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Supplementary Data from Development of a Multiplex RNA Urine Test for the Detection and Stratification of Transitional Cell Carcinoma of the Bladder

Purpose: New markers that enable the percentage of transitional cell carcinomas (TCC) of the bladder that are diagnosed before invasion of the bladder muscle layers to be increased would reduce the morbidity and mortality associated with this disease. The purpose of this study was to develop a simple, accurate urine test based on mRNA markers and simple gene signatures that (a) could detect TCC before muscle invasion while maintaining high specificity in patients with hematuria or urinary tract infections and (b) identify patients most likely to have grade 3 or stage ≥T1 disease.Experimental Design: RNA markers with high overexpression in stage Ta tumors and/or T1 to T4 tumors but low expression in blood or inflammatory cells were characterized by quantitative reverse transcription-PCR using 2 mL of voided urine from 75 TCC patients and 77 control patients with other urological diseases.Results: A combination of the RNAs CDC2, MDK, IGFBP5, and HOXA13 detected 48%, 90%, and 100% of stage Ta, T1, and >T1 TCCs, respectively, at a specificity of 85%. Detection of Ta tumors increased to 60% for primary (non-recurrent) Ta tumors and 76% for Ta tumors ≥1 cm in diameter. Test specificity was 80% for the 20 control patients with urinary tract infections. The combination of CDC2 and HOXA13 distinguished between grade 1 to 2 TCCs and grade 3 or stage ≥T1 TCCs with ∼80% specificity and sensitivity.Conclusions: Simple gene expression signatures can be used as urine markers for the accurate detection and characterization of bladder cancer.

Objective: The aim of the study is to assess the effect of perioperative chemo-therapy (CTX) in patients with grade II-III extremity soft tissue sarcoma (eSTS) on overall survival (OS) and evaluate whether the PERSARC prediction tool could identify patients with eSTS more likely to benefit from CTX.Methods: Patients (18-70 years) with primary high-grade eSTS surgically treated with cura-tive intent were included in the retrospective cohort study. The effect of any perioperative CTX and anthracycline + ifosfamide (AI)-based CTX on OS was investigated in three PERSARC-risk groups (high/intermediate/low). The PERSARC-risk groups were defined by the 33% and 66% quantile of the predicted 5-year OS of the study population equal to a 5-year OS of 65.8% and 79.8%, respectively. The effect of CTX on OS was investigated with weighted Kaplan-Meier curves and multivariable Cox models with an interaction between risk group and CTX.Results: This study included 5683 patients. The weighted Kaplan-Meier curves did not demonstrate a beneficial effect of any CTX and AI-based CTX on OS in the overall population. However, in the high PERSARC-risk group the 5-year OS of AI-based CTX was significantly better than no CTX (69.8% vs 59.0%, respectively, p Z 0.004) (HR 0.66, 95% CI 0.53-0.83).Conclusions: This study demonstrated a beneficial effect of AI-based CTX on OS in a selected group of high-risk patients with an absolute survival benefit of 11% as stratified by the PERSARC prediction tool. However, no beneficial effect of CTX on OS was found in the overall population of patients with primary high-grade eSTS younger than 70 years.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Benign primary bone tumours are rare, occurring most commonly in skeletally immature patients, arising from cartilage or bone. The commonest locations are the distal femur, proximal tibia and proximal humerus. They present with pain, swelling or pathological fracture. Diagnosis is by plain x-rays, MRI scans and a core needle biopsy if indicated. More aggressive tumours may appear radiologically to be similar to malignant tumours. Treatment depends on the anatomical location, symptoms, the natural history of the tumour and the morbidity of treatment and in most cases involves either simple excision or curettage although occasionally it is necessary to perform a complete excision using the same principles as for malignant tumours.

