Total sacrectomy and Galveston L-rod reconstruction for malignant neoplasms. Technical note.

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.

Reoperation for recurrent metastatic brain tumors.

Results of reoperation in 48 patients who developed recurrent brain metastases between January 1984 and April 1993 are presented. Median time from first craniotomy to diagnosis of recurrence (time to recurrence) was 6.7 months. Median Karnofsky performance scale (KPS) score prior to reoperation was 80. Recurrence was local in 30 patients, distant in 16 patients, and both local and distant in two patients. Median survival time after reoperation was 11.5 months. There were no operative mortalities. Multivariate analysis revealed that presence of systemic disease (p = 0.008), KPS scores less than or equal to 70 (p = 0.008), time to recurrence of less than 4 months (p = 0.008), age greater than or equal to 40 years (p = 0.51), and primary tumor type of breast or melanoma (p = 0.028) negatively affected patient survival time. These five factors were used to develop a grading system (Grades I-IV). Patients categorized in Grade I had a 5-year survival rate of 57%, whereas the median survival time of patients in Grades II, III, and IV was 13.4, 6.8, and 3.4 months, respectively (p < 0.0001). Overall, 26 patients developed a second recurrence after reoperation. Seventeen patients underwent a second reoperation, whereas nine did not. Patients undergoing a second reoperation survived a median of 8.6 additional months versus 2.8 months for those who did not (p < 0.0001). This study concludes that reoperation for recurrent brain metastasis can prolong survival and improve quality of life. A second reoperation can also increase survival. Five factors influence survival: status of systemic disease, KPS score, time to recurrence, age, and type of primary tumor. The grading system using these five factors correlates with survival time. Reoperation should be approached with caution in Grade IV patients because of their poor prognosis.

Sarcoma metastatic to the brain: results of surgical treatment.

We report on 21 patients surgically treated for intraparenchymal brain metastasis from sarcoma, including six osteosarcomas, four leiomyosarcomas, three malignant fibrous histiocytomas, two alveolar soft-part sarcomas, two Ewing's bone sarcomas, one extraskeletal osteosarcoma, one extraskeletal Ewing's sarcoma, and two unclassified sarcomas. Median survival after craniotomy was 11.8 months. Patients with a preoperative Karnofsky performance score of > 70 survived for 15.7 versus 6.6 months for those with a Karnofsky performance score < or = 70. Patients. undergoing complete resection survived 14.0 versus 6.2 months for patients undergoing incomplete resection. Patients with evidence of lung metastases at the time of surgery survived 11.8 months, which was similar to the 10.5-month survival for patients with disease limited to the brain. The two patients with alveolar soft-part sarcoma are alive at 16 and 25 months after surgery. We conclude that surgery is effective in treating selected patients with sarcoma metastatic to the brain and that patients with metastasis from alveolar soft-part sarcoma may have a relatively good prognosis if they are surgically treated. The complete removal of all brain metastases and a Karnofsky performance score > 70 are associated with a favorable prognosis, whereas the presence of concurrent lung metastases is not a contraindication to surgery.

Surgical treatment of multiple brain metastases.

The authors conducted a retrospective review of the charts of 56 patients who underwent resection for multiple brain metastases. Of these, 30 had one or more lesions left unresected (Group A) and 26 underwent resection of all lesions (Group B). Twenty-six other patients with a single metastasis who underwent resection (Group C) were selected to match Group B by type of primary tumor, time from first diagnosis of cancer to diagnosis of brain metastases, and presence or absence of systemic cancer at the time of surgery. Statistical analysis indicated that Groups A and B were also homogeneous for these prognostic indicators. Median survival duration was 6 months for Group A, 14 months for Group B, and 14 months for Group C. There was a statistically significant difference in survival time between Groups A and B (p = 0.003) and Groups A and C (p = 0.012) but not between Groups B and C (p > 0.5). Brain metastasis recurred in 31% of patients in Group B and in 35% of those in Group C; this difference was not significant (p > 0.5). Symptoms improved after surgery in 65% of patients in Group A, 83% in Group B, and 84% in Group C. Symptoms worsened in 13% of patients in Group A, 6% in Group B, and 0% in Group C. Groups A, B, and C had complication rates per craniotomy of 8%, 9%, and 8%, and 30-day mortality rates of 3%, 4%, and 0%, respectively. Guidelines for management of patients with multiple brain metastases are discussed. The authors conclude that surgical removal of all lesions in selected patients with multiple brain metastases results in significantly increased survival time and gives a prognosis similar to that of patients undergoing surgery for a single metastasis.

