Intestinal lipid esterification and aging in mice and rats

BACKGROUND AND PURPOSE: The risk of side effects of low activity (i.e. <20 mCi) Iodine-125I (125I) interstitial radiotherapy was analyzed in patients with low-grade gliomas. MATERIALS AND METHODS: Permanent (247 patients) or temporary 125I-implants (268 patients) were used with a median reference dose of 60 Gy and 100 Gy, respectively, which was calculated to the outer rim of the tumour. The mean dose rate for temporary implants was low (median, 10 cGy/h). Risk factors were obtained from the multivariate proportional-hazards model. RESULTS: Radiogenic complications occurred in 39/515 patients (28 patients with transient symptoms and 11 patients with progressive symptoms). The most important risk factor was the volume of the intratumoural 200 Gy isodose. Available experimental data have associated a high dose zone in this range with the size of the treatment induced radionecrosis. Rapid tumour shrinkage (decrease of the tumour volume > or =50%) within the first 6 months with subsequent centripetal movement of non-pathologic tissue into the high dose zone and a reimplantation were additional risk factors. Radiation injury after rapid tumour shrinkage could be better avoided with temporary implants. A 200 Gy isodose volume <4.5 ml corresponded to an estimated risk of radiogenic complications <3%. There was a steep increase of the risk beyond this limit. Translation of the 200 Gy isodose volume in terms of the treatment volume and the reference dose allows rational treatment planning. The estimated risk of a temporary implant with an applied reference dose of 60 Gy and a treatment volume <23 ml was <3%. CONCLUSIONS: The intratumoural necrotizing effect of a low activity 125I implant limits its application to small treatment volumes. Radiation injury outside the treatment volume can be better avoided with temporary implants in the case of rapid tumour shrinkage.     

Comparison of stereotactic radiosurgery and brachytherapy in the treatment of recurrent glioblastoma multiforme

The purpose of this study was to compare the efficacy of stereotactic radiosurgery (SRS) and brachytherapy in the treatment of recurrent glioblastoma multiforme (GBM). The patients had either progressive GBM or pathologically proven GBM at recurrence after previous treatment for a lower grade astrocytoma. Thirty-two patients were treated with interstitial brachytherapy, and 86 received treatment with stereotactic radiosurgery (SRS). The patient characteristics were similar in the two groups. Those patients treated with SRS had a median tumor volume of 10.1 cm3 and received a median peripheral tumor dose of 13 Gy. Patients treated with brachytherapy had a median tumor volume of 29 cm3. Median dose to the periphery of the tumor volume was 50 Gy delivered at a median dose rate of 43 cGy/hour. Twenty-one patients (24%) treated with SRS were alive, with a median follow-up of 17.5 months. Median actuarial survival, measured from the time of treatment for recurrence, for all patients treated with SRS was 10.2 months, with survivals of 12 and 24 months being 45 and 19%, respectively. A younger age and a smaller tumor volume were predictive of better outcome. The tumor dose, the interval from initial diagnosis, and the need for reoperation were not predictive of outcome after SRS. Five patients (16%) treated with brachytherapy were alive, with a median follow-up of 43.3 months. The median actuarial survival for all patients treated with brachytherapy was 11.5 months. Survivals of 12 and 24 months were 44 and 17%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlation of medical dosimetry quality indicators to the local tumor control in patients with prostate cancer treated with iodine-125 interstitial implants

