Online courses for dentist continuing education: A new trend after the COVID-19 pandemic.

Background/purpose: Online courses have been widely used in all levels of education during the COVID-19 pandemic. This study explored the effectiveness of a dentist continuing education (DCE) course through the online devices in Taiwan. Materials and methods: The practicing dentists who participated in the online course of dental radiation technology for DCE offered by the Taiwan Dental Association (TWDA) in October 2022 and in March 2023 were enrolled in this study. The composition of participating dentists was confirmed by the public inquiry system and their learning effectiveness was evaluated by a questionnaire-based survey after the online DCE class. Results: All participating dentists (132 in October 2022 and 117 in March 2023) obtained consistent good learning outcomes in this online DCE course. Of these 249 dentists, there were 170 (68.27%) males and 79 (31.73%) females, 127 (51.00%) dental specialists and 122 (49.00%) general dentists, as well as 50 (20.08%) hospital dentists and 199 (79.92%) clinic dentists. The participation rates for this course of practicing dentists in non-municipalities (4.70%), counties (3.88%), eastern region (8.08%), and outlying islands (3.60%) were much higher than those in municipalities (0.79%), cities (1.16%), and the western region including the northern region (0.88%), central region (1.96%), and southern region (1.94%), respectively. Conclusion: The participating dentists express positive feedback on the online DCE courses, and the online DCE courses can reduce the urban-rural gap in dental education resources. The use of online DCE courses in dental education will be a future trend.

[Simultaneous determination of seven quaternary ammonium compounds in frozen food by ultra performance liquid chromatography-tandem mass spectrometry combined with modified QuEChERS method].

Quaternary ammonium compounds (QACs) are a class of cationic surfactants that can be used as the main active ingredient of disinfectants. The increased use of QACs is concerning as exposure from inhalation or ingestion to these compounds that has been associated with adverse effects on the reproductive and respiratory systems. Humans are exposed to QACs primarily by food consumption and inhalation of air. QAC residues pose significant threats to public health. Given the importance of assessing potential residue levels for QACs in food, therefore, a method was developed for the simultaneous detection of six common QACs and one emerging QAC (Ephemora) in frozen food by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) coupled with the modified QuEChERS method. The main factors governing the response, recovery, and sensitivity of the method, including extraction solvents, types and dosages of adsorbents, apparatus conditions, and mobile phases, were optimized in the course of sample pretreatment and instrument analysis. QAC residues in frozen food were extracted using 20 mL methanol-water (90∶10, containing 0.5% formic acid) for 20 min by the vortex shock method. The mixture was ultrasonicated for 10 min and centrifuged at 10000 r/min for 10 min. A 1-mL aliquot of the supernatant was transferred to a new tube and purified using 100 mg of PSA adsorbents. After mixing and centrifugation at 10000 r/min for 5 min, the purified solution was analyzed. Target analytes were separated on an ACQUITY UPLC BEH C8 chromatographic column (50 mm×2.1 mm, 1.7 µm) at a column temperature of 40 ℃ and a flow rate of 0.3 mL/min. The injection volume was 1 µL. Gradient elution was performed using methanol and 5 mmol/L ammonium acetate solution as the mobile phases. Multiple reaction monitoring (MRM) was conducted in the positive electrospray ionization (ESI+) mode. The matrix-matched external standard method was used to quantify seven QACs. The optimized chromatography-based method completely separated the seven analytes. Good linear relationships were obtained for the seven QACs in the range of 0.1-100.0 ng/mL. The correlation coefficient (r2) ranged from 0.9971 to 0.9983. The limits of detection and limits of quantification ranged from 0.5 to 1.0 µg/kg and 1.5 to 3.0 µg/kg, respectively. Accuracy and precision were determined by spiking salmon and chicken samples with 3.0, 10.0, and 100.0 µg/kg of analytes, in compliance with the current legislation, with six replicates per determination. The average recoveries of the seven QACs ranged from 65.4% to 101%. The relative standard deviations (RSDs) were between 0.64% and 16.8%. Matrix effects of the analytes were between -27.5% and 33.4% in salmon and chicken samples after purifying using PSA. The developed method was applied to the determination of seven QACs in rural samples. QACs were detected in only one sample; the level did not exceed European Food Safety Authority specified residue limit standards. The detection method has high sensitivity, good selectivity and stability, and the results are accurate and reliable. It is suitable for the simultaneous rapid determination of seven QAC residues in frozen food. The results provide valuable information for future risk assessment studies targeting this class of compounds.