Management of pituitary adenomas.

Pituitary adenomas arise from the anterior lobe of the pituitary gland and may secrete, in poorly controlled fashion, one or more of the hormones normally produced at this site, leading to specific endocrine syndromes. Pituitary tumors may also compress or invade adjacent structures, and the function of the normal pituitary may be compromised when a sellar mass exerts pressure on the stalk or on the gland itself. Advances in radiologic imaging and in microsurgical apparatus have made pituitary tumors more amenable to treatment, with surgery the treatment of choice. Radiotherapy is used mainly to control residual tumor after incomplete excision. Remission can be obtained in up to 90% of patients with microadenomas and in about 50% to 60% of those with macroadenomas.

Brain metastases in patients with well-differentiated thyroid carcinoma: study of 11 cases.

Eleven patients, three males and eight females, developed brain metastases from well-differentiated thyroid carcinoma 1 to 20 years after their original diagnosis. Two had brain metastases only and nine had metastases to the lungs and bones as well. Most patients died within a year of diagnosis of brain metastases. We conclude that brain metastasis from thyroid carcinoma carries a poor prognosis and that newer modalities of therapy may be needed.

Pilot study of PCNU and cranial radiation therapy in the treatment of patients with malignant gliomas.

A pilot study was performed administering PCNU with radiation therapy to treat patients with high-grade astrocytomas and to explore the toxic effects of this drug regimen. PCNU at an initial dose of 110 mg/m2 i.v. was administered to 14 patients within 4 weeks after completion of cranial irradiation. Courses were repeated every 6-8 weeks upon recovery from myelosuppression. Radiation therapy consisted of 5,000 rad to the whole brain followed by an additional 1,500 rad to the tumor site. Patients were followed by CT scan and neurologic examination. The median survival for the group was 80 weeks. Larger, randomized trials comparing PCNU to other nitrosoureas will be needed to assess its value as adjuvant therapy in patients with malignant gliomas. Myelosuppression, particularly, thrombocytopenia, was the main toxic effect in this study. Pulmonary infiltrates developed in 2 patients and was progressive and fatal in 1 patient after a total cumulative PCNU dose of 850 mg/m2. Hepatic dysfunction with hyperbilirubinemia also developed in 1 patient. PCNU can produce pulmonary and hepatic toxicity similar to that reported for other nitrosoureas. Regular monitoring of pulmonary and hepatic function tests should be performed during treatment with PCNU in future trials.

Metastatic Ewing's sarcoma to the brain: case report and review of treatment.

An unusual case of Ewing's sarcoma metastatic to the brain is presented. Neurosurgical intervention has a role in the treatment of patients with central nervous system metastasis of this rare tumor.

Pregnancy after treatment in patients with prolactinoma: operation versus bromocriptine.

Prolactinoma was diagnosed in 190 women of the same age range, among whom 88 were treated with transsphenoidal microadenectomy and 102 with bromocriptine. The purpose of this study was to compare the two groups according to classification of the adenomas by size and invasiveness, pregnancy rates, prolactin levels after pregnancy, sella turcica changes after pregnancy, and serum prolactin levels and radiologic changes in patients who were operated on but did not become pregnant or did not desire pregnancy. In the group with operation, 91% of patients who had microadenoma and 88% of those with diffuse adenoma conceived, but none who had invasive tumors did so. In the bromocriptine-treated group, among patients with no visible microadenoma or with microadenoma seen radiologically 56% conceived; among those with diffuse adenoma 66% conceived; no patients with invasive adenoma were in this group. In the group with operation, 21% had higher serum prolactin levels and amenorrhea after pregnancy, compared with 19% in the medical treatment group and 19% in the group with operation who did not conceive. Of all patients studied, radiologic changes in the pituitary fossa were seen in only one patient undergoing operation.

