Defining the role of radiosurgery in the management of brain metastases.

The role of stereotactic radiosurgery in the management of recurrent and newly diagnosed brain metastases was evaluated prospectively. From December 1988 to March 1991, 58 lesions in 40 patients were treated with accelerator-based stereotactic radiosurgery. All patients were followed for a minimum of 6 months or to death. The primary purpose was to determine the impact of radiosurgery on local control and its subsequent effects on quality of life. An overall tumor control rate of 82% with a complete response rate of 43% were achieved. As anticipated, the response rate for smaller tumors was substantially better than that for larger tumors (78% for lesions < 2 cm3; 50% for lesions > or = 10 cm3). Although the overall in-field progression rate was 18.5%, only 1/23 (4%) complete responders subsequently recurred. The in-field failure rate is highly comparable with recently published surgical data. Progression outside the brain was noted in two-thirds of patients. One quarter of the deaths were neurologic. The median survival for this minimally selected patient population was 6.5 months. Stereotactic radiosurgery was also associated with improved quality of life as measured by Karnofsky score, neurologic function, and steroid dependence. Long-term steroid dependence was encountered in only four patients. We conclude that stereotactic radiosurgery can be used effectively in patients with brain metastases. In this series, a high tumor response rate was achieved which was associated with improved quality of life.

Early changes in tumor metabolism after treatment: the effects of stereotactic radiotherapy.

Four patients with intracranial neoplasms, two with malignant gliomas and two with brain metastases, were treated with stereotactic radiotherapy. Patients received between 15 and 27.5 Gray of photon irradiation to the central tumor target point; the 80% isodose line covered the periphery of the tumor as determined by contrast enhanced computed tomography. Patients underwent a sequence of three Positron Emission Tomographic scans using [18F]-fluorodeoxyglucose (PET-FDG)--a baseline scan the day before treatment, and follow-up scans 1 and 7 days after treatment. Ratios between the maximal tumor regional cerebral metabolic rate for glucose (rCMRGlu) (T*) and the contralateral remote white matter rCMRGlu (RW), that is, the glucose uptake ratio (T*/RW), were calculated. The percent change in ratios relative to each patient's baseline scan were calculated. Ratios increased 25% to 42% 1 day post-radiotherapy, then decreased to between 10% above and 12% below the baseline value 7 days post-radiotherapy. The T*/RW increased acutely after stereotactic radiotherapy in a fashion similar to that previously described following chemotherapy with a complex multi-drug regimen. A common metabolic pathway may underlie the increase in T*/RW after these different treatments.

Radiosurgery in the initial management of malignant gliomas: survival comparison with the RTOG recursive partitioning analysis. Radiation Therapy Oncology Group.

PURPOSE: To evaluate the impact of stereotactic radiosurgery on the survival of patients treated with malignant gliomas. METHODS AND MATERIALS: A total of 115 patients from three institutions (75 from the Joint Center for Radiation Therapy, 30 from the University of Wisconsin, and 10 from the University of Florida) were treated with a combination of surgery, external beam radiation therapy, and linac-based radiosurgery as part of similar institutional protocols from March 1988 through July 1993. Patients were stratified into six prognostic classes (classes 1-6) based on the recursive partitioning analysis of multiple prognostic factors previously reported by the Radiation Therapy Oncology Group. RESULTS: The actuarial 2-year and median survival for all patients analyzed was 45% and 96 weeks, respectively. In comparison to the results from a previously published analysis of 1578 patients entered on three Radiation Therapy Oncology Group external beam radiotherapy protocols from 1974 to 1989, those patients treated with radiosurgery had a significantly improved 2-year and median survival (p = 0.01) corresponding with a standardized mortality risk ratio of 0.51 [95% confidence interval (CI): 0.31, 0.85]. This improvement in survival was seen predominantly for the worse prognostic classes (classes 3-6). The 2-year survival for the radiosurgical patients compared with the previously reported patients was 81% vs. 76% for classes 1/2, 75% vs. 35% for class 3, 34% vs. 15% for class 4, and 21% vs. 6% for classes 5/6, respectively. Although Karnofsky performance status and prognostic class were significant on univariate analysis, only the Karnofsky score was a significant predictor of outcome on multivariate analysis. Median and 2-year survival for patients with a Karnofsky score > or = 70 was 106 weeks and 51%, respectively, as compared to 38 weeks and 0% for patients with a Karnofsky score < 70% (p = 0.001). CONCLUSIONS: The addition of radiosurgery to conventional treatment (surgery and external beam radiotherapy) of malignant gliomas appears to improve survival when compared to historical reports. These results should be interpreted with caution because the recursive partitioning model does not completely predict the prognosis of the patients treated in the present study. Although this study suggests that radiosurgery may prolong survival in patients with malignant gliomas, the role of radiosurgery in the management of these patients remains to be defined by a prospective randomized trial.

A multiinstitutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasis.

PURPOSE: Recent randomized trials of selected patients with single brain metastasis comparing resection followed by whole-brain radiotherapy (WBRT) to WBRT alone have shown a statistically significant survival advantage for surgery and WBRT. A multiinstitutional retrospective study was performed, which identified comparable patients who were treated with stereotactic radiosurgery (RS) and WBRT. METHODS AND MATERIALS: The RS databases of four institutions were reviewed to identify patients who met the following criteria: single-brain metastasis; no prior cranial surgery or WBRT; age > 18 years; surgically resectable lesion; Karnofsky Performance Status (KPS) > or = 70 at time of RS; nonradiosensitive histology. One hundred twenty-two patients were identified who met these criteria. Patients were categorized by: (a) status of the primary, (b) status of non-CNS metastasis, (c) age, (d) baseline KPS (from 70-100), (e) histology, (f) time from diagnosis of primary to the detection of the brain metastasis, (g) gender, and (h) tumor volume. RS was performed with a linear accelerator based technique (peripheral dose range was 10-27 Gy, median was 17 Gy). WBRT was performed in all but five patients who refused WBRT (dose range was 25-40 Gy, median was 37.5 Gy). RESULTS: The median follow-up for all patients was 123 weeks. The overall local control rate (defined as lack of progression in the RS volume) was 86%. Intracranial recurrence outside of the RS volume was seen in 27 patients (22%). The actuarial median survival from date of RS is 56 weeks, and the 1-year and 2-year actuarial survival rates are 53% and 30%. The median duration of functional independence (sustained KPS > or = 70) is 44 weeks. Nineteen of 77 deaths were attributed to CNS progression (25% of all deaths). Multivariate analysis revealed the following factors to be statistically significant predictors of survival: baseline KPS (p < .0001) and absence of other sites of metastasis (p = 0.008). CONCLUSION: The RS in conjunction with WBRT for single brain metastasis can produce substantial functional survival, especially in patients with good performance status and without extracranial metastasis. These results are comparable to recent randomized trials of resection and WBRT. The advantages of RS over surgery in terms of cost, hospitalization, morbidity, and wider applicability strongly suggest that a randomized trial to compare RS with surgery is warranted.

The use of a fiberoptic intracranial pressure monitor in clinical practice.

Four years of clinical experience with a fiberoptic intracranial pressure monitor are presented. One hundred forty patients were monitored, of whom 80 had increased intracranial pressure. Of the patients with nontraumatic intracerebral hematoma and subarachnoid hemorrhage, 100% had increased pressure. Forty-seven of 69 patients with head injuries had elevated pressure; of these, 28 had pressure significant enough to require therapy. Both the patients with head injuries and those with nontraumatic hemorrhage were more effectively treated by using the results of pressure monitoring to determine when therapy was required and to indicate the response of the patient to that therapy. Despite the evidence, monitoring of intracranial pressure is not routine due to a lack of acceptance and effectiveness. To overcome such problems, a system must meet the criteria of ease of insertion, reliability, and lack of complications. These criteria are fulfilled by the fiberoptic system presented.

Pain relief after hypophysectomy.

Thirteen series of patients who underwent surgical or chemical hypophysectomy for the relief of pain associated with cancer were reviewed. In 10 series, involving 334 patients with breast or prostate cancer, surgical hypophysectomy produced pain relief in 70% of the patients afflicted with either tumor, including some with no evidence of hormone dependence. These results were then compared with the results of chemical hypophysectomy. This procedure was performed in 3 series involving 533 patients, of whom 24% had cancer other than breast or prostate. Chemical hypophysectomy produced pain relief in over 75% of the patients, regardless of tumor type or hormonal dependence. The possible role of the pituitary, the hypothalamus, and endogenous opiates in mediating the pain relief associated with hypophysectomy was examined. The mechanism by which pain relief is achieved remains unclear, but there is significant evidence that this relief is not related directly to the expected fall in the levels of known pituitary hormones. Evidence is provided that pain relief is the result of a hypothalamic pain-suppressing capability triggered by hypophysectomy. On the basis of both clinical data and the mechanism of action, we conclude that surgical and chemical hypophysectomy are fundamentally similar procedures.

Effect of prophylactic methicillin on cerebrospinal fluid shunt infections in children.

