Effects of rice bran on sensory and physico-chemical properties of emulsified pork meatballs.

Four kinds of bran, which are milled from important rice cultivators in Taiwan, have high contents of dietary fiber, fat and protein. The use of rice bran in Kung-wan, an emulsified pork meatball, was investigated. It was found that protein and fat contents, and white index of meatballs decreased as the amount of bran increased. A texture profile analysis (TPA) also indicated the hardness, gumminess and chewiness of the Kung-wan decreased. The sensory scores of taste, texture and overall acceptability of meatballs with less than 10% added bran showed no significant difference from those for meatballs without bran. However, the added amount of 15% enriched meatballs resulted in inferior sensory scores. The bran's particle size profoundly affected the sensory and physico-chemical properties of the meat products. Meatballs enriched with smaller bran particles possessed higher TPA indices and sensory scores than those added with larger ones. No significant differences in proximate composition, cooking yield, color and sensory quality were found among emulsified meatballs enriched with four different kinds of bran. Conclusively, the suitable amount of rice bran that should be added to emulsified pork meatballs was less than 10% and a smaller particle size would result in better quality.

Delta-L-(alpha-aminoadipoyl)-L-cysteinyl-D-valine synthetase: isolation of L-cysteinyl-D-valine, a 'shunt' product, and implications for the order of peptide bond formation.

L-Cysteinyl-D-valine was isolated from incubations of L-glutamate, L-cysteine and L-valine with delta-L-(alpha-aminoadipoyl)-L-cysteinyl-D-valine synthetase and identified by 1H NMR and electrospray ionization MS. This is entirely consistent with our prior proposal (Shiau, C.-Y., Baldwin, J.E., Byford, M.F., Sobey, W.J. and Schofield, C.J. (1995) FEBS Lett. 358, 97-100) that the alpha-peptide bond between cysteine and valine is formed before the delta-peptide bond between alpha-aminoadipate and cysteine. The inclusion of L-glutamate, an analogue of L-alpha-aminoadipate, did not result in a detectable amount of tripeptide product, but did increase apparent yields of L-cysteinyl-D-valine. Conceivably, formation of the L-glutamyladenylate stimulates synthesis of the cysteinyl-valine dipeptide indirectly via a conformational change in the enzyme.

delta-L-(alpha-aminoadipoyl)-L-cysteinyl-D-valine synthetase: the order of peptide bond formation and timing of the epimerisation reaction.

delta-L-(alpha-Aminoadipoyl)-L-cysteinyl-D-valine (ACV) synthetase catalyses the formation of the common precursor tripeptide of both the penicillin and cephalosporin antibiotics from the L-enantiomers of its constituent amino acids. Replacement of cysteine with L-O-methylserine in preparative-scale incubations led to the isolation of both L-O-methylserinyl-L-valine and L-O-methylserinyl-D-valine dipeptides. The dipeptides were characterized with the aid of authentic synthetic standards by both 1H NMR and electrospray ionization MS. A revised mechanism for ACV biosynthesis involving formation of the cysteinyl-valine peptide bond before the epimerisation of valine and subsequent condensation with the delta-carboxyl of L-alpha-aminoadipate is therefore proposed.

Relationship between pattern of enhancement and local control of brain metastases after radiosurgery.

PURPOSE: A desired goal in the radiosurgery (RS) of brain metastases is improved local control. Our earlier retrospective review identified pattern of enhancement on day-of-treatment imaging as a prognostic indicator for freedom from progression (FFP) after RS in 219 brain metastases. The current study was performed to corroborate this preliminary finding. METHODS AND MATERIALS: Records and imaging studies of patients treated with RS from 1991 to 1997 were reviewed. Each metastasis was categorized as homogeneously-, heterogeneously-, or ring-enhancing. Kaplan-Meier FFP was calculated from the date of RS to the first imaging showing tumor progression. Univariate and multivariate analyses were performed using Cox proportional hazard models stratified by primary site and type of RS (alone, as a boost, or for recurrence). RESULTS: Of 682 lesions in 258 patients, 518 lesions in 193 patients were evaluable. Pattern of enhancement was homogeneous in 59%, heterogeneous in 32%, and ring-like in 8% of lesions. One-year FFP probabilities for homogeneously-, heterogeneously-, and ring-enhancing lesions were 90% (95% confidence interval, 84-93%), 76% (64-84%), and 57% (35-74%), respectively. The p-value for pattern of enhancement from the stratified multivariate analysis was 0.019 adjusting for RS dose and treatment period (1991-1994 vs. 1995-1997). Similar results were achieved adjusting for tumor volume instead of RS dose. CONCLUSION: Pattern of enhancement is confirmed as a significant prognostic factor for FFP of brain metastases treated with RS, independent of dose and volume. A possible explanation is radioresistance of hypoxic tumor cells associated with necrotic regions, suggesting future investigations with radiosensitizers, hypoxic cell sensitizers, or strategies to improve tumor oxygenation.

