Benign leiomyoma with multiple metastases to vertebrae and calvarium: An index case with comprehensive review of endocrine targets.

"Benign" metastatic leiomyomas (BML) are indolently growing metastatic tumors which mostly associate with uterine leiomyomas in women in reproductive ages. The reason to define these lesions as "benign" despite metastasis is their pathological features with low mitotic counts, lack of or minimal nuclear atypia, pseudocyst formation, and coagulative necrosis unlike leiomyosarcomas. Despite lack of pathological malignant features, they may cause significant morbidity and even mortality. Here, we describe a BML case with metastases to vertebrae and skull bones. Vertebral and skull metastases of BMLs were very rarely reported. In treatment of these tumors, hysterectomy and GnRH modifier treatments are widely employed. GnRH agonists act by desensitization and downregulation of the GnRH receptors, while GnRH antagonists act via the canonical competitive blockage. These treatments reduce FSH and LH levels, thereby reducing the systemic levels of sex steroids which stimulate leiomyoma growth. However, leiomyomas inherently harbor aromatase activity and synthesize their own estrogen; hence, treatment with systemic estrogen antagonists may provide better tumor control. Another important factor in BML pathogenesis is progesterone, and both progesterone receptor antagonists and high-dose progesterone receptor agonists may reduce BML growth. Following surgical treatment of the calvarial mass and radiotherapy of the vertebral metastatic foci, our BML case was successfully managed with hysterectomy and anastrozole treatment. Higher awareness of BML cases and their molecular endocrinological features in the neurosurgical community may pave to develop better strategies for treatment of these tumors causing high morbidity.

Cauda equina compression in metastatic prostate cancer.

A 67-year-old man presented to his general practitioner with intermittent episodes of unilateral sciatica over a 2-month period for which he was referred for an outpatient MRI of his spine. This evidenced a significant lumbar vertebral mass that showed tight canal stenosis and compression of the cauda equina. The patient was sent to the emergency department for management by orthopaedic surgeons. He was mobilising independently, pain free on arrival and without neurological deficit on assessment. Clinically, this patient presented with no red flag symptoms of cauda equina syndrome or reason to suspect malignancy. In these circumstances, National Institute for Health and Care Excellence guidelines do not support radiological investigation of the spine outside of specialist services. However, in this case, investigation helped deliver urgent care for cancer that otherwise may have been delayed. This leads to the question, do the current guidelines meet clinical requirements?

Minimal Access vs. Open Spine Surgery in Patients With Metastatic Spinal Cord Compression - A One-Center Randomized Controlled Trial.

BACKGROUND/AIM: We conducted a randomized controlled trial to investigate whether minimally access spine surgery (MASS) is less morbid than open surgery (OS) in patients with metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: A total of 49 MSCC patients were included in the trial. The outcome measures were bleeding (L), operation time (min), re-operations and prolonged wound healing. RESULTS: The median age was 67 years (range=42-85 years) and 40% were men. The peri-operative blood loss in the MASS-group was significantly lower than that in the OS-group; 0.175L vs. 0.500L, (p=0.002). The median operation time for MASS was 142 min (range=72-203 min) vs. 103 (range=59-435 min) for OS (p=0.001). There was no significant difference between the two groups concerning revision surgery or delayed wound healing. CONCLUSION: The MASS technique in MSCC patients is associated with less blood loss, but a longer operation time when compared to the OS technique.

Developing an Improved Statistical Approach for Survival Estimation in Bone Metastases Management: The Bone Metastases Ensemble Trees for Survival (BMETS) Model.

