. The average interval from initial operation to lung metastasis was six months. Treating GCT with the above management minimizes diagnostic failures. Literature shows local recurrence rate as high as 50% in stage III GCTs. The present study shows that recurrence rate can be significantly reduced and good functional outcome can be achieved by carefully planning approach and wide excision of the tumor

Tartrate-resistant acid phosphatase is contained in multinucleated giant cells of giant cell tumour of bone (GCT) and chondroblastoma (CBL) as well as in osteo-clasts. Yet few studies have so far been done regarding serum acid phosphatase (AcP) level in patients of GCT or CBL. The purpose of this study is to elucidate the clinical significance of serum AcP as a tumour marker for GCT and CBL. Serum AcP value was examined in nine GCT patients and three CBL patients before and after surgery. In the GCT cases, serum AcP values before surgery were high in five cases. They were 14.0 IU/L, 68.7 IU/L, 45.9 IU/L, 21.9 and 31.3 IU/L (normal value; 7.1–12.6 IU/L). They decreased after surgery to 7.7 IU/L (55% of the preoperative value), 8.2 IU/L (12%), 7.8 IU/L (17%), 6.1 IU/L (28%) and 10.0 IU/L (32%), respectively. Serum AcP values before surgery were within normal limits in the remaining four GCT cases. Even in these four cases, postoperative serum AcP level was lower than the preoperative level. Postoperative/preoperative AcP ratios in these four cases were 67%, 80%, 69% and 76%. In the CBL cases, serum AcP values were high in all cases. They were 15.1 IU/L, 13.1 IU/L and 13.7 IU/L. They decreased after surgery to 10.3 IU/L (68% of the pre-operative value), 10.2 IU/L (78%) and 9.7 IU/L (71%), respectively, all within normal limits. Therefore, it is concluded that serum AcP is a useful tumour marker for GCT and CBL in diagnosing the tumour as well as in evaluating the efficacy of treatment

Summary. We demonstrate that osteoclast-like cells of GCT result from the spontaneous fusion and differentiation of CD14+ cells of the monoblastic lineage by an autocrine mechanism mediated by RANKL, rather than induced by stromal cells. This process is further enhanced by the simultaneous impairment of the negative feed-back regulation of osteoclastogenesis by interferon β. Introduction. Giant cell tumor of bone (GCT) is a benign osteolytic lesion with a complex histology, comprising prominent multinucleated osteoclast-like cells (OC), mononuclear stromal cells (SC), and monocyte-like elements. So far, most studies have focused on SC as the truly transformed elements that sustain osteoclast differentiation, while less attention has been paid on the monocyte-like cell fraction. On the contrary, we have previously shown that SC are non-transformed element that can induce osteoclastogenesis of monocytes at levels that do not exceed that of normal mesenchymal stromal cells. We therefore focused on CD14+ monocyte-like cells as an alternative key candidate for the pathogenesis of GCT. Methods. We isolated CD14+ enriched cell fraction from tumor samples by immunomagnetic separation. We analyzed CD14+ cells for ultrastructural morphology, mRNA levels of haematopoietic, monocytic, and dendritic markers, and for RANKL, and M-CSF. Due to the very high number of OC in GCT, we hypothesised that the IFN-b pathway might be impaired. In fact, IFN-b functions as a negative-feedback regulator that inhibits osteoclast differentiation. We assayed IFN-b mRNA and protein expression in both cultures and tumor samples. Finally, we verified the ability of CD14+ cells to spontaneously form osteoclasts. Results. In the CD14+ enriched fraction we identified two different cell populations, both positive for TRACP activity and negative for Ki-67 nuclear localization, one with an undefined histotype and the other showing characteristics of the monoblastic lineage, mainly monoblasts and promonocytes. Isolated cells were positive for CD45, MSE-1, RANK, CD14, and CD80, and negative for CD144, and were able to spontaneously form collagen-resorbing multinucleated cells, a process that was strongly impaired by the addition of osteoprotegerin. The expression of RANKL and M-CSF mRNA in cultured cells demonstrated the presence of an autocrine circuit inducing osteoclast formation. Finally, we found very low expression of IFN-b both in the in vitro formed OC and in tissue samples. Conclusions. These data show that CD14+ cells in GCT are monocyte-like cells that can spontaneously form bone-resorbing multinucleated cells through impaired IFN-b expression. Taken together, these data raise questions regarding the role of the CD14+ cell component and of their regulating mechanisms that may be relevant for the development of effective therapeutic strategies

Aim. Giant cell tumour (GCT) of bone is a benign but locally aggressive tumour. Although topical adjuvants have been used in the past, local recurrence following intralesional excision of GCT of bone continues to remain a problem. The use of bisphosphonates as an anti-osteoclastic agent in the management of osteolytic bone metastases is well accepted. Therefore our study aims to retrospectively demonstrate whether the administration of bisphosphonate as an adjuvant can control aggressive local recurrence of GCT and prevent wide resections of bones or amputations. Method. A retrospective study was performed between 2004 and 2010. 6 patients were diagnosed with aggressive local recurrence of appendicular GCT. All patients were treated for the primary tumour by surgical curettage and cryoablation followed by cementation or biological reconstruction. In 5 patients the tumour was located in the distal radius and in one in the first metacarpal bone. All recurrences were in the bone with large soft-tissue extension. After histological diagnosis – by CT core needle biopsy – the patients were treated by intravenous bisphosphonate, followed by clinical & radiological assessments. Results. Average follow-up of 42 months, ranging from 12 to 72 consecutive months. All patients showed good response to bisphosphonate treatment: lesions become calcified gradually as shown in x-rays & CT scans, reduction in size of soft tissue components, patient reported relief of pain & improvement of the affected limb. All treated patients did not report any untoward effects. Conclusion. In the current study bisphosphonate treatment is found to be an effective treatment for local control of aggressive local recurrence of GCT of the extremities and can therefore be a good alternative to wide resections of bone and complicated reconstructions. Functional results are shown to be promising as well. The study results need further investigation & a larger scale of patients

