Tenosynovial giant cell tumours: experience at an Australian tertiary referral centre for musculoskeletal tumours with minimum two-year follow-up.

Aims: Tenosynovial giant cell tumour (TGCT) is a rare benign tumour of the musculoskeletal system. Surgical management is fraught with challenges due to high recurrence rates. The aim of this study was to describe surgical treatment and evaluate surgical outcomes of TGCT at an Australian tertiary referral centre for musculoskeletal tumours and to identify factors affecting recurrence rates. Methods: A prospective database of all patients with TGCT surgically managed by two orthopaedic oncology surgeons was reviewed. All cases irrespective of previous treatment were included and patients without follow-up were excluded. Pertinent tumour characteristics and surgical outcomes were collected for analysis. Results: There were 111 total cases included in the study; 71 (64%) were female, the mean age was 36 years (SD 13.6), and the knee (n = 64; 57.7%) was the most commonly affected joint. In all, 60 patients (54.1%) had diffuse-type (D-TGCT) disease, and 94 patients (84.7%) presented therapy-naïve as "primary cases" (PC). The overall recurrence rate was 46.8% for TGCT. There was a statistically significant difference in recurrence rates between D-TGCT and localized disease (75.0% vs 13.7%, relative risk (RR) 3.40, 95% confidence interval (CI) 2.17 to 5.34; p < 0.001), and for those who were referred in the "revision cases" (RC) group compared to the PC group (82.4% vs 48.9%, RR 1.68, 95% CI 1.24 to 2.28; p = 0.011). Age, sex, tumour volume, and mean duration of symptoms were not associated with recurrence (p > 0.05). Conclusion: Recurrence rates remain high even at a tertiary referral hospital. Highest rates are seen in D-TGCT and "revision cases". Due to the risks of recurrence, the complexity of surgery, and the need for adjuvant therapy, this paper further supports the management of TGCT in a tertiary referral multi-disciplinary orthopaedic oncology service.

Improving Surgical Outcomes in Pelvic Exenteration Surgery: Comparison of Prone Sacrectomy With Anterior Cortical Sacrectomy Techniques.

OBJECTIVE: To assess the effect of changing our sacrectomy approach from prone to anterior on surgical and oncological outcomes. BACKGROUND: In patients with advanced pelvic malignancy involving the sacrum, pelvic exenteration (PE) with en-bloc sacrectomy is the only potential curative option but morbidity is high. Over time sacrectomy techniques have evolved from prone sacrectomy (PS) to abdominolithotomy sacrectomy (ALS, ≤S3) and high anterior cortical sacrectomy (HACS, >S3) to optimize surgical outcomes. METHODS: A retrospective, single institution analysis of prospectively collected data for patients undergoing PE with en-bloc sacrectomy between 1994 and 2021 was performed. RESULTS: A total of 363 patients were identified and divided into PS (n=77, 21.2%), ALS (n=247, 68.0%), and HACS (n=39, 10.7%). Indications were: locally advanced (n=92) or recurrent (n=177) rectal cancer, primary other (n=31), recurrent other (n=60), and benign disease (n=3). PS resulted in longer operating time ( P <0.01) and more blood loss ( P <0.01). Patients with HACS had more major nerve (87.2%) and vascular (25.6%) resections ( P <0.01). Vertical rectus abdominis myocutaneous flap repair was less common following HACS (7.7%) than ALS (25.5%) and PS (27.3%) ( P =0.040). R0 rate was 80.8%, 65.8%, and 76.9% following ALS, PS, and HACS, respectively ( P =0.024). Wound-related complications and re-operations were significantly reduced following ALS and HACS compared with PS. CONCLUSIONS: Changing our practice from PS to an anterior approach with ALS or HAS has been safe and improved overall surgical and perioperative outcomes, while maintaining good oncological outcomes. Given the improved perioperative and surgical outcomes, it would be important for surgeons to learn and adopt the anterior sacrectomy approaches.

Programmed cell death-1 blockade in recurrent disseminated Ewing sarcoma.

BACKGROUND: Ewing sarcoma (EWS) is a malignant tumour of bone and soft tissue, and although many patients are cured with conventional multimodal therapy, those with recurrent or metastatic disease have a poor prognosis. Genomic instability and programmed cell death ligand-1 (PD-L1) expression have been identified in EWS, providing a rationale for treatment with agents that block the programmed cell death-1 (PD-1) receptor. CASE PRESENTATION: In this report, we describe a heavily pre-treated patient with recurrent metastatic EWS who achieved a clinical and radiological remission with PD-1 blockade. CONCLUSIONS: To our knowledge, this is the first reported case demonstrating efficacy of PD-1 blockade in EWS. This warrants further investigation in particular given the poor prognosis in patients with recurrent or metastatic disease.

Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumor of bone.

