Leiomyosarcomas of Vascular Origin in the Extremity

Between 1996 and 2006 a total of 278 patients with soft tissue Leiomyosarcoma were treated at our centre. We identified 16 patients (5.8%) where the tumour directly arose from the blood vessels. These tumours were studied to determine their prognosis and behaviour. All tumors were in the lower limbs: 11 from the femoral vein, 3 popliteal vein, and 2 from the posterior tibial vein. Mean tumour size was 10.4 cm (3 to 33). Histological grade was high in all patients. Surgical treatment was amputation in one, excision with or without vascular reconstruction in 12 followed by radiotherapy, and 3 patients had no surgery because of advanced disease at diagnosis. Seven out of the 16 patients (44%) had metastasis at diagnosis, and five patients without metastasis at diagnosis rapidly developed metastases at a median time of 5 months from diagnosis (2–30 months). The overall survival of the patients at 5 years was 25% which was considerably worse than those with nonvascular leiomyosarcoma. We conclude that patients with leiomyosarcoma of vascular origin have a very high risk of metastases and poor prognosis when treated in the conventional way

Locally recurrent chondrosarcoma of the pelvis and limbs can only be controlled by wide local excision

Aims The purpose of this study was to investigate the potential for achieving local and systemic control after local recurrence of a chondrosarcoma of bone. Patients and Methods A total of 126 patients with local recurrence (LR) of chondrosarcoma (CS) of the pelvis or a limb bone were identified from a prospectively maintained database, between 1990 and 2015 at the Royal Orthopaedic Hospital, Birmingham, United Kingdom. There were 44 female patients (35%) and 82 male patients (65%) with a mean age at the time of LR of 56 years (13 to 96). The 126 patients represented 24.3% of the total number of patients with a primary CS (519) who had been treated during this period. Clinical data collected at the time of primary tumour and LR included the site (appendicular, extremity, or pelvis); primary and LR tumour size (in centimetres); type of operation at the time of primary or LR (limb-salvage or amputation); surgical margin achieved at resection of the primary tumour and the LR; grade of the primary tumour and the LR; gender; age; and oncological outcomes, including local recurrence-free survival and disease-specific survival. A minimum two years' follow-up and complete histopathology records were available for all patients included in the study. Results For patients without metastases prior to or at the time of local recurrence, the disease-specific survival after local recurrence was 62.5% and 45.5% at one and five years, respectively, After univariable analysis, significant factors predicting disease-specific survival were grade (p <0.001) and surgical margin (p = 0.044). After multivariable analysis, grade, increasing age at the time of diagnosis of local recurrence, and a greater time interval from primary surgery to local recurrence were significant factors for disease-specific survival. A secondary local recurrence was seen in 26% of patients. Wide margins were a good predictor of local recurrence-free survival for subsequent recurrences after univariable analysis when compared with intralesional margins (p = 0.002) but marginal margins did not reach statistical significance when compared with intralesional margins (p = 0.084). Conclusion In cases of local recurrence of a chondrosarcoma of bone, we have shown that if the tumour is non-metastatic at re-staging, an increase in disease-specific survival and in local recurrence-free survival is achievable, but only by resection of the local recurrence with a wide margin.Peer reviewe

‘‘Two-Week Waits”—Are They Leading to Earlier Diagnosis of Soft-Tissue Sarcomas?

Introduction. The ‘‘two-week wait” was established as a potential means of diagnosing malignant tumours earlier. This paper investigated whether these clinics are leading to earlier diagnosis of malignant soft-tissue lumps. Method. We identified all referrals to our centre from a database over a 4-year period. Results. 2225 patients were referred to our unit for investigation of a soft-tissue mass. 576 (26%) were referred under the ‘‘two-week wait” criteria. 153 (27%) of which were found to have a malignant or borderline malignant diagnosis. 1649 patients were referred nonurgently. 855 (52%) of which were diagnosed with a malignant or borderline lesion. The average size at diagnosis was 9.4 cm with no difference in size between the different referral routes. Conclusion. There is little evidence that the two-week wait clinic is leading to earlier diagnosis of soft-tissue sarcomas with the majority still being referred nonurgently

Primary Leiomyosarcoma of Bone: Analysis of Prognosis

Leiomyosarcoma of bone is just one of the variants of spindle cell sarcoma of bone characterised by the expression of desmin and other markers indicating a significant element of smooth muscle in the tumour, without osteoid production we have investigated the management and outcome of this rare type of primary malignant bone tumour. Method. Retrospective review of data stored on a prospective database. Results. In a database of 3364 patients with primary malignant bone sarcomas, 31 patients were identified with a primary leiomyosarcoma of bone. There were 12 males and 19 females with a mean age of 46 and tumour size of 8 cm. The most common site was the distal femur followed by the proximal tibia. Treatment was with chemotherapy and surgical resection. Seven of the patients had metastases at diagnosis. Surgery was carried out in 28 patients, 8 having amputation and 20 limb salvage. Three patients developed local recurrence, but half developed metastases. All patient disease-specific survival was 57% at five years and 44% at 10 yrs but for those without metastases was 82% and 60%, respectively. The only prognostic factors were metastases at diagnosis. Conclusion. Leiomyosarcoma of bone is a very rare primary malignant bone tumour affecting a predominantly older population. Despite the high incidence of metastases, survival is better than for other bone sarcomas for those without metastases at diagnosis