Ommaya reservoirs in 387 cancer patients: a 15-year experience.

We reviewed records of 387 patients with cancer who had Ommaya reservoirs placed between October 1967 and December 1982. Complications of reservoir placement were reported in 27 patients, including intracranial hemorrhage (5 patients) and reservoir malfunction (15 patients). In 15 of 19 patients with meningitis, the infection was linked to the reservoir. The organism most frequently implicated was Staphylococcus epidermidis. Seizures, leukoencephalopathy, and pericatheter necrosis were seen in 10 patients who had received intraventricular chemotherapy.

Phase I clinical trial of intralesional or intraventricular leukocyte interferon for intracranial malignancies.

Eight patients were treated with leukocyte interferon for a variety of neurological malignancies that had failed or recurred after conventional therapy. Three patients with malignant astrocytoma received intratumoral interferon in dosages up to 9 million units 3X/week, with total dosages of up to 160 million units. Interferon was administered intraventricularly in 4 patients with leptomeningeal metastases and one patient with multiple brain metastases. Dosages increased from 1 to 10 million units 3X/week, and total dosages of up to 113 million units were given intraventricularly. Acute side effects of fever, nausea, vomiting, and headache occurred almost exclusively with intraventricular injections, and these subsided after the initial injection. Fatigue, loss of appetite, weight loss, and hematologic toxicity developed a few weeks after onset of treatment, independent of the dose given. A modest tumor regression was seen on CT scans of one patient with a malignant astrocytoma, who was treated with interferon for 8 months. In all 4 patients with leptomeningeal metastases, the CSF became free of malignant cells for 6 to 10 weeks, while clinical improvement was less dramatic.

Cerebral radiation necrosis following treatment of extracranial malignancies.

Nine patients with cerebral radiation necrosis following radiation therapy for extracranial neoplasms were seen at MD Anderson Hospital between 1956 and 1982. The diagnosis was confirmed at autopsy in one case, by surgical intervention in six cases, and strongly suspected based upon CT scan findings and radiation records in two cases. The world literature is reviewed, and diagnostic criteria using the CT scan and radiation doses presented.

Intracarotid infusion of cis-diamminedichloroplatinum in the treatment of recurrent malignant brain tumors.

Thirty-five patients with malignant brain tumors (23 with primary brain tumors and 12 with brain metastases) progressing after cranial irradiation +/- chemotherapy received cisplatin, 60 to 120 mg/m2, into the internal carotid artery by a transfemoral approach. Courses of therapy were repeated every 4 weeks. Therapeutic evaluation was performed monthly using the CT scan of the brain and clinical neurologic examination. Thirty patients were evaluable for response. Of 20 evaluable patients with primary malignant brain tumors, 6 responded to therapy and 5 had stable disease. The median time to tumor progression for responding patients was 33 weeks, for stable patients 16 weeks, and 13 weeks for all patients. Five of 10 evaluable patients with brain metastases responded to intracarotid cisplatin, and 2 patients had stable disease. The estimated median time to progression for responding patients was 30+ weeks and 12+ weeks for patients with stable disease. Side effects included seizures in 5 courses, mental agitation and motor restlessness in 1, and transient hemiparesis in 7. One patient may have had a drug-related death, and one patient appeared to develop encephalopathy after treatment. Five patients had clinical deterioration in vision; in two patients it was bilateral. Intracarotid cisplatin has definite activity in patients with malignant primary brain tumors and in patients with brain metastases. The recommended starting dose for intracarotid cisplatin is 60 to 75 mg/m2. At this dose level side effects are uncommon, but includes the risk of neurologic and retinal toxicity.

Occult Cushing's disease presenting with acute psychosis.