This study retrospectively and prospectively analyzes uncomplicated, noninfected, primary ventriculoperitoneal shunting procedures and ventriculoperitoneal shunt revisions in children done at the University of Wisconsin Hospital from July 1973 to December 1979. We compared the infection rates between patients whose procedures were done without prophylactic antibiotics and those who received prophylactic single dose methicillin at the time of operation. Among 105 procedures done without prophylactic methicillin, there were 8 infections; 4 occurred after 73 primary shunt placements and 4 followed 32 shunt revisions. Among 66 procedures done with prophylactic methicillin, there were 3 infections; all followed primary shunt insertions. There was no infection after 32 shunt revisions in which prophylactic antibiotics were used.

Nonsurgical management of spontaneous intracerebral hematoma.

This report describes our experience with the use of osmotic diuretics, governed by continuous monitoring of intracranial pressure (ICP), as the primary treatment for 12 consecutive patients suffering from an acute, supratentorial intracerebral hematoma. In all cases the hematoma, as shown by computed tomographic scan, had a long axis of greater than 4.0 cm. ICP and cerebral perfusion pressure were successfully maintained within the assigned limits in all patients, and in none was surgical evacuation required. There was one death during the 6-month follow-up period. With appropriate weighting to differences in admission status, statistical comparison of the patient outcome in the present series with that reported by McKissock et al. suggests that ICP monitoring can improve the outcome of conservatively (and perhaps surgically) treated patients.

Treatment of pain of diffuse metastatic cancer by stereotactic chemical hypophysectomy: long term results and observations on mechanism of action.

Stereotactic instillation of absolute alcohol into the sella turcica for pituitary destruction was carried out in 29 patients divided into two groups. Seventeen with prostatic carcinoma underwent a total of 19 injections with 94% good to excellent results that persisted throughout the remainder of the patient's life-span. The longest survival was 9 months. Brief relapses did occur, but spontaneous remissions were the rule. A second group of mixed cancers contained 12 patients who received a total of 13 injections. Eleven patients had good to excellent results that persisted in all but 1 patient. The longest survival was 7 months. Hormonal levels and prolactin stimulation tests failed to show any correlation between hormonal changes and pain relief. Naloxone reversal of analgesia did not occur. There was no loss of cognitive function shown on psychological testing. Pathological studies showed destruction of the pituitary gland, which was subtotal in some patients despite good pain relief. All examinations showed that the pituitary stalk was destroyed. Patients who survived longer also showed degeneration of the supraoptic and paraventricular nuclei of the hypothalamus and the median eminence. All but 1 patient with pain relief exhibited a lack of antidiuretic hormone (ADH) production. Interpretation of the data indicates that ADH or its associated neurophysins act as central pain transmitters. The production of these transmitters is decreased or abolished by chemical hypophysectomy through the destruction of hypothalamic nuclei.

Treatment of increased intracranial pressure: a comparison of different hyperosmotic agents and the use of thiopental.

Long term intracranial pressure (ICP) monitoring was carried out in over 200 patients with various intracranial abnormalities; a fiberoptic epidural intracranial pressure monitor was used. Ninety of these patients had significantly elevated ICP or exhibited pressure waves requiring therapy. Initial therapy consisted of hyperventilation with a respirator and administration of hyperosmotic agents. Comparison studies utilizing 30% urea, 20% mannitol, and furosemide intravenously and 30% urea and 10% glycerol orally were randomly done. In 45 patients two or more of these agents were used at different times in the same patient for comparison of effectiveness. When equimolar amounts of intravenous urea and mannitol were used, similar effects on increased ICP were obtained. There was no significant reduction of increased ICP with the use of furosemide alone. No rebound effect was observed with either mannitol or urea. Orally, urea was more effective than glycerol in equimolar amounts. Again no rebound was observed. In 14 patients who required doses of hyperosmotic agents more frequently than every 4 hours, continuous infusion of thiopental was used in conjunction with the hyperosmotic agents to control pressure. This regimen resulted in good ICP control in 12 patients. A rational protocol for the medical management of increased ICP utilizing hyperosmotic agents and, in refractory cases, hyperosmotic agents plus thiopental has resulted in effective control of ICP in 96% of our patients throughout their course without the need to resort to decompressive surgery. (Neurosurgery, 5: 570--575, 1979).

The use of stereotaxic chemical hypophysectomy in the treatment of thalamic pain syndrome.