Purpose: No studies extensively compared the young adults (YA, 18-39 years), middle-aged (40-69 years), and elderly (≥70 years) population with primary high-grade extremity soft tissue sarcoma (eSTS). This study aimed to determine whether the known effect of age on overall survival (OS) and disease progression can be explained by differences in tumour characteristics and treatment protocol among the YA, middle-aged and elderly population in patients with primary high-grade eSTS treated with curative intent. Methods: In this retrospective multicentre study, inclusion criteria were patients with primary high-grade eSTS of 18 years and older, surgically treated with curative intent between 2000 and 2016. Cox proportional hazard models and a multistate model were used to determine the association of age on OS and disease progression. Results: A total of 6260 patients were included in this study. YA presented more often after 'whoops'-surgery or for reresection due to residual disease, and with more deep-seated tumours. Elderly patients presented more often with grade III and larger (≥10 cm) tumours. After adjustment for the imbalance in tumour and treatment characteristics the hazard ratio for OS of the middle-aged population is 1.47 (95% confidence interval [CI]: 1.23-1.76) and 3.13 (95% CI: 2.59-3.78) in the elderly population, compared with YA. Discussion: The effect of age on OS could only partially be explained by the imbalance in the tumour characteristics and treatment variables. The threefold higher risk of elderly could, at least partially, be explained by a higher other-cause mortality. The results might also be explained by a different tumour behaviour or suboptimal treatment in elderly compared with the younger population. Keywords: Adolescents and young adults; Elderly; Extremities; Metastasis; Middle-aged; Recurrence; Soft tissue sarcoma; Survival.

A broad framework of management, from initial evaluation to treatment, is appropriate for all patients with primary bone tumors. Historically the use of radiotherapy in the treatment of primary bone tumors has been of limited value due to the radio-resistance of these tumors and also the inability of primitive radiotherapy delivery techniques safely delivering high doses of radiotherapy. The relationship between the tumor, the adjacent joint, and the neurovascular structures is determined and a resection strategy is formulated. Expert interpretation of the biopsy is essential as most pathologists will be unfamiliar with primary bone tumors and the appearances are often misleading, for instance when distinguishing reactive from tumor bone in bone-forming tumors such as osteosarcoma. Staging is completed by examination of a bone marrow aspirate and trephine biopsy. Chemotherapy is often given after biopsy has established an appropriate diagnosis and before definitive local therapy, so-called neoadjuvant therapy.

Background: Dedifferentiated chondrosarcoma (DDC) accounts for a small proportion of chondrosarcomas. They demonstrate aggressive behaviour with a high rate of local recurrence and systemic progression resulting in poor long-term survival rates. Due to its relatively low incidence, previous studies have grouped different histiotypes together to achieve adequate study numbers for analysis. Methods: This retrospective study examines the clinical course and the role of chemotherapy in the subgroup of patients with DDC where osteosarcoma is the predominant dedifferentiated component. Between 2000-2010, 21 patients were identified. Results: The mean age at presentation was 64 years (range 35-80 years). 12 patients were considered unfit for chemotherapy, whilst 2 patients declined chemotherapy. 5 patients received neoadjuvant chemotherapy, with less than 90% necrosis demonstrated in all these cases. 3 patients received post-operative chemotherapy. The median survival for the entire group was 9.5 months. In the 7 patients who received chemotherapy, the median survival was 17 months, and those who had chemotherapy had a greater median time to local recurrence. Conclusion: This study demonstrates that cytotoxic chemotherapy may be offered to appropriately selected patients.

Soft tissue sarcomas (STS) are rare tumours that require prompt diagnosis and treatment at a specialist centre. Magnetic resonance imaging (MRI) has become the modality of choice for identification, characterisation, biopsy planning and staging of soft tissue masses. MRI enables both the operating surgeon and patient to be optimally prepared prior to surgery for the likelihood of margin-negative resection and to anticipate possible sacrifice of adjacent structures and consequent loss of function. The aim of this review is to aid the radiologist in performing and reporting MRI studies of soft tissue sarcomas, with particular reference to the requirements of the surgical oncologist.

