✓ The authors present a series of 25 patients who underwent single-stage complete spondylectomy, vertebral body reconstruction, and posterior segmental spinal stabilization for malignant metastatic disease involving multiple columns of the thoracolumbar spine. Patients were selected for this approach primarily because they were poor candidates for a transcavitary or lateral extracavitary approach or because the tumor involved both anterior and posterior columns of the spine. The operative approach used combines radical local resection of tumor via a bilateral transpedicular route, methylmethacrylate vertebral body reconstruction, and Luque rectangle stabilization in a single operation. Following surgery, the majority of patients experienced improvement in their neurological status, reduction in pain, or both. Most patients were functionally improved, or at least no worse, and spinal alignment was maintained in all. There was one local recurrence in a long-term survivor. Complications included cerebrospinal fluid fistulas, migrating graft material, and wound healing problems. The authors conclude that this surgical approach is safe and feasible for the radical resection of vertebral metastasis when combined with reconstruction and stabilization. This technique represents a useful alternative to other commonly used surgical approaches for the treatment of spinal metastases, and it should aid surgeons in selecting the optimum approach for individual patients.
Edward W. Akeyson and Ian E. McCutcheon
Thomas S. F. Chow and Ian E. McCutcheon
✓ The authors retrospectively reviewed the surgical outcomes in 10 cases of symptomatic intradural extramedullary spinal metastases of nonneurogenic origin because the collective experience in treating this rare manifestation of systemic cancer is limited. Pain and weakness were the presenting complaints in 70% of the patients and sensory changes were found in all cases. Cytological tests on one specimen of cerebrospinal fluid (CSF) from each of seven patients showed malignant cells in two cases. Gadolinium contrast-enhanced biplanar magnetic resonance (MR) imaging was effective in localizing the lesion and showed evidence of leptomeningeal carcinomatosis in two cases; myelography showed leptomeningeal carcinomatosis in one case and erroneously identified the lesion as intramedullary in the other. Eight of 10 cases had antecedent intracranial metastatic foci with the interval from presentation of the intracranial lesion to appearance of the spinal disease ranging from 3 to 51 months. The majority of the spinal lesions occurred in the thoracolumbar area. The most frequent histological type was adenocarcinoma and the most frequent source was the lung. In all cases laminectomies, intradural exploration, and biopsy or subtotal excision aided by microscopy and ultrasonography were performed. Results of surgical decompression were poor with only 30% of the patients showing improvement, at a 20% risk of perioperative mortality and a 60% risk of morbidity. Plans for surgical intervention in patients with intradural extramedullary metastases from a distant nonneurogenic source should be weighed against the high association with intracranial lesions, overall poor prognosis, and modest symptomatic results of decompression. Comprehensive evaluation including multiple specimens of CSF for cytology and contrast-enhanced MR imaging should be undertaken to exclude patients with diffuse leptomeningeal involvement, who should be treated by means other than surgery.
Frederick F. Lang, Raymond Sawaya, Dima Suki, Ian E. McCutcheon and Kenneth R. Hess
Ben A. Strickland, Ian E. McCutcheon, Indro Chakrabarti, Laurence D. Rhines and Jeffrey S. Weinberg
Metastasis to the spinal cord is rare, and optimal management of this disease is unclear. The authors investigated this issue by analyzing the results of surgical treatment of spinal intramedullary metastasis (IM) at a major cancer center.
The authors retrospectively reviewed the medical records of 13 patients who underwent surgery for IM. Patients had renal cell carcinoma (n = 4), breast carcinoma (n = 3), melanoma (n = 2), non–small cell lung cancer (n = 1), sarcoma (n = 1), adenoid cystic carcinoma (n = 1), and cervical cancer (n = 1). Cerebrospinal fluid was collected before surgery in 11 patients, and was negative for malignant cells, as was MRI of the neuraxis. Eleven patients presented with neurological function equivalent to Frankel Grade D.
Radiographic gross-total resection was achieved in 9 patients, and tumor eventually recurred locally in 3 of those 9 (33%). Leptomeningeal disease was diagnosed in 4 patients after surgery. In the immediate postoperative period, neurological function in 6 patients deteriorated to Frankel Grade C. At 2 months, only 2 patients remained at Grade C, 8 were at Grade D, and 1 had improved to Grade E. One patient developed postoperative hematoma resulting in Frankel Grade A. Radiotherapy was delivered in 8 patients postoperatively. The median survival after spine surgery was 6.5 months. Three patients are still living.
Surgery was performed as a last option to preserve neurological function in patients with IM. In most patients, neurological function returned during the immediate postoperative period and was preserved for the patients’ remaining lifetime. The data suggest that surgery can be effective in preventing further decline in selected patients with progressive neurological deficit.
Michele R. Aizenberg, Benjamin D. Fox, Dima Suki, Ian E. McCutcheon, Ganesh Rao and Laurence D. Rhines
Patients presenting with spinal metastases from unknown primary tumors (UPTs) are rare. The authors reviewed their surgical experience to evaluate outcomes and identify predictors of survival in these patients.
