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Supplementary Movie 1 from Real-time Imaging of Tumor-Cell Shedding and Trafficking in Lymphatic Channels

Supplementary Movie 2 from Development of Real-time Subcellular Dynamic Multicolor Imaging of Cancer-Cell Trafficking in Live Mice with a Variable-Magnification Whole-Mouse Imaging System

Supplementary Movie 3 from Development of Real-time Subcellular Dynamic Multicolor Imaging of Cancer-Cell Trafficking in Live Mice with a Variable-Magnification Whole-Mouse Imaging System

With the use of dual-color fluorescent cells and a highly sensitive whole-mouse imaging system with both macro-optics and micro-optics, we report here the development of subcellular real-time imaging of cancer cell trafficking in live mice. To observe cytoplasmic and nuclear dynamics in the living mouse, tumor cells were labeled in the nucleus with green fluorescent protein and with red fluorescent protein in the cytoplasm. Dual-color cancer cells were injected by a vascular route in an abdominal skin flap in nude mice. The mice were imaged with an Olympus OV100 whole-mouse imaging system with a sensitive CCD camera and five objective lenses, parcentered and parfocal, enabling imaging from macrocellular to subcellular. We observed the nuclear and cytoplasmic behavior of cancer cells in real time in blood vessels as they moved by various means or adhered to the vessel surface in the abdominal skin flap. During extravasation, real-time dual-color imaging showed that cytoplasmic processes of the cancer cells exited the vessels first, with nuclei following along the cytoplasmic projections. Both cytoplasm and nuclei underwent deformation during extravasation. Different cancer cell lines seemed to strongly vary in their ability to extravasate. With the dual-color cancer cells and the highly sensitive whole-mouse imaging system described here, the subcellular dynamics of cancer metastasis can now be observed in live mice in real time. This imaging technology will enable further understanding of the critical steps of metastasis and provide visible targets for antimetastasis drug development. (Cancer Res 2006; 66(8): 4208-14)

Supplementary Movie 1 from Development of Real-time Subcellular Dynamic Multicolor Imaging of Cancer-Cell Trafficking in Live Mice with a Variable-Magnification Whole-Mouse Imaging System

Supplementary Movie 3 from Real-time Imaging of Tumor-Cell Shedding and Trafficking in Lymphatic Channels

Aims To evaluate the perioperative complications associated with total en bloc spondylectomy (TES) in patients with spinal tumours, based on the extent and level of tumour resection. Methods In total, 307 patients who underwent TES in a single centre were reviewed retrospectively. There were 164 male and 143 female patients with a mean age at the time of surgery of 52.9 years (SD 13.3). A total of 225 patients were operated on for spinal metastases, 34 for a malignant primary tumour, 41 for an aggressive benign tumour, and seven with a primary of unknown origin. The main lesion was located in the thoracic spine in 213, and in the lumbar spine in 94 patients. There were 97 patients who underwent TES for more than two consecutive vertebrae. Results Major and minor perioperative complications were observed in 122 (39.7%) and 84 (27.4%) patients respectively. The breakdown of complications was as follows: bleeding more than 2,000 ml in 60 (19.5%) patients, hardware failure in 82 (26.7%), neurological in 46 (15.0%), surgical site infection in 23 (7.5%), wound dehiscence in 16 (5.2%), cerebrospinal fluid leakage in 45 (14.7%), respiratory in 52 (16.9%), cardiovascular in 11 (3.6%), digestive in 19 (6.2%)/ The mortality within two months of surgery was four (1.3%). The total number of complications per operation were 1.01 (SD 1.0) in the single vertebral resection group and 1.56 (SD 1.2) in the group with more than two vertebral resections. Cardiovascular and respiratory complications, along with hardware failure were statistically higher in the group who had more than two vertebrae resected. Also, in this group the amount of bleeding in patients with a lumbar lesion or respiratory complication in patients with a thoracic lesion, were statistically higher. Multivariate analysis showed that using a combined anterior and posterior approach, when more than two vertebral resections were significant independent factors. Conclusion The characteristics of perioperative complications after TES were different depending on the extent and level of the tumour resection. In addition to preoperative clinical and pathological factors, it is therefore important to consider these factors in patients who undergo en bloc resection for spinal tumours. Cite this article: Bone Joint J 2021;103-B(5):976–983.

Background aims Activated γδT cells have been shown to exhibit cytotoxicity against tumor cells. However, the efficacy of γδT cell immunotherapy for a large number of patients with solid tumors remains unclear. In this study, we examined the efficacy of γδT cell immunotherapy using in vitro-activated γδT lymphocytes in combination with standard therapies in terms of the survival of patients with solid tumors, and determined prognostic factor for γδT cell immunotherapy. Methods 131 patients enrolled in this study received γδT cell immunotherapy with or without standard therapies. Their overall survival was analyzed by the Kaplan-Meier with log-rank test and Cox regression methods. Immunological analysis was performed by flow cytometry (FCM) before and after six cycles of γδT cell immunotherapy. Results Multivariable analysis revealed that patients who showed stable disease (SD) and partial response (PR) to γδT cell immunotherapy showed better prognosis than those with a progressive disease (PD) (P = 0.0269, hazard ratio [HR], 0.410, 95% confidence interval [CI], 0.190–0.901). Furthermore, when immunological parameters were examined by FCM, the high Vγ9/γδT ratio (i.e., the high purity of the Vγ9 cells within the adoptively transferred γδT cells) before treatment was found to be a good prognostic factor for γδT cell immunotherapy (P = 0.0142, HR, 0.328, 95% CI, 0.125–0.801). No serious adverse events were reported during γδT cell immunotherapy. Conclusion Thus, γδT cell immunotherapy might extend the survival of patients with solid tumors.

Background The use of surgical metastasectomy (SM) has increased across cancer types in recent decades despite the increasing efficacy of modern systemic treatment modalities. Symptomatic spinal metastases severely compromise patients’ performance status. However, as spinal SM is a complex surgery with potentially significant complications, it is not considered the treatment of choice. Methods We reviewed the articles on SM in several primary cancers with different types of metastatic lesions and extracted the data from relevant articles to provide a comprehensive review including the surgical techniques, indications, reported outcomes, and future prospects of SM in spinal metastases. Results Total en bloc spondylectomy (TES) is a method of spinal SM associated with a lower risk of tumor recurrence and complications. Intralesional transpedicular osteotomy using a fine threadwire saw allows prevention of spinal cord and nerve root injuries. Spinal SM is considered suitable for patients with controlled primary disease having no evidence of disseminated extraspinal metastases, a completely resectable solitary lesion in the spine, and adequate cardiopulmonary reserve to tolerate the surgery. Metastatic lesions from kidney and thyroid cancers have been reported as the best candidates for spinal SM. Although data about spinal SM are limited, the reported outcomes are favorable with acceptable local recurrence rates in long-term follow-up. Conclusion In patients with isolated resectable spinal metastases, complete SM including TES is a useful option as it can improve function and survival. However, appropriate patient selection and surgical feasibility remain the most important aspects of management. Implications for Practice Surgical metastasectomy for spinal metastases may be a potentially curative treatment option with a low risk of local recurrence and lead to prolonged long-term survival if appropriate patients are selected and if the surgery is carried out by experienced surgeons in high-volume centers.