Nonsyndromic supernumerary teeth in patients in National Taiwan University Children's hospital.

Background/purpose: A literature review reveals limited data for supernumerary teeth in Taiwan. This study aimed to analyze the characteristics of nonsyndromic supernumerary teeth in patients in the National Taiwan University Children's Hospital. Materials and methods: This retrospective study analyzed the nonsyndromic supernumerary teeth in 1280 patients (710 boys and 570 girls) based on examination of mainly panoramic radiographs and related radiographs. Chi-square test was used for trend analysis. Results: The incidence of nonsyndromic supernumerary teeth was 11.25% (179 supernumerary teeth in 144 of the 1280 patients). There was a male predominance (4.33: 1, P < 0.0001) for our 144 patients. Most supernumerary teeth were single (63.69%), conical-shaped (78.77%), and unerupted (77.09%). Supernumerary teeth also tended to be located in the premaxilla (93.85%), fully developed (51.40%), invertedly oriented (45.25%), sagittally located in a palatal/lingual position (67.60%), and adjacent to the root and root apex of permanent teeth (70.39%). The supernumerary teeth with a normal orientation (64.52%) had a high potential to erupt into the oral cavity, but the majority of the supernumerary teeth with a transverse orientation (97.22%) or an inverted orientation (100%) were unerupted. Conclusion: The nonsyndromic supernumerary teeth occur most commonly in male patients with a male to female ratio of 4.33: 1. The incidence of nonsyndromic supernumerary teeth in our 1280 patients is 11.25%, and the most frequent location of supernumerary teeth is the anterior maxillary region. More than three quarters of supernumerary teeth are conical-shaped or unerupted. Inverted supernumerary teeth are all embedded in the jawbones.

Novel predictive epigenetic signature for temozolomide in non-G-CIMP glioblastomas.

OBJECTIVE: To identify novel epigenetic signatures that could provide predictive information that is complementary to promoter methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) gene for predicting temozolomide (TMZ) response, among glioblastomas (GBMs) without glioma-CpGs island methylator phenotype (G-CIMP) METHODS: Different cohorts of primary non-G-CIMP GBMs with genome-wide DNA methylation microarray data were included for discovery and validation of a multimarker signature, combined using a RISK score model. Different statistical analyses and functional experiments were performed for clinical and biological validation. RESULTS: By employing discovery cohorts with radiotherapy (RT) and TMZ versus RT alone and a strict multistep selection strategy, we identified seven CpGs, each of which was significantly correlated with overall survival (OS) of non-G-CIMP GBMs with RT/TMZ, independent of age, MGMT promoter methylation status, and other identified CpGs. A RISK score signature of the 7 CpGs was developed and validated to distinguish non-G-CIMP GBMs with differential survival outcomes to RT/TMZ, but not to RT alone. The interaction analyses also showed differential outcomes to RT/TMZ versus RT alone within the RISK score-based subgroups. The signature could also improve the risk classification by age and MGMT promoter methylation status. Functional experiments showed that HSBP2 appeared to be epigenetically regulated by one identified CpG and was associated with TMZ resistance, but it was not associated with cell proliferation or apoptosis in GBM cell lines. The predictive value of the single CpG methylation of HSBP2 by pyrosequencing was observed in a local cohort of isocitrate dehydrogenase 1 (IDH1) R132H wild-type GBMs. CONCLUSIONS: This novel epigenetic signature might be a promising predictive (but not a general prognostic) biomarker and be helpful for refining the MGMT-based guiding approach to TMZ usage in non-G-CIMP GBMs.