This study is a retrospective analysis of patients undergoing surgery for metastatic spine disease from UPTs between June 1993 and February 2007 at The University of Texas M. D. Anderson Cancer Center.
Fifty-one patients undergoing 52 surgical procedures were identified. The median age at spine surgery was 60 years. The median survival from time of diagnosis was 15.8 months (95% CI 8.1–23.6) and it was 8.1 months (95% CI 1.6–14.7) from time of spine surgery. Postoperative neurological function (Frankel score) was the same or improved in 94% of patients. At presentation, 77% had extraspinal disease, which was associated with poorer survival (6.4 vs 18.1 months; p = 0.041). Multiple sites (vs a single site) of spine disease did not impact survival (12.7 vs 8.7 months; p = 0.50). Patients with noncervical spinal disease survived longer than those with cervical disease (11.8 vs 6.4 months, respectively; p = 0.029). Complete versus incomplete resection at index surgery had no impact on survival duration (p > 0.5) or local recurrence (p = 1.0). Identification of a primary cancer was achieved in 31% of patients.
This is the first reported surgical series of patients with an unknown source of spinal metastases. The authors found that multiple sites of spinal disease did not influence survival; however, the presence of extraspinal disease had a negative impact. The extent of resection had no effect on survival duration or local recurrence. With an overall median survival of 8.1 months following surgery, aggressive evaluation and treatment of patients with metastatic disease of the spine from an unknown primary source is warranted.
Daryl R. Fourney, Dima Abi-Said, Frederick F. Lang, Ian E. McCutcheon and Ziya L. Gokaslan
Object. Few reports are available on the use of pedicle screw fixation for cancer-related spinal instability. The authors present their experience with pedicle screw fixation in the management of malignant spinal column tumors.
Methods. Records for patients with malignant spinal tumors who underwent pedicle screw fixation at the authors' institution between September 1994 and December 1999 were retrospectively reviewed.
Results. Ninety-five patients with malignant spinal tumors underwent 100 surgeries involving pedicle screw fixation: metastatic spinal disease was present in 81 patients, and locally invasive tumors were demonstrated in 14 patients. Indications for surgery were pain (98%) and/or neurological dysfunction (80%). A posterior (48%) or a combined anterior—posterior (52%) approach was performed depending on the extent of tumor and the patient's condition. At the mean follow up of 8.2 months, 43 patients (45%) had died; median survival, as determined by Kaplan—Meier analysis, was 14.8 months. At 1 month postsurgery, self-reported pain had improved in 87% of cases (p < 0.001), which is a finding substantiated by reductions in analgesic use, and 29 (47%) of 62 patients with preoperative neurological impairments were functionally improved (p < 0.001). Postoperative complications were associated only with preoperative radiation therapy (p = 0.002) and with preexisting serious medical conditions (p = 0.04). In two patients asymptomatic violation of the lateral wall of the pedicle was revealed on postoperative radiography. The 30-day mortality rate was 1%.
Conclusions. For selected patients with malignant spinal tumors, pedicle screw fixation after tumor resection may provide considerable pain relief and restore or preserve ambulation with acceptable rates of morbidity and mortality.
Ric Jensen, Ian E. McCutcheon and Franco DeMonte
✓ Two cases of florid swelling of pericranial pedicle grafts are reported. Intracranial mass effect produced by the grafts necessitated reoperation with graft removal in one case and graft revision in the other. No permanent neurological deficits were incurred by either patient. Venous congestion and associated swelling within the graft were considered to be related to constriction of the graft base at the frontal bone flap-skull base interface in one patient and torsion of the graft base in the other.
Julie E. York, Garrett L. Walsh, Frederick F. Lang, Joe B. Putnam, Ian E. McCutcheon, Stephen G. Swisher, Ritsuko Komaki and Ziya L Gokaslan
Traditionally, superior sulcus tumors of the lung that involve the chest wall and spinal column have been considered to be unresectable, and historically, patients harboring these tumors have been treated with local radiation therapy with, at best, modest results. The value of gross-total resection remains unclear in this patient population; however, with the recent advances in surgical technique and spinal instrumentation, procedures involving more radical removal of such tumors are now possible. At The University of Texas M. D. Anderson Cancer Center, the authors have developed a new technique for resecting superior sulcus tumors that invade the chest wall and spinal column. They present a technical description of this procedure and results in nine patients in whom stage IIIb superior sulcus tumors extensively invaded the vertebral column. These patients underwent gross-total tumor resection via a combined approach that included posterolateral thoracotomy, apical lobectomy, chest wall resection, laminectomy, vertebrectomy, anterior spinal column reconstruction with methylmethacrylate, and placement of spinal instrumentation. There were six men and three women, with a mean age of 55 years (range 36–72 years). Histological examination revealed squamous cell carcinoma (three patients), adenocarcinoma (four patients), and large cell carcinoma (two patients). The mean postoperative follow-up period was 16 months. All patients are currently ambulatory or remained ambulatory until they died. Pain related to tumor invasion improved in four patients and remained unchanged in five. In three patients instrumentation failed and required revision. There was one case of cerebrospinal leak that was treated with lumbar drainage and one case of wound breakdown that required revision. Two patients experienced local tumor recurrence, and one patient developed a second primary lung tumor. The authors conclude that in selected patients, combined radical resection of superior sulcus tumors of the lung that involve the chest wall and spinal column may represent an acceptable treatment modality that can offer a potential cure while preserving neurological function and providing pain control.
