Effects of adoptive T-cell immunotherapy on immune cell profiles and prognosis of patients with unresectable or recurrent cholangiocarcinoma.

The identification of immune cell profiles (ICP) involved in anti-tumor immunity is crucial for immunotherapy. Therefore, we herein investigated cholangiocarcinoma patients (CCA) who received adoptive T-cell immunotherapy (ATI). Eighteen unresectable or recurrent CCA received ATI of αß T cells alone or combined with chemotherapy. ICP were evaluated by flow cytometry. There were 14 patients with intrahepatic cholangiocarcinoma (iCCA) and four with distal cholangiocarcinoma (dCCA). After one course of treatment, nine iCCA and four dCCA had progressive disease (PD), while five iCCA had stable disease (SD). Median overall survival (OS) was prolonged to 21.9 months. No significant differences were observed in OS between the PD and SD groups of iCCA. The frequency of helper T cells (HT) in iCCA decreased from 70.3% to 65.5% (P = .008), while that of killer T cells (KT) increased from 27.0% to 30.6% (P = .005). dCCA showed no significant changes of immune cells. OS was prolonged in iCCA with increased frequencies of CD3+ T cells (CD3) (P = .039) and αß T cells (αß) (P = .039). dCCA showed no immune cells associated with OS. The frequencies of CD3+ T cells and αß T cells in the PD group for iCCA decreased from 63.5% to 53% (P = .038) and from 61.6% to 52.2% (P = .028), respectively. In the SD group, the frequency of HT decreased from 65.8% to 56.9% (P = .043), whereas that of KT increased from 30.1% to 38.3% (P = .043). In conclusions, ATI affected ICP and prolonged OS. Immune cells involved in treatment effects differed according to the site of cholangiocarcinoma.

Safety evaluation of immune-cell therapy for malignant tumor in the Cancer Immune-cell Therapy Evaluation Group (CITEG).

BACKGROUND AIMS: With the aim of strengthening the scientific evidence of immune-cell therapy for cancer and further examining its safety, in October 2015, our hospital jointly established the Cancer Immune-Cell Therapy Evaluation Group (CITEG) with 39 medical facilities nationwide. METHODS: Medical information, such as patients' background characteristics, clinical efficacy and therapeutic cell types obtained from each facility, has been accumulated, analyzed and evaluated by CITEG. In this prospective study, we analyzed the adverse events associated with immune-cell therapy until the end of September 2022, and we presented our interim safety evaluation. RESULTS: A total of 3839 patients with malignant tumor were treated with immune-cell therapy, with a median age of 64 years (range, 13-97 years) and a male-to-female ratio of 1:1.08 (1846:1993). Most patients' performance status was 0 or 1 (86.8%) at the first visit, and 3234 cases (84.2%) were advanced or recurrent cases, which accounted for the majority. The total number of administrations reported in CITEG was 31890, of which 960 (3.0%) showed adverse events. The numbers of adverse events caused by treatment were 363 (1.8%) of 19661 administrations of αßT cell therapy, 9 of 845 administrations of γδT-cell therapy (1.1%) and 10 of 626 administrations of natural killer cell therapy (1.6%). The number of adverse events caused by dendritic cell (DC) vaccine therapy was 578 of 10748 administrations (5.4%), which was significantly larger than those for other treatments. Multivariate analysis revealed that αßT cell therapy had a significantly greater risk of adverse events at performance status 1 or higher, and patients younger than 64 years, women or adjuvant immune-cell therapy had a greater risk of adverse events in DC vaccine therapy. Injection-site reactions were the most frequently reported adverse events, with 449 events, the majority of which were associated with DC vaccine therapy. Among all other adverse events, fever (228 events), fatigue (141 events) and itching (131 events) were frequently reported. In contrast, three patients had adverse events (fever, abdominal pain and interstitial pneumonia) that required hospitalization, although they were weakly related to this therapy; rather, it was considered to be the effect of treatment for the primary disease. CONCLUSIONS: Immune-cell therapy for cancer was considered to be a safe treatment without serious adverse events.

Surgical Metastasectomy in the Spine: A Review Article.

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.

Perioperative complications of total en bloc spondylectomy for spinal tumours.

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.

Effect of adoptive T-cell immunotherapy on immunological parameters and prognosis in patients with advanced pancreatic cancer.

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 αß 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.

Clinical outcomes and survivals after total en bloc spondylectomy for metastatic leiomyosarcoma in the spine.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Identification of prognostic factors for γδT cell immunotherapy in patients with solid tumor.

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.

How good are the outcomes of instrumented debulking operations for symptomatic spinal metastases and how long do they stand? A subgroup analysis in the global spine tumor study group database.

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.

Motor and Sensory Impairments of the Lower Extremities After L2 Nerve Root Transection During Total en Bloc Spondylectomy.

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.

A novel risk calculator to predict outcome after surgery for symptomatic spinal metastases; use of a large prospective patient database to personalise surgical management.

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.

Prediction Accuracy of Common Prognostic Scoring Systems for Metastatic Spine Disease: Results of a Prospective International Multicentre Study of 1469 Patients.

