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Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_23 | Pages 70 - 70
1 Dec 2016
Aubin G Gouin F Lepelletier D Jacqueline C Heymann D Asehnoune K Corvec S
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Aim

Propionibacterium acnes is an emerging pathogen especially in orthopedic implant infection. Interestingly, we previously reported a difference in the distribution of the clades involved in spine versus hip or knee prosthetic infection. To date, no study has previously explored the direct impact and close relationship of P. acnes on bone cells according to their own genetic background. The aim of this study was to investigate this interaction of P. acnes clinical strains involved in spine material infections, arthroplasty infections and acne lesions with bone cells.

Method

From a large collection of 88 P. acnes clinical isolates collected between January 2003 and December 2014, a subset of 11 isolates was studied. Four isolates were recovered from spine infections, two from prosthetic infections (knee and hip), three from acne lesions and two reference strains (ATCC11827 and ATCC6919). Implant-associated infections were confirmed according to Infectious Diseases Society of America guidelines for bone and joint infections. Multi-Locus Sequence Typing (MLST) was carried out on all isolates as described by Lomholt et al. PLoS ONE 2010. Bacterial internalization experiments with MG63 osteosarcoma cells were adapted from Crémet et al. Pathog Dis 2015.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_15 | Pages 76 - 76
1 Dec 2015
Aubin G Gouin F Lepelletier D Jacqueline C Ashenoune K Corvec S
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Propionibacterium acnes is an emerging pathogen especially in orthopedic implant infection. Aim of this study was to investigate P. acnes phylogeny and to screen for virulence factors among a large collection of clinical isolates involved in spine material infections, arthroplasty infections and acne lesions.

88 P. acnes clinical isolates were collected between January 2003 and December 2014 at Nantes University Hospital (France). Fifty-eight isolates came from spine infections, 14 from prosthetic infections (knee, hip or shoulder), 14 from acne lesions and two reference strains (ATCC11827 and ATCC6919). Implant associated infections were confirmed using Infectious Diseases Society of America criteria for bone and joint infections. Phylotypes and Multi-Locus Sequence Typing (MLST) was carried out on all isolates as described by Lomholt et al. All isolates were tested by established PCR-based assays for 21 putative virulence factor genes characteristic of P. acnes.

MLST analysis revealed an association between clonal complexes (CCs) and origin of P. acnes isolates (p = 0,027). Regarding CCs distribution between different origins, CC36 and phylotype II P. acnes isolates are more frequently observed in prosthetic joint infections. On the other hand, CC18 (IA) and CC28 (IB) P. acnes isolates are more frequently involved in spine infections and acne lesions.

Among all virulence factors screened, hyaluronate lyase gene was only present in CC36 and phylotype II P acnes isolates. Other virulence factors were present in all isolates, whatever their origin or CC.

Regarding molecular typing results, P. acnes involved in spine infections seem to have a skin origin (same CC as isolates from acne lesion). Interestingly, the origin of prosthetic joint infection isolates seems different and they all carry one more virulence factor.

Hyaluronate lyase (Hyl) is a major surface protein of P. acnes with potential antigenetically variable properties that might be essential for P. acnes virulence. Increased tissue permeability caused by the action of hyaluronidase on the extracellular matrix appears to play a role in wound infections, pneumonia, and other sepsis such as bacteremia and meningitis. It could be also take a prominent part in P. acnes prosthetic joint infection pathogenesis.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_15 | Pages 31 - 31
1 Dec 2015
Aubin G Lavigne J Guyomarch B Dina C Gouin F Lepelletier D Corvec S
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Staphylococcus aureus is a leading cause of implant-associated infections (IAI). The aim of this study was to identify bacterial and/or clinical features involved in the pathogenesis of S. aureus IAI.

57 IAI S. aureus and 31 nasal carriage (NC) S. aureus isolates were studied. S. aureus genetic background was obtained by microarray analysis. Multi-Locus Sequence Typing was performed to determine clonal complexes (CC). The ability of S. aureus isolates to produce biofilm was investigated by resazurin and crystal violet methods. Clinical data were retrospectively collected from the patient's medical records.

Fifty-five IAI patients were included. Two of them had two different S. aureus IAI episodes. The median age was 73 years (range: 21–96 years) with 29 women (52.7%). The main diagnosis for arthroplasty was arthrosis (38%). Implants were hip prosthesis (n=35), knee prosthesis (n=18) and osteosynthesis (n=4). Infectious and nasal carriage isolates belonged respectively to 18 and 13 different sequence types (STs) without significant difference. Among IAI isolates, five strains were methicillin resistant. IAI isolates were classified as strong (14%), moderate (42.1%) and weak (43.9%) biofilm producers. For NC isolates, distribution was 12.9%, 25.8% and 61.3% for strong, moderate and weak, respectively. Staphylokinase gene was associated with the occurrence of S. aureus IAI (p<0.001). Patients’ ABO blood group phenotype was associated with IAI S. aureus genetic background (sasG, slpB, lukD and set12/ssl8) (p≤0.01). In vitro, CC8 S. aureus strains produce more biofilm than others (p≤0.0001). Two alleles of bbp gene were significantly associated with CC8 S. aureus strains (p≤0.0001). No specific CC involved in IAI compared to NC S. aureus isolates was revealed.