Ian E. McCutcheon, Allan Flyvbjerg, Holly Hill, Jessica Li, William F. Bennett, John A. Scarlett and Keith E. Friend
Object. The authors have previously demonstrated that modulation of the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis can significantly affect meningioma growth in vitro. These studies were performed to evaluate the efficacy of GH receptor blockade in vivo.
Methods. Primary cultures from 15 meningioma tumors obtained in humans were xenografted into athymic mice. Approximately 1.5 million cells from each of the 15 tumors were implanted into the flanks of two female mice, one pair for each tumor. One animal from each of the 15 pairs was then treated with the GH receptor antagonist pegvisomant and the other with vehicle alone for 8 weeks. The tumor volume was measured using digital calipers three times per week. The mean tumor volume at the initiation of injections was 284 ± 18.8 mm3 in the vehicle group and 291.1 ± 20 mm3 in the pegvisomant group. After 8 weeks of treatment, the mean volume of tumors in the pegvisomant group was 198.3 ± 18.9 mm3 compared with 350.1 ± 23.5 mm3 for the vehicle group (p < 0.001). The serum IGF-I concentration in the vehicle group was 319 ± 12.9 µg/L compared with 257 ± 9.7 in the pegvisomant group (p < 0.02). A small but significant decrease was observed in circulating IGF binding protein (IGFBP)—3 levels, whereas slight increases occurred with respect to serum IGFBP-1 and IGFBP-4 levels. In the placebo group the tumor weight was 0.092 ± 0.01 g compared with 0.057 ± 0.01 g in the pegvisomant group (p < 0.02). The IGF-I and IGF-II concentrations were measured in the tumors by using a tissue extraction method. These human-specific immunoassays demonstrated that there was no autocrine production of IGF-I in any of the tumors, either in the pegvisomant or vehicle group. The IGF-II levels were highly variable (0–38.2 ng/g tissue) and did not differ significantly between treatment groups.
Conclusions. In an in vivo tumor model, downregulation of the GH/IGF-I axis significantly reduces meningioma growth and, in some instances, causes tumor regression. Because the concentrations of IGF-II in tumor did not vary with pegvisomant treatment and there was no autocrine IGF-I production by the tumors, the mechanism of the antitumor effect is most likely a decrease of IGF-I in the circulation and/or surrounding host tissues. Because the authors have previously demonstrated that the GH receptor is ubiquitously expressed in meningiomas, direct blockade of the GH receptor on the tumors may also be contributing to inhibitory actions.
Ian E. McCutcheon, Keith E. Friend, Tammy M. Gerdes, Bing-Mei Zhang, David M. Wildrick and Gregory N. Fuller
Object. Although human meningioma cells have been heterotopically implanted in nude mice, introducing these cells into intracranial locations seems more likely to reproduce normal patterns of tumor growth. To provide an orthotopic xenograft model of meningioma, the authors implanted a controlled quantity of meningioma cells at subdural and intracerebral sites in athymic mice.
Methods. Malignant (one tumor), atypical (two tumors), or benign (three tumors) meningiomas were placed into primary cell cultures. Cells (106/10 µl) from these cultures and from an immortalized malignant meningioma cell line, IOMM-Lee, were injected with stereotactic guidance into the frontal white matter or subdural space of athymic mice. Survival curves were plotted for mice receiving tumor cells of each histological type and according to injection site. Other mice were killed at intervals and their heads were sectioned whole. Hematoxylin and eosin staining of these sections revealed the extent of tumor growth.
Conclusions. The median length of survival for mice with malignant, atypical, or benign tumors was 19, 42, or longer than 84 days, respectively. Atypical and malignant tumors were invasive, but did not metastasize extracranially. Malignant tumors uniformly showed leptomeningeal dissemination and those implanted intracerebrally grew locally and spread noncontiguously to the ventricles, choroid plexus, convexities, and skull base. Tumors formed in only 50% of mice injected with benign meningioma cells, whereas injection of more aggressive cells was uniformly successful at tumor production. The three types of human meningiomas grown intracranially in athymic mice maintained their relative positions in the spectrum of malignancy. However, atypical meningiomas became more aggressive after xenografting and acquired malignant features, implying that there had been immune constraint in the original host. Tumor cells injected into brain parenchyma migrated to more optimal environments and grew best there. This model provides insights into the biology of meningiomas and may be useful for testing new therapies.