BACKGROUND: Surgical resection with curative intent for giant cell tumor of bone (GCTB) may be associated with severe morbidity. This interim analysis evaluated reduction in surgical invasiveness after denosumab treatment in patients with resectable GCTB. METHODS: Patients with primary or recurrent GCTB, for whom the initially planned surgery was associated with functional compromise or morbidity, received denosumab 120 mg subcutaneously every 4 weeks (additional doses on days 8 and 15 of the first cycle). Planned and actual GCTB-related surgical procedures before and after denosumab treatment were reported. Patients were followed for surgical outcome, adverse events, and recurrence following resection. RESULTS: Overall, 222 patients were evaluable for surgical downstaging (54 % were women; median age 34 years). Lesions (67 % primary and 33 % recurrent) were located in the axial (15 %) and appendicular skeleton (85 %). At the data cutoff date, most patients had not yet undergone surgery (n = 106; 48 %) or had a less morbid procedure (n = 84; 38 %) than originally planned. Median (interquartile range) time on denosumab was 19.5 (12.4-28.6) months for the 106 patients who had not undergone surgery and were continuing on monthly denosumab. Native joint preservation was 96 % (n = 24/25) for patients with planned joint/prosthesis replacement and 86 % (n = 30/35) for patients with planned joint resection/fusion. Of the 116 patients who had surgery (median postsurgical follow-up 13.0 [8.5-17.9] months), local recurrence occurred in 17 (15 %) patients. CONCLUSION: For patients with resectable GCTB, neoadjuvant denosumab therapy resulted in beneficial surgical downstaging, including either no surgery or a less morbid surgical procedure.

Bilateral total hip arthroplasty in Severe Hereditary Multiple Exostosis: a report of two cases.

Staged bilateral hip arthroplasties were carried out in two patients with osteoarthritis of the hip secondary to the development of hip dysplasia in Hereditary Multiple Exostosis (HME).Both patients had near ankylosis of their hips with pain and difficulty in performing activities of daily living. A proximal femur replacing prosthesis was implanted through an extended trochanteric osteotomy, with preservation of as much proximal bone stock as possible. At latest followup (two to five years), there was a sustained improvement in range of motion and symptoms. The Harris Hip Scores improved from 25 and 31 to 83 and 78. The Toronto Extremity Salvage Scores improved from 49% and 55% to 88% and 75%. Radiographs show bony ingrowth and healing of the trochanteric fragments. In severe HME, hip arthroplasty with replacement of the proximal femur provides good symptomatic relief and return of hip joint movement.

The role of intra-operative pathological evaluation in the management of musculoskeletal tumours.

A tissue biopsy is usually a critical aspect in guiding appropriate initial management in patients with musculoskeletal tumours. We have previously outlined the role of intra-operative frozen section in both the determination of adequacy of a biopsy and for its diagnostic utility. In this article, the options and techniques for intra-operative pathological evaluation, namely frozen section, fine needle aspiration cytology and touch imprint cytology are reviewed. Frozen section examination may be applicable in the following Sections, including (1) at core biopsy, (2) at surgical margins, (3) at confirming diagnosis prior to definitive treatment or to evaluate tumour spread, and (4) at establishing a diagnosis of a metastasis prior to intramedullary nailing. There are also situations in which frozen section is inappropriate. Pitfalls associated with frozen sections are also highlighted. There are also cost implications, which we have quantified, of performing frozen sections. In our experience that the use of intra-operative pathological evaluation reduces the non-diagnostic rate of bone and soft tissue sarcoma biopsies, eliminates the need for re-biopsy hence alleviating stress, and is a useful addition to the armamentarium in evaluating musculoskeletal tumours.

Reconstruction of the proximal humerus with a composite of extracorporeally irradiated bone and endoprosthesis following excision of high grade primary bone sarcomas.

INTRODUCTION: Functional reconstruction of the shoulder joint following excision of a malignant proximal humeral tumour is a difficult proposition. METHOD: Eleven patients with primary osteosarcoma or Ewing's sarcoma underwent reconstruction with a composite of extra-corporeally irradiated autograft with the addition of a long stemmed hemiarthroplasty. At a mean follow-up of 5.8 years two patients had died from disseminated disease and one patient had undergone amputation for local recurrence. The eight patients with a surviving limb were examined clinically and radiographically. RESULT: The mean Toronto Extremity Salvage Score was 74 and Musculo-Skeletal Tumour Society score 66. Rotation was well preserved but abduction (mean 32 degrees ) and flexion (40 degrees ) were poor. There was a high rate of secondary surgery, with five out of eleven patients requiring re-operation for complications of reconstruction surgery. Radiographic estimate of graft remaining at follow up was 71%. There were no infections, revisions or radiographic failures. CONCLUSION: Whilst the reconstructions were durable in the medium term, the functional outcome was no better than with other reported reconstructive methods. The composite technique was especially useful in subtotal humeral resections, allowing preservation of the elbow joint even with very distal osteotomy. Bone stock is restored, which may be useful for future revision surgery in this young group of patients.

