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.
Myxofibrosarcoma (MFS) is the second most common subtype of soft tissue sarcoma (STS) and is associated with a high rate of local recurrence after resection. These tumours frequently present with peri-lesional edema, termed “tumour tails” on staging MRI scans [1]. Tumour tails(TT) may contain satellite neoplastic cells or can represent benign reactive edema. There are no clear radiological features to distinguish malignant from reactive peri-lesional edema which limits accurate surgical planning, resulting in either high rates of inadvertently positive resection margins and local recurrences or overly-aggressive resections which negatively impact function and increase morbidity [2]. The objective of this pilot study was to prospectively study a cohort of MFS patients with TTs in an attempt to identify radiological features that predict which type of edema is malignant and requires resection together with the main tumour mass. Patients diagnosed with MFS on biopsy at an orthopaedic oncology referral centre between January 1-December 31 2018 who also had TTs on staging MRI scans were prospectively recruited for the study. Tumours were treated with wide surgical excision, including the TTs, and (neo)adjuvant radiotherapy as per institutional protocol. Staging MRI scans were reviewed in a blinded fashion by two musculoskeletal radiologists to distinguish malignant from reactive TTs. The main tumour mass underwent standard histological evaluation while the regions encompassing the TTs were photographed and sectioned into grids. Each tissue section was examined histologically for the presence of satellite neoplastic cells based on morphological criteria. Radiological and histological findings were compared. Six patients met the inclusion criteria and underwent analysis. All tumours were located in the extremities and were deep to fascia. Mean age at presentation was 67 years (range 51 – 85), with a male:female ratio of 4:2. All patients received radiotherapy (50 Gy), either pre- (n=4) or post-operatively (n=2) based on multidisciplinary tumor board discussion or enrolment in a prospective clinical trial. Radiologically, TTs were labelled as malignant in four patients (66.7%) and as benign TTs in two others. The tails were recognised to be malignant due to the differing signal characteristics to reactive edema on mixed MRI sequences. The radiological evaluation correlated exactly with histological analysis, as satellite neoplastic cells were identified microscopically in the same four cases in which the TTs were designated to be malignant by MRI (specificity&sensitivity=100%). Surgical resection margins were microscopically positive in 50% of cases in the TTs themselves, and 75% of cases in which TTs were designated as malignant on staging MRI. “The malignant nature of peri-lesional edema in MFS, also known as the TT, was accurately predicted in this small pilot study based on specific radiological features which correlated exactly with histologic identification of isolated tumor cells. These findings validate development of a larger prospective study to recruit additional patients with tumor tails beyond just MFS, in order to more robustly study the correlation between the MRI appearance and histological distribution of satellite sarcoma cells in peri-lesional edema in STS. We are already recruiting to this expanded radiological-histological investigation including evaluation of additional novel MRI sequences.
Myxoid or Myxoid Round Cell liposarcoma (MLS) is a mesenchymal malignancy with adipocyte differentiation accounting for 15–20% of liposarcomas and 5% of all adult soft tissue sarcomas (STS). Like other STS, treatment of MLS is generally by wide surgical resection in conjunction with radiotherapy and this approach is associated with low rates of local recurrence [1]. However, most MLS are located between muscles so wide local excision(WLE) can be quite morbid with adverse functional results. MLS are known to be extremely sensitive to radiotherapy which has led to development of treatment protocols utilizing neoadjuvant radiation. Given the radiosensitivity of MLS, we hypothesize that resection with marginal margins (1mm) does not result in higher rates of local recurrence or disease-free survival if performed following pre-operative radiotherapy. We identified all patients with localized MLS who underwent preoperative radiation and surgical resection between January 2000 and January 2018 from a prospectively collected sarcoma database. We calculated the ellipsoid tumour volume(ETV=h x w x d x ()) at diagnosis and after radiation, and documented the necrosis percentage of the tumour and margin status following resection based on histological analysis [2]. Marginal resection was identified by the operative report describing no or only very minimal resection of muscle surrounding the tumour, and a negative surgical margin 0.1cm/1mm as defined histologically. In comparison, WLE was defined if the operative note described an attempt to remove the tumour