Study design Retrospective study. Objective The purpose of this study was to examine motor and sensory impairments of the lower extremities after L2 nerve root transection during total en bloc spondylectomy (TES) for spinal tumors. Summary of background data At our institute, for TES at L3 to L5 lumbar levels, the nerve roots are preserved. However, at the level of L1 and L2, the vertebral resection and spinal reconstruction via a posterior approach is employed with transection of the nerve roots during dissection and resection of the vertebra. Methods This study included 13 patients who had undergone TES for spinal tumors involving L2 between 2007 and 2016. Postoperative motor function of the lower extremities was quantified using the Manual Muscle Testing grade for the iliopsoas (IP) and quadriceps femoris (QF) muscles, and a grade of the modified Frankel Classification. Postoperative sensory impairment was quantified by the sites of lower extremity pain and numbness. Results An initial decrease in strength of the IP and QF muscles in more than 60% of the patients, with a decline in the modified Frankel grade in 76.9%, was observed at 1-week after surgery. All patients recovered by the final follow-up, with 12 of the 13 patients walking without a gait aid. The other patient, who had undergone a bilateral dissection of L3 nerve root during TES of L2 and L3, had a mild QF muscle weakness, requiring a cane for walking. Eleven of 13 patients developed pain or numbness in the groin or thigh area after surgery, with the most common area being the anterior aspect of the thigh. Conclusion Although IP and QF weakness was observed in the majority of patients who underwent bilateral transection of L2 nerve roots during TES, these deficits recovered over time and did not finally affect activities of daily living. Level of evidence 4.

AIM: Surgery for spinal metastases can improve symptoms, but sometimes complications can negate the benefits. Operations may have different indications, complexities and risks, and the choice for an individual is a tailor-made personalised decision. Previous prognostic scoring systems are becoming out of date and inaccurate. We designed a risk calculator to estimate survival after surgery, to inform clinicians and patients when making management decisions. METHODS: A prospective cohort study was performed, including 1430 patients with spinal metastases who underwent surgery. Of them, 1264 patients from 20 centres were used for model development using a Cox frailty model. Calibration slope, D-statistic and C-index were used for model validation based on 166 patients. Follow-up was to death or minimum of 2 years after surgery. Pre-operative indices (examination findings, pain, Karnofsky physical functioning score, and radiology) were assessed. RESULTS: An algorithm to predict survival was constructed including the tumour type, ambulatory status, analgesic use, American Society of Anesthesiologists score, number of spinal metastases, previous radiotherapy or chemotherapy, presence of visceral metastases, cervical or thoracic spine involvement, as predictors. An Internet-based risk calculator was developed based on this algorithm, with similar or improved accuracy compared to other validated prognostic scoring systems (C-index, 0.68; 95% confidence interval, 0.63--0.73, and calibration slope, 1.00; 95% confidence interval, 0.68--1.32). CONCLUSION: A large, prospective, surgical series of patients with symptomatic spinal metastases was used to create a validated risk calculator that can help clinicians to inform patients about the most appropriate treatment plan. The calculator is available at www.spinemet.com. ispartof: EUROPEAN JOURNAL OF CANCER vol:107 pages:28-36 ispartof: location:England status: published

Study Design. A prospective multicenter cohort study.Objective. To assess the clinical accuracy of six commonly cited prognostic scoring systems for patients with spinal metastases.Summary of Background Data. There are presently several available methods for the estimation of prognosis in metastatic spinal disease, but none are universally accepted by surgeons for clinical use. These scoring systems have not been rigorously tested and validated in large datasets to see if they are reliable enough to inform day-to-day patient management decisions. We tested these scoring systems in a large cohort of patients. A total of 1469 patients were recruited into a secure internet database, and prospectively collected data were analyzed to assess the accuracy of published prognostic scoring systems.Methods. We assessed six prognostic scoring systems, described by the first authors Tomita, Tokuhashi, Bauer, van der Linden, Rades, and Bollen. Kaplan-Meier survival estimates were created for different patient subgroups as described in the original publications. Harrell's C-statistic was calculated for the survival estimates, to assess the concordance between estimated and actual survival.Results. All the prognostic scoring systems tested were able to categorize patients into separate prognostic groups with different overall survivals. However none of the scores were able to achieve "good concordance" as assessed by Harrell's C-statistic. The score of Bollen and colleagues was found to be the most accurate, with a Harrell's C-statistic of 0.66.Conclusion. No prognostic scoring system was found to have a good predictive value. The scores of Bollen and Tomita were the most effective with Harrell's C-statistic of 0.66 and 0.65, respectively. Prognostic scoring systems are calculated using data from previous years, and are subject to inaccuracies as treatments advance in the interim. We suggest that other methods of assessing prognosis should be explored, such as prognostic risk calculation.

Background aims Immunotherapy is effective for many types of cancer, but its benefits in advanced pancreatic cancer, which has a poor prognosis, are not well established. In this study, the authors examined the effects of adoptive T-cell immunotherapy (ATI) on immune cell profiles and prognosis in patients with unresectable advanced pancreatic cancer. Methods Seventy-seven patients with unresectable advanced pancreatic cancer were treated with six cycles of αβ T cells alone or in combination with chemotherapy or chemoradiation. Immune cell profiles in peripheral blood samples obtained before and after treatment were comprehensively evaluated by flow cytometry. Furthermore, associations between changes in immune cell frequencies and prognosis were determined. Results ATI prolonged survival to 18.7 months compared with previous estimates of 6.2–11.1 months for patients treated with chemotherapy alone. ATI decreased CD3+CD4+CD8− T cell frequency in peripheral blood and increased CD3+CD4−CD8+ T cell frequency. An increase in CD3+ T cells and CD3+TCRγδ− T cells in peripheral blood after treatment was associated with a good prognosis. Conclusions ATI altered the immune profile in peripheral blood, including CD3+CD4−CD8+ T cells, and improved prognosis in pancreatic cancer.

