Improved nationwide survival of sarcoma patients with a network of reference centers.

BACKGROUND: We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients' characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020. RESULTS: A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n = 9266 before 2013, n = 12 274 between 2013 and 2015, n = 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients >18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P < 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P < 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers. CONCLUSIONS: The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved.

Parosteal osteosarcoma associated with a low-grade component mimicking well-differentiated liposarcoma: a case report.

Parosteal osteosarcomas and well-differentiated liposarcomas are both well-differentiated locally aggressive tumors. They both have simple karyotypes with amplification of the 12q13-15 regions including MDM2 and CDK4 genes. In this report, we describe the case of a parosteal osteosarcoma intertwined with a low-grade component similar to a well-differentiated liposarcoma. The association of a bone component with an adipose component was initially overlooked. We describe the histological, imaging, and molecular characteristics of this tumor stressing the importance of radio-pathological correlation. To our knowledge, this is the second report of a parosteal osteoliposarcoma. Awareness of this rare presentation may allow radiologists and surgeons to recognize the peripheral fatty component as an integral part of the tumor.

Surgery in reference centers improves survival of sarcoma patients: a nationwide study.

BACKGROUND: NETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry. PATIENTS AND METHODS: Patients' characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497). RESULTS: Among the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li-Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P < 0.001 for all, with a hazard ratio of 0.681 (95% CI 0.618-0.749) for OS]. CONCLUSION: This nationwide registry of sarcoma patients shows that surgical treatment in a reference center reduces the risk of relapse and death.

[Review of patient-specific instrumentation for total knee prosthesis]. / Revue des guides personnalisés à usage unique dans les prothèses totales de genou.

OBJECTIVES: Single use patient-specific instruments (PSI) for total knee prosthesis are introduced as a new alternative to conventional ancillaries and computer assisted surgery by improving implants positioning. An exhaustive review was carried out to identify their specific characteristics, with their advantages and disadvantages. METHODS: Medical devices suppliers were consulted in 2015 for reviewing their PSI. Their technical, clinical and economic data were compared. The results had been submitted to an orthopaedics expert commission of our university hospital for clinical and financial opinion. RESULTS: Ten companies have provided the documentation for the analysis. PSI are manufactured by suppliers using a three dimensional printing method based on CT scans or MRI images. PSI are produced according to the surgeon's preferences after a preliminary data check, which can be performed by the suppliers' engineers, the surgeon and automatic calculation. Five suppliers can produce sterile PSI with optional delivery of 3D bone models. According to the experts, the studies failed to demonstrate the superiority of a PSI or hospital economic gain. The prices listed remain high and operating room time is not always significantly reduced. CONCLUSIONS: With the development of personalized medicine, the role of PSI grows in importance. They facilitate the surgeon's work by fully respecting the anatomy. These systems offer an interesting perspective in their technical and pedagogical aspects. But it seems premature to take them into routine use given the low number of high-level studies that were currently done.

Improved survival using specialized multidisciplinary board in sarcoma patients.

BACKGROUND: Sarcomas are rare but aggressive diseases. Specialized multidisciplinary management is not implemented for all patients in most countries. We investigated the impact of a multidisciplinary tumor board (MDTB) presentation before treatment in a nationwide study over 5 years. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized MDTB, funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients in France. Patients' characteristics and follow-up are collected in a database regularly monitored and updated. The management and survival of patients presented to these MDTB before versus after initial treatment were analyzed. RESULTS: Out of the 12 528 patients aged ≥15 years, with a first diagnosis of soft tissue and visceral sarcoma obtained between 1 January 2010 and 31 December 2014, 5281 (42.2%) and 7247 (57.8%) were presented to the MDTB before and after the initiation of treatment, respectively. The former group had generally worse prognostic characteristics. Presentation to a MDTB before treatment was associated with a better compliance to clinical practice guidelines, for example, biopsy before surgery, imaging, quality of initial surgery, and less reoperations (all P < 0.001). Local relapse-free survival and relapse-free survival were significantly better in patients presented to a MDTB before initiation of treatment, both in univariate and multivariate analysis. CONCLUSION: The compliance to clinical practice guidelines and relapse-free survival of sarcoma patients are significantly better when the initial treatment is guided by a pre-therapeutic specialized MDTB.