The treatment of prostate cancer by 125I interstitial implants has been extensively studied with mixed results by one institution or another. A recent study from Hahnemann [Int. J. Radiat. Oncol., Biol., Phys. 21,955-960 (1991)] reported results that were extremely poor compared to those reported in an earlier study at Yale [Int. J. Radiat. Oncol., Biol., Phys. 14, 1153-1157 (1988)] or those in an Eastern Virginia Study [Cancer 63, 2415-2420 (1989)]; differences in 5-yr survival rates being more than a factor of 2. Such large discrepancies from institution to institution led us to a reexamination of the dosimetry. This study analyzed quantitatively three-dimensional dosimetric parameters of 110 prostate cancer patients treated with 125I interstitial implants. The study searched for "cutoff" values in each parameter that divided the patients into two groups with statistically significant differences in the local recurrence-free survival rates. A comparison of the three-dimensional isodose surfaces of patients with favorable values in all of the parameters to those patients with all unfavorable parameters show how these characteristics translated into poor dose coverage and much inhomogeneity within the implant even for cases that met the traditional criteria for adequacy (160 Gy to the tumor volume). Patients in the favorable group had 10-yr survival rates higher by a factor of up to 2 compared to those in the unfavorable group. The strong correlation of three-dimensional volume-dose parameters to the local control rate observed in this study further emphasizes how important it is to assess the three-dimensional dosimetric adequacy of interstitial implants before deciding on their clinical efficacy. If implants are performed with appropriate attention to dosimetry parameters, excellent clinical results are obtained. On the other hand, if dosimetry parameters are not correct, the implant results can be poor.     

Central nervous system lesions in liver transplant recipients: prospective assessment of indications for biopsy and implications for management

BACKGROUND: Precise diagnosis of central nervous system (CNS) lesions in liver transplant recipients remains problematic. Brain biopsies are often not feasible as a result of coagulopathy. We sought to determine whether selected clinical or radiologic characteristics can predict the likely etiology of CNS lesions in liver transplant recipients and thus obviate the need for diagnostic brain biopsies. METHODS: A 4-year prospective, observational, cohort study was conducted at liver transplant centers at four geographically diverse medical institutions. A total of 1730 consecutive liver transplant recipients were evaluated for CNS lesions; 60 patients with radiologically documented CNS lesions comprised the study sample. RESULTS: Vascular events (52%, 31/60), infections (181%, 11/60), immunosuppressive associated leukoencephalopathy (12%, 7/60), central pontine myelinolysis (8%, 5/60), and malignancy (3%, 2/60) were the predominant etiologies of CNS lesions. CNS lesions were most likely to occur within 30 days of transplantation (43%, 26/60); central pontine myelinolysis, subdural hematoma, acute infarcts, and Aspergillus brain abscesses were the predominant etiologies during this time. All brain abscesses were fungal; 73% (8/11) of these patients concurrently had documented extraneural (pulmonary) infection as a result of the same fungal pathogen. Thus, a diagnostic brain biopsy is not warranted in these patients. Patients on dialysis were more likely to have ischemic or infectious CNS lesions (P=0.03). Vascular events were more likely to occur in repeat transplant recipients (P=0.03). Twenty-five percent (15/60) of the CNS lesions occurred more than 1 year after transplantation; small vessel ischemic lesions, malignancy, or non-Aspergillus fungal brain abscesses accounted for all such lesions. CONCLUSIONS: A presumptive etiologic diagnosis can be established in a vast majority of CNS lesions in liver transplant recipients based on identifiable presentation that includes time of onset, unique risk factors, and neuroimaging characteristics. Empiric therapy of brain abscesses in liver transplant recipients should include antifungal and not antibacterial agents.     

A technique for accurate planning of stereotactic brain implants prior to head ring fixation

PURPOSE: A two-step procedure is described for accurate planning of stereotactic brain implants prior to head-ring fixation. METHODS AND MATERIALS: Approximately 2 weeks prior to implant a CT scan without the head ring is performed for treatment-planning purposes. An entry point and a reference point, both marked with barium and later tattooed, facilitate planning and permit correlation of the images with a later CT scan. A plan is generated using a conventional treatment-planning system to determine the number and activity of I-125 seeds required and the position of each catheter. I-125 seed anisotropy is taken into account by means of a modification to the treatment planning program. On the day of the implant a second CT scan is performed with the head ring affixed to the skull and with the same points marked as in the previous scan. The planned catheter coordinates are then mapped into the coordinate system of the second CT scan by means of a manual translational correction and a computer-calculated rotational correction derived from the reference point coordinates in the two scans. RESULTS: The rotational correction algorithm was verified experimentally in a Rando phantom before it was used clinically. For analysis of the results with individual patients a third CT scan is performed 1 day following the implant and is used for calculating the final dosimetry. CONCLUSION: The technique that is described has two important advantages: 1) the number and activity of seeds required can be accurately determined in advance; and 2) sufficient time is allowed to derive the best possible plan.     

