Does Patellar Height Influence Range of Motion and Anterior Knee Pain after Distal Femur Endoprosthesis Reconstruction?

Objectives: This study aims to evaluate the patellar height changes after distal femur (DF) endoprosthetic replacement (EPR) and its impact on anterior knee pain (AKP) and range of motion (ROM). Methods: A retrospective review of three institutions' databases was performed. The patellar height was determined using the modified Insall-Salvati ratio (MIS), the Blackburne-Peel (BP) and the Caton-Deschamps (CD) indexes. Data regarding AKP and ROM were collected. Results: A total of 199 patients were included. The mean age at presentation was 37.9 ± 23.1 years. The mean one-year follow-up MIS, BP and CD were 1.52 (sd: 0.41), 0.82 (sd: 0.33) and 0.93 (sd: 0.33). Patellar height decreased significantly compared to the pre-operative values according to all three scores (p < 0.001). AKP was reported by 34 (17.1%) patients at 1 year follow-up. Patients with patella baja (MIS < 1.2) or pseudo patella baja (CD < 0.6) had a higher incidence of AKP (p = 0.037 and p = 0.024, respectively). The mean flexion ROM was 91°, with a direct correlation with patellar height (MIS p = 0.020, BP p = 0.036 and CD p = 0.036). Conclusion: The restoration of the native position of the joint line in DF EPR is important to maintain optimal patellofemoral biomechanics. Despite surgeons' tendency toward a reduction in patellar height with respect to pre-operative values, an increase in patellar height might help to achieve better knee flexion and reduce AKP.

Extended distal femur resection: Megaprosthesis with telescopic bone allograft augmentation versus total femur prosthesis.

BACKGROUND AND OBJECTIVE: Oncological distal femur resections can leave a proximal femur too short to host a stem. Reconstructive techniques are then challenging. The purpose of the study is to compare implant survival, complication rate and MSTS of two different options. METHODS: We retrospectively divided 33 patients with primary bone tumours of distal femur in Group 1 (16 patients reconstructed with knee megaprosthesis with proximal bone augmentation, APC) and Group 2 (17 patients reconstructed with total femur prosthesis, TFP). Less than 12 cm of remaining proximal femur were planned for all resections. RESULTS: MSTS score at 2 years is 25 ± 5 for Group 1 and 19 ± 7 for Group 2 (confidence interval [C.I.] 95%, p = 0.02). At 5 years it is 27 ± 2 for Group 1 and 22 ± 6 for Group 2 (C.I. 95%, p = 0.047). Failure and complication rates are lower for Group 1, but no statistical significance was reached. In APC reconstruction, union at the host-allograft junction was achieved in 16 out of 16 patients using the telescopic bone augmentation technique. CONCLUSIONS: APC provides higher functional results compared to TFP after extended distal femur resection. In APC reconstruction, telescopic augmentation is excellent for achieving union at the host-allograft junction.

Imaging of Spondylodiscitis: A Comprehensive Updated Review-Multimodality Imaging Findings, Differential Diagnosis, and Specific Microorganisms Detection.

Spondylodiscitis is defined by infectious conditions involving the vertebral column. The incidence of the disease has constantly increased over the last decades. Imaging plays a key role in each phase of the disease. Indeed, radiological tools are fundamental in (i) the initial diagnostic recognition of spondylodiscitis, (ii) the differentiation against inflammatory, degenerative, or calcific etiologies, (iii) the disease staging, as well as (iv) to provide clues to orient towards the microorganisms involved. This latter aim can be achieved with a mini-invasive procedure (e.g., CT-guided biopsy) or can be non-invasively supposed by the analysis of the CT, positron emission tomography (PET) CT, or MRI features displayed. Hence, this comprehensive review aims to summarize all the multimodality imaging features of spondylodiscitis. This, with the goal of serving as a reference for Physicians (infectious disease specialists, spine surgeons, radiologists) involved in the care of these patients. Nonetheless, this review article may offer starting points for future research articles.

Lengthening Patients Previously Treated for Massive Lower Limb Reconstruction for Bone Tumors with the PRECICE 2 Nail.