Effect of hypoxia/reoxygenation on the cytokine-induced production of nitric oxide and superoxide anion in cultured osteoarthritic synoviocytes.

OBJECTIVE: Hypoxia/reoxygenation (H/R) is an important feature in the osteoarthritis (OA) physiopathology. Nitric oxide (NO) is a significant proinflammatory mediator in the inflamed synovium. The purpose of this study was to investigate the effects of H/R on inducible NO synthase (iNOS) activity and expression in OA synoviocytes. In addition we studied the relationship between nitrosative stress and NADPH oxidase (NOX) in such conditions. METHODS: Human cultured synoviocytes from OA patients were treated for 24 h with interleukin 1-ß (IL-1ß), tumour necrosis factor α (TNF-α) or neither; for the last 6 h, they were submitted to either normoxia or three periods of 1-h of hypoxia followed by 1-h of reoxygenation. ·NO metabolism (iNOS expression, nitrite and peroxynitrite measurements) was investigated. Furthermore, superoxide anion O2(·-) production, NOX subunit expression and nitrosylation were also assessed. RESULTS: iNOS expression and nitrite (but not peroxynitrite) production were ~0.20 to ~0.12 nmol min(-1) mg proteins(-1) (P < 0.05), while NOXs' subunit expression and p47-phox phosphorylation were increased. NOXs and p47-phox were dramatically nitrosylated under H/R conditions (P < 0.05 vs normoxia). Using NOS inhibitors under H/R conditions, p47-phox nitrosylation was prevented and O2(·-) production was restored at normoxic levels (0.21 nmol min(-1) mg of proteins(-1)). CONCLUSIONS: Our results provide evidence for an up-regulation of iNOS activity in OA synoviocytes under H/R conditions, associated to a down-regulation of NOX activity through nitrosylation. These findings highlight the importance of radical production to OA pathogenesis, and appraise the metabolic modifications of synovial cells under hypoxia.

Psychometric properties of the OARSI/OMERACT osteoarthritis pain and functional impairment scales: ICOAP, KOOS-PS and HOOS-PS.

OBJECTIVES: To evaluate the psychometric properties of the OARSI-OMERACT questionnaires in comparison to the existing validated scales. METHODS: Consecutive hip or knee osteoarthritis patients consulting in an orthopedic department were enrolled in the study. Data collected were pain using the Intermittent and Constant Osteoarthritis Pain (ICOAP), a Numeric Rating Scale (NRS), the Western Ontario McMaster Universities' Osteoarthritis Index (WOMAC) pain subscale, the Lequesne pain subscale; functional impairment using the Knee disability and Osteoarthritis Outcome Score-Physical Function Shortform (KOOS-PS), the Hip disability and Osteoarthritis Outcome Score-Physical Function Shortform (HOOS-PS), a NRS, the WOMAC function sub-scale, the Lequesne function subscale. Validity was assessed by calculating the Spearman's correlation coefficient between all the scales. Reliability was assessed in out-patients with stable disease comparing the data collected within 2 weeks using the intra-class correlation coefficient (ICC). Responsiveness was assessed on the data from hospitalised patients prior to and 12 weeks after a total joint replacement (TJR) using the standardised response mean. RESULTS: Three hundred patients (mean age=68 years, females=62%, hip OA=57%) were included. There was a moderate to good correlation between ICOAP, KOOS-PS, HOOS-PS and the WOMAC, NRS and Lequesne scales. Reliability of the ICOAP hip OA HOOS-PS and KOOS-PS was good (ICC range 0.80-0.81) whereas it was moderate for knee ICOAP (ICC=0.65). Responsiveness of the ICOAP, KOOS-PS and HOOS-PS 12 weeks after TJR was comparable to responsiveness of other scales (SRM range: 0.54-1.82). CONCLUSIONS: The psychometric properties of the ICOAP, KOOS-PS and HOOS-PS were comparable to those of the WOMAC, Lequesne and NRS.

[Dedifferentiated chondrosarcoma: radiologic-pathologic correlation]. / Chondrosarcomes dédifférenciés: revue iconographique radio-pathologique.