PURPOSE: To determine whether a machine learning approach optimizes survival estimation for patients with symptomatic bone metastases (SBM), we developed the Bone Metastases Ensemble Trees for Survival (BMETS) to predict survival using 27 prognostic covariates. To establish its relative clinical utility, we compared BMETS with 2 simpler Cox regression models used in this setting. METHODS AND MATERIALS: For 492 bone sites in 397 patients evaluated for palliative radiation therapy (RT) for SBM from January 2007 to January 2013, data for 27 clinical variables were collected. These covariates and the primary outcome of time from consultation to death were used to build BMETS using random survival forests. We then performed Cox regressions as per 2 validated models: Chow's 3-item (C-3) and Westhoff's 2-item (W-2) tools. Model performance was assessed using cross-validation procedures and measured by time-dependent area under the curve (tAUC) for all 3 models. For temporal validation, a separate data set comprised of 104 bone sites treated in 85 patients in 2018 was used to estimate tAUC from BMETS. RESULTS: Median survival was 6.4 months. Variable importance was greatest for performance status, blood cell counts, recent systemic therapy type, and receipt of concurrent nonbone palliative RT. tAUC at 3, 6, and 12 months was 0.83, 0.81, and 0.81, respectively, suggesting excellent discrimination of BMETS across postconsultation time points. BMETS outperformed simpler models at each time, with respective tAUC at each time of 0.78, 0.76, and 0.74 for the C-3 model and 0.80, 0.78, and 0.77 for the W-2 model. For the temporal validation set, respective tAUC was similarly high at 0.86, 0.82, and 0.78. CONCLUSIONS: For patients with SBM, BMETS improved survival predictions versus simpler traditional models. Model performance was maintained when applied to a temporal validation set. To facilitate clinical use, we developed a web platform for data entry and display of BMETS-predicted survival probabilities.

Laboratory markers as useful prognostic measures for survival in patients with spinal metastases.

BACKGROUND CONTEXT: Laboratory values have been found to be useful predictive measures of survival following surgery. The utility of laboratory values for prognosticating outcomes among patients with spinal metastases has not been studied. PURPOSE: To determine the prognostic capacity of laboratory values at presentation including white blood cell count, serum albumin and platelet-lymphocyte ratio (PLR) in patients with spinal metastases. STUDY DESIGN: Retrospective review of records from two tertiary care centers (2005-2017). PATIENT SAMPLE: Patients, aged 40 to 80, who received operative or nonoperative management for spinal metastases. OUTCOME MEASURES: Survival, complications, or hospital readmissions within 90 days of treatment and a composite measure for treatment failure accounting for changes in ambulatory function and mortality at 6 months following presentation. METHODS: Multivariable Cox proportional hazard regression analysis was used to analyze the relationship between laboratory values and length of survival, adjusting for confounders. Multivariable logistic regression was used in analyses related to 6-month and 1-year mortality, complications, readmissions, and treatment failure. A scoring rubric was developed based on the performance of laboratory values in the multivariable tests. Internal validation was performed using a bootstrap simulation that consisted of sampling with replacement and 1,000 replications. RESULTS: We included 1,216 patients. Thirty-seven percent of patients received a surgical intervention and 63% were treated nonoperatively. Median survival for the cohort as a whole was 255 days (interquartile range 93-642 days). The PLR (hazard ratio [HR] 1.53; 95% confidence interval [CI] 1.29, 1.80; p<.001) and albumin (HR 0.54; 95% CI 0.45, 0.64; p<.001) were significantly associated with survival, whereas WBC count (HR 1.08; 95% CI 0.86, 1.36; p=.50) was not associated with this outcome. Similar findings were encountered for 6-month and 1-year mortality as well as the composite measure for treatment failure. The PLR and albumin performed well in our scoring rubric and findings were preserved in the bootstrapping validation. CONCLUSIONS: Individuals with low serum albumin and elevated PLR should be advised regarding the impact of these laboratory markers on outcomes including survival, irrespective of treatments received. An effort should also be made to optimize nutrition and PLR, if practicable, before treatment to minimize the potential for development of adverse events.

Metastatic dissemination patterns of different primary tumors to the spine and other bones.