with a cuff of surrounding muscle, and the final histology reported a negative margin 0.1cm/1mm which included skeletal muscle. The third group for analysis included patients with positive resection margins. There were 91 patients with MLS of mean age 48 years (range 18–88) with 69% male and 31% female. The mean pre-radiotherapy ETV was 507cm3(16.1cm3 to 6961cm3) and decreased to 361cm3(8.7cm3 to 5695cm3) following radiation, with an average percentage reduction in ETV of −45%(+129%to-99%). Mean patient follow-up was 7.3 years (0.2–18) with no differences between margin groups(p=0.284). Only 10(11%) patients had positive margins, of which 43(47%) underwent marginal resection and 38(42%) WLE. Overall the mean necrosis as measured histologically following preoperative radiation was 69% (range 0–100%) with no differences between the 3 resection groups(p-0.151). Similarly, there was no significant difference in reduction in mean ETV between the three resection groups(p=0.311), there was no significant difference between the three treatment groups in 5-year LR-free survival (p=0.469), metastasis-free survival (p=0.841) or overall survival (p=0.873). Most patients with MLS experienced significant reduction in tumour size and necrosis following preoperative radiation. We found no differences in the risk of local recurrence or survival based on the type of surgical approach for patients with MLS. Based on these results, we conclude that MLS can be safely removed by marginal resection following preoperative radiotherapy with high rates of local tumour control. Even following a positive margin resection, local recurrence remains uncommon after preoperative radiation. A marginal surgical approach for patients with MLS reduces the need for major muscle resection and is associated with improved functional outcomes with less complications.
Paediatric bone sarcomas around the knee are often amenable to either endoprosthetic reconstruction or rotationplasty. Cosmesis and durability dramatically distinguish these two options, although patient-reported functional satisfaction has been similar among survivors. However, the impact on oncological and surgical outcomes for these approaches has not been directly compared. We retrospectively reviewed all wide resections for bone sarcoma of the distal femur or proximal tibia that were reconstructed either with an endoprosthesis or by rotationplasty at our institution between June 2004 and December 2014 with a minimum two year follow-up. Pertinent demographic information, surgical and oncological outcomes were reviewed. Survival analysis was performed using the Kaplan-Meier method with statistical significance set at p<0.05. Thirty eight patients with primary sarcomas around the knee underwent wide resection and either endoprosthetic reconstruction (n=19) or rotationplasty (n=19). Groups were comparable in terms of demographic parameters and systemic tumour burden at presentation. We found that selection of endoprosthetic reconstruction versus rotationplasty did not impact overall survival for the entire patient cohort but was significant in subgroup analysis. Two-year overall survival was 86.7% and 85.6% in the endoprosthesis and rotationplasty groups, respectively (p=0.33). When only patients with greater than 90% chemotherapy-induced necrosis were considered, overall survival was significantly better in the rotationplasty versus endoprosthesis groups (100% vs. 72.9% at two years, p=0.013). Similarly, while event-free survival was not affected by reconstruction method (60.2% vs. 73.3% at two years for endoprosthesis vs rotationplasty, p=0.27), there was a trend towards lower local recurrence in rotationplasty patients (p=0.07). When surgical outcomes were considered, a higher complication rate was seen in patients that received an endoprosthesis compared to those who underwent rotationplasty. Including all reasons for re-operation, 78.9% (n=15) of the endoprosthesis patients required a minimum of one additional surgery compared with only 26.3% (n=5) among rotationplasty patients (p=0.003). The most common reasons for re-operation in endoprosthesis patients were wound breakdown/infection (n=6), limb length discrepancy (n=6) and periprosthetic fracture (n=2). Excluding limb length equalisation procedures, the average time to re-operation in this patient population was 5.6 months (range 1 week to 23 months). Similarly, the most common reason for a secondary procedure in rotationplasty patients was wound breakdown/infection, although only two patients experienced this complication. Average time to re-operation in this group was 23.8 months (range 5 to 49 months). Endoprosthetic reconstruction and rotationplasty are both viable limb-salvage options following wide resection of high-grade bony sarcomas located around the knee in the paediatric population. Endoprosthetic reconstruction is associated with a higher complication rate and may negatively impact local recurrence. Study of a larger number of patients is needed to determine whether the reconstructive choice affects survival.