Radiosurgery for brain metastases: relationship of dose and pattern of enhancement to local control.

PURPOSE: This study aimed to analyze dose, initial pattern of enhancement, and other factors associated with freedom from progression (FFP) of brain metastases after radiosurgery (RS). METHODS AND MATERIALS: All brain metastases treated with gamma-knife RS at the University of California, San Francisco, from 1991 to 1994 were reviewed. Evaluable lesions were those with follow-up magnetic resonance or computed tomographic imaging. Actuarial FFP was calculated using the Kaplan-Meier method, measuring FFP from the date of RS to the first imaging study showing tumor progression. Controlled lesions were censored at the time of the last imaging study. Multivariate analyses were performed using a stepwise Cox proportional hazards model. RESULTS: Of 261 lesions treated in 119 patients, 219 lesions in 100 patients were evaluable. Major histologies included adenocarcinoma (86 lesions), melanoma (77), renal cell carcinoma (21), and carcinoma not otherwise specified (17). The median prescribed RS dose was 18.5 Gy (range, 10-22) and the median tumor volume was 1.3 ml (range, 0.02-30.9). The initial pattern of contrast enhancement was homogeneous in 68% of lesions, heterogeneous in 12%, and ring-enhancing in 19%. The actuarial FFP was 82% at 6 months and 77% at 1 year for all lesions, and 93 and 90%, respectively, for 145 lesions receiving > or = 18 Gy. Multivariate analysis showed that longer FFP was significantly associated with higher prescribed RS dose, a homogeneous pattern of contrast enhancement, and a longer interval between primary diagnosis and RS. Adjusted for these factors, adenocarcinomas had longer FFP than melanomas. No significant differences in FFP were noted among lesions undergoing RS for recurrence after prior radiotherapy (119 lesions), RS alone as initial treatment (45), or RS boost (55). CONCLUSION: A minimum prescribed radiosurgical dose > or = 18 Gy yields excellent local control of brain metastases. The influence of pattern of enhancement on local control, a new finding in this retrospective analysis, needs to be confirmed.

Studies on quinazolines. 5. 2,3-dihydroimidazo[1,2-c]quinazoline derivatives: a novel class of potent and selective alpha 1-adrenoceptor antagonists and antihypertensive agents.

A series of 2-[(substituted phenylpiperazin-1-yl)methyl]- and 2-[(substituted phenylpiperidin-1-yl)methyl]-2,3-dihydroimidazo[1,2- c]quinazolin-5(6H)-ones or -5(6H)-thiones, and 3-[(substituted phenylpiperazin-1-yl)methyl]-2,3-dihydroimidazo[1,2-c]quinaz oline derivatives were synthesized, as conformationally restricted analogues of SGB-1534 and ketanserin, for evaluation as alpha-antagonists and antihypertensive agents. Most compounds containing a (substituted phenylipiperazinyl)methyl side chain displayed high binding affinity for alpha 1-adrenoceptor with no significant activity at alpha 2-sites. Compounds having a (substituted phenylpiperazinyl)methyl at the 3-position of 2,3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one ring system had a better activity than those with the same substituent at the 2-position. Structure-activity relationships for alpha 1-adrenoceptor affinity are presented and indicate that compounds with substitution at the ortho position on the benzene ring of the phenylpiperazine side chain moiety are more potent than those without substitution and/or substitutions at the 3- and 4-positions. Computer-assisted superimposition of SGB-1534 and 20b showed little structural correspondence between the quinazolinone and 2,3-dihydroimidazo[1,2-c]quinazoline nucleus, and specific interactions of these molecular fragments with the receptor protein appear unlikely. Antihypertensive activity was evaluated via intravenous administration of each compound to spontaneously hypertensive rats, and compounds (16a, 16b, 20b, and 28b) illustrated similar efficacy to SGB-1534 when assessed after 6 h. The pA2 value for 16a against phenylephedrine in rat aorta was much higher than that of prazosin. On the basis of alpha 1-adrenoceptor affinity/selectivity in vitro and duration of antihypertensive action in vivo, compounds 20b and 28b warrant further evaluation.