Our results suggested that occurrence of IAI may depend on patients’ ABO blood group and staphylokinase gene detection. We also observed a strong biofilm producer phenotype in CC8 S. aureus. Further studies are needed to prove whether one bbp gene variant is correlated to this phenotype.

This study was supported by a grant number WS1106649 from Pfizer, France and by the French “Ministère de l'Enseignement Supérieur et de la Recherche”.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_16 | Pages 11 - 11
1 Oct 2014
Paul L Cartiaux O Odri G Gouin F
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Resecting bone tumours within the pelvis is highly challenging and requires good cutting accuracy to achieve sufficient margins. Computer-assisted technologies such as intraoperative navigation have been developed for pelvic bone tumour resection. Patient-specific instruments have been transposed to tumour surgery. The present study reports a series of 11 clinical cases of PSI-assisted bone tumour surgery within the pelvis, and assesses how accurately a preoperative resection strategy can be replicated intraoperatively with the PSI.

The patient series consisted in 11 patients eligible for curative surgical resection of primary bone tumor of the pelvis. Eight patients had a bone sarcoma of iliac bone involving the acetabulum, two patients had a sacral tumor, and one patient had a chondrosarcoma of proximal femur with intra-articular hip extension. Resection planning was preoperatively defined including a safe margin defined by the surgeon from 3 up to 15 mm. PSI were designed using a computer-aided design software according to the desired resection strategy and produced by additive manufacturing technology. Intraoperatively, PSI were positioned freehand by the surgeon and fixed on the bone surface using K-wires. The standard surgical approach has been used for each patient. Dissection was in accordance with the routine technique. There was no additional bone exposure to position the PSI. Histopathological analysis of the resected tumor specimens was performed to evaluate the achieved resection margins. Postoperative CT were acquired and matched to the preoperative CT to assess the local control of the tumor. Two parameters were measured: achieved resection margin (minimum distance to the tumor) and location accuracy (maximum distance between achieved and planned cuttings; ISO1101 standard).

PSI were quick and easy to use with a positioning onto the bone surface in less than 5 minutes for all cases. The positioning of the PSI was considered unambiguous for all patients. Histopathological analysis classified all achieved resection margins as R0 (tumor-free), except for two patients : R2 because of a morcelised tumour and R1 in soft tissues. The errors in safe margin averaged −0.8 mm (95% CI: −1.8 mm to 0.1 mm). The location accuracy of the achieved cut planes with respect to the desired cut planes averaged 2.5 mm (95% CI: 1.8 to 3.2 mm).

Results in terms of safe margin or the location accuracy demonstrated how PSI enabled the surgeon to intraoperatively replicate the resection strategies with a very good cutting accuracy. These findings are consistent with the levels of bone-cutting accuracy published in the literature. PSI technology described in this study achieved clear bone margins for all patients. Longer follow-up period is required but it appears that PSI has the potential to provide clinically acceptable margins.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 400 - 400
1 Sep 2012
Odri G Fraquet N Isnard J Redon H Frioux R Gouin F
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Cam type femoroacetabular impingement (FAI) is due to an aspheric femoral head, which is best quantified by the alpha angle described on MRI and CT-scan. Radiographic measurement of the alpha angle is not well codified and studies from the literature cannot conclude on the best view to measure it. Most authors also describe a mixed type FAI which associates an aspheric femoral head with an excessive anterior acetabular coverage of the femoral head. Anterior center edge (ACE) angle has been described on the false profile view to measure anterior acetabular coverage in hip dysplasia and has never been evaluated in FAI. In this study, we developed a new lateral hip view which associates a lateral view of the femoral neck and a false profile view of the acétabulum, which we called profile view in impingement position (PVIP).

Twenty six patients operated for FAI had CT-scan, the PVIP and the false profile view of one or two hips according to pain. A control group of 19 patients who did not suffer from the hip had the PVIP. Alpha angles were measured twice on 17 CT scan of FAI patients by two observers and compared with the alpha angles measured on the corresponding hip PVIP by a correlation analysis. Alpha angles were measured twice on 45 PVIP in FAI patient and on 19 PVIP in the control group by three observers. ACE angles were measured once on 15 PVIP and on 15 false profile views. Means were compared by two tail paired t-tests, intra- and inter-observer reliability were measured by intraclass correlation coefficient.