BACKGROUND: The benefits of surgery for symptomatic spinal metastases have been demonstrated, largely based on series of patients undergoing debulking and instrumentation operations. However, as cancer treatments improve and overall survival lengths increase, the incidence of recurrent spinal cord compression after debulking may increase. The aim of the current paper is to document the postoperative evolution of neurological function, pain, and quality of life following debulking and instrumentation in the Global Spine Tumor Study Group (GSTSG) database. METHODS: The GSTSG database is a prospective multicenter data repository of consecutive patients that underwent surgery for a symptomatic spinal metastasis. For the present analysis, patients were selected from the database that underwent decompressive debulking surgery with instrumentation. Preoperative tumor type, Tomita and Tokuhashi scores, EQ-5D, Frankel, Karnofsky, and postoperative complications, survival, EQ-5D, Frankel, Karnofsky, and pain numeric rating scores (NRS) at 3, 6, 12, and 24 months were analyzed. RESULTS: A total of 914 patients underwent decompressive debulking surgery with instrumentation and had documented follow-up until death or until 2 years post surgery. Median preoperative Karnofsky performance index was 70. A total of 656 patients (71.8%) had visceral metastases and 490 (53.6%) had extraspinal bone metastases. Tomita scores were evenly distributed above (49.1%) and below or equal to 5 (50.9%), and Tokuhashi scores almost evenly distributed below or equal to 8 (46.3%) and above 8 (53.7%). Overall, 12-month survival after surgery was 56.3%. The surgery resulted in EQ-5D health status improvement and NRS pain reduction that was maintained throughout follow-up. Frankel scores improved at first follow-up in 25.0% of patients, but by 12 months neurological deterioration was observed in 18.8%. CONCLUSION: We found that palliative debulking and instrumentation surgeries were performed throughout all Tomita and Tokuhashi categories. These surgeries reduced pain scores and improved quality of life up to 2 years after surgery. After initial improvement, a proportion of patients experienced neurological deterioration by 1 year, but the majority of patients remained stable. ispartof: ACTA NEUROCHIRURGICA vol:162 issue:4 pages:943-950 ispartof: location:Austria status: published

Leiomyosarcoma (LMS) is generally resistant to radiation and chemotherapy. Our study aimed to examine the outcomes of total en bloc spondylectomy (TES) for spinal metastatic LMS and to analyze potential factors associated with survival. This study included 10 consecutive patients who underwent TES for spinal metastatic LMS at our institute between 2005 and 2016 and were followed up at a minimum of 3 years after surgery. At the time of TES, all the 10 patients had solitary bone metastases in the spine. Seven patients had a lowered performance status (PS) with an eastern cooperative oncology group (ECOG) grade of 2 or 3 due to back pain or neurological symptoms. The cancer-specific survival (CSS) time from TES to death or last follow-up was the main endpoint. Potential factors associated with survival were evaluated using the Kaplan–Meier analysis and the log-rank test. Five patients underwent a single vertebral resection, and the other five patients underwent two or three consecutive vertebral resections. Three patients developed perioperative complications including pulmonary thromboembolism and pneumothorax. Nine patients improved or fairly maintained their PS with an ECOG grade of 1. The 1-, 3-, and 5-year CSS rates after TES were 90%, 70%, and 47%, respectively. Only postoperative disability (ECOG PS grade 3) was significantly associated with short-term survival after TES. The clinical outcomes of 10 patients who underwent TES for spinal metastatic LMS were favorable without severe complications. Postoperative disability was significantly associated with short-term survival after TES.

BACKGROUND: As survival after treatment for symptomatic spinal metastases increases, the incidence of local tumor recurrence also may increase. However, data regarding incidence and timing of recurrence or duration of survival after second surgeries are not readily available and may help to inform clinicians when to perform second surgeries. OBJECTIVE: To identify features associated with loss of local control (LLC) at a previously treated or new spinal level. METHODS: Clinical and surgical data were collected from a prospective cohort of 1421 patients who had surgery for symptomatic spinal metastases. Patients undergoing repeat spinal surgery for symptomatic LLC at the same or a different level were identified and analyzed. RESULTS: In total, 3.0% patients underwent repeat surgery for symptomatic LLC after a median interval of 184 days from the first surgery; median survival was 6.1 months after second surgery. Factors associated with second surgery for LLC were the primary tumor type, number of spinal levels, Tomita staging, Tokuhashi and Karnofsky scores, anterior surgical approach, more aggressive surgical resection, and postoperative radiotherapy. In total, 1.5% patients were admitted for surgery for a different spinal level than the index operation after median 338 days from the first operation. CONCLUSIONS: The likelihood for repeat surgery due to LLC cannot be accurately predicted at the time of initial presentation. Factors associated with second surgery for LLC relate to less aggressive tumor biology and better survival. Most patients had a reasonable duration of survival after second surgery. ispartof: WORLD NEUROSURGERY vol:117 pages:E8-E16 ispartof: location:United States status: published

Introduction: Multilevel total en bloc spondylectomy (TES) is required to secure oncologically adequate resection margins. However, no useful information has been reported for spinal reconstruction after multilevel TES. Therefore, this study set out to assess the clinical and radiological outcomes of spinal reconstruction after multilevel TES. Methods: Forty-eight patients treated with multilevel TES at our institute were included in the analysis. Reconstruction was achieved with posterior pedicle screw fixation and an anterior titanium mesh cage filled with iliac autograft in all cases. Spinal shortening was performed to increase spinal stability from the reconstruction. Instrumentation failure and radiological findings were evaluated with radiography and computerized tomography (CT). Results: After excluding one patient whose general condition was deteriorating, radiological evaluations of 47 patients were performed over a period of more than a year. The follow-up time was 17 to 120 months (mean: 70.2 months). Instrumentation failure occurred in one patient (5.9%) after thoracic multilevel TES, in 4 patients (25.0%) after thoracolumbar multilevel TES, and in 3 patients (42.9%) after lumbar multilevel TES. No instrumentation failure was observed in cervicothoracic cases. Cage subsidence (>2 mm) occurred in 30 patients (63.8%). In 22 of them, subsidence appeared on the CT one month after surgery. The risk factors of instrumentation failure included a multilevel TES below the thoracolumbar level and a long span of vertebral resection. There was no instrumentation failure in any of the 11 “disc-to-disc cutting” cases. Conclusions: This study identified the risk factors of instrumentation failure after multilevel TES. There is a high risk of instrumentation failure in cases of long vertebral resection below the thoracolumbar level. On the other hand, our reconstruction method can be successful for multilevel TES above the thoracic level.

