Spinal column chordoma: prognostic significance of clinical variables and T (brachyury) gene SNP rs2305089 for local recurrence and overall survival.

Background: Chordomas are rare, locally aggressive bony tumors associated with poor outcomes. Recently, the single nucleotide polymorphism (SNP) rs2305089 in the T (brachyury) gene was strongly associated with sporadic chordoma development, but its clinical utility is undetermined. Methods: In 333 patients with spinal chordomas, we identified prognostic factors for local recurrence-free survival (LRFS) and overall survival and assessed the prognostic significance of the rs2305089 SNP. Results: The median LRFS was 5.2 years from the time of surgery (95% CI: 3.8-6.0); greater tumor volume (≥100cm3) (hazard ratio [HR] = 1.99, 95% CI: 1.26-3.15, P = .003) and Enneking inappropriate resections (HR = 2.35, 95% CI: 1.37-4.03, P = .002) were independent predictors of LRFS. The median overall survival was 7.0 years (95% CI: 5.8-8.4), and was associated with older age at surgery (HR = 1.11 per 5-year increase, 95% CI: 1.02-1.21, P = .012) and previous surgical resection (HR = 1.73, 95% CI: 1.03-2.89, P = .038). One hundred two of 109 patients (93.6%) with available pathologic specimens harbored the A variant at rs2305089; these patients had significantly improved survival compared with those lacking the variant (P = .001), but there was no association between SNP status and LRFS (P = .876). Conclusions: The ability to achieve a wide en bloc resection at the time of the primary surgery is a critical preoperative consideration, as subtotal resections likely complicate later management. This is the first time the rs2305089 SNP has been implicated in the prognosis of individuals with chordoma, suggesting that screening all patients may be instructive for risk stratification.

Mobile spine chordoma: results of 166 patients from the AOSpine Knowledge Forum Tumor database.

OBJECT: A chordoma is an indolent primary spinal tumor that has devastating effects on the patient's life. These lesions are chemoresistant, resistant to conventional radiotherapy, and moderately sensitive to proton therapy; however, en bloc resection remains the preferred treatment for optimizing patient outcomes. While multiple small and largely retrospective studies have investigated the outcomes following en bloc resection of chordomas in the sacrum, there have been few large-scale studies on patients with chordomas of the mobile spine. The goal of this study was to review the outcomes of surgically treated patients with mobile spine chordomas at multiple international centers with respect to local recurrence and survival. This multiinstitutional retrospective study collected data between 1988 and 2012 about prognosis-predicting factors, including various clinical characteristics and surgical techniques for mobile spine chordoma. Tumors were classified according to the Enneking principles and analyzed in 2 treatment cohorts: Enneking-appropriate (EA) and Enneking-inappropriate (EI) cohorts. Patients were categorized as EA when the final pathological assessment of the margin matched the Enneking recommendation; otherwise, they were categorized as EI. METHODS: Descriptive statistics were used to summarize the data (Student t-test, chi-square, and Fisher exact tests). Recurrence and survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and multivariate Cox proportional hazard modeling. RESULTS: A total of 166 patients (55 female and 111 male patients) with mobile spine chordoma were included. The median patient follow-up was 2.6 years (range 1 day to 22.5 years). Fifty-eight (41%) patients were EA and 84 (59%) patients were EI. The type of biopsy (p < 0.001), spinal location (p = 0.018), and if the patient received adjuvant therapy (p < 0.001) were significantly different between the 2 cohorts. Overall, 58 (35%) patients developed local recurrence and 57 (34%) patients died. Median survival was 7.0 years postoperative: 8.4 years postoperative for EA patients and 6.4 years postoperative for EI patients (p = 0.023). The multivariate analysis showed that the EI cohort was significantly associated with an increased risk of local recurrence in comparison with the EA cohort (HR 7.02; 95% CI 2.96-16.6; p < 0.001), although no significant difference in survival was observed. CONCLUSIONS: EA resection plays a major role in decreasing the risk for local recurrence in patients with chordoma of the mobile spine.

Soft-tissue reconstruction after total en bloc sacrectomy.

