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Joyce Koueik, Mark R. Kraemer, David Hsu, Elias Rizk, Ryan Zea, Clayton Haldeman and Bermans J. Iskandar

OBJECTIVE

Recent evidence points to gravity-dependent chronic shunt overdrainage as a significant, if not leading, cause of proximal shunt failure. Yet, shunt overdrainage or siphoning persists despite innovations in valve technology. The authors examined the effectiveness of adding resistance to flow in shunt systems via antisiphon devices (ASDs) in preventing proximal shunt obstruction.

METHODS

A retrospective observational cohort study was completed on patients who had an ASD (or additional valve) added to their shunt system between 2004 and 2016. Detailed clinical, radiographic, and surgical findings were examined. Shunt failure rates were compared before and after ASD addition.

RESULTS

Seventy-eight patients with shunted hydrocephalus were treated with placement of an ASD several centimeters distal to the primary valve. The records of 12 of these patients were analyzed separately due to a complex shunt revision history (i.e., > 10 lifetime shunt revisions). The authors found that adding an ASD decreased the 1-year ventricular catheter obstruction rates in the “simple” and “complex” groups by 67.3% and 75.8%, respectively, and the 5-year rates by 43.3% and 65.6%, respectively. The main long-term ASD complication was ASD removal for presumed valve pressure intolerance in 5 patients.

CONCLUSIONS

Using an ASD may result in significant reductions in ventricular catheter shunt obstruction rates. If confirmed with prospective studies, this observation would lend further evidence that chronic shunt overdrainage is a central cause of shunt malfunction, and provide pilot data to establish clinical and laboratory studies that assess optimal ASD type, number, and position, and eventually develop shunt valve systems that are altogether resistant to siphoning.

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Cheng-Chia Lee, Hsiu-Mei Wu, Wen-Yuh Chung, Ching-Jen Chen, David Hung-Chi Pan and Sanford P. C. Hsu

Object

Resection of vestibular schwannoma (VS) after Gamma Knife surgery (GKS) is infrequently performed. The goals of this study were to analyze and discuss the neurological outcomes and technical challenges of VS resection and to explore strategies for treating tumors that progress after GKS.

Methods

In total, 708 patients with VS underwent GKS between 1993 and 2012 at Taipei Veterans General Hospital. The post-GKS clinical courses, neurological presentations, and radiological changes in these patients were analyzed. Six hundred patients with imaging follow-up of at least 1 year after GKS treatment were included in this study.

Results

Thirteen patients (2.2%) underwent microsurgery on average 36.8 months (range 3–107 months) after GKS. The indications for the surgery included symptomatic adverse radiation effects (in 4 patients), tumor progression (in 6), and cyst development (in 3). No morbidity or death as a result of the surgery was observed. At the last follow-up evaluation, all patients, except 1 patient with a malignant tumor, had stable or near-normal facial function.

Conclusions

For the few VS cases that require resection after radiosurgery, maximal tumor resection can be achieved with modern skull-based techniques and refined neuromonitoring without affecting facial nerve function.

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Mark R. Kraemer, Joyce Koueik, Susan Rebsamen, David A. Hsu, M. Shahriar Salamat, Susan Luo, Sara Saleh, Taryn M. Bragg and Bermans J. Iskandar

OBJECTIVE

Ventricular shunts have an unacceptably high failure rate, which approaches 50% of patients at 2 years. Most shunt failures are related to ventricular catheter obstruction. The literature suggests that obstructions are caused by in-growth of choroid plexus and/or reactive cellular aggregation. The authors report endoscopic evidence of overdrainage-related ventricular tissue protrusions (“ependymal bands”) that cause partial or complete obstruction of the ventricular catheter.

METHODS

A retrospective review was completed on patients undergoing shunt revision surgery between 2008 and 2015, identifying all cases in which the senior author reported endoscopic evidence of ependymal tissue in-growth into ventricular catheters. Detailed clinical, radiological, and surgical findings are described.

