Yaszemski, Michael J.

AbstractBackground and ObjectivesChordomas of the mobile spine (C1–L5) are rare malignant tumors. The purpose of this study was to review the outcome of surgical treatment for patients with primary mobile spine chordomas.MethodsThe oncologic outcomes and survival of 26 patients undergoing surgical resection for a primary mobile spine chordoma were assessed over a 25‐year period. The mean follow‐up was 12 ± 6 years.ResultsThe 2‐, 5‐, and 10‐year disease‐free survivals were 95%, 61%, and 55%. The local recurrence‐free survival was improved in patients receiving en bloc resection with negative margins (83% vs. 35%, p = 0.02) and similar in patients receiving adjuvant radiation therapy (43% vs. 45%, p = 0.30) at 10 years. Debulking of the tumor (hazard ratio [HR] = 6.41, p = 0.01) and a local recurrence (HR = 9.52, p = 0.005) were associated with death due to disease. Complications occurred in 19 (73%) patients, leading to reoperation in 9 (35%) patients; this rate was similar in intralesional and en bloc procedures.ConclusionSurgical resection of mobile spine chordomas is associated with a high rate of complications; however, en bloc resection can provide a hope for cure and appears to confer better oncologic outcomes for these tumors without an increase in complications compared to lesser resections.

This review extensively summarized the properties and synthesis methods for phosphorene nanosheets, quantum dots, nanoribbons and their most-recent biomedical applications in bone, nerve, skin, brain, kidney, biosensor, and cancer related fields.

The spinal column is the most common site for bone metastasis. Vertebral metastases with instability have historically been treated with corpectomy of the affected vertebral body and adjacent intervertebral discs, and have more recently been treated with separation surgery. With demographics shifting towards an elderly population, a less-invasive surgical approach is necessary for the repair of vertebral defects. We modified a previously reported expandable hollow cage composed of an oligo[poly(ethylene glycol) fumarate] (OPF) containment system that could be delivered via a posterior-only approach. Then, the polymer of interest, poly (methyl methacrylate) (PMMA) bone cement, was injected into the lumen of the cage after expansion to form an OPF/PMMA cage. We compared six different cage formulations to account for vertebral body and defect size, and performed a cage characterization via expansion kinetics and mechanical testing evaluations. Additionally, we investigated the feasibility of the OPF/PMMA cage in providing spine stability via kinematic analyses. The in-vitro placement of the implant using our OPF/PMMA cage system showed improvement and mechanical stability in a flexion motion. The results demonstrated that the formulation and technique presented in the current study have the potential to improve surgical outcomes in minimally invasive procedures on the spine.

Background: Sacral tumor resections require a multidisciplinary approach to achieve a cure and a functional outcome. Currently, there is no accepted classification system that provides a means to communicate among the multidisciplinary teams in terms of approach, osseous resection, reconstruction, and acceptable functional outcome. The purpose of this study was to report the outcome of sacral tumor resection based on our classification system. Methods: In this study, 196 patients (71 female and 125 male) undergoing an oncologic en bloc sacrectomy were reviewed. The mean age (and standard deviation) was 49 ± 16 years, and the mean body mass index was 27.2 ± 6.4 kg/m 2 . The resections included 130 sarcomas (66%). The mean follow-up was 7 ± 5 years. Results: Resections included total sacrectomy (Type 1A: 20 patients [10%]) requiring reconstruction, subtotal sacrectomy (Type 1B: 5 patients [3%]) requiring reconstruction, subtotal sacrectomy (Type 1C: 104 patients [53%]) not requiring reconstruction, hemisacrectomy (Type 2: 29 patients [15%]), external hemipelvectomy and hemisacrectomy (Type 3: 32 patients [16%]), total sacrectomy and external hemipelvectomy (Type 4: 5 patients [3%]), and hemicorporectomy (Type 5: 1 patient [1%]). The disease-specific survival was 66% at 5 years and 52% at 10 years. Based on the classification, the 5-year disease-specific survival was 34% for Type 1A, 100% for Type 1B, 71% for Type 1C, 65% for Type 2, 57% for Type 3, 100% for Type 4, and 100% for Type 5 (p < 0.001). Tumor recurrence occurred in 67 patients, including isolated local recurrence (14 patients), isolated metastatic disease (31 patients), and combined local and metastatic disease (22 patients). At 5 years, the local recurrence-free survival was 77% and the metastasis-free survival was 68%. Complications occurred in 153 patients (78%), most commonly wound complications (95 patients [48%]). Following the procedure, 154 patients (79%) were ambulatory, and the mean Musculoskeletal Tumor Society (MSTS93) score was 60% ± 23%. Conclusions: Although resections of sacral malignancies are associated with complications, they can be curative in a majority of patients, with a majority of patients ambulatory with an acceptable functional outcome considering the extent of the resection. At our institution, this classification allows for communication between surgical teams and implies a surgical approach, staging, reconstruction, and potential functional outcomes. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Characterizing the release profile for materials-directed local delivery of bioactive molecules and its effect on bone regeneration is an important step to improve our understanding of, and ability to optimize, the bone healing response. This study examined the local delivery of parathyroid hormone (PTH) using a thiol-ene hydrogel embedded in a porous poly(propylene fumarate) (PPF) scaffold for bone regeneration applications. The aim of this study was to characterize the degradation-controlled in vitro release kinetics of PTH from the thiol-ene hydrogels, in vivo hydrogel degradation in a subcutaneous implant model, and bone healing in a rat critical size bone defect. Tethering PTH to the hydrogel matrix eliminated the early timepoint burst release that was observed in previous in vitro work where PTH was free to diffuse out of the matrix. Only 8% of the tethered PTH was released from the hydrogel during the first 2 weeks, but by day 21, 80% of the PTH was released, and complete release was achieved by day 28. In vivo implantation revealed that complete degradation of the hydrogel alone occurred by day 21; however, when incorporated in a three-dimensional printed osteoconductive PPF scaffold, the hydrogel persisted for >56 days. Treatment of bone defects with the composite thiol-ene hydrogel–PPF scaffold, delivering either 3 or 10 μg of tethered PTH 1-84, was found to increase bridging of critical size bone defects, whereas treatment with 30 μg of tethered PTH resulted in less bone ingrowth into the defect area. Continued development of this biomaterial delivery system for PTH could lead to improved therapies for treatment of nonunion fractures and critical size bone defects.

