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.

Sclerosing Epithelioid Fibrosarcoma (SEF) versus Low Grade Fibromyxoid Sarcoma (LGFMS): Presentation and outcome in the nationwide NETSARC+ series of 330 patients over 13 years.

Sclerosing Epithelioid Fibrosarcoma (SEF) and Low Grade Fibromyxoid Sarcoma (LGFMS) are ultrarare sarcomas sharing common translocations whose natural history are not well known. We report on the nationwide exhaustive series of 330 patients with SEF or LGFMS in NETSARC+ since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTB). Since 2010, (i) pathological review has been mandatory for sarcoma,and (ii) tumour/patients' characteristics have been collected in the NETSARC+ nationwide database. The characteristics of patients with SEF and LGFMS and their outcome are compared. RESULTS: 35/73 (48%) and 125/257(49%) of patients with SEF and LGFMS were female. More visceral, bone and trunk primary sites were observed in SEF (p < 0.001). 30% of SEF vs 4% of LGFMS patients had metastasis at diagnosis (p < 0.0001). Median size of the primary tumor was 51 mm (range 10-90) for LGFMS vs 80 (20-320) for SEF (p < 0.001). Median age for LGFMS patients was 12 years younger than that of SEF patients (43 [range 4-98] vs 55 [range 10-91], p < 0.001). Neoadjuvant treatment was more often given to SEF (16% vs 9%, p = 0.05). More patients with LGFMS were operated first in reference centers (51% vs 26%, p < 0.001). The R0 rate on the operative specimen was 41% in LGFMS vs 16% in SEF (p < 0.001). Median event-free survival (EFS) of patients with SEF and LGFMS were 32 vs 136 months (p < 0.0001). The median overall survival (OS) was not reached. Fifty-months OS was 93% vs 81% for LGFMS vs SEF (p = 0.05). Median OS was 77 months after first relapse, similar for SEF and LGFMS. In multivariate analysis, age, tumor size, metastasis at diagnosis were independent prognostic factors for OS in LGFMS. CONCLUSIONS: Although sharing close molecular alterations, SEF and LGFMS have a different natural history, clinical presentation and outcome, with a higher risk of metastatic relapse in SEF. Survival after relapse is longer than with other sarcomas, and similar for SEF and LGFMS.

Epithelioid hemangio-endothelioma (EHE) in NETSARC: The nationwide series of 267 patients over 12 years.

EPITHELIOID HEMANGIOENDOTHELIOMA: A NATIONWIDE STUDY: Epithelioid hemangioendothelioma (EHE) is an ultrarare sarcoma whose natural history and treatment is not well defined. We report on the presentation and outcome of 267 patients with EHE in the NETSARC+ network since 2010 in France. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centres with specialised multidisciplinary tumour boards (MDTB), funded by the French National Cancer Institute (NCI), Institut National du Cancer (INCA). Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients. Patients' characteristics are collected in a nationwide database regularly monitored with stable incidence since 2013. The characteristics of patients with EHE at diagnosis are presented as well as progression-free survival (PFS), overall survival (OS), and outcome under treatment. RESULTS: Two hundred and sixty-seven patients with EHE were included in the NETSARC+ database since 2010. Median age in the series was 51 (range 10-90) years, 58% were women. Median tumour size was 37 mm (4-220). Forty-eight percent, 42%, and 10% were visceral, soft parts, or bone primaries. The most frequent sites were liver (28%), lung (13%). 40% were reported to have systemic (i.e. multifocal or metastatic disease) at diagnosis. With a median follow-up of 20 months, OS and PFS rates at 24 months were 82% and 67%, with 10-year projected OS and PFS of 62% and 21% respectively. Male and M+ patients at diagnosis had a significantly worse OS, but not PFS. Local treatment was associated with a favourable survival in localised but not in patients with advanced stage at diagnosis. For 23 patients receiving medical treatment, PFS and OS were 50.2% and 33.2% at 60 months were respectively. CONCLUSIONS: EHE is a frequently metastatic sarcoma at diagnosis with a unique natural history. This study shows in a nationwide series over 12 years that most patients progressed but are still alive at 10 years, both in localised and metastatic stages.

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.

Lung metastases of diffuse giant cell tumour of the fibular tendon sheath at the ankle: A case report.

Diffuse giant cell tumours of the tendon sheaths are described in the literature as locally aggressive soft-tissue tumours. We report the case of a 56-year-old male with a history of multiple surgical procedures for a giant cell tumour of the fibular tendon sheath at the right ankle. The multiple recurrences prompted monitoring by positron-emission tomography, which showed lung tumours. Biopsies confirmed that the tumours were metastases from the giant cell tumour of the tendon sheath. In patients with recurrent and/or diffuse giant cell tumour, positron-emission tomography is an effective monitoring tool.