OBJECT Total en bloc sacrectomy is a dramatic procedure that results in extensive sacral defects. The authors present a series of patients who underwent flap reconstruction after total sacrectomy, report clinical outcomes, and provide a treatment algorithm to guide surgical care of this unique patient population. METHODS After institutional review board approval, data were collected for all patients who underwent total sacrectomy between 2002 and 2012 at The Johns Hopkins Hospital. Variables included demographic data, medical history, tumor characteristics, surgical details, postoperative complications, and clinical outcomes. All subtotal sacrectomies were excluded. RESULTS Between 2002 and 2012, 9 patients underwent total sacrectomy with flap reconstruction. Diagnoses included chordoma (n = 5), osteoblastoma (n = 1), sarcoma (n = 2), and metastatic colon cancer (n = 1). Six patients received gluteus maximus (GM) flaps with a prosthetic rectal sling following a single-stage, posterior sacrectomy. Four required additional paraspinous muscle (PSM) or pedicled latissimus dorsi (LD) fasciocutaneous flaps. Three patients underwent multistage sacrectomy with an anterior-posterior approach, 2 of whom received pedicled vertical rectus abdominis myocutaneous (VRAM) flaps, and 1 of whom received local GM, LD, and PSM flaps. Flap complications included dehiscence (n = 4) and infection (n = 1). During the 1st year of follow-up, 2 of 9 patients (22%) were able to ambulate with an assistive device by the 1st postoperative month, and 6 of 9 (67%) were ambulatory with a walker by the 3rd postoperative month. By postoperative Month 12, 5 of 9 patients (56%)-or 5 of 5 patients not lost to follow-up (100%)-were able to able to ambulate independently. CONCLUSIONS The authors' experience suggests that the GM and pedicled VRAM flaps are reliable options for softtissue reconstruction of total sacrectomy defects. For posterior-only operations, GM flaps with or without a prosthetic rectal sling are generally used. For multistage operations including a laparotomy, the authors consider the pedicled VRAM flap to be the gold standard for simultaneous reconstruction of the pelvic diaphragm and obliteration of dead space.

Tokuhashi score is predictive of survival in a cohort of patients undergoing surgery for renal cell carcinoma spinal metastases.

PURPOSE: Renal cell carcinoma (RCC) is an aggressive disease that metastasizes to the spine often requiring surgery. However, selecting the appropriate surgical intervention can be challenging. The Tokuhashi scoring system can be used to predict survival and inform the surgical strategy. We set out to determine the Tokuhashi score for patients with RCC spine metastases and compare expected and observed survival. METHODS: Records were reviewed for all patients who underwent surgery for spinal metastases at a single institution from January 2000 to December 2011 to determine the Tokuhashi score and survival. Kaplan-Meier estimates and log-rank test for univariate analysis were performed with R version 2.15.12 (R Foundation, 2012). RESULTS: Thirty patients underwent 40 spinal operations for metastatic RCC. Median survival was 11.4 months. Preoperative Tokuhashi scores were: 12-15, 15 patients; 9-11, seven patients; 0-8, eight patients. Median survival was 32.9, 11.7, and 5.4 months, respectively. Bone (p=0.01) and visceral metastases (p=0.005), and KPS (p=0.002) significantly affected survival. Tokuhashi score predicted survival (p=0.016); survival differed between the high and low score groups (p=0.006). CONCLUSIONS: RCC is an aggressive disease with short life expectancy when metastatic to the spine. However, patients with low systemic disease burden and solitary spinal metastases can have long survival and benefit from excisional surgery. Tokuhashi score can be useful in selecting surgical intervention in patients with RCC spinal metastases, and may be more relevant than in other cancers with spinal metastases.

Outcomes following surgical intervention for impending and gross instability caused by multiple myeloma in the spinal column.

OBJECT: Multiple myeloma is the most common primary tumor of the spine and is the most common primary malignant tumor of bone. Although spinal myeloma is classically a radiosensitive lesion, clinical or radiographic signs of instability merit surgical intervention. The authors present the epidemiology, surgical indications, and outcome data of a series of consecutive cases involving 31 surgically treated patients with diagnoses of multiple myeloma and plasmacytoma of the spine (the largest such series reported to date). METHODS: Surgical instability was the criterion for operative intervention in this patient cohort. The Spinal Instability Neoplastic Score (SINS) was used to make this assessment of instability. The cases were analyzed using location of the lesion, spinal levels involved, Frankel score, adjuvant therapy, functional outcome, and patient survival. RESULTS: All patients undergoing surgical intervention were determined to have indeterminate or gross spinal column instability according to SINS criteria. The median survival was 78.9 months. No significant difference in survival was seen for patients with higher SINS scores or for older patients (> 55 years). There was a statistically significant difference in survival benefit observed for patients receiving chemotherapy and radiation versus radiation alone as an adjuvant to surgery (p = 0.02). CONCLUSIONS: In this 10-year analysis, the authors report outcomes of surgical intervention for patients with indeterminate or gross spinal instability due to multiple myeloma and plasmacytoma of the spine with improved neurological function following surgery and low rates of instrumentation failure.