A 37-year-old woman presented with acute psychosis and cognitive impairment. Skull x-ray showed an enlarged sella turcica with erosion of the floor. Endocrinologic workup suggested the diagnosis of Cushing's disease and hyperprolactinemia. She had no cushingoid feature, and the only physical sign was mild generalized obesity. She showed a paradoxic response to dexamethasone suppression, and underwent trans-sphenoidal resection of a pituitary macroadenoma. Electron microscopy showed the tumor to be a Crooke's cell adenoma. Results of immunohistochemical staining were positive only for ACTH and beta-endorphin. The neuropsychiatric manifestations resolved after surgery.

The effects of pregnancy on patients with hyperprolactinemia.

Seventy women with amenorrhea with or without galactorrhea associated with high serum prolactin levels and radiologic evidence of pituitary tumors were treated with transsphenoidal tumor resection. The prolactin level was measured in 29 patients before pregnancy, at 3 months post partum or cessation of lactation, and at 6-month intervals thereafter. The results were compared to those of 18 patients who had hyperprolactinemia but no demonstrable radiologic evidence of a pituitary tumor and who responded to bromocriptine and conceived. Our investigations showed that operation resulted in normalization of serum prolactin levels in 74% of patients. Forty of the 49 patients less than 36 years old conceived (80%). Five of 29 patients who were studied before and after operation as well as after delivery showed an increase in serum prolactin levels post partum and persistent amenorrhea suggesting recurrence. Six of the 18 patients who became pregnant after bromocriptine also showed a significant rise in serum prolactin levels above the treatment level. None of the patients in the two groups developed visual changes or symptoms or radiologic changes during pregnancy. These results showed that transsphenoidal operation has a high incidence of success, but some patients may show a rise of serum prolactin levels and persistent amenorrhea after pregnancy or passage of time, suggesting recurrence. Some patients who become pregnant after bromocriptine therapy may have further rises in prolactin greater than pretreatment levels. Follow-up of these patients is indicated.

A phase II trial of 2,5,-diaziridinyl 3,6-bis (carboethoxy amino) 1,4-benzoquinone (AZQ, NSC 182986) in recurrent primary brain tumors.

Forty-one patients with recurrent primary malignant brain tumors were treated with 2,5-diaziridinyl 3,6-bis (carboethoxyamino), 1,4-benzoquinone (AZQ) at an initial dose of 6-8 mg/m2/day X 5 days. Courses were repeated monthly upon recovery of myelosuppression. Six of 25 evaluable patients (24%) showed definite tumor regression, and 7 (28%) showed disease stability as determined by monthly CT scans and neurologic examination. For all patients receiving one course of AZQ, the response rate was 16% (6 of 37 patients) and the stable disease rate 19%. The estimated median time to tumor progression with AZQ was 54 weeks for the responding patients and 36 weeks for the stable patients. Toxicity consisted of myelosuppression, primarily thrombocytopenia, which was delayed and cumulative. Other toxicities were uncommon. Further clinical trials in patients with malignant primary brain tumors, including combination studies with other drugs, are indicated.

Phase-I trial of intracarotid BCNU and cisplatin in patients with malignant intracerebral tumors.

Eighteen patients with progressive or recurrent intracerebral malignant neoplasms after cranial radiation therapy were entered in a phase-I trial of intracarotid bis-chloroethylnitrosourea (BCNU) and cisplatin. Thirty-six courses of varying doses of BCNU and cisplatin were infused intraarterially via a percutaneous, trasfemoral approach. Courses were repeated every 4-6 weeks upon patients' recovery from toxicity. Intraarterial cisplatin or BCNU alone was administered if the blood counts were still subnormal. CT scans and neurologic examinations were performed monthly. Major toxic effects included ipsilateral retinal (amaurosis) in 4 patients and neurologic toxicity in 2 patients (minor focal seizure, reversible obtundation in one patient, and transient hemiparesis in one patient). One patient was infused by a catheter inserted into the supraclinoid internal carotid artery and had no further visual deterioration and no major side effects. Tumor regression was observed in patients previously treated with radiation and/or systemic chemotherapy, including 4 of 9 who had recurrent malignant gliomas, and 2 of 9 who had metastatic tumors. Recommended dose for phase-II trials is BCNU 100 mg/m2 and cisplatin 60 mg/m2 every 4-6 weeks. Retinal and neurologic toxicity are possible side effects.