Dedifferentiated chondrosarcomas are highly malignant tumors characterized by conventional low-grade chondrosarcoma with abrupt transition to foci that have dedifferentiated into a higher-grade noncartilaginous more aggressive sarcoma. The dedifferentiated component, an osteosarcoma or fibrosarcoma, determines the prognosis. Its identification is key for management. A diagnosis of dedifferentiated chondrosarcoma should be suggested by the presence of "tumoral dimorphism" with cartilaginous component and aggressive lytic component invading adjacent soft tissues.

Six-week antibiotic therapy after one-stage replacement arthroplasty for hip and knee periprosthetic joint infection.

OBJECTIVES: One-stage replacement arthroplasty for treatment of periprosthetic joint infection (PJI) results in similar cure rate than two-stage (around 85-92%), but antibiotic therapy duration is not well established. The aim of this study was to evaluate the efficacy of a short six-week antibiotic course in periprosthetic joint infections after onstage exchange. PATIENTS AND METHODS: Retrospective, observational study conducted at Orthopaedic Department of Cochin Hospital, Paris, between 1st January 2010 and 31 December 2015. Patients with a microbiologically proven PJI, treated with one-stage replacement and 6 weeks (+/1week) of antimicrobial therapy were included. Pearson's-χ2 and Wilcoxon tests were used to compare categorical and continuous variables. RESULTS: Fifty patients with periprosthetic joint infections (42 hip, 8 knee PJI) treated with one-stage replacement arthroplasty were included. Median age was 69.3 years (IQR 24.5-97.4). Infections occurred after a mean of 36 months (IQR 1-216). Bone biopsy cultures were positive for Staphylococcus spp. in 29 patients (58%), Cutibacterium acnes in 19 (38%), Gram-negative bacilli in 6 (12%). Polymicrobial infections occurred in 12 (24%). Intravenous antibiotics were administered for a median of 11 days (IQR 4-45) and 46 patients (92%) were switched to an oral therapy. Medium follow-up was of 32 months (IQR 12-101). Overall remission rate was 90%. CONCLUSIONS: A six-week course of antibiotics in knee and hip PJIs treated with one-stage RA has a satisfactory remission rate in this open study.

Pain after total hip arthroplasty: a psychiatric point of view.

After total hip arthroplasty (THA), many studies report that a small percentage of patients mention painful symptoms, whose origin remains more or less obscure. We investigated 1,000 patients who had undergone a THA at least one year before their inclusion in the survey protocol. Among these 1,000 patients, 64 were complaining of pain in the region of the operated hip. These were later examined and investigated, both clinically (physical and psychiatric examination) and paraclinically (radiography, biology). Those requiring it received adequate treatment and the others were only regularly followed up. We identified the cause of all but one patient's pain. In all cases except one, the symptoms of pain without physical cause had a psychiatric origin. The results of our study show that, if the clinical picture is not perfectly clear, a psychiatric screening before surgery could contribute to decreasing the incidence of pain syndrome after THA.

Multifocal Scedosporium apiospermum spondylitis in a cystic fibrosis patient.

We report the first case of multifocal Scedosporium apiospermum spondylitis in a cystic fibrosis patient. The infection, which occurred during voriconazole prophylaxis, disseminated contiguously from the base of the left lung and pleura and spread to vertebrae via the epidural space. S. apiospermum osteoarticular infections are rare, and are difficult to diagnose and cure because of their resistance to anti-fungal drugs.

The indications and donor-site morbidity of tibial cortical strut autografts in the management of defects in long bones.