Epidemiologic, functional, and oncologic outcome analysis of spinal sarcomas treated surgically at a single institution over 10 years.

BACKGROUND CONTEXT: Spinal sarcomas are aggressive tumors that originate from the cells of mesechymal origin, specifically fat, cartilage, bone, and muscle. They are high-grade lesions, and treatment of spinal sarcomas can involve chemotherapy, radiation therapy, and surgery. In the appendicular skeleton, sarcomas are often treated with amputation, however, in the spinal column, surgical resection poses a unique set of challenges. PURPOSE: To better understand the optimal treatment regimens and the impact of en bloc or intralesional resection on patient outcome. STUDY DESIGN: A cohort of 25 sarcoma patients treated at a single medical institution between 2002 and 2012 was reviewed. PATIENT SAMPLE AND OUTCOME MEASURES: Patients were classified by tumor type for subgroup analysis, including chondrosarcoma, osteosarcoma, and other malignant spinal sarcomas. Demographic data for review included patient age, tumor type, tumor location, surgery type, exposure to chemotherapy, and radiation therapy. METHODS: Survival statistics and Kaplan-Meier curves were calculated using GraphPad Prism 5.0. The threshold for statistical significance was set at p<.05. Unpaired, two-tailed, equal variance t tests were performed for statistical analyses in Microsoft Excel 2010. RESULTS: Twenty-five patients with spinal sarcomas were treated over the 10-year period. Diagnosis included chondrosarcoma (n=9), osteosarcoma (n=4), and other sarcomas (n=12). Mean age at the time of diagnosis was 42 years. Pain was present at the time of diagnosis in 92% patients. Median survival after surgery was 59.5 months for chondrosarcoma, undefined for other sarcomas, and 16.8 months for osteosarcoma. Median survival after en bloc resection was undefined. Median survival after intralesional resection was 17.8 months. The difference in median survival between en bloc and intralesional resection was statistically significant (p=.049). CONCLUSIONS: The authors report the largest cohort of patients with spinal sarcoma. Median survival in this cohort was the longest for patients with sarcomas of varying pathologies. Median survival was longer for chondrosarcoma. En bloc resection demonstrated a survival advantage over intralesional resection. Long-term follow-up is needed for patients with spinal sarcoma to establish definitive survival data.

Fusion following lateral mass reconstruction in the cervical spine.

OBJECT: Recently, aggressive surgical techniques and a push toward en bloc resections of certain tumors have resulted in a need for creative spinal column reconstruction. Iatrogenic instability following these resections requires a thoughtful approach to adequately transfer load-bearing forces from the skull and upper cervical spine to the subaxial spine. METHODS: The authors present a series of 7 cases in which lateral mass reconstruction with a cage or fibular strut graft was used to provide load-bearing support, including 1 case of bilateral cage placement. RESULTS: The authors discuss the surgical nuances of en bloc resection of high cervical tumors and explain their technique for lateral mass cage placement. Additionally, they provide their rationale for the use of these constructs throughout the craniocervical junction and subaxial spine. CONCLUSIONS: Lateral mass reconstruction provides a potential alternative or adjuvant method of restoring the load-bearing capabilities of the cervical spine.

Maintenance of bowel, bladder, and motor functions after sacrectomy.

BACKGROUND CONTEXT: Repeated cohort studies have consistently demonstrated a survival advantage after en bloc resection for locally aggressive primary tumors in the sacrum. A sacrectomy is often required to remove the tumor en bloc, which may necessitate the sacrifice of sacral nerves. This can potentially result in functional complications, including the impairment of gait, bowel function, or bladder function. PURPOSE: To assess the bladder, bowel, and motor functions of patients after resection of a primary sacral tumor. STUDY DESIGN: This was a retrospective cohort study at a single academic institution. PATIENT SAMPLE: Consecutive patients who underwent an en bloc sacral tumor resection at a single institution between December 2002 and June 2012 were included. The study population comprised 73 patients. OUTCOME MEASURES: Patients were classified as having had a low, middle, high, or total sacrectomy based on the level of sacral nerves sacrificed, if applicable. METHODS: Patient data were collected from clinic notes and hospital records that included operative notes, lab studies, and rehabilitation notes. RESULTS: Across all patients, there was no change in bowel function after sacrectomy, whereas bladder and motor functions returned to preoperative (pre-op) levels at 3 and 6 months, respectively. Higher level sacrectomies were associated with worse bowel (p<.001), bladder (p<.001), and motor (p=.027) functions 12 months postoperatively (post-op). At 1 year, none of the six patients with a high or total sacrectomy had intact bladder function and 14.3% (N=7) had intact bowel function. Of patients with a middle sacrectomy, 62.5% (N=8) had intact bladder function and 71.4% (N=7) had intact bowel function at 1 year. Of patients with a low sacrectomy, 91.7% (N=12) had intact bladder function and 91.7% (N=12) had intact bowel function. CONCLUSIONS: Preoperative bladder, bowel, and motor functions, level of sacral tumor involvement, and corresponding level of sacrectomy were the greatest predictors of long-term bladder, bowel, and motor functions. There were no statistically significant changes in bladder, bowel, or motor functions from pre-op to 6 months post-op, and therefore, pre-op functional status was predictive of long-term function.

