David M. Wildrick

Stereotactic biopsy is often performed for diagnostic purposes before treating patients whose imaging studies highly suggest glioma. Indications cited for biopsy include diagnosis and/or the "inoperability" of the tumor. This study questions the routine use of stereotactic biopsy in the initial management of gliomas. At The University of Texas M. D. Anderson Cancer Center, we retrospectively reviewed a consecutive series of 81 patients whose imaging studies suggested glioma and who underwent stereotactic biopsy followed by craniotomy/resection (within 60 days) between 1993 and 1998. All relevant clinical and imaging information was reviewed, including computerized volumetric analysis of the tumors based on pre- and postoperative MRI. Stereotactic biopsy was performed at institutions other than M. D. Anderson in 78 (96%) of 81 patients. The majority of tumors were located either in eloquent brain (36 of 81 = 44%) or near-eloquent brain (41 of 81 = 51%), and this frequently was the rationale cited for performing stereotactic biopsy. Gross total resection (>95%) was achieved in 46 (57%) of 81 patients, with a median extent of resection of 96% for this series. Diagnoses based on biopsy or resection in the same patient differed in 40 (49%) of 82 cases. This discrepancy was reduced to 30 (38%) of 80 cases when the biopsy slides were reviewed preoperatively by each of three neuropathologists at M. D. Anderson. Major neurologic complications occurred in 10 (12.3%) of 81 surgical patients and 3 (3.7%) of 81 patients undergoing biopsy. Surgical morbidity was probably higher in our series than it would be for glioma patients in general because our patients represent a highly selected subset of glioma patients whose tumors present a technical challenge to remove. Stereotactic biopsy is frequently inaccurate in providing a correct diagnosis and is associated with additional risk and cost. If stereotactic biopsy is performed, expert neuropathology consultation should be sought.

OBJECT: Anterior approaches to the spine for the treatment of spinal tumors have gained acceptance; however, in most published reports, patients with primary, metastatic, or chest wall tumors involving cervical, thoracic, or lumbar regions of the spine are combined. The purpose of this study was to provide a clear perspective of results that can be expected in patients who undergo anterior vertebral body resection, reconstruction, and stabilization for spinal metastases that are limited to the thoracic region. METHODS: Outcome is presented for 72 patients with metastatic spinal tumors who were treated by transthoracic vertebrectomy at The University of Texas M. D. Anderson Cancer Center. The predominant primary tumors included renal cancer in 19 patients, breast cancer in 10, melanoma or sarcoma in 10, and lung cancer in nine patients. The most common presenting symptoms were back pain, which occurred in 90% of patients, and lower-extremity weakness, which occurred in 64% of patients. All patients underwent transthoracic vertebrectomy, decompression, reconstruction with methylmethacrylate, and anterior fixation with locking plate and screw constructs. Supplemental posterior instrumentation was required in seven patients with disease involving the cervicothoracic or thoracolumbar junction, which was causing severe kyphosis. After surgery, pain improved in 60 of 65 patients. This improvement was found to be statistically significant (p < 0.001) based on visual analog scales and narcotic analgesic medication use. Thirty-five of the 46 patients who presented with neurological dysfunction improved significantly (p < 0.001) following the procedure. Thirty-three patients had weakness but could ambulate preoperatively. Seventeen of these 33 regained normal strength, 15 patients continued to have weakness, and one patient was neurologically worse postoperatively. Of the 13 preoperatively nonambulatory patients, 10 could walk after surgery and three were still unable to walk but showed improved motor function. Twenty-one patients had complications ranging from minor atelectasis to pulmonary embolism. The 30-day mortality rate was 3%. The 1-year survival rate for the entire study population was 62%. CONCLUSIONS: These results suggest that transthoracic vertebrectomy and spinal stabilization can improve the quality of life considerably in cancer patients with spinal metastasis by restoring or preserving ambulation and by controlling intractable spinal pain with acceptable rates of morbidity and mortality.