Ewing Sarcoma is the second most common primary bone sarcoma in young patients, however, there remains geographical variation in the treatment of these tumours. All patients receive neoadjuvant chemotherapy and, in most cases, the soft tissue mass diminishes significantly in volume. Controversy surrounds whether to then treat the pre- or post-chemotherapy tumour volume. Many centres advocate either (1) resection of the pre-chemotherapy volume or (2) treatment of the pre-chemotherapy volume with radiation followed by resection of the post-chemotherapy volume. These approaches increase both the short and long-term morbidity for this young patient population. In this study, we retrospectively reviewed our experience resecting only the post-chemotherapy volume without the use of (neo)adjuvant radiotherapy. A retrospective analysis of all patients with Ewing Sarcoma treated at a tertiary orthopaedic oncology centre was conducted. All patients were treated as per the consensus opinion of the multidisciplinary tumour board. Demographic and oncological variables were collected from our institutional database. Presentation and re-staging MRI scans were reviewed to evaluate pre- and post-chemotherapy tumour volumes. Operative and pathology reports were utilized to determine the extent of the surgical resection. Outcome variables included local recurrence free-, metastasis free- and overall survival. Sixty-five patients were identified in our institutional database of which 56 did not receive (neo)adjuvant radiotherapy. Median age at diagnosis was 24 years (range 13–64), 60% of patients were male and 67.6% of tumours were located in the appendicular skeleton. All 56 patients not treated with radiotherapy had resection of the post-chemotherapy tumour volume. There were 3 local recurrences in this group with a mean follow-up of 70.8 months (range 2 to 328). The median overall survival was 47 months and the mean of 70.8months. The rate of local recurrence is comparable to reports in the literature in which patients had their entire pre-chemotherapy tumour volume treated by radiation and/or surgery. Similarly, two-year overall survival for our patient cohort is not significantly different from previous studies in which more aggressive local control measures were employed. Resecting the post-chemotherapy tumour volume in Ewing Sarcoma without the use of (neo)adjuvant radiotherapy does not appear to increase the risk of local recurrence or negatively impact overall survival. This approach should be studied further as it reduces the risk of short and long-term complications for this patient population.”
Sixty eight consecutive patients underwent proximal humeral replacement with a fixed fulcrum massive endoprosthesis, for tumour, between 1997 and 2007. The mean age was 46 years, (7–87). Ten patients were lost to follow up and 16 patients died. The 42 surviving patients were assessed using the Musculoskeletal Tumour Society (MSTS) Score and the Toronto Extremity Salvage Score (TESS). The mean MSTS score was 72.3% and the mean TESS was 77.2%. Four of 42 patients received a new constrained humeral liner to reduce the risk of dislocation. This sub group of 4 patients had a mean MSTS score of 77.7% and a mean TESS of 80.0%. Endoprosthetic replacement for tumour of the proximal humerus using this prosthesis is a reliable operation yielding good functional results without the documented problems of unconstrained prostheses. The performance of this prosthesis is expected to improve further with the new constrained humeral liner.
The surgical treatment of bone tumours can result in large perioperative blood loss due to their large sizes and hypervascularity. Preoperative embolisation has been successfully used to downgrade vascularity, thus reducing perioperative blood loss and its associated complications. Prior to embolization era, blood loss as high as 18,500mL have been reported peri-opratively. Twenty-six patients with a variety of bone tumours (average size 10.5×7.5×5.5cm), who underwent pre-operative embolisation between 2005 and 2009, were retrospectively studied. The group comprised of 17 females and 9 males. Their mean age was 38 years old. All patients underwent surgical resection within 48 hours of embolization. Mean blood loss was 796mL and required on average 1.1units of blood. We experienced no complications. Pre-operative arterial embolisation of large, richly vascular bone tumours in anatomically difficult positions, is a safe and effective method of downstaging vascularity and reducing blood loss.