The chemotherapy of adult primary brain tumors

Adult patients with primary malignant brain tumors are a heterogeneous group. Most patients will have high-grade astrocytomas and can be expected to obtain minimal benefit from current standard chemotherapy regimens. Intra-arterial chemotherapy, high-dose chemotherapy with autologous bone marrow rescue, and new chemotherapeutic agents designed to penetrate the blood-brain barrier have not resulted in significant advances to date. However, there are exciting new directions in the chemotherapy of high-grade astrocytomas which are entering clinical trials. Two potentially promising approaches include interstitial chemotherapy using surgically implanted polymers and the continuous infusion of combinations of active chemotherapeutic agents. Other therapeutic modalities such as radioactive seed implants, stereotactic radiosurgery, and gene therapy are also being evaluated. Hopefully, this intense activity by subspecialists with a wide range of interests and expertise will produce novel and effective treatments for the large number of patients with malignant astrocytomas. In contrast, patients with many of the less common neoplasms of the central nervous system may benefit from the addition of chemotherapy to their treatment. Primary germ cell tumors or lymphomas of the central nervous system are very sensitive to chemotherapy. The germ cell tumors respond to the cisplatin-containing regimens developed for testicular malignancies. The optimal chemotherapy for CNS lymphoma is not clear but exciting results have been reported with a combination of radiation, systemic and intrathecal methotrexate, and systemic cytosine arabinoside. Although limited, the available literature suggests that patients with anaplastic oligodendrogliomas may also benefit from chemotherapy at diagnosis or at relapse. Studies in children suggest a benefit for adjuvant chemotherapy and radiation therapy in poor risk patients with medulloblastomas although these findings have not been confirmed in adults. Finally, anecdotal reports suggest that chemotherapy may be useful in the very rare patient who presents with a pineal tumor or an ependymoma.     

Computer-assisted CT-guided stereotactic biopsy and brachytherapy of brain tumors

From March 1991 to September 1993, 26 patients (aged 4-78 years) with brain tumors (4 glioblastoma multiforme, 10 nonglioblastoma multiforme, 1 mixed oligoastrocytoma, 2 carniopharyngiomas, 2 meningiomas and 7 metastases) were treated with stereotactic techniques at the Centro Internacional de Restauración Neurológica, La Habana, Cuba. A total of 28 stereotactic surgical procedures were performed with no operative mortality; they included biopsies in all cases, 1 stereotactic microsurgical resection and 12 permanent implants of 192Ir, followed by external beam fractionated radiation therapy (40-60 Gy). The present paper shows that the combined use of a stereotactic approach, a comprehensive and reliable stereotactic dosimetric planning system, stereotactic brachytherapy with 192Ir and complementary percutaneous radiation treatment constitutes a promising strategy for brain tumor management.     

Secondary brain tumors in children treated for acute lymphoblastic leukemia at St Jude Children's Research Hospital

PURPOSE: To evaluate the incidence of and potential risk factors for second malignant neoplasms of the brain following treatment for childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: The study population consisted of 1,612 consecutively enrolled protocol patients treated on sequential institutional protocols for newly diagnosed ALL at St Jude Children's Research Hospital (SJCRH) between 1967 and 1988. The median follow-up duration is 15.9 years (range, 5.5 to 29.9 y). RESULTS: The cumulative incidence of brain tumors at 20 years is 1.39% (95% confidence interval [CI], 0.63% to 2.15%). Twenty-two brain tumors (10 high-grade gliomas, one low-grade glioma, and 11 meningiomas) were diagnosed among 21 patients after a median latency of 12.6 years (high-grade gliomas, 9.1 years; meningiomas, 19 years). Tumor type was linked to outcome, with patients who developed high-grade tumors doing poorly and those who developed low-grade tumors doing well. Risk factors for developing any secondary brain tumor included the presence of CNS leukemia at diagnosis, treatment on Total X therapy, and the use of cranial irradiation, which was dose-dependent. Age less than 6 years was associated with an increased risk of developing a high-grade glioma. CONCLUSION: This single-institution study, with a high rate of long-term data capture, demonstrated that brain tumors are a rare, late complication of therapy for ALL. We report many more low-grade tumors than others probably because of exhaustive long-term follow-up evaluation. The importance of limiting cranial radiation is underscored by the dose-dependent tumorigenic effect of radiation therapy seen in this study.     