Aims The aim of this study is to assess outcomes of patients ≤12 years who undergo Stanmore noninvasive extendible endoprosthetic replacement of the distal femur (DF NIEPR). Patients and methods A total of 101 children (mean age 9.6 years) were included. All complications which required further surgery were recorded. Clinical and functional outcomes were evaluated with Musculoskeletal Tumor Society (MSTS) scores at a mean follow-up of 64 months (range 6-174). Results Thirty-one (30.7%) patients died at a mean of 33 months. Forty had prosthesis removed after a mean of 43 months (range, 7-103). Attaining of the full lengthening potential before skeletal maturity was the most frequent reason for revision surgery, particularly in those with smaller lengthening potential (P = 0.039). Implant survival rate for other causes was 61.7% at 5 years and 45.0% at 10 years. At final follow-up mean MSTS score was 26 (range, 13-29). Twenty-two (21.5%) patients had a final limb-length discrepancy (LLD) > 2 cm. Conclusions DF NIEPR produces a good functional outcome, with the prevention of major LLD at skeletal maturity in the majority of the cases. We suggest patient selection criteria to account for the stage of the disease due to the high cost of the NIEPR, and high percentage requiring revision, and a 60% mortality rate in those patients presenting with distant disease burden.

Purpose There is increasing interest in personalized prediction of disease progression for soft tissue sarcoma patients. Currently, available prediction models are limited to predictions from time of surgery or diagnosis. This study updates predictions of overall survival at different times during follow-up by using the concept of dynamic prediction. Patients and methods Information from 2232 patients with high-grade extremity soft tissue sarcoma, who underwent surgery at 14 specialized sarcoma centers, was used to develop a dynamic prediction model. The model provides updated 5-year survival probabilities from different prediction time points during follow-up. Baseline covariates as well as time-dependent covariates, such as status of local recurrence and distant metastases, were included in the model. In addition, the effect of covariates over time was investigated and modelled accordingly in the prediction model. Results Surgical margin and tumor histology show a significant time-varying effect on overall survival. The effect of margin is strongest shortly after surgery and diminishes slightly over time. Development of local recurrence and distant metastases during follow-up have a strong effect on overall survival and updated predictions must account for their occurrence. Conclusion The presence of time-varying effects, as well as the effect of local recurrence and distant metastases on survival, suggest the importance of updating predictions during follow-up. This newly developed dynamic prediction model which updates survival probabilities over time can be used to make better individualized treatment decisions based on a dynamic assessment of a patient's prognosis.

Background A two-stage revision remains the gold standard to eradicate deep infection in total knee arthroplasty. Higher failure rates are associated with a number of factors including poly-microbial infections, multiresistant organisms and previous operations. The aims are to investigate [1] the overall success rate of a two-stage revision for infections in TKA, [2] the outcome of repeat two-stage revisions in recurrent infections and [3] the factors affecting the outcomes of such cases. Methods We present the outcomes of a consecutive, retrospective case series of 51 periprosthetic joint infections managed with a two-stage revision knee arthroplasty over a three year period. Results Forty-six (90%) of 51 were referred from other hospitals. Infection was successfully eradicated in 24 (65%) of 37 patients undergoing an initial two-stage procedure. Following a failed two-stage revision, a repeat two-stage revision was performed in 19 patients eradicating infection in 8 (42%). A third two-stage was performed in five of these patients eradicating infection in three with an average follow-up of 43months. Multidrug resistance was present in 69%, and 47% of the patients were infected with multiple organisms. All unsuccessful outcomes involved at least one multidrug-resistant organism compared to 43% in the successful cohort ( P =0.0002). Serological markers prior to a second-stage procedure were not significantly different between successful and unsuccessful outcome groups. Conclusion Single or multiple two-stage revisions can eradicate infection despite previous failed attempts. In this series, failure is associated with multidrug resistance, previous failed attempts to eradicate infection and a less favourable host response. Level of evidence IV

Background To support shared decision-making, we developed the first prediction model for patients with primary soft-tissue sarcomas of the extremities (ESTS) which takes into account treatment modalities, including applied radiotherapy (RT) and achieved surgical margins. The PERsonalised SARcoma Care (PERSARC) model, predicts overall survival (OS) and the probability of local recurrence (LR) at 3, 5 and 10 years. Aim Development and validation, by internal validation, of the PERSARC prediction model. Methods The cohort used to develop the model consists of 766 ESTS patients who underwent surgery, between 2000 and 2014, at five specialised international sarcoma centres. To assess the effect of prognostic factors on OS and on the cumulative incidence of LR (CILR), a multivariate Cox proportional hazard regression and the Fine and Gray model were estimated. Predictive performance was investigated by using internal cross validation (CV) and calibration. The discriminative ability of the model was determined with the C-index. Results Multivariate Cox regression revealed that age and tumour size had a significant effect on OS. More importantly, patients who received RT showed better outcomes, in terms of OS and CILR, than those treated with surgery alone. Internal validation of the model showed good calibration and discrimination, with a C-index of 0.677 and 0.696 for OS and CILR, respectively. Conclusions The PERSARC model is the first to incorporate known clinical risk factors with the use of different treatments and surgical outcome measures. The developed model is internally validated to provide a reliable prediction of post-operative OS and CILR for patients with primary high-grade ESTS. Level of significance level III.

