Wen-Yuan Lee

Adjuvant Immunotherapy with Whole-Cell Lysate Dendritic Cells Vaccine for Glioblastoma Multiforme: A Phase II Clinical Trial

BACKGROUND This study sought to evaluate effectiveness of autologous dendritic cell vaccine (immunotherapy) for glioblastoma multiforme (GBM). METHODS Patients 14 to 70 years of age with newly diagnosed GBM and Karnofsky Performance Scale (KPS) score >70 who were receiving initial treatment were enrolled and were randomized into 2 groups during the 5-year study period. Eighteen patients underwent conventional treatment (surgery, radiotherapy, and chemotherapy) and received adjuvant autologous dendritic cell vaccine, and 16 patients (control group) underwent conventional treatment only. Administration of the vaccine was begun within 1 to 2 months postoperatively, with 10 inoculations given over 6 months. Outcome measures were overall survival (OS); progression-free survival (PFS); 1-, 2-, and 3-year survival rates, and quality of life (QoL). RESULTS Follow-up time ranged from 14 to 56 months (median, 33 months). The 1-, 2-, and 3-year survival rates were 88.9%, 44.4%, and 16.7% for the vaccine group, respectively, and 75.0%, 18.8%, and 0%, respectively, for the control group, (P = 0.299, 0.0035, 0.0014, respectively). The median OS for the vaccine group was 31.9 months and for the control group was 15.0 months (P < 0.002). The median progression-free survival (PFS) for the vaccine group was 8.5 months, and 8.0 months for the control group (P = 0.075). The surviving fraction was significantly higher in the vaccine group based on Kaplan-Meier analysis. CONCLUSIONS Adjuvant immunotherapy with whole-cell lysate dendritic cell vaccine may improve short-term survival. It seems to be safe, and its long-term effectiveness is worthy of further investigation.

Targeting cancer stem cells for treatment of glioblastoma multiforme

Cancer stem cells (CSCs) in glioblastoma multiforme (GBM) are radioresistant and chemoresistant, which eventually results in tumor recurrence. Targeting CSCs for treatment is the most crucial issue. There are five methods for targeting the CSCs of GBM. One is to develop a new chemotherapeutic agent specific to CSCs. A second is to use a radiosensitizer to enhance the radiotherapy effect on CSCs. A third is to use immune cells to attack the CSCs. In a fourth method, an agent is used to promote CSCs to differentiate into normal cells. Finally, ongoing gene therapy may be helpful. New therapeutic agents for targeting a signal pathway, such as epidermal growth factor (EGF) and vascular epidermal growth factor (VEGF) or protein kinase inhibitors, have been used for GBM but for CSCs the effects still require further evaluation. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as cyclooxygenase-2 (Cox-2) inhibitors have proven to be effective for increasing radiation sensitivity of CSCs in culture. Autologous dendritic cells (DCs) are one of the promising immunotherapeutic agents in clinical trials and may provide another innovative method for eradication of CSCs. Bone-morphogenetic protein 4 (BMP4) is an agent used to induce CSCs to differentiate into normal glial cells. Research on gene therapy by viral vector is also being carried out in clinical trials. Targeting CSCs by eliminating the GBM tumor may provide an innovative way to reduce tumor recurrence by providing a synergistic effect with conventional treatment. The combination of conventional surgery, chemotherapy, and radiotherapy with stem cell-orientated therapy may provide a new promising treatment for reducing GBM recurrence and improving the survival rate.

A new Modified Intracerebral Hemorrhage score for treatment decisions in basal ganglia hemorrhage--a randomized trial.

Objectives:To develop a Modified Intracerebral Hemorrhage (MICH) score to determine optimal cut-offs for conservative treatment vs surgical intervention for basal ganglia hemorrhage and to predict outcomes. Design:Prospective randomized trial. Setting:A 1,720-bed medical center affiliated with a university. Patients:In all, 226 patients with basal ganglia hemorrhage who presented at our hospital from 2001–2005. Interventions:Group A (n = 113) underwent endoscopic surgery; group B (n = 113) underwent conservative treatment. Score differences on the Glasgow Outcome Scale and 1-yr Barthel Index were analyzed by chi-square test and Student’s t-tests. Cut-offs for MICH scoring were evaluated using receiver operating characteristic curves for calculating the Youden Index. The treatment odds ratio was analyzed by univariate, multivariate, and multiple logistic regressions. Measurements and Main Results:The optimal cut-off point for mortality was a MICH score ≥3 in which the Youden Index is 0.66 (sensitivity, 76.3%; specificity, 89.8%; area under the receiver operating characteristic curve, 0.897). The positive and negative predictive values were 81.8% and 86.3%, respectively. The treatment odds ratio for surgical treatment was 6.87 (95% confidence interval, 3.13–14.5) at MICH scores ≥3. The best cut-off for good functional outcomes (Glasgow Outcome Scale ≥4 or Barthel index ≥55) was MICH ≥2. Conservative treatment achieved a better mean Barthel Index at MICH = 0 or 1 than surgical treatment, p < .01. At MICH scores = 3 or 4, 6-month mortality for conservative treatment was higher than for surgical treatment, p < .01 and p = .04, respectively. At MICH scores of 5, all patients died. Conclusions:MICH scoring provides a simple, reliable system for treatment decisions regarding basal ganglia hemorrhage and may accurately predict functional outcomes. Conservative treatment is recommended for basal ganglia ICH patients with low MICH scores (0, 1) to preserve neurologic function. Surgery is recommended for patients with a midlevel MICH score to obtain better functional outcomes (MICH = 2) and to reduce mortality (MICH = 3 or 4). At MICH scores = 5, there are no indications for surgery.