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. LEVEL OF EVIDENCE: 3.

Total en bloc spondylectomy for primary tumors of the lumbar spine.

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.

Loss of Local Tumor Control After Index Surgery for Spinal Metastases: A Prospective Cohort Study.

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.

Metastatic Spine Tumor Epidemiology: Comparison of Trends in Surgery Across Two Decades and Three Continents.

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.

Risk factors of instrumentation failure after multilevel total en bloc spondylectomy.

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.

Characteristics of Patients Who Survived < 3 Months or > 2 Years After Surgery for Spinal Metastases: Can We Avoid Inappropriate Patient Selection?

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.

Rapid improvements in pain and quality of life are sustained after surgery for spinal metastases in a large prospective cohort.

Introduction Metastatic spinal cancer is a common condition that may lead to spinal instability, pain and paralysis. In the 1980s, surgery was discouraged because results showed worse neurological outcomes and pain compared with radiotherapy alone. However, with the advent of modern imaging and spinal stabilisation techniques, the role of surgery has regained centre stage, though few studies have assessed quality of life and functional outcomes after surgery. Objective We investigated whether surgery provides sustained improvement in quality of life and pain relief for patients with symptomatic spinal metastases by analysing the largest reported surgical series of patients with epidural spinal metastases. Methods A prospective cohort study of 922 consecutive patients with spinal metastases who underwent surgery, from the Global Spine Tumour Study Group database. Pre- and post-operative EQ-5D quality of life, visual analogue pain score, Karnofsky physical functioning score, complication rates and survival were recorded. Results Quality of life (EQ-5D), VAS pain score and Karnofsky physical functioning score improved rapidly after surgery and these improvements were sustained in those patients who survived up to 2 years after surgery. In specialised spine centres, the technical intra-operative complication rate of surgery was low, however almost a quarter of patients experienced post-operative systemic adverse events. Conclusion Surgical treatment for spinal metastases produces rapid pain relief, maintains ambulation and improves good quality of life. However, as a group, patients with cancer are vulnerable to post-operative systemic complications, hence the importance of appropriate patient selection.

Spinal metastasectomy of renal cell carcinoma: A 16-year single center experience with a minimum 3-year follow-up.

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;113:587-592. © 2016 Wiley Periodicals, Inc.

Prediction of Quality of Life and Survival After Surgery for Symptomatic Spinal Metastases: A Multicenter Cohort Study to Determine Suitability for Surgical Treatment.

BACKGROUND: Surgery for symptomatic spinal metastases aims to improve quality of life, pain, function, and stability. Complications in the postoperative period are not uncommon; therefore, it is important to select appropriate patients who are likely to benefit the greatest from surgery. Previous studies have focused on predicting survival rather than quality of life after surgery. OBJECTIVE: To determine preoperative patient characteristics that predict postoperative quality of life and survival in patients who undergo surgery for spinal metastases. METHODS: In a prospective cohort study of 922 patients with spinal metastases who underwent surgery, we performed preoperative and postoperative assessment of EuroQol EQ-5D quality of life, visual analog score for pain, Karnofsky physical functioning score, complication rates, and survival. RESULTS: The primary tumor type, number of spinal metastases, and presence of visceral metastases were independent predictors of survival. Predictors of quality of life after surgery included preoperative EQ-5D (P = .002), Frankel score (P < .001), and Karnofsky Performance Status (P < .001). CONCLUSION: Data from the largest prospective surgical series of patients with symptomatic spinal metastases revealed that tumor type, the number of spinal metastases, and the presence of visceral metastases are the most useful predictors of survival and that quality of life is best predicted by preoperative Karnofsky, Frankel, and EQ-5D scores. The Karnofsky score predicts quality of life and survival and is easy to determine at the bedside, unlike the EQ-5D index. Karnofsky score, tumor type, and spinal and visceral metastases should be considered the 4 most important prognostic variables that influence patient management.

Spinal Metastasis from Subcutaneous Sacrococcygeal Ependymoma: A Case Report with Long-Term Follow-Up.

Objective To present a previously unreported patient with recurrent spinal metastasis from subcutaneous sacrococcygeal ependymoma who was followed for 16 years. Methods A 50-year-old man who had T9 metastasis from subcutaneous sacrococcygeal ependymoma underwent piecemeal total T9 excision at a local hospital. He was referred to our institute because of weakness in both legs and bowel-bladder dysfunction with the presence of recurrent spinal metastasis at levels T9-T11. Additional tumor excision was performed circumferentially around the dura, along with spinal reconstruction via a posterior-anterior-posterior approach. Subsequently, the patient could walk again. Thereafter, this patient was treated by repeated surgical resection, reinstrumentation, and bone grafting for thoracic spinal metastases, and an additional 14 thoracic nerve root transections (bilateral T6-T12) as a result of eight operations. Results These repeated operations have prevented paralysis and allowed the patient to maintain activities of daily living for 16 years. Conclusions We illustrated the feasibility of repeated surgical resection of thoracic spinal metastases, involving eight operations over 16 years. We believe that this case emphasizes the need to repeatedly resect this type of tumor before the onset of paralysis to maintain normal activity levels.