Platinum sensitivity and CD133 expression as risk and prognostic predictors of central nervous system metastases in patients with epithelial ovarian cancer.

BACKGROUND: To characterize prognostic and risk factors of central nervous system (CNS) metastases in patients with epithelial ovarian cancer (EOC). METHODS: A retrospective analysis of Xijing Hospital electronic medical records was conducted to identify patients with pathologically confirmed EOC and CNS metastases. In addition to patient demographics, tumor pathology, treatment regimens, and clinical outcomes, we compared putative cancer stem cell marker CD133 expression patterns in primary and metastatic lesions as well as in recurrent EOC with and without CNS metastases. RESULTS: Among 1366 patients with EOC, metastatic CNS lesions were present in 29 (2.1%) cases. CD133 expression in primary tumor was the only independent risk factor for CNS metastases; whilst the extent of surgical resection of primary EOC and platinum resistance were two independent factors significantly associated with time to CNS metastases. Absence of CD133 expression in primary tumors was significantly associated with high platinum sensitivity in both patient groups with and without CNS metastases. Platinum resistance and CD133 cluster formation in CNS metastases were associated with decreased survival, while multimodal therapy including stereotactic radiosurgery (SRS) for CNS metastases was associated with increased survival following the diagnosis of CNS metastases. CONCLUSIONS: These data suggest that there exist a positive association between CD133 expression in primary EOC, platinum resistance and the increased risk of CNS metastases, as well as a less favorable prognosis of EOC. The absence of CD133 clusters and use of multimodal therapy including SRS could improve the outcome of metastatic lesions. Further investigation is warranted to elucidate the true nature of the association between platinum sensitivity, CD133 expression, and the risk and prognosis of CNS metastases from EOC.

The predictive but not prognostic value of MGMT promoter methylation status in elderly glioblastoma patients: a meta-analysis.

BACKGROUND: The clinical implication of O6-methylguanine-DNA methyltransferase (MGMT) promoter status is ill-defined in elderly glioblastoma patients. Here we report a meta-analysis to seek valid evidence for its clinical relevance in this subpopulation. METHODS: Literature were searched and reviewed in a systematic manner using the PubMed, EMBASE and Cochrane databases. Studies investigating the association between MGMT promoter status and survival data of elderly patients (≥65 years) were eligible for inclusion. RESULTS: Totally 16 studies were identified, with 13 studies included in the final analyses. The aggregate proportion of MGMT promoter methylation in elderly patients was 47% (95% confidence interval [CI]: 42-52%), which was similar to the value for younger patients. The analyses showed differential effects of MGMT status on overall survival (OS) of elderly patients according to assigned treatments: methylated vs. unmethylated: (1) temozolomide (TMZ)-containing therapies: hazard ratio [HR] 0.49, 95% CI 0.41-0.58; (2) TMZ-free therapies: HR 0.97, 95% CI 0.77-1.21. More importantly, a useful predictive value was observed by an interaction analysis: TMZ-containing therapies vs. RT alone: (1) methylated tumors: HR 0.48, 95% CI 0.36-0.65; (2) unmethylated tumors: HR 1.14; 95% CI 0.90-1.44. CONCLUSION: The meta-analysis reports an age-independent presence of MGMT promoter methylation. More importantly, the study encouraged routine testing of MGMT promoter status especially in elderly glioblastoma patients by indicating a direct linkage between biomarker test and individual treatment decision. Future studies are needed to justify the mandatory testing in younger patients.

A meta-analysis of temozolomide versus radiotherapy in elderly glioblastoma patients.

