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Fujun Liu, Wei Chen, and Jing Chen

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Chun-Wei Yu, Kuan-Ting Chen, Yu-Lan Liu, Yi-Chiao Hsieh, Dun-Wei Huang, Yi-Feng Lee, Tsui-Jung Chien, and Dueng-Yuan Hueng

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Wei-Ying Yue, Su-Huan Yu, Shi-Guang Zhao, and Zhong-Ping Chen

Object

Astrocytoma may progress rapidly or remain stable for many years. To clarify whether molecular characteristics could be prognostic factors, several cell cycling–associated molecular alterations in the diffuse astrocytoma have been investigated.

Methods

Thirty-three patients in whom WHO Grade II astrocytoma had been initially diagnosed were assigned to 1 of 3 groups. Group 1 consisted of 10 patients with malignant progression; the tumor had recurred within 5 years and histological analysis had confirmed that the tumor progressed to Grade III or IV. Group 2 consisted of 10 patients in whom there was no malignant progression; the tumor recurred within 5 years, but histological analysis confirmed that the tumor remained at Grade II. Group 3 consisted of 13 patients who did not experience recurrence within 5 years. Expression of Ki 67, TP53, p27, and p21 was examined using immunohistochemical analysis for the tumor samples obtained during the first and second (in recurrent cases) surgeries. Exons 5, 7, and 8 of TP53 were scanned by DNA sequencing.

Results

The Ki 67 labeling index expression was significantly higher in Group 1 (even though it was similar between initial and recurrent tumors) than that of Group 3 (p < 0.05). However, there was no difference between Group 2 (both initial and recurrent tumors) and Group 3. The TP53 protein accumulation was also higher in Group 1 than in Group 2 or 3 (p < 0.05); a difference in TP53 expression was not found between Groups 2 and 3. The p27 and p21 was expressed in all cases, but no predictive values were found. The p53 mutation was found only in 6 cases in Group 1.

Conclusions

Overexpression of TP53, TP53 mutation, and Ki 67 labeling index could be molecular markers in astrocytomas predicting malignant progression.

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Cheng-Loong Liang, Meng-Wei Ho, Kang Lu, Yu-Duan Tsai, Po-Chou Liliang, Kuo-Wei Wang, and Han-Jung Chen

Object

The authors conducted a study to assess the eye lens dosimetry in trigeminal neuralgia (TN) treatment when using the Leksell Gamma Knife model C.

Methods

Phantom studies were used to measure the maximal dose reaching the eye lens with and without eye shielding. Six consecutive patients with TN were evaluated for Gamma Knife surgery (GKS). The maximum prescribed dose of 80 Gy was delivered with a single shot using the 4-mm collimator helmet. High-sensitivity thermoluminescence dosimeter chips (TLDCs) were used to measure the dosimetry.

In vitro, the Leksell GammaPlan (LGP) system predicted the mean maximal doses of 1.08 ± 0.08 and 0.15 ± 0.01 Gy (mean ± standard deviation) to the lens ipsilateral to the treated trigeminal nerve without and with eye shielding, respectively. The TLDCs-measured dosimetry indicated the mean maximal doses of 1.12 ± 0.09 and 0.17 ± 0.01 Gy without and with eye shielding, respectively. The maximal doses to the lens contralateral to the nerve were similar.

In vivo, the LGP predicted the mean maximal doses to the lens ipsilateral to the treated nerve as 1.1 ± 0.07 and 0.16 ± 0.02 Gy, respectively, without and with eye shielding. The dosimetry measured by TLDCs indicated the mean maximal dose to the lens ipsilateral to the treated nerve as 0.17 ± 0.02 Gy with eye shielding. The mean maximal doses to the lens contralateral to the nerve were similar. Using the 110 and 125˚ gamma angles, the LGP predicted the mean maximal doses of 0.32 ± 0.04 and 0.12 ± 0.04 Gy to the lens without and with eye shielding, respectively.

Conclusions

Patients with TN undergoing GKS without eye shielding may develop cataracts due to the high radiation dose to the eye lenses. The authors suggest the routine use of bilateral eye shielding for the patients.

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Chia-Hua Chen, Pin-Yuan Chen, You-Yu Lin, Li-Ying Feng, Shin-Han Chen, Chia-Yuan Chen, Yin-Cheng Huang, Chiung-Yin Huang, Shih-Ming Jung, Leslie Y. Chen, and Kuo-Chen Wei

OBJECTIVE

Despite intensive medical treatment, patients with glioblastoma (grade IV glioma [GBM]) have a low 5-year survival rate of 5.5%. In this study, the authors tried to improve currently used therapies by identification of a therapeutic target, IGFBP3, for glioma treatment.

