A Reassessment of the Barrier Effect of the Physis against Metaphyseal Osteosarcoma: A Comprehensive Pathological Study with Its Radiological and Clinical Follow-Up Correlations.

Osteosarcoma is a primary malignant bone tumor usually arising at the metaphysis of long bones, particularly around the knee. The physis has been regarded as a barrier capable of blocking tumor extension, thus allowing it to preserve their epiphysis and therefore improve functional results. With the objective of clarifying how effective the physis is as a barrier to tumor spread, a large series of skeletally immature patients with osteosarcoma were reviewed. From 452 metaphyseal osteosarcomas a selection of 282 cases in which the tumor was close or crossing the physis were carried out. This sub-sample was split into two groups according to the surgical treatment (epiphyseal preservation or not). The specimens obtained by resection were studied, and the physeal and metaphyseal areas were studied by multiple sections. Immunostaining against VEGF of physis was obtained in selected cases. In about half of the patients affected by metaphyseal malignant bone tumors, the growth plate and epiphysis were not compromised by the tumor. Three sequential invasive growth patterns of an osteosarcoma in its relationship with the physis could be distinguished. An intense angiogenesis and osteoclastic reaction could be observed in the growth plate in the free zone between the tumor and the physis. The local recurrence incidence was lower in the epiphyseal preservation treated patients than it was in the conventional treatment (8% vs. 12%). Most local recurrences appeared in the first 2 years. The overall survival of patients treated with epiphyseal preservation was better than that of the patients treated without preserving the epiphysis (73% vs. 59%; p = 0.03) at a mean follow-up of 18 years. We have described an angiogenic and osteoclastic reaction in the base of the growth plate in the proximity of the advance front of the tumor, which could facilitate the osteosarcoma invasion. It is also shown that the preoperative imaging method for examination is a valid approach for the decision to carry out epiphyseal preservation. Finally, we concluded that epiphyseal preservation combined with protective chemotherapy is an excellent clinical approach for selected patients with metaphyseal osteosarcoma.

Ultra-low dose whole-body CT for attenuation correction in a dual tracer PET/CT protocol for multiple myeloma.

PURPOSE: To investigate within phantoms the minimum CT dose allowed for accurate attenuation correction of PET data and to quantify the effective dose reduction when a CT for this purpose is incorporated in the clinical setting. METHODS: The NEMA image quality phantom was scanned within a large parallelepiped container. Twenty-one different CT images were acquired to correct attenuation of PET raw data. Radiation dose and image quality were evaluated. Thirty-one patients with proven multiple myeloma who underwent a dual tracer PET/CT scan were retrospectively reviewed. 18F-fluorodeoxyglucose PET/CT included a diagnostic whole-body low dose CT (WBLDCT: 120 kV-80mAs) and 11C-Methionine PET/CT included a whole-body ultra-low dose CT (WBULDCT) for attenuation correction (100 kV-40mAs). Effective dose and image quality were analysed. RESULTS: Only the two lowest radiation dose conditions (80 kV-20mAs and 80 kV-10mAs) produced artifacts in CT images that degraded corrected PET images. For all the other conditions (CTDIvol ≥ 0.43 mGy), PET contrast recovery coefficients varied less than ± 1.2%. Patients received a median dose of 6.4 mSv from diagnostic CT and 2.1 mSv from the attenuation correction CT. Despite the worse image quality of this CT, 94.8% of bone lesions were identifiable. CONCLUSION: Phantom experiments showed that an ultra-low dose CT can be implemented in PET/CT procedures without any noticeable degradation in the attenuation corrected PET scan. The replacement of the standard CT for this ultra-low dose CT in clinical PET/CT scans involves a significant radiation dose reduction.

The utility of ADC value in diffusion-weighted whole-body MRI in the follow-up of patients with multiple myeloma. Correlation study with 18F-FDG PET-CT.

OBJECTIVES: To analyze the feasibility of DWI-MRI and ADC to evaluate treatment response in patients with multiple myeloma (MM). To correlate the variations of ADC and SUVmax in 18F-FDG PET-CT. METHODS: 27 patients with MM that had a whole-body MRI and 18F-FDG PET-CT performed at baseline and after treatment were retrospectively recruited between February 2018 and May 2020. Three target bone lesions were selected for each patient and their ADC, SUVmax and Deauville score were measured in every study. Correlation between ADC and SUVmax of the lesions was evaluated, as well as changes in mean ADC, SUVmax, and Deauville score between studies. Patients were classified as responder or non-responder according to the IMWG, MRI (MY-RADS) and PET-CT (IMPeTUs) response criteria. Agreement between the MRI and PET-CT criteria with the IMWG criteria was evaluated. RESULTS: The correlation between the ADC and SUVmax of all the target lesions was strong, negative and significant (r=-0.603; p < 0.001). After treatment, mean ADC in lesions from responders was significantly higher than in non-responders (1585.51 × 10-6 mm2/s vs 698.17 × 10-6 mm2/s; p < 0.001). SUVmax of the same lesions was significantly lower in responders than in non-responders (2.05 vs 5.33; p < 0.001). There was a very strong or strong agreement of the IMWG response criteria with both MRI (κ = 0.852; p < 0.001) and PET (κ = 0.767; p < 0.001) criteria. CONCLUSION: DWI-MRI and ADC may be used to assess treatment response in MM patients, showing a good correlation with 18F-FDG PET-CT and the IMWG response criteria.

Phase II multicenter randomized controlled clinical trial on the efficacy of intra-articular injection of autologous bone marrow mesenchymal stem cells with platelet rich plasma for the treatment of knee osteoarthritis.

