Endoprosthetic reconstruction for lower extremity soft tissue sarcomas with bone involvement.

BACKGROUND AND OBJECTIVES: Bone resection and endoprosthetic reconstruction (EPR) in the setting of soft tissue sarcoma (STS) management is rare and incurs unique challenges. We aim to report on the surgical and oncological outcomes of this relatively previously undocumented cohort. METHODS: This is a single-center retrospective review of prospectively collected data for patients who required EPRs following resection of STSs of the lower extremity. Following inclusion criteria, we assessed 29 cases of EPR for primary STS of the lower limb. RESULTS: The mean age was 54 years (range 18-84). Of the 29 patients, there were 6 total femur, 11 proximal femur, 4 intercalary, and 8 distal femur EPRs. Fourteen of 29 patients (48%) underwent re-operations for surgical complications, with 9 relating to infection (31%). When a matched cohort analysis was performed comparing our cohort to STSs that did not necessitate EPR, a reduced rate of overall survival and metastasis-free survival was found in those requiring EPR. CONCLUSION: This series identifies a high rate of complication from EPRs performed for STS. Patients should be cautioned about the high rate of infection, surgical complications, and lower overall survival in this setting.

Management of meningeal solitary fibrous tumors/hemangiopericytoma; surgery alone or surgery plus postoperative radiotherapy?

INTRODUCTION: A meningeal solitary fibrous tumor (SFT), also called hemangiopericytoma, is a rare mesenchymal malignancy. Due to anatomic constrains, even after macroscopic complete surgery with curative intent, the local relapse risk is still relatively high, thus increasing the risk of dedifferentiation and metastatic spread. This study aims to better define the role of postoperative radiotherapy (RT) in meningeal SFTs. PATIENTS AND METHODS: A retrospective study was performed across seven sarcoma centers. Clinical information was retrieved from all adult patients with meningeal primary localized SFT treated between 1990 and 2018 with surgery alone (S) compared to those that also received postoperative RT (S + RT). Differences in treatment characteristics between subgroups were tested using independent samples t-test for continuous variables and chi-square tests for proportions. Local control (LC) and overall survival (OS) rates were calculated as time from start of treatment until progression or death from any cause. LC and OS in groups receiving S or S + RT were compared using Kaplan-Meier survival curves. RESULTS: Among a total of 48 patients, 7 (15%) underwent S and 41 (85%) underwent S + RT. Median FU was 65 months. LC was significantly associated with treatment. LC after S at 60 months was 60% versus 90% after S + RT (p = 0.052). Furthermore, R1 resection status was significantly associated with worse LC (HR 4.08, p = 0.038). OS was predominantly associated with the mitotic count (HR 3.10, p = 0.011). CONCLUSION: This retrospective study, investigating postoperative RT in primary localized meningeal SFT patients, suggests that combining RT to surgery in the management of this patient population may reduce the risk for local failures.

Author Correction: Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study.

Since the publication of this paper, the authors noticed an error in Fig. 1. The X-axis on all the figure panels should read 'Time (years)', not 'Time (months)'. The corrected Fig. 1 is shown below.

Epithelioid sarcomas: How important is loco-regional control?

AIMS: To investigate the impact of the method of treatment on the oncological outcomes in patients with epithelioid sarcomas managed at two international speciality sarcoma centres. METHODS: The databases of two centres were used to identify patients treated for epithelioid sarcomas between 1985 and 2012. Patient, tumor, treatment and outcome data was collected. RESULTS: There were 36 males and 18 females with a mean age of 38.3 years (range 9-79). Of 49 patients who were treated surgically, limb salvage surgery was carried out in 38 patients (78%) and limb amputation in 11 (22%). Of 49 total patients who underwent surgery for ES, 48 (98%) with ES had negative margin resection and 24 (49%) received (neo) adjuvant radiotherapy. Regional lymph node metastases developed in 5 (13%) patients. The five-year risk of local recurrence was 14%. The overall survival rate at five and ten years was 70% and 66% respectively. In multivariate analysis of patients with localized disease and negative margins, survival and risk of metastases was worse in those treated by amputation. CONCLUSION: This series has shown that although the rate of local recurrence is not influenced by the type of surgery, the risk of metastases is higher following amputation. This finding is likely due to patients with larger, deeper and more locally advanced tumors requiring amputation. However, we could not prove that immediate amputation was likely to affect overall survival.

Intercalary allograft augmented with intramedullary cement and plate fixation is a reliable solution after resection of a diaphyseal tumour.