Intracerebral penetration and tissue distribution of 2,5-diaziridinyl 3,6-bis(carboethoxyamino) 1,4-benzoquinone (AZQ, NSC-182986).

[14C]AZQ (2-4 mg/m2, 100-200 mCi) was administered at varying times to five patients undergoing surgical resection of intracerebral tumors. Plasma, cerebrospinal fluid (CSF), edematous brain, and tumor specimens were obtained during surgery and the concentration of AZQ was determined radiochemically and chromatographically. Total [14C]AZQ equivalent concentration in tumor for two patients was determined to be 47.5% and 85% of concurrent plasma concentration which was similar to that found in normal brain (60.4% and 75.5% respectively). Only 18-45% of the total radioactivity in tumor tissue and 30-56% in plasma were accounted for by unchanged AZQ. These findings suggest that AZQ may be metabolized to a certain extent. Tissue samples from various organs were obtained during autopsy in a patient who expired ten days after AZQ administration. The highest AZQ concentration was found in the liver, followed by the kidney. Comparable amounts were found in normal brain and brain tumor (22 ng/g vs. 31 ng/g respectively). These results indicate that AZQ penetrates readily into the normal brain and brain tumor with a tendency to persist.

A phase II trial of 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea (PCNU, NSC 95466) in recurrent malignant brain tumors.

Twenty-nine patients with recurrent primary malignant brain tumors were treated with 1-(2-chlorethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea (PCNU) at an initial dose of 110 mg/m2 with subsequent doses determined by the degree of delayed toxicity. The interval between treatments was usually weeks. Eleven of 25 evaluable patients (44%) showed definite improvement and ten (40%) showed disease stability as determined by sequential CT scans and neurologic examination. The estimated median time to tumor progression for all 25 patients treated with PCNU was 28 weeks, 37 weeks for the responding patients but only 20 weeks for patients with stable disease. Toxicity consisted of delayed myelosuppression which was cumulative and occurred mainly with the platelets. Gastrointestinal toxicity occurred in a minority of the patients. PCNU has definite activity in primary malignant brain tumors which appears to be comparable to that reported for BCNU alone, but with less reported gastrointestinal side effects. Further clinical trials in patients with primary malignant brain tumors are indicated.

Concentration of vinblastine in human intracerebral tumor and other tissues.

Uptake of vinblastine into human cerebrospinal fluid, intracerebral tumor and autopsy tissues was quantitated radiochemically after separating vinblastine from its metabolites by high pressure liquid chromatography. Only low concentrations of vinblastine were found in cerebrospinal fluid from a single patient. A second patient who received a tracer dose of radiolabelled vinblastine prior to surgical resection of an intracerebral tumor had slightly less radioactivity in tumor than in temporalis muscle, but more in tumor than in edematous brain surrounding the tumor. The radioactivity in tumor increased gradually and exceeded concurrent plasma radioactivity by 2 hr after drug administration. A third patient died 4 hr into a planned 24-hr infusion of radiolabeled vinblastine. Highest vinblastine concentrations were found in organs with high blood flow such as kidney and heart. Intermediate concentrations were found in liver and lung, and low concentrations were found in prostate, gastrointestinal tract, spleen, muscle, bladder, and hepatic and lymph node metastases. A fourth patient died one month after receiving radiolabeled vinblastine. Highest concentrations were in liver and next highest concentrations were in intracerebral tumor. Moderately high concentrations were found in pancreas, thyroid, lung, spleen, ovary, kidney, and kidney metastases. Lowest concentrations were found in omental metastases, heart, breast, and brain. Vinblastine concentration decreased with increasing distance into brain from the brain metastases. Thus, vinblastine was not selectively localized in tumors. The concentrations in tumor did not reflect the concentration in the organ in which the tumor was located. There was no indication that uptake into intracerebral tumor was impaired. Cerebrospinal fluid and brain concentrations of vinblastine did not give any indication of the concentration attainable in intracerebral tumor.