The objective of this study was to determine the efficacy of the PRECICE 2® nail in the treatment of lower limb length discrepancy in patients with a history of bone tumors. This study reports on outcomes, complications, and the safety of the PRECICE 2 limb lengthening nail in a cohort of pediatric patients with limb length discrepancy after surgery for bone tumors. Seventeen patients were treated with intramedullary magnetic nails. The average patient age at the time of surgery was 19 (range 11-32). The PRECICE 2 nail was used on 14 femurs (6 retrograde and 8 anterograde) and 3 tibias. The average consolidation time was 141 days (range 50-360) with a mean CI of 31 ± 12 days/cm. The ASAMI bone score showed 14 (82%) excellent results, 1 (6%) good result, and 2 (12%) poor results. The ASAMI functional score showed 13 (84.6%) excellent results, 3 (11.5%) good results, and 1 (3.8%) fair result. Patients treated with chemotherapy for bone cancer did not show any increase in distraction time or consolidation time. A total of 3 (17%) problems, 1 obstacle (5.5%), and 1 complication (5.5%) were encountered in our case series. The PRECICE 2 nail allows for effective and accurate lengthening preserving the range of motion in patients treated for bone tumors.

Silver-Coated Distal Femur Megaprosthesis in Chronic Infections with Severe Bone Loss: A Multicentre Case Series.

Periprosthetic joint infections (PJI) and fracture-related infections (FRI) of the distal femur (DF) may result in massive bone defects. Treatment options include articulated silver-coated (SC) megaprosthesis (MP) in the context of a two-stage protocol. However, there is limited evidence in the literature on this topic. A retrospective review of the prospectively maintained databases of three Institutions was performed. Forty-five patients were included. The mean follow-up time was 43 ± 17.1 months. Eight (17.8%) patients had a recurrent infection. The estimated recurrence-free survival rate was 91.1% (93.5% PJI vs. 85.7% FRI) 2 years following MP implantation, and 75.7% (83.2% PJI vs. 64.3% FRI; p = 0.253) after 5 years. No statistically relevant difference was found according to the initial diagnosis (PJI vs. FRI). Among possible risk factors, only resection length was found to significantly worsen the outcomes in terms of infection control (p = 0.031). A total of eight complications not related to infection were found after reimplantation, but only five of them required further surgery. Above-the-knee amputation was performed in two cases (4.4%), both for reinfection. Articulated DF SC MP in a two-stage protocol is a safe and effective treatment for chronic knee infection with severe bone loss.

Aneurysmal bone cyst: Is selective arterial embolization effective as curettage and bone grafting?

INTRODUCTION: Aneurysmal bone cyst (ABC) is a lytic benign bone lesion representing about 1% of all primary bone tumors. Method to treat ABC's have developed over time. The standard of care cure for ABC has been curettage with or without bone grafting of the defect but is burdened by recurrence rates of approximately 25%-31%. Based on the assumption that ABCs usually supplied by one or more pathological feeding arteries, selective arterial embolization has been described as an adjuvant preoperative procedure to reduce intra-operative hemorrhage, and as primary treatment for lesions in difficult surgical access. In the current study, we therefore asked whether (1) a single or a repeat selective arterial embolization (SAE) for treating ABCs would produce comparable healing rates compared with curettage and bone grafting; (2) evaluated the relationship of recurrence in relation to the site of the cyst, the age, and gender of the patients; and (3) the two techniques differ in term of long-term complication. MATERIAL AND METHODS: We retrospectively reviewed 265 patients who underwent curettage and bone grafting or SAE performed at our institute from 1994 to 2018. The diagnosis of ABC was always established with percutaneous CT-guided biopsy or open biopsy. Patients were followed clinically with plain radiographs or CT scan at 3, 6, 9, and 12 months then annually in the absence of symptoms. Treatment success was determined evaluating pre- and postprocedural imaging according to Chang classification. RESULTS: Two hundred and nineteen were treated with curettage and bone grafting (curettage group), and 46 with SAE Group. Of the 219 patients treated with Curettage and bone grafting (curettage group), 165 out of 219 (75.3%) experienced bone healing, while local recurrence was observed in 54 cases (24.7%) after 12 months on average (range: 3-120 months) from surgery. After the first SAE, bone ossification was seen in 27 (58.7%), without needing any further treatment. Eleven recurred patients were treated with SAE (four patients need two while seven need three SAE to heal), and eight patients with curettage and bone grafting. Thirty-eight out of 46 (82%) patients experienced bone ossification regardless the number of SAE. The overall rate of local recurrence for all patients was 26.7%. SAE group presented a lower complication rate (6%) where two patients experienced skin necrosis, and one limb-length discrepancies (2% of all cohort). DISCUSSION: The use of SAE is an attractive option to treat ABC as it combines on one hand a lower complication rate than curettage and bone grafting, on the other it can be carried out in case of nonresectable ABCs, significantly reducing the size of viable ABC lesions, fostering bone remodeling and mineralization, and most importantly, significantly improving the patient's quality of life.