AIMS: Intercalary allografts following resection of a primary diaphyseal tumour have high rates of complications and failures. At our institution intercalary allografts are augmented with intramedullary cement and fixed using compression plating. Our aim was to evaluate their long-term outcomes. PATIENTS AND METHODS: A total of 46 patients underwent reconstruction with an intercalary allograft between 1989 and 2014. The patients had a mean age of 32.8 years (14 to 77). The most common diagnoses were osteosarcoma (n = 16) and chondrosarcoma (n = 9). The location of the tumours was in the femur in 21, the tibia in 16 and the humerus in nine. Function was assessed using the Musculoskeletal Tumor Society (MSTS) scoring system and the Toronto Extremity Salvage Score (TESS). The survival of the graft and the overall survival were assessed using the Kaplan-Meier method. RESULTS: The median follow-up was 92 months (4 to 288). The mean MSTS 87 score was 29.1 (19 to 35), the mean MSTS 93 score was 82.2 (50 to 100) and the mean TESS score was 81.2 (43 to 100). Overall survival of the allograft was 84.8%. A total of 15 patients (33%) had a complication. Five allografts were revised for complications and one for local recurrence. CONCLUSION: Intercalary allografts augmented with intramedullary cement and compression plate fixation provide a reliable and durable method of reconstruction after the excision of a primary diaphyseal bone tumour, with high levels of function and satisfaction. Cite this article: Bone Joint J 2017;99-B:973-8.

Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study.

BACKGROUND: An increasing number and proportion of cancer patients with apparently localised disease are treated with chemotherapy and radiation therapy in contemporary oncology practice. In a pilot study of radiation-induced sarcoma (RIS) patients, we demonstrated that chemotherapy was associated with a reduced time to development of RIS. We now present a multi-centre collaborative study to validate this association. METHODS: This was a retrospective cohort study of RIS cases across five large international sarcoma centres between 1 January 2000 to 31 December 2014. The primary endpoint was time to development of RIS. RESULTS: We identified 419 patients with RIS. Chemotherapy for the first malignancy was associated with a shorter time to RIS development (HR 1.37; 95% CI: 1.08-1.72; P=0.009). In the multi-variable model, older age (HR 2.11; 95% CI 1.83-2.43; P<0.001) and chemotherapy for the first malignancy (HR 1.61; 95% CI 1.26-2.05; P<0·001) were independently associated with a shorter time to RIS. Anthracyclines and alkylating agents significantly contribute to the effect. CONCLUSIONS: This study confirms an association between chemotherapy given for the first malignancy and a shorter time to development of RIS.

Patient, tumour and treatment factors affect complication rates in soft tissue sarcoma flap reconstruction in a synergistic manner.

INTRODUCTION: Flap reconstruction plays an essential role in the management of soft tissue sarcoma, facilitating wide resection while maximizing preservation of function. The addition of reconstruction increases the complexity of the surgery and identification of patients who are at high risk for post-operative complications is an important part of the preoperative assessment. This study examines predictors of complications in these patients. METHODS: 294 patients undergoing flap reconstruction following sarcoma resection were evaluated. Data on patient, tumour and treatment variables as well as post-operative complications were collected. Bivariate and multivariate regression analysis was performed to identify independent predictors of complications. Analysis of synergistic interaction between key patient and tumour risk factors was subsequently performed. RESULTS: A history of cerebrovascular events or cardiac disease were found to be the strongest independent predictors of post-operative complications (OR 14.84, p = 0.003 and OR 5.71, p = 0.001, respectively). Further strong independent tumour and treatment-related predictors were high grade tumours (OR 1.91, p = 0.038) and the need for additional reconstructive procedures (OR 2.78, p = 0.001). Obesity had significant synergistic interaction with tumour resection diameter (RERI 1.1, SI 1.99, p = 0.02) and high tumour grade (RERI 0.86, SI 1.5, p = 0.01). Comorbidities showed significant synergistic interaction with large tumour resections (RERI 0.91, SI 1.83, p = 0.02). CONCLUSION: Patient, tumour and treatment-related variables contribute to complications following flap reconstruction of sarcoma defects. This study highlights the importance of considering the combined effect of multiple risk factors when evaluating and counselling patients as significant synergistic interaction between variables can further increase the risk of complications.

The effect of surgical synovectomy and radiotherapy on the rate of recurrence of pigmented villonodular synovitis of the knee: an individual patient meta-analysis.