Chondroblastoma of bone in extremities. - A single centre study of 177 cases

Introduction Chondroblastoma is a rare benign bone tumour that usually occurs in children and young adults. They are cartilaginous tumours arising in the epiphysis or apophysis of a long bone. The tumour is classified as benign, although rare cases of pulmonary metastases have been reported. The aims of this study were to describe clinical, radiographic characteristics of chondroblastoma; to analyse the local recurrence rate and complications associated with surgery. Material and methods This retrospective study included 177 patients, who had been diagnosed with a chondroblastoma in extremity between 1990 and 2015. Results The most common site was proximal tibia 20%, followed by proximal humerus 19%, proximal femur 18%, distal femur 16% and foot 15%. One patient has died of the disease and one patient is alive after being operated for lung metastases. There was local recurrence in 25/177 (14%) patients. The median time to local recurrence was 10 months (range 3-158 months). The most common site for local recurrence was proximal tibia (22.2%). The proximal femur was the location in 32/178 (18%) of the cases. 18/32 (56%) were in the greater trochanter and 14/32 (44%) in the femoral head. The mean age was lower in tumours located in femoral head when compared to the greater trochanter; 19.5 years and 13.9 years respectively (p=0.004). Tumours located in greater trochanter were all curetted without further complications. Local recurrence was seen more often in femoral head tumours, though without statistical significance; 3/14 (21%) and none, respectively (p=0.073). Conclusions Chondroblastoma is a rare benign to intermediate grade bone tumour with a potential to metastasise. Femoral head chondroblastoma is rare, presenting 4.5% of all chondroblastoma cases. Around 50% of the chondroblastoma in femoral head. occur in patients with open growth plates.Peer reviewe

Preoperative surgical risk stratification in osteosarcoma based on the proximity to the major vessels

Aims The aim of this study was to determine the risk of local recurrence and survival in patients with osteosarcoma based on the proximity of the tumour to the major vessels. Patients and Methods A total of 226 patients with high-grade non-metastatic osteosarcoma in the limbs were investigated. Median age at diagnosis was 15 years (4 to 67) with the ratio of male to female patients being 1.5:1. The most common site of the tumour was the femur (n = 103) followed by tibia (n = 66). The vascular proximity was categorized based on the preoperative MRI after neoadjuvant chemotherapy into four types: type 1 > 5 mm; type 2 ≤ 5 mm, > 0 mm; type 3 attached; type 4 surrounded. Results Limb salvage rate based on the proximity type was 92%, 88%, 51%, and 0% for types 1 to 4, respectively, and the overall survival at five years was 82%, 77%, 57%, and 67%, respectively (p Conclusion The proximity of osteosarcoma to major blood vessels is a poor prognostic factor for local control and survival. Amputation offers better local control for tumours attached to the blood vessels but does not improve survival. Limb salvage surgery offers similar local control if the tumour attachment to blood vessels is limited

RNA sequencing and functional studies of patient-derived cells reveal that neurexin-1 and regulators of this pathway are associated with poor outcomes in Ewing sarcoma

Purpose The development of biomarkers and molecularly targeted therapies for patients with Ewing sarcoma (ES) in order to minimise morbidity and improve outcome is urgently needed. Here, we set out to isolate and characterise patient-derived ES primary cell cultures and daughter cancer stem-like cells (CSCs) to identify biomarkers of high-risk disease and candidate therapeutic targets. Methods Thirty-two patient-derived primary cultures were established from treatment-naïve tumours and primary ES-CSCs isolated from these cultures using functional methods. By RNA-sequencing we analysed the transcriptome of ES patient-derived cells (n = 24) and ES-CSCs (n = 11) to identify the most abundant and differentially expressed genes (DEGs). Expression of the top DEG(s) in ES-CSCs compared to ES cells was validated at both RNA and protein levels. The functional and prognostic potential of the most significant gene (neurexin-1) was investigated using knock-down studies and immunohistochemistry of two independent tumour cohorts. Results ES-CSCs were isolated from all primary cell cultures, consistent with the premise that ES is a CSC driven cancer. Transcriptional profiling confirmed that these cells were of mesenchymal origin, revealed novel cell surface targets for therapy that regulate cell-extracellular matrix interactions and identified candidate drivers of progression and relapse. High expression of neurexin-1 and low levels of regulators of its activity, APBA1 and NLGN4X, were associated with poor event-free and overall survival rates. Knock-down of neurexin-1 decreased viable cell numbers and spheroid formation. Conclusions Genes that regulate extracellular interactions, including neurexin-1, are candidate therapeutic targets in ES. High levels of neurexin-1 at diagnosis are associated with poor outcome and identify patients with localised disease that will relapse. These patients could benefit from more intensive or novel treatment modalities. The prognostic significance of neurexin-1 should be validated independently

Solid-state laser system for laser cooling of Sodium

We demonstrate a frequency-stabilized, all-solid laser source at 589 nm with up to 800 mW output power. The laser relies on sum-frequency generation from two laser sources at 1064 nm and 1319 nm through a PPKTP crystal in a doubly-resonant cavity. We obtain conversion efficiency as high as 2 W/W^2 after optimization of the cavity parameters. The output wavelength is tunable over 60 GHz, which is sufficient to lock on the Sodium D2 line. The robustness, beam quality, spectral narrowness and tunability of our source make it an alternative to dye lasers for atomic physics experiments with Sodium atoms