Mid-Term Results of Single-Stage Surgery for Patients with Chronic Osteomyelitis Using Antibiotic-Loaded Resorbable PerOssal® Beads.

This retrospective study reports on the treatment of chronic osteomyelitis with local debridement combined with PerOssal®. The diagnosis of chronic osteomyelitis was confirmed in all cases and classified according to the Cierny-Mader (C-M) classification. The primary outcome was the eradication of infection at a minimum of one year after surgery. A total of 93 patients (median age: 40 years) were included. The most represented sites were the femur (24, 25.8%) and tibia (52, 55.9%). Twenty-six patients (28.0%) had significant local or systemic comorbidities (C-M Class B hosts). According to anatomic type, 31 cases were type I, 13 type II, 21 type III and 28 type IV. Vancomycin was added to PerOssal® in most cases (80, 86.0%). In 24 (25.8%) cases, Vancomycin and Rifampicin were combined. In 32 (34.4%) cases, intraoperative cultures were negative. Staphylococcus aureus was isolated in 39 (63.9%) patients, and Gram-negative bacteria were isolated in 12 cases. The median follow-up was 21 months (range 12-84). A total of 21 (22.6%) patients developed an infection recurrence (IR) after a median follow-up of 11 months (range: 1-47). PerOssal® holds several practical advantages compared to other bone void fillers. Thus, due to its good biocompatibility and sufficient antibiotic release, it represents a viable adjuvant treatment in chronic osteomyelitis.

Is the association of electrochemotherapy and bone fixation rational in patients with bone metastasis?

BACKGROUND: Bone metastases are frequent in patients with cancer. Electrochemotherapy (ECT) is a minimally invasive treatment based on a high-voltage electric pulse combined with an anticancer drug. Preclinical and clinical studies supported the use of ECT in patients with metastatic bone disease, demonstrating that it does not damage the mineral structure of the bone and its regenerative capacity, and that is feasible and efficient for the treatment of bone metastases. Year 2014 saw the start of a registry of patients with bone metastases treated with ECT, whose data are recorded in a shared database. QUESTIONS/PURPOSES: (1) Among patients who underwent ECT and internal fixation for bone metastasis, how many experienced a reduction of pain? (2) How many cases showed a radiological response? (3) How many patients presented local or systemic complication after ECT and fixation? PATIENTS AND METHODS: Patients were treated in Bologna at Rizzoli Orthopaedic Institute between March 2014 and February 2022 and recorded in the REINBONE registry (a shared database protected by security passwords): clinical and radiological information, ECT session, adverse events, response, quality of life indicators, and duration of follow-up were registered. We consider only cases treated with ECT and intramedullary nail during the same surgical session. Patients included in the analysis were 32: 15 males and 17 females, mean age 65 ± 13 years (median 66, range 38-88 years), mean time since diagnosis of primary tumor 6.2 ± 7.0 years (median 2.9, range 0-22 years). Nail was indicated in 13 cases for a pathological fracture in, 19 for an impending fracture. Follow-up was available for 29 patients, as 2 patients were lost to follow-up and 1 was unable to return to controls. Mean follow-up time was 7.7 ± 6.5 months (median 5, range 1-24), and 16 patients (50%) had a follow-up longer than 6 months. RESULTS: A significant decrease in pain intensity was observed at the mean Visual Numeric Scale after treatment. Bone recovery was observed in 13 patients. The other 16 patients remained without changes, and one presented disease progression. One patient presented a fracture occurrence during the ECT procedure. Among all patients, bone recovery was observed in 13 patients: complete recovery in 1 patient (3%) and partial recovery in 12 patients (41%). The other 16 patients remained without changes, and one presented disease progression. One patient presented a fracture occurrence during the ECT procedure. However, healing was possible with normal fracture callus quality and healing time. No other local or systemic complications were observed. CONCLUSION: We found that pain levels decreased after treatment in 23 of the 29 cases for a pain relief rate of 79% at final follow-up. Pain is one of the most important indicators of quality of life in patients that undergo palliative treatments. Even if conventional external body radiotherapy is considered a noninvasive treatment, it presents a dose-dependent toxicity. ECT provides a chemical necrosis preserving osteogenic activity and structural integrity of bone trabeculae; this is a crucial difference with other local treatments and allows bone healing in case of pathological fracture. The risk of local progression in our patient population was small, and 44% experienced bone recovery while 53% of the cases remained unchanged. We observe intraoperative fracture in one case. This technique, in selected patients, improves outcome in bone metastatic patients combing both the efficacy of the ECT in the local control of the disease and the mechanical stability with the bone fixation to synergize their benefits. Moreover, the risk of complication is very low. Although encouraging data, comparative studies are required to quantify the real efficacy of the technique. Level of Evidence Level I, therapeutic study.