Giant cell tumors (GCT) of the sacrum have a high recurrence rate, up to 33%. Treatment of Giant Cell Tumors (GCT) of the sacrum has many options. Although curettage is more often performed than partial sacral resection the indications are not well described. Large resection in the sacral area is limited, and adequate local adjuvant therapy potentially damages the nervous system. Therefore the type of surgical treatment of sacral GCT is still under debate. The purpose of this study was to compare clinical outcome after surgical treatment in GCT of the sacrum using two different surgical techniques: curettage and Extended Cortical Excision (ECE). Pre-operative embolisation was routinely performed, followed by curettage or PSR followed by reconstruction if indicated. Between 1994–2005 11 patients were treated for GCT of the sacrum. Eight were female, 3 men. The median age was 43.5 (14–66) years. The median follow-up period was 60 (6–156) months. Five patients were eventually treated by ECE. The other patients were operated on using different techniques, mainly curettage and/or adjuvant therapy. Two patients died disease-related 42 and 6 months after primary treatment, both metastasized. All other patients are alive and currently disease-free. Six patients had a recurrence, after 33 (4–140) months. Three patients had a recurrence twice. Three patients received radiotherapy, 1 as palliative treatment and 2 as (adjuvant) therapy for recurrence. No recurrences were seen after ECE compared to 86% (6/7) after curettage only, and 50% (2/4) after curettage with adjuvant therapy. Extended cortical excision may improve the recurrence rate in sacral GCT

The giant cell tumor of bone (GCT) is a locally aggressive intraosseous neoplasm, with an uncertain biological behavior, constituted of giant multinuclear cells spread over tumoral tissue with a nucleus presenting the same features of the ovoid and fusiform cells forming its stroma. The local recurrence of GCT is often observed, mainly in the first three years after treatment, giving a rate of recurrence ranging in 20 to 50% of cases. Further aggravating the recurrence is the fact that after the relapse, the patient often also presents metastases in other organs. The aim of this study was to identify and to characterize differentially expressed genes that can be used in the prognostic, treatment and understanding of this physiopathology. To identify novel genes differentially expressed in GCT, we have applied rapid subtractive hybridization (RaSH). Samples of GCT and normal tissues were obtained at Tumor Bank of Barretos Cancer Hospital. After RNA extraction and cDNA synthesis the samples were submitted to Rapid hybridization Subtraction (RaSH) methodology for subtractive libraries elaboration. The RaSH subtractive libraries reveals the presence of 619 different clones including both normal and tumor tissues were identified. Of these, 450 in tumor sample and 169 in control tissue. Four biomarkers candidates were selected for validation: ZAK, KTN1, NEB, and ROCK1 genes, whose functions are, related to cell cycle checkpoint, transport of organelles, cytoskeletal matrix and cell adhesions. The validation of selected differentially expressed genes was performed using real time PCR. The putative molecular markers found in this work may help to find the basis for a molecular comprehension of GCT, thus improving diagnosis, treatment and outcome for patients with this tumor

Purpose. Secondary degenerative changes of the knee are a well recognized complication of Giant Cell Tumor (GCT). Osteoarthritis (OA) may be a consequence of the lesion itself or its treatment. Total Knee Arthroplasty (TKA) is a treatment option for end stage knee arthritis. In the current study we describe the short term follow up of three patients that underwent TKA for treatment of GCT related OA between 2006–2007. Method. The records of 180 consecutive patients treated for giant cell tumor of the knee between 1989 and 2007 in our institution were reviewed. Three patients were identified that had total knee arthroplasty following treatment of giant cell tumor of the knee, confirmed by tissue biopsy. The review included all clinical notes, pathology and operative reports. Outcomes were assessed based on knee scores and functional scores calculated according to the clinical rating system of The Knee Society, with the assignment of a maximum of 100 points for each. Patient ages range from 29–75 years of age. Assessment occurred pre-operatively as well as post-operatively at six weeks, three months, six months and then yearly. The development of osteoarthritis with severe knee pain was the primary indication for performing TKA. Results. Patients had a low mean preoperative knee score of 23, with mean function score of 50. All patients reported severe pain preoperatively. Mean range of motion was five degrees of fixed flexion contracture to to 75 degrees of flexion. Intraoperatively, there were no complications, although mean tourniquet time was prolonged in comparison to standard TKA at 106.7 minutes. This reflects a procedure of greater complexity than routine TKA. At last follow up at a mean of 35.5 months the mean knee score was 58, mean function score was 93, mean pain score of two (none to moderate), and mean range of motion was zero to 93 degrees. No recurrences of GCT were noted in any of the cases. Conclusion. In the cases we currently report, the preoperative pain scores as well as functional scores have all improved following TKA. While the range of motion did not seem to improve significantly and one patient developed TKA instability requiring revision surgery to resolve the issue, no other complications or recurrences of the GCT were noted. Thus while range of motion was inferior to routine TKA, this procedure can provide a pain-free, well functioning knee joint in a patient with arthritis secondary to GCT. In summary, our experience with TKA for osteoarthritis secondary to giant cell tumor of the knee is a reliable treatment option providing acceptable range of motion, pain and functional score results for patients