METHODS

IGFBP3 RNA expression in 135 patients newly diagnosed with glioma was correlated with clinicopathological factors. Immunohistochemical analysis was performed to determine IGFBP3 protein expression in glioma specimens. The effect of IGFBP3 depletion on cell proliferation was examined using IGFBP3 knockdown glioma cells. Intracranial infusion of IGFBP3 siRNAs was performed to evaluate the effect of IGFBP3 depletion in mouse intracranial xenograft models.

RESULTS

We demonstrated higher IGFBP3 expression in GBM than in tumor margin and grade II glioma. IGFBP3 expression was not only positively correlated with tumor grades but also associated with tumor histology and IDH1/2 mutation status. Additionally, higher IGFBP3 expression predicted shorter overall survival in glioma and GBM proneural subgroup patients. In vitro cell culture studies suggested IGFBP3 knockdown suppressed cell proliferation and induced cell cycle G2/M arrest as well as apoptosis in glioma cells. Also, accumulation of DNA double-strand breaks and γH2AX was observed in IGFBP3 knockdown cells. IGFBP3 knockdown delayed in vivo tumor growth in mouse subcutaneous xenograft models. Furthermore, convection-enhanced delivery of IGFBP3 siRNA to mouse brain suppressed intracranial tumor growth and prolonged survival of tumor-bearing mice.

CONCLUSIONS

Our findings suggest IGFBP3 predicts poor outcome of glioma patients and is a potential therapeutic target for which depletion of its expression suppresses tumor growth through inducing apoptosis and accumulation of DNA damage in glioma cells.

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Ching-Chung Ko, Tai-Yuan Chen, Sher-Wei Lim, Yu-Ting Kuo, Te-Chang Wu, and Jeon-Hor Chen

OBJECTIVE

A subset of benign, nonfunctioning pituitary macroadenomas (NFMAs) has been shown to undergo early progression/recurrence (P/R) during the first years after surgical resection. The aim of this study was to determine preoperative MR imaging features for the prediction of P/R in benign solid NFMAs, with emphasis on apparent diffusion coefficient (ADC) values.

METHODS

We retrospectively investigated the preoperative MR imaging features for the prediction of P/R in benign solid NFMAs. Only the patients who had undergone preoperative MRI and postoperative MRI follow-ups for more than 1 year (at least every 6–12 months) were included. From November 2010 to December 2016, a total of 30 patients diagnosed with benign solid NFMAs were included (median follow-up time 45 months), and 19 (63.3%) patients had P/R (median time to P/R 24 months).

RESULTS

Benign solid NFMAs with cavernous sinus invasion, failed chiasmatic decompression, large tumor height and tumor volume, high diffusion-weighted imaging (DWI) signal, and lower ADC values/ratios were significantly associated with P/R (p < 0.05). The cutoff points of ADC value and ADC ratio for prediction of P/R are 0.77 × 10−3 mm/sec and 1.01, respectively, with area under the curve (AUC) values (0.9 and 0.91) (p < 0.01). In multivariate Cox proportional hazards analysis, low ADC value (< 0.77 × 10−3 mm/sec) is a high-risk factor of P/R (p < 0.05) with a hazard ratio of 14.07.

CONCLUSIONS

Benign solid NFMAs with low ADC values/ratios are at a significantly increased risk of P/R, and aggressive treatments accompanied by close follow-up with imaging studies should be considered.

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Chun-Lung Chou, Hsin-Hung Chen, Huai-Che Yang, Yi-Wei Chen, Ching-Jen Chen, Yu-Wei Chen, Hsiu-Mei Wu, Wan-Yuo Guo, David Hung-Chi Pan, Wen-Yuh Chung, Tai-Tong Wong, and Cheng-Chia Lee

OBJECTIVE

Hypothalamic obesity is common among patients with craniopharyngioma. This study examined whether precise stereotactic radiosurgery reduces the risk of hypothalamic obesity in cases of craniopharyngioma with expected long-term survival.

METHODS

This cohort study included 40 patients who had undergone Gamma Knife radiosurgery (GKRS; n = 22) or fractionated radiotherapy (FRT; n = 18) for residual or recurrent craniopharyngioma. Neurological presentations, tumor volume changes, and BMI values were meticulously reviewed. The median clinical follow-up durations were 9.7 years in the GKRS group and 10.8 years in the FRT group.