Pigmented villonodular synovitis (PVNS) is a rare proliferative process of the synovium which most commonly affects the knee and occurs in either a localised (LPVNS) or a diffuse form (DPVNS). The effect of different methods of surgical synovectomy and adjuvant radiotherapy on the rate of recurrence is unclear. We conducted a systematic review and identified 35 observational studies in English which reported the use of surgical synovectomy to treat PVNS of the knee. A meta-analysis included 630 patients, 137 (21.8%) of whom had a recurrence after synovectomy. For patients with DPVNS, low-quality evidence found that the rate of recurrence was reduced by both open synovectomy (odds ration (OR) = 0.47; 95% CI 0.25 to 0.90; p = 0.024) and combined open and arthroscopic synovectomy (OR = 0.19, 95% CI = 0.06 to 0.58; p = 0.003) compared with arthroscopic surgery. Very low-quality evidence found that the rate of recurrence of DPVNS was reduced by peri-operative radiotherapy (OR = 0.31, 95% CI 0.14 to 0.70; p = 0.01). Very low-quality evidence suggested that the rate of recurrence of LPVNS was not related to the surgical approach. This meta-analysis suggests that open synovectomy or synovectomy combined with peri-operative radiotherapy for DPVNS is associated with a reduced rate of recurrence. Large long-term prospective multicentre observational studies, with a focus on both rate of recurrence and function, are required to confirm these findings.

Reconstruction of sarcoma defects following pre-operative radiation: free tissue transfer is safe and reliable.

BACKGROUND: Neoadjuvant radiotherapy followed by surgical resection and soft tissue reconstruction provides the best possibility of achieving superior limb function in soft tissue sarcomas. The aim of this study was to report our experience of free flap microsurgical reconstruction of recently irradiated soft tissue sarcoma defects. METHODS: A retrospective study of microsurgical outcome in consecutively treated extremity and trunk sarcoma patients undergoing free tissue transfer between 2007 and 2012 was conducted from a prospectively collected database. Outcomes in pre-operatively irradiated patients were compared with non-irradiated patients. Demographic data, operative details, limb salvage rate, post-operative including microsurgical complications, and long-term limb function (Toronto Extremity Salvage score, TESS; Musculoskeletal Tumour Society Rating Scale, MSTS) were recorded and analysed for differences between the two study groups. RESULTS: Forty-six patients underwent 46 free flaps (pre-irradiated n = 32, non-irradiated n = 14) over the study period. Microvascular complications (intra-operative revision, flap re-exploration, flap loss) were uncommon and similar between the two groups (4/32 and 2/14 respectively, p > 0.05). Recipient site wound healing complications (i.e. not flap related) occurred more frequently in pre-irradiated patients (16 events) compared with the control group (2 events, p = 0.03). There was no significant difference in limb salvage rate, or TESS/MSTS functional outcome scores between the two patient groups. CONCLUSIONS: Free tissue transfer is safe and effective in patients undergoing surgical resection and reconstruction following neoadjuvant radiotherapy.

Fixation of pathological humeral fractures by the cemented plate technique.

Pathological fractures of the humerus are associated with pain, morbidity, loss of function and a diminished quality of life. We report our experience of stabilising these fractures using polymethylmethacrylate and non-locking plates. We undertook a retrospective review over 20 years of patients treated at a tertiary musculoskeletal oncology centre. Those who had undergone surgery for an impending or completed pathological humeral fracture with a diagnosis of metastatic disease or myeloma were identified from our database. There were 63 patients (43 men, 20 women) in the series with a mean age of 63 years (39 to 87). All had undergone intralesional curettage of the tumour followed by fixation with intramedullary polymethylmethacrylate and plating. Complications occurred in 14 patients (22.2%) and seven (11.1%) required re-operation. At the latest follow-up, 47 patients (74.6%) were deceased and 16 (25.4%) were living with a mean follow-up of 75 months (1 to 184). A total of 54 (86%) patients had no or mild pain and 50 (80%) required no or minimal assistance with activities of daily living. Of the 16 living patients none had pain and all could perform activities of daily living without assistance. Intralesional resection of the tumour, filling of the cavity with cement, and plate stabilisation of the pathological fracture gives immediate rigidity and allows an early return of function without the need for bony union. The patient's local disease burden is reduced, which may alleviate tumour-related pain and slow the progression of the disease. The cemented-plate technique provides a reliable option for the treatment of pathological fractures of the humerus.

Clinical features, treatment, and outcome in 102 adult and pediatric patients with localized high-grade synovial sarcoma.

Background. There remains controversy on the routine use of chemotherapy in localized SS. Methods. The records of 87 adult (AP) and 15 pediatric (PP) patients with localized SS diagnosed between 1986 and 2007 at 2 centres in Toronto were reviewed. Results. Median age for AP and PP was 37.6 (range 15-76) and 14 (range 0.4-18) years, respectively. 65 (64%) patients had large tumours (>5 cm). All patients underwent en bloc surgical resection resulting in 94 (92.2%) negative and 8 (7.8%) microscopically positive surgical margins. 72 (82.8%) AP and 8 (53%) PP received radiotherapy. Chemotherapy was administered to 12 (13.8%) AP and 13 (87%) PP. 10 AP and 5 PP were evaluable for response to neoadjuvant chemotherapy, with response rate of 10% and 40%, respectively. 5-year EFS and OS was 69.3 ± 4.8% and 80.3 ± 4.3%, respectively, and was similar for AP and PP, In patients with tumors >5 cm, in whom chemotherapy might be considered most appropriate, relapse occurred in 9/19 (47%) with chemotherapy, compared to 17/46 (37%) In those without. Conclusions. Patients with localized SS have a good chance of cure with surgery and RT. Evidence for a well-defined role of chemotherapy to improve survival In localized SS remains elusive.

