Bone morphogenetic proteins and growth factors: Emerging role in regenerative orthopaedic surgery

Bone morphogenetic proteins (BMPs) were discovered by Urist and colleagues in 1965 and later defined as multifunctional cytokines involved in osteoinduction. BMPs are members of the transforming growth factor-β superfamily, with the exception of the BMP-1. Presently, at least 20 BMPs have been identified and studied, but only BMP 2, 4 and 7 have been able in vitro to stimulate the entire process of stem cell differentiation into osteoblastic mature cells. In preclinical and clinical studies, BMPs have demonstrated potential in osteoinduction and have been approved for clinical use in treating open fractures of the long bones and nonunions and in vertebral arthrodesis. Additional clinical uses of these molecules are under investigation and the possibility of using gene therapy in selected pathologies seems the most appealing

The surgical treatment of pelvic bone metastases

Pelvic bone metastases are a growing concern in the field of orthopedic surgery. Patients with pelvic metastasis are individually different with different needs of treatment in order to attain the best possible quality of life despite the advanced stage of disease. A holistic collaboration among the oncologist, radiation therapist, and orthopedic surgeon is mandatory. Special attention has to be directed to osteolytic lesions in the periacetabular region as they can provoke pathological fractures and subsequent functional impairment. Different reconstruction techniques for the pelvis are available; the choice depends on the patient's prognosis, size of the bone defect, and response of the tumor to adjuvant treatment. If all the conservative treatments are exhausted and the patient is not eligible for surgery, one of the various percutaneous ablation procedures can be considered. We propose a pelvic analogue to the treatment algorithm in long bone metastasis and a scoring system in pelvic metastasis. This algorithm aims to simplify the teamwork and to avoid under-or overtreatment of pelvic bone metastases

Contribution of Raman Spectroscopy to Diagnosis and Grading of Chondrogenic Tumors

In the last decade, Raman Spectroscopy has demonstrated to be a label-free and non-destructive optical spectroscopy able to improve diagnostic accuracy in cancer diagnosis. This is because Raman spectroscopic measurements can reveal a deep molecular understanding of the biochemical changes in cancer tissues in comparison with non-cancer tissues. In this pilot study, we apply Raman spectroscopy imaging to the diagnosis and grading of chondrogenic tumors, including enchondroma and chondrosarcomas of increasing histologic grades. The investigation included the analysis of areas of 50×50 μm2 to approximately 200×200 μm2, respectively. Multivariate statistical analysis, based on unsupervised (Principal Analysis Components) and supervised (Linear Discriminant Analysis) methods, differentiated between the various tumor samples, between cells and extracellular matrix, and between collagen and non-collagenous components. The results dealt out basic biochemical information on tumor progression giving the possibility to grade with certainty the malignant cartilaginous tumors under investigation. The basic processes revealed by Raman Spectroscopy are the progressive degrading of collagen type-II components, the formation of calcifications and the cell proliferation in tissues ranging from enchondroma to chondrosarcomas. This study highlights that Raman spectroscopy is particularly effective when cartilaginous tumors need to be subjected to histopathological analysis

What was the survival of megaprostheses in lower limb reconstructions after tumor resections?