Imaging of Musculoskeletal Soft-Tissue Infections in Clinical Practice: A Comprehensive Updated Review.

Musculoskeletal soft-tissue infections include a wide range of clinical conditions that are commonly encountered in both emergency departments and non-emergency clinical settings. Since clinical signs, symptoms, and even laboratory tests can be unremarkable or non-specific, imaging plays a key role in many cases. MRI is considered the most comprehensive and sensitive imaging tool available for the assessment of musculoskeletal infections. Ultrasound is a fundamental tool, especially for the evaluation of superficially located diseases and for US-guided interventional procedures, such as biopsy, needle-aspiration, and drainage. Conventional radiographs can be very helpful, especially for the detection of foreign bodies and in cases of infections with delayed diagnosis displaying bone involvement. This review article aims to provide a comprehensive overview of the radiological tools available and the imaging features of the most common musculoskeletal soft-tissue infections, including cellulitis, necrotizing and non-necrotizing fasciitis, foreign bodies, abscess, pyomyositis, infectious tenosynovitis, and bursitis.

Periacetabular Tumour Resection under Anterosuperior Iliac Spine Allows Better Alloprosthetic Reconstruction than Above: Bone Contact Matters.

BACKGROUND: Periacetabular resections are more affected by late complications than other pelvic resections. Reconstruction using bone allograft is considered a suitable solution. However, it is still not clear how the bone-allograft contact surface impacts on mechanical and functional outcome. MATERIALS AND METHODS: This paper presents the results of a retrospective analysis of 33 patients with resection of the entire acetabulum and reconstruction with an allograft-prosthetic composite for the period 1999 to 2010. Patients were divided in two groups, based on type of resection. In Group 1. patients had resections under anterosuperior iliac spine allowing the highest bone-allograft surface contact in reconstruction, while in Group 2 patients had resections over it. RESULTS: Mechanical survival of the implant and Musculoskeletal Tumor Society functional score were calculated. Impact of age and artificial ligament were investigated as well. Patients in Group 1 had 38% mechanical failure rate of the implant while patients in Group 2 had 88%. Average functional score was higher in Group 1 compared with patients in Group 2. An artificial ligament was shown to have non-significant impact on survival of the reconstruction in Group 1, while significantly improving survival of reconstruction in Group 2. CONCLUSION: Bone-allograft contact matters: resection under anterosuperior iliac spine allows better mechanical survival and offers better reconstruction functional scores.

Bone Turnover Marker (BTM) Changes after Denosumab in Giant Cell Tumors of Bone (GCTB): A Phase II Trial Correlative Study.

Background: Giant cell tumors of bone (GCTB) are osteolytic tumors. Denosumab, a RANK-L inhibitor, is approved for GCTB. Data on serum bone turnover marker (sBTM) changes are lacking. We present a phase II correlative study on sBTMs in GCTB patients treated with denosumab. Methods: All GCTB patients receiving denosumab within a multicentre, open-label, phase 2 study were enrolled. Serum levels of carboxyterminal-crosslinked-telopeptide of type I collagen (s-CTX), alkaline phosphatase (ALP), bone-alkaline phosphatase (bALP), parathyroid hormone (sPTH), and osteocalcin (OCN) were prospectively assessed (baseline, T0, 3 months, T1, 6 months, T2). The primary endpoint was assessment of sBTM changes after denosumab; the secondary endpoints were disease-free survival (DFS) and sBTM correlation. Results: In 54 cases, sBTMs decreased during denosumab treatment except for sPTH. With a median follow-up of 59 months, 3-year DFS was 65% (%CI 52−79), with a significantly worse outcome for patients with high (≥500 UI/mL) s-CTX at baseline, as compared to low s-CTX (<500 UI/mL) (3-year DFS for high CTX 45% (95%CI 23−67) vs. 75% (95%CI 59−91) for low s-CTX. Higher median ALP and s-CTX were found for patients with tumor size ≥ 5 cm (p = 0.0512; p = 0.0589). Conclusion: Denosumab induces ALP/OCN and s-CTX reduction. High baseline s-CTX identifies a group of patients at higher risk of progression of the disease.

