QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Comparison of outcomes of peripheral nerve schwannoma excision in neurofibromatosis type 2 patients and non-neurofibromatosis type 2 patients: A case control study

Background Patients with neurofibromatosis type 2 (NF2) are an important subgroup of patients undergoing peripheral nerve schwannoma excision, however data on their outcomes are lacking. Co-existing peripheral neuropathy can complicate the clinical presentation and recovery in NF2. We designed a study to compare outcomes of peripheral nerve schwannoma excision in NF2 patients with excision of isolated, sporadic schwannomas in non-NF2 patients. Methods 30 peripheral nerve schwannoma excisions from 15 NF2 patients were compared to 30 excised isolated schwannomas. These were matched for age, size, nerve and level of involvement. Final outcomes were scored on a scale of 0 (no improvement) to 3 (complete symptom resolution). Data were analysed by McNemars test and Wilcoxen matched pairs test. Results NF2 patients had multiple lesions and more pre-operative weakness (p = 0.041) and sensory loss (p = 0.133) compared to controls. Post-operative neurological morbidity occurred in both groups after schwannoma excision. Final outcome scores of 2.4 in NF2 and 2.2 in controls indicate great improvement or complete resolution in the majority. Conclusions Outcomes in the NF2 group are not different to controls, despite NF2 patients having more significant pre-operative deficit and co-existing neuropathology. These findings suggest that surgical intervention should be offered to NF2 patients with peripheral nerve schwannomas

Functional and oncological outcomes after limb-salvage surgery for primary sarcomas of the upper limb.

The surgical treatment of upper limb sarcoma poses an oncological and reconstructive challenge. Limb-salvage surgery aims to balance adequate excision margins for disease control and preservation of all important structures to retain maximum function. Reported here is an assessment of the functional and oncological outcomes of limb salvage surgery for primary sarcoma of the upper limb and limb girdle in 72 patients referred to a specialist musculoskeletal tumour unit over 9 years. All patients underwent excision of the sarcoma with reconstruction and adjuvant treatment as needed. Functional outcome was assessed using the Toronto Extremity Salvage Score (TESS) after discharge from hospital. The upper limb sarcomas treated by limb-salvage surgery achieved planned margins of excision in 85% of cases with primary surgery. This increased to 100% with re-excision, resulting in local recurrence in 15% and survival of 75% among those at 5 years or more after surgery, while retaining good to excellent function (TESS mean of 87 out of 100). A total of 38 patients completed TESS questionnaires and, as a single group, had a mean TESS of 87. Patient age, anatomical site of tumour and adjuvant treatment made no significant difference to TESS. Liposarcomas had a significantly better TESS than leiomyosarcomas, chondrosarcomas and malignant peripheral nerve sheath tumours. Oncological outcome was assessed in terms of excision margins achieved, local recurrence, re-excision and disease-free survival. Eight patients died of disease, all with high-grade primary tumours. Fourteen had local recurrence, four low-grade disease and the remaining high-grade disease. All four low-grade recurrences were successfully re-excised, as were five of the high-grade recurrences. The remaining five died of disease, with or without further recurrences. Consistently good functional results as measured by TESS were reported by responders, but high-grade disease and early recurrence were identified as predictors of recurrence and death from disease, respectively

Subungual melanoma with osteocartilaginous differentiation.

Osteocartilaginous metaplasia is known to occur rarely in melanomas, particularly in subungual melanomas. We present a case of a calcified subungual soft tissue tumour in which biopsy of the lesion showed malignant round and spindle-shaped tumour cells, many of which were associated with the formation of cartilage and osteoid-like material. Subsequent resection showed clear histological evidence of a subungual melanoma. Tumour cells expressed S100, melan-A and neurone-specific enolase but were negative for HMB45. Diagnostic radiological and histological features and the nature of the osteocartilaginous differentiation within this lesion is discussed

Phenotypic and molecular studies of giant-cell tumors of bone and soft tissue.