RESULTS

The median ages at the time of GKRS and FRT were 9.0 years and 10.0 years, respectively. The median margin dose of GKRS was 12.0 Gy (range 10.0–16.0 Gy), whereas the median dose of FRT was 50.40 Gy (range 44.1–56.3 Gy). Prior to GKRS or FRT, the median BMI values were 20.5 kg/m2 in the GKRS cohort and 20.0 kg/m2 in the FRT cohort. The median BMIs after radiation therapy at final follow-up were 21.0 kg/m2 and 24.0 kg/m2 for the GKRS and FRT cohorts, respectively. In the FRT cohort, BMI curves rapidly increased beyond the 85th percentile of the upper limit of the general population. BMI curves in the GKRS cohort increased more gradually, and many of the patients merged into the normal growth curve after adolescence. However, the observed difference was not statistically significant (p = 0.409).

CONCLUSIONS

The study compared the two adjuvant radiation modalities most commonly used for recurrent and residual craniopharyngioma. The authors’ results revealed that precise radiosurgery dose planning can mediate the subsequent increase in BMI. There is every indication that meticulous GKRS treatment is an effective approach to treating craniopharyngioma while also reducing the risk of hypothalamic obesity.

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Tsung-Ying Yu, Chao-Hung Chen, Man-Wei Hua, Chiao-Chin Lee, and Dueng-Yuan Hueng

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Ching-Chang Chen, Shao-Wei Chen, Po-Hsun Tu, Yin-Cheng Huang, Zhuo-Hao Liu, Alvin Yi-Chou Wang, Shih-Tseng Lee, Tien-Hsing Chen, Chi-Tung Cheng, Shang-Yu Wang, and An-Hsun Chou

OBJECTIVE

Burr hole craniostomy is an effective and simple procedure for treating chronic subdural hematoma (CSDH). However, the surgical outcomes and recurrence of CSDH in patients with liver cirrhosis (LC) remain unknown.

METHODS

A nationwide population-based cohort study was retrospectively conducted using data from the Taiwan National Health Insurance Research Database. The study included 29,163 patients who underwent first-time craniostomy for CSDH removal between January 1, 2001, and December 31, 2013. In total, 1223 patients with LC and 2446 matched non-LC control patients were eligible for analysis. All-cause mortality, surgical complications, repeat craniostomy, extended craniotomy, and long-term medical costs were analyzed.

RESULTS

The in-hospital mortality rate (8.7% vs 3.1% for patients with LC and non-LC patients, respectively), frequency of hospital admission, length of ICU stay, number of blood transfusions, and medical expenditures of patients with LC who underwent craniostomy for CSDH were considerably higher than those of non-LC control patients. Patients with LC tended to require an extended craniotomy to remove subdural hematomas in the hospital or during long-term follow-up. The surgical outcome worsened with an increase in the severity of LC.

CONCLUSIONS

Even for simple procedures following minor head trauma, LC remains a serious comorbidity with a poor prognosis.

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Xiao-Dong Wu, Wen Yuan, Hua-Jiang Chen, Yu Chen, Jian-Xi Wang, Peng Cao, Ying Zhang, Xin-Wei Wang, Li-Li Yang, Yuan-Yuan Chen, and Nicholas Tsai

Object

Multilevel anterior cervical decompression and fusion is indicated for patients with multilevel compression or stenosis of the spinal cord. Some have reported that this procedure would lead to a loss of cervical range of motion (CROM). However, few studies have demonstrated the exact impact of the procedure on CROM. Here, the authors describe short- and midterm postoperative CROM following multilevel anterior cervical decompression and fusion.

Methods

Thirty-five patients underwent a 3- or 4-level anterior cervical decompression and fusion. In all patients, active CROM was measured preoperatively and at both the short-term (3–4 months) and midterm (12–15 months) follow-ups by using a CROM device. The preoperative and postoperative data were analyzed using ANOVA (α = 0.05).

Results

Patients had significantly less ROM in all planes of motion postoperatively. The greater limitation in CROM was observed at the short-term follow-up. However, at the midterm follow-up, an obvious increase in CROM was observed in each cardinal plane compared with that in the short-term (sagittal plane 17.4%, coronal plane 14.1%, and horizontal plane 19.5%). A gradual increase in the CROM in each cardinal plane was observed during the recovery period in 5 patients. In the 6 conventional motions, the major recovery of CROM was observed in flexion (27.5%), while relatively less recovery was seen in extension (10.5%).

Conclusions

Patients had an obvious reduction in active CROM following multilevel anterior cervical decompression and fusion. The greater limitation in CROM was observed at the short-term follow-up. In the midterm follow-up, however, an obvious recovery in CROM was observed in each cardinal plane, reducing the restriction of neck motion further.