Julie E. York

Sacral chordoma: 40-Year experience at a major cancer center

OBJECTIVE Sacral chordomas are relatively rare, locally invasive, malignant neoplasms. Despite surgical resection, adjuvant radiation therapy, and chemotherapy, recurrence is common. This study reviews our experience during the last 40 years at The University of Texas M.D. Anderson Cancer Center, to determine the effects of various treatment methods on the overall course of this disease process. METHODS A retrospective study was performed. From 1954 to 1994, 27 patients with sacral chordomas were evaluated at our institution. RESULTS There were 19 male and 8 female patients, with a mean age of 56 years (range, 27-80 yr). All except one of the patients presented with pain, and 17 of 27 showed evidence of autonomic dysfunction at initial presentation. Based on microscopic examination of surgical specimen margins, surgical procedures were categorized as either radical resection or subtotal excision. All patients underwent at least one surgical procedure, for a total of 67 procedures (28 radical resections and 39 subtotal excisions). Twelve patients underwent one operation, whereas nine underwent two procedures and six underwent more than two operations (range, 3-16 operations). Radiation therapy was used in conjunction with 13 of the 67 surgical procedures. The median Kaplan-Meier estimate of the overall survival time for the entire group was 7.38 years (range, 4 mo to 34 yr). Tumors recurred after 47 of the 67 procedures. The overall disease-free interval for patients undergoing radical resection was 2.27 years for each procedure, compared with 8 months for each procedure for patients treated with subtotal excision (log-rank test for the inequality between the two curves, 19.58; P<0.0001). The addition of radiation therapy prolonged the disease-free interval for patients undergoing subtotal resection (2.12 yr versus 8 mo; log-rank test for the inequality between the two curves, 5.82; P<0.02). CONCLUSION Our results suggest frequent recurrences in the majority of patients with chordomas. Radical resection is associated with a significantly longer disease-free interval, compared with subtotal removal of the tumor. Addition of radiation after subtotal resection improves the disease-free interval, although radiation therapy can generally be used only once. Based on these findings, we think that, whenever possible, radical resection should be the treatment of choice for sacral chordomas.

Gastric Cancer and Metastasis to the Brain

Background: Metastasis of gastric carcinoma to the brain is very uncommon. At The University of Texas M. D. Anderson Cancer Center (M. D. Anderson), less than 1% of patients with primary gastric carcinoma are found to have brain metastases. Little has been published regarding the evaluation and treatment of these patients. The purpose of this study was to review our experience with gastric cancer metastatic to the brain and to describe the efficacy of the treatment used.Methods: Between 1957 and 1997, a total of 218,690 patients were seen for evaluation of malignant tumors at M. D. Anderson. Of these patients, 3320 (1.5%) had a diagnosis of gastric cancer; however, only 24 patients (0.7%) were found to have brain metastases on imaging studies or at autopsy. We performed a retrospective review of these 24 patients and divided them into three groups on the basis of the treatment they received.Results: Group 1 included patients who received steroids alone (16 mg of dexamethasone, daily). Group 2 patients received 3000 cGy of whole-brain radiation therapy (WBRT) delivered in 10 fractions in addition to steroids. Group 3 patients were managed with surgical resection, WBRT, and steroids. There were 18 male and 6 female patients, with a median age of 53 years. The most common presenting symptoms were weakness, difficulty with balance, and headache. Of the 19 patients diagnosed antemortem, 11 patients developed neurological symptoms after the primary diagnosis of gastric carcinoma, whereas 8 patients developed neurological symptoms before the diagnosis of gastric cancer. Forty-five percent of patients had a single brain metastasis, whereas 55% had multiple lesions. All patients had systemic disease, with bone, liver, and lung involvement seen in 46%, 42%, and 29%, respectively. Nineteen of 24 patients received treatment after diagnosis of brain metastases. Four patients received steroids only (group 1), 11 patients received WBRT and steroids (group 2), and 4 patients were treated with surgery, WBRT, and steroids (group 3). Median survival was approximately 2 months for patients in groups 1 and 2, whereas group 3 patients had a median survival of slightly greater than 1 year.Conclusions: Our results suggest that the overall prognosis of patients with brain metastases from gastric cancer is extremely poor (median survival, 9 weeks). WBRT, as an adjuvant to steroid treatment, was not effective in improving outcome in our series. In selected patients, most of whom were relatively young and had less advanced systemic disease, surgical resection followed by WBRT was associated with relatively long survival times (median survival, 54 weeks).

Expression and role of matrix metalloproteinases MMP-2 and MMP-9 in human spinal column tumors.