Purpose: Giant cell tumor (GCT) of bone is a rare, usually benign, primary skeletal lesion. The disease’s clinical course may be complicated by local recurrence subsequent to surgical treatment or the development of benign pulmonary metastases. Intra-lesional curettage is the standard treatment of primary GCT of bone. However, the value of intralesional procedures in recurrent GCT has not been well established. Method: Forty-six patients with recurrent GCT of long bones treated between 1983 and 2005 were followed retrospectively. Minimum follow-up was three years; mean follow-up was 11.1 (±4.8) years. Results: Wide resections were performed in 18 patients. Intralesional, joint preserving procedures were performed in 28 patients. Subsequent recurrence occurred in nine patients (20%). Wide resection was performed if joint salvage was not achievable due to expansion of the tumor. Reconstructions following wide resection included arthroplasty (n=4), osteoarticular allograft (n=3), APC (n=1) and fibular autograft reconstruction of the wrist (n=3). Amputations were performed in two patients. Patients undergoing wide resections for local recurrence had a significantly smaller risk of subsequent recurrence as compared to patients treated with intra-lesional surgery (6% versus 32%, hazard ratio: 0.28, p< 0.05). In patients treated with intralesional surgery, application of polymethylmethacrylate (PMMA) in addition to local phenol treatment significantly reduced the risk of subsequent recurrence (PMMA + phenol: 7% vs. Phenol: 25%, hazard ratio: 0.23, p< 0.05). Soft tissue expansion was not associated with an increased risk of subsequent recurrence. At follow-up, all patients with subsequent recurrence were without local disease after additional intralesional surgery (n=3) or wide resection (n=5). Metachronous benign pulmonary metastases evolved in five cases. There was no correlation between the development of pulmonary metastases and the type of treatment of recurrent disease found. Conclusion: In recurrent disease of GCT of long bones and the possibility to salvage the adjacent joint intra-lesional surgery is the treatment of choice independent of whether soft tissue expansion is present. Intra-lesional surgery does not increase the risk of development benign pulmonary metastases. In cases with extensive tumor formation and without the possibility to preserve the adjacent joint wide resection has a high chance for long-term recurrence free disease

The October 2013 Oncology Roundup. 360 . looks at: En bloc resection, irradiation and re-implantation; Metastasis and osteosarcoma; Mobile spine and osteosarcoma; Denosumab miraculous for GCT; Fevers, megaprostheses and sarcomas; PET and prognosis; Canine sarcomas not so different?; Bone cement and giant cell tumours

Giant cell tumor (GCT) of bone is an osteolytic tumor that is locally aggressive and potentially metastatic. The pathogenesis of GCT is poorly understood. The purpose of this study was to harvest and culture primary cell lines from clinical specimens of GCT of bone and identify specific bone degradation proteases (matrix metalloproteinases: MMP-2, MMP-9) produced by the neoplastic stromal cells in vitro. With approval by the McMaster University Biohazards and Ethics Review Boards, we acquired consent from five patients with GCT of bone, and harvested specimens intraoperatively. The specimens were chopped in DMEM containing 10% Fetal Bovine Serum, 2 mM L-glutamine, 100 U/ml penicillin and 100 mg/ml streptomycin. The cell suspensions were incubated at thirty-seven degrees (5% CO2 and 95% air) and cultivated. The cells were grown to confluence and taken through several passages until only proliferative cells were present. Immunocytochemistry with TRAP (Tartrate Resistant Acid Phosphatase) was used to confirm the stem cell origin of the propagative cells. Protein electrophoresis with embedded gelatin was used for detecting protease activity (MMP-2, MMP-9) on cell lysates and medium. P-aminophenyl mercuric acetate (APMA) was used to activate and ethylenediaminetetraacetic acid (EDTA) was used to block MMP-2 and MMP-9 activity. Our controls included serum free media, Human Osteosarcoma and Fibroblast cell lines. Immunocytochemistry with TRAP confirmed that our propagative cells were not hematopoietic in origin but rather mesenchymal. Protein electrophoresis on cell lysates and medium identified the protease activity of MMP-2 and MMP-9 with lytic bands at appropriate molecular weights. APMA activated MMP-2 more than MMP-9, as indicated by increased relative density of bands. EDTA blocked the activity of both MMPs. Our study confirmed the ability to cultivate the neoplastic stromal cells of GCT of bone from clinical specimens. Protein electrophoresis showed that activated MMP-2 and MMP-9 are secreted from the neoplastic stromal cells in vitro, suggesting a role for the tumor cells in bone destruction. These results are intriguing, as novel therapies in specific MMP inhibitors are currently underway for numerous disease processes

The April 2015 Oncology Roundup. 360 . looks at: New hope for skull base tumours; Survival but at what cost?; Synovial sarcoma beginning to be cracked?; Wound complications facing soft-tissue sarcoma surgeons; Amputation may offer no survival benefit over reconstruction; Giant cell tumour in the longer term; Intralesional treatment comparable with excision in GCT of the radius?; Imaging prior to oncological referral; And finally…