Objectives This study investigates the effect of surgical margins and radiotherapy, in the presence of individual baseline characteristics, on survival in a large population of high-grade soft tissue sarcoma of the extremities using a multistate model. Design A retrospective multicentre cohort study. Setting 4 tertiary referral centres for orthopaedic oncology. Participants 687 patients with primary, non-disseminated, high-grade sarcoma only, receiving surgical treatment with curative intent between 2000 and 2010 were included. Main outcome measures The risk to progress from ‘alive without disease’ (ANED) after surgery to ‘local recurrence’ (LR) or ‘distant metastasis (DM)/death’. The effect of surgical margins and (neo)adjuvant radiotherapy on LR and overall survival was evaluated taking patients9 and tumour characteristics into account. Results The multistate model underlined that wide surgical margins and the use of neoadjuvant radiotherapy decreased the risk of LR but have little effect on survival. The main prognostic risk factors for transition ANED to LR are tumour size (HR 1.06; 95% CI 1.01 to 1.11 (size in cm)) and (neo)adjuvant radiotherapy. The HRs for patients treated with adjuvant or no radiotherapy compared with neoadjuvant radiotherapy are equal to 4.36 (95% CI 1.34 to 14.24) and 14.20 (95% CI 4.14 to 48.75), respectively. Surgical resection margins had a protective effect for the occurrence of LR with HRs equal to 0.61 (95% CI 0.33 to 1.12), and 0.16 (95% CI 0.07 to 0.41) for margins between 0 and 2 mm and wider than 2 mm, respectively. For transition ANED to distant metastases/Death, age (HR 1.64 (95% CI 0.95 to 2.85) and 1.90 (95% CI 1.09 to 3.29) for 25–50 years and >50 years, respectively) and tumour size (1.06 (95% CI 1.04 to 1.08)) were prognostic factors. Conclusions This paper underlined the alternating effect of surgical margins and the use of neoadjuvant radiotherapy on oncological outcomes between patients with different baseline characteristics. The multistate model incorporates this essential information of a specific patient9s history, tumour characteristics and adjuvant treatment modalities and allows a more comprehensive prediction of future events.

Dear Mr John Hunter, Thank you very much for the thorough history of your patient, who presented with a mass in the thigh. We have now had the opportunity to review the case notes and specimens at the Sarcoma Unit at the Royal Marsden Hospital. We apologise for the breach of requirements on waiting times for cancer treatment, but your patient’s presentation in 1786 predated our founding in 1851. #### John Hunter (1728-93) John Hunter was one of the most distinguished surgeons of his day. He worked at St George’s Hospital in his later career and was appointed as surgeon to King George III. He is said to have died after an argument over the admission of medical students. The specimens and notes reviewed in this article are kept within the Hunterian museum at The Royal College of Surgeons. For our records we quote the following extract from your original notes: > “A man came into St George’s Hospital, November 1786, with a hard swelling of the lower part of the thigh. It appeared to be a thickening of the bone. It was increasing very rapidly, and at this time so large as to interfere with the motion of the joint, so as to render the leg useless. The tumour was hard as bone. > > The man had been in perfect health in this part, till about 5 months before, and then began to feel shooting or darting pains in that part of the thigh. The part began evidently to enlarge, although at first very slowly; but in the …

We present a first case of synovial sarcoma in an HIV-positive pregnant woman. This 28-year-old woman was diagnosed with synovial sarcoma, a high-grade malignant soft tissue sarcoma, involving her left thigh during the first trimester of her pregnancy. She underwent surgical treatment in the form of hip disarticulation at 30 weeks’ gestation. She was subsequently delivered by emergency caesarean section (CS) at 34 weeks’ gestation when she presented with wound sepsis and a scan revealed static growth in a small for gestational age fetus. Prompt diagnosis and treatment of this aggressive tumour is important and should involve a multidisciplinary approach, with a balanced consideration of the maternal and fetal outcomes.