Purpose Survival after metastatic cancer has improved at the cost of increased presentation with metastatic spinal disease. For patients with pathologic spinal fractures and/or spinal cord compression, surgical intervention may relieve pain and improve quality of life. Surgery is generally considered to be inappropriate if anticipated survival is < 3 months. The aim of this international multicenter study was to analyze data from patients who died within 3 months or 2 years after surgery, to identify preoperative factors associated with poor or good survival, and to avoid inappropriate selection of patients for surgery in the future. Patients and Methods A total of 1,266 patients underwent surgery for impending pathologic fractures and/or neurologic deficits and were prospectively observed. Data collected included tumor characteristics, preoperative fitness (American Society of Anesthesiologists advisory [ASA]), neurologic status (Frankel scale), performance (Karnofsky performance score [KPS]), and quality of life (EuroQol five-dimensions questionnaire [EQ-5D]). Outcomes were survival at 3 months and 2 years postsurgery. Univariable and multivariable logistic regression analyses were used to find preoperative factors associated with short-term and long-term survival. Results In univariable analysis, age, emergency surgery, KPS, EQ-5D, ASA, Frankel, and Tokuhashi/Tomita scores were significantly associated with short survival. In multivariable analysis, KPS and age were significantly associated with short survival (odds ratio [OR], 1.36; 95% CI, 1.15 to 1.62; and OR, 1.14; 95% CI, 1.02 to 1.27, respectively). Associated with longer survival in univariable analysis were age, number of levels included in surgery, KPS, EQ-5D, Frankel, and Tokuhashi/Tomita scores. In multivariable analysis, the number of levels included in surgery (OR, 1.21; 95% CI, 1.06 to 1.38) and primary tumor type were significantly associated with longer survival. Conclusion Poor performance status at presentation is the strongest indicator of poor short-term survival, whereas low disease load and favorable tumor histology are associated with longer-term survival.

Background and Objectives Metastasectomy of spinal lesions from renal cell carcinoma (RCC) is a promising strategy. However, its clinical outcome after spinal metastasectomy is unknown owing to the difficulty of curative surgical resection. This is the first study to examine the survival rates of patients who underwent metastasectomy of solitary spinal metastases from RCC. Methods A retrospective cohort study of 36 consecutive patients with RCC who underwent nephrectomy and complete removal of solitary spinal lesions between 1995 and 2010 at our institution. Cancer-specific survival (CSS) time from the spinal metastasectomy to death or last follow-up was the main endpoint. Potential factors associated with survival were evaluated with Kaplan–Meier analysis and the long-rank test. Results For all patients, the estimated median CSS time was 130 months. The 3, 5, and 10-year CSS rates were 77.8%, 69.1%, and 58.0%, respectively, for all patients, and 72.7%, 54.5%, and 27.3%, respectively, for patients with lung metastases at the time of surgery. Only the presence of liver metastases was significantly associated with short-term survival after spinal metastasectomy. Conclusions Liver metastases were associated with short-term survival, although lung metastases were not. For selected patients, curative resection of solitary spinal metastases can potentially prolong survival. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

BACKGROUND: Indications for surgery for symptomatic spinal metastases have become better defined in recent years, and suitable outcome measures have been established against a changing backdrop of patient characteristics, tumor behavior, and oncologic treatments. Nonetheless, variations still exist in the local management of patients with spinal metastases. In this study, we aimed to review global trends and habits in the surgical treatment of symptomatic spinal metastases, and to examine how these have changed over the last 25 years. METHODS: In this cohort study of consecutive patients undergoing surgery for symptomatic spinal metastases, data were collected using a secure Internet database from 22 centers across 3 continents. All patients were invited to participate in the study, except those unable or unwilling to give consent. RESULTS: There was a higher incidence of colonic, liver, and lung carcinoma metastases in Asian countries, and more frequent presentation of breast, prostate, melanoma metastases in the West. Trends in surgical technique were broadly similar across the centers. Overall survival rates after surgery were 53% at 1 year, 31% at 2 years, and 10% at 5 years after surgery (standard error 0.013 for all). Survival improved over successive time periods, with longer survival in patients who underwent surgery in 2011-2016 compared with those who underwent surgery in earlier time periods. CONCLUSIONS: Surgical habits have been fairly consistent among countries worldwide and over time. However, patient survival has improved in later years, perhaps due to medical advances in the treatment of cancer, improved patient selection, and operating earlier in the course of disease. ispartof: WORLD NEUROSURGERY vol:114 pages:E809-E817 ispartof: location:United States status: published

Study design A biomechanical study using human cadaveric thoracic spine specimens. Objective To evaluate and compare the biomechanical effects of spinal shortening and cross-links in reconstruction after total en bloc spondylectomy (TES). Summary of background data There have been no studies that have examined the biomechanical effects of spinal reconstruction after multilevel TES or the biomechanical effects of spinal shortening in reconstruction after TES. Methods Eight human cadaveric spines (T2-T9) were used. After the intact specimen had been biomechanically tested to determine the stiffness in compression, flexion, extension, left and right lateral bending, and left and right axial rotation, a TES at T5-6 was carried out. Three reconstruction methods were tested biomechanically (same as for the intact specimen) for their ability to restore stiffness to the specimen: (1) anterior short cage and multilevel posterior instrumentation at T3-8 with 2 cross-links (S2C), (2) anterior short cage and multilevel posterior instrumentation at T3-8 with 1 cross-link (S1C), and (3) anterior long cage and multilevel posterior instrumentation at T3-8 with 2 cross-links (L2C). A cage that was 6-10 mm shorter in height than the space created by the TES at T5-6 was selected as the "short cage" and a cage 10 mm taller in height than the short cage was selected as the "long cage" in each specimen. Results All 3 reconstruction methods using an anterior cage and multilevel posterior instrumentation provides a stiffer construct than that shown by the intact specimen. The reconstruction method using the 10-mm shorter cage (S2C vs. L2C) provided more stiffness than the one using the longer cage. The reconstruction using 2 cross-links (S2C vs. S1C) did not provide a stiffer construct than the one using 1 cross-link. Conclusions The reconstructions using an anterior cage and multilevel posterior instrumentation provided a stiffer construct than that shown by the intact specimen. The reconstruction using a 10-mm shorter cage provided a stiffer construct than the reconstruction using the longer cage.

Purpose Standardized indications for treatment of tumor-related spinal instability are hampered by the lack of a valid and reliable classification system. The objective of this study was to determine the interobserver reliability, intraobserver reliability, and predictive validity of the Spinal Instability Neoplastic Score (SINS). Methods Clinical and radiographic data from 30 patients with spinal tumors were classified as stable, potentially unstable, and unstable by members of the Spine Oncology Study Group. The median category for each patient case (consensus opinion) was used as the gold standard for predictive validity testing. On two occasions at least 6 weeks apart, each rater also scored each patient using SINS. Each total score was converted into a three-category data field, with 0 to 6 as stable, 7 to 12 as potentially unstable, and 13 to 18 as unstable. Results The κ statistics for interobserver reliability were 0.790, 0.841, 0.244, 0.456, 0.462, and 0.492 for the fields of location, pain, bone quality, alignment, vertebral body collapse, and posterolateral involvement, respectively. The κ statistics for intraobserver reliability were 0.806, 0.859, 0.528, 0.614, 0.590, and 0.662 for the same respective fields. Intraclass correlation coefficients for inter- and intraobserver reliability of total SINS score were 0.846 (95% CI, 0.773 to 0.911) and 0.886 (95% CI, 0.868 to 0.902), respectively. The κ statistic for predictive validity was 0.712 (95% CI, 0.676 to 0.766). Conclusion SINS demonstrated near-perfect inter- and intraobserver reliability in determining three clinically relevant categories of stability. The sensitivity and specificity of SINS for potentially unstable or unstable lesions were 95.7% and 79.5%, respectively.