Mean alpha angle on CT scan was 65.8° and 65.6° for observers 1 and 2 respectively (p>0.05). It was 63.6° and 64.3° on the PVIP (p>0.05). No significant difference was found between CT scan and radiographic measurements, and Pearson's correlation coefficients were good at 0.74 and 0.8. ICC was 0.86 for inter-rater reliability, and 0.91 for intra-rater reliability for CT-scan alpha angle measures. ICC for PVIP measures varied from 0.82 to 0.9 for intra-rater reliability and from 0.6 to 0.9 for inter-rater reliability. Mean alpha angle measured on PVIP in FAI patients was 63.3° and was 44.9° in control subjects and the difference was significant (p<0.001) for the three observers. None of the FAI patients and 88% of the control subjects had an alpha angle < 50°. Mean ACE angle was 26.8° on PVIP and 32.8° on the false profile view, the difference was significant (p=0.015), and the Pearson's correlation coefficient was moderate (r=0.58).

The PVIP is a reliable radiographic view to measure the alpha angle. It allows a good quantification of the alpha angle comparable to CT-scan measurements and permits to differentiate patients from control subjects. PVIP is not a good view to quantify anterior edge angle probably because of acetabular retroversion due to the hip flexion needed in this view. Mean ACE angle measured on the false profile view in FAI patient was comparable to ACE angle in general population reported in the literature.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 300 - 300
1 Sep 2012
Lintz F Waast D Odri G Moreau A Maillard O Gouin F
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Purpose

To investigate the prognostic effect of surgical margins in soft tissue sarcoma on Local Recurrence (LRFS), Metastasis (MFS) and Disease Free Survival (DFS).

Patients and Methods

This is a retrospective, single center study of 105 consecutive patients operated with curative intent. Quality of surgery was rated according to the International Union Against Cancer classification (R0/R1) and a modification of this classification (R0M/R1M) to take into account growth pattern and skip metastases in margins less than 1mm. Univariate and multivariate analysis was done to identify potential risk factors. Kaplan-Mayer estimated cumulative incidence for LRFS, MFS and DFS were calculated. Survival curves were compared using Log rank tests.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 49 - 49
1 Apr 2012
Mascard E Rosset P Beaudet P Missenard G Salles de Gauzy G Mathieu G Oberlin O Eid A Plantaz D Wicart P Glorion C Gouin F
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For many surgeons amputation is the usual treatment in sarcoma of the foot. The aim of our study was to report the functional and oncologic results of treatment in 54 sarcomas of the foot to assess if conservative treatment was acceptable

We retrospectively reviewed the records of 54 patients with sarcomas of the foot, aged 6 to 50 (mean 17), 30 females and 26 males. At time of referral, 18 had a local recurrence of a previous inadequate treatment. There were 27 soft tissue sarcomas (STS: 10 synovial sarcomas, 6 rhadomyosarcomas, 1 liposarcomas and 10 others) and 27 bone tumours (16 Ewing's, 8 chondrosarcomas, 3 osteosarcomas). Toes tumours were excluded, 18 tumours involved the metatarsal, 12 the plantar soft tissues, 11 the calcaneum, 3 the talus, 2 the midtarsal bones.

Surgery consisted in 19 resection without reconstruction, 21 resections with bone reconstruction, 9 partial amputations of the foot, and 6 trans tibial amputations.

In 34 cases surgical margins were adequate (R0), in 13 patients resection was inadequate (9 R1 and 4 R2). In 7 cases the margins were not assessed.

After a 5.5 years average follow-up (3m to 17y), 31 patients had no evidence of disease, 8 were in second remission, 4 had an evolutive disease and 11 were deceased. The mean MSTS score was 26/30 (31 cases).

In conclusion, a conservative treatment is feasible in metatarsal bones with skin coverage by flap if necessary. In STS adequate margins are difficult to achieve with a high rate of local recurrence. In calcaneus and talus, a conservative treatment is possible in tumours limited to bone after good response to chemotherapy. In other cases conservative treatment is debatable because amputation gives excellent functional results.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 499 - 499
1 Nov 2011
Philippeau J Lopes R Waast D Passuti N Gouin F
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Purpose of the study: Follow-up of patients with a total hip arthroplasty with an Atlas® cup revealed unique acetabular osteolytic defects which remained asymptomatic for long periods. We thus conducted a systematic review.

Material and method: Our retrospective analysis included 217 Atlas® elastic impactable cups implanted consecutively from January 1993 to June 1995 and reviewed clinically and radiographically at mean 13.1 years.

Results: The incidence of acetabular osteolysis was 16%, the leading cause of replacements which occurred on average 8.8 years after the initial implantation. The overall actuarial cup survival was 76% at 13.5 years and 81% taking revision for periprosthetic osteolysis as the endpoint. Univariate analysis found a significant link between osteolysis defects and significant wear (p< 0.0001), Devane activity 4 or 5 (p=0.0005), low thickness polyethylene (p=0.006), and use of Zircone or alumina heads versus metal heads (diameter 22). There was no statistical link between the presence or not of a hydroxyapatite coating, despite a trend for less osteolysis with hydroxyapatite coating. At multivariate analysis, the only factors significantly linked with the presence of osteolysis were significant wear and thin polyethylene insert in the metal back.