Analisi retrospettiva delle ricostruzioni dell'arto inferiore con protesi modulariBackground: Prosthetic replacement is the most commonly used option for reconstruction of osteoarticular bone loss resulting from bone neoplasm resection or prosthetic failure. Starting in late 2001, we began exclusively using a single system for large-segment osteoarticular reconstruction after tumor resection; to our knowledge, there are no published series from one center evaluating the use of this implant. Questions/purposes: We investigated the following issues: (1) What is the overall survival, excluding local tumor recurrence, for these endoprostheses used for tumor reconstructions of the lower extremities (knee and hip)? (2) What types of failure were observed in these reconstructions? (3) Do the survival and complications vary according to site of implant? Methods: Between September 2001 and March 2012, we exclusively used this implant for tumor reconstructions. During that time, 278 patients underwent tumor reconstructions of the hip or knee, of whom 200 (72%) were available at a minimum 2 years followup. Seventy-eight patients were excluded from the study for insufficient followup as a result of early death (42) or loss at followup (36). The reconstruction types were the following: proximal femur (69 cases), distal femur (87), proximal tibia (32), and total knee (12). Failures were classified according to the Henderson classification. Nine patients among those with followup shorter than 2 years had presented one or more failures and they were included in our analysis but separately evaluated. Results: Overall survival (no further surgical procedures of any type after primary surgery), excluding Type 5 failure (tumor recurrence), was 75.9% at 5 years and 66.2% at 10 years. Seventy-one failures occurred in 58 implants (29%). Mechanical failures accounted for 59.2% and nonmechanical failures for 40.8%. The first causes of failure of the implants were the result of soft tissue failure in 6%, aseptic loosening in 3%, structural failure in 7%, infection in 8.5%, and tumor recurrence in 4.5% of the whole series. Nine implants sustained two or more failures. Overall incidence of infection was 9.5%. No statistically significant differences were observed according to anatomical site. Conclusions: Like in the case with many such complex oncologic reconstructions, the failure rate at short- to midterm in this group was over 20%. Comparative trials are called for to ascertain whether one implant is superior to another. Infection and structural failure were the most frequent modes of failure in our experience. Level of Evidence: Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence

Allograft Reconstruction of the Extensor Mechanism after Resection of Soft Tissue Sarcoma

Soft tissue tumors around the knee joint still pose problems for the excision and subsequent reconstruction. Methods. In the 6 included patients the soft tissue sarcoma has its base on the anterior surface of the extensor mechanism and expands towards the skin. The entire extensor apparatus (quadriceps tendon, patella, and patellar tendon) was resected and replaced by a fresh-frozen allograft. Results. The mean follow-up was 6.7 years (range: 2-12.4 years). In two patients a local recurrence occurred, resulting in a 5-year local recurrence-free rale of 66.7% (95% CI: 19.5%-90.4%). Distant metastases were found in 4 patients resulting in a 5-year metastasis-free rate of 33.3% (95% CI: 4.6%-67.5%). Two patients underwent at least one revision surgery, including one patient in whom the allograft had to be removed. According to the ISOLS function score 24.7 points (range: 19-28 points) were achieved at the last follow-up. The mean active flexion of the knee joint was 82.5 degrees (range: 25-120 degrees) and a mean extension lag of 10 degrees (range: 0-30 degrees) was observed. Conclusions. Ihe replacement of the extensor mechanism by an allograft is a reasonable option, allowing wide margins and restoration of active extension in most patients. Trial Registration. The presented study is listed on the ISRCTN registry with trial number ISRCTN63060594

Surgical management of villonodular-pigmented synovitis of knee: decisional algorithm

Pigmented villonodular synovitis (PVNS) of knee is an uncommon disease defined as benign despite presenting local aggressiveness and high propensity to recurrence. Etiology is still not completely understood. It seems to be a chronic inflammation process involving synovial membranes characterized by hemosiderin deposition which leads to pain, limitation of range of motion and, if not treated, bone erosion and osteoarthritis of knee. The gold standard for treatment is surgical excision; other adjuvant or alternative therapies are described, too. We present a case series of PVNS of the knee treated with surgical excision at our institution. Functionality was assessed using the Muscoloskeletal Tumor Society (MSTS) Score for lower limbs and Oxford Knee Score (OKS). Statistical analysis were performed. At the latest follow-up, our patients' mean MSTS score was 26.4 (30-18): 27.4 for those treated with posterior approach and 26.1 for the anterior ones. Only 5% of patients suffered local complications and 15% had a local recurrence of the disease. Adequate pre-operative study and careful surgical excision, that should be tailored to each patient are the key to obtain a low recurrence rate

Bone Marrow Concentrate in the Treatment of Aneurysmal Bone Cysts: A Case Series Study