The Baylor College of Medicine experience with gold seed implantation

Advances in imaging technology and implant technique have led to the resurgent interest and practice of brachytherapy for the treatment of prostate cancer. Brachytherapy is a form of radiation treatment in which radioactive sources are placed directly into the tumor; it offers the advantage of maximizing the radiation dose delivered to the tumor while sparing the adjacent normal tissue. Permanent implants have become an important component of radiation delivery. Interstitial gold radioisotope (Au-198) implants for prostate cancer were introduced at Baylor College of Medicine in 1965. The rationale for using Au-198, instead of the two most commonly used radioisotopes, Palladium-103 (Pd-103) and Iodine-125 (I-125), is discussed, and the Baylor implant technique is compared to that used in other centers. Retrospective review divides the patient population into pre-ultrasound versus post-ultrasound eras. Dosimetric calculation and disease control with the Au-198 seed implant for prostatic cancer are reviewed for the two different eras; toxicity is evaluated in the post-ultrasound era only. In the pre-ultrasound era, 510 patients were treated with pelvic lymph node sampling and gold seed insertion of the prostate followed by external beam radiation. In the post-ultrasound era, 54 patients were treated definitively with ultrasound-guided transperineal Au-198 implant followed by external beam irradiation. A small group of 30 patients in the post-ultrasound era were evaluated for the efficacy of Au-198 re-implantation for locally recurrent disease.     

Low risk of urinary incontinence following prostate brachytherapy in patients with a prior transurethral prostate resection

PURPOSE: To review post implant morbidity in patients with prior transurethral prostate resection (TURP). METHODS AND MATERIALS: Nineteen patients with stage T1-T2 prostatic carcinoma and prior TURP were treated with I-125 or Pd-103 implantation from 1991 through 1994. Follow-up ranged from 1 to 6 years (median: 3 years). The time from TURP to implantation ranged from 2 months to 15 years (median: 3 years). RESULTS: Only one patient developed mild urinary stress incontinence, 6 months following his I-125 implant. The actuarial freedom from permanent urinary incontinence at 3 years after implantation was 94%. No patient required urethral dilatation for urethral stricture. Eleven patients were sexually potent prior to implantation. At 3 years after treatment, all patients had maintained potency. CONCLUSION: In our experience, there has been remarkably little adverse sequelae following I-125 or Pd-103 implantation in patients with a prior history of TURP.     

Long-term access to cystic brain stem lesions using the Ommaya reservoir: technical case report

OBJECTIVE AND IMPORTANCE: Unresectable cystic brain stem lesions are often responsible for neurological dysfunction. Stereotactic aspiration of such lesions can lead to clinical improvement, but cyst recurrence is common and multiple aspirations may be necessary. CLINICAL PRESENTATION: Three children with unresectable cystic brain stem lesions were treated at the University of Florida. Two patients initially underwent stereotactic biopsy and cystic aspiration, both improving after cystic decompression. Both patients returned 3 months later with symptomatic cyst recurrences requiring further intervention. Six years after surgical resection of a posterior fossa medulloblastoma, the third patient presented with a dorsal midbrain cyst. INTERVENTION: All three patients had catheters placed into the cyst cavities under stereotactic guidance. A subcutaneous Ommaya reservoir was attached to the existing catheter. In the event of symptomatic cyst recurrence, the Ommaya reservoir can be tapped in an outpatient setting. CONCLUSION: Cystic decompression resulted in clinical improvement in all three children. Multiple aspirations were necessary in two patients for symptomatic cyst recurrences. The Ommaya reservoir allows for cyst aspiration in an outpatient setting and avoids multiple stereotactic manipulations. This system may also be used to instill radioisotopes or it may be converted to a cyst-peritoneal shunt if multiple aspirations fail to achieve cystic control.     