Metastatic spine disease (MSD) is a severe event in cancer patients. Experimental data indicate that bone metastasis is mostly mediated by blood flow-dependent, passive arrest of circulating tumor cells to the bone metastatic niche (BMN). Here, we have set out to test these experimental observations in a clinical, human setting to improve our understanding of MSD. 507 patients, treated on spinal metastases in our institution from 2005 to 2015 were retrospectively evaluated. We identified 259 patients with accessible staging reports of the skeleton before and at initial diagnosis of MSD. Data analysis comprised localizations of bone metastases, underlying malignancy and time to development of MSD. Dissemination pattern of bone metastasis was correlated with red bone marrow (RBM) content of the respective bone as a measure of blood flow. Spinal metastases occurred most frequently in lung cancer (21%), prostate cancer (19%), and breast cancer (12%). At the diagnosis of MSD, majority of patients have multiple extra-spinal bone metastases (2/3). The distribution of metastases to extra-spinal bones and to the spine is mostly proportional to the RBM content of the involved bone. Corresponding to the high RBM content, thoracic spine, pelvic bones and ribs represent a predilection site for bone metastasis. We confirm a distinct preference of cancer types to metastasize to bones. When it comes to bone metastases all primaries show uniform distribution pattern, which supports the hypothesis of a predominantly blood flow-dependent distribution of tumor cells and passive arrest to the BMN rather than a spine-specific homing mechanism.

Clinical significance of traditional clinical parameters and inflammatory biomarkers for the prognosis of patients with spinal chondrosarcoma: a retrospective study of 150 patients in a single center.

BACKGROUND: To investigate the clinical significance of five inflammatory biomarkers and conventional clinical parameters in prognostic prediction of spinal chondrosarcoma. METHODS: Univariate and multivariate analyses were performed to investigate independent prognostic factors for recurrence and death of patients with spinal chondrosarcoma. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier curve, and differences were analyzed by log-rank test. The optimal cutoff values for NLR, PLR, LMR, and CAR were determined by X-tile program. RESULTS: The optimal cutoff value for NLR, PLR, LMR, AGR, and CAR was 2.7, 200, 3.0, 1.5, and 0.2, respectively. Of the 150 patients included, recurrence was detected in 105 patients, and death occurred in 78 patients. Multivariate analysis indicated that Tomita I-III, total resection, and CAR < 0.2 were significantly associated with longer DFS. Meanwhile, preoperative Frankel score D-E, total resection, and CAR < 0.2 were favorable prognostic factors for OS. Subtype analysis showed that only total resection was an independent prognostic factor for DFS of recurrent spinal chondrosarcoma. CONCLUSION: Total resection could significantly reduce the recurrence rate of spinal chondrosarcoma and improve OS of chondrosarcoma patients. Tomita classification I-III was a favorable factor for DFS, and preoperative Frankel score A-C was an adverse prognostic factor for OS. CAR was the most robust prognostic indicator with a discriminatory ability as compared with other inflammatory indicators. These slides can be retrieved under Electronic Supplementary Material.

Do routine blood test results help in the diagnosis of spine tumors? A retrospective study of the significance of pretreatment neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios from 503 spine tumor patients.

The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are not fully evaluated for the diagnosis of musculoskeletal tumors, especially spine tumors. The objective of our study was to assess the feasibility of NLR and PLR as indicators for pretreatment diagnosis of spine tumors.Patients who underwent surgical treatment in our hospital for spine tumors were retrospectively analyzed. Blood test results (neutrophil, lymphocyte, and platelet counts) and final pathological results from surgery or biopsy specimen were collected. Spine tumors were divided into 4 groups. Diagnostic values of NLR and PLR were analyzed using the area under the receiver operating characteristic (ROC) curve (AUC).There were 503 patients included. The average age of all patients was 46.3 years. Age, NLR, and PLR were significantly different between benign and malignant tumors groups (P < .05), and ROC analysis showed that the AUC was 0.704 and 0.637 for NLR and PLR. Age, location, NLR, and PLR were significantly different between primary and nonprimary tumor groups (P < .05), and ROC analysis showed that the AUC was 0.713 and 0.647 for NLR and PLR. Age, location, NLR, and PLR were significantly different between primary benign and primary malignant tumor groups (P < .05), and ROC analysis showed that the AUC was 0.624 and 0.577 for NLR and PLR.Pretreatment NLR and PLR had clinical significance in the identification and pretreatment diagnosis of spine tumors. Additionally, NLR and PLR were significantly different between benign and malignant tumors, primary and nonprimary tumors, and primary benign and primary malignant tumors.