Undifferentiated pleomorphic sarcoma (formerly known as malignant fibrous histiocytoma: MFH) is a relatively rare primary malignant bone tumor first described by Norman and Feldman [1] as a malignant histiocytoma. It comprises approximately 6% of all bone tumors [2, 3]. It was reported that the osteosarcoma adjuvant or neoadjuvant chemotherapeutic regimen is beneficial [4], and a good pathological response predicted better disease-free survival [5]. Caffeine is a xanthine analog that has a biochemical modulating effect as an inhibitor of DNA repair, and may inhibit the post-replication repair of sublethally damaged DNA [6, 7]. Caffeine-potentiated chemotherapy has been administered to patients with high-grade bone and soft-tissue sarcomas since 1989, because caffeine enhances the cytocidal effects of anticancer drugs through the inhibition of DNA repair. Approximately 15% of primary malignant bone tumors involve the pelvic girdle [8]. Periacetabular lesions are the most difficult sites to reconstruct because of their complicated anatomical structure, and complication rates—including deep infection (12–47%), implant dislocation (2–22%), or local recurrence (28–35%)—are still high in pelvic lesions [9–13].

金沢大学附属病院リハビリテーション部, There is an urgent need to develop methods that lower costs of using recombinant human bone morphogenetic proteins (BMPs) to promote bone induction. In this study, we demonstrate the osteogenic effect of a low-molecular weight compound, SVAK-12, that potentiated the effects of BMP-2 in inducing transdifferentiation of C2C12 myoblasts into the osteoblastic phenotype. Here, we report a specific compound, SVAK-12, which was selected based on in silico screenings of small-molecule databases using the homology modeled interaction motif of Smurf1-WW2 domain. The enhancement of BMP-2 activity by SVAK-12 was characterized by evaluating a BMP-specific reporter activity and by monitoring the BMP-2-induced expression of mRNA for osteocalcin and alkaline phosphatase (ALP), which are widely accepted marker genes of osteoblast differentiation. Finally, we confirmed these results by also measuring the enhancement of BMP-2-induced activity of ALP. Smurf1 is an E3 ligase that targets osteogenic Smads for ubiquitin-mediated proteasomal degradation. Smurf1 is an interesting potential target to enhance bone formation based on the positive effects on bone of proteins that block Smurf1-binding to Smad targets or in Smurf1-/- knockout mice. Since Smads bind Smurf1 via its WW2 domain, we performed in silico screening to identify compounds that might interact with the Smurf1-WW2 domain. We recently reported the activity of a compound, SVAK-3. However, SVAK-3, while exhibiting BMP-potentiating activity, was not stable and thus warranted a new search for a more stable and efficacious compound among a selected group of candidates. In addition to being more stable, SVAK-12 exhibited a dose-dependent activity in inducing osteoblastic differentiation of myoblastic C2C12 cells even when multiple markers of the osteoblastic phenotype were parallelly monitored. © 2010 Springer Science+Business Media, LLC.

seikei@pop01.kanazawa-u.ac.jp, Background Each vertebra can be regarded as a compartment surrounded by several anatomically characterized barriers. However, in some cases tumorsextend beyond these barriers. The route of vertical extension to the adjacent vertebrae is unclear. The extent ofvertical extension of a metastatic spinal tumor is important in making the preoperative decision regarding the cranio-caudal surgical margin. The objective of this study was toinvestigate the route of vertical extension of metastatic vertebral tumors. Methods We examined 20 en bloc resected metastatic vertebral bodies in which the tumors had extendedoutside the vertebral body. Five to eight sagittal sections including the pedicle, and the lateral and central parts of the PLL were prepared from each resected specimen. The sections were stained with hematoxylin and eosin, and elastica van Gieson. Histological examination focused on the routes of the vertical extension of the tumor at each barrier tissue and the degree of tumor extension along each route. Results Vertical extension ofthe tumor was observed at the ALL in 6 cases, at the central part of the PLL in 14 cases, at the lateral part of the PLL in 20 cases, at the cartilaginous endplate in 3 cases, and at the periosteum on the lateral side of vertebral body in 7 cases. The tumor had extended the farthest at the lateral part of the PLL in 18 cases, at the lateral side of the vertebral body in 1 case, and through the disc in 1 case. Conclusions Metastatic vertebral tumors most commonly extend vertically at the lateral part of the PLL. The lateralpart of the PLL is raised by the tumor, which extends between the PLL and the posterior aspect of the disc. © The Japanese Orthopaedic Association 2011.

Object Thyroid carcinoma generally has a favorable prognosis, and patients rarely present with distant metastases. Authors of several studies have proposed piecemeal resection for spinal metastases in thyroid carcinoma; however, few have analyzed the impact of local curative surgery such as total en bloc spondylectomy (TES) for thyroid carcinoma. The purposes of the present study are to determine the strategy of surgical treatment for spinal metastases of thyroid carcinoma and to evaluate the surgical results of and the prognosis associated with TES. Methods Twenty-four cases of spinal metastases were retrospectively reviewed. The patients included 16 women and 8 men, with a mean age of 60.7 years. Histological examination showed follicular carcinoma in 15 cases, papillary carcinoma in 8, and medullary carcinoma in 1. Total en bloc spondylectomy was performed in 10 cases; debulking surgery, such as piecemeal excision or eggshell curettage, was performed in 14. The average follow-up time was 55 months (12–180 months). Results Four patients had no evidence of disease, 8 were alive with the disease, and 12 had died of the disease. The overall survival rate from the time of surgery was 74% at 5 years. Patients with visceral metastases had a significant, higher risk of death. The survival rate of patients following TES was 90% at 5 years, which was higher than the rate in patients who underwent debulking surgery (63%). However, no significant difference was observed between the 2 types of surgery. There was a local recurrence after debulking surgery in 8 (57%) of 14 cases. Because of the recurrences, reoperation was required after a mean of 41 months. In contrast, there was a local recurrence after TES in only 1 (10%) of 10 cases. The difference between debulking surgery and TES regarding local recurrence was statistically significant. Conclusions Total en bloc spondylectomy with enough of a margin provided favorable local control of spinal metastases of thyroid carcinoma during a patient's lifetime.