Temozolomide (TMZ) alone has been proposed as a promising alternative to radiotherapy (RT) in elderly glioblastoma (GBM) patients. We report a meta-analysis to systematically evaluate TMZ monotherapy in older GBM patients. A systematic literature search was performed using PubMed, EMBASE and the Cochrane database. Studies comparing TMZ versus RT in elderly patients (≥ 65 years) with newly diagnosed GBM were eligible for inclusion. Two randomized clinical trials (RCTs) and three comparative studies were included in the analyses, which revealed an overall survival (OS) advantage for TMZ compared with RT (HR [hazard ratio] 0.86, 95 % CI [confidence interval] 0.74-1.00). However, a sensitivity analysis of 2 RCTs only supported its non-inferiority (HR 0.91, 95 % CI 0.66-1.27). Most elderly patients tolerated TMZ despite an increased risk of grade 3-4 (G3-4) toxicities, especially hematological toxicities. The quality of life was similar between the groups. In the MGMT analysis, methylated tumors were associated with a longer OS than unmethylated tumors among elderly patients receiving TMZ monotherapy (HR 0.50, 95 % CI 0.35-0.70). Moreover, in patients with methylated tumors, TMZ was more beneficial than RT alone in improving OS (TMZ vs. RT: HR 0.66, 95 % CI 0.47-0.93) whereas the opposite was true for those with unmethylated tumors (HR 1.32, 95 % CI 1.00-1.76). Although the meta-analysis demonstrated the non-inferiority to RT in improving OS, TMZ alone was not a straightforward solution for elderly GBM patients because of an increased risk of G3-4 toxicities, especially hematological toxicities. MGMT testing might be helpful for determining individualized treatment.

Radiotherapy plus concurrent or sequential temozolomide for glioblastoma in the elderly: a meta-analysis.

BACKGROUND: Many physicians are reluctant to treat elderly glioblastoma (GBM) patients as aggressively as younger patients, which is not evidence based due to the absence of validated data from primary studies. We conducted a meta-analysis to provide valid evidence for the use of the aggressive combination of radiotherapy (RT) and temozolomide (TMZ) in elderly GBM patients. METHODS: A systematic literature search was conducted using the PubMed, EMBASE and Cochrane databases. Studies comparing combined RT/TMZ with RT alone in elderly patients (≥65 years) with newly diagnosed GBM were eligible for inclusion. RESULTS: No eligible randomized trials were identified. Alternatively, a meta-analysis of nonrandomized studies (NRSs) was performed, with 16 studies eligible for overall survival (OS) analysis and nine for progression-free survival (PFS) analysis. Combined RT/TMZ was shown to reduce the risk of death and progression in elderly GBM patients compared with RT alone (OS hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.48-0.72; PFS: HR 0.58, 95% CI 0.41-0.84). Evaluable patients were reported to tolerate combined treatment but certain toxicities, and especially hematological toxicities, were more frequently observed. Limited data on O6-methylguanine-DNA methyltransferase (MGMT) promoter status and quality of life were reported. CONCLUSION: The meta-analysis of NRSs provided level 2a evidence (Oxford Centre for Evidence-Based Medicine) that combined RT/TMZ conferred a clear survival benefit on a selection of elderly GBM patients who had a favorable prognosis (e.g., extensive resection, favorable KPS). Toxicities were more frequent but acceptable. Future randomized trials are warranted to justify a definitive conclusion.

The treatment of glioblastomas: a systematic update on clinical Phase III trials.

Glioblastomas (GBMs) are invariably associated with unavoidable tumor recurrence and overall poor prognosis. The present study is to summarize the results of clinical Phase III studies on GBMs over the past seven years. A systematic literature search was performed using major electronic databases and by screening meeting abstracts. Totally, 16 studies of patients with newly diagnosed GBMs, recurrent GBMs, and elderly patients with GBMs were selected for this review. Although the outcomes of the experimental therapies were not encouraging, these studies produced a considerable amount of potentially clinically relevant information. Such aspects as surgical outcomes, radiation schedules, temozolomide (TMZ) schedules, methylation status of the O6-methylguanine DNA methyltransferase (MGMT) gene, combination of therapies, novel drug delivery methods and use of targeted agents have come to light and are being addressed here. In addition, we discuss the existing controversies of (1) surgical studies, (2) evaluations of recurrence, (3) salvage treatment bias, and (4) studies on elderly patients.