RESULTS

Fifty patients underwent 83 endoscopic shunt revision procedures that revealed in-growth of ventricular wall tissue into the catheter tip orifices (ependymal bands), producing partial, complete, or intermittent shunt obstructions. Endoscopic ventricular explorations revealed ependymal bands at various stages of development, which appear to form secondarily to siphoning. Ependymal bands are associated with small ventricles when the shunt is functional, but may dilate at the time of obstruction.

CONCLUSIONS

Ventricular wall protrusions are a significant cause of proximal shunt obstruction, and they appear to be caused by siphoning of surrounding tissue into the ventricular catheter orifices.

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Wesley Hsu, Ahmed Mohyeldin, Sagar R. Shah, Colette M. ap Rhys, Lakesha F. Johnson, Neda I. Sedora-Roman, Thomas A. Kosztowski, Ola A. Awad, Edward F. McCarthy, David M. Loeb, Jean-Paul Wolinsky, Ziya L. Gokaslan and Alfredo Quiñones-Hinojosa

Object

Chordoma is a malignant bone neoplasm hypothesized to arise from notochordal remnants along the length of the neuraxis. Recent genomic investigation of chordomas has identified T (Brachyury) gene duplication as a major susceptibility mutation in familial chordomas. Brachyury plays a vital role during embryonic development of the notochord and has recently been shown to regulate epithelial-to-mesenchymal transition in epithelial-derived cancers. However, current understanding of the role of this transcription factor in chordoma is limited due to the lack of availability of a fully characterized chordoma cell line expressing Brachyury. Thus, the objective of this study was to establish the first fully characterized primary chordoma cell line expressing gain of the T gene locus that readily recapitulates the original parental tumor phenotype in vitro and in vivo.

Methods

Using an intraoperatively obtained tumor sample from a 61-year-old woman with primary sacral chordoma, a chordoma cell line (JHC7, or Johns Hopkins Chordoma Line 7) was established. Molecular characterization of the primary tumor and cell line was conducted using standard immunostaining and Western blotting. Chromosomal aberrations and genomic amplification of the T gene in this cell line were determined. Using this cell line, a xenograft model was established and the histopathological analysis of the tumor was performed. Silencing of Brachyury and changes in gene expression were assessed.

Results

The authors report, for the first time, the successful establishment of a chordoma cell line (JHC7) from a patient with pathologically confirmed sacral chordoma. This cell line readily forms tumors in immunodeficient mice that recapitulate the parental tumor phenotype with conserved histological features consistent with the parental tumor. Furthermore, it is demonstrated for the first time that silencing of Brachyury using short hairpin RNA renders the morphology of chordoma cells to a more differentiated-like state and leads to complete growth arrest and senescence with an inability to be passaged serially in vitro.

Conclusions

This report represents the first xenograft model of a sacral chordoma line described in the literature and the first cell line established with stable Brachyury expression. The authors propose that Brachyury is an attractive therapeutic target in chordoma and that JHC7 will serve as a clinically relevant model for the study of this disease.

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Cheng-Chia Lee, Sanford P. C. Hsu, Chung-Jung Lin, Hsiu-Mei Wu, Yu-Wei Chen, Yung-Hung Luo, Chi-Lu Chiang, Yong-Sin Hu, Wen-Yuh Chung, Cheng-Ying Shiau, Wan-Yuo Guo, David Hung-Chi Pan and Huai-Che Yang

OBJECTIVE

The presence of epidermal growth factor receptor (EGFR) mutations in non–small cell lung cancer (NSCLC) has been associated with elevated radiosensitivity in vitro. However, results from clinical studies on radiosensitivity in cases of NSCLC with EGFR mutations are inconclusive. This paper presents a retrospective analysis of patients with NSCLC who underwent regular follow-up imaging after radiotherapy for brain metastases (BMs). The authors also investigated the influence of EGFR mutations on the efficacy of Gamma Knife radiosurgery (GKRS).