Discussion: Mid-term follow-up appeared sufficient to assess the development of osteolysis considering the delays describe by others. The incidence of osteolysis, despite the high incidence and early appearance in our series, was very probably underestimated by the radiographic analysis. These results suggest we should search for defects systematically with this type of implant, especially if there is measurable wear. Although it is difficult to set a cut off, a polyethylene thickness less than 10mm should be avoided to limit the high risk of osteolysis defects. A more powerful statistical analysis and examination of explants is advisable in order to ascertain the reasons for this abnormally high level of failure by osteolysis at 13 years follow-up.

Conclusion: Systematic radiological and clinical review of all patients demonstrated an insufficient overall actuarial survival and an important rate of periprosthetic osteolysis. The association between periprosthetic osteolysis and polyethylene were was confirmed. Thin inserts appear to play an important role in this osteolysis via an abnormal wear and poor tolerance to wear debris from these implants.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 496 - 497
1 Nov 2011
Lintz F Colombier J Letenneur J Gouin F
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Purpose of the study: Acute compartment syndrome of the leg can lead to serious sequelae affecting patient autonomy. Retractile postischemic fibrosis leads to various deformities of the ankle and foot from simple claw toe to complex multidirectional dislocations. Aggressive surgery, or even amputation, may be needed to save soft tissue. Data are scarce on management practices for these deformities. We present a long-term follow-up.

Material and method: From 1981 to 2006, 150 patients with a compartment syndrome of the leg were managed in our unit. Ten of these patients later required repeated surgery directly related to the sequelae of the compartment syndrome affecting the foot and ankle. These patients were followed in our unit. Personal data, as well as potential risk factors and sequelae were noted. Data were analysed and compared with reports in the literature.

Results: For nine of the ten patients, the initial diagnosis was established late, for seven, more than 24 hours after onset. The anterior and lateral compartments were involved (10/10 and 9/10) and less often the deep posterior compartment (3/10), motor deficit (3/10) and sensorial deficit (5/10) of the tibial nerve. The deep posterior loge was the cause of late equine deformity in eight patients. Functional outcome was good in eight patients after secondary surgery. For the other two cases, leg amputation was the only solution.

Discussion: Complicated acute compartment syndrome of the leg most commonly involves the anterior and anterolateral compartments. Conversely, the posterior compartment is implicated in the development of invalidating sequelae. We analysed the different procedures used in the literature for managing these sequelae and established a classification. Effective treatment of the foot and ankle affected by a late postischemic syndrome depends on a rigorous surgical strategy taking into account the multidirectional and multifactorial aspects of the resulting deformity. Prevention nevertheless remains the most effective treatment, both by early initial aponeurotomy and by prevention of the secondary deformity.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 210 - 210
1 May 2011
Gouin F Lopes R
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Background: Because of his tribologic properties Alumina on alumina bearing for THA is an attractive alternative to the the other traditional bearings surfaces and is used since about forty years, especially for young peoples. In order to resolve the problem caused by the rigidity of ceramic, the ceramic sandwich liner was introduced but some cases of ceramic fracture were reported.

The purpose of this study was to quantify and analyse these specific failure.

Methods: Between November 1999 and February 2008, a total of 353 CÉRASUL® (Zimmer, Winterthour, Suisse) liner acetabular component with a 28 mm alumina head were implanted in 298 patients. The results were reviewed at a mean of 3,5 years postoperatively with 6 patients loss to follow-up. Clinical follow-up with the PMA score and plain radiographic evaluation were performed. Based on Xray analysis, ceramic sandwich liner fractures were counted and analyzed.

Results: The mean PMA was 17,5 (10 to 18) at the final review

Kaplan-Meier survival curves were constructed for the outcomes of revision for any reasons and for ceramic liner fracture.

Seven fractures (2%) of ceramic sandwich liner were found and occured at a mean of 4,3 years after surgery without trauma. Fractures (20%) were the third diagnosis leading to the liner revision after dislocation (43%) and sepsis (26%). Neither patient related factors nor X ray position of the implants could be isolated as risk factor of liner fracture.

Discussion: Despite promising short term results in term of clinical and Xray analysis, ceramic sandwich liner is associated with a high rate of fracture. This complication have been already reported by other authors for different devices of the same concept ; instead of their conclusions, we were unabled to identify any risk factor of fracture. We hypothesised that repetitive impingement of the stem neck could be the first event of that disappointing complication. Due to this high rate of fracture we discontinued to implant ceramic sandwich liner for THA.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 461 - 461
1 Jul 2010
Gouin F Moreau A Cassagnau E Bompas E Waast D Lintz F
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Planning resection margins for soft tissue sarcomas is a compromise between functional sacrifice and therapeutic safety. In practice, the histological analysis of the resection margins often shows that the preoperative objective has not been achieved. We studied the prevalence and factors of risk of this surgical outcome.