Analyses of the bone mass alone of osteoporotic vertebrae are not sufficient to predict fracture risks and assess the recovery of bone strength during drug treatment. Instead, finite element analyses (FEAs) is superior, because changes in the vertebral strength are strongly dependent on the inner vertebral stress distribution, which is related to the individual bone shape and bone density distribution in cancellous and cortical region. To investigate how FEAs can detect drug effects, we performed patient-specific FEAs of the first lumbar vertebra of osteoporotic patients at five time points (before therapy, and after 6 and 12 months and 2 and 3 years of therapy) during a 3-year drug treatment with alendronate and vitamin D, in four osteoporotic female patients in this study. The FEAs revealed notable decreases in the compressive principal strains in cancellous bone, but these decreases did not necessarily correspond to increases in the bone densities. In addition, statistical analyses by Friedman's test (nonparametric analysis) showed that evaluation based only on the average compressive principal strains over the 3-year treatment identified drug effects significantly, suggesting that compressive principal strain is an useful indicators for monitoring drug effects. Our data implied that compressive fracture of the vertebrae may be prevented as a result of the drug treatment, in a manner that was optimally detectable by patient-specific FEAs.

Study design Ten patients with a spinal tumor of the lower lumbar spine underwent total en bloc spondylectomy (TES) by combined posterior-anterior approach. The oncological and neurologic results are analyzed. Objective To describe the surgical technique and evaluate the clinical outcome of this surgery. Summary of the background data TES at lower lumbar spine is technically challenging because of its anatomy such as the presence of major vessels and lumbosacral plexus nerves. Methods Six aggressive benign tumors and 4 solitary spinal metastases involving L4 or L5 were treated. The approache of operative procedure are discussed as follows: Posterior approach: Dissection of the lumbar nerve roots to the conjunction of the adjacent nerves were performed after en bloc laminectomy by T-saw pediculotomy. The psoas muscle was dissected away, from the vertebral body. The posterior halves of the anterior column at the craniocaudal adjacent levels of the lumbar tumor were cut. Anterior approach: Major vessels were dissected from the vertebral body. Anterior halves of the anterior column were cut at the corresponding levels. The tumor vertebral body was removed en bloc, followed by anterior spinal reconstruction. Results Seven of 10 cases had no evidence of disease at 57 months on average, 1 case was alive with disease at 66 months, 1 case had death of disease at 42 months, and 1 case had death of another disease at 14 months after surgery. All patients improved or preserved neurologic in the last follow up. The resected specimen of vertebral bodies and laminae showed marginal or wide margin in all cases, although pedicles showed intralesional margin in 8 cases. No local recurrence was observed during lifetime with mean 52 months. Conclusion TES for spinal tumor of L4 or L5 preserving lumbar nerves was achieved by combined posterior- anterior approach.

Object The prognosis in patients with a distant spinal metastasis from the lung is dismal. The role of radical surgery in such cases has been questioned because of the excessive morbidity, blood loss, and operative time as well as the tumor's extreme malignancy. The purpose of this study was to evaluate the surgical results and the prognosis associated with radical surgery for lung cancer metastasis to the spine in carefully selected patients and to clarify whether there is an indication for radical surgery such as total en bloc spondylectomy (TES) in lung cancer metastasis. Methods The author performed a retrospective review of patients with lung cancer spinal metastasis treated by TES during a 10-year period. Total en bloc spondylectomy for lung cancer metastasis to the spine was performed in 6 patients without visceral or other bony metastases. Outcome measures were prognostic score, mean survival time, and perioperative complications. The histological type was adenocarcinoma in all 6 cases. In 4 cases the surgical strategy prognostic score was 5. In the other 2 cases the score was 6 because there were skip metastases to adjacent vertebra. In the 2 cases with adjacent vertebral metastasis, the adjacent vertebra was excised en bloc together. Results The mean estimated blood loss was 1076 ml and the mean operative time was 7 hours 20 minutes. Perioperative complications were found in 2 cases. One was deep infection after CSF leakage, and the other was paralysis due to postoperative hematoma. At the end of follow-up period, 4 of 6 patients are still living after a mean of 46.3 months (range 36–62 months). In the other 2 cases, 1 patient died of a heart attack and the other of mediastinitis due to surgical site infection by methicillin-resistant Staphylococcus aureus. In this series, local recurrence was not found. Conclusions Total en bloc spondylectomy has been shown to be associated with excessive morbidity, blood loss, and operative time; however, the procedure is becoming less invasive. The authors conclude that TES is appropriate in selected cases with controllable primary lung cancer, localized spinal metastasis, and no visceral metastasis. In such patients, improvement in the prognosis can be expected after TES. However, even in selected cases and with skilled surgical technique, the complication rate remains high. Total en bloc spondylectomy should be performed after a thorough discussion of the risks and benefits.

This was a retrospective clinical study. This study aimed to evaluate our institution's experience with total en bloc spondylectomy (TES) in patients treated for primary lumbar spine tumors and investigate postoperative clinical outcomes. TES is a widely accepted by spinal and musculoskeletal surgical oncologists and results in favorable health-related quality of life outcomes. However, this procedure still imposes major risks and complications. The cases of TES performed for primary lumbar spine tumors between 1993 and 2015 were retrospectively analyzed. Primary outcome measures were the rates of perioperative complications and reoperation for instrumentation failure. We enrolled 30 patients (13 men and 17 women; median age and follow-up, 38 years and 87 months, respectively). Three, 7, and 5 cases involved previous radiotherapy, intralesional resection, and chemotherapy, respectively. The most common tumor was giant cell tumor (14 cases) followed by osteosarcoma (4 cases) and plasmacytoma (3 cases). The median estimated blood loss was 1450 mL, and the median operative time was 11 hours. At least 1 perioperative complication occurred in 26 patients (86.7%), with the most common being postoperative muscle weakness (24 patients, 80.0%) followed by surgical site infection and postoperative cerebrospinal fluid leakage (7 patients, respectively; 23.3% each). Revision surgery for instrumentation failure was required in 6 patients (20.0%) at a median of 33 months after the index TES. Four patients experienced local tumor recurrence (13.3%), and their 10-year disease-free rate was 75.0%. TES is a feasible and effective procedure for primary lumbar spine tumors, but the risks of perioperative complications and late instrumentation failure should be acknowledged. Surgical oncologic outcomes were good, especially in patients who underwent TES as their first surgical treatment. Therefore, being familiar with the indications for TES and the surgical technique is important.

Although metal intoxication after arthroplasty causes various symptoms, polyneuropathy has never been the focus of clinical investigation. We report the case of a 56-year-old woman with metal neuropathy. She had metallosis after hip arthroplasty with a cobalt-chromium alloy prosthesis. She developed progressive sensory disturbance, hearing loss, and hypothyroidism. Sural nerve biopsy indicated axonopathy. After exchange arthroplasty, blood levels of cobalt and chromium decreased, and her symptoms improved. Cobalt or chromium can cause axonopathy.