Outcomes following attempted en bloc resection of cervical chordomas in the C-1 and C-2 region versus the subaxial region: a multiinstitutional experience.

OBJECT: Chordomas involving the mobile spine are ideally managed via en bloc resection with reconstruction to optimize local control and possibly offer cure. In the cervical spine, local anatomy poses unique challenges, limiting the feasibility of aggressive resection. The authors present a multi-institutional series of 16 cases of cervical chordomas removed en bloc. Particular attention was paid to clinical outcome, complications, and recurrence. In addition, outcomes were assessed according to position of tumor at the C1-2 level versus the subaxial (SA) spine (C3-7). METHODS: The authors reviewed cases involving patients who underwent en bloc resection of cervical chordoma at 4 large spine centers. Patients were included if the lesion epicenter involved the C-1 to C-7 vertebral bodies. Demographic data and details of surgery, follow-up course, exposure to adjuvant therapy, and complications were obtained. Outcome was correlated with presence of tumor in C1-2 versus subaxial spine via a Student t-test. RESULTS: Sixteen patients were identified (mean age at presentation 55 ± 14 years). Seven cases (44%) cases involved C1-2, and 16 involved the subaxial spine. Median survival did not differ significantly different between the C1-2 (72 months) and SA (60 months) groups (p = 0.65). A combined (staged anteroposterior) approach was used in 81% of the cases. Use of the combined approach was significantly more common in treatment of subaxial than C1-2 tumors (100% vs 57%, p = 0.04). En bloc resection was attempted via an anterior approach in 6% of cases (C1-2: 14.3%; SA: 0%; p = 0.17) and a posterior approach in 13% of cases (C1-2: 29%; SA: 0%; p = 0.09). The most commonly reported margin classification was marginal (56% of cases), followed by violated (25%) and wide (19%). En bloc excision of subaxial tumors was significantly more likely to result in marginal margins than excision of C1-2 tumors (C1-2: 29%; SA: 78%; p = 0.03). C1-2 tumors were associated with significantly higher rates of postoperative complications (C1-2: 71%; SA: 22%; p = 0.03). Both local and distant tumor recurrence was greatest for C1-2 tumors (local C1-2: 29%; local SA: 11%; distant C1-2: 14%; distant SA: 0%). Statistical analysis of tumor recurrence based on tumor location was not possible due to the small number of cases. There was no between-groups difference in exposure to postoperative adjuvant radiotherapy. There was no difference in median survival between groups receiving proton beam radiotherapy or intensity-modulated radiotherapy versus no radiation therapy (p = 0.8). CONCLUSIONS: Compared with en bloc resection of chordomas involving the subaxial cervical spine, en bloc resection of chordomas involving the upper cervical spine (C1-2) is associated with poorer outcomes, such as less favorable margins, higher rates of complications, and increased tumor recurrence. Data from this cohort do not support a statistically significant difference in survival for patients with C1-2 versus subaxial disease, but larger studies are needed to further study survival differences.

En bloc hemisacrectomy and internal hemipelvectomy via the posterior approach.

OBJECT: Traditionally, hemisacrectomy and internal hemipelvectomy procedures have required both an anterior and a posterior approach. A posterior-only approach has the potential to complete an en bloc tumor resection and spinopelvic reconstruction while reducing surgical morbidity. METHODS: The authors describe 3 cases in which en bloc resection of the hemisacrum and ilium and subsequent lumbopelvic and pelvic ring reconstruction were performed from a posterior-only approach. Two more traditional anterior and posterior staged procedures are also included for comparison. RESULTS: In all 3 cases, an oncologically appropriate surgery and spinopelvic reconstruction were performed through a posterior-only approach. CONCLUSIONS: The advantage of a midline posterior approach is the ability to perform a lumbosacral reconstruction, necessary in cases in which the S-1 body is iatrogenically disrupted during tumor resection.