This was a prospective monocentric study of 133 patients. The resection objectives, pathological results and operative reports were examined. Margins were classified according to the UICC (R0, R1, R2). Data were included in a grid which also included patient related and tumour related preoperative information. Inadequate resection was noted as planned R0 with R1 or R2 outcome. Statistical analysis was performed with Statview 5.0.

The prevalence of inadequate resection was 25.2%. Among the factors analysed, the aspect of tumor limits (badely or well defined) was significantly related to poor surgical results (odds ration 2.85 [1.47–5.52], p < 0.005). No other significant risk factor could be identified. Margins greater than two mm were associated with adequate surgery in every case.

No preoperative risk factor predictive of inadequate resection margins was clearly identified in this study. Postoperatively, the microscopic aspect of the proliferation limits at the final pathology examination is for us significantly associated with inadequate resection. However the current classification for resection margins lacks precision, especially regarding R0 and R1 when margins are small, in defining the risk of inadequate resection. This appears to be the source of the difficulties encountered in interpreting pathology samples and therefore in choosing the right treatment. Further follow-up is needed to clarify such questions.

We conclude that where resection margins are thin (less than two mm), the definition of R0 or R1 resections should be clarified to optimize patient care. To achieve this, potential risk factors for inadequate resection such as tumor limits should be taken into account and further studied.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 440 - 441
1 Jul 2010
Verdegaal S Bovée J Pansuriya T Grimer R Toker B Jutte P Julian MS Biau D van der Geest I Leithner A Streitburger A Lenke F Gouin F Campanacci D Hogendoorn P Taminiau A
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Enchondromatosis is a non-hereditary disease, characterised by the presence of multiple enchondromas. While Ollier Disease is typified by multiple enchondromas, in Maffucci Syndrome they are combined with haemangioma.

Due to the rarity of these diseases, systematic studies on clinical behaviour providing information how to treat patients are lacking.

This study intends to answer the following questions: What are predictive factors for developing chondrosarcoma? When is extensive surgery necessary? How often patients die due to dedifferentiation or metastasis?

Twelve institutes in eight countries participated in this descriptive retrospective EMSOS-study. 118 Patients with Ollier Disease and 15 patients with Maffucci Syndrome were included. Unilateral localization of disease was found in 60% of Ollier patients and 40% of patients with Maffucci Syndrome.

One of the predictive factors for developing chondrosarcoma is the location of the enchondromas; the risk increases especially when enchondromas are located in the scapula (33%), humerus (18%), pelvis (26%) or femur (15%). For the phalanges, this risk is 14% in the hand and 16% in the feet. The decision whether or not to perform extensive surgery is difficult, especially in patients who suffer multiple chondrosarcomas.

Malignant transformation was found in fourty-four patients with Ollier Disease (37%) and eight patients with Maffucci Syndrome (53%). Multiple synchronous or metachronous chondrosarcomas were found in 15 patients.

Nine patients died (range 21–54 yrs). Seven of them died disease related due to pulmonary metastasis (2 humerus, 2 pelvis, 3 femur). Two patients died from glioma of the brain.

In conclusion, one important predictive factor for developing chondrosarcoma is the location of the enchondromas; interestingly, only patients with chondrosarcoma outside the small bones died of their disease. In this series, no dedifferentiation of chondrosarcoma was seen. A first design flow-chart how to approach chondrosarcoma in patients with Ollier Disease and Maffucci Syndrome is in preparation.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 465 - 465
1 Jul 2010
Odri G Lamoureux F Picarda G Battaglia S Dumoucel S Trichet V Tirode F Laud K Burchill S Gouin F Heymann D Rédini F
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The development of multidisciplinary therapy for Ewing’s sarcoma (ES) has increased current long-term survival rates to greater than 50%, but only 20% for patients with clinically detectable metastases at diagnosis, or not responding to therapy or with disease relapse. Anti-bone resorption bisphosphonates (BP) may represent promising adjuvant molecules to limit the osteolytic component of bone tumor.

The combination of zoledronic acid (ZOL) and ifosfamide (IFOS) or mafosfamide (MAFOS) was studied in ES models and in 8 human cell lines all expressing the EWS-FLI1 fusion gene. Cell proliferation, viability, apoptosis and cell cycle distribution were analysed. The ES models were developed in immuno-deficient mice by inoculating the human tumor cells either intra-muscular (soft tissue tumor development) or intra-osseous (bone tumor development). Mice were then treated with ZOL (100 μg/kg twice or 4 times/week) and/or ifosfamide (IFOS 30 mg/kg, one to 3 sequences of 3 injections).