10531 Background: Osteosarcoma (OS) is a clinically challenging primary malignant bone tumor that has a high rateof local recurrence and metastasis. Disease free survival has been reported to be as low as 19% despite contemporary chemotherapy regimens and surgery. Wnt signaling is known to play a role in osteogenesis and cancer pathogenesis, therefore is a promising target for therapeutic intervention in OS. Secreted Frizzled Related Proteins (sFRPs), Dickkopf-1 (DKK1), and Sclerostin (SOST) are secreted Wnt inhibitor proteins that regulate Wnt signaling in bone. This study investigates the activity of sFRP3, DKK1, and SOST in serum from OS patients with the goal of developing therapeutic Wnt inhibitors and clinically useful biomarkers. Methods: Enzyme linked immunosorbent assayswere used to quantify sFRP3, DKK1 and SOST levels in human serum (n=40 pairs; 20 OS patients, 20 aged matched non-diseased controls). Patients were stratified into 2 age groups: >35 (n=26 pairs) and <30 (n=14 pairs) years of age. Clinical data from the medical records was correlated with experimental results. Using a Wilcoxon signed rank test, a p–value <0.05 was significant. Results: sFRP3 levels were significantly decreased in 55% (22/40) of diseased samples compared to 20% (8/40) of the non-diseased controls (p= 0.007). DKK1 levels were elevated in 40% (16/40) of OS samples compared to 30% (12/40) of the non-diseased controls (p= 0.08). SOST levels were increased in 42.5% (17/40) of diseased samples compared to 32.5% (13/40) of the non-diseased controls (p= 0.38). When stratified by age, the younger patients showed a statistically significant decrease in sFRP3 expression (p<0.001). Serum levels of sFRP3, DKK1, and SOST were not statistically significant between metastatic and non-metastatic OS. Conclusions: Serum sFRP3 levels were significantly decreased in OS patients, a difference that was even more pronounced in the pediatric strata. Since sFRP3 is differentially expressed in patient serum it has potential as a clinical biomarker for initial tumor diagnosis and early detection of recurrence. Decreased sFRP3 expression may be responsible for the up regulation of Wnt signaling in OS. Wnt inhibitors such as sFRP3 have potential as therapeutic agents in OS warranting further investigation.

AbstractBackground and ObjectivesThe ACS‐NSQIP surgical risk calculator is an online tool that estimates the risk of postoperative complications. Sacrectomies for chordoma are associated with a high rate of complications. This study was to determine if the ACS‐NSQIP calculator can predict postoperative complications following sacrectomy.MethodsSixty‐five (42 male, 23 female) patients who underwent sacrectomy were analyzed using the Current Procedural Terminology (CPT) codes: 49215 (excision of presacral/sacral tumor), 63001 (laminectomy of sacral vertebrae), 63728 (laminectomy for biopsy/excision of sacral neoplasm) and 63307 (sacral vertebral corpectomy for intraspinal lesion). The predicted rates of complications were compared to the observed rates.ResultsComplications were noted in 44 (68%) patients. Of the risk factors available to input to the ACS‐NSQIP calculator, tobacco use (OR, 20.4; P < .001) was predictive of complications. The predicted risk of complications based off the CPT codes were: 49215 (16%); 63011 (6%); 63278 (11%) and 63307 (15%). Based on ROC curves, the use of the ACS‐NSQIP score were poor predictors of complications (49215, AUC 0.65); (63011, AUC 0.66); (63307, AUC 0.67); (63278, AUC 0.64).ConclusionThe ACS‐NSQIP calculator was a poor predictor of complications and was marginally better than a coin flip in its ability to predict complications following sacrectomy for chordoma.

Accurate clinical evaluation of renal osteodystrophy (ROD) is currently accomplished using invasive in vivo transiliac bone biopsy, followed by in vitro histomorphometry. In this study, we demonstrate that an alternative method for ROD assessment is through a fast, label-free Raman recording of multiple biomarkers combined with computational analysis for predicting the minimally required number of spectra for sample classification at defined accuracies. Four clinically relevant biomarkers: the mineral-to-matrix ratio, the carbonate-to-matrix ratio, phenylalanine, and calcium contents were experimentally determined and simultaneously considered as input to a linear discriminant analysis (LDA). Additionally, sample evaluation was performed with a linear support vector machine (LSVM) algorithm, with a 300 variable input. The computed probabilities based on a single spectrum were only marginally different (~80% from LDA and ~87% from LSVM), both providing an unacceptable classification power for a correct sample assignment. However, the Type I and Type II assignment errors confirm that a relatively small number of independent spectra (7 spectra for Type I and 5 spectra for Type II) is necessary for a p < 0.05 error probability. This low number of spectra supports the practicality of future in vivo Raman translation for a fast and accurate ROD detection in clinical settings.