Prognostic value of serum alkaline phosphatase in spinal metastatic disease.

BACKGROUND: Determination of the appropriateness of invasive management in patients with spinal metastatic disease requires accurate pre-operative estimation of survival. The purpose of this study was to examine serum alkaline phosphatase as a prognostic marker in spinal metastatic disease. METHODS: Chart reviews from two tertiary care centres were used to identify spinal metastatic disease patients. Bivariate and multivariate analyses were used to determine if serum alkaline phosphatase was an independent prognostic marker for survival. RESULTS: Overall, 732 patients were included with 90-day and 1-year survival of n = 539 (74.9%) and n = 324 (45.7%), respectively. The 1-year survival of patients in the first quartile of alkaline phosphatase (≤73 IU/L) was 78 (57.8%) compared to 31 (24.0%) for patients in the fourth quartile (>140 IU/L). Preoperative serum alkaline phosphatase levels were significantly elevated in patients with multiple spine metastases, non-spine bone metastasis, and visceral metastasis but not in patients with brain metastasis. On multivariate analysis, elevated serum alkaline phosphatase was identified as an independent prognostic factor for survival in spinal metastatic disease. CONCLUSION: Serum alkaline phosphatase is associated with preoperative metastatic tumour burden and is a biomarker for overall survival in spinal metastatic disease.

Establishment of a Nomogram-Based Model for Predicting the Prognostic Value of Inflammatory Biomarkers and Preoperative D-Dimer Level in Spinal Ewing's Sarcoma Family Tumors: A Retrospective Study of 83 Patients.

BACKGROUND: Ewing's sarcoma family tumors (ESFTs) are the second most common malignancy in children and adolescents. The purpose of the present retrospective study was to evaluate the prognostic role of inflammatory biomarkers and preoperative D-dimer levels in patients with spinal ESFTs. METHODS: The neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, lymphocyte/monocyte ratio, albumin/globulin ratio, C-reactive protein/albumin ratio (CAR), preoperative D-dimer level, and clinical parameters were evaluated and analyzed. Univariate and multivariate analyses for disease-free survival (DFS) and overall survival (OS) were performed using the log-rank test and Cox regression analysis, respectively. The DFS and OS rates were calculated using the Kaplan-Meier method. Nomograms were established to predict DFS and OS quantitatively. RESULTS: The optimal cutoff values for D-dimer, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, lymphocyte/monocyte ratio, CAR, and albumin/globulin ratio were 0.3, 3.2, 168, 2.2, 1.5, and 1.4, respectively. The patients were stratified into 2 groups according to the cutoff values. Multivariate analysis revealed that age, resection mode, and D-dimer level were favorable prognostic factors for DFS and OS (P < 0.05). Metastasis and CAR <1.5 were significantly associated with OS (P < 0.05). Nomograms with all significant factors were established to predict DFS and OS. CONCLUSIONS: Our results have indicated that the preoperative D-dimer level is an effective prognostic factor with discriminatory ability for DFS and OS, superior to other indicators. Also, CAR was favorable prognostic factor for OS. Nomograms of DFS and OS can be recommended as practical models to evaluate the prognosis for patients with spinal ESFTs.

Prognostic Significance of Preoperative Plasma D-Dimer Level and Clinical Factors in Patients with Spinal Giant Cell Tumor: Retrospective Analysis of 153 Patients in a Single Center.

