Guillaume Odri

Zoledronic Acid as a New Adjuvant Therapeutic Strategy for Ewing's Sarcoma Patients

Ewings sarcoma (ES) is the second most frequent pediatric bone tumor also arising in soft tissues (15% of cases). The prognosis of patients with clinically detectable metastases at diagnosis, not responding to therapy or with disease relapse, is still very poor. Among new therapeutic approaches, bisphosphonates represent promising adjuvant molecules to chemotherapy to limit the osteolytic component of bone tumors and to protect from bone metastases. The combined effects of zoledronic acid and mafosfamide were investigated on cell proliferation, viability, apoptosis, and cell cycle distribution of human ES cell lines differing in their p53 and p16/ink4 status. ES models were developed to reproduce both soft tissue and intraosseous tumor development. Mice were treated with 100 μg/kg zoledronic acid (two or four times per week) and/or ifosfamide (30 mg/kg, one to three cycles of three injections). ES cell lines showed different sensitivities to zoledronic acid and mafosfamide at the cell proliferation level, with no correlation with their molecular status. Both drugs induced cell cycle arrest, but in the S or G(2)M phase, respectively. In vivo, zoledronic acid had no effect on soft tissue tumor progression, although it dramatically inhibited ES development in bone. When combined with ifosfamide, zoledronic acid exerted synergistic effects in the soft tissue model: Its combination with one cycle of ifosfamide resulted in an inhibitory effect similar to three cycles of ifosfamide alone. This very promising result could allow clinicians to diminish the doses of chemotherapy.

Computer-Assisted Planning and Patient-Specific Instruments for Bone Tumor Resection within the Pelvis: A Series of 11 Patients

Pelvic bone tumor resection is challenging due to complex geometry, limited visibility, and restricted workspace. Accurate resection including a safe margin is required to decrease the risk of local recurrence. This clinical study reports 11 cases of pelvic bone tumor resected by using patient-specific instruments. Magnetic resonance imaging was used to delineate the tumor and computerized tomography to localize it in 3D. Resection planning consisted in desired cutting planes around the tumor including a safe margin. The instruments were designed to fit into unique position on the bony structure and to indicate the desired resection planes. Intraoperatively, instruments were positioned freehand by the surgeon and bone cutting was performed with an oscillating saw. Histopathological analysis of resected specimens showed tumor-free bone resection margins for all cases. Available postoperative computed tomography was registered to preoperative computed tomography to measure location accuracy (minimal distance between an achieved and desired cut planes) and errors on safe margin (minimal distance between the achieved cut planes and the tumor boundary). The location accuracy averaged 2.5 mm. Errors in safe margin averaged −0.8 mm. Instruments described in this study may improve bone tumor surgery within the pelvis by providing good cutting accuracy and clinically acceptable margins.

Oversized Cups as a Major Risk Factor of Postoperative Pain After Total Hip Arthroplasty

After total hip arthroplasty (THA) some patients have persistent postoperative pain (POP). Some of these POP are anterior and are caused by an anterior iliopsoas impingement (AIPI). We have hypothesized that oversized implanted cups could be responsible for POP and especially AIPI. We screened 237 patients who had a primary THA and compared the size difference (ΔS) between the native femoral head and the implanted cup, in patients with and without POP. Median ΔS was 2 mm [-6; 11 mm] and patients with POP had a significantly increased ΔS (P < 0.0001). The threshold above which pain was significantly more frequent was ΔS ≥ 6 mm. Odds ratio was 14.4 for POP and 26 for AIPI pain when ΔS ≥ 6 mm.

Do outcomes of outpatient ACL reconstruction vary with graft type

BACKGROUND Studies establishing the feasibility of anterior cruciate ligament (ACL) reconstruction as an outpatient procedure in France were usually conducted with hamstring tendon grafts. The objective of this study was to evaluate the outcomes of outpatient ACL reconstruction according to whether the graft was harvested from the hamstring tendons or patellar tendon. HYPOTHESIS Outpatient ACL reconstruction can be performed using any type of graft. METHODS A single-centre retrospective study was conducted in consecutive patients older than 16 years who had primary ACL reconstruction using patellar tendon or hamstring tendons, with or without lateral tenodesis. Patients who underwent other procedures on bones or peripheral ligaments and those with a previous history of ACL reconstruction were excluded. The primary evaluation criterion was the occurrence of complications within 45 days after surgery. Secondary evaluation criteria were the visual analogue scale (VAS) for pain during the first 3 postoperative days, patient satisfaction on day 3, and the IKDC and Lysholm clinical scores on day 45. RESULTS The analysis included 104 knees (one knee per patient). Hamstring tendons were used in 77 (74%) knees and patellar tendon in 27 (26%) knees. In the hamstring group, 2 (2.6%) patients spent the first postoperative night in the hospital and 2 others were re-admitted. No hospitalisations were recorded in the patellar-tendon group. None of the patients required revision surgery within 45 days of the reconstruction procedure. None of the postoperative criteria studied showed statistically significant differences between the two groups. DISCUSSION ACL reconstruction can be performed on an outpatient basis using any type of graft. The main determinants of successful outpatient ACL reconstruction are a standardised clinical management strategy and an appropriate anaesthesia protocol. LEVEL OF EVIDENCE Level IV, retrospective study.