All the cell lines studied were more or less sensitive to ZOL and MAFOS in terms of cell proliferation. Both drugs induced cell cycle arrest respectively in S and G2M phase and final apoptosis associated to caspase 3 activation. In vivo, ZOL had no effect on soft tumor progression although it dramatically inhibits ES development in bone site. When combined with IFOS, ZOL exerts synergistic effects in the soft tissue model leading to a similar quantitative inhibitory effect when associated with 1 sequence IFOS as compared to 3 sequences of IFOS alone. In the bone model, ZOL prevents tumor recurrence observed with a lonely sequence of IFOS.

Combination of ZOL with conventional chemotherapy showed promising results in both ES models and could allow the clinicians to diminish the doses of chemotherapy. Moreover, as ZOL and MAFOS induce cell death by different pathways, respective resistance may be circumvented.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 308 - 309
1 May 2010
Pidhorz L Gouin F Dujardin F Merle V Moret L Czernichow P Lombrail P
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The fractures of the hip are a main problem of health care. These fractures will be multiply by 2 in 2025 and 3 in 2050. In the population of old people, 1/3 of the women and 1/9 of the men will have a fracture of their hip. Some authors used the name of “EPIDEMIC”.

The aima of the INPECH project (Indicators of the Performance for the comparison between hospital) was to check if the comparison of performances of clinical teams, on the basis of indicators chosen by themselves, allowed to improve their performances. It was an experimentation of a volonteer processes of comparison of performance between 3 multidisciplinary teams.

The study followed some stages:

in every hospital, description of the process of care of the hip fractures with a choice of indicators of performance (difficulties of the care percepted by the professionals, possibilities of improvement, feasibility of the record of the indicators during the whole process)

a first meeting of concertation with the three hospitals where a common choice of 20 indicators was done: 5 factors of adjustement corresponding to the prefracture status, 10 factors of the processes and 5 factors recorded at 3 months postoperatively

a first period of inclusion (433 patients of more than 65 years-old)

a second meeting of confrontation in order to analyze the results of the first inclusion period and to have exchange between the different teams about the disparities

- the age, the autonomy and the mobility of the patients did not differ between the hospitals

- the preoperative time was significantly different: 0.7 to 3.6 days

- the time of the first get up (2 to 4 days), of the first social demand 3 to 7 days), of the hospitalization in surgery (9 to 14 days) and the rate of transfert in rehabilitation centers varied significantly between the centers.

- At three months, the mortality, the levels of dependance and of autonomy were not significantly different.

Each team had a reflexion about the opportunities of improvement and the actions to begin

A second period of inclusion was realized in order to objectivize if the proposed improvements allowed a real change of our professional practices. (423 patients)

The analysis of this second inclusion authorized a real change in our professional practices and showed the efficacy of the indicators which were improved.

This study had permitted to show qualitative differences of care of hip fractures between the hospitals. The confrontation between the teams had authorized a positive reflexion of some of our professional practices and the improvement was underlined by the second series of inclusion.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 281 - 281
1 May 2010
Lintz F Moreau A Cassagnau E Waast D Bompas E Gouin F
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Purpose of the study: Planning resection margins for soft tissue sarcomas is a compromise between functional sacrifice and therapeutic safety. In practice, the histological analysis of the resection margins often shows that the preoperative objective has not been achieved. We defined this as anatomo-surgical discordance and studied its prevalence and factors of risk.

Materials and Methods: This was a prospective mono-centric study of 133 patients. The resection objectives, pathological results and operative reports were examined. Margins were classified according to the UICC (R0, R1, R2). Data were included in a grid which also included patient related and tumour related preoperative information. Discordance was noted as planned R0 with R1 or R2 outcome. Statistical analysis was performed with Statview 5.0.

Results: The prevalence of anatomo-surgical discordance was 25.2%. Among the factors analysed, the aspect of the margins was significantly related to poor surgical results (odds ration 2.85 [1.47–5.52], p=0.0031). No other significant risk factor could be identified. Margins greater than 2mm were associated with adequate surgery in every case.

Discussion: No preoperative risk factor predictive of inadequate resection margins was clearly identified in this study. Postoperatively, the microscopic aspect of the proliferation margins at the final pathology examination is for us significantly associated with inadequate resection. But the current classification of resection margins (R0 and R1), especially for poorly delimited tumours lacks precision. This appears to be the source of the difficulties encountered in interpreting pathology samples and therefore in choosing the right treatment. Further follow-up is needed to clarify such questions.