Analysis of the radiobiology of ytterbium-169 and iodine-125 permanent brachytherapy implants

Recently, Yb-169 has been considered as a potential replacement for I-125 and Pd-103 in permanent implants. In spite of the uncertainties in the parameters necessary for an accurate radiobiological modelling, the linear quadratic model can be useful in the comparative evaluation of the radiotherapeutic merit of similar implants. In order to find out if a Yb-169 permanent implant can be made biologically 'equivalent' to an I-125 implant, we studied the dependence of local control on the tumour cell radiosensitivity and on the balance between the rate of tumour cell killing and tumour cell proliferation, for rapidly and slowly proliferating tumours. The extrapolated response dose (ERD) has been calculated for tumour and late reacting normal tissue for both types of implants and the possible biological restrictions due to the normal tissue tolerance have been discussed. Our theoretical analysis is consistent with the clinical results published for I-125 permanent implants in prostate tumours and meningiomas. It predicts that Yb-169, which has only recently been used in human tumours, can provide comparable tumour control for permanent implants in slowly proliferating tumours with an initial dose rate of 13 cGy h-1. Control might be extended to rapidly proliferating tumours by increasing the initial dose rate within a range consistent with an acceptable level of normal tissue late reaction.     

Chronic lymphocytic leukemia presenting as pyogenic arthritis of the proximal interphalangeal joint

PURPOSE: To evaluate the results of 125I brachytherapy in colorectal cancers recurrent in the pelvis and paraortics. METHODS AND MATERIALS: From September 1989 to January 1997, 29 patients with colorectal adenocarcinoma recurrent in the pelvis or the paraortic nodes were treated intraoperatively with permanent 125iodine seed implantation at the James Cancer Center of The Ohio State University (OSU). All patients had undergone prior surgery; 72% had prior EBRT. The implanted residual tumor volume was microscopic in 38% and gross in 62%. The implanted area (median 25 cc) received a median minimal peripheral dose of 140 Gy to total decay. An omental pedicle was used to minimize irradiation of the bowel. Five patients received additional postimplant EBRT (20-50 Gy; median 30 Gy). RESULTS: The 1-, 2-, and 4-year actuarial local-regional control rates were 38%, 17%, and 17%, respectively, with a median time to local failure of 11 months (95% CI 10-12 months). The first manifestation of disease progression in 52 % of the patients was local-regional. In addition, 22 patients (75%) developed distant metastases. The 1-, 2-, and 4-year actuarial overall survival rates were 70%, 35%, and 21%, (median = 18 months; 95% CI: 14-22 months). Overall survival was better for patients smaller volume implants (p = 0.007), with a lower total activity implanted (p = 0.0003), with a smaller number of implanted sites (p = 0.004), and with microscopic residual disease (p = 0.01). Patients receiving additional EBRT also had a better prognosis (p = 0.005). Local tumor progression was the cause of death in 34% of the patients who have died at the time of this report and 56% died of distant metastases. Of the patients, 13 (45%) experienced 15 toxic events, including 3 patients (10%) with enteric fistula. Neuropathy was not observed. CONCLUSIONS: 125I brachytherapy can be successfully used for salvage in patients with recurrent colorectal cancer. Patients with isolated, microscopic, or minimal gross residual disease requiring small-volume implants and those receiving additional EBRT have a better prognosis. Postimplant EBRT is now routinely added, even for previously irradiated patients, in an attempt to improve local control. Compared to IOERT and IOHDR, 125I brachytherapy is not associated with clinical neuropathy, probably due to the continuous low dose rate irradiation delivered by the 125I seeds.     

