A short-term in vivo model for giant cell tumor of bone

<p>Abstract</p> <p>Background</p> <p>Because of the lack of suitable <it>in vivo </it>models of giant cell tumor of bone (GCT), little is known about its underlying fundamental pro-tumoral events, such as tumor growth, invasion, angiogenesis and metastasis. There is no existing cell line that contains all the cell and tissue tumor components of GCT and thus <it>in vitro </it>testing of anti-tumor agents on GCT is not possible. In this study we have characterized a new method of growing a GCT tumor on a chick chorio-allantoic membrane (CAM) for this purpose.</p> <p>Methods</p> <p>Fresh tumor tissue was obtained from 10 patients and homogenized. The suspension was grafted onto the CAM at day 10 of development. The growth process was monitored by daily observation and photo documentation using <it>in vivo </it>biomicroscopy. After 6 days, samples were fixed and further analyzed using standard histology (hematoxylin and eosin stains), Ki67 staining and fluorescence <it>in situ </it>hybridization (FISH).</p> <p>Results</p> <p>The suspension of all 10 patients formed solid tumors when grafted on the CAM. <it>In vivo </it>microscopy and standard histology revealed a rich vascularization of the tumors. The tumors were composed of the typical components of GCT, including (CD51+/CD68+) multinucleated giant cells whichwere generally less numerous and contained fewer nuclei than in the original tumors. Ki67 staining revealed a very low proliferation rate. The FISH demonstrated that the tumors were composed of human cells interspersed with chick-derived capillaries.</p> <p>Conclusions</p> <p>A reliable protocol for grafting of human GCT onto the chick chorio-allantoic membrane is established. This is the first <it>in vivo </it>model for giant cell tumors of bone which opens new perspectives to study this disease and to test new therapeutical agents.</p

Analysis of Failed Two-Stage Procedures with Resection Arthroplasty as the First Stage in Periprosthetic Hip Joint Infections

Resection arthroplasty can be performed as the first stage of a two-stage procedure in some patients with severe periprosthetic hip joint infections with poor bone stock. This retrospective study aimed to evaluate factors associated with the subsequent failure or success of these patients. Between 2011 and 2020; in 61 (26.4%) of 231 patients who underwent a two-stage protocol of periprosthetic hip joint infections; no spacer was used in the first stage. The minimum follow-up period was 12 months. Patient’s demographics and various infection risk factors were analyzed. In total, 37/61 (60.7%) patients underwent a successful reimplantation, and four patients died within the follow-up period. Patients within the failure group had a significantly higher Charlson comorbidity index (p = 0.002); number of operations prior to resection arthroplasty (p = 0.022) and were older (p = 0.018). Failure was also associated with the presence of a positive culture in the first- and second-stage procedures (p = 0.012). Additional risk factors were persistent high postoperative CRP values and the requirement of a negative-pressure wound therapy (p ≤ 0.05). In conclusion, multiple factors need to be evaluated when trying to predict the outcome of patients undergoing resection arthroplasty as the first stage of a two-stage procedure in patients with challenging periprosthetic hip joint infections

Tumour response of osteosarcoma to neoadjuvant chemotherapy evaluated by magnetic resonance imaging as prognostic factor for outcome

PURPOSE: This study evaluated the feasibility of computed magnetic resonance imaging (MRI) volumetry in conventional osteosarcomas. Secondly, we investigated whether computed volumetry provides new prognostic indicators for histological response of osteosarcomas after neoadjuvant chemotherapy. METHODS: In a retrospective cohort study, data from the Vienna Bone Tumour Registry was used. MR images from 14 patients (male:female = 1.8, mean age 19 years) were analysed prior to and after neoadjuvant chemotherapy according to current therapy regimens. Histological response to chemotherapy was graded according to the Salzer-Kuntschik classification. Computed volumetry was performed for the intraosseous part, as well as the soft-tissue component and the tumour as a whole. RESULTS: In a setting of appropriate radiological equipment, the method has been considered to be well implementable into clinical routine. The mean tumour volume prior to chemotherapy was 321 (±351) ml. In good responders (n = 6), overall tumour volume decreased by 47 % (p = 0.345), whereas poor responders (n = 8) showed a 19 % decrease (p = 0.128). Neoadjuvant multidrug therapy remarkably changed the tumour composition. This is seen in a decrease of the mean ratio of soft-tissue to intraosseous tumour volume from 8.67 in poor responders and 1.15 in good responders to 1.26 and 0.45 (p = 0.065), respectively. Interestingly, the bony compartment of good responders showed a volume increase during neoadjuvant chemotherapy (p = 0.073). However, we did not find prognostic markers for histological tumour response to pre-operative chemotherapy. CONCLUSIONS: Separated volumetry of tumour segments revealed interesting insights into therapy-induced growth patterns. If verified in a larger study population, these results should be taken into account when planning ablative surgery

LARS® band and tube for extensor mechanism reconstructions in proximal tibial modular endoprostheses after bone tumors.