Conclusion: We were unable to identify any preoperative factor predictive of inadequate resection. A poorly-defined microscopic aspect of the tumour is significantly associated with inadequate resection but the current classification system raises certain interpretation problems for resections with margins less than 2 mm. Concerning these cases, the definition of margins must be clarified to optimize patient care.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 239 - 240
1 Jul 2008
GOUIN F RÉDINI F HEYMANN D
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Purpose of the study: Wide en bloc surgical resection is the treatment of choice for cure of chondrosarcoma. Despite local control of this primary bone tumor in 60–80% of patients, mortality remains high. Recent studies suggest that biphosphonates can provide promising perspectives for the treatment of malignant bone tumors, even for primary tumors such as osteosarcoma. We report here the results obtained when using zoledronate for Swarm chondrosarcoma in an in vivo rat model and the effect of this compound on tumor cells in vitro.

Material and methods: Swarm chondrosarcoma was implanted in three series of 12 male Sprague Dawley rats. In series A, the animals were treated after implantation to death or sacrifice. In series B and C, the animals were treated a few days before curettage-resection then to death or sacrifice. Tumor growth was assessed by tumor size, presence of metastasis and death. Control series with PBS injections were also studied.

Results: Treatment with zoledronate inhibited tumor growth in all series. In series A, tumor size was significantly smaller in the treated animals (p=0.046). Tumor progression from day 19 to day 32 was significantly less for treated animals (p=0.046). Chance of survival was 0.667 for treated animals versus 0.3 for the controls. For series B and C, recurrence developed later in animals given zoledronate. Tumor size was greater in control animals compared with treated animals (p=0.043). Tumor progression from day 39 to day 49 was significantly greater in the control group (p=0.025). Cultures of cells extracted from the Swarm chondrosarcoma tumor also showed significantly inhibited growth in vitro for concentrations of zoledronic acid from 10 to 100 ml/l.

Discussion and conclusion: Zoledronic acid appears to inhibit growth of Swarm chondrosarcoma in all in vivo therapeutic schemas studied, confirming in vitro data. A more precise animal model better fitting clinical situations should provide more detailed information for use of this treatment after recurrence or in the event of intralesional surgery.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 252 - 252
1 Jul 2008
WAAST D YAOUANC F MELCHIOR B PERRIER C PASSUTI N GOUIN F
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Purpose of the study: We conducted a prospective randomized study to compare use of macroporous biphasic calcium phosphate ceramic and bone autografts for filling medial open wedge osteotomies of the proximal tibia.

Material and methods: This phase III pragmatic clinical trial was designed for direct patient benefit. Randomization was performed in the operating room after completing the osteotomy. Twenty-six men and 14 women, mean age 51 years (range 19–75 years) were included. A biomaterial implant was used for 22 patients and an autograft for 18. Mean correction was 10 mm (range 6–15). One patient was excluded from the analysis, no patient was lost to follow-up. All patients were reviewed at minimum two years follow-up.

Results: At three months, knees were less painful with less subjective functional impact after filling with an autograft (pain VAS 3.1 versus 2.1 and function VAS 3.4 versus 2.5). These results were more balanced at six months (pain 1.6 versus 1.8 and function 1.8 versus 2.1) and remained stable at one and two years. The IKS knee scores were symmetrical at one at two years for both groups (IKS1 93 versus 86 and IKS2 90 versus 90). Bone healing was achieved within the usual delay. Axial alignment was stable at two years in both groups. There were eleven complications (28%), nine requiring revision: infected hematoma (n=1), intraoperative vascular injury without serious consequences (n=1), loss of correction (n=2), nonunion after filling with biomaterial (n=1), iliac abscess after filling with autograft (n=2) and painful calcification of the iliac region requiring resection (n=1).

Discussion: We observed three factors which can favor mechanical failure after filling with a ceramic material: intraoperative rupture of the lateral hinge, obesity, and excessively early unprepared weight bearing.

Conclusion: Although the difference did not reach significance, the risk of mechanical complications appears greater with macroporous en bloc ceramic filling. This material is less tolerant to comorbid conditions (obesity) and requires very precise technique as well as careful observance of postoperative care (no early weight bearing). Nevertheless, this method does have the advantage of avoiding painful sequelae and complications related to harvesting the iliac graft.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 250 - 250
1 Jul 2008
GOUIN F FRIOUX R BAUDRY C YAOUANC F REDON H
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Purpose of the study: Labrum lesions can be an important source of hip pain. Besides the classical causes, certain morophological anomalies can be associated with labrum lesions. The purpose of this work was to study the contribution of plain x-rays to the search for morphological anomalies of the hip in patients with labrum lesions.

Materials and methods: Twenty-six patients with labrum lesions were included in this study. The plain x-rays protocol included an anteroposterior view of the pelvis in the standing position, a Lequesne oblique view and a lateral view of the neck in the hip flexion position. Patients with severe hip dysplasia (VCA or VCI < 15° or THE > 15°) were excluded. Measurements were made after digitalization using a dedicated software. Measures were: neck-shaft angle, acetabular cover, lateral alpha (neck axis, center of the head, most lateral point of the head sphere), lateral offset, acetabular version. Femoral data in flexion were compared with 20 controls.