Aims: The primary aim of this study was to determine the morbidity of a tibial strut autograft and characterize the rate of bony union following its use. Patients and Methods: We retrospectively assessed a series of 104 patients from a single centre who were treated with a tibial strut autograft of > 5 cm in length. A total of 30 had a segmental reconstruction with continuity of bone, 27 had a segmental reconstruction without continuity of bone, 29 had an arthrodesis and 18 had a nonunion. Donor-site morbidity was defined as any event that required a modification of the postoperative management. Union was assessed clinically and radiologically at a median of 36 months (IQR, 14 to 74). Results: Donor-site morbidity occurred in four patients (4%; 95% confidence interval (CI) 1 to 10). One patient had a stress fracture of the tibia, which healed with a varus deformity, requiring an osteotomy. Two patients required evacuation of a haematoma and one developed anterior compartment syndrome which required fasciotomies. The cumulative probability of union was 90% (95% CI 80 to 96) at five years. The type of reconstruction (p = 0.018), continuity of bone (p = 0.006) and length of tibial graft (p = 0.037) were associated with the time to union. Conclusion: The tibial strut autograft has a low risk of morbidity and provides adequate bone stock for treating various defects of long bones. Cite this article: Bone Joint J 2018;100-B:667-74.

Supervised or unsupervised exercise for the treatment of hip and knee osteoarthritis. Clinical practice recommendations.

OBJECTIVES: To develop clinical practice guidelines concerning supervised or unsupervised kinesiotherapy for treating lower-limb osteoarthritis (OA). METHOD: The SOFMER (French Physical Medicine and Rehabilitation Society) methodology, associating systematic literature review, collection of everyday clinical practice, and external review by a multidisciplinary expert panel, was used to develop guidelines. RESULTS-CONCLUSION: Physical exercise is a part of the treatment of lower-limb OA. An educational pre-program is recommended to inform the patient about the ease and effectiveness of the physical exercise. Use of the SOFMER methodology led to recommending a program of initial physical exercise supervised by a physiotherapist, then an unsupervised program at home with compliance. The type, intensity, and frequency of the exercises must be adapted to each patient. Complementary randomized controlled studies are necessary to characterize the best exercises and their intensity and frequency. The OA location and gravity, functional need, and characteristics of patients will be useful in future studies.

[Bizarre parosteal osteochondromatous proliferation (Nora's lesion): two cases]. / La lésion de Nora ou Bizarre Parosteal Osteochondromatous Proliferation: à propos de 2 cas

The lesion Nora described in 1983 as a bizarre parosteal osteochondromatous proliferation (BPOP) is a member of a group of osteocartilaginous surface lesions. BPOP is infrequent but new cases are regularly reported. We report two new cases with an unusual localization (ilion and distal humerus) and unusual size (9 cm for the iliac lesion). In light of these cases and reports in the literature, the main differential diagnoses of BPOP are exostosis and parosteal osteosarcoma.

[Multicentric giant-cell tumor]. / Tumeur à cellules géantes multifocale.

Nearly all (99) giant-cell tumors are solitary. The multicentric presentation is exceptional and not well elucidated. We report the case of a patient presenting five foci identified over an eleven-year period (right tibia, left 4th metacarpal, sacrum, right femur, left femur). The proliferation index was identified for each focus. A review of the literature shows that the development of a new center after treatment for giant-cell tumor is a well-known event, with a wide variability in localizations, number and time to development. The most recent data suggest that each center would be independent progressing according to an individual course. Since histological transformation is not observed and multicenter forms are very exceptional, we suggest that it would not be necessary to propose specific screening for patients with a giant-cell tumor but that it would be good to inform the patient of the possibility of multicentric presentations.

Metastatic fractures of long limb bones.

The diagnosis of pathological fracture should be considered routinely in patients with long limb-bone fractures. Investigations must be performed to establish the diagnosis of pathological fracture then to determine that the bone lesion is a metastasis. In over 85% of cases, the clinical evaluation combined with a detailed analysis of the radiographs is sufficient to determine that the fracture occurred at a tumour site. Aetiological investigations establish that the tumour is a metastasis. In some patients, the diagnosis of metastatic cancer antedates the fracture. When this is not the case, a diagnostic strategy should be devised, with first- to third-line investigations. When these fail to provide the definitive diagnosis, a surgical biopsy should be performed. The primaries most often responsible for metastatic bone disease are those of the breast, lung, kidney, prostate, and thyroid gland. However, the survival gains provided by newly introduced treatments translate into an increased frequency of bone metastases from other cancers. The optimal treatment of a pathological fracture is preventive. The Mirels score is helpful for determining whether preventive measures are indicated. When selecting a treatment for a pathological fracture, important considerations are the type of tumour, availability of effective adjuvant treatments, and general health of the patient. Metastatic fractures are best managed by a multidisciplinary team. The emergent treatment should start with optimisation of the patient's general condition, in particular by identifying and treating metabolic disorders (e.g., hypercalcaemia) and haematological disorders. Treatment decisions also depend on the above-listed general factors, location of the tumour, and size of the bony defect. Prosthetic reconstruction is preferred for epiphyseal fractures and internal fixation for diaphyseal fractures.