A randomized controlled study comparing omeprazole and cimetidine for the prophylaxis of stress-related upper gastrointestinal bleeding in patients with intracerebral hemorrhage.

OBJECT: Patients with intracerebral hemorrhage (ICH) are at high risk for severe stress-related upper gastrointestinal (UGI) bleeding, which is predictive of higher mortality. The aim of this study was to evaluate the effectiveness of omeprazole and cimetidine compared with a placebo in the prevention and management of stress-related UGI bleeding in patients with ICH. METHODS: In a single-center, randomized, placebo-controlled study, 184 surgically treated patients with CT-proven ICH within 72 hours of ictus and negative results for gastric occult blood testing were included. Of these patients, 165 who were qualified upon further evaluation were randomized into 3 groups: 58 patients received 40 mg intravenous omeprazole every 12 hours, 54 patients received 300 mg intravenous cimetidine every 6 hours, and 53 patients received a placebo. Patients whose gastric occult blood tests were positive at admission (n = 70) and during/after the prophylaxis procedure (n = 48) were treated with high-dose omeprazole at 80 mg bolus plus 8 mg/hr infusion for 3 days, followed by 40 mg intravenous omeprazole every 12 hours for 7 days. RESULTS: Of the 165 assessable patients, stress-related UGI bleeding occurred in 9 (15.5%) in the omeprazole group compared with 15 patients (27.8%) in the cimetidine group and 24 patients (45.3%) in the placebo group (p = 0.003). The occurrence of UGI bleeding was significantly related to death (p = 0.022). Nosocomial pneumonia occurred in 14 patients (24.1%) receiving omeprazole, 12 (22.2%) receiving cimetidine, and 8 (15.1%) receiving placebo (p > 0.05). In patients with UGI bleeding in which high-dose omeprazole was initiated, UGI bleeding arrested within the first 3 days in 103 patients (87.3%). CONCLUSIONS: Omeprazole significantly reduced the morbidity of stress-related UGI bleeding in patients with ICH due to its effective prophylactic effect without increasing the risk of nosocomial pneumonia, but it did not reduce the 1-month mortality or ICU stay. Further evaluation of high-dose omeprazole as the drug of choice for patients presenting with UGI bleeding is warranted. Clinical trial registration no.: ChiCTR-TRC-12001871, registered at the Chinese clinical trial registry (http://www.chictr.org/en/proj/show.aspx?proj=2384).

Gypenosides improve cognitive impairment induced by chronic cerebral hypoperfusion in rats by suppressing oxidative stress and astrocytic activation.

Gypenosides (GP), the saponin extract derived from the Gynostemma pentaphyllum Makino, a widely reputed medicinal plant in China, has been reported to have some neuroprotective effects. We used a rat model of chronic cerebral hypoperfusion to investigate the protective effects of GP on the cortex and hippocampal CA1 region and the underlying mechanisms for its inhibition of cognitive decline. Daily doses of 100 and 200 mg/kg GP were orally administered to adult male Sprague-Dawley rats for 61 days after inducing cerebral hypoperfusion experimentally, and spatial learning and memory were assessed using the Morris water maze. Antioxidative capability was measured biochemically. The levels of lipid peroxidation and oxidative DNA damage were assessed by immunohistochemical staining for 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine, respectively. Activated astrocytes were assessed by immunohistochemical staining and western blotting with GFAP antibodies. Rats receiving 200 mg/kg GP had better spatial learning and memory than saline-treated rats. GP 200 mg/kg/day were found to markedly enhance antioxidant abilities, decrease lipid peroxide products and oxidative DNA damage, and reduce the activation of inflammatory astrocytes. However, GP 100 mg/kg had no significant effects. GP may have therapeutic potential for the treatment of dementia induced by chronic cerebral hypoperfusion and further evaluation is warranted.

The validation of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) in pre-operative patients with brain tumor in China.