The aim of this study is to investigate whether MoM implants result in more chromosome aberrations and increased blood metal ions postoperatively whe compared to MoP implants. MoM arthroplasties are being inserted in increasing numbers of younger patients due to the increased durability and reduced requirements for revision in these implants. Recent studies have raised many concerns over possible genotoxicity of MoM implants. This is a prospective study of patients who have undergone elective total hip replacement, they were selected and then randomised into two groups. Group A received a MoP implant and group B received a MoM implant. Patients are reviewed pre-operatively (control group), at 3 months, 6 months, 1 year and 2 years post-operatively. On each occasion blood tests are taken to quantify metal ion levels (chromium, cobalt, titanium, nickel and vanadium) using HR-ICPMS method and chromosome aberrations in T lymphocytes using 24 colour fluorescent in situ hydridisation (FISH). 51 patients have been recruited to date, 23 of whom had MoP prosthesis and 28 a MoM. 47 of these had their 1 year follow-up with blood analysis and 38 have had 2 year follow up. There appeared to be a bedding period for both MoM and MoP groups, with an increase in metal ion release. The blood concentration of chromium, cobalt and titanium rise significantly in the MoM group at the 2 year stage. Chromosome aberrations occurred in both groups. Both the MoM and MoP groups showed increase frequency of aneuploidy aberrations and structural damage. The greatest increase in metal ion levels occurred at the 1 to 2 year interval corresponding to significant rise in chromosome aberrations. Preliminary results of this study show that the levels of chromium, cobalt and titanium are significantly higher in the MoM group compared to the MoP group. This corresponds to increases in chromosome aberrations in the groups with increases in structural chromosome damage after two years.
Articular cartilage implantation (ACI) and associated procedures (MACI = Matrix-assisted cartilage implantation) are now established treatments for osteochondral defects in the knee. The quality of repair in terms of histological appearance is frequently not known, whilst the correlation of histology results with functional outcomes remains undefined. Histological data of the quality of the repair tissue is sparse and a precise classification proved difficult. This was a single-centre, prospective study. Over 12 years (1998-2010) 406 patients that underwent articular cartilage implantation procedures at our institution (ACI = 170, MACI = 205) had biopsies taken at the 1-2 year interval, in order to assess whether these contained ‘hyaline-like’ cartilage, ‘mixed hyaline-like with fibrocartilage’, fibrocartilage or fibrous tissue alone. Histological sections of the biopsies were prepared and stained with haematoxylin, eosin and proteoglycan stains and viewed under polarised light. All biopsies were studied by a single histopathologist in a specialist, dedicated musculoskeletal laboratory. All patients were assessed by the Cincinnati, Bentley and Visual Analogue scores both pre-operatively and at the time of the review. The findings revealed that 56 patients healed with ‘hyaline-like’ cartilage (14.9%), 103 with ‘mixed’ (27.5%), 179 with fibrocartilage (47.7%) and 37 with fibrous tissue (9.9%). These findings showed that 42.4% of defects were filled with ‘hyaline-like’ or ‘mixed’ cartilage, with 70% of these achieving a ‘fair’ to ‘excellent’ functional outcome. This was also observed in the fibrocartilage group, where 72% achieved similar results. Predictably 89% of the patients that healed by fibrous tissue had a poor functional outcome. This study shows that 71% of patients whose osteochondral defects healed by either ‘hyaline-like’, ‘mixed’ or fibrocartilage experienced an improvement in the function. In contrast, only 11% of the patients whose defects filled with fibrous tissue, showed some functional improvement. Additionally, this data indicates the advantage of biopsies in assessing the overall results of cartilage implantation procedures.
Sixty eight consecutive patients underwent proximal humeral replacement with a fixed fulcrum massive endoprosthesis for tumour between 1997 and 2007. The mean age was 46 years (7-87). Ten patients were lost to follow up and 16 patients died. The 42 surviving patients were assessed using the Musculoskeletal Tumour Society (MSTS) Score and the Toronto Extremity Salvage Score (TESS). The mean MSTS score was 72.3 % and the mean TESS was 77.2 %. Four of 42 patients received a new constrained humeral liner to reduce the risk of dislocation. This sub group of 4 patients had a mean MSTS score of 77.7 % and a mean TESS of 80.0%. Endoprosthetic replacement for tumour of the proximal humerus using this prosthesis is a reliable operation yielding good functional results without the documented problems of unconstrained prostheses. The performance of this prosthesis is expected to improve further with the new constrained humeral liner.