Critical study of resection margins in adult soft-tissue sarcoma surgery.

INTRODUCTION Resection margins constitute a recognized risk factor for local recurrence, but their impact on survival is less clear. HYPOTHESIS Infiltrative proliferation and satellite nodules are prognostic factors for local and systemic aggressiveness. TYPE OF STUDY Retrospective cohort study. PATIENTS AND METHODS In 105 patients under curative treatment, resection quality was assessed on UICC criteria (R0/R1) and on a modified version (R0M/R1M) taking account of proliferation contours and satellite nodules for narrow margins (<1mm). Uni- and multi-variate analysis was performed, and Kaplan-Meier survival curves were compared on log-rank. RESULTS Mean 5-year local recurrence-free survival (LRFS) was 0.64 [0.52-0.76] after R1 surgery, 0.9 [0.85-0.95] after R0, 0.64 [0.519-0.751] after R1M and 0.92 [0.87-0.96] after R0M. Resection type according to R classification correlated with disease-free survival (DFS) (P=0.028), but not with metastasis-free survival (MFS) (P=0.156). Resection type according to RM classification correlated with DFS and MFS. Multivariate analysis disclosed correlations between LRFS rate and RM resection type (HR 6.77 [1.78-25.7], P=0.005), DFS rate and RM resection type (HR 2.83 [1.47-5.43], P=0.001) and grade (HR=3.17 [1.38-7.27], P=0.003), and MFS and grade (HR=3.96 [1.50-10.5], P=0.006). DISCUSSION The microscopic aspect of the proliferation contours and presence of satellite nodules were confirmed as prognostic factors for local and systemic aggressiveness. They impact both disease-free survival and metastasis-free survival in case of margins less than 1mm. Their systematic consideration may help identify patients with elevated systemic risk. LEVEL OF EVIDENCE IV.

Drugs targeting the bone microenvironment: new therapeutic tools in Ewing's sarcoma?

Introduction: Ewings sarcoma (ES) is the second most frequent malignant primary bone tumour in children, adolescents and young adults. The overall survival is 60 – 70% at 5 years but still very poor for patients with metastases, disease relapse or for those not responding to chemotherapy. For these high risk patients, new therapeutic approaches are needed beyond conventional therapies (chemotherapy, surgery and radiation) such as targeted therapies. Areas covered: Transcriptomic and genomic analyses in ES have revealed alterations in genes that control signalling pathways involved in many other cancer types. To set up more specific approaches, it is reasonable to think that the particular microenvironment of these bone tumours is essential for their initiation and progression, including in ES. To support this hypothesis, preclinical studies using drugs targeting bone cells (bisphosphonate zoledronate, anti-receptor activator of NF-κB ligand strategies) showed promising results in animal models. This review will discuss the new targeted therapeutic options in ES, focusing more particularly on the ones modulating the bone microenvironment. Expert opinion: Targeting the microenvironment represents a new option for patients with ES. The proof-of-concept has been demonstrated in preclinical studies using relevant animal models, especially for zoledronate, which induced a strong inhibition of tumour progression in an orthotopic bone model.

Does thoracoscopic anterior release of rigid idiopathic scolioses associated with correction by posterior instrumentation result in better long-term frontal and sagittal balance?

INTRODUCTION The aim of treatment of scolioses is to reduce deformities and restore balance in the spine. HYPOTHESES In rigid forms of scoliosis, associating anterior release could provide greater frontal and/or sagittal plane correction and improve balance in the spine. PATIENTS AND METHODS This study compared correction and long-term balance on two planes between two homogeneous groups of idiopathic rigid scolioses treated with and without thoracoscopic release. The study included rigid scolioses with less than 35% reducibility and a Cobb angle of more than 60°, who all underwent posterior correction using a rod rotation technique. There were 29 patients, 14 who underwent a one-step procedure (group A) and 15 a two-step procedure (group B), with the subgroups of kyphoscolioses and lordoscolioses determined in each group. Frontal balance, Cobb angle, thoracic kyphosis and the Jackson plumbline were measured on pre- and postoperative X-rays and at the final follow-up. RESULTS The mean long-term final follow-up was 144 months for group A and 54 months for group B. Frontal plane correction was identical in groups A and B. Frontal balance was preserved in all cases at the final follow-up. Sagittal balance was not modified with or without anterior release. The thoracoscopic release step resulted in an additional correction of 15.5° (23%) of thoracic hyperkyphosis in patients with kyphoscoliosis (P=0.003). DISCUSSION Thoracoscopy did not improve short term results in the Cobb angle or frontal or saggital balance. Nevertheless, enhanced correction of thoracic hyperkyphosis was obtained with this procedure. In this study, the association of thoracoscopic anterior release with posterior correction by rod rotation to treat rigid scolioses did not appear to improve results, except for the correction of thoracic hyperkyphosis.

