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1.
Asian J Surg ; 47(4): 1746-1755, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38148260

ABSTRACT

OBJECTIVE: This study aims to predict new-onset secondary adrenal insufficiency (NOSAI) after transsphenoidal pituitary tumor resection surgery using perioperative growth hormone (GH) and prolactin (PRL) levels, among other factors. METHODS: A cohort of 124 adult patients who underwent transsphenoidal resection for non-functioning pituitary adenoma, with routine perioperative glucocorticoid use, was used to develop the predictive regression model. An additional 46 patients served as the validation cohort. Generalized additive models were used to identify optimal cut-off points for the variables. RESULTS: The GH level on postoperative day one (POD1) can be a simple predictor by implementing a cut-off point of 0.41 ng/ml. A value ≤ 0.41 ng/mL predicted NOSAI with 0.6316 sensitivity and 0.7810 specificity for the original cohort and 1.0000 sensitivity and 0.7143 specificity for the validation cohort. The multiple logistic regression model included perioperative PRL level difference, perioperative GH level difference, intraoperative cerebrospinal fluid (CSF) leakage, tumor size, and the combined effect of diabetes insipidus (DI) and relative perioperative GH level difference. The areas under the receiver operating characteristic curves were 0.9410 (original cohort) and 0.9494 (validation cohort) for the regression model. CONCLUSION: Early morning GH level on POD1 can predict NOSAI with fair accuracy when perioperative stress dose glucocorticoid is administered. Prediction accuracy can be improved by considering CSF leakage, DI, and perioperative changes in GH and PRL in the final regression model.


Subject(s)
Adenoma , Adrenal Insufficiency , Pituitary Neoplasms , Adult , Humans , Pituitary Neoplasms/surgery , Adenoma/surgery , Adenoma/pathology , Glucocorticoids , Growth Hormone , Adrenal Insufficiency/diagnosis , Adrenal Insufficiency/etiology , Retrospective Studies
2.
Laryngoscope Investig Otolaryngol ; 7(6): 1695-1703, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36544964

ABSTRACT

Objectives: Endoscopic endonasal transsphenoidal adenomectomy (TSA) is the most frequently performed skull base surgery, and researchers have recently focused on preserving nasal function. The endoscopic transseptal approach is a promising procedure due to its reduced injury to the nasal mucosa; however, there are no studies comparing rhinological and neurosurgical outcomes concurrently with the standard endoscopic transnasal approach. Therefore, we conducted this study to investigate whether the transseptal approach could reduce nasal morbidities with comparable neurosurgical outcomes. Methods: We retrospectively reviewed 25 patients who underwent endoscopic endonasal transseptal TSA for pituitary adenoma without encasement of internal carotid artery from January 2019 to December 2020. Another 25 patients who received transnasal approach from January 2017 to December 2018 were selected as controls. Patients with diseases affecting the nasal cavity/olfaction or usage of a nasoseptal flap were excluded for a better comparison of the two procedures. We collected data from radiological studies, endocrine studies, endoscopic evaluations, 22-item sinonasal outcome tests (SNOT-22) and Top International Biotech Smell Identification Test (TIBSIT) for comparison. Results: Lower postoperative SNOT-22 and Lund-Kennedy endoscopic scores were observed in the transseptal group. The effect size of differences were classified as large effect (The absolute value of Cohen's d > 0.8). Nevertheless, the TIBSIT scores were not significantly different. The rates of gross total resection, recovery of hormonal abnormalities, and complications were not significantly different. After controlling possible confounding factors using multivariate analysis, the endoscopic transseptal approach remained an independent factor for lower SNOT-22 scores and Lund-Kennedy endoscopic scores. Conclusions: The endoscopic transseptal approach provides improved recovery of nasal mucosa and intact olfaction without compromising neurosurgical outcomes. Level of Evidence: 2b.

3.
Radiother Oncol ; 126(2): 368-374, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29111173

ABSTRACT

PURPOSE: The impact of epidermal growth factor receptor (EGFR) mutations on radiotherapy for brain metastases (BM) is undetermined. We evaluated the effects of EGFR mutation status on responses and outcomes in non-small cell lung cancer (NSCLC) patients with BM, treated with upfront or salvage stereotactic radiosurgery (SRS). METHODS AND MATERIALS: From 2008 to 2015, 147 eligible NSCLC patients with 300 lesions were retrospectively analyzed. Patterns of tyrosine kinase inhibitor (TKI) therapy were recorded. Radiographic response was assessed. Brain progression-free survival (BPFS) and overall survival were calculated and outcome prognostic factors were evaluated. RESULTS: Median follow-up time was 13.5 months. Of the EGFR-genotyped patients, 79 (65%) were EGFR mutants, and 42 (35%) were wild type. Presence of EGFR mutations was associated with higher radiographic complete response rates (CRR). Median time to develop new BM after SRS was significantly longer for mutant-EGFR patients (17 versus 10.5 months, p = 0.02), predominantly for those with adjuvant TKI therapy (26.3 versus 15 months, p = 0.01). EGFR mutations independently predicted better BPFS (HR = 0.55, p = 0.048) in multivariate analysis. CONCLUSIONS: In patients with NSCLC treated with SRS for BM, the presence of EGFR mutations is associated with a higher CRR, longer time for distant brain control, and better BPFS. The combination of SRS and TKI in selective patient group can be an effective treatment choice for BM with favorable brain control and little neurotoxicity.