Electrochemotherapy Is Effective in the Treatment of Bone Metastases.

Bone metastases induce pain, risk of fracture, and neural compression, and reduced mobility and quality of life. Electrochemotherapy (ECT) is a minimally invasive local treatment based on a high-voltage electric pulse combined with an anticancer drug. Preclinical and clinical studies have supported the use of ECT in patients with metastatic bone disease, demonstrating that it does not damage the mineral structure of the bone and its regenerative capacity, and that is feasible and efficient for the treatment of bone metastases. Since 2009, 88 patients with bone metastasis have received ECT at the Rizzoli Institute. 2014 saw the start of a registry of patients with bone metastases treated with ECT, whose data are recorded in a shared database. We share the Rizzoli Institute experience of 38 patients treated with ECT for a bone metastasis, excluding patients not included in the registry (before 2014) and those treated with bone fixation. Mean follow-up was 2 months (1-52). Response to treatment using RECIST criteria was 29% objective responses, 59% stable disease, and 16% progressive disease. Using PERCIST, the response was 36% OR, 14% SD, and 50% PD with no significant differences between the two criteria. A significant decrease in pain and better quality of life was observed at FU.

The Role of Imaging in Computer-Assisted Tumor Surgery of the Sacrum and Pelvis.

The use of a navigation system allows precise resection of a tumor and accurate reconstruction of the resultant defect thereby sparing important anatomical structures and preserving function. It is an "image-based" system where the imaging (computed tomography and magnetic resonance imaging) is required to supply the software with data. The fusion of the preoperative imaging provides pre-operative information about local anatomy and the extent of the tumor so that it allows accurate preoperative planning. Accurate pre-operative imaging is mandatory in order to minimize CATS errors, thus performing accurate tumor resections.

Vascular Proximity Increases the Risk of Local Recurrence in Soft-Tissue Sarcomas of the Thigh-A Retrospective MRI Study.

The aim of this study was to establish the prognostic effects of the proximity of the tumor to the main vessels in patients affected by soft tissue sarcomas (STS) of the thigh. A total of 529 adult patients with deeply seated STS of the thigh and popliteal fossa were included. Vascular proximity was defined on MRI: type 1 > 5 mm; type 2 ≤ 5 mm and >0 mm; type 3 close to the tumor; type 4 enclosed by the tumor. Proximity to major vessels type 1-2 had a local recurrence (LR) rate lower than type 3-4 (p < 0.001). In type 4, vascular by-pass reduced LR risk. On multivariate analysis infiltrative histotypes, high FNLCC grade, radiotherapy administration, and type 3-4 of proximity to major vessels were found to be independent prognostic factors for LR. We observed an augmented risk of recurrence, but not of survival as the tumor was near to the major vessels. When major vessels were found to be surrounded by the tumor on preoperative MRI, vascular resection and bypass reconstruction offered a better local control.

Fungal spondylodiscitis: imaging findings and brief review of the literature.

A 57-year-old man was admitted to our department reporting persistent low back and leg pain; this patient had undergone chemotherapy 1 year earlier for acute myeloid leukaemia (AML). During chemotherapy, he exhibited bilateral pneumonia due to Candida tropicalis, which was treated by specific antibiotic therapy, and septicaemia by Enterococcus faecalis MRI showed the presence of spondylodiscitis. A CT-guided needle biopsy was performed and the culture from the excised material tested positive for C. tropicalis We report a rare case of spondylodiscitis by C. tropicalis in a patient treated for AML, which, in turn, was followed by sepsis from E. faecalis and C. tropicalis Without adequate treatment, the disease is progressive, and leads to vertebral destruction with secondary kyphosis and neural or spinal cord compression. Although MRI has high sensitivity in the diagnosis of spondylodiscitis, open or needle biopsy allows to identify the aetiology.

Minimally invasive treatment of long bone non-unions with bone marrow concentrate, demineralized bone matrix and platelet-rich fibrin in 38 patients.