Aims Pigmented villonodular synovitis (PVNS) is a rare, locally aggressive and potentially recurrent synovial disease. We present the largest single-centre experience of knee PVNS. Our aim was to evaluate our tertiary hospital's experience in the management of knee PVNS. Patients and methods Retrospective data collection of consecutive cases of knee PVNS from 2002 to 2015. Results In total, 214 cases of knee PVNS were identified which represented 53.4% of all PVNS (12.1% were recurrent at presentation). 100 were localised PVNS (LPVNS), 114 diffuse PVNS (DPVNS) and two malignant PVNS. Knee PVNS was more likely to occur in females with a mean age of 39. Following surgery, 47.6% had recurrence with DPVNS as opposed to 8.6% with LPVNS. In LPVNS, there was no significant difference in recurrence between open and arthroscopic synovectomy (8.7% vs 9.1%, P >0.05). However, in DPVNS, there was a significantly higher risk of recurrence with arthroscopic compared to open synovectomy (83.3% vs 44.8%, RR =1.86 95% CI 1.32–2.62, P =0.0004). Conclusion PVNS can be difficult to treat. We found no difference in local recurrence rates between open and arthroscopic treatment of LPVNS but significantly increased rates of recurrence for DPVNS following arthroscopic treatment. We would therefore recommend open synovectomy for DPVNS.

Bone metastasis is a common problem affecting a significant proportion of patients with metastatic cancer. Bone metastasis can present in a number of ways and the patients may need surgical stabilisation of their lesions. There are many important considerations in the care of these patients that need to be borne in mind including their increased anesthetic risks and potential risk of complications. There are continuous developments in the prevention, diagnosis and treatment with advances in imaging, orthopaedic technique and medication, particularly radiopharmaceuticals and cytotoxic, endocrine treatments with newer treatments based around the tumour cell-osteoclast interaction. Having a better understanding of these considerations and developments is important in allowing the optimisation of the care of the patient with bone metastasis.

Polymethyl methacrylate spacers are commonly used during staged revision knee arthroplasty for infection. In cases with extensive bone loss and ligament instability, such spacers may not preserve limb length, joint stability and motion. We report a retrospective case series of 19 consecutive patients using a custom-made cobalt chrome hinged spacer with antibiotic-loaded cement. The “SMILES spacer” was used at first-stage revision knee arthroplasty for chronic infection associated with a significant bone loss due to failed revision total knee replacement in 11 patients (58%), tumour endoprosthesis in four patients (21%), primary knee replacement in two patients (11%) and infected metalwork following fracture or osteotomy in a further two patients (11%). Mean follow-up was 38 months (range 24–70). In 12 (63%) patients, infection was eradicated, three patients (16%) had persistent infection and four (21%) developed further infection after initially successful second-stage surgery. Above knee amputation for persistent infection was performed in two patients. In this particularly difficult to treat population, the SMILES spacer two-stage technique has demonstrated encouraging results and presents an attractive alternative to arthrodesis or amputation.

Neuritis ossificans is an extremely rare reactive process affecting peripheral nerves, which can be challenging to diagnose and treat. Magnetic resonance imaging (MRI) is an excellent imaging modality for these lesions, showing inflammatory reaction around the nerve. Only a few cases have been previously reported, and all of the patients underwent surgical resection. In this article we report the first case of neuritis ossificans affecting the common peroneal nerve, treated non-operatively, and we review the literature.

Metastatic pathological fractures of the proximal femur are increasingly treated by endoprosthetic proximal femoral replacement. We report the results and the costs incurred performing these procedures at our supra-regional sarcoma unit. Sixty-two patients underwent 63 proximal femoral replacements for metastatic bone disease over a seven-year period. Breast cancer was the most common primary pathology. One patient underwent a revision procedure for infection. Twenty-two patients suffered dislocations, most commonly those undergoing a conventional arthroplasty articulation. The estimated cost of a proximal femoral replacement is 18,002 pounds at our centre. Less than half of this is reimbursed under Payment by Results. Endoprosthetic replacement of the proximal femur is an effective treatment of metastases, but is poorly reimbursed under current funding arrangements.