Proximal femoral osteosarcoma: Diagnostic challenges translate into delayed and inappropriate management.

BACKGROUND: The proximal femuris is an uncommon site of osteosarcoma. The unusual manifestations at this site may lead to diagnostic and therapeutic mistakes. We therefore performed a retrospective study to estimate the proportions of patients with imaging study findings and/or clinical manifestations typical for osteosarcoma and/or inappropriate treatment decisions. HYPOTHESIS: Proximal femoral osteosarcoma often produces atypical clinical and radiological presentations. MATERIAL AND METHODS: Consecutive patients who underwent surgery at our center to treat proximal femoral osteosarcoma were included. For each patient, we collected the epidemiological characteristics, clinical symptoms, imaging study findings, treatment, and tumor outcome. Proportions were computed with their confidence intervals. RESULTS: Twelve patients had surgery for proximal femoral osteosarcoma between 1986 and 2015. Imaging findings were typical in 1 (8%) patient; they consisted of ill-defined osteolysis in 11/12 (92%) patients, a periosteal reaction in 1/12 (8%) patient, soft tissue involvement in 7/12 (58%) patients, and immature osteoid matrix in 11/12 (92%) patients. No patient had the typical combination of pain with a soft tissue swelling. Management was inappropriate in 2/12 (17%) patients, who did not undergo all the recommended imaging studies before surgery and were treated in another center before the correct diagnosis was established. At last follow-up, 4 patients had died (after a mean of 7 years) and 8 were alive (after a mean of 4 years). CONCLUSION: Proximal femoral osteosarcoma is uncommon and rarely produces the typical clinical and imaging study findings. The atypical presentation often results in diagnostic errors and inappropriate treatments. Ill-defined osteolysis on standard radiographs should prompt computed tomography or magnetic resonance imaging of the proximal femur. Treatment in a specialized center is imperative. LEVEL OF EVIDENCE: IV, retrospective study.

Is it safe to preserve the deltoid when resecting the proximal humerus for a primary malignant bone tumour? A comparative study.

AIMS: Resection of the proximal humerus for the primary malignant bone tumour sometimes requires en bloc resection of the deltoid. However, there is no information in the literature which helps a surgeon decide whether to preserve the deltoid or not. The aim of this study was to determine whether retaining the deltoid at the time of resection would increase the rate of local recurrence. We also sought to identify the variables that persuade expert surgeons to choose a deltoid sparing rather than deltoid resecting procedure. PATIENTS AND METHODS: We reviewed 45 patients who had undergone resection of a primary malignant tumour of the proximal humerus. There were 29 in the deltoid sparing group and 16 in the deltoid resecting group. Imaging studies were reviewed to assess tumour extension and soft-tissue involvement. The presence of a fat rim separating the tumour from the deltoid on MRI was particularly noted. The cumulative probability of local recurrence was calculated in a competing risk scenario. RESULTS: There was no significant difference (adjusted p = 0.89) in the cumulative probability of local recurrence between the deltoid sparing (7%, 95% confidence interval (CI) 1 to 20) and the deltoid resecting group (26%, 95% CI 8 to 50). Patients were more likely to be selected for a deltoid sparing procedure if they presented with a small tumour (p = 0.0064) with less bone involvement (p = 0.032) and a continuous fat rim on MRI (p = 0.002) and if the axillary nerve could be identified (p = 0.037). CONCLUSION: A deltoid sparing procedure can provide good local control after resection of the proximal humerus for a primary malignant bone tumour. A smaller tumour, the presence of a continuous fat rim and the identification of the axillary nerve on pre-operative MRI will persuade surgeons to opt for a deltoid resecting procedure. Cite this article: Bone Joint J 2017;99-B:1244-9.