Standardizing limb salvage surgery for malignant bone tumors should result in improved limb function after tumor excision and reconstruction. Recently, we developed and clinically applied a method of biological reconstruction using tumor-bearing autografts treated with liquid nitrogen. We report this newly modified technique using pedicle frozen autografts to save the continuity of anatomical structures.We treated 33 malignant bone tumor patients. Diagnoses of the tumors were 17 osteosarcomas, 11 metastatic tumors, 2 Ewing's sarcomas, 2 chondrosarcomas, and 1 undifferentiated pleomorphic sarcoma. The sites of the tumors were 23 femurs, 5 tibias, 4 humeri, and 1 calcaneus. Operative procedures consisted of exposing the tumor, performing one-site osteotomy or joint dislocation, rotating and freezing the tumor lesion in liquid nitrogen for 20 min, and reconstruction using intramedullary nailing, plates, or composite arthroplasty.Postoperative function was excellent in 25 patients (75.7%), good in 5 patients (15.1%), and fair in 3 patients (9.0%). At the final follow-up, 8 patients had died at a mean of 17 months postoperatively, and 18 patients remained disease-free for a mean follow-up period of 30 months (range 7-69 months). Seven patients were alive but with disease. Complications were encountered in 12 patients, including 4 deep infections, 3 fractures, 3 local recurrences from surrounding soft tissue, 2 nonunions, and 1 collapse. All were managed successfully.The pedicle frozen autograft, which was newly developed to solve drawbacks of previously reported free frozen autografts, achieved success for reconstruction of malignant bone tumors. This is a new, simple, effective surgical technique for biological reconstruction that is still investigated but has potential for development.

The rapidly aging population and improved long-term survival due to advancement of cancer treatment have expanded the role of surgical treatment in elderly patients with metastatic spinal disease. The purpose of this study was to evaluate in elderly patients the perioperative complications and prognosis for metastatic spinal disease. Thirty-two elderly patients (>70 years) who underwent surgical treatment based on Tomita's surgical strategy for spinal metastasis since 1999 were retrospectively reviewed. Mean survival time of 15 patients with 2 to 4 points in surgical strategy was 23.6 months; of 10 patients with 5 to 7 points was 15.2 months; and of 7 patients with 8 to 10 points was 5.2 months. In 5 elderly patients (15.6%), the appropriate surgical choice based on the surgical strategy was not possible due to their preoperative conditions. Perioperative complications encountered were respiratory in 6 patients (18.8%), cardiovascular in 3 (9.4%), and delirium in 4 (12.5%). In the nonelderly 161 patients, respiratory complications occurred in 4 patients (2.5%), cardiovascular in 1 (0.6%), and delirium in 2 (1.2%). Respiratory complications and delirium occurred at a significantly higher frequency in the elderly group. Even for elderly patients, the postoperative prognosis could be predicted by the surgical strategy. However, the optimal surgical procedure may deviate from that predicted by the surgical strategy due to their preoperative conditions and an increased risk for perioperative complications. Despite the increased potential for complications, more radical procedures, such as total en bloc spondylectomy, should not be avoided solely due to advanced patient age.

Object Total en bloc spondylectomy (TES) for thoracic spinal tumors may in theory produce neurological dysfunction as a result of ischemic or mechanical damage to the spinal cord. Potential insults include preoperative embolization at 3 levels, intraoperative ligation of segmental arteries, nerve root ligation, and circumferential dural dissection. The purpose of this study was to assess neurological function after thoracic TES. Methods The authors performed a retrospective review of 79 patients with thoracic-level spinal tumors that had been treated with TES between 1989 and 2006. Neurological function was retrospectively analyzed according to the Frankel grading system. Of the 79 cases, 26 involved primary tumors and 53 involved metastatic tumors. The number of excised vertebrae was 1 in 60 cases, 2 in 13, and ≥ 3 in 6. The Frankel grade before surgery was B in 1 case, C in 16, D in 29, and E in 33. Results At the follow-up, the Frankel grade was C in 2 cases, D in 24, and E in 53. Of 46 cases with neurological deficits before surgery, neurological improvement of at least 1 Frankel grade was achieved in 25 cases (54.3%). Although the Frankel grade did not change in 21 patients, improvement in neurological symptoms within the same Frankel grade did occur in these patients. There were no cases of neurological deterioration. Conclusions There was no neurological deterioration due to preoperative embolization, ligation of segmental arteries, or ligation of thoracic nerve roots. Each of the cases with preoperative neurological deficits showed improvement in neurological symptoms. Data in the current study clinically proved that TES is a safe operation with respect to spinal cord blood flow. In TES, the spinal cord is circumferentially decompressed and the spinal column is shortened. An increase in spinal cord blood flow due to spinal shortening in addition to decompression was considered to have brought about a resolution of neurological symptoms with TES.

Osteoporosis can lead to bone compressive fractures in the lower lumbar vertebrae. In order to assess the recovery of vertebral strength during drug treatment for osteoporosis, it is necessary not only to measure the bone mass but also to perform patient-specific mechanical analyses, since the strength of osteoporotic vertebrae is strongly dependent on patient-specific factors, such as bone shape and bone density distribution in cancellous bone, which are related to stress distribution in the vertebrae. In the present study, patient-specific general (not voxel) finite element analyses of osteoporotic vertebrae during drug treatment were performed over time. We compared changes in bone density and compressive principal strain distribution in a relative manner using models for the first lumbar vertebra based on computer tomography images of four patients at three time points (before therapy, and after 6 and 12 months of therapy). The patient-specific mechanical analyses indicated that increases in bone density and decreases in compressive principal strain were significant in some osteoporotic vertebrae. The data suggested that the vertebrae were strengthened structurally and the drug treatment was effective in preventing compression fractures. The effectiveness of patient-specific mechanical analyses for providing useful and important information for the prognosis of osteoporosis is demonstrated.

Purpose This study was performed to evaluate the therapeutic effect of hepatocyte growth factor (HGF) on tendon-bone healing in a rabbit model. Methods In adult rabbits the long digital extensor tendon was detached from the lateral femoral condyle, and the free end of the tendon was inserted into a tunnel drilled into the proximal tibial metaphysis. Cancellous bone obtained during drilling of the tibial hole was soaked in saline solution or solution containing 100-μg/mL human recombinant HGF and then transplanted into the bone tunnel. Junctional healing between the tendon and the bone was evaluated by histologic analysis and uniaxial load-to-failure testing at 2, 4, 6, 8, and 12 weeks after surgery. Results In the saline solution–treated control group, Sharpey-like fibers, which connected the tendon graft and the bone tissue, appeared 6 weeks after treatment. At 8 weeks after treatment, maturation of lamellar bone was seen, and at 12 weeks, the adhesion between tendon and bone appeared to be supported by indirect insertion of fibrocartilaginous tissue, wherein the border between the fibrocartilaginous tissue and tendon or bone was significant. In the HGF-treated group, the fibrous tissues were parallel to the load axis, and lamellar bone and Sharpey-like fibers appeared as early as 4 weeks after treatment. At 12 weeks, junctional tissue, characterized by a continuous 4-layer structure of bone, calcified cartilage, fibrocartilage, and tendon, was regenerated by a direct insertion. On biomechanical testing, the HGF-treated group had significantly better biomechanical properties than the control group at 2 and 4 weeks. The histologic improvement caused by HGF treatment was associated with the biomechanical improvement. Conclusions Local administration of recombinant HGF promotes the adhesive healing process at the tendon-bone junction, both histologically and mechanically, after ligament reconstruction in a rabbit model. Clinical Relevance Application of HGF may be considered as a new therapeutic approach to accelerate healing and rehabilitation after ligament reconstruction.