The February 2013 Children’s orthopaedics Roundup. 360 . looks at: the human genome; new RNA; cells, matrix and gene enhancement; the histology of x-rays; THR and VTE in the Danish population; potential therapeutic targets for GCT; optimising vancomycin elution from cement; and how much sleep is enough

Aim. To analyse our results after en-block resection of aggressive GCT during 20 years period. Methods. We review 86 patients with skeletal GCT during the last 20 years, from 1990 until 2009, retrospectively. In the cases of latent and active type, extended curettage and bone graft or cement were our treatment of choice, while in aggressive ones we performed en block resection and reconstruction by fibular autograft (e.g. in distal part of radius) or fusion/hinge joint prosthesis (e.g. in GCT around the knee joint). We describe the recurrences, metastases and complications according to treatment. Results. There was no recurrence in 18 cases of en block resection and segmental bone defects were reconstructed with fibular autograft (5), joint fusion (4) and hinge joint arthroplasty (9). We had 2 cases of pulmonary metastasis that underwent resection of the metastasis. In one case, internal fixation failed and the graft broke; thus revision was performed. The rest 68 cases underwent extended curettage and bone graft (51) or cement (17). We had 7 cases of recurrence, 6 treated with repeated curettage and bone cement and one with en lock resection. No death or major complication was reported. Conclusions. In comparison of en block resection with extended curretage, the recurrence rate is greater with the latter; however it results in good control of the disease with less morbidity. In recent years, the invention of hinge knee prosthesis has increased the quality of patients' life in whom we could not preserve the involved joint

Introduction. The role of adjuvants in curettage for giant cell tumours (GCT) is still controversial. Our aim was to determine if adjuvant cementation lowers local recurrence (LR) rates for GCTs treated with curettage. Methods. Detailed curettage has been the principal treatment for GCT for the past 30 years. Cement was used from 1996 onwards for tumours where there was concern about structural stability. We investigated factors affecting LR and also the incidence of complications for treatment with or without cement. Results. From 1975 to 2008, 330 patients with GCT were treated primarily with curettage. Eighty-four (25%) received adjuvant treatment with acrylic bone cementation. Cement was only used in Campannacci grade 2 or 3 GCTs. LR for curettage was 30% compared with 14% for curettage plus cementation. (p = 0.001). LR was halved by the use of cement for both stage 2 and stage 3 tumours (Stage 2, 8% LR with cement, 21% without (p=0.02); Stage 3, 19% with cement, 48% without (p⋋0.001)). On multivariate analysis both stage and use of cement were independent significant factors in predicting LR. Site was not significant although the distal tibia and proximal humerus had lower risk of LR than other sites. Cement was however associated with a higher risk for subsequent joint replacement surgery. In patients without LR, 18% with cement needed a joint replacement compared to 2% without. In patients with LR, 75% with cement required a joint replacement, compared to 44% without. Discussion. Although adjuvant cementation seems to give better local control for curettage of GCT, it is associated with an increased need for subsequent joint replacement

Curettage and packing with polymethylmethacrylate cement is a routine treatment for giant-cell tumour (GCT) of bone. We performed an in vitro evaluation of the cytotoxic effect of a combination of cement and methotrexate, doxorubicin and cisplatin on primary cell cultures of stromal GCT cells obtained from five patients. Cement cylinders containing four different concentrations of each drug were prepared, and the effect of the eluted drugs was examined at three different time intervals. We found that the cytotoxic effect of eluted drugs depended on their concentration and the time interval, with even the lowest dose of each drug demonstrating an acceptable rate of cytotoxicity. Even in low doses, cytotoxic drugs mixed with polymethylmethacrylate cement could therefore be considered as effective local adjuvant treatment for GCTs

Introduction and Objectives: Giant cell tumour (GCT) of the bone is an “aggressive tumor characterized by highly-vascularized tissue consisting of ovoid or fusiform cells and the presence of numerous gigantic osteoclast-like cells distributed uniformly throughout the tumor tissue” (WHO). The aim of this report is to present our experience over the past 19 years (1983–2002) with GCT of the bone treated in our unit. Materials and Methods: From January 1983 to January 2002, we have treated 67 cases of GCT of the bone, excluding all cases with less than 12 months of follow up. Age at presentation ranged 10 to 17 years. There was a higher incidence from 20 to 40 years of age. There was a moderately higher rate in women compared to men (1.5:1). The most common locations were the distal epiphysis of the femur, proximal epiphysis of the tibia, and the distal end of the radius. This type of tumour generally localises to the epiphysis and subsequently invades the metaphysis. Localization to the axial skeleton is rare. Radiologic diagnosis was achieved by simple local radiology, CT scan, and MRI. Histopathologic diagnosis was done by means of biopsy using a trocar guided by an image intensifier. In cases of central localization, we obtained the sample by CT-guided biopsy. The treatment of choice is aggressive curettage (high-velocity burr) and filling with frozen cancellous chips. Radiation therapy is useful in cases of localization that are not accessible by surgery. Results: GCT of the bone possesses several unique characteristics, which make it different from other intermediate tumors: a high rate of recurrence (up to 50%), the possibility of sarcomatous degeneration, and the possibility of pulmonary metastasis (even in non-malignant cases). We believe the ideal treatment is resection of the bone where the tumour is located (useful on the head of the fibula, distal end of the ulna, ribs, some bones of the hand and feet, and the patella). In view of its usual localization near the knee (50%), our usual treatment is aggressive curettage (high-speed burr) and filling with frozen cancellous chips. We have treated 26 recurrent cases out of 67 patients treated in our unit (38.8%). Of these, approximately 50% were referred from other centres. Treatment of recurrence has generally been aggressive curettage and addition of allografts. Sarcomatous degeneration occurred in 3 cases (4.5%), all of which were high grade sarcomas of the malignant fibrous histiocytoma type. One case survived following amputation of the extremity, and the other 2 cases died as a result of pulmonary metastasis. Discussion and Conclusions: Alternative local treatment methods exist for GCT of the bone such as cryosurgery, phenolization, and cementing. However, we cannot comment on these methods due to a lack of experience with them. The aim of all these methods is to cauterize the tumour bed. We prefer aggressive curettage and filling with cancellous bone in an attempt to use a more biological treatment