Isolated limb infusion for advanced soft tissue sarcoma of the extremity.

BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive technique for delivering high-dose regional chemotherapy. We report our experience with ILI for the treatment of soft tissue sarcoma (STS). METHODS: From our prospective database, 21 patients with STS of the limb treated with ILI between 1994 and 2007 were identified. In all patients, a high-dose cytotoxic drug combination was used. RESULTS: There were 14 men, and the median age was 60 years (range, 18-85 years). Eighteen patients (86%) had lower limb tumors. All patients had advanced local disease. The procedure was well tolerated. Fourteen patients (67%) received ILI before definitive surgery. The overall response rate was 90% (complete response [CR] rate 57%, partial response rate 33%). The disease-specific overall survival was 61.9% (median follow-up, 28 months). Only American Joint Committee on Cancer stage was associated with overall survival. The local recurrence rate was 42%. CR and malignant fibrous histiocytoma tumor subtype were associated with a lower local recurrence rate. A lower initial skin temperature (median 35.8 degrees C) was associated with a CR (P = .033). Patients who had a steep increase in intramuscular temperature during the procedure were more likely to have a CR (P = .055). Classification tree analysis identified patients with an initial PaO(2) of >/=194 mmHg as being more likely to have a CR. Ultimately, the overall limb salvage rate was 76%. CONCLUSION: The outcomes after ILI are comparable to those achieved by conventional isolated limb perfusion. ILI is a minimally invasive alternative to isolated limb perfusion for patients with advanced STS of the extremity.

A robust assay for alternative lengthening of telomeres in tumors shows the significance of alternative lengthening of telomeres in sarcomas and astrocytomas.

PURPOSE AND EXPERIMENTAL DESIGN: Telomeres of tumor cells may be maintained by telomerase or by alternative lengthening of telomeres (ALT). The standard ALT assay requires Southern analysis of high molecular weight genomic DNA. We aimed to establish and validate an ALT assay suitable for archived paraffin-embedded tumors and to use it to examine the prevalence and clinical significance of ALT in various types of tumors that are often telomerase negative. RESULTS: To assay for ALT, we detected ALT-associated promyelocytic leukemia (PML) bodies (APBs) by combined PML immunofluorescence and telomere fluorescence in situ hybridization. APBs are PML nuclear domains containing telomeric DNA and are a known hallmark of ALT in cell lines. The APB assay concurred with the standard ALT assay in 62 of 62 tumors and showed that 35% of 101 soft tissue sarcomas (STS), 47% of 58 osteosarcomas (especially younger patients), 34% of 50 astrocytomas, and 0% of 17 papillary thyroid carcinomas were ALT positive (ALT+). The prevalence of ALT varied greatly among different STS subtypes: malignant fibrous histiocytomas, 77%; leiomyosarcomas, 62%; liposarcomas, 33%; synovial sarcomas, 9%; and rhabdomyosarcomas, 6%. ALT correlated with survival in glioblastoma multiforme and occurred more often in lower-grade astrocytomas, but ALT+ and ALT- sarcomas were equally aggressive in terms of grade and clinical outcome. CONCLUSION: The APB assay for ALT is suitable for paraffin-embedded tumors. It showed that a substantial proportion of STS, osteosarcomas, and astrocytomas, but not papillary thyroid carcinomas use ALT. APB positivity correlated strongly with survival of patients with astrocytomas.

Biopsy of musculoskeletal tumours--beware.

BACKGROUND: Biopsy of musculoskeletal tumours is hazardous and, when poorly performed, can compromise limb salvage surgery and patient survival. The aim of the present paper is to examine the early management of such patients referred to the Department of Orthopaedic Surgery, Royal Prince Alfred Hospital, Sydney, Australia with particular reference to biopsy. METHODS: We conducted a prospective audit of all patients referred to our musculoskeletal tumour service during 2002. Inclusion criteria were: all patients with primary tumours of the musculoskeletal system. We compared the outcome of patients biopsied prior to referral with that of patients biopsied in a recognized treatment centre. RESULTS: One hundred and forty-two patients were included. The referring surgeon performed biopsies in 29 cases, of which 20 were malignant lesions. The senior author biopsied the remaining 113 cases, of which 57 were malignant. Definitive treatment was hindered by a badly performed biopsy in 38% of patients biopsied by the referring surgeon. In 25% the definitive treatment had to be changed either to a more radical procedure than would have originally been necessary or to palliative rather than curative intent. Patients biopsied elsewhere were more likely to have an incomplete excision requiring re-excision, more likely to require amputation, and more likely to require adjuvant radiotherapy. CONCLUSIONS: There is a high complication rate when patients with musculoskeletal tumours are biopsied by surgeons inexperienced in their management. These patients are better served by early referral to a specialist centre where staging investigations including biopsy can be performed with minimal morbidity.