Giant-cell tumor of bone (GCTB) and giant-cell tumor of soft tissue (GCTST) are tumors that contain a prominent osteoclastlike giant-cell component. The precise relationship between these morphologically similar tumors is unclear, and the cellular mechanism whereby giant cells accumulate within these and other locally aggressive tumors is uncertain. In this study, we have examined the cytochemical, functional, and molecular phenotype of the mononuclear and multinucleated components of GCTB and GCTST. Giant cells in GCTB and GCTST exhibited an osteoclast phenotype expressing tartrate-resistant acid phosphatase and vitronectin receptor and being capable of lacunar resorption. The mononuclear stromal cells derived from GCTB and GCTST exhibited an osteoblast phenotype, expressing alkaline phosphatase, and the receptor activator for nuclear factor kappaB ligand (RANKL), a factor that is essential for osteoclast formation. These cells also expressed osteoprotegerin (OPG), an inhibitor of osteoclastogenesis, and TRAIL, a receptor that binds OPG. Lacunar resorption by giant cells isolated from GCTB and GCTST was inhibited by OPG, zoledronate, and calcitonin. These findings indicate that the mononuclear and giant-cell components of GCTB and GCTST have similar phenotypic features and that the accumulation of osteoclasts in these giant-cell-rich tumors occurs by a RANKL-dependent process. RANKL expression by osteoblastlike mononuclear stromal cells in these tumors stimulates osteoclast formation and resorption; this would account for the osteolysis associated with these giant-cell-rich tumors. Inhibitors of osteoclast formation and activity are likely to be effective in controlling the osteolysis associated with GCTB and possibly other giant-cell-rich lesions

Giant cell tumour of the distal radius/ulna: Response to pre-operative treatment with short-term denosumab

Background Treatment of giant cell tumour of bone (GCTB) of the distal radius/ulna poses a surgical challenge, as complex reconstructive surgery may be required. This study evaluates the clinical, radiological and pathological findings in five cases of GCTB of the distal forearm where a 3 month course of denosumab was given prior to surgery. Methods Patients with biopsy proven distal forearm GCTB, treated for 3 months with denosumab, followed by salvage surgery (curettage and cementation) were included. Wrist pain and function were assessed using the modified Mayo Wrist Score (MMWS). Plain radiographs, MRI and PET/CT were performed pre-treatment and 2 months after initiation of denosumab therapy. Histological comparison was made between the original biopsy and surgical curettage specimens. Results Five patients with an average age of 25 years were included in the study. Improvement in wrist pain and function was seen in all patients with the average MMWS increasing from 30 pre-treatment to 85 at 3 months. Plain radiographs demonstrated marginal sclerosis in all cases with reconstitution of cortical and subarticular bone by 2 months; internal matrix sclerosis and osseous consolidation was more variable. Increased tumour heterogeneity and low signal were observed on T2-weighted MR images. PET/CT revealed a decrease in average SUV from 14.8 pre-treatment to 4.7 at 2 months. Histology showed disappearance of osteoclasts and increased fibro-osseous tissue. Denosumab treatment has the potential to facilitate salvage surgery, thus avoiding bone resection and graft reconstruction. A good outcome was achieved apart from local recurrence in one case. Follow up ranged from 17 to 54 months. Conclusion Distal forearm GCTB responds clinically, radiologically and histologically to a short course of pre-operative denosumab therapy, which has the potential to facilitate salvage surgery.</p

Giant cell tumour of the distal radius/ulna: Response to pre-operative treatment with short-term denosumab

Background Treatment of giant cell tumour of bone (GCTB) of the distal radius/ulna poses a surgical challenge, as complex reconstructive surgery may be required. This study evaluates the clinical, radiological and pathological findings in five cases of GCTB of the distal forearm where a 3 month course of denosumab was given prior to surgery. Methods Patients with biopsy proven distal forearm GCTB, treated for 3 months with denosumab, followed by salvage surgery (curettage and cementation) were included. Wrist pain and function were assessed using the modified Mayo Wrist Score (MMWS). Plain radiographs, MRI and PET/CT were performed pre-treatment and 2 months after initiation of denosumab therapy. Histological comparison was made between the original biopsy and surgical curettage specimens. Results Five patients with an average age of 25 years were included in the study. Improvement in wrist pain and function was seen in all patients with the average MMWS increasing from 30 pre-treatment to 85 at 3 months. Plain radiographs demonstrated marginal sclerosis in all cases with reconstitution of cortical and subarticular bone by 2 months; internal matrix sclerosis and osseous consolidation was more variable. Increased tumour heterogeneity and low signal were observed on T2-weighted MR images. PET/CT revealed a decrease in average SUV from 14.8 pre-treatment to 4.7 at 2 months. Histology showed disappearance of osteoclasts and increased fibro-osseous tissue. Denosumab treatment has the potential to facilitate salvage surgery, thus avoiding bone resection and graft reconstruction. A good outcome was achieved apart from local recurrence in one case. Follow up ranged from 17 to 54 months. Conclusion Distal forearm GCTB responds clinically, radiologically and histologically to a short course of pre-operative denosumab therapy, which has the potential to facilitate salvage surgery.</p