To determine the efficacy of percutaneous injection of autologous bone marrow concentrated (BMC), demineralized bone matrix (DBM), and platelet rich fibrin (PRF) in the treatment of long bone non-unions. From January 2011 to January 2018 patients with non-union of the lower limbs who were on the waiting list for open grafting with established tibial or femoral non-union and minimal deformity were eligible to participate in this study. Patients were treated with a single percutaneous injection of DBM, BMC and PRF. Our study group comprised 38 patients (26 males and 12 females; mean age 39, range 18 to 65). Non-unions were located in the femur (18 cases) and in the tibia (20 cases). Clinical and imaging follow-up ranged from 4 to 60 months (mean 20 months). Bone union occurred in 30 out of 38 patients (79%) in an average of 7 months (range 3 to 12) and all healed patients had full weight bearing after 9 months on average (range 6 to 12) from injection. In 19 cases the osteosynthesis was removed 12 months on average (range 3 to 36) from surgery. One patient developed infection at the non-union site after treatment. Percutaneous injection of DBM, BMC, and PRF is an effective treatment for long-bone non-unions. This technique allows the bone to heal with a minimally invasive approach and with a hospitalization of 2 days. Key elements of bone regeneration consist of a combination of biological and biomechanical therapeutic approach.

Operating procedures for electrochemotherapy in bone metastases: Results from a multicenter prospective study on 102 patients.

INTRODUCTION: Bone metastases are frequent in patients with cancer. Electrochemotherapy (ECT) is a minimally invasive treatment. Preclinical and clinical studies supported the use of ECT in patients with metastatic bone disease (MBD). The purposes of this multicentre study are to confirm the safety and efficacy of ECT, and to identify appropriate operating procedures in different MBD conditions. MATERIALS AND METHODS: 102 patients were treated in 11 Centres and recorded in the REINBONE registry (a shared database protected by security passwords): clinical and radiological information, ECT session, adverse events, response, quality of life indicators and duration of follow-up were registered. RESULTS: 105 ECT sessions were performed (one ECT session in 99 patients, two ECT sessions in 3 patients). 24 patients (23.5%) received a programmed intramedullary nail after ECT, during the same surgical procedure. Mean follow-up was 5.9 ± 5.1 months (range 1.5-52). The response to treatment by RECIST criteria was 40.4% objective responses, 50.6% stable disease and 9% progressive disease. According to PERCIST criteria the response was: 31.4% OR; 51.7% SD, 16.9% PD with no significant differences between the 2 criteria. Diagnosis of breast cancer and ECOG values 0-1 were significantly associated to objective response. A significant decrease in pain intensity and significant better quality of life was observed after ECT session at follow-up. CONCLUSION: The results are encouraging on pain and tumour local control. ECT proved to be an effective and safe treatment for MBD and it should be considered as an alternative treatment as well as in combination with radiation therapy.

Is percutaneous injection of bone marrow concentrate, demineralized bone matrix and PRF an alternative to curettage and bone grafting for treating aneurysmal bone cyst?

To determine the efficacy and safety of a single injection with autologous bone marrow concentrate (BMC) combined with demineralized bone matrix (DBM) and platelet-rich fibrin (PRF) compared to curettage and bone grafting for treating aneurysmal bone cysts (ABC). Two hundred thirty-nine patients were treated with curettage and bone grafting (Curettage Group), and 21 with percutaneous injection of DBM associated with autologous BMC and PRF (DBM + BMC + PRF Group). All patients attended the outpatient clinic to assess ABC healing and clinical results at the first 3, 6, 9 and 18 months after surgery and then annually in the absence of symptoms. The mean follow-up was 42 months for the Curettage Group (range 6-180 months) and 28 months for the DBM + BMC + PRF Group (range, 6-85 months). Out of the 21 patients who had injection with BMC, DBM, and PRF, 17 (80%) require no additional treatment and they were considered healed. Of the 239 patients treated with curettage and bone grafting after core needle or open biopsy, 177 (74%) were considered healed after the first treatment. Injection in comparison with curettage presented the same risk for local recurrence. The overall rate of local recurrence for all patients was 25%. Univariate and multivariate analyses showed a significant difference in local recurrence rates in patients younger than 15 years, and for the cyst located in the long bones of the lower limbs than the cyst located in the long bones of the upper limbs.