Minimally invasive spine surgery for adult degenerative lumbar scoliosis.

OBJECT: Historically, adult degenerative lumbar scoliosis (DLS) has been treated with multilevel decompression and instrumented fusion to reduce neural compression and stabilize the spinal column. However, due to the profound morbidity associated with complex multilevel surgery, particularly in elderly patients and those with multiple medical comorbidities, minimally invasive surgical approaches have been proposed. The goal of this meta-analysis was to review the differences in patient selection for minimally invasive surgical versus open surgical procedures for adult DLS, and to compare the postoperative outcomes following minimally invasive surgery (MIS) and open surgery. METHODS: In this meta-analysis the authors analyzed the complication rates and the clinical outcomes for patients with adult DLS undergoing complex decompressive procedures with fusion versus minimally invasive surgical approaches. Minimally invasive surgical approaches included decompressive laminectomy, microscopic decompression, lateral and extreme lateral interbody fusion (XLIF), and percutaneous pedicle screw placement for fusion. Mean patient age, complication rates, reoperation rates, Cobb angle, and measures of sagittal balance were investigated and compared between groups. RESULTS: Twelve studies were identified for comparison in the MIS group, with 8 studies describing the lateral interbody fusion or XLIF and 4 studies describing decompression without fusion. In the decompression MIS group, the mean preoperative Cobb angle was 16.7° and mean postoperative Cobb angle was 18°. In the XLIF group, mean pre- and postoperative Cobb angles were 22.3° and 9.2°, respectively. The difference in postoperative Cobb angle was statistically significant between groups on 1-way ANOVA (p = 0.014). Mean preoperative Cobb angle, mean patient age, and complication rate did not differ between the XLIF and decompression groups. Thirty-five studies were identified for inclusion in the open surgery group, with 18 studies describing patients with open fusion without osteotomy and 17 papers detailing outcomes after open fusion with osteotomy. Mean preoperative curve in the open fusion without osteotomy and with osteotomy groups was 41.3° and 32°, respectively. Mean reoperation rate was significantly higher in the osteotomy group (p = 0.008). On 1-way ANOVA comparing all groups, there was a statistically significant difference in mean age (p = 0.004) and mean preoperative curve (p = 0.002). There was no statistically significant difference in complication rates between groups (p = 0.28). CONCLUSIONS: The results of this study suggest that surgeons are offering patients open surgery or MIS depending on their age and the severity of their deformity. Greater sagittal and coronal correction was noted in the XLIF versus decompression only MIS groups. Larger Cobb angles, greater sagittal imbalance, and higher reoperation rates were found in studies reporting the use of open fusion with osteotomy. Although complication rates did not significantly differ between groups, these data are difficult to interpret given the heterogeneity in reporting complications between studies.

High incidence of morbidity following resection of metastatic pheochromocytoma in the spine.

Pheochromocytomas of the spine are uncommon and require careful preoperative planning. The authors retrospectively reviewed the charts of 5 patients with metastatic spinal pheochromocytoma who had undergone surgical treatment over the past 10 years at their medical center. They reviewed patient age, history of pheochromocytoma resection, extent and location of metastases, history of alpha blockage, surgical level, surgical procedure, postoperative complications, tumor recurrence, and survival. Metastases involved the cervical (1 patient), thoracic (3 patients), and lumbar (2 patients) levels. Preoperative treatment included primary pheochromocytoma resection, chemotherapy, alpha blockade, embolization, and radiation. Three patients had tumor recurrence, and 2 underwent 2-stage reoperations for tumor extension. Hemodynamic complications were common: 2 patients developed pulseless electrical activity arrest within 4 months after surgery, 1 patient had profound postoperative tachycardia with fever and an elevated creatine kinase level, and 1 patient experienced transient postoperative hypotension and paraplegia. One patient died of complications related to disseminated cerebral and spinal disease. With careful preoperative and surgical management, patients with symptomatic metastatic spinal pheochromocytoma can benefit from aggressive surgical treatment. Postoperative cardiovascular complications are common even months after surgery, and patients should be closely monitored long term.

Characterization of intratumor magnetic nanoparticle distribution and heating in a rat model of metastatic spine disease.