Human basophil activation measured by CD63 expression and LTC4 release in IgE-mediated food allergy

BACKGROUNDS AND OBJECTIVES: We present the interim findings of our in-house protocol treating the tumor bed alone after lumpectomy with low-dose-rate (LDR) interstitial brachytherapy in selected patients with early-stage breast cancer treated with breast conserving therapy (BCT). METHODS: From 1 March 1993 through 1 January 1995, 50 women with early-stage breast cancer were entered into a protocol of tumor bed irradiation alone using an interstitial LDR implant. Patients were eligible if their tumor was an infiltrating ductal carcinoma < or =3 cm in diameter, surgical margins were clear by at least 2 mm, the tumor did not contain an extensive intraductal component, the axilla was surgically staged with < or =3 nodes involved with cancer, and a postoperative mammogram was performed. Implants were positioned using a template guide delivering 50 Gy over 96 hr to the lumpectomy bed plus a 1-2-cm margin. Local control, cosmetic outcome, and complications were assessed. RESULTS: Patients ranged in age from 40 to 84 years (median, 65). The median tumor size was 10 mm (range, 1-25). Seventeen of 50 patients (34%) had well-differentiated tumors, 22 (44%) had moderately differentiated tumors, and in 11 (22%) the tumor was poorly differentiated. Forty-five patients (90%) were node-negative while five (10%) had 1-3 positive nodes. A total of 23 (46%) patients were placed on tamoxifen and 3 (6%) received adjuvant systemic chemotherapy. No patient was lost to follow-up. The median follow-up for surviving patients is 47 months (range, 37-59). No patient has experienced a local, regional, or distant failure. Three patients have died at 19, 33, and 39 months after treatment. All were without clinical evidence of recurrent disease and all deaths were unrelated to treatment. Good-to-excellent cosmetic results have been observed in 49 of 50 patients (98%) (median cosmetic follow-up was 44 months with a range of 19-59). No patient has experienced significant sequelae related to their implant. CONCLUSIONS: Interim results with treatment of the tumor bed alone with an LDR interstitial implant appear promising. Long-term follow-up of these patients and additional studies will be necessary to establish the equivalence of this treatment approach compared to standard BCT.     

Studies on the method of the analysis of sapogenin. III. Coulometric titration of diosgenin (author''s transl)

Fifteen of 146 (10%) adult patients with non-Hodgkin's lymphoma showed clinical and pathologic evidence of involvement of the central nervous system (CNS): in 6 patients, the CNS lymphoma was present at the onset of disease, in 3 of them it was the only sign detected. In the remaining 9 cases, CNS involvement appeared during the course of systemic disease. In all cases symptoms related to infiltration of the CNS were associated with advanced disease (stage IV); bone marrow or bone involvement was found in 9 patients (60%). The histologic subtypes were mostly of high-grade malignancy according to the Kiel classification: immunoblastic (3), centroblastic (3), Burkitt type (2), lymphoblastic (1), LP immunocytoma in polymorphic variant (3), unclassifiable (3). The prominent signs and symptoms of CNS lymphoma are listed: the cranial nerve palsies are the most common finding. The principal means of detecting CNS involvement are discussed: cerebrospinal fluid cytology, brain scan and CAT scan were the most useful diagnostic procedures. The reported data allow identification of patients at high risk of CNS lymphoma: this includes histologies of high-grade malignancy, advanced stage of disease, and bone marrow or bone infiltration. Therefore, either intensive systemic chemotherapy or CNS prophylaxis are recommended for patients with high risk of CNS disease.     

Respiratory rate and pattern disturbances in acute brain stem infarction

Respiratory rates and patterns were studied in 23 patients with acute brain stem infarction using impedance pneumography. Autopsy was obtained in six of eight fatal cases. Pontine lesions were present in all patients, with coexistent infarction of midbrain in four and of medulla in nine. Respiratory rate and pattern abnormalities observed included Cheyne-Stokes respiration, Cheynb-Stokes variant pattern and tachypnea. Abnormalities of respiratory rate and pattern of varying duration were observed at some time in all patients. All patients in whom prominent Cheyne-Stokes respiration or tachypnea were observed had extensive bilateral pontine lesions involving both basal and tegmental portions. However, not all patients with large pontine infarcts had Cheyne-Stokes respiration or tachypnea. Cheyne-Stokes respiration was prominent in four patients (two fatal, two nonfatal). Cheyne-Stokes variant pattern was present frequently in four patients (one fatal, three nonfatal). Sustained tachypnea developed in five patients, four of whom died. In ten patients (one fatal, nine nonfatal), normal respiratory rate and pattern predominated with only rare or occasional apperance of Cheyne-Stokes respiration or Cheyne-Stokes variant pattern, especially during sleep. The types of respiratory rate and pattern abnormalities in acute brain stem infarction were not specifically related to the level of lesions, but rather to the size and bilaterality of the lesions. Respiratory alkalosis was present in varying degrees in most patients with either tachypnea or prominent CSR.     