Introduction. Local recurrence of Giant cell tumours of bone (GCT) is considered the main complication of surgical treatment (50%). Intra-lesional curettage with adjuvants like phenol or polymethylmethacrylate (PMMA) is recommended as initial treatment, decreasing the risk of recurrence. However, risk factors for local recurrence in skeletal GCT have not yet been firmly established and a golden standard for treatment remains controversial. Aim of this study is identification of risk factors for recurrence in GCT, specifically after intra-lesional curettage with or without adjuvants. Methods. In a retrospective single-institution study 191 patients treated for GCT between 1964 and 2009 were included. Mean follow-up was 111 months (range 12-415). The recurrence-free survival and hazards for different treatment strategies and various patient and tumour characteristics were determined. Results. Overall risk of recurrence was 36.1% (n=66, 95% CI: 28.3-42.1). Recurrence rate after wide resection was 20%, after curettage with adjuvants 33% and after curettage alone 77%. Hogendoorn-grade III (Hazard Ratio: 5.7, p⋋0.001), localisation in axial skeleton (HR: 3.7, p⋋0,001), primary treatment in a non-specialised centre (HR: 2.8, p⋋0.001) and extension into soft tissue (HR: 2.0, p=0.02) were significant risk factors for local recurrence. Curettage with adjuvants proved superior to curettage alone (p⋋0.004 p=0.07, HR: 0.54), but the application of both PMMA and phenol did not present a significantly better outcome than PMMA alone (HR: 1.07, p=0.9). Discussion. Of all possible risk factors only soft tissue extension and localisation in distal radius significantly influenced the risk of local recurrence for all treatments. We found that high-grade tumours and localisation in the axial skeleton were additional risk factors for local recurrence after intra-lesional surgery. Although wide resection increases morbidity, it can be the therapy of choice in high risk patients. Intra-lesional therapy can be advised for low risk patients using curettage adjuvants and PMMA

Aim: To investigate the outcome of our management of patients with giant cell tumour of the sacrum and draw lessons from this. Method: Retrospective review of medical records and scans for all patients treated at our unit over the past 20 years with a giant cell tumour (GCT) of the sacrum. Results: Of 517 patients treated at our unit for GCT over the past 20 years, only 9 (1.7%) had a GCT in the sacrum. 6 were female, 3 male with a mean age of 34 (range 15–52). All but two tumours involved the entire sacrum and there was only one purely distal to S3. The mean size was 10cm and the most common symptom was back or buttock pain. Five had abnormal neurology at diagnosis but only one presented with cauda equina syndrome. The first four patients were treated by curettage alone but two patients had intra-operative cardiac arrests and although both survived all subsequent curettages were preceeded by embolization of the feeding vessels. Of 7 patients who had curettage, 3 developed local recurrence but all were controlled with a combination of further embolisation, surgery or radiotherapy. One patient elected for treatment with radiotherapy and another had excision of the tumour distal to S3. All the patients are alive and only two patients have worse neurology than at presentation, one being impotent and one with stress incontinence. All are mobile and active at a follow up between 2 and 21 years. Conclusion: GCT of the sacrum can be controlled with conservative surgery rather than sacrectomy. Embolisation and curettage are the preferred first option with radiotherapy as a possible adjunct. Spino-pelvic fusion may be needed if the sacrum collapses

Introduction and Aims: The treatment of Giant Cell Tumor (GCT) of bone ranges from resection to intra-lesional excision. The latter procedure preserves the joint and function. The purpose of this paper is to review functional and oncological outcomes for GCT treated by intralesional excision. Method: The medical records including radiology and pathology of 40 consecutive patients with GCT were retrospectively reviewed. Demographics, complications, tumor local control were determined. Functional evaluation using the MSTS system was performed on 23 patients. The data was subject to statistical analysis. Results: Forty patients (19M/21F). Mean age 28 years. Sites: femur 17, tibia 14, radius five, other four. Mean follow-up 90.3 months (26–178). Functional outcome: 93.2% (50–100). Complications: DJD two, fracture one. Recurrence: five (12.5%). Recurrence sites: Tibia two, femur one, radius one, and talus one. Recurrence treatment: 1/5 resection, 4/5 repeat intralesional excision. Recurrence outcome: 5/5 NED (mean 58.2 months). Conclusion: GCT treated by intralesional excision had excellent functional and oncological outcomes. The joint was preserved in most patients (95%) except due to recurrence 1 and fracture 1. The recurrences were successfully treated by repeat excision in 4/5 patients. Intralesional excision should be considered the preferred treatment for most giant cell tumors