First case of osteomyelitis due to Erysipelothrix rhusiopathiae: pubic osteomyelitis in a gored farmer.

We report the first proven case of osteomyelitis due to Erysipelothrix rhusiopathiae. This infection occurred almost 20 years after traumatic inoculation of the bacterium, when the patient was gored by one of his cows. Diagnosis was made by bone biopsies, and treatment included rifampicin and levofloxacin for 3 months.

[Total hip arthroplasty for treatment of acute acetabular fracture in elderly patients]. / L'arthroplastie totale de hanche dans le traitement des fractures récentes de l'acétabulum du sujet âgé

PURPOSE OF THE STUDY: The standard treatment of displaced acetabular fractures is open reduction and internal fixation (ORIF). In elderly patients, ORIF may not be the best option because of osteoporotic bone and the necessary period of bed rest. Primary total hip arthroplasty (THA) for displaced acetabular fractures was initiated by Westerborn in 1954. Since then, several authors described their experience and since 1986 many studies have reported good results with this type of treatment. This study assessed outcome obtained in patients treated by primary THA for acetabular fracture in the orthopedic department of the Dupuytren Teaching Hospital in Limoges. MATERIAL AND METHODS: Between 1981 and 2001, 16 patients, mean age 76.1 years (range 64-89) were treated with primary THA for recent displaced acetabular fractures. Bone loss was quantified using the SOFCOT classification for acetabular revision THA: stage III was noted in four patients (25%) and stage IV in twelve (75%). No attempts were made to achieve anatomic reduction of fracture fragments, but a reinforcement ring was used, coupled with autologous bone graft for the acetabulum. All patients were assessed clinically using the Postel-Merle d'Aubigné et Harris scores and the Devane activity scale. Radiographs were used to assess union and signs of loosening according to De Lee and Charnley and the Gruen classifications. Ossifications were quantified with the Brooker classification. RESULTS: Mean follow-up was three years. The mean Harris hip score was 73.6 (range 47-93), and the mean Postel-Merle d'Aubigné score 13.8 (range 10-17). Twelve patients (75%) returned to their initial activity level on the Devane scale; only four decreased their daily activity by one level. All patients but one were satisfied. There was one case of partial neurological sensorial deficit. There were no postoperative dislocations. All fractures healed. There were six cases (37%) of heterotopic bone formation including grade IV ossification in one patient with a stiff hip which required surgical resection. There were five cases of radiolucent halo in one zone of the cup, and one case in two zones; all these lucencies were non-progressive and there was not sign of loosening at last follow-up. DISCUSSION: Orthopedic treatment for displaced acetabular fractures in elderly patients may not be suitable because of the risk of complications due to the prolonged period of decubitus. ORIF requires one surgery, but may nevertheless lead to a second operation because of osteoarthritis. Primary THA has many advantages: full weight bearing is achieved rapidly, decubitus complications are avoided, functional outcome was good with union for all of the fractures in our series. Nevertheless, despite differences between surgical procedures reported in the literature, ectopic ossifications are common and the overall rate of dislocation reaches 7% considering all reported series. CONCLUSIONS: In selected patients with a displaced acetabular fracture, we believe that an acute THA may provide several advantages including only one procedure and quick weight bearing with a lower rate of decubitus complications. In this small series, functional outcome was good for most of the patients who recovered their initial activity level.

Is troponin I gene therapy effective for osteosarcoma treatment? Study on a human-like orthotopic rat model.

BACKGROUND: An anti-angiogenesis strategy has been widely recognized as a viable approach to fight cancer and more and more anti-angiogenic factors are continually being identified. Among them, the muscular isoform of Troponin I (TnI) has been described as being a powerful anti-angiogenic agent in vitro as well as in vivo. We investigated the therapeutic efficacy of TnI gene therapy in a human-like orthotopic rat osteosarcoma model. MATERIALS AND METHODS: In this tumor model, we evaluated whether the administration of the secreted TnI coding sequence complexed to cationic liposomes (named TnITag cDNA/lCLP) could induce a delay in tumor growth and reduce tumor vasculature. RESULTS: Although TnI specifically inhibited endothelial cell growth in vitro, we were not able to demonstrate any therapeutic efficacy of TnI in the transplantable osteosarcoma model. CONCLUSION: This lack of efficacy probably resulted from the rapid degradation of recombinant TnI by matrix metalloproteinases, especially MMP2, which are present in large amounts in tumors.