Results: Acetabular cover was considered moderately insufficient in five patients (VCA and/or VCE 15–25°). These patients had the same alpha angle as the control population (56°), i.e. no anomaly of the neck-head junction. The 21 patients with non-dysplastic hips exhibited a significantly greater alpha angle (64±9° versus 54.6±8°, p< 0.01) than the controls. All controls presented an alpha angle ≤ 69°. Among the 21 non-dysplastic patients, five presented coxa vara (< 125°), five acetabular retroversion, nine an alpha angle > 69°. In all, 77% of patients presented morphological anomalies of the hip. Among the six «normal» hips using these measures, three presented a pistol-grip aspect which could not be quantified with these measures.

Discussion: This analysis confirms the association between morphological anomalies detectable on plain x-rays and labrum lesions in patients who do no present severely insufficient acetabular coverage. We were unable to detect any difference in femoral offset compared with the control population.

Conclusion: A standard x-ray protocol can, in the majority of cases, detect morphological anomalies of the hip, an important etiological diagnostic element for understanding pathogenic mechanisms.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 67 - 67
1 Mar 2006
Cyril P Gouin F Perrier C Waast D Delecrin J Passuti N
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Purpose of the study: Revision acetabular surgery with bone stock deficiency is a difficult problem. The use of cementless component and bioactive ceramics seemed to be a promising alternative.

Since 1996, we have been filling bone defect at the time of revision with macroporous calcium phosphate ceramic. We reported our first experience between 1996 and 1999.

Material and methods: The procedure was carried out in 35 hip reconstructions ( 35 patients ) at a mean follow-up of 6 years ( range 5 to 7,4). The average age of the patients was 56 years( range 28 to 83).

2 patients died of a cause unrelated to the procedure and 2 patients were lost of follow-up. Bone defect were classified into type I ( 4 hips), type IIA ( 8 hips ), type IIB ( 5 hips), type IIC ( 9 hips), IIIA ( 4 hips ), type IV ( 5 hips ) according to Paprosky classification.

The functional status of the patients was evaluated according to the Merle d’Aubign ip rating.. The interfaces bioactive ceramics/bone base and bioactive ceramics/cementless component, as well as the homogeneity and the density of the graft were examined radiologically.

Results: Functionally, the Merle d’Aubigné hip rating improved, increasing from11,3 to 15,9. Failure of fixation of the acetabular component occurred in 11,4 % of the acetabular reconstructions ( 4 hips in 35 patients). One was diagnosed as loose on the basis of radiographic criteria alone and the other three hips had a loose acetabular component at reoperation. We observed no failed reconstruction when the acetabular component is in direct contact with host bone on 50 % or more of its surface area.

We saw no radiolucent lines or spaces at the interface between bioactive ceramics and the host bone. Morphological changes or a decreased in graft volume were not seen, except for the patient with the loose cup.

Discussion-Conclusion: The findings of the present study support the use of bioactive ceramics and cement-less acetabular component in the presence of loss bone in order to achieve the goals of a revision hip replacement, provided that at least 50 % support of the cup can be obtained with host-bone.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_II | Pages 99 - 99
1 Apr 2005
Gouin F Heymann D Blanchard F Coipeau P Thiery J Passuti N Rédini F
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Purpose: In osteosarcoma, tumour progression leads to osteolysis via direct proteolytic mechanisms and/or osteoclast activation. Nitrogen biphosphonates (N-BP) like zolebronate inhibit osteoclast function and apoptosis of osteoclasts and other tumour cells. In animal models, N-BP decrease bony progression of myeloma, bone metastasis, and breast and prostatic tumours. In vitro studies have demonstrated a synergetic action with classical anti-cancer drugs on apoptosis for myeloma and breast cancer cell lines. The purpose of the present study was to investigate the effect of zoebronic acid on osteosarcoma growth, alone or in combination with ifosfamide.

Material and methods: A rat model accepting osteosarcoma transplant was used for the study. Four series of seven rats were treated with zoledronate (100 mg/kg on day 7, 14, 21 and 28 after implantation) in combination or not with ifosfamide (30 mg/kg on day 1”, 14 and 15). Thirty-five days after implantation, the rats were sacrificed to evaluate tumour volume, presence of metastasis, radiography, and pathological examination of the tumour. Zoledronate was also studied in vitro on an OSRGA osteosarcoma cell line isolated from the same tumour.

Results: Zoledronate demonstrated efficacy by reducing the osteolysis induced by the sarcoma, but also on local tumour progression (75%) in comparison with untreated animals. In vitro, zoledronate inhibited cell proliferation by 60%. The ifosfsamide-zoledrnoate combination produced greater reduction in tumour progression than ifosfamide alone.

Conclusion: This work demonstrates for the first time that zoledronate has an effect on osteosarcoma tumour progression, either by a direct effect or by an antiosteoclastic effect and that the effet increases the efficacy of classical antitumour drugs such as ifosfamide.