Introduction: Tumours of sacrum are rare. Treatment depends on malignancy or local aggressiveness: resection is indicated for malignant lesions, intralesional surgery for benign. Purpose of this study was to analyse risk of infection and its treatment after surgery for the two most common primary sacral tumours. Material and Methods: Between 1976 and 2005, 82 patients with sacral chordoma or giant cell tumour were treated in our Institution. Demographic data, surgery and adjuvant treatments were analysed in the two histotypes. All patients were periodically checked with imaging studies. Special attention was given to the assessment of deep infections, their treatment and outcome. Patients included 44 females and 38 males, ranging in age from 14 to 74 years. Mean follow-up was 9.5 years (min. 3, max. 27). Histopathological findings included chordomas in 55 cases and giant cell tumor (GCT) in 27. Most pts. had iv antibiotic therapy with amikacin and teicoplanin. Surgery of chordoma was resection, surgery of GCT was intralesional excision. In 6 sacral resections a miocutaneous transabdominal flap of rectus abdominis was used for posterior closure. Results: No deep infections were observed in the GCT series. Three patients with sacral chordoma died for postoperative complications and were excluded from this analysis. Of the remaining 52 patients with chordoma, 23/52 had deep wound infection (44%), that required one or more additional operative procedures. In 16 pts. (70%) infection occurred within 4 weeks postoperatively, in 7 within 6 months. Most frequent bacteria causing infection were Enterococcus (23%), Escherichia Coli (20%), Pseudomonas Aeruginosa (18%). In 74% of cases a multiagent infection was detected. Surgical treatment consisted in 1 (52%) or more (48%) surgical debridements, combined with antibiotics therapy according to coltural results. Mean surgical time was 14 hours for resections and 6 hours for excisions. No significant difference was found comparing deep wound infections with levels of resection (15/33 resections proximal to S3-45% and 8/19 resections below or at S3-42%), previous intralesional surgery elsewhere (4/9 patients previous treated elsewhere-44% and 19/46 primarily treated patients-41%) and age at surgery. Conclusions: Type of surgery was the prominent factor related with a major risk of infection. Operating procedure time correlated as well. Resection of sacral chordomas with wide margins improves survival although extensive soft-tissue resection in proximity to the rectum favours deep infections. Intralesional excision is the recommended surgical treatment for GCT of the sacrum and does not imply a significant risk of infection

The February 2014 Oncology Roundup. 360 . looks at: suspicious lesions; limb salvage in pelvic sarcomas; does infection affect oncological survival?; cancer patient pathways; radiological arthritis with cement augmentation in GCT; and post-chemotherapy increase in tumour volume as a predictor of poor prognosis

Aims

The aim of this study was to determine the rate of indocyanine green (ICG) staining of bone and soft-tissue tumours, as well as the stability and accuracy of ICG fluorescence imaging in detecting tumour residuals during surgery for bone and soft-tissue tumours.

Background: Giant-cell tumour (GCT) of bone is a benign but aggressive tumour, usually treated by radical surgical curettage. Surgical treatment of GCT involving the ischium is associated with a high local recurrence rate. We describe a case in which serial arterial embolisation and bisphosphonate treatment resulted in radiological healing of the tumour. So far we have avoided surgical treatment. Case Report: A 40-year-old lady was referred to the bone tumour unit following a fall. A plain radiograph of the pelvis revealed a lytic lesion in the ischium, extending into the posterior column of the acetabulum and associated with a pathological fracture. Biopsy confirmed a diagnosis of GCT. Given the anatomic location, the tumour was treated with serial arterial embolisation and intravenous zoledronate infusions. Follow up at one-year shows healing of the lesion, with no radiological evidence of recurrence. The patient has so far avoided surgery. Discussion: Serial arterial embolisation has been described in the treatment of giant cell tumours in anatomical regions where surgery is likely to be associated with significant morbidity, such as the sacrum. There is a sound theoretical basis for the use of bisphosphonates in this disease; they have been shown to cause apoptosis of the osteoclast-like giant cells and interfere with osteoclast recruitment. As far as we are aware this is the first case described in which embolisation and bisphosphonate treatment appears to have led to healing and stabilisation of the lesion. The durability of this response remains uncertain

Background. Giant cell tumours of bone (GCT) are benign bone tumours with a locally aggressive character. Local recurrence is considered the main complication of surgical treatment and is described in up to 50% of patients. Intralesional curettage with the use of adjuvants like phenol or polymethylmetacrylate (PMMA) is recommended as initial treatment, significantly decreasing the risk of recurrence. However, risk factors for local recurrence in skeletal GCT have not yet been firmly established and a golden standard for local therapy remains controversial. Objective. The identification of risk factors predisposing for an increased risk of local recurrence. In addition, different surgical techniques are compared to identify the optimal surgical approach for the identified risk factors. Methods. In a retrospective study all 215 patients with bone GCT treated between 1964 and 2009 in one centre were included, of which 193 were suitable for analysis. All patients had minimal follow-up of 12 months (mean 115; range 12–445). Using a Kaplan Meier survival analysis recurrence free survival rates were calculated. Cox-regression was used to determine the influence of different types of therapy, the use of adjuvants, and various patient and tumour characteristics. Results. The mean local recurrence rate for all patients was 35.2% (n=68, 95%CI: 28.3–42.1). Recurrence rate after wide resection was 0.17 (n=6, 95%CI: 0.04–0.29), after curettage with adjuvants 0.32 (n=42, 95%CI 0.24–0.41) and after curettage alone 0.74 (n=20, 95%CI: 0.57–0.91, p < 0.001). Soft tissue extension (Hazard Ratio: 3.8, p < 0.001), localisation in radius and ulna (HR: 2.6, p=0.013), and surgical experience (HR: 2.2, p=0.022) were identified as significant general risk factors for local recurrence. For intralesional resection, Campanacci grade III (HR: 3.9, p=0.019) and location in axial skeleton (HR: 3.3, p=0.016) additionally significantly increased this risk. Comparing treatments our data showed that curettage followed by adjuvants was superior to curettage alone (p < 0.004), and the application of both phenol and PMMA did not present a significantly better outcome than curettage and PMMA alone (HR: 1.07, p=0.881). Conclusion. Of all possible risk factors only soft tissue extension, localisation in radius and ulna and non-radical resections significantly influenced the risk of local recurrence for all treatments. In addition, we found that high-grade tumours and localisation in the axial skeleton were additional risk factors for local recurrence after intralesional surgery. Although wide resection increases patient morbidity, it can be the therapy of choice in high risk patients. Intralesional therapy can be advised for low recurrence risk patients using curettage and PMMA only, whereas our study could not confirm the predicted effect of phenol as an additional adjuvant