Radiographs of 33 patients who had an expandable prosthesis inserted after tumor resection in the distal femur were evaluated. We hypothesized that, when a sleeve was present, there was greater stem migration and cortical reaction. The thickness of medial and lateral cortices of the tibia was measured at 6 months and on the last follow-up radiograph. The distance from the edge of the prosthesis to the cortical edge was also compared. When a sleeve was present, there was greater stem migration (P < .001) and a greater increase in lateral cortical thickness (P < .001). There was a higher revision rate when a sleeve was used, but this was not statistically significant. There was no difference in function according to the Toronto Extremity Salvage Score (TESS) between the 2 groups. This is the first study to demonstrate that the presence of a polyethylene sleeve is associated with a tendency for the tibial prosthesis to migrate laterally and cause a greater sclerotic reaction.

The authors review the outcome of a consecutive series of 24 free vascularized fibular grafts performed as part of a limb-salvage procedure following tumor excision. There were 15 women and nine men with a mean age of 26 years (range: 6 to 52 years). The minimum follow-up was 12 months. The mean length of the graft was 13.1 cm. (range: 4.5 to 25 cm). Fifteen grafts were used in the upper limb, eight in the lower limb, and one in the pelvis. Bony union was achieved in 21/24 patients at a mean of 9.3 months. Complications occurred in 13/24 patients of whom 11 required a second operation. Four patients died of metastatic disease. The mean Musculoskeletal Tumor Society (MSTS) functional score in the remaining 20 was 84.5 percent, with 16 patients having a good or excellent outcome. Free vascularized fibula grafts offer a reliable method of reconstruction after excision of bone tumors. Although the incidence of complications appears high, they are relatively easy to correct, bony union is achieved in the majority, and functional outcome is good.

Significantly reduced distance between the ischium and the femur can result in symptomatic hip pain as a result of impingement. We present the case of a 16-year-old boy who presented with groin pain which had been affecting him for a year and a half following an innocuous football injury. Plain radiograph revealed a chronic apophyseal avulsion fracture of the ischium with excessive callus formation. CT scan and MRI revealed that the bony protuberance was responsible for symptomatic ischiofemoral impingement. In this case, he was successfully treated with non-operative management involving slow re-introduction to exercise. An unusual example of acquired ischiofemoral impingement, unrelated to surgery or significant trauma, this case highlights the need to consider such a diagnosis in otherwise unexplained groin pain.

To describe the imaging and histopathology of pseudomyogenic hemangioendothelioma. Five cases of pseudomyogenic hemangioendothelioma, which presented over the last 5 years, were retrieved from the files of the Royal National Orthopaedic Hospital. The imaging and histopathology were reviewed in all cases. Magnetic resonance imaging, which was available from all cases, was assessed for the following features: the number of lesions, location in soft tissue (superficial and or deep/subfascial) and bone, and the signal characteristics and morphology of individual lesions. Immunohistochemistry was performed in all cases to characterize the lesions. Four of the five patients had multiple lesions involving a single limb. Bone was involved in 3 of the 5 individuals. All tumors diffusely expressed ERG and cytokeratins AE1/3, but not MNF116. CD31 was weakly positive in 4 cases. INI-1 expression was retained in all cases. Imaging features included ill-defined, infiltrative lesions in subcutaneous fat with extension to the adjacent skin, poor- to well-defined intramuscular nodules and predominantly intracortical focal bone lesions with rare medullary involvement. Pseudomyogenic hemangioendothelioma represents a distinct recently characterized tumor type presenting in young adults, with a tendency towards multicentric bone and soft tissue involvement.