OBJECT: The goal of this study was to optimize local delivery of magnetic nanoparticles in a rat model of metastatic breast cancer in the spine for tumor hyperthermia while minimizing systemic exposure. METHODS: A syngeneic mammary adenocarcinoma was implanted into the L-6 vertebral body of 69 female Fischer rats. Suspensions of 100-nm starch-coated iron oxide magnetic nanoparticles (micromod Partikeltechnologie GmbH) were injected into tumors 9 or 13 days after implantation. For nanoparticle distribution studies, tissues were harvested from a cohort of 36 rats, and inductively coupled plasma mass spectrometry and histopathological studies with Prussian blue staining were used to analyze the samples. Intratumor heating was tested in 4 anesthetized animals with a 20-minute exposure to an alternating magnetic field (AMF) at a frequency of 150 kHz and an amplitude of 48 kA/m or 63.3 kA/m. Intratumor and rectal temperatures were measured, and functional assessments of AMF-exposed animals and histopathological studies of heated tumor samples were examined. Rectal temperatures alone were tested in a cohort of 29 rats during AMF exposure with or without nanoparticle administration. Animal studies were completed in accordance with the protocols of the University Animal Care and Use Committee. RESULTS: Nanoparticles remained within the tumor mass within 3 hours of injection and migrated into the bone at 6, 12, and 24 hours. Subarachnoid accumulation of nanoparticles was noted at 48 hours. No evidence of lymphoreticular nanoparticle exposure was found on histological investigation or via inductively coupled plasma mass spectrometry. The mean intratumor temperatures were 43.2°C and 40.6°C on exposure to 63.3 kA/m and 48 kA/m, respectively, with histological evidence of necrosis. All animals were ambulatory at 24 hours after treatment with no evidence of neurological dysfunction. CONCLUSIONS: Locally delivered magnetic nanoparticles activated by an AMF can generate hyperthermia in spinal tumors without accumulating in the lymphoreticular system and without damaging the spinal cord, thereby limiting neurological dysfunction and minimizing systemic exposure. Magnetic nanoparticle hyperthermia may be a viable option for palliative therapy of spinal tumors.

Surgical management of primary and metastatic spinal tumors.

BACKGROUND: The axial skeleton is a common site for primary tumors and metastatic disease, with metastatic disease being much more common. Primary and metastatic spinal tumors have a diverse range of aggressiveness, ranging from benign lesions to highly infiltrative malignant tumors. METHODS: The authors reviewed the results of articles describing the treatment and outcomes of patients with metastatic disease or primary tumors of the spinal column. RESULTS: En bloc resection is the mainstay of treatment for malignant primary tumors of the spinal column. Intralesional resection is generally appropriate for benign primary tumors. Low-quality evidence supports the use of chemotherapy in select primary tumors; however, radiation therapy is often used for incompletely resected or unresectable lesions. Surgical considerations for the treatment of metastatic disease are more nuanced and require that the health care professional consider patient performance status and the pathology of the primary tumor. CONCLUSIONS: The treatment of metastatic and primary tumors of the spinal column requires a multidisciplinary approach in order to offer patients the best opportunity for long-term survival.

Prolonged survival following aggressive treatment for metastatic breast cancer in the spine.

In 2007, members of our group reported a 21 month median survival for patients undergoing surgery for metastatic breast cancer in the spinal column. Cervical spine metastases were associated with decreased survival, Estrogen receptor positivity was associated with improved survival, and age and visceral metastases did not significantly impact survival. In the current study, we reassess these variables in the context of modern adjuvant therapies, and investigate the impact of the Spinal Instability Neoplastic Score (SINS). We report an observational cohort of 43 patients undergoing surgical resection for metastatic breast cancer of the spine treated at a single academic institution from June 2002 to August 2011. Patient medical records were reviewed in accordance with policies outlined by the University Institutional Review Board. Median overall survival following surgery for metastatic breast cancer in the spine was 26.8 months. 1 year overall survival was 66%. 5 year-overall survival was 4%. Age (p=0.12), preoperative functional status (p=0.17), location of metastasis (p=0.34), the presence of visceral metastases (p=0.68), and spinal instability (p=0.81) were not significant variables on survival analysis. Postoperative adjuvant therapy with a single modality (radiation or chemotherapy) was associated with a significantly lower median survival compared to dual therapy with chemotherapy and radiation (p=0.042). Patients that received radiation and chemotherapy after surgery were younger but demonstrated prolonged median survival versus single modality therapy. This data supports the concept that visceral metastases do not impact survival, however cervical spine lesions were not associated with decreased survival.

Alveolar soft-part sarcoma in the sacrum: a case report and review of the literature.