Objective. was to review the experience of the Rizzoli with megaprosthetic reconstruction of the extremities in musculoskeletal oncology. Material and methods. Between April 1983 and December 2007, 1036 modular uncemented megaprostheses of the lower limbs were implanted in 605 males and 431 females: 160 KMFTR(r), 633 HMRS(r) prostheses, 68 HMRS(r) Rotating Hinge and 175 GMRS(r). Sites: distal femur 659, proximal tibia 198, proximal femur 145, total femur 25, distal femur and proximal tibia 9. Histology showed 612 osteosarcomas, 113 chondrosarcomas, 72 Ewing's sarcoma, 31 metastatic carcinomas, 89 GCT, 36 MFH,68 other diagnoses. Between 1975 and 2006 at Rizzoli 344 reconstructions of the humerus using prosthetic devices (alone or in association with allografts) were performed: 289 MRS(r), 37 HMRS(r), 2 Osteobridge(r), 4 composite prostheses, 8 Coonrad-Morrey(r), 4 custom made prostheses. Sites of reconstruction were: proximal humerus 311, distal humerus 19, diaphysis 5, total humerus 9. Histology showed 146 osteosarcomas, 56 chondrosarcomas, 23 Ewing's sarcoma, 67 metastatic carcinomas, 14 GCT, 10 MFH, 28 other diagnoses. Patients were followed periodically in the clinic. Information were obtained from clinical charts and imaging studies with special attention to major complications requiring revision surgery. Major prostheses-related complications were analysed and functional results evaluated according to the MSTS system. Univariate analysis by Kaplan-Meier actuarial curves was used for studying implant survival to major complications. Results. Major complications causing implants failure in lower limbs were 80 infections (7.7%), 64 aseptic loosening (6.2%) and 33 breakages (3.2%). In lower limbs infection occurred in 18 KMFTR(r), 47 HMRS(r), 5 HMRS(r) Rotating Hinge, 10 GMRS(r). Breakage of the prosthetic reconstruction occurred in 16 KMFTR(r), 16 HMRS(r), 1 HMRS(r) Rotating Hinge. Aseptic loosening occurred in 15 KMFTR(r), 28 HMRS(r), 18 HMRS(r) Rotating Hinge, 3 GMRS(r). Major complications causing implants failure in upper limbs were 15 infections (4.3%), 8 aseptic loosening (2.3%) and 4 breakages (1.2%). In upper limbs infection occurred in 14 MRS(r) and 1 Coonrad-Morrey(r). Aseptic loosening in 8 cases MRS(r). Breakage in 4 cases MRS(r) prostheses. Most patients in both lower and upper extremities series showed satisfactory function (good or excellent) according to the MSTS evaluation system. Implant survival to all major complications of lower limb megaprostheses evaluated with Kaplan-Meier curve was 80% at 10 years and 60% at 20 years. Implant survival for the newer designs (GMRS(r)) available only at middle term follow up showed an implant survival to major complications at about 90% at 5 years. Implant survival to all major complications was over 80% at 10 years and 78% at 20 years. Conclusions. Megaprostheses are the most frequently used type of reconstruction after resection of the extremities, since they provide good function and a relatively low incidence of major complications. Both function and implant survival improved in the last decades with the introduction of newer designs and materials

Aims

This study aimed to analyze the accuracy and errors associated with 3D-printed, patient-specific resection guides (3DP-PSRGs) used for bone tumour resection.

The August 2023 Knee Roundup³⁶⁰ looks at: Curettage and cementation of giant cell tumour of bone: is arthritis a given?; Anterior knee pain following total knee arthroplasty: does the patellar cement-bone interface affect postoperative anterior knee pain?; Nickel allergy and total knee arthroplasty; The use of artificial intelligence for the prediction of periprosthetic joint infection following aseptic revision total knee arthroplasty; Ambulatory unicompartmental knee arthroplasty: development of a patient selection tool using machine learning; Femoral asymmetry: a missing piece in knee alignment; Needle arthroscopy – a benefit to patients in the outpatient setting; Can lateral unicompartmental knees be done in a day-case setting?

Aims

The aim of this study was to investigate the feasibility of application of a 3D-printed megaprosthesis with hemiarthroplasty design for defects of the distal humerus or proximal ulna following tumour resection.