Three patients with neurological injuries consistent with cerebral stroke subsequently developed pain over portions of the body contralateral to the injured hemisphere. Stereotaxic chemical hypophysectomy was used in the management of this pain after other surgical procedures and medical management had failed to provide relief. Postoperatively, all patients were treated for hypopituitarism. All developed transient diabetes insipidus, and one patient developed transient right third nerve palsy. No other complications were encountered. All three patients experienced significant pain relief within 48 hours of the procedure. By the date of discharge, two of the three patients reported complete, and the third greater than 80% pain relief. At the initial follow-up visit all patients were essentially pain-free. These patients have now been followed for 58, 39 and 19 months, and remain free of their original pain. During this time the intravenous administration of naloxone has failed to reproduce the preoperative pain. Pituitary function testing 1 year or more following operation demonstrated that none of the patients had an endocrinologically complete hypophysectomy. Recovery from transient diabetes insipidus was not associated with return of the original pain. The mechanism of action of stereotaxic chemical hypophysectomy in the relief of pain related to thalamic lesions remains unknown. The observation that naloxone failed to reproduce the preoperative pain casts doubt on the theory that augmentation of endogenous opiate release is the primary mechanism. Additional observations suggest that pain relief after hypophysectomy may be more directly the result of stimulation of a hypothalamic pain-suppressing mechanism than due to the elimination of pituitary hormones.

Stereotactic radiosurgery for glioblastoma: a final report of 31 patients.

From February 1989 to December 1992, 31 patients who presented with an initial pathological diagnosis of glioblastoma multiforme underwent tumor debulking or biopsy, stereotactic radiosurgery, and standard radiation therapy as part of their primary treatment. Presenting characteristics in the 22 men and nine women included a median age of 57 years, Karnofsky Performance Scale score median of 80, and median tumor volume of 16.4 cm3. Stereotactic radiosurgery delivered a central dose of 15 to 35 Gy with the isocenter location, collimator size, and beam paths individualized by means of three-dimensional software developed at the University of Wisconsin. The peripheral isodose line varied from 40% to 90% with a median of 72.5% and a mode of 80%. The mean follow-up period was 12.84 months with a median of 9.5 months. Statistical analysis was performed using Kaplan-Meier analysis and log-rank comparison of risk factor groups. The parameters of age, initial Karnofsky Performance Scale score, and biopsy were significantly different in patient survival from debulking; but no difference was noted between single and multiple isocenters and patterns of steroid requirement. Radiographic recurrences were divided by location into the following categories: central (within central stereotactic radiosurgery dose), 0; peripheral (within 2 cm of central dose), 19; and distant (> 2 cm), 4. There is no evidence of recurrence in five surviving patients. Actuarial 12-month survival was 37%, with a median survival of 9.5 months. These values are similar to previous results for surgery and standard radiotherapy alone. The results suggest that the curative value of radiosurgery is significantly limited by peripheral recurrences.

[Streptococcus pneumoniae serotypes in children with acute pneumonia and pleurisy]. / Serotipy Streptococcus pneumoniae u detei, bol'nykh ostroi pnevmoniei i plevritom.

The study of pneumococci of different serotypes, isolated from patients with acute pneumonia and pleuritis and from healthy children was carried out. Among the pneumococcal serotypes causing pneumonia and pleuritis in children serotypes 1, 6, 19, 14 and 3 were most widely spread and constituted 62.3% of all isolated pneumococci. In young children cases of acute pneumonia and pleuritis were more often induced by serotypes 6 and 14 and in older children, by serotypes 1 and 3. In patients with uncomplicated pneumonia and pleuritis differences in the detected serotypes of pneumococci were observed, and the disease course differed in severity. Serotypes 14, 3 and 3 induced destructive processes in the lungs more often than other serotypes. Monitoring of the sensitivity of pneumococci to antibiotics showed that most of the strains retained high sensitivity to penicillin and ampicillin. In most cases the detected resistant pneumococcal strains belonged to serogroup 19.

[Radioisotopic diagnosis of Meckel's diverticulum in children]. / O radioizotopnoi diagnostike divertikula Mekkelia u detei.

The serial scintiphotography following intravenous injection of Tc99m-ertechnetate was used for examination of 50 children aged from 11 months to 14 years. The method is founded on the Tc99m-pertechnetate property of selective accumulation in the gastric mucous membrane and in Meckel's diverticulum when the latter contains the ectopic gastric mucous membrane. The inflamed diverticulum can accumulate the radionuclide, as well. Meckel's diverticulum was suspected in 7 children during examination; in 6 of them Meckel's diverticulum was found peroperatively, and in one case there was enterocyst of the ileum.

[Acute suppurative destructive pneumonias in children]. / Ostrye gnoinye destruktivnye pnevmonii u detei.

Their experience with the observation of 1112 children with acute purulent destructive pneumonias allowed the authors to considerably improve the method of complex curative-diagnostic measures which resulted in lower lethality among this critical contingent of patients and better remote results of their treatment.