BACKGROUND: Giant cell tumor (GCT) of the spine is a benign tumor with local aggressiveness and potential for recurrence. No published study has discussed the prognostic role of preoperative D-dimer (D-D) level in spinal GCT. The purpose of this retrospective study was to evaluate the prognostic value of preoperative plasma D-D level and clinical factors. METHODS: Routine clinical parameters and plasma D-D level were analyzed preoperatively. The disease-free survival (DFS) rate was estimated using Kaplan-Meier analysis. Variables with P value <0.1 were subjected to multivariate analysis by Cox regression analysis. P values <0.05 were considered statistically significant. RESULTS: The recurrence rate of spinal GCT was 21.6% in our series. A total of 153 patients were stratified into 2 groups by preoperative D-D level of ≤0.5 µg/mL or >0.5 µg/mL. We found that several clinicopathologic features were associated with the D-D level, including tumor location, the segment involved, Jaffe grade, and recurrence (P < 0.05). Multivariate analysis indicated that the treatment history, resection mode, bisphosphonate treatment, and preoperative D-D level were prognostic factors of DFS (all P < 0.05). In addition, the Jaffe grading system stratified by preoperative plasma D-D level was correlated with DFS of patients with spinal GCT (P < 0.05). CONCLUSIONS: Our study demonstrated that preoperative plasma D-D level, total spondylectomy, bisphosphonate treatment, and treatment history were powerful independent prognostic factors for DFS of patients with spinal GCT, suggesting that preoperative plasma D-D level may be a useful biomarker for predicting recurrence and prognosis of spinal GCT.

Serum alkaline phosphatase and 30-day mortality after surgery for spinal metastatic disease.

BACKGROUND: Elevated serum alkaline phosphatase has been previously studied as a biomarker for progression of metastatic disease and implicated in adverse skeletal events and worsened survival. The purpose of this study was to determine if serum alkaline phosphatase was a predictor of short-term mortality of patients undergoing surgery for spinal metastatic disease. METHODS: The American College of Surgeons National Surgical Quality Improvement Program was queried for patients undergoing spinal surgery for metastatic disease. Bivariate and multivariable analyses was undertaken to determine the relationship between serum alkaline phosphatase and 30-day mortality. RESULTS: For the 1788 patients undergoing operative intervention for spinal metastatic disease between 2009 and 2016 the 30-day mortality was 8.49% (n = 151). In patients who survived beyond 30-days after surgery, n = 1627 (91.5%) the median [interquartile range] serum alkaline phosphatase levels were 126.4 [75-138], whereas in patients who had 30-day mortality, the serum alkaline phosphatase levels were 179.8 [114-187]. The optimal cut-off for alkaline phosphatase was determined to be 113 IU/L. On multivariable analysis, elevated serum alkaline phosphatase levels were associated with 30-day mortality (OR 1.61, 95% CI 1.12-2.32, p = 0.011). CONCLUSION: Elevated preoperative serum alkaline phosphatase is a marker for 30-day mortality in patients undergoing surgery for spinal metastatic disease. Future retrospective and prospective study designs should incorporate assessment of this serum biomarker to better understand the role for serum alkaline phosphatase in improving prognostication in spinal metastatic disease.

White Blood Cell Count and C-Reactive Protein Variations After Posterior Surgery With Intraoperative Radiotherapy for Spinal Metastasis.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To evaluate the feasibility of blood test parameters [white blood cell (WBC) count and C-reactive protein (CRP)] for predicting and diagnosing postoperative infection after posterior surgery with intraoperative radiotherapy (IORT) for spinal metastasis. SUMMARY OF BACKGROUND DATA: Posterior surgery with IORT is effective for treating spinal metastasis, as we previously reported. However, the procedure requires that the patient be transferred from the operating room to the irradiation room. In addition, the patient's general status is often poor, and the risk of postoperative infection is high. MATERIALS AND METHODS: A total of 279 patients who underwent IORT for the treatment of spinal metastasis between August 2004 and June 2013 were included in this study. The WBC count (/10 µL) and CRP level (mg/dL) were recorded in all patients preoperatively and on alternative days for up to 7 days after surgery. We assessed the development of surgical-site infection (SSI) for up to 1 month after surgery. RESULTS: SSI occurred in 41 patients (14.7%). The preoperative WBC count and CRP level did not differ between the infected and noninfected patients. The WBC counts on postoperative day (POD) 1 and POD 7 and the CRP levels on POD 7 were significantly higher in the infected patients (8.8 vs. 10.0, P=0.04; 6.1 vs. 8.8, P=0.002; 3.89 vs. 9.50, P<0.001). A receiver-operating characteristic curve analysis of the WBC count and CRP level for detecting SSI showed cutoff values of 9.6 (WBC count, POD 1), 6.5 (WBC count, POD 7), and 5.0 (CRP level, POD 7). CONCLUSIONS: A high WBC count and CRP level on POD 7 may be used to predict or detect SSI. In particular, a CRP level of 5.0 mg/dL on POD 7 strongly suggests the future development of SSI (sensitivity: 78%, specificity: 74%).