BACKGROUND: Health related quality of life (HRQOL) has increasingly emphasized on cancer patients. The psychometric properties of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30, version 3.0) in brain tumor patients wasn't proven, and there was no baseline HRQOL in brain tumor patients prior to surgery. METHODS: The questionnaire EORTC QLQ-C30 (version 3.0) was administered at three time points: T1, the first or the second day that patients were hospitalized after the brain tumor suspected or diagnosed by MRI or CT; T2, 1 to 2 days after T1, (T1 and T2 were both before surgery); T3, the day before discharge. Clinical variables included disease histologic types, cognitive function, and Karnofsky Performance Status. RESULTS: Cronbach's alpha coefficients for multi-item scales were greater than .70 and multitrait scaling analysis showed that most of the item-scale correlation coefficients met the standards of convergent and discriminant validity, except for the cognitive functioning scale. All scales and items exhibited construct validity. Score changes over peri-operation were observed in physical and role functioning scales. Compared with mixed cancer patients assessed after surgery but before adjuvant treatment, brain tumor patients assessed pre-surgery presented better function and fewer symptoms. CONCLUSIONS: The standard Chinese version of the EORTC QLQ-C30 was overall a valid instrument to assess HRQOL in brain tumor patients in China. The baseline HRQOL in brain tumor patients pre-surgery was better than that in mixed cancer patients post-surgery. Future study should modify cognitive functioning scale and examine test-retest reliability and response validity.

Hemorrhagic pituitary macroadenoma: characteristics, endoscopic endonasal transsphenoidal surgery, and outcomes.

PURPOSE: This study aims to assess the effect of endoscopic endonasal transsphenoidal surgery (EETSS) of hemorrhagic pituitary macroadenoma (HPMA). PATIENTS AND METHODS: We retrospectively reviewed 52 cases with HPMA collected from the Xijing Hospital from April 1995 to April 2009. There were 39 males and 13 females, ranging in age from 18 to 79 years (average 51.6 years). Patients presented with headache or acute ophthalmological symptoms after adenoma hemorrhage. Computed tomography (CT) scan and magnetic resonance imaging (MRI) showed pituitary macroadenoma with hemorrhage in all cases. Twenty-eight adenomas showed marked suprasellar extension, 19 showed moderate extension, and another 5 showed slight extension. All patients were promptly treated by emergency EETSS, usually within 24 h after hospitalization. RESULTS: Total removal of tumor was achieved in 46 cases (88.5%), and subtotal removal in 6 cases (11.5%). Postoperative radiotherapy and reoperation of the tumor were required in five patients with either residual or relapsed tumors. Follow-up ranged from 8 to 93 months (mean 41.6 months) for 43 cases. Visual acuity and visual field recovery and improvement was recorded in 92.1% and 94.3% of patients who had preoperative visual symptoms, respectively. CONCLUSIONS: The majority of macroadenomas are hemorrhagic, and they often occur in middle-aged, male subjects. Detection by imaging in the setting of pituitary apoplexy accurately predicts the nature of the apoplectic process and helps to guide the type and timing of surgery. Early EETSS is the most effective therapy and significantly improves visual outcomes and systemic conditions.

Global histone modification patterns as prognostic markers to classify glioma patients.