The aim of this study was to establish whether the proximity of significant neurovascular structures around the surgical excision results in higher rates of recurrence and poorer survival outcomes. A retrospective study of all patients treated at a regional bone tumour unit for proximal fibula Ewing's tumours and osteosarcomas was conducted, and in total 17 patients were identified. The recurrence rate of all cases was 29.4% and the overall 5 year survival was 70.5%. The recurrence rate just for osteosarcoma was 50%, which compared poorly to published recurrence rates throughout the appendicular skeleton. The 5-year survival for proximal fibula osteosarcoma of 50% was also worse than generalised survivorship data reported in non-metastatic osteosarcoma. This series demonstrates that malignant proximal fibula tumours are a difficult entity to manage and recurrence rates and patient survival are poor for osteosarcoma.

The optimal reconstructive method after resection of malignant bone tumours of the proximal ulna is unknown.We report the outcome of endoprosthetic replacement in a young patient population.This was a retrospective review of four patients[three males and one female; mean age 17.5 (range 11–31)years] who underwent limb salvage with a proximal ulnar endoprosthetic replacement following excision of malignant bone tumour. Mean follow-up was 85 (range 14–194) months.All patients were alive at final follow-up and reported an improvement in pain. One patient required transhumeral amputation for intralesional excision complicating a local recurrence at one month. Two patients developed fixed flexion deformities of the elbow, one of whom required radial-head excision. Mean Musculoskeletal Tumour Society (MSTS)score and Toronto Extremity Salvage Score (TESS) were 27(range 25–28) and 81 (73–88), respectively.Custom-made proximal ulna endoprosthetic replacement following resection of malignant bone tumours in young patients provides a stable reconstruction option with satisfactory function and without apparent compromise in patient survival.

We describe a patient who developed a mass extending into the pelvis, five years after a metal-on-polyethylene total hip arthroplasty (THA). The histological pattern of perivascular lymphocytic infiltrate and fibrinoid necrosis was more in keeping with a metal-on-metal bearing failure. The pseudotumour compressed the femoral vein causing a deep venous thrombosis.

♦ Unicameral bone cyst♦ Aneurysmal bone cyst♦ Non-ossifying fibroma/fibrous cortical defect♦ Bone island♦ Fibrous dysplasia♦ Osteochondroma♦ Enchondroma♦ Langerhans cell histiocytosis♦ Chondroblastoma♦ Giant cell tumour♦ Osteoblastoma/osteoid osteoma♦ 12.Periosteal chondroma.

♦ Total hip replacements (THRs) may fail in various ways. They may become infected, they may be subject to aseptic loosening, they may dislocate, or a periprosthetic fracture may occur. The patient with a failed THR must be thoroughly assessed before treatment is contemplated♦ Infection may be acute or chronic. Assessment involves clinical assessment, plain radiographs, blood tests (C-reactive protein and erythrocyte sedimentation rate), hip aspiration, and, sometimes, nuclear medicine. The acutely infected hip may be treated with one-stage revision. This involves thorough lavage, debridement, and exchange of all modular components as well as long-term antibiotic therapy. The gold standard of treatment for a chronically infected THR is a two-stage revision. Success rates of 80–90% can be expected♦ Aseptic loosening typically occurs at the cement bone interface in hips where a metal-on-polyethylene bearing couple has been used. Bone resorption takes place as a result of an inflammatory response to small wear particles. After infection has been excluded the treatment of choice is a single-stage revision♦ Dislocation may be the result of patient factors, implant factors, or poor surgical technique. It is imperative for the clinician to minimize the risk by selecting patients carefully, using the correct combination of implants and performing surgery accurately♦ The management of periprosthetic fractures depends on how well the implants are fixed and quality of bone stock. Treatment ranges from simple fixation of the fracture through to revision augmented with strut allograft.

♦ Ganglion cyst♦ Intramuscular myxoma♦ Myositis ossificans♦ Nodular fasciitis♦ Haemangioma♦ Lipoma♦ Cavernous lymphangioma♦ Glomus tumour♦ Neurofibroma♦ Desmoid tumour♦ Elastofibroma♦ Schwannoma♦ Synovial chondromatosis.