Patient-specific nonlinear finite element analysis (FEA) is promising for evaluating the recovery of vertebral strength. Vertebral strength is closely related to inner vertebral stress distribution and is used to assess the fracture risk for individual osteoporotic patients during drug treatment. Moreover, stress distribution is affected by individual bone shape, bone density distribution and nonlinear behavior of the mechanical properties of bone. To investigate the effectiveness of FEA considering these factors for the evaluation of drug treatment effects, patient-specific nonlinear FEAs of the first lumbar vertebrae in patients undergoing a 3-year drug treatment were performed. Changes in fracture load and distribution of failure elements in the FE models at four time points (before therapy, and after 6 and 12 months and 3 years of therapy) were compared with those of average bone density. The FEAs demonstrated that failure elements decreased notably, and fracture load increased gradually by the 3-year time point, suggesting that the vertebrae were strengthened as a result of drug treatments. Furthermore, statistical tests indicated that mechanical evaluation using the nonlinear FEAs is more sensitive for evaluating drug effects on osteoporotic bone than assessments based on average bone density.

We report a 66-year-old male patient with solitary spinal metastasis of L1–3 that expanded outside the vertebrae. It originated from a renal cell carcinoma, with 18 years dormancy after right nephrectomy. It had been already irradiated. Total en bloc spondylectomy was planned for the metastatic lumbar lesion, including the paravertebral tumor, which had invaded the soft tissue around the vertebral body. Here we describe how to excise the lesion including the tumor margin and how to reconstruct the large bone and soft tissue defects without complications (e.g., postoperative infection or instrumentation failure).

Study Design. Systematic review of literature. Objective. To determine whether surgical approach and technique to be used in thoracolumbar metastases is influenced by anatomic region of the spine. Summary of Background Data. There is a significant debate about the best surgical approach for the treatment of thoracolumbar metastasis. Methods. Two research questions below were determined through a consensus among a panel of spine experts. A systematic review of literature was conducted using Pubmed. The search terms included "spin * " and "metasta*." This was to include the terms, "metastatic," "metastasis," "metastases," "spinal," and "spine." Specific Questions 1. In the T2 to T5 region, what is the impact of different surgical approaches (anterior, posterior, combined anteroposterior [AP]) on local recurrence, adverse events, pain alleviation, and neurologic recovery? 2. Within the thoracolumbar spine (T6-T10; T11-L2; and L3-L5) what is the impact of different surgical approaches on outcomes as per question one. The results of the systematic review were discussed with spine oncology experts through a modified Delphi technique to arrive at treatment recommendations. Results. From the search terms used 5176 abstracts were found. Based on the review of these abstracts, 161 were deemed acceptable. These abstracts were reviewed according to an inclusion and exclusion criteria, leaving 60 articles. These 60 articles were reviewed in detail leaving 32 articles for inclusion. There was no level I study. There was 1 level II study, 5 level III studies, and 26 level IV studies. Most of these studies selected their approach by tumor topography. The quality of evidence was very low. Conclusion. There is very low quality evidence to support the superiority of one approach over another. There is a strong recommendation for posterior or posterior-lateral approach from T2 through T5. For the T6-L5 regions of the spine we recommend either anterior, posterior, or combined anterior and posterior surgery depending on the clinical presentation, surgeon and patient preference.

Improving survival rates for sarcoma patients are necessitating more functional and durable methods of reconstruction after tumor resection. Frozen osteoarticular grafts are utilized for joint reconstruction, but the joint may develop osteoarthritic change. We used a frozen autologous whole-rabbit knee joint graft model to investigate the influence of freezing on joint components. Thirty rabbit knee joints that had been directly immersed into liquid nitrogen (L) or saline (C) without use of cryoprotectants were re-implanted. Histological observations were made after 4, 8, and 12 weeks. Both groups had bone healing. In group L, despite restoration of cellularity to the menisci and ligaments, no live chondrocytes were observed and cartilage deterioration progressed over time. It was concluded that cryoinjury of chondrocytes caused osteoarthritic change. Then we tested whether a vitrification method could protect cartilage from cryoinjury. Full-thickness articular cartilage of rabbit knee was immersed into liquid nitrogen with and without vitrification. Histology, ultrastructure, and chondrocyte viability were examined before and after 24 h of culture. Vitrified cartilage cell viability was >85% compared with that of fresh cartilage. Transmission electron microscopy revealed preservation of original chondrocyte structure. Our vitrification method was effective for protecting chondrocytes from cryoinjury. Since reconstructing joints with osteoarticular grafts containing living cartilage avert osteoarthritic changes, vitrification method may be useful for storage of living cartilage for allografts or, in Asian countries, for reconstruction with frozen autografts containing tumors. © 2009 Elsevier Inc. All rights reserved.

Cancer metastasis is the life-threatening aspect of cancer and is usually resistant to standard treatment. We report here a targeted therapy strategy for cancer metastasis using a genetically-modified strain of Salmonella typhimurium. The genetically-modified strain of S. typhimurium is auxotrophic for the amino acids arginine and leucine. These mutations preclude growth in normal tissue but do not reduce bacterial virulence in cancer cells. The tumor-targeting strain of S. typhimurium, termed A1-R, and expressing green fluorescent protein (GFP), was administered to both axillary lymph and popliteal lymph node metastasis of human pancreatic cancer and fibrosarcoma, respectively, as well as lung metastasis of the fibrosarcoma in nude mice. The bacteria were delivered via a lymphatic channel to target the lymph node metastases and systemically via the tail vein to target the lung metastasis. The cancer cells expressed red fluorescent protein (RFP) in the cytoplasm and GFP in the nucleus linked to histone H2B, enabling color-coded real-time imaging of the bacteria targeting the metastatic tumors. After 7-21 days of treatment, the metastases were eradicated without the need of chemotherapy or any other treatment. No adverse effects were observed. This new strategy demonstrates the clinical potential of targeting and curing cancer metastasis with engineered bacteria without the need of toxic chemotherapy.