Aims

Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone.

Aim. Improving the quality of clinical and radiologic differential diagnosis of intramedullary tumours of long bones. Methods. A database includes clinical and radiologic (X-ray, CT and MRI methods) signs of 106 patients with osteosarcoma (n = 44), chondrosarcoma (n = 31) and giant cell tumour (n = 31). Multivariate analysis of clinical and radiologic characteristics and developing informative set of criteria (decision rule) for the differential diagnosis of osteosarcoma, chondrosarcoma and giant cell tumour were provided with program «ASTA». Results. Before examination in Blokhin Oncology Research Centre in 70% of the osteosarcomas and chondrosarcomas and 60% of GCTs the size of the tumour was more than 8 cm. The reason of the late patients' admission to a specialized medical department is inaccurate diagnosis of these tumours. In our study diagnostic accuracy of the differential diagnosis of osteosarcoma, chondrosarcoma and GCT was 89% in case if the decision rules were based on 14 the most informative clinical and X-ray features, 84% if based on 14 clinical and CT features and 88% if based on 9 MRI features. The comparative analysis revealed a high accuracy in determination of these tumours by using decision rules developed on the basis of multivariate analysis of clinical and X-ray criteria. Conclusion. The comparative accuracy of the developed differential diagnostic criteria (decision rules) of clinical and X-ray, clinical and CT and MRI features proved high informative of each method. The diagnostic accuracy of clinical and X-ray decision rule (89%) exceeded the diagnostic accuracy of radiologist's examination before (62%) and after (83%) admission to Oncology Centre. It proves the necessity for further development and practical application of diagnostic expert systems

Aim. To study the efficacy of Zoledronic acid in the treatment of benign osteolytic tumours or tumour like conditions of bone as a therapeutic or as an adjuvant agent. Method. 31 patients- 19 female, 12 male, age from 8 yrs to 42 yrs, were treated with intravenous zoledronic acid. In 17 patients (fibrous dysplasia-10, nonossifying fibroma- 4, UBC- 3) zoledronic acid alone was used as a therapeutic agent. In 14 patients (ABC- 3, GCT- 11), it was used as an adjuvant agent after curettage. Four patients presented with pathological fracture. In all patients, 4 mg. zoledronic acid was given at 2 monthly intervals. In 12 adult patients, in addition oral bisphosphonates - alendronate was given weekly for at least 6 months. Results. Patients were evaluated using visual analog pain scale and x-rays. At last follow-up (6-40 months), in 15 patients, treated with zoledronic acid alone, there was thickening of cortices and reduction in the size of the lesion. Pain score decreased from an average of 8 to 2. All four fractures healed. In 2 patients, there was progression in size of the lesion. In 14 patients, where it was used as an adjuvant agent, there was early thickening of bone cortices. There was no local recurrence in this group. There was no adverse reaction to the drug in any of the patient. Conclusion. Zoledronic acid is a third generation bisphosphonates and a proven anti-osteolytic agent. It has proved effective in the treatment of number of osteolytic conditions. Our study also suggests that Zoledronic acid not only help to stabilize these lesions but also resulted in pronounced healing in majority of the patients. It also reduced recurrence rate in aggressive benign bone tumours such as ABC or GCT when used as an adjuvant treatment

Giant-cell tumour of bone (GCT) is a locally benign aggressive tumour. The use of adjuvant agents, such as phenol or liquid nitrogen has been recommended to destroy the remaining tumour cells after curettage, and filling of the defect with methylmethacrylate cement has been advocated. Between 1957 and 1992 we treated 92 patients with a GCT with 50% aqueous zinc chloride solution and bone grafting. Their mean age at the time of surgery was 31 years (15 to 59) and the mean follow-up was 11 years (5 to 31). Twelve (13%) had a local recurrence and one had a wound infection. Two developed degenerative changes around the knee. Eighty-six (93%) achieved good or excellent function. Three had moderate function, and three needed amputation. Our findings indicate that treatment with an aqueous solution of zinc chloride and reconstructive bone grafting after curettage gives good results

Objectives: To analyse functional outcome of giant cell tumor (GCT) distal radius treated with en bloc excision and reconstruction with ulnar translocation and wrist arthrodesis. Methods: Between June 2005 and March 2008 fourteen patients of Campanacci grade 3 GCT distal radius treated with en bloc excision were reconstructed with ulnar translocation (radial transposition of ulna) and wrist arthrodesis. Seven (50%) patients had recurrent disease. Average resection length was 7.9 cm (range 5.5cm–15 cm). Twelve cases were fixed with a plate and in 2 an intramedullary nail was used. Union at both junctions was evaluated and functional assessment done using MSTS score. Results: All 14 patients had followed up till bony union. Eleven patients were available at time of final review with an average follow up of 24.5 months (range 13–48 months). Average time for union at ulnocarpal junction was 4 months and ulnoradial junction was 5 months. No case required any additional procedure to augment union. Three cases had a soft tissue recurrence and one had pulmonary metastasis. Average range of prono supination was 80 degrees, one patient with synostosis had complete restriction of prono supination. Average MSTS Score at last follow up was 26 (86.6%). Conclusions: Ulnar translocation provides a local vascularised bone graft to bridge the defect after excision of distal end radius tumors without the need for microvascular procedures. Unlike centralization of the ulna it retains prono supination while maintaining good hand function