Radiosurgery as a treatment alternative for dural arteriovenous fistulas of the cavernous sinus.

PURPOSE: Radiosurgery is an effective treatment for cerebral arteriovenous malformations. We conducted the present study to investigate the feasibility and efficacy of gamma knife radiosurgery for dural arteriovenous fistulas (DAVFs) of the cavernous sinus. METHODS: Eighteen patients (12 women and six men; 29-75 years old [mean age, 55 years]) with DAVFs of the cavernous sinus (Barrow's type B:1, C:7, and D:10) treated by gamma knife radiosurgery were enrolled in the study. DAVFs were bilateral in six patients and unilateral in 12. Stereotactic X-ray angiography and MR imaging were performed for targeting the radiosurgery. Areas of arteriovenous communication targeted for irradiation were first outlined on the X-ray angiograms. The target regions were then transferred to and displayed on the MR images. Dose planning was based on findings on the integrated images. Prescribed maximum target doses were 22 to 38 Gy (mean, 28 Gy). The targets were covered by 50% to 90% isodose levels. Radiation doses to the surrounding optic apparatus were kept to less than 8 Gy. The patients were followed up with color Doppler sonography and MR imaging. When noninvasive imaging suggested obliteration, X-ray angiography was performed to verify the results. RESULTS: The DAVFs were totally obliterated in 12 (80%) of the 15 patients. In the other three, one was almost completely obliterated at 14 months and two were partially obliterated at 19 and 27 months, respectively, after radiosurgery. No complications or symptom worsening occurred during the follow-up period. CONCLUSION: Gamma knife radiosurgery is a feasible, effective, and safe treatment for DAVFs of the cavernous sinus. Integration of stereotactic X-ray angiography and MR imaging not only aids treatment efficacy but also protects the relevant vital structures, especially the optic apparatus, from the hazards of radiation.

Gamma knife radiosurgery for craniopharyngiomas.

OBJECT: The goal of this study was to elucidate the role of gamma knife radiosurgery (GKS) and adjuvant stereotactic procedures by assessing the outcome of 31 consecutive patients harboring craniopharyngiomas treated between March 1993 and December 1999. METHODS: There were 31 consecutive patients with craniopharyngiomas: 18 were men and 13 were women. The mean age was 32 years (range 3-69 years). The mean tumor volume was 9 cm3 (range 0.3-28 cm3). The prescription dose to the tumor margin varied from 9.5 to 16 Gy. The visual pathways received 8 Gy or less. Three patients underwent stereotactic aspiration to decompress the cystic component before GKS. The tumor response was classified by percentage reduction of tumor volume as calculated based on magnetic resonance imaging studies. Clinical outcome was evaluated according to improvement and dependence on replacement therapy. An initial postoperative volume increase with enlargement of a cystic component was found in three patients. They were treated by adjuvant stereotactic aspiration and/or Ommaya reservoir implantation. Tumor control was achieved in 87% of patients and 84% had fair to excellent clinical outcome in an average follow-up period of 36 months. Treatment failure due to uncontrolled tumor progression was seen in four patients at 26, 33, 49, and 55 months, respectively, after GKS. Only one patient was found to have a mildly restricted visual field; no additional endocrinological impairment or neurological deterioration could be attributed to the treatment. There was no treatment-related mortality. CONCLUSIONS: Multimodality management of patients with craniopharyngiomas seemed to provide a better quality of patient survival and greater long-term tumor control. It is suggested that GKS accompanied by adjuvant stereotactic procedures should be used as an alternative in treating recurrent or residual craniopharyngiomas if further microsurgical excision cannot promise a cure.