BACKGROUND: An altered pattern of epigenetic modifications is central to the development and progression of various tumors. We studied epigenetic changes involving multiple modifications of histones to better predict prognosis of glioma patients. METHODS: Immunohistochemistry was done to investigate global histone modification expression of histone 3 lysine 4 dimethylation (H3K4diMe), histone 4 arginine 3 monomethylation (H4R3monoMe), histone 4 lysine 20 trimethylation (H4K20triMe), and acetylation of histone 3 lysine 9 (H3K9Ac), histone 3 lysine 18 (H3K18Ac), histone 4 lysine 12 (H4K12Ac), and histone 4 lysine 16 (H4K16Ac) in resected tumor samples of 230 glioma patients. Data were analyzed using a recursive partitioning analysis (RPA). RESULTS: RPA classified the patients into 10 distinct prognostic groups based on WHO grade, histology, and histone modifications: H3K9Ac (<88% or ≥88% tumor cells), H3K4diMe (<64% or ≥64% tumor cells), H3K18Ac (<74% or ≥74% tumor cells), and H4K20triMe (<75% or ≥75% tumor cells). The 10 groups were associated with significantly different progression-free (P < 0.0001) and overall survival (P < 0.0001). Cox proportional hazards models including age, sex, WHO grade, histology, extent of tumor resection, Karnofsky performance status score, and RPA groups retained age and RPA groups as the sole independent factors significantly influencing overall survival. For progression-free survival, RPA grouping was the only independent prognostic factor. CONCLUSIONS: Multiple histone modifications seem to have prognostic relevance in glioma. IMPACT: Further evaluation of histone modifications as prognostic markers of treatment and predictors of chemotherapy response using histone deacetylase inhibitors is warranted.

Health-related quality of life in glioma patients in China.

BACKGROUND: Health-related quality of life (HRQOL) has been increasingly emphasized in cancer patients. There are no reports comparing baseline HRQOL of different subgroups of glioma patients prior to surgery. METHODS: HRQOL assessments by the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30, version 3.0), the Mini-Mental State Examination and Karnofsky Performance Status were obtained from glioma patients prior to surgery. RESULTS: Ninety-two pathologically confirmed glioma patients were recruited. There were 84.8% patients with emotional impairment, 75% with social and cognitive impairment, 70.7% with physical impairment, and 50% with role impairment. Eighty-two percent of patients reported fatigue symptoms, 72.8% reported pain, 50% reported appetite loss, 39.1% reported insomnia, and 36.9% reported nausea/vomiting, whereas other symptoms (dyspnea, diarrhea, constipation) in the QLQ-C30 were reported by fewer than 30% of patients. Fatigue and pain symptoms and all "functioning" scales were strongly correlated with global health status/quality of life (QoL). Fatigue was strongly related to all functioning scales, pain, appetite loss, and global health status/QoL. No difference in baseline HRQOL prior to surgery was reported between females and males, among different lesion locations, or between normal- and abnormal-cognition subgroups of glioma patients. Age, KPS, WHO grade, and tumor recurrence significantly affected HRQOL in glioma patients. CONCLUSIONS: These data provided the baseline HRQOL in glioma patients prior to surgery in China. Most pre-surgery glioma patients indicated emotional, social, cognitive, physical, and role impairment. Fatigue, pain, appetite loss, insomnia, and nausea/vomiting were common in these patients. The fatigue and pain symptoms and all types of functioning strongly affected global health status/QoL. Old age, worse performance status, WHO grade IV and tumor recurrence had deleterious effects on HRQOL.

Quantitative detection of multiple gene promoter hypermethylation in tumor tissue, serum, and cerebrospinal fluid predicts prognosis of malignant gliomas.

Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the malignant transformation in gliomas. We hypothesized that quantitative analysis of methylated genes will provide prognostic values in malignant glioma patients. We used an immunocapturing approach followed by real-time polymerase chain reaction analysis to detect altered patterns of promoter methylation in O-6-methylguanine-DNA methyltransferase (MGMT), p16INK4a, tissue inhibitor of metalloproteinase-3 (TIMP-3), and thrombospondin 1 (THBS1). The tumor tissue and paired serum as well as cerebrospinal fluid (CSF) from 66 patients with malignant gliomas were studied. Serum and CSF from 20 age-matched noncancer individuals were used as control. Promoter hypermethylation in MGMT, p16INK4a, TIMP-3, and THBS1 was detected at high frequencies in tumor tissue, serum, and CSF. None of the control serum or CSF showed aberrant methylation. Hypermethylation in serum and CSF DNA was all accompanied with methylation in the corresponding tumor tissues with 100% specificity. Highly elevated MGMT, p16INK4a, and THBS1 methylation levels in gliomas serum were the sole independent factors predicting inferior overall survival in this cohort. For progression-free survival, hypermethylation of MGMT and THBS1 in CSF were the independent prognostic factors. Multiple gene promoter hypermethylation analysis appears to be promising as a prognostic factor in glioma and as a mini-invasive tumor marker in serum and/or CSF DNA. Evaluation of these changes may help in selecting glioma patients for optimal adjuvant treatments and modifying chemotherapy.