Alveolar soft part sarcoma (ASPS) is a rare disease of the soft tissue. Although the disease is rare, it is refractory to chemotherapy and radiation. En bloc surgical resection offers the best chance of cure. In this article we report the case of a 28-year-old woman who presented with buttock and leg pain, bowel, bladder and gait impairment and a large mass in the sacrum. Following surgical excision, the lesion was proven to be ASPS. On pathology, the mass was TFE3 (transcription factor E3) positive, indicating the presence of the ASPL-TFE3 (novel gene-transcription factor) translocation. Following surgery, the patient had improvement in her pain and ambulation; however, she refused adjuvant therapy to pursue hospice care and succumbed to her disease 2 years after surgery. On a review of the literature, it was found that ASPS of the bone constitutes a rare and formidable subset of this disease. Further, metastases related to ASPS are common in the lungs, liver, brain, and lymph nodes. The degree of dissemination is a predictor of outcome, with 5-year survival of 81-88% in patients with local disease and only 20-46% in patients with metastatic disease at the time of presentation. Brain metastases at the time of presentation portend the worst prognosis.

A rat model of metastatic spinal cord compression using human prostate adenocarcinoma: histopathological and functional analysis.

BACKGROUND CONTEXT: Cancer is a major global public health problem responsible for one in every four deaths in the United States. Prostate cancer alone accounts for 29% of all cancers in men and is the sixth leading cause of death in men. It is estimated that up to 30% of patients with cancer will develop metastatic disease, the spine being one of the most frequently affected sites in patients with prostate cancer. PURPOSE: To study this condition in a preclinical setting, we have created a novel animal model of human metastatic prostate cancer to the spine and have characterized it histologically, functionally, and via bioluminescence imaging. STUDY DESIGN: Translational science investigation of animal model of human prostate cancer in the spine. METHODS: Luciferase-positive human prostate tumor cells PC3 (PC3-Luc) were injected in the flank of athymic male rats. PC3-Luc tumor samples were then implanted into the L5 vertebral body of male athymic rats (5 weeks old). Thirty-two rats were randomized into three surgical groups: experimental, control, and sham. Tumor growth was assessed qualitatively and noninvasively via bioluminescence emission, upon luciferin injection. To determine the functional impact of tumor growth in the spine, rats were evaluated for gait abnormalities during gait locomotion using video-assisted gait analysis. Rats were euthanized 22 days after tumor implantation, and spines were subjected to histopathological analyses. RESULTS: Twenty days after tumor implantation, the tumor-implanted rats showed distinct signs of gait disturbances: dragging tail, right- or left-hind limb uncoordination, and absence of toe clearance during forward limb movement. At 20 days, all rats experienced tumor growth, evidenced by bioluminescent signal. Locomotion parameters negatively affected in tumor-implanted rats included stride length, velocity, and duration. At necropsy, all spines showed evidence of tumor growth, and the histological analysis found spinal cord compression and peritumoral osteoblastic reaction characteristic of bony prostate tumors. None of the rats in the sham or control groups demonstrated any evidence of bioluminescence signal or signs of gait disturbances. CONCLUSIONS: In this project, we have developed a novel animal model of metastatic spine cancer using human prostate cancer cells. Tumor growth, evaluated via bioluminescence and corroborated by histopathological analyses, affected hind limb locomotion in ways that mimic motor deficits present in humans afflicted with metastatic spine disease. Our model represents a reliable method to evaluate the experimental therapeutic approaches of human tumors of the spine in animals. Gait locomotion and bioluminescence analyses can be used as surrogate noninvasive methods to evaluate tumor growth in this model.

Factors associated with improved outcomes following decompressive surgery for prostate cancer metastatic to the spine.

BACKGROUND: Metastatic spinal cord compression from prostate cancer is a debilitating disease causing neurological deficits, mechanical instability, and intractable pain. Surgical management may improve quality of life. OBJECTIVE: To define postoperative outcomes and explore associations with prolonged survival for patients with metastatic prostate cancer. METHODS: Retrospective chart reviews were performed of all patients undergoing spinal surgery for metastatic cancer from June 1, 2002 to August 31, 2011. Patient demographics, surgical details, adjuvant therapies, outcomes, complications, and postoperative survival were reviewed. RESULTS: Twenty-seven patients with prostate cancer underwent surgery at a median age of 65 years (range, 46-82 years). After surgery, 93% of patients had preserved or improved neurological status, 56% of nonambulatory patients recovered ambulation, 43% of incontinent patients recovered continence, and 23% experienced complications. Postoperative Frankel grades were significantly improved by at least 1 letter grade at 1 month (P = .03). The median analgesic and steroid usage was significantly lower up to 3 months and 6 months postoperatively, respectively (P = .007, .005). Median survival following surgery was 10.2 months, and patients with castration-resistant prostate cancer had a shorter median survival than those with hormone-naïve disease (9.8 vs 40 months). Better preoperative performance status was an independent predictor of survival (P = .02). Younger age (P = .005) and instrumentation greater than 7 spinal levels (P = .03) were associated with complications. CONCLUSION: Spinal surgery for prostate metastases improves neurological function and decreases analgesic requirements. Our findings support surgical intervention for carefully selected patients, and knowledge of preoperative hormone sensitivity and performance status may help with risk stratification.