The efficacy of chemical adjuvants on giant-cell tumour of bone. An in vitro study.

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.

Does the method of treatment affect the outcome in soft-tissue sarcomas of the adductor compartment?

We have investigated the significance of the method of treatment on the oncological and functional outcomes and on the complications in 184 patients with soft-tissue sarcomas of the adductor compartment managed at three international centres. The overall survival at five years was 65% and was related to the grade at diagnosis and the size of the tumour. There was no difference in overall survival between the three centres. There was, however, a significant difference in local control with a rate of 28% in Centre 1 compared with 10% in Centre 2 and 5% in Centre 3. The overall mean functional score using the Toronto Extremity Salvage Score in 70 patients was 77% but was significantly worse in patients with wound complications or high-grade tumours. The scores were not affected by the timing of radiotherapy or the use of muscle flaps. This large series of soft-tissue sarcomas of the adductor compartment has shown that factors influencing survival do not vary across the international boundaries studied, but that methods of treatment affect complications, local recurrence and function.

Pseudarthrosis of the middle metacarpal following intramedullary fixation of a wrist arthrodesis.

We describe the case of a 36-year-old woman who presented with an unusual seronegative monoarthropathy of the right wrist and who was treated with fusion by the method of Clayton (1965). The patient probably sustained a metacarpal fracture during intramedullary Steinmann pin insertion, and subsequently developed a pseudarthrosis.

Intradermal injection of autologous dermal fibroblasts improves wound healing in irradiated skin.

BACKGROUND: Despite its well-recognized benefits in the management of several solid tumors, the use of radiotherapy prior to surgery is associated with a high incidence of significant surgical wound healing complications. Radiation-induced damage to dermal fibroblasts has been proposed as an important cause. We hypothesized that the introduction of normal, unirradiated fibroblasts into previously irradiated skin would enhance healing of the subsequent surgical wound. MATERIALS AND METHODS: Four groups of wounds were examined in female Wistar rats: (1) unirradiated skin (n = 10), (2) irradiated skin injected with tissue culture medium alone (n = 17), (3) irradiated skin injected with autologous dermal fibroblasts (n = 17), and (4) irradiated skin injected with irradiated autologous dermal fibroblasts (n = 7). Wounds were evaluated biomechanically and histologically. RESULTS: The biomechanical values of breaking load, ultimate tensile strength, elastic modulus, and toughness were significantly greater in the irradiated wounds injected with fibroblasts than those injected with medium only. These cell-injected wounds did not perform as well biomechanically as those in unirradiated skin. Irradiating the cells prior to injection resulted in biomechanical results no better than those in medium-injected wounds. CONCLUSIONS: These results demonstrate that injection of normal, unirradiated fibroblasts significantly improves healing of the irradiated surgical wound. These cells are likely better able to respond to the proliferative, migratory, and synthetic demands of the wound healing environment, as injection of irradiated cells has an equivalent effect on healing as injection of medium alone.

Primary patellar tumors.

Eight cases of primary tumors of the patella were identified in a consecutive series of 587 patients treated surgically for benign or malignant bone tumors. Six cases were benign (5 giant cell tumors and 1 chondroblastoma), and there were 2 malignant tumors (osteosarcoma and malignant fibrous histiocytoma). Both patients with malignant lesions had Rothmund-Thomson syndrome. Benign pulmonary metastases developed in 2 of the patients with giant cell tumor and 1 patient now is deceased 72 months after surgery. Two patients were treated before referral to a tertiary care center; 1 with patellectomy before histologic diagnosis and 1 with curettage. Both resulted in extension of disease into the knee joint. Tumors of the patella require careful assessment before surgical management. Conservation of the bone can be achieved in benign lesions that have adequate residual bone remaining at the articular surface. Conservation of the extremity is possible in malignant tumors, but reconstruction of the extensor mechanism is difficult.

Foreign-body abscesses presenting as soft-tissue tumours: two case reports.

Foreign bodies in the extremities often present as bony extensions of soft-tissue masses. Wooden foreign bodies can be detected by computed tomography and magnetic resonance imaging, but these studies are often nonspecific and cannot detect small bodies. As illustrated by two cases reported in this paper, these masses are difficult to distinguish from primary soft-tissue sarcomas when the history and imaging findings suggestive of a foreign-body reaction are absent.