The results of endoprosthetic replacement for tumours of the distal humerus.

Ten patients underwent endoprosthetic replacement of the distal humerus for bone tumours over a period of 30 years. There were eight primary and two secondary tumours in four men and six women with a mean age of 47.5 years (15 to 76). The mean follow-up was eight years (9 months to 31 years). Four patients required further surgery, three having revision for aseptic loosening; two of these and one other later needing a rebushing. There were no cases of postoperative nerve palsy, infection, local recurrence or mechanical failure of the implant. Four patients died from their disease, all with the prosthesis functioning satisfactorily. At follow-up the mean flexion deformity of the elbow was 15 degrees (0 to 35) and the mean range of lexion was 115 degrees (110 to 135). The functional results showed a mean Toronto extremity salvage score of 73% of normal. Endoprosthetic replacement of the distal humerus and elbow is a satisfactory method of treating these rare tumours.

Risk factors for survival and local control in chondrosarcoma of bone.

We studied 153 patients with non-metastatic chondrosarcoma of bone to determine the risk factors for survival and local tumour control. The minimum follow-up was for five years; 52 patients had axial and 101 appendicular tumours. Surgical treatment was by amputation in 27 and limb-preserving surgery in 126. The cumulative rate of survival of all patients, at 10 and 15 years, was 70% and 63%, respectively; 40 patients developed a local recurrence between 3 and 87 months after surgery and 49 developed metastases. Local recurrence was associated with poor survival in patients with concomitant metastases but not in those without. On multivariate analysis independent risk factors for rates of survival include extracompartmental spread, development of local recurrence and high histological grade. Independent risk factors for local recurrence include inadequate surgical margins and tumour size greater than 10 cm. Location within the body, the type of surgery and the duration of symptoms are of no prognostic significance. Surgical excision with an oncologically wide margin provides the best prospect both for cure and local control in these patients.

[White finger and hypertrophy of the lumbrical muscles]. / Doigt blanc et hypertrophie des muscles lombricaux.

Within the digital vascularization diseases, we found a compression of the radial and ulnar collateral arteries of a finger by hypertrophy of the lumbrical muscles which was presented clinically in the form of a chronic sub-ischemia. A surgical release made it possible to recover a vascularized and sensitive finger.

[Elastofibroma in the scapular region. A case report and review of the literature]. / Elastofibrome de l'espace scapulo thoracique. Revue de la littérature à propos d'un cas.

PURPOSE OF THE STUDY: We report a case of elastofibroma and have collected 280 cases in the literature. MATERIAL AND METHODS: A 56 year-old man presented with a right subscapular mass. The patient was asymptomatic but he reported a "clicking"sensation associated with mobilization of the shoulder. Physical examination revealed a round mass clearly demonstrated with forward elevation of the arm. The MRI scan showed a heterogeneous soft tissue composed of inhomogeneous density with areas of more intense signal suggesting adipose tissue. The tumor was surgically excised and the diagnosis of elastofibroma was established by histopathologic examination. RESULTS: Six months after removal of the mass, there were no functional complications. DISCUSSION: Elastofibromas usually occur in active patients generally older than 55 years of age. They are typically located in the right subscapular region. The tumor remains asymptomatic in more than 50 percent of cases. 25 percent of the patients may report a simple discomfort sometimes with a "clicking" or "catching" sensation associated with mobilization of the arm. Pain is present in less than 10 percent of cases. Physical examination may reveal a rubbery, asymptomatic mass located in the subscapular region and barely noticable when the arm lies again the chest. Plain radiographs and preoperative laboratory data were unremarkable. CT scan or MRI scan may show an heterogeneous fibrous mass of intermediate density with entrapped signals of higher intensity. However, a definitive diagnosis requires a biopsy showing the distinctive feature of elastofibroma: elastic fibers in a collagenized fibrous tissue with entrapped adipose tissue. Pathogenesis of elastofibromas may result from the friction of the scapula against the thorax thus generating tumor growth. CONCLUSION: Complete surgical excision in symptomatic patients is considered to be the treatment of choice. However, once the diagnosis of elastofibroma has been established, excision of lesions smaller than 5 cm can be avoided in asymptomatic patients.

Extensible endoprostheses of the humerus after resection of bone tumours.