Cellular and humoral mechanisms of osteoclast formation in Ewing's sarcoma.

Cellular mechanisms that account for tumour osteolysis associated with Ewing's sarcoma are uncertain. Osteoclasts are marrow-derived multinucleated cells (MNCs) that effect tumour osteolysis. Osteoclasts are known to form from macrophages by both receptor activator for nuclear factor-kappaB (RANK) ligand (RANKL)-dependent and -independent mechanisms. In this study, our aim has been to determine whether tumour-associated macrophages (TAMs) isolated from Ewing's sarcoma are capable of differentiating into osteoclasts and to characterise the cellular and humoral mechanisms whereby this occurs. Tumour-associated macrophages were isolated from two Ewing's sarcomas and cultured on both coverslips and dentine slices for up to 21 days with soluble RANKL and macrophage colony stimulating factor (M-CSF). Osteoclast formation from TAMs (CD14+) was evidenced by the formation of tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor (VNR)-positive MNCs, which were capable of carrying out lacunar resorption. This osteoclast formation was inhibited by the addition of bisphosphonates. Both Ewing's sarcoma-derived fibroblasts and some bone stromal cells expressed RANKL and supported osteoclast formation by a contact-dependent mechanism. We also found that osteoclast differentiation occurred when Ewing's TAMs were cultured with tumour necrosis factor (TNF)-alpha in the presence of M-CSF and that TC71 Ewing's sarcoma cells stimulated osteoclast formation through the release of a soluble factor, the action of which was abolished by an antibody to TNF-alpha. These results indicate that TAMs in Ewing's sarcoma are capable of osteoclast differentiation by both RANKL-dependent and TNF-alpha-dependent mechanisms and that Ewing's sarcoma cells produce osteoclastogenic factor(s). Our findings suggest that anti-resorptive and anti-osteoclastogenic therapies may be useful in inhibiting the osteolysis of Ewing's sarcoma

Functional and oncological outcome following marginal excision of well-differentiated forearm Liposarcoma with nerve involvement

Purpose Liposarcoma is one of the most common soft tissue sarcomas in adults. It is often low-grade and can occasionally involve neurovascular structures. We present the functional and oncological outcome resulting from planned marginal excision of a series of forearm low-grade liposarcomas with nerve involvement. Methods The Oxford tumor registry was used to identify cases of histologically proven, well-differentiated liposarcoma of the forearm, with nerve involvement, treated surgically between 1997 and 2006. Nerve involvement was identified clinically with symptoms or signs of nerve compression, or by images showing direct contact of the tumor with a nerve on magnetic resonance imaging. This was then further defined at the time of surgery as tumor abutting (capsular involvement) or encasing a peripheral nerve. Demographic and clinical data were collected and oncological outcome was assessed by noting local and distant recurrence during follow-up. Postoperative functional outcome was assessed using the Toronto Extremity Salvage Scores. Results Eight cases were identified, 6 with preoperative neurological symptoms. The total group comprised 6 men and 2 women with a mean age of 61 (range, 3071) years. At surgery, all had their tumors successfully excised, with preservation of the involved nerves. In those with preoperative neurological symptoms, complete recovery occurred by 18 months after surgery. The average follow-up was 5 years (range, 39 y). There were no cases of either local or distant recurrence of disease, with a mean Toronto Extremity Salvage Score of 99%. Conclusions Planned marginal excision of a well-differentiated liposarcoma, arising in the forearm and involving nerve, can result in excellent functional and oncological outcome. Type of study/level of evidence Therapeutic IV. © 2011 American Society for Surgery of the Hand