A stainless steel sheath for endoscopic surgery and its application in surgical evacuation of putaminal haemorrhage

A stainless steel tube was used as an endoscope sheath in combination with a working channel endoscope to evacuate hypertensive putaminal intracerebral haematoma (ICH). A frontal entry point ipsilateral to the haematoma was selected for insertion of the sheath. From January to June 2004, seven patients with putaminal ICH underwent endoscopic surgery in our hospital. There were no surgical complications. Haematoma evacuation rates were greater than 90% (median of 93%). Six patients (87%) regained consciousness within one week. Six patients, including four who had no residual disability and two who had moderate disability, were able to function independently. One patient remained in a persistent vegetative state at clinical follow-up after 6 months. Use of a stainless steel endoscopic sheath combined with working channel endoscopy via a frontal approach facilitates evacuation of putaminal ICH.

Glasgow Coma Scale and hematoma volume as criteria for treatment of putaminal and thalamic intracerebral hemorrhage

BACKGROUND The decision to administer conservative or surgical treatment for putaminal and thalamic ICH is still a controversial issue. This study was undertaken to examine the decision-making criteria for these 2 treatments. METHODS In a retrospective study, case records of 400 patients with spontaneous putaminal and thalamic hemorrhage who underwent conservative treatment (n = 201) and surgical treatment (n = 199) over the past 5 years were examined. Conservative treatment included hypertonic solution treatment and hypertension control. Surgical treatments included endoscopic surgery, craniotomy, and stereotactic aspiration. Preoperative GCS score and ICH volume were the major evaluating factors, and comparison of the 30-day mortality rate and 6-month BI score was used for outcome evaluation. RESULTS In patients with a GCS score of 13 to 15, there was no difference in mortality between conservative and surgical treatments. At a GCS score of 9 to 12 and ICH volume of less than 30 mL, the mortality rate with surgical treatment (10.5%) was lower than that with conservative treatment (20.0%, P < .05). At a GCS score of 3 to 8 and ICH volume of at least 30 mL, surgical treatment was for life saving. Mortality rates were lower for conservative treatment than for surgical treatment when the GCS score was 3 to 12 and ICH volume less than 30 mL. Endoscopic surgery had a better functional outcome compared with craniotomy and stereotactic aspiration when the GCS score was at least 9 (P < .001 and P < .02, respectively). Those in conservative treatment received a better BI score than those in surgical treatment did when the ICH volume was less than 40 mL (P < .001). CONCLUSIONS Intracerebral hemorrhage volume is probably more important than GCS score in determining treatment. Our nonrandomized data could be interpreted to show that conservative treatment is suggested at GCS score of at least 13 or when ICH volume is less than 30 mL, regardless of GCS score. Surgical treatment could be recommended at GCS score of less than 12 with ICH volume of at least 30 mL for life saving. Endoscopic surgery may improve the functional outcomes because it is less invasive and effectively removes the ICH at GCS score of at least 9.

Socioeconomic costs of open surgery and gamma knife radiosurgery for benign cranial base tumors.

OBJECTIVE:The aim of this study was to evaluate the relative socioeconomic costs of benign cranial base tumors treated with open surgery and gamma knife radiosurgery. METHODS:In a retrospective study, we studied 174 patients with benign cranial base tumors, less than 3 cm in diameter (or volume less than 30 ml), admitted in the past 5 years. Group A (n = 94) underwent open surgery for removal of the tumors, whereas Group B (n = 80) underwent gamma knife radiosurgery. The socioeconomic costs were evaluated by both direct and indirect cost. The direct costs comprised intensive care unit cost, ward cost, operating room cost, and outpatient visiting cost. The indirect costs included loss of workdays and mortality. The length of hospital stay, the number of lost workdays, surgical complications, mortality, and cost-effectiveness analysis were calculated as well. Student t test and &khgr;2 test were used for statistical analysis. RESULTS:The mean length of hospital stay for open surgery was 18.2 ± 30.4 days including 5.0 ± 14.7 days of intensive care unit stay and 13.0 ± 15.2 days of ward stay, P < 0.01. The mean hospital stay for gamma knife was 2.2 ± 0.9 days with no need of intensive care unit stay, P < 0.01. The mean loss of workdays for open surgery was 160 ± 158 days and 8.0 ± 9.0 days for gamma knife, P < 0.01. The gamma knife cost per hour (US

Limbic leukotomy for intractable major affective disorders: A 7-year follow-up study using nine comprehensive psychiatric test evaluations

1435) is higher than the open surgery cost per hour (US

Mutations in the OTOF gene in Taiwanese patients with auditory neuropathy.

450), P < 0.01. The direct cost for gamma knife (US

A Higher Dosage of Oral Alendronate Will Increase the Subsequent Cancer Risk of Osteoporosis Patients in Taiwan: A Population-Based Cohort Study

9677 ±

Risk of prostate and bladder cancers in patients with spinal cord injury: A population-based cohort study1

6700) is higher than that for open surgery (US