Background : The surgical treatment of bone tumours can result in large peri-operative blood loss, due to their large sizes and hypervascularity. Pre-operative embolisation has been successfully used to downgrade vascularity, thus reducing peri-operative blood loss and its associated complications. Methods : Pre-operative embolisation was successfully undertaken on twenty-six patients with a variety of primary and secondary bone tumours. Results : Mean blood loss was 796 mL and we experienced no complications. Conclusion : 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. doi:10.4021/wjon389w

Chondrosarcoma is the second most common primary malignant bone tumour. Distinguishing between grades is not necessarily straightforward and may alter the disease management. We evaluated the correlation between histological grading of the preoperative image-guided needle biopsy and the resection specimen of 78 consecutive cases of chondrosarcoma of the femur, humerus, and tibia. In 11 instances, there was a discrepancy in histological grade between the biopsy and surgical specimen. Therefore, there was an 85.9% (67/78) accuracy rate for pre-operative histological grading of chondrosarcoma, based on needle biopsy. However, the accuracy of the diagnostic biopsy to distinguish low-grade from high-grade chondrosarcoma was 93.6% (73/78). We conclude that accurate image-guided biopsy is a very useful adjunct in determining histological grade of chondrosarcoma and the subsequent treatment plan. At present, a multidisciplinary approach, comprising experienced orthopaedic surgeons, radiologists, and pathologists, offers the most reliable means of accurately diagnosing and grading of chondrosarcoma of long bones.

Purpose: New markers that enable the percentage of transitional cell carcinomas (TCC) of the bladder that are diagnosed before invasion of the bladder muscle layers to be increased would reduce the morbidity and mortality associated with this disease. The purpose of this study was to develop a simple, accurate urine test based on mRNA markers and simple gene signatures that (a) could detect TCC before muscle invasion while maintaining high specificity in patients with hematuria or urinary tract infections and (b) identify patients most likely to have grade 3 or stage ≥T1 disease. Experimental Design: RNA markers with high overexpression in stage Ta tumors and/or T1 to T4 tumors but low expression in blood or inflammatory cells were characterized by quantitative reverse transcription-PCR using 2 mL of voided urine from 75 TCC patients and 77 control patients with other urological diseases. Results: A combination of the RNAs CDC2, MDK, IGFBP5, and HOXA13 detected 48%, 90%, and 100% of stage Ta, T1, and >T1 TCCs, respectively, at a specificity of 85%. Detection of Ta tumors increased to 60% for primary (non-recurrent) Ta tumors and 76% for Ta tumors ≥1 cm in diameter. Test specificity was 80% for the 20 control patients with urinary tract infections. The combination of CDC2 and HOXA13 distinguished between grade 1 to 2 TCCs and grade 3 or stage ≥T1 TCCs with ∼80% specificity and sensitivity. Conclusions: Simple gene expression signatures can be used as urine markers for the accurate detection and characterization of bladder cancer.

Desmoid fibromatosis (DF) is a heterogeneous condition with lack of consensus regarding therapy. Fatality is rare but repeated surgery prevalent. Functional assessment for this group is not well established, although we believe it to be an important marker of treatment success. At present there is no validated objective or subjective functional assessment tool designed for benign but locally invasive disease.

After surgical treatment of high-grade soft tissue sarcomas, local recurrences, metastases and survival remain a great concern. Further knowledge on factors with a possible impact on these endpoints, specifically resection margins, is relevant for decision-making regarding the aggressiveness of local treatment. The aim of this study is to investigate the impact of prognostic factors on local recurrence and overall survival for patients with high-grade soft tissue sarcomas of the extremities.In a retrospective cohort study of 127 patients (mean age 48 years, range five to 91; median follow-up 71 months) the prognostic effect of margin status and other clinicopathologic characteristics on local recurrence and overall survival were analysed by employing a multivariate Cox regression.Five-year cumulative incidence of local recurrence and distant metastases was 26% and 40%, respectively. The estimated five-year overall survival was 59%. Tumour size proved a consistent adverse prognostic factor for local recurrence (hazard ratio (HR) 3.9), distant metastasis (HR 4.9) and overall survival (HR 2.4). The significant association of resection margins with local recurrence (HR 10.2) was confirmed. Margins were however not significantly associated with the occurrence of distant metastasis or overall survival. The occurrence of local recurrence had a significant impact on overall survival (HR 2.0).The results of this study confirm the critical role of tumour size on survival and margins on local recurrence, and stress the need for further investigation concerning the association between margins, local recurrence and survival.