Influence of lower limb rotation on hindfoot alignment using a conventional two-dimensional radiographic technique

BACKGROUND Rotation is one of the variables explaining lack of reproducibility in assessing hindfoot alignment. The hypothesis for this study was that a mathematical model predicts how this modifies radiographic hindfoot alignment measurements. METHODS A cadaveric lower limb, disjointed at knee level, was used. Sagittal and coronal planes were fixed using a custom clamp. Standard AP views were shot every five degrees and measured hindfoot alignments were compared to theoretical values obtained from a mathematical simulation. RESULTS Hindfoot angle was 7.04° at 0° rotation and 2.11° at -90°. Intra-class and inter-investigator correlation was 0.863. The t-test showed no significant difference (p=0.73). Intra-investigator correlation was 0.957. The R2 correlation index was 0.852. CONCLUSIONS The mathematical model accurately predicted the variations of the hindfoot angle which was maximum when the foot was aligned with the X-rays source. It then decreased when the foot rotated away, following a parabolic curve.

Scapulo-humeral arthrodesis using a pedicled scapular pillar graft following resection of the proximal humerus.

BACKGROUND Scapulo-humeral arthrodesis (SHA) is a proven reconstruction method in patients with proximal humerus malignancies requiring resection of the shoulder abduction apparatus (rotator cuff and deltoid muscles) or its nerve supply. Standard practice consists in using a pedicled fibular flap. We use instead a pedicled autologous bone graft harvested from the ipsilateral scapular pillar. HYPOTHESIS The objective of this study was to assess functional outcomes and radiological healing after SHA using a pedicled scapular pillar graft. MATERIALS AND METHODS We retrospectively reviewed the charts of the 12 patients managed at a single center by a single surgeon between 1994 and 2011. SHA was performed using a vascularised ipsilateral scapular pillar graft after proximal humerus resection to treat a bone malignancy. The graft was harvested from the ipsilateral scapular pillar, pedicled on the circumflex scapular artery, fitted into the remaining proximal humerus, and secured to the glenoid using screws. A humerus-scapular spine plate was added to stabilize the arthrodesis. Radiographic results were assessed on standard radiographs obtained at last follow-up. Functional outcomes were evaluated using the MusculoSkeletalTumour Society (MSTS) score and Toronto Extremity Salvage Score (TESS). RESULTS After a mean follow-up of 4.9 years, 87.5% of SHA junctions were healed, mean MSTS score was 71%, and mean TESS score was 70%. DISCUSSION The outcomes in our patients were similar to those reported after SHA using a pedicled fibular flap. However, our technique does not require microsurgery. It is simple, reproducible, and effective. Its indications of choice are intra- or extra-articular resection of the proximal humerus including the attachments of the rotator cuff and deltoid muscle tendons or the nerves supplying these muscles. LEVEL OF EVIDENCE Level IV (retrospective study).

Reliability of a new hip lateral view to quantify alpha angle in femoroacetabular impingement

BACKGROUND Radiographic measurement of the alpha angle (AA) in femoroacetabular impingement (FAI) is not well codified and invasive techniques such as MR- or CT-arthrography remain the gold standard. Excessive acetabular coverage described in pincer-type FAI can be seen on plain radiographs but has never been quantified and anterior center edge (ACE) angle, described on the false-profile view (FP) to measure anterior acetabular coverage has never been evaluated in FAI. HYPOTHESIS In this study we wanted to determine if a plain radiograph could efficiently measure AA compared to CT-arthrography and if ACE could quantify the acetabular coverage in FAI. MATERIALS AND METHODS We developed a hip view combining a lateral view and a FP, called profile view in impingement position (PIP). Twenty-six patients operated for FAI had CT-arthrography, PIP and FP. Nineteen control subjects had the PIP. AA were measured twice by three raters and ACE once. We compared AA measured on patients between CT and PIP, on PIP between patients and controls, ACE measured on patients between PIP and FP, and did a reproducibility analysis. Means were compared by paired or unpaired t-tests; reproducibility was measured by intraclass correlation coefficient (ICC). RESULTS Mean AA was 65.8° (range, 48-85°) on CT-arthrography and 63.9° (range, 50-87°) on PIP (P>0.05). ICC for PIP measures were 0.8-0.9 for intra-rater and 0.6-0.9 for inter-rater reliability. Mean AA on PIP in patients was 63.3° (range, 52-87°) and 44.9° (range, 34-67°) in controls (P<0.001). Mean ACE was 26.8° (range, 14-41°) on PIP and 32.8° (range, 18-56°) on the FP (P=0.015). DISCUSSION The PIP is a reliable view to measure the AA in FAI as measures on PIP and CT-arthrography were not significantly different with a good reproducibility. All of the painful hips and 2 controls had an AA>50°. PIP was not efficient to measure ACE. LEVEL OF EVIDENCE Level III, case-control study.