Recently, tumor-specific allele loss has been shown to be an important characteristic of some tumors. When such loss includes one or more growth-regulatory genes, it may allow the expression of tumorigenicity. Using Southern blots, we analyzed normal and tumor DNA samples from 19 ovarian cancer patients, using a series of polymorphic DNA probes that map to a variety of chromosomal loci. Of 14 informative cases, tumor-specific allelic loss was observed in nine (64%) at the estrogen receptor (ESR) gene locus on chromosome 6q. On chromosome 17p at the D17S28 and D17S30 loci, allelic losses were also detected in 6 of 8 (75%) and 9 of 14 (64%) cases, respectively. Allelic loss at the HRAS1 gene locus on chromosome 11p occurred in 5 of 11 (46%) informative cases. The relatively high incidence of these allelic losses observed on chromosome 6q represents the first implication by molecular genetic analysis of this chromosomal region in a human malignancy, and it thus appears to be a genetic change specific to ovarian carcinoma. DNA sequence losses on 11p and 17p, also reported for other cancers, may reflect the presence of tumor- or growth-suppressor genes on these chromosomes that are important in the genesis of many tumor types, including ovarian malignancies.

OBJECTIVE: Two main forms of cell death are encountered in biology: apoptosis (i.e., programmed cell death) and necrosis (i.e., accidental cell death). Because necrosis and apoptosis can lead to cell removal, one might intuit that they are both desirable in cancer treatment. However, in the setting of glioblastoma multiforme, a malignant brain tumor for which the presence of necrosis is an important diagnostic feature, clinical studies indicate that as the degree of necrosis advances, the patient's prognosis worsens. Despite the apparent importance of this form of cell death, the mechanism of development of necrosis in glioblastomas remains unelucidated. The purpose of this article is to try to resolve this dilemma by hypothesizing the mechanism of necrosis formation in these tumors. METHODS: On the basis of an extensive review of the literature, we present a hypothesis for the mechanism of necrosis formation in glioblastoma multiforme. RESULTS: One of the many possible pathways leading to necrosis formation may involve increased tumor cell secretion of tumor necrosis factor. Procoagulation and antiapoptotic mechanisms resulting from certain pathways could prevent the completion of tumor necrosis factor-induced apoptosis and could promote necrosis as the final mode of cell death. Such a hypothesis would explain the inverse correlation that exists between tumor necrosis and the survival of patients with glioblastomas, because the hypoxia that results from procoagulation selects for tumor cells that are more aggressive and more resistant to apoptosis-inducing therapies. CONCLUSION: A complete understanding of the series of events surrounding necrosis development in glioblastomas that is evidence-based is likely to provide targets for future therapies. On the basis of the potential mechanisms of development of necrosis described in this article, we postulate that effective therapies may have to be directed against the pathways that result in the formation of necrosis.

Although radical resection is the best treatment for malignant sacral tumors, total sacrectomy for such tumors has been performed in only a few instances. Total sacral resection requires reconstruction of the pelvic ring plus establishment of a bilateral union between the lumbar spine and iliac bone. This technique is illustrated in two patients harboring large, painful, sacral giant-cell tumors that were unresponsive to prior treatment. These patients were treated with complete en bloc resection of the sacrum and complex iliolumbar reconstruction/stabilization and fusion. Surgery was performed in two stages, the first consisting of a midline celiotomy, dissection of visceral/neural structures, and ligation of internal iliac vessels, followed by an anterior L5-S1 discectomy. The second stage consisted of mobilization of an inferiorly based myocutaneous rectus abdominis pedicle flap for wound closure, followed by an L-5 laminectomy, bilateral L-5 foraminotomy, ligation of the thecal sac, division of sacral nerve roots, and transection of the ilia lateral to the tumor and sacroiliac joints. Placement of the instrumentation required segmental fixation of the lumbar spine from L-3 down by means of pedicle screws and the establishment of a bilateral liaison between the lumbar spine and the ilia by using the Galveston L-rod technique. The pelvic ring was then reestablished by means of a threaded rod connecting left and right ilia. Both autologous (posterior iliac crest) and allograft bone were used for fusion, and a tibial allograft strut was placed between the remaining ilia. The patients were immobilized for 8 weeks postoperatively and underwent progressive rehabilitation. At the 1-year follow-up review, one patient could walk unassisted, and the other ambulated independently using a cane. Both patients controlled bowel function satisfactorily with laxatives and diet and could maintain continence but required self-catheterization for bladder emptying. The authors conclude that in selected patients, total sacrectomy represents an acceptable surgical procedure that can offer not only effective local pain control, but also a potential cure, while preserving satisfactory ambulatory capacity and neurological function.