Matrix metalloproteinases (MMPs) have been implicated in the process of tumor invasion and metastasis formation. Thus, we determined the expression of MMPs in various primary and metastatic spinal tumors in order to assess the role of these enzymes in spinal invasion. MMP expression was examined by immuno-histochemical localization, and quantitative evaluation of MMP protein content was determined by enzyme-linked immunosorbant assay (ELISA) and Western blotting. MMP enzyme activity was determined by gelatin zymography. Lung carcinomas and melanomas metastatic to the spine were shown to have higher levels of MMP-9 activity than those of breast, thyroid, renal metastases and primary spinal tumors. Immunohistochemical analysis revealed similar difference in expression of MMP-9 in tissue samples. When the tissue samples were subjected to gelatin zymography for examination of MMP-2 and MMP-9 activity and to ELISA and Western blotting for quantitative estimation of protein content, the most striking results were obtained for lung carcinomas and melanomas relative to the other tumors. Lung carcinomas and melanomas metastatic to the spine had considerably higher levels of MMP-9 activity than those of primary spinal tumor or breast, thyroid, and renal carcinoma metastases. Within the metastatic tumor category, neoplasms that are known to be associated with the shortest overall survival rates and most aggressive behavior, such as lung carcinomas and melanomas, had the highest levels of MMP-2 and MMP-9 activity compared to those less aggressive metastatic tumors such as breast, renal cell, and thyroid carcinomas. Our results suggest that MMPs may contribute to the metastases to the spinal column, and overexpression of these enzymes may correlate with enhanced invasive properties of both primary and metastatic spinal tumors.© Kluwer Academic Publishers 1998

Expression and localization of urokinase-type plasminogen activator in human spinal column tumors.

The Institute for Molecular Medicine, Huntington Beach CA 92649 USA We have sought to determine the production and activity of serine proteases in primary and metastatic spinal tumors and the association of these enzymes with the invasive and metastatic properties of spinal column tumors. Using immunohistochemical techniques, the cellular localization and expression of uroki-nase- type plasminogen activator (uPA) was assessed, whereas its activity was determined by fibrin zymog-raphy, and the amounts of enzyme were measured by an enzyme-linked immunosorbent assay (ELISA) in primary spinal column tumors (chordoma, chondrosarcoma, and giant cell tumor) and metastatic tumors of the spine arising from various malignancies (breast, lung, thyroid, and renal cell carcinomas, and melanomas). Metastatic tumors displayed higher levels of uPA activity than did primary spinal tumors (P < 0.001). Immunohistochemical analysis revealed that uPA expression was highest in metastases from lung and breast carcinomas and melanomas, followed by metastatic tumors from thyr oid and renal cell carcinomas. Similar results were obtained for uPA activity and enzyme level as determined by fibrin zymography and ELISA, respectively. We conclude that metastatic spinal tumors possess higher levels of uPA expression and activity than the primary spinal tumors, which tend to be less aggressive and only locally invasive malignancies. The results suggest that the plasminogen system may participate in the metastasis of tumors to the spinal column.© Kluwer Academic Publishers 1998

The anatomical suitability of C1-2 transarticular screw placement in pediatric patients

OBJECT Craniovertebral instability is a challenging problem in pediatric spinal surgery. Recently, C1-2 transarticular screw fixation has been used to assist in craniovertebral joint stabilization in pediatric patients. Currently there are no available data that define the anatomical suitability of this technique in the pediatric population. The authors report their experience in treating 31 pediatric patients with craniovertebral instability by using C 1-2 transarticular screws. METHODS From March 1992 to October 1998, 31 patients who were 16 years of age or younger with atlantooccipital or atlantoaxial instability, or both, were evaluated at our institution. There were 21 boys and 10 girls. Their ages ranged from 4 to 16 years (mean age 10.2 years). The most common causes of instability were os odontoideum (12 patients) and ligamentous laxity (eight patients). Six patients had undergone a total of nine previous attempts at posterior fusion while at outside institutions. All patients underwent extensive preoperative radiological evaluation including fine-slice (1-mm) computerized tomography scanning with multiplanar reconstruction to evaluate the anatomy of the C1-2 joint space. Preoperatively, of the 62 possible C1-2 joint spaces in 31 patients, 55 sides (89%) were considered suitable for transarticular screw placement. In three patients the anatomy was considered unsuitable for bilateral screw placement. In three patients the anatomy was considered inadequate on one side. Fifty-five C1-2 transarticular screws were subsequently placed, and there were no neurological or vascular complications. CONCLUSIONS The authors conclude that C1-2 transarticular screw fixation is technically possible in a large proportion of pediatric patients with craniovertebral instability.