We carried out extensible endoprosthetic replacement of the proximal or total humerus in 18 children aged between six and 12 years, after resection of primary bone tumours mainly for osteosarcoma and Ewing's sarcoma. In 11 patients we performed 44 lengthening procedures, with an average of two per child annually and a mean total extension of 29.9 mm per patient. We were able to achieve lengthening of the operated limb with few complications and a mean functional rating of 79.3% according to the Enneking system. Progressive lengthening of these prostheses does not adversely affect the overall function of the arm, and superior subluxation of the head of the prosthesis has not been a problem.

[Use of a Russel-Taylor nail for stabilizing fractures of the femur. Apropos of 57 fractures with 30 computed tomographies of the rotation]. / Utilisation d'un clou non fendu de Russel-Taylor pour la stabilisation des fractures du fémur. A propos de 57 fractures avec 30 études tomodensitométriques de la rotation.

PURPOSE OF THE STUDY: A clinical and radiographical study with CT in 30 cases was undertaken in femoral fractures fixed with Russel-Taylor intramedullary nail. MATERIAL AND METHODS: In this retrospective study of 57 femoral fractures (mean follow-up 22 months), all fractures were analysed according to the classification of Wiss and Winquist-Hansen-Clawson. Fixation was performed with Russel-Taylor intramedullary mailing. Fifty fractures were classified as unstable due to the type of fracture and for its localization. Analysis of the clinical and radiographical results was performed immediately postoperatively and later by CT (30 cases). RESULTS: Clinical results showed seven cases of hip pain and limited walking capability; twenty with decreased hip mobility; twenty-one with functional impairment of the knee with limited flexion (11 cases) and/or knee sprain (15 cases). Radiographical results showed sixteen cases of leg shortening inferior to 1 cm, three between 1 and 2 cm, and one exceeded 2 cm; nine with varus angulation of 5 degrees, one with valgus angulation of 5 degrees, and seven with external rotation exceeding 10 degrees, five with internal rotation exceeding 10 degrees. Results were determined according to Thorensen's criteria. DISCUSSION: The use of Russel-Taylor intramedullary nail for the management of complex femoral fractures is discussed. Rotational deformities appeared related to the quality of reduction during surgery. Because of the stiffness of this type of nail, a smaller diameter can be used. Result analysis demonstrates that static nailing should probably be used more frequently in unstable femoral fractures.

Molecular basis of alpha-thalassemia in Sicily.

To evaluate the allelic frequency and genetic diversity of alpha-thalassemia defects in Sicily, both epidemiological and patient-oriented studies were carried out. For the epidemiological study, phenotypic data were collected on more than 1000 Sicilian individuals. Among them, 427 were explored at the molecular level for nine alpha-thalassemic variants known to be common in the Mediterranean region. Our data reveal an allele frequency of 4.1% for alpha(+)-thalassemia matching that of beta-thalassemia in this region. The presence of alpha0-thalassemia (--MEDI and --CAL) was observed only in the group of referred patients. Newly acquired nucleotide sequence data on the deletional breakpoint of --CAL allowed us to design a simple PCR-based procedure for exploring this allele. The data also provide additional information concerning the genetic mechanisms involved in such large deletions.

Occult dysraphism in adulthood. A series of 24 cases.

The results of a retrospective study of 24 adult patients with occult dysraphism are described. There were 15 males and 9 females, with an average age of 31.1 years. Specific circumstances precipitated symptomatic onset in 67% of patients. Pain, often referred to the anorectal region, was the most common presenting symptom. Bladder and bowel dysfunction were also common findings. The most common tethering lesions were intradural lipoma and a short thickened filum terminale. Myelography revealed the diagnosis of tethered conus in most cases, but the addition of CT and MRI images provided valuable structural details. The surgical outcome was gratifying in relation to pain and sensory-motor deficits but disappointing in the resolution of sphincter disorders. Our conclusion is that symptoms and/or signs of TCS with onset in adult life are not invariably irreversible.

[The lateral retromalleolar groove: a radio-anatomic study]. / La gouttière rétromalléolaire latérale: étude radio-anatomique.

The anatomy of the malleolar peroneal groove is presented. The results are based on a coupled osteological and CTscan study of 20 samples of fibulae. The average distal fibular torsion was 64 degrees. The peroneal groove was oriented posteriorly (mean value: 78 degrees). Three types of morphological variations were found: concave, flat, convex (the convex shaped groove was the most frequent one: 70%). The average width of the groove was 9 mm. These morphometric results were compared to "clinical" ones performed on patients with a peroneal tendons dislocation syndrome: CTscan study showed an osseous dysplasia concerning the groove depth (flat or convex) and/or a torsional insufficiency. Hypothesis of a bone dysplasia in peroneal dislocation syndrome is discussed.