Assessing Heterogeneity of Osteolytic Lesions in Multiple Myeloma by ¹H HR-MAS NMR Metabolomics.

Multiple myeloma (MM) is a malignancy of plasma cells characterized by multifocal osteolytic bone lesions. Macroscopic and genetic heterogeneity has been documented within MM lesions. Understanding the bases of such heterogeneity may unveil relevant features of MM pathobiology. To this aim, we deployed unbiased ¹H high-resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) metabolomics to analyze multiple biopsy specimens of osteolytic lesions from one case of pathological fracture caused by MM. Multivariate analyses on normalized metabolite peak integrals allowed clusterization of samples in accordance with a posteriori histological findings. We investigated the relationship between morphological and NMR features by merging morphological data and metabolite profiling into a single correlation matrix. Data-merging addressed tissue heterogeneity, and greatly facilitated the mapping of lesions and nearby healthy tissues. Our proof-of-principle study reveals integrated metabolomics and histomorphology as a promising approach for the targeted study of osteolytic lesions.

How do we estimate survival? External validation of a tool for survival estimation in patients with metastatic bone disease-decision analysis and comparison of three international patient populations.

BACKGROUND: We recently developed a clinical decision support tool, capable of estimating the likelihood of survival at 3 and 12 months following surgery for patients with operable skeletal metastases. After making it publicly available on www.PATHFx.org , we attempted to externally validate it using independent, international data. METHODS: We collected data from patients treated at 13 Italian orthopaedic oncology referral centers between 2010 and 2013, then applied to PATHFx, which generated a probability of survival at three and 12-months for each patient. We assessed accuracy using the area under the receiver-operating characteristic curve (AUC), clinical utility using Decision Curve Analysis (DCA), and compared the Italian patient data to the training set (United States) and first external validation set (Scandinavia). RESULTS: The Italian dataset contained 287 records with at least 12 months follow-up information. The AUCs for the three-month and 12-month estimates was 0.80 and 0.77, respectively. There were missing data, including the surgeon's estimate of survival that was missing in the majority of records. Physiologically, Italian patients were similar to patients in the training and first validation sets. However notable differences were observed in the proportion of those surviving three and 12-months, suggesting differences in referral patterns and perhaps indications for surgery. CONCLUSIONS: PATHFx was successfully validated in an Italian dataset containing missing data. This study demonstrates its broad applicability to European patients, even in centers with differing treatment philosophies from those previously studied.

Pseudoaneurysm overlying an osteochondroma: a noteworthy complication.

Pseuodaneurysms are an extremely rare complication of osteochondromas. We describe a case of traumatic pseudoaneurysm of the brachial artery presenting as a soft tissue mass in a patient who was treated for an osteochondroma 3 years earlier. This case demonstrates that radiographic follow-up of large osteochondromas is mandatory and that, in patients with soft tissue masses and a history of osteochondroma, pseudoaneurysms should be included in the differential diagnosis.

Carbon-fiber reinforced intramedullary nailing in musculoskeletal tumor surgery: a national multicentric experience of the Italian Orthopaedic Society (SIOT) Bone Metastasis Study Group.

INTRODUCTION: Carbon fiber reinforced (CFR) implants have been proposed for the treatment of fractures or impending fractures of the long bones in the oncology patient. Aim of this study is to present the largest cohort of oncology patients operated by CFR nailing by the Italian Orthopaedic Society (SIOT) Bone Metastasis Study Group. METHODS: 53 adult oncology patients were operated on with a CFR-PEEK nail. All the data from adjuvants therapies were collected. Bone callus formation, response to radiotherapy, relapse or progression of the osteolysis were recorded. Hardware survival and failure, breakage and need for implant revision were also analysed. RESULTS: Anatomical implantation of nails include humerus (n = 35), femur (n =11) and tibia (n = 7). The most frequent tumors affecting the bone were myeloma (n = 13), breast (n = 11), lung (n = 8), and renal cell cancer (n = 7). Acrylic cement reinforcement was used in 2 patients. One patient was subjected to electrochemotherapy after nail insertion. Intraoperative and early postoperative complications occurred in 13.2% and 7.54% of patients respectively. Eight patients had local progression and one developed a stress fracture proximally to the distal static screw. Radiographic union occurred in 14 patients; one screw loosening was recorded. DISCUSSION: There is currently a lack of solid evidence on the clinical use of CFR nails in oncologic patients. This is the first and largest study of CFR nailing, with the longest available follow up. CONCLUSIONS: Implant related complications and surgery-related morbidity should be taken into account in the decision-making process for the surgical management of these patients. These data can improve the surgeon-patient communication and guide further studies on patients' survival and complications with respect to surgery.