Introduction. A recent attractive option regarding mesenchymal stem cells (MSC) application is the treatment of bone cystic lesions and in particular aneurysmal bone cysts (ABC), in order to stimulate intrinsic healing. We performed a retrospective evaluation of the results obtained at our institution.Methods. The study group consisted of 46 cases with an average follow-up of 33 months. Forty-two patients underwent percutaneous treatment as the first approach; four patients had curettage as first treatment. In all cases, autologous bone marrow concentrate (BMC) was associated too. The healing status was followed up through a plain radiograph 45 days and 2 months after the procedure.Results and Conclusions.At the final follow-up, thirty-six patients healed with a Neer type II aspect, nine healed with a type I aspect, and one patient was not classified having total hip arthroplasty. Bone marrow concentrate is easy to obtain and to manipulate and can be immediately available in a clinical setting. We can assert that the use of BMC must be encouraged being harmless and having an unquestionable high osteogenic and healing potential in bone def

Risks and benefits of combining denosumab and surgery in giant cell tumor of bone-a case series

BACKGROUND The RANK ligand inhibitor denosumab is being investigated for treatment of giant cell tumor of bone, but the available data in the literature remains sparse and controversial. This study analyzes the results of combining denosumab with surgical treatment and highlights possible changes for the oncologic surgeon in daily practice. METHODS A total of 91 patients were treated surgically for giant cell tumor of bone between 2010 and 2014 in an institution, whereas 25 patients of the total additionally received denosumab and were part of this study. The average age of the patients was 35 years. Eleven patients received denosumab pre- and postoperatively, whereas with 14 patients, the denosumab treatment was applied either before (7 patients) or after (7 patients) the surgery. The average preoperative therapy duration was 3.9 months and the postoperative therapy 6 months by default. RESULTS Sixteen patients presented a large tumor extension necessitating a resection of the involved bone or joint. In 10 of these patients, the indication for a resection procedure was abandoned due to the preoperative denosumab treatment and a curettage was performed. In the remaining six cases, the surgical indication was not changed despite the denosumab treatment, and two of them needed a joint replacement after the tumor resection. Also with patients treated with curettage, denosumab seems to facilitate the procedure as a new peripheral bone rim around the tumor was built, though a histologic analysis reveals viable tumor cells persisting in the denosumab-induced bone formation. After an average follow-up of 23 months, one histologically proven local recurrence occurred, necessitating a second curettage. A second patient showed a lesion in the postoperative imaging highly suspicious for local relapse which remained stable under further denosumab treatment. No adverse effect of the denosumab medication was observed in this study. CONCLUSIONS Denosumab can be a help to the oncologic surgeon by reconstituting a peripheral rim and switching the stage from aggressive to active or latent disease. But as tumor cells remain in the new-formed bone, the surgical technique of curettage has to be changed from gentle to more aggressive to avoid higher local recurrence rates

Medial pivot vs posterior stabilized total knee arthroplasty designs: a gait analysis study

Aim To compare a medial pivot (MP) total knee arthroplasty (TKA) with posterior stabilized (PS) TKA designs from a subjective, clinical and biomechanical point of view, in a single-centre, single-surgeon, case-control non-randomized trial. Methods Sixteen patients were randomly picked up from case series into each group. Subjective outcome was assessed using the Forgotten Joint Score Questionnaire (FJSQ). Clinical evaluation included range of motion (ROM). All patients underwent gait analysis by a treadmill with force-measuring plaques and videorecording device; data were recorded for 30 seconds and included cadence, step length, stance time and walking speed. A blinded qualitative analysis of the pattern of gait was defined as biphasic or non-biphasic. Descriptive statistics for the continuous study variables and statistical significance were calculated for all parameters with independent-samples t-test and χ2 test to analyse difference in pattern of gait between groups. Results Mean FJSQ in the MP group was 91.87 (CI 95%: 88.12- 95.46) and 75.31 (CI 95%: 67.97-81.56) in the PS group (p=0.029). Mean post-operative ROM was 117° (CI 95%: 113°-122°) in the MP group and 112° (CI 95%: 108°-117°) in the PS group (p=0.14). No statistical difference was found between groups regarding all gait analysis parameters which have been recorded. Conclusion MP TKA design showed better subjective results using the FJSQ, but it did not improve significantly clinical and functional outcomes compared to PS TKA design, at a short-term follow-up