Antineuronal Nuclear Autoantibody Type 1/Anti-Hu-Associated Opsoclonus Myoclonus and Epilepsia Partialis Continua: Case Report and Literature Review.

BACKGROUND: Opsoclonus-myoclonus syndrome is a rare clinical condition that has been associated with neuroblastoma. There are few reported examples of ANNA-1/anti-Hu antibodies in children with neuroblastoma and opsoclonus-myoclonus, all in children aged less than three years of age. METHODS: We describe the new onset of focal seizures without alteration of consciousness and opsoclonus-myoclonus in an 11-year-old girl with ANNA-1/anti-Hu positivity and a paraspinal ganglioneuroblastoma. A systematic review of the literature of children with ANNA-1/anti-Hu positivity and malignancy was also performed. RESULTS: Fourteen patients were identified, eight of whom had opsoclonus-myoclonus. Although epilepsia partialis continua has been described in association with several neuronal autoantibodies, association with ANNA-1/anti-Hu has not been reported. CONCLUSIONS: We describe epilepsia partialis continua in a child with ANNA-1/anti-Hu antibodies and neuroblastoma. Testing for antineuronal antibodies should be considered in children presenting with either opsoclonus-myoclonus or epilepsia partialis continua.

Nonamyloid tumoral light-chain-deposition disease (aggregoma) of the paraspinal region.

Aggregomas are rare localized masses of monoclonal nonamyloid immunoglobulin light-chain deposits. To date, there have been only a few reports of isolated aggregomas, with the majority detailing renal, lymph node and brain deposition. We present a rare case of paraspinal aggregoma in a 67-year-old female who presented with a complaint of cough and chest pain. Imaging demonstrated a left-sided paravertebral mass extending from T7-T10. Pathological analysis showed lamellar deposition of extracellular eosinophilic material with an associated lymphoplasmacytic nonamyloid infiltrate. To our knowledge, this is the first report of a paraspinal aggregoma. While exceedingly rare, this tumor can be included in the radiologic differential diagnosis of paravertebral soft tissue tumors in adults. The observation of our case adds to the limited understanding of the etiology, pathogenesis, natural history, and treatment of nonamyloid light-chain depositions.

S100B, intraoperative neuromonitoring findings and their relation to clinical outcome in surgically treated intradural spinal lesions.