Gamma knife radiosurgery as a single treatment modality for large cerebral arteriovenous malformations.

OBJECT: A consecutive series of 240 patients with arteriovenous malformations (AVMs) treated by gamma knife radiosurgery (GKS) between March 1993 and March 1999 was evaluated to assess the efficacy and safety of radiosurgery for cerebral AVMs larger than 10 cm3 in volume. METHODS: Seventy-six patients (32%) had AVM nidus volumes of more than 10 cm3. During radiosurgery, targeting and delineation of AVM nidi were based on integrated stereotactic magnetic resonance (MR) imaging and x-ray angiography. The radiation treatment was performed using multiple small isocenters to improve conformity of the treatment volume. The mean dose inside the nidus was kept between 20 Gy and 24 Gy. The margin dose ranged between 15 to 18 Gy placed at the 55 to 60% isodose centers. Follow up ranged from 12 to 73 months. There was complete obliteration in 24 patients with an AVM volume of more than 10 cm3 and in 91 patients with an AVM volume of less than 10 cm3. The latency for complete obliteration in larger-volume AVMs was significantly longer. In Kaplan-Meier analysis, the complete obliteration rate in 40 months was 77% in AVMs with volumes between 10 to 15 cm3, as compared with 25% for AVMs with a volume of more than 15 cm3. In the latter, the obliteration rate had increased to 58% at 50 months. The follow-up MR images revealed that large-volume AVMs had higher incidences of postradiosurgical edema, petechiae, and hemorrhage. The bleeding rate before cure was 9.2% (seven of 76) for AVMs with a volume exceeding 10 cm3, and 1.8% (three of 164) for AVMs with a volume less than 10 cm3. Although focal edema was more frequently found in large AVMs, most of the cases were reversible. Permanent neurological complications were found in 3.9% (three of 76) of the patients with an AVM volume of more than 10 cm3, 3.8% (three of 80) of those with AVM volume of 3 to 10 cm3, and 2.4% (two of 84) of those with an AVM volume less than 3 cm3. These differences in complications rate were not significant. CONCLUSIONS: Recent improvement of radiosurgery in conjunction with stereotactic MR targeting and multiplanar dose planning has permitted the treatment of larger AVMs. It is suggested that gamma knife radiosurgery is effective for treating AVMs as large as 30 cm3 in volume with an acceptable risk.

Decreased fecundity among male lead workers.

AIMS: To investigate time to pregnancy (TTP) in male lead workers in order to determine the dose-response relation between blood lead and decreased fecundity. METHODS: A total of 163 currently employed married male lead battery workers were classified into five categories of exposure based on questionnaire information and annual individual blood lead measurement. Information pertaining to the TTP was collected using personal interviews with 133 men and their spouses, with 280 valid pregnancies. The fecundability ratios (FRs) were calculated with the Cox discrete proportional hazard regression technique to evaluate the effects of lead exposure. RESULTS: After other factors associated with TTP were controlled for, there was a dose-response relation between blood lead level and TTP. The measured FRs were 0.90 (95% CI 0.61 to 1.34), 0.72 (0.46 to 1.11), 0.52 (0.35 to 0.77), and 0.40 (0.27 to 0.59) for concurrent blood lead levels of <20, 20-29, 30-39, and > or =40 microg/dl, respectively. Paired self comparison was also performed for 41 couples that had pregnancies prior to lead exposure and pregnancies with male occupational lead exposure. The TTP was prolonged for 0.15 cycles by a 1 microg/dl increase in blood lead. CONCLUSIONS: These results corroborate the hypothesis that a raised blood lead level affects fecundity. A blood lead level of less than 40 microg/dl may still significantly prolong TTP.

Effect of starvation on free histidine and amino acids in white muscle of milkfish Chanos chanos.