METHODS

This study included 264 patients (1069 BMs) who underwent GKRS treatment and for whom EGFR mutation status, demographics, performance status, and tumor characteristics were available. Radiological images were obtained at 3 months after GKRS and at 3-month intervals thereafter. Kaplan-Meier plots and Cox regression analysis were used to correlate EGFR mutation status and other clinical features with tumor control and overall survival.

RESULTS

The tumor control rates and overall 12-month survival rates were 87.8% and 65.5%, respectively. Tumor control rates in the EGFR mutant group versus the EGFR wild-type group were 90.5% versus 79.4% at 12 months and 75.0% versus 24.5% at 24 months. During the 2-year follow-up period after SRS, the intracranial response rate in the EGFR mutant group was approximately 3-fold higher than that in the wild-type group (p < 0.001). Cox regression multivariate analysis identified EGFR mutation status, extracranial metastasis, primary tumor control, and prescribed margin dose as predictors of tumor control (p = 0.004, p < 0.001, p = 0.004, and p = 0.026, respectively). Treatment with a combination of GKRS and tyrosine kinase inhibitors (TKIs) was the most important predictor of overall survival (p < 0.001).

CONCLUSIONS

The current study demonstrated that, among patients with NSCLC-BMs, EGFR mutations were independent prognostic factors of tumor control. It was also determined that a combination of GKRS and TKI had the most pronounced effect on prolonging survival after SRS. In select patient groups, treatment with SRS in conjunction with EGFR-TKIs provided effective tumor control for NSCLC-BMs.

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Sabareesh K. Natarajan, Paresh Dandona, Yuval Karmon, Albert J. Yoo, Junaid S. Kalia, Qing Hao, Daniel P. Hsu, L. Nelson Hopkins, David J. Fiorella, Bernard R. Bendok, Thanh N. Nguyen, Marilyn M. Rymer, Ashish Nanda, David S. Liebeskind, Osama O. Zaidat, Raul G. Nogueira, Adnan H. Siddiqui and Elad I. Levy

Object

The authors evaluated the prognostic significance of blood glucose level at admission (BGA) and change in blood glucose at 48 hours from the baseline value (CG48) in nondiabetic and diabetic patients before and after endovascular therapy for acute ischemic stroke (AIS).

Methods

The BGA and CG48 data were analyzed in 614 patients with AIS who received endovascular therapy at 7 US centers between 2006 and 2009. Data reviewed included demographics, stroke risk factors, diabetic status, National Institutes of Health Stroke Scale (NIHSS) score at presentation, recanalization grade, intracranial hemorrhage (ICH) rate, and 90-day outcomes (mortality rate and modified Rankin Scale score of 3–6 [defined as poor outcome]). Variables with p values < 0.2 in univariate analysis were included in a binary logistic regression model for independent predictors of 90-day outcomes.

Results

The mean patient age was 67.3 years, the median NIHSS score was 16, and 27% of patients had diabetes. In nondiabetic patients, BGA ≥ 116 mg/dl (≥ 6.4 mmol/L) and failure of glucose level to drop > 30 mg/dl (> 1.7 mmol/L) from the admission value were both significant predictors of 90-day poor outcome and death (p < 0.001). In patients with diabetes, BGA ≥ 116 mg/dl (≥ 6.4 mmol/L) was an independent predictor of poor outcome (p = 0.001). The CG48 was not a predictor of outcome in diabetic patients. A simplified 6-point scale including BGA, Thrombolysis in Myocardial Infarction (TIMI) Grade 2–3 Reperfusion, Age, presentation NIHSS score, CG48, and symptomatic ICH (BRANCH) corresponded with poor outcomes at 90 days; the area under the curve value was > 0.79.

Conclusions

Failure of blood glucose values to decrease in the first 48 hours after AIS intervention correlated with poor 90-day outcomes in nondiabetic patients. The BRANCH scale shows promise as a simple prognostication tool after endovascular therapy for AIS, and it merits prospective validation.