BACKGROUND: Neurophysiological monitoring (IOM) consisting of somatosensory (SEPs), muscle (MEPs) and spinal motor evoked (D-wave; spinal MEPs) potentials is used to indicate injury related to surgical treatment of intradural and intramedullary lesions. Combining spinal and muscle MEPs reliably predicts long-term motor deficit. If spinal MEPs recording is not possible, additional markers-e.g. S100B, a serum marker for glial injury-may be a helpful adjunct. Thus, serial serum S100B measurements were related to both the intraoperative IOM recordings and the long-term neurological outcome in patients surgically treated for cervical and thoracic intradural lesions. METHODS: In 33 patients (9 men, 24 women, 54 ± 17 years) during intramedullary (8) or intradural (25) cervical or thoracic spinal surgeries significant intraoperative SEP-amplitude decrement >50 % or MEP loss and serial S100B serum concentration (perioperative days 0, 1-3, 5) were related to outcome (>1 year after discharge, grouped into improved and unchanged/altered neurological symptoms). RESULTS: Differences in S100B levels between patients with improved and unchanged/altered neurological outcome were significantly on postoperative days 2 (0.085 ± 0.08 µg/l vs 0.206 ± 0.07 µg/l, p = 0.005) and 3 (0.076 ± 0.03 µg/l vs 0.12 ± 0.05 µg/l, p = 0.007). All patients with permanent altered neurological symptoms developed S100B levels >0.08 µg/l (0.09-0.35 µg/l). Eighty-one percent of patients with improved neurological symptoms presented with S100B levels ≤0.08 µg/l (0.02-0.08 µg/l). Nine out of ten patients (90 %) without changes in EP and S100B had an improved long-term outcome, whereas 9/13 patients (69 %) with changes in EP and S100B had altered neurological symptoms in long-term outcome. CONCLUSION: Intraoperative stable EPs and S100B ≤0.08 µg/l may be used as a marker to predict long-term neurological improvement, whereas EP-changes and elevated S100B levels on the 3rd postoperative day may be useful as a marker to predict long-term neurological alteration. In summary, the combined use of S100B and EPs might be helpful in the prediction of the severity of adverse spinal cord affection following surgery and guidance of patients.

Systemic antitumor immune response following reconstruction using frozen autografts for total en bloc spondylectomy.

BACKGROUND CONTEXT: Total en bloc spondylectomy (TES) is a surgery designed to achieve complete resection of a malignant spinal tumor, such as spinal metastasis. Although this procedure decreases the rate of local recurrence, it is questionable whether local control prolongs a patient's survival. In cryosurgery, antitumor immunity is activated after percutaneous cryoablation of tumors. We applied this tumor-induced cryoimmunology to TES surgery and developed a "second-generation TES" that brings about TES enhancing antitumor immunity to prolong a patient's survival. PURPOSE: To present a second-generation TES applied tumor-induced cryoimmunology and assess the immunity-enhancing effect after implementing this surgery. STUDY DESIGN: This is a retrospective review of prospectively collected data. PATIENT SAMPLE: The sample consisted of 65 consecutive patients who underwent second-generation TES. OUTCOME MEASURES: Interferon gamma (IFN-γ) and interleukin-12 (IL-12) before surgery and at both 1 and 3 months after surgery was used to assess the immunity-enhancing effect. METHODS: In second-generation TES, instead of harvesting autograft from the ilium or fibula, the resected lamina and vertebral body from TES are frozen using liquid nitrogen and used as grafted bone for spinal reconstruction. In the most recent 33 of the 65 cases, in addition to the TES procedure, a small amount of the tumor tissue from the resected tumor-bearing vertebra was also placed into liquid nitrogen. This small amount of tumor tissue was then implanted subcutaneously on one side of the axilla at the end of the TES surgery. In 60 of 65 cases, measurement of IFN-γ and IL-12 was performed. RESULTS: IFN-γ increased after surgery in 45 (75%) of 60 cases. The mean IFN-γ relative concentrations at both 1 and 3 months after surgery, as compared with before surgery, were significantly higher (284%±596% and 275%±354%: p<.05). IL-12 increased after surgery in 44 (73.3%) of 60 cases. The mean IL-12 relative concentrations at both 1 and 3 months after surgery, as compared with before surgery, were significantly higher (277%±385% and 486%±1032%: p>.05 and p<.01) at 3 months. At final follow-up, 13 of the 65 patients died due to progression of metastases (mean 12.6 months after TES), 15 remained free from disease, and 36 patients were alive with disease. CONCLUSIONS: The second-generation TES using frozen tumor-bearing autograft inside a cage affords three benefits: (1) no pain at the bone harvest site, (2) shortening of operation time, and (3) decrease of blood loss. Moreover, our results show that second-generation TES provides not only a local radical cure but also a systemic immunological enhancement.