En bloc resection of a pheochromocytoma metastatic to the spine for local tumor control and for treatment of chronic catecholamine release and related hypertension.

Resection of metastatic pheochromocytomas may be complicated by transient postoperative neurological deficits due to hypotension. The authors report the first case of en bloc excision of a spinal pheochromocytoma with associated long-term hypertensive management off all medication. Interestingly, this is the first case of transient hypotension following en bloc resection of pheochromocytoma associated with temporary hypotension-associated neurological decline that resolved completely after correction of hypotension postoperatively. A 23-year-old man with a prior adrenalectomy for pheochromocytoma presented with focal thoracic pain. He had a known T-10 vertebral body lesion for which he received chemotherapy and radiation therapy. Imaging demonstrated increased destruction of the T-10 vertebral body, which was concerning for tumor growth. The patient underwent angiographic embolization followed by single-stage posterior en bloc vertebrectomy with placement of a cage and posterior instrumentation and fusion without event. However, approximately 24 hours after surgery, the patient's systolic blood pressure was consistently no higher than 70 mm Hg. During this time, he began suffering from severe bilateral lower-extremity weakness. His systolic blood pressure increased with dopamine, and his strength immediately improved. The patient's oral regimen of adrenergic blockade was stopped, and he recovered without event. Since that time, the patient has been symptom free and requires no antihypertensive medication. The role of en bloc resection for metastatic lesions of the spine is controversial but may be warranted in cases of metastatic pheochromocytoma. En bloc resection avoids intralesional tumor resection and thus may help prevent complications of hypertensive crisis associated with hormonal secretion and extensive blood loss, which are not uncommon with pheochromocytoma resection surgeries. Additionally, the role of en bloc spondylectomy in this setting may allow for metabolic treatment as patients with actively secreting tumors may no longer require antiadrenergic medications.

A cohort cost analysis of lumbar laminectomy--current trends in surgeon and hospital fees distribution.

BACKGROUND CONTEXT: Spine-related health-care expenditures accounted for $86 billion dollars in 2005, a 65% increase from 1997. However, when adjusting for inflation, surgeons have seen decreased reimbursement rates over the last decade. PURPOSE: To assess contribution of surgeon fees to overall procedure cost, we reviewed the charges and reimbursements for a noninstrumented lumbar laminectomy and compared the amounts reimbursed to the hospital and to the surgeon at a major academic institution. STUDY DESIGN/SETTING: Retrospective review of costs associated with lumbar laminectomies. PATIENT SAMPLE: Seventy-seven patients undergoing lumbar laminectomy for spinal stenosis throughout an 18-month period at a single academic medical center were included in this study. OUTCOME MEASURES: Cost and number of laminectomy levels. METHODS: The reimbursement schedule of six academic spine surgeons was collected over 18 months for performed noninstrumented lumbar laminectomy procedures. Bills and collections by the hospital and surgeon professional fees were comparatively analyzed and substratified by number of laminectomy levels and patient insurance status. Unpaired two-sample Student t test was used for analysis of significant differences. RESULTS: During an 18-month period, patients underwent a lumbar laminectomy involving on average three levels and stayed in the hospital on average 3.5 days. Complications were uncommon (13%). Average professional fee billing for the surgeon was $6,889±$2,882, and collection was $1,848±$1,433 (28% overall, 30% for private insurance, and 23% for Medicare/Medicaid insurance). Average hospital billing for the inpatient hospital stay minus professional fees from the surgeon was $14,766±$7,729, and average collection on such bills was $13,391±$7,256 (92% overall, 91% for private insurance, and 85% for Medicare/Medicaid insurance). CONCLUSION: Based on this analysis, the proportion of overall costs allocated to professional fees for a noninstrumented lumbar laminectomy is small, whereas those allocated to hospital costs are far greater. These findings suggest that the current focus on decreasing physician reimbursement as the principal cost saving strategy will lead to minimal reimbursement for surgeons without a substantial drop in the overall cost of procedures performed.