BACKGROUND: Mesenchymal stromal cells are a safe and promising option to treat knee osteoarthritis as previously demonstrated in different clinical trials. However, their efficacy, optimal dose and addition of adjuvants must be determined. Here, we evaluated the clinical effects of a dose of 100 × 106 bone marrow mesenchymal stromal cells (BM-MSCs) in combination with Platelet Rich Plasma (PRGF®) as adjuvant in a randomized clinical trial. METHODS: A phase II, multicenter, randomized clinical trial with active control was conducted. Sixty patients diagnosed with knee OA were randomly assigned to 3 weekly doses of PRGF® or intraarticular administration of 100 × 106 cultured autologous BM-MSCs plus PRGF®. Patients were followed up for 12 months, and pain and function were assessed using VAS and WOMAC and by measuring the knee range of motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage. RESULTS: No adverse effects were reported after BM-MSC administration or during follow-up. According to VAS, the mean value (SD) for PRGF® and BM-MSC with PRGF® went from 5 (1.8) to 4.5 (2.2) (p = 0.389) and from 5.3 (1.9) to 3.5 (2.5) (p = 0.01), respectively at 12 months. In WOMAC, the mean (SD) baseline and 12-month overall WOMAC scores in patients treated with PRGF® was 31.9 (16.2) and 22.3 (15.8) respectively (p = 0.002) while that for patients treated with BM-MSC plus PRGF® was 33.4 (18.7) and 23.0 (16.6) (p = 0.053). Although statistical significances between groups have been not detected, only patients being treated with BM-MSC plus PRGF® could be considered as a OA treatment responders following OARSI criteria. X-ray and MRI (WORMS protocol) revealed no changes in knee joint space width or joint damage. CONCLUSIONS: Treatment with BM-MSC associated with PRGF® was shown to be a viable therapeutic option for osteoarthritis of the knee, with clinical improvement at the end of follow-up. Further phase III clinical trials would be necessary to confirm the efficacy. Trial registration Clinical Trials.gov identifier NCT02365142. Nº EudraCT: 2011-006036-23.

Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II).

BACKGROUND: Mesenchymal stromal cells are a promising option to treat knee osteoarthritis. Their safety and usefulness must be confirmed and the optimal dose established. We tested increasing doses of bone marrow mesenchymal stromal cells (BM-MSCs) in combination with hyaluronic acid in a randomized clinical trial. MATERIALS: A phase I/II multicenter randomized clinical trial with active control was conducted. Thirty patients diagnosed with knee OA were randomly assigned to intraarticularly administered hyaluronic acid alone (control), or together with 10 × 10(6) or 100 × 10(6) cultured autologous BM-MSCs, and followed up for 12 months. Pain and function were assessed using VAS and WOMAC and by measuring the knee motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage. RESULTS: No adverse effects were reported after BM-MSC administration or during follow-up. BM-MSC-administered patients improved according to VAS during all follow-up evaluations and median value (IQR) for control, low-dose and high-dose groups change from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 4 (3, 5), 2 (1, 3) and 2 (0,4) respectively at 12 months (low-dose vs control group p = 0.005 and high-dose vs control group p < 0.009). BM-MSC-administered patients were also superior according to WOMAC, although improvement in control and low-dose patients could not be significantly sustained beyond 6 months. On the other hand, the BM-MSC high-dose group exhibited an improvement of 16.5 (12, 19) points at 12 months (p < 0.01). Consistent with WOMAC and VAS values, motion ranges remained unaltered in the control group but improved at 12 months with BM-MSCs. X-ray revealed a reduction of the knee joint space width in the control group that was not seen in BM-MSCs high-dose group. MRI (WORMS protocol) showed that joint damage decreased only in the BM-MSC high-dose group, albeit slightly. CONCLUSIONS: The single intraarticular injection of in vitro expanded autologous BM-MSCs together with HA is a safe and feasible procedure that results in a clinical and functional improvement of knee OA, especially when 100 × 10(6) cells are administered. These results pave the way for a future phase III clinical trial. CLINICAL TRIALS: gov identifier NCT02123368. Nº EudraCT: 2009-017624-72.

The Relationship Between the Sesamoid Complex and the First Metatarsal After Hallux Valgus Surgery Without Lateral Soft-Tissue Release: A Prospective Study.

Some investigators have emphasized restoring the relationship between the sesamoid complex and the first metatarsal head to reduce the risk of hallux valgus recurring after surgical reconstruction. In a prospective study, we analyzed whether the first metatarsophalangeal joint could be realigned after scarf-Akin bunionectomy without lateral soft tissue release. A total of 25 feet, in 22 patients, were prospectively enrolled and analyzed using anteroposterior radiographs and coronal computed tomography scans obtained before and 3 months after surgery. The Yildirim sesamoid position decreased from a preoperative of 2 (range 1 to 3) to a postoperative position of 0 (range 0 to 1; p < .001), the mean first intermetatarsal angle decreased from 12.6° ± 2.4° to 5.8° ± 2.1° (p < .001), and the mean distance between the second metatarsal and the tibial sesamoid changed from 25.7 ± 4.6 to 25.9 ± 4.6 (p = .59). Our findings suggest that dislocation of the sesamoid complex is actually caused by displacement of the first metatarsal. In conclusion, the scarf-Akin bunionectomy adequately restores the alignment of the first metatarsophalangeal joint, including restoration of the sesamoid apparatus, without direct plantar-lateral soft tissue release.