Milkfish (Chanos chanos) decreased their body weight from 47 to 28 g over the 60-day period of starvation. Starvation also resulted in the reduction of muscle lipid and protein, and hepatosomatic index. The predominant free amino acid (FAA) in white muscle of milkfish was histidine, followed by taurine and glycine. In the first 25 days of starvation, no significant change in histidine was found. After 40 days of starvation, however, the histidine concentration was significantly decreased by 46%, and remained unchanged thereafter. As compared to control group fish, the 60-day-starved fish possessed only half the amount of histidine. Taurine and glycine, on the other hand, showed no significant changes throughout starvation. Taurine became the most predominant in the FAA pool after 40 days of starvation, and the concentration of 60-day-starved fish was two times higher than that of control group fish without starvation. The ratios of histidine, taurine, and glycine to total FAAs remained approximately the same although the individual contributions varied considerably to the total FAAs during starvation. The results of this study suggested that a good strategy would be to keep taurine and glycine in milkfish muscle at relatively high levels for physiological function as histidine decreased drastically for energy source under conditions of food deprivation.

Salvage surgery for recurrent nasopharyngeal carcinoma in anterior marginal miss after radiotherapy.

Nasopharyngeal carcinoma (NPC) is treated primarily by radiotherapy. Marginal miss after radiotherapy is a potential cause for treatment failure in NPC. Anterior marginal miss after irradiation results in recurrent tumors in the nasal cavity outside the nasopharynx. From 1991 to January 1997, 6 recurrent NPCs arising in the anterior marginal miss zone after radiotherapy were confirmed by pathologic and radiologic evaluation. One patient had infiltrating growth of the original NPC tumor into the anterior part of nasal septum, and the other 5 had microscopic extensions from the original NPC tumors into the nasal cavity that were beyond detection by endoscopy or CT scan. In some cases the tumors extended further to include the hard palate or the lacrimal sac. Medial maxillectomy and partial maxillectomy with or without resection of the hard palate were necessary to encompass the extent of the tumors. Surgical margins were free of cancer cells in 5 patients. No further treatment was given in these 5 patients. Another patient with tumor extending to the lacrimal sac received postoperative radiotherapy. Five of the 6 patients survived with no evidence of disease for 8 to 65 months. One patient had distant metastasis 14 months after surgery but was free from tumor at the primary site. Radical surgery can result in good and sustained local control for anterior marginal miss of NPC after radiotherapy.

Topoisomerase 2alpha plays a pivotal role in the tumor biology of stage IV thymic neoplasia.

BACKGROUND: Microsatellite studies in histologic types B3 and C thymic neoplasia detected gains on chromosome 17q, which contains the Her-2/neu and its juxtaposed topoisomerase 2alpha (T2alpha) genes. The study aimed to evaluate their impact on tumor biology and survival of advanced thymic neoplasia patients. METHODS: From 1991 to 2005, 36 consecutive stage IV thymic carcinoma patients were treated, 18 men and 18 women, aged 11 to 84 years. There were 22 thymic carcinoma, 13 type B3, and 1 type B2 thymoma. Patients received treatment consisting of surgical resection, combination chemotherapy with the CAP (cyclophosphamide, Adriamycin, cisplatin) regimen, or radiation therapy potentiated by high-dose weekly 5-fluorouracil infusion. Permutations of these 3 treatment modalities were prescribed as necessary. RESULTS: T2alpha gene amplification was detected in 4 of 14 thymic carcinoma and 1 of 15 type B3 thymoma. Three thymic carcinoma patients had Her-2/neu coamplification and these 3 patients had rapidly growing tumor and extensive disease at initial diagnosis. CAP was prescribed in 28 patients and 20 patients responded (response rate, 71.4%, 95% confidence interval [CI]: 52.8% to 85%); all responders overexpressed (> or = 10% nuclei positive) the T2alpha protein, whereas 4 nonresponders had very low expression. T2alpha overexpression predicts CAP response, and its absence predicts resistance (P = .001). Overall survival was significantly prolonged if the tumor was resectable (P = .001), of type B3 histology (P = .0039), and had no Her-2 gene amplification (P = .0081). CONCLUSION: T2alpha and Her-2/neu genes play a pivotal role in the tumor biology, CAP response, and survival of advanced thymic neoplasia patients.

Substrate specificity of L-delta-(alpha-aminoadipoyl)-L-cysteinyl-D-valine synthetase from Cephalosporium acremonium: demonstration of the structure of several unnatural tripeptide products.