UNLABELLED Wide tumor resections around the proximal tibia (pT) are related to compromised function and high complication rates. This retrospective study aims to present the technique employed as well as functional and surgical outcomes of patients undergoing a Ligament Advanced Reinforcement System (LARS®) reconstruction of the knee extensor apparatus after tumor resection and modular endoprosthetic reconstruction of the proximal tibia. Twenty-five patients who received an artificial ligament after pT resection (11 men and 14 women; mean age, 29years; range 11 to 75years, with a minimum follow-up of 24months) were analyzed regarding the ISOLS failure mode classification. Twenty patients received LARS® during primary surgery, five patients during a revision of a pT modular endoprosthesis. LARS® was available as a band or a tube. The mean extension lag was nine degrees (range, 0 to 30°), the mean flexion was 103° (range, 60 to 130°). The mean extension lag and active flexion in primary implanted LARS were 7.8° and 101° versus secondarily implanted 45° and 115° (p<0.0001; p=0.15). Eleven out of 14 primary implanted LARS® band/tubes (71%) did well with extension lag (0 to 10°). LARS® usage as a band or as a tube showed similar results. The estimated five-year survival of LARS® was 92%. The median survival of LARS® implanted primarily was better than in the case of secondary implantation (p=0.006). Extensor mechanism reconstruction by LARS® band or tube shows excellent function and satisfactory implant survival after primary reconstruction of the extensor mechanism after proximal tibia resection. We experienced no LARS® rupture for only mechanical reasons. LEVEL OF EVIDENCE Level IV retrospective study

Intensified Adjuvant IFADIC Chemotherapy for Adult Soft Tissue Sarcoma: A Prospective Randomized Feasibility Trial

Purpose. The present prospective randomized adjuvant trial was carried out to compare the toxicity, feasibility and efficacy of augmented chemotherapy added to hyperfractionated accelerated radiotherapy after wide or marginal resection of grade 2 and grade 3 soft tissue sarcoma (STS)

Effects of denosumab on pain and analgesic use in giant cell tumor of bone: Interim results from a phase II study

Background. Giant cell tumor of bone (GCTB) is an aggressive primary osteolytic tumor. GCTB often involves the epiphysis, usually causing substantial pain and functional disability. Denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor. kappa beta ligand (RANKL), is an effective treatment option for patients with advanced GCTB. This analysis of data from an ongoing, open-label study describes denosumab's effects on pain and analgesic use in patients with GCTB. Material and methods. Patients with unresectable disease (e. g. sacral or spinal GCTB, or multiple lesions including pulmonary metastases) were enrolled into Cohort 1 (N = 170), and patients with resectable disease whose planned surgery was associated with severe morbidity (e. g. joint resection, limb amputation, or hemipelvectomy) were enrolled into Cohort 2 (N = 101). Patients received denosumab (120 mg) subcutaneously every four weeks, with additional doses on study days 8 and 15. Patients assessed worst pain severity with the Brief Pain Inventory - Short Form (BPI-SF) at baseline, at each visit for the first six months, and every three months thereafter. Results. Clinically relevant pain improvement was reported by 29% of patients in Cohort 1 and 35% in Cohort 2 during week 1 and by >= 50% of patients in each cohort at each study visit from months 2-30. Median time to clinically relevant improvement was 30 (95% CI 16, 57) days in Cohort 1 and 15 (95% CI 15, 29) days in Cohort 2. Results in patients with moderate/severe pain at baseline were similar. Fewer than 30% of patients in Cohort 1 and 10% in Cohort 2 experienced clinically relevant pain worsening at any visit through 27 months. Most patients had no/low analgesic use during the study. Conclusion. Most patients treated with denosumab experienced clinically relevant decreases in pain within two months