Systemic Inflammation Is Associated with Oncological Outcome in Patients with High-Grade Myxofibrosarcoma of the Extremities: A Retrospective Analysis.

BACKGROUND: The aim of this retrospective study is to verify whether preoperative systemic inflammatory markers (serum C-reactive protein [CRP] and neutrophil-lymphocyte ratio [NLR]) can help in predicting the disease-specific survival (DSS) and local recurrence (LR) rate in adult patients affected by localized myxofibrosarcoma (MFS) of the extremities. METHODS: We reviewed 126 adult patients with primary, localized MFS of the limbs. We analyzed DSS and LR. RESULTS: Median age at the time of surgery was 68 years (range 19-92). Median CRP was 0.4 mg/dL and median NLR was 2.8. A worse DSS was found in patients who had preoperative CRP >0.5 mg/dL (p = 0.002) and in those with NLR >3.5 (p < 0.001). In multivariate analysis, tumor size and grade as well as preoperative CRP values and NLR were confirmed to be prognostic factors in terms of DSS. An increased risk of LR was found in multivariate analysis in patients with a tail sign and with high gadolinium enhancement at preoperative MRI. CONCLUSIONS: Patients with high preoperative CRP and NLR levels, as well as large and high-grade tumors, might be considered as candidates for additional, more aggressive treatment approaches or more stringent follow-up schedules.

Mesenchymal stromal cells mediated delivery of photoactive nanoparticles inhibits osteosarcoma growth in vitro and in a murine in vivo ectopic model.

BACKGROUND: Osteosarcoma (OS) is an aggressive malignant neoplasm that still suffers from poor prognosis in the case of distal metastases or occurrence of multi-drug resistance. It is therefore crucial to find novel therapeutic options able to go beyond these limitations and improve patients' survival. The objective of this study is to exploit the intrinsic properties of mesenchymal stromal cells (MSCs) to migrate and infiltrate the tumor stroma to specifically deliver therapeutic agents directly to cancer cells. In particular, we aimed to test the efficacy of the photoactivation of MSCs loaded with nanoparticles in vitro and in a murine in vivo ectopic osteosarcoma model. METHODS: AlPcS4@FNPs were produced by adding tetra-sulfonated aluminum phthalocyanine (AlPcS4) to an aqueous solution of positively charged poly-methyl methacrylate core-shell fluorescent nanoparticles (FNPs). The photodynamic therapy (PDT) effect is achieved by activation of the photosensitizer AlPcS4 in the near-infrared light with an LED source. Human MSCs were isolated from the bone marrow of five donors to account for inter-patients variability and used in this study after being evaluated for their clonogenicity, multipotency and immunophenotypic profile. MSC lines were then tested for the ability to internalize and retain the nanoparticles, along with their migratory properties in vitro. Photoactivation effect was evaluated both in a monolayer (2D) co-culture of AlPcS4@FNPs loaded MSCs with human OS cells (SaOS-2) and in tridimensional (3D) multicellular spheroids (AlPcS4@FNPs loaded MSCs with human OS cells, MG-63). Cell death was assessed by AnnexinV/PI and Live&Dead CalceinAM/EthD staining in 2D, while in the 3D co-culture, the cell killing effect was measured through ATP content, CalceinAM/EthD staining and TEM imaging. We also evaluated the effectiveness of AlPcS4@FNPs loaded MSCs as delivery systems and the ability of the photodynamic treatment to kill cancer cells in a subcutaneous mouse model of OS by bioluminescence imaging (BLI) and histology. RESULTS: MSCs internalized AlPcS4@FNPs without losing or altering their motility and viability in vitro. Photoactivation of AlPcS4@FNPs loaded MSCs induced high level of OS cells death in the 2D co-culture. Similarly, in the 3D co-culture (MSCs:OS ratios 1:1 or 1:3), a substantial decrease of both MSCs and OS cells viability was observed. Notably, when increasing the MSCs:OS ratio to 1:7, photoactivation still caused more than 40% cells death. When tested in an in vivo ectopic OS model, AlPcS4@FNPs loaded MSCs were able to decrease OS growth by 68% after two cycles of photoactivation. CONCLUSIONS: Our findings demonstrate that MSCs can deliver functional photosensitizer-decorated nanoparticles in vitro and in vivo and inhibit OS tumor growth. MSCs may be an effective platform for the targeted delivery of therapeutic nanodrugs in a clinical scenario, alone or in combination with other osteosarcoma treatment modalities.