Potential substrates for L-delta-(alpha-aminoadipoyl)-L-(cysteinyl)-D-valine (ACV) synthetase were initially identified using both the amino-acid-dependent ATP<-->pyrophosphate exchange reaction catalysed by the enzyme and the incorporation of 14C-radiolabelled cysteine and valine into potential peptide products. S-Carboxymethylcysteine was an effective substitute for alpha-aminoadipate and both allylglycine and vinylglycine could substitute for cysteine, indicating that the thiol group of cysteine is not essential for peptide formation. L-allo-Isoleucine but not L-isoleucine substituted effectively for valine. The structures of the presumed peptide products derived from these amino acids were confirmed by combined use of electrospray-ionization m.s. (e.s.m.s.) and 1H n.m.r. These results clearly indicate that, in common with other peptide synthetases, but in contrast with ribosomal peptide synthesis, ACV synthetase has a relatively broad substrate specificity.

L-delta-(alpha-Aminoadipoyl)-L-cysteinyl-D-valine synthetase: thioesterification of valine is not obligatory for peptide bond formation.

L-delta-(alpha-Aminoadipoyl)-L-cysteinyl-D-valine (ACV) synthetase is probably the simplest known peptide synthetase in terms of the number of reactions catalyzed. In the "thiol-template" proposal for nonribosomal peptide synthesis, a key step is transfer of aminoacyl groups derived from the substrates to enzyme-bound thiols prior to peptide bond formation. No incorporation of 18O was seen in AMP isolated from the reaction mixture when di[18O]valine was incubated with relatively large amounts of active synthetase and MgATP. We therefore utilized di[18O]valine as a substrate for the biosynthesis of the diastereomeric dipeptides L-O-(methylserinyl)-L-valine and L-O-(methylserinyl)-D-valine [Shiau, C.-Y., Baldwin, J. E., Byford, M. F., Sobey, W. J., & Schofield, C. J. (1995) FEBS Lett. 358, 97-100]. In the L-O-(methylserinyl)-L-valine product, no significant loss of 18O was observed. However, in the L-O-(methylserinyl)-D-valine product, a significant loss of one or both 18O labels was observed. Thus, both peptide bond formation and the epimerization of the valine residue can both occur before formation of any thioester bond to the valine carboxylate in the biosynthesis of these dipeptides. The usual qualitative test for thioesterification of substrates to the synthetase, lability of enzyme-bound radiolabeled amino acid to performic acid, proved inconclusive in our hands. These results require a new mechanism for the enzymic synthesis of L-O-(methylserinyl)-L-valine and L-O-(methylserinyl)-D-valine and imply that a revised mechanism for ACV synthesis is also required.

Early effects of Gamma Knife surgery on malignant and benign intracranial tumors.

To assess the early response of intracranial tumors to Gamma Knife surgery, we performed a prospective investigation of 42 patients treated by Gamma Knife surgery for different types of intracranial tumors. The clinical condition, tumor volume, treatment results and their temporal correlation with the irradiation were analyzed, based on MRI performed on the same MR scanner. Volume reduction in the tumors measured at the latest follow-up ranged from 0.2 to 100%. All except 1 malignant tumor showed decreasing size and improving peritumoral edema 1-7 months after radiosurgery. In 30 benign tumors, 13 showed either a decrease or no change in volume. However, an initial volume increase was observed in 17 tumors, with a maximum at 3-9 months, which subsequently regressed. In 2 meningioma patients, peritumoral edema increased and needed steroid treatment. Sequential PET-FDG imaging of the patients showed decreasing FDG uptake, indicating a decrease tumor in metabolism. The PET findings correlated well with the loss of contrast enhancement on MR images. In conclusion, intracranial tumors respond to Gamma Knife surgery from an early stage. Different tumors have different responses to radiosurgery. It is too early to offer a prognosis of long-term effects based on the limited material. However, sequential clinical, MR and PET follow-ups provide an excellent opportunity to investigate the evolving irradiation effects in vivo.

Prognostic factors and therapeutic options of radiotherapy in pediatric brain stem gliomas.