Controversies concerning the application of brachytherapy in central nervous system tumors.

INTRODUCTION: Brachytherapy (BRT) is defined as a therapy technique where a radioactive source is placed a short distance from or within the tumor being treated. Much expectation has been placed on its efficacy to improve the outcome for patients with central nervous system (CNS) tumors due to the initial promising results from single institution retrospective studies. However, these optimistic findings have been highly debated since the selection criteria itself is preferable to other therapeutic modalities. The fact that BRT demonstrated no significant survival advantage in two prospective studies, together with the emerging role of stereotactic convergence therapy as a promising alternative, has further decreased the enthusiasm for BRT. Despite all the negative aspects, BRT continues to be conducted for the management of CNS tumors including gliomas, meningiomas and brain metastases. MATERIAL AND METHODS: As many controversies have been aroused concerning the experience and future application of BRT, this article reviews the existing heterogeneities in terms of implants choice, optimal dose rate, targeting volume, timing of BRT, patients selection, substantial efficacy, BRT in comparison with stereotactic convergence therapy techniques and BRT in combination with other treatment modalities (data were identified by Pubmed searches). RESULTS AND CONCLUSION: Though it is inconvincible to argue for the routine use of BRT, BRT may provide a choice for patients with large recurrent or inoperable deep-seated tumors, especially with the Glia-site technique. Radiotherapies including BRT may hold more promise if biologic mechanisms of radiation could be better understand and biologic modifications could be added in clinical trials.

Limited role of surgery in the management of primary central nervous system lymphoma (Review).

Primary central nervous system lymphoma (PCNSL) is a nervous-system-seeking extranodal non-Hodgkin's lymphoma whose incidence has increased in both immunocompromised and immunocompetent patients. Corticosteroids are used for symptomatic management but can interfere with pathological diagnosis. The well-established treatments such as radiotherapy, chemotherapy or a combination of both remain the mainstays. Traditionally, the most important role for surgery is to obtain and sample adequate tissue to confirm a diagnosis with stereotactic biopsy. Though no benefit could be demonstrated for debulking surgery, a subset of patients with large space occupying lesions which could be well circumscribed and surgically accessible may benefit from tumor resection. Moreover, surgical procedures to carry out interstitial chemotherapy and/or brachytherapy with or without tumor resection hold promise. Complications such as hydrocephalus could be managed by ventriculoperitoneal shunting. Further application of surgical procedures in the treatment of PCNSL is recommended with caution and strict patient selection criteria, and should be used in combination with radiotherapy and/or chemotherapy.

How powerful is CD133 as a cancer stem cell marker in brain tumors?

Cancer stem cells (CSCs) have been identified in a growing number of hematopoietic and solid tissue malignancies and are typically recognized by virtue of the expression of cell surface markers. CD133, a stem cell marker, is now extensively used as a surface marker to identify and isolate brain tumor stem cells (BTSCs) in malignant brain tumors. However, CD133 as the marker to sort BTSCs suffered some controversies. In this review, we reviewed the rise of CD133, analyzed the efficiency of CD133 on identification and isolation of BTSCs, explained some controversial study results and summed up the role of CD133 and other effective CSCs markers in sorting CSCs in other tumors. We analyzed current limited reports and found that the expression of CD133 was correlated with poor clinical prognosis in brain tumors. Finally, we summarized the mechanisms of chemo- and radio- resistance of CD133+ brain tumor cell, especially emphasized that the aberrant activation of development pathways in BTSCs can be potential targets to BTSCs, and outlined current preclinical studies on killing BTSCs or sensitizing BTSCs to chemo- and radio-therapies.