Glial tumourettes (glial microtumours): their clinical and histopathological manifestations

This study represents our experience with eight cases (males: 4; females: 4; 13-47 years old, average age 28.5 years) of a "glial tumourette" (minute glioma), which measured less than 15 mm in diameter on an MRI. Four tumours were located in the frontal lobe, one in the rostrum of the corpus callosum, two in the midbrain, and one in the thalamus. The symptoms and signs lasted from two days to 15 months prior to diagnosis, and they consisted of epileptic seizures in five patients and increased intracranial pressure due to hydrocephalus resulting from aqueductal stenosis in three. All patients had a CT scan and an MRI as a part of their initial neuroimaging evaluations. While the CT findings failed to show the lesion in four patients, MRI demonstrated it in all cases. Five tumours were either totally or subtotally removed while the remaining three were biopsied. Histological examinations revealed six tumours to be low-grade gliomas (fibrillary astrocytoma: 4; oligoastrocytoma: 2) and two to be high-grade gliomas (anaplastic astrocytoma: 1; anaplastic oligodendroglioma: 1). Regarding adjuvant therapy, three patients received radiation and/or chemotherapy. One of the patients with midbrain fibrillary astrocytoma died of the disease 38 months after the operation, however, no evidence of progression in the remaining seven has been observed in the follow-up period ranging from five to 65 months after the operation (average: 25.4 months). The histogenesis of benign and malignant gliomas and the importance of surgical exploration in the management of such patients with minute intracerebral tumours are also discussed.     

Chemotherapy with the "8 in 1" protocol for malignant brain tumors in children: a population-based study in Finland

We evaluated the outcome of 68 children with malignant brain tumors treated with the "8 in 1" chemotherapy protocol in Finland from 1986 to 1993, comparing 5-year survival rates with those for a historical control group (from 1975 to 1985). For all malignant brain tumors, overall survival was 43% (vs 28% in the control group; P <0.05), and progression-free survival (PFS) was 43% (vs 23%; P <0.05). For medulloblastoma and primitive neuroectodermal tumor, survival was 63% (vs 35%; P <0.05), and the corresponding PFS was 59% (vs 35%; P = 0.15). For high-grade glioma, both the survival rate and the PFS were 27% (vs 17%; P = NS). Thus the outcome was significantly better for our "8 in 1" -treated patients than for the historical controls, especially among the children with primitive neuroectodermal tumor and medulloblastoma. In contrast, those with high-grade gliomas and brain stem tumors seem to have received little benefit; different, more effective treatments are needed for these patients.     

Diffuse brain stem gliomas. Are we improving outcome?

We reviewed our experience with diffuse brain stem glioma (dBSG) to evaluate whether any improvement of outcome had occurred in our patients over the years. Of the 24 children referred to our department with suspected dBSG from 1981 to 1997, 5 had a different final diagnosis based on the clinical course. Mean survival in the remainder was 16+/-9.8 months from diagnosis. Survival increased with a longer interval from onset of symptoms to diagnosis (12.9+/-9.0 months with an interval of 1-4 weeks; 19.50+/-10.8 months with a longer interval). Visual symptoms at presentation were associated with a poorer prognosis. Survival was better in the 3- to 5-year age group (at diagnosis). Overall, a trend toward a slight improvement in survival was seen over the years, which we presumptively attribute to the introduction of intensive chemotherapy for these patients. We suggest that chemotherapy may be important in the management of dBSG until a better modality is found.