BACKGROUND: A retrospective analysis was made to clarify the relationship between prognosis, radiation dose and survival of brain stem gliomas. METHODS: From 1983 to 1995, 22 children with brain stem tumors were treated by radiotherapy in the Veterans General Hospital-Taipei. Twelve patients had pathology proof and the remainder were diagnosed by computerized tomography and/or magnetic resonance imaging. Seven patients had postoperative radiotherapy. Fifteen patients had radiotherapy as primary management, five of whom had adjuvant chemotherapy. All patients received 4000-7060 cGy, either in conventional daily or hyperfractionated twice daily radiotherapy. Survival from date of diagnosis was calculated by the Kaplan-Meier method. Univariate analyses and multivariate analyses were calculated by the log rank test and the Cox proportional hazard model, respectively. RESULTS: Most patients showed improvement following treatment. The overall 2-year survival rate was 55.5% with a median survival of 27.1 months. Two-year survival for patients with primary management of operation and radiotherapy (n = 7), radiotherapy alone (n = 10) and radiotherapy with adjuvant chemotherapy (n = 5) were 66.7, 50 and 53.3%, respectively. In univariate analysis, the study revealed that the growth pattern of tumors and the simultaneous presence of cranial neuropathy and long tract sign were significant prognostic factors (P = 0.017 and 0.036). A trend of better outcome with radiation dose > 6600 cGy and the hyperfractionation scheme was also noted in our study (P = 0.0573 and 0.0615). However, only the hyperfractionation scheme was also noted in our study (P = 0.0573 and 0.0615). However, only the hyperfractionation scheme showed significance in multivariate analyses (P = 0.0355). Survival was not significantly affected by age, gender or method of diagnosis. CONCLUSION: Radiotherapy appears to be an effective treatment modality of brain stem tumors. Patients with both cranial neuropathy and long tract signs had a poorer outcome. Hyperfractionated radiotherapy may give better local control and lead to better survival.

The effectiveness and factors related to treatment results of gamma knife radiosurgery for meningiomas.

A retrospective analysis was conducted on 80 patients with intracranial mengiomas treated with Gamma Knife radiosurgery between 1993 and 1996. The purpose was to analyze the efficacy of the treatment and to assess appropriate treatment parameters. The results were assessed by regular MR examinations, and tumor volume was measured at 6-month intervals. Mean follow-up duration was 21 months (range 6-45 months). 63 meningiomas were at the skull base and 17 were distal from the skull base. Tumor volumes <5 ml (n=38), 5-10 ml (n=21), 10-15 ml (n=14), 15-20 ml (n=7). The patients were divided into 3 groups according to the radiation dose. The groups were high-dose (peripheral dose 17-20 Gy, n=19), medium-dose (15-16 Gy, n=33) and low-dose (12-14 Gy, n=28) groups. A statistical method (Generalized Estimation Equation) was applied to compare treatment results in these groups with different doses and tumor volumes. The volume measurement at the latest follow-up showed 74% (59/80) meningiomas decreased in volume, 17% (14/80) had no tumor enlargement and 9% (7/80) had increased in volume. The increased volume was found more frequently in the patients with a short (6-12 months) follow-up period. In this series, the tumors had 32&percnt reduction in average tumor volume at 3 years after radiosurgery. At the range of 12-20 Gy peripheral dose (PD), radiosurgery was effective to reduce tumor volume 0.7% per month (p<0.05). However, higher doses had no significant difference on tumor volume reduction (p>0.05). On the other hand, high-dose (PD>17 Gy) treatment was associated with a higher risk of temporary tumor swelling and the development of adverse radiation effects (AREs). The AREs detected on MR images occurred in (25/80) 31% patients. Only 6/25 AREs were symptomatic and 2 had neurological sequelae. Peripheral doses, tumor volumes and their locations had significant impacts on the ARE (p<0. 05). In conclusion, a peripheral dose of 15-16 Gy may be adequate for meningiomas with small volumes (<5 ml). In larger tumors (>10 ml) a lower PD is preferred (12-14 Gy). To avoid initial tumor swelling and ARE, high-dose irradiation (PD>17 Gy) is not recommended for meningiomas larger than 5 ml.