Subject(s)
Brain Neoplasms/radiotherapy , Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/radiotherapy , ErbB Receptors/genetics , Lung Neoplasms/radiotherapy , Radiosurgery/methods , Adult , Aged , Aged, 80 and over , Brain Neoplasms/enzymology , Brain Neoplasms/genetics , Carcinoma, Non-Small-Cell Lung/enzymology , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Female , Humans , Lung Neoplasms/enzymology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Mutation , Predictive Value of Tests , Retrospective Studies , Salvage Therapy
4.
Radiother Oncol ; 125(2): 248-257, 2017 11.
Article in English | MEDLINE | ID: mdl-29056290

ABSTRACT

BACKGROUND AND PURPOSE: Irradiating glioblastoma preoperative edema (PE) remains controversial. We investigated the associations between tumors' PE extent with invasion into synchronous subventricular zone and corpus callosum (sSVZCC) and treatment outcomes to provide the clinical evidence for radiotherapy decision-making. MATERIAL AND METHODS: Extensive PE (EPE) was defined as PE extending ≥2 cm from the tumor edge and extensive progressive disease (EPD) as tumors spreading ≥2 cm from the preoperative tumor edge along PE. The survival and progression patterns were analyzed according to EPE and sSVZCC invasion. RESULTS: In total, 136 patients were followed for a median of 74.9 (range, 47.6-102.1) months. The median overall survival and progression-free survival were 19.7 versus 28.6 months (p = 0.005) and 11.0 versus 17.4 months (p = 0.011) in patients with EPE+ versus EPE-, and were 18.7 versus 25.4 months (p = 0.021) and 10.7 versus 14.6 months (p = 0.020) in those with sSVZCC+ versus sSVZCC-. The EPD rates for tumors with EPE-/sSVZCC-, EPE-/sSVZCC+, EPE+/sSVZCC-, and EPE+/sSVZCC+ were 2.8%, 7.1%, 37.0%, and 71.9%, respectively. In EPE+/sSVZCC+, tumor migration was associated with the PE extending along the corpus callosum (77.8%) and subventricular zone (50.0%). CONCLUSIONS: Our results support the need for developing individualized irradiation strategies for glioblastomas according to EPE and sSVZCC.


Subject(s)
Brain Neoplasms/radiotherapy , Corpus Callosum/pathology , Edema/pathology , Glioblastoma/radiotherapy , Lateral Ventricles/pathology , Adult , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Corpus Callosum/diagnostic imaging , Disease Progression , Disease-Free Survival , Female , Glioblastoma/diagnostic imaging , Glioblastoma/pathology , Humans , Lateral Ventricles/diagnostic imaging , Male , Middle Aged , Neoplasm Invasiveness , Neoplasms, Multiple Primary , Treatment Outcome
5.
Cancer Med ; 5(8): 1830-9, 2016 08.
Article in English | MEDLINE | ID: mdl-27367901

ABSTRACT

Aberrant methylation has been associated with transcriptional inactivation of tumor-related genes in a wide spectrum of human neoplasms. The influence of DNA methylation in oligodendroglial tumors is not fully understood. Genomic DNA was isolated from 61 oligodendroglial tumors for analysis of methylation using methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA). We correlated methylation status with clinicopathological findings and outcome. The genes found to be most frequently methylated in oligodendroglial tumors were RASSF1A (80.3%), CASP8 (70.5%), and CDKN2A (52.5%). Kaplan-Meier survival curve analysis demonstrated longer duration of progression-free survival in patients with 19q loss, aged less than 38 years, and with a proliferative index of less than 5%. Methylation of the ESR1 promoter is significantly associated with shorter duration of overall survival and progression-free survival, and that methylation of IGSF4 and RASSF1A is significantly associated with shorter duration of progression-free survival. However, none of the methylation status of ESR1, IGSF4, and RASSF1A was of prognostic value for survival in a multivariate Cox model. A number of novel and interesting epigenetic alterations were identified in this study. The findings highlight the importance of methylation profiles in oligodendroglial tumors and their possible involvement in tumorigenesis.


Subject(s)
Astrocytoma/genetics , DNA Methylation , Genes, Tumor Suppressor , Oligodendroglioma/genetics , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Astrocytoma/pathology , Astrocytoma/therapy , Cell Proliferation , Child , Chromosome Aberrations , DNA, Neoplasm/genetics , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multiplex Polymerase Chain Reaction/methods , Neoplasm Grading , Oligodendroglioma/pathology , Oligodendroglioma/therapy , Prognosis , Risk Factors , Treatment Outcome , Young Adult
6.
J Formos Med Assoc ; 115(6): 475-80, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27117887

ABSTRACT

The aim of the present study was to evaluate the serial changes of GH and IGF-1 in seven patients with naïve, active acromegaly following presurgical treatment of the somatostatin analog pasireotide long-acting release (LAR) and octreotide LAR. The patients were treated with pasireotide LAR with or without octreotide LAR for two years and underwent transsphenoidal adenomectomy. After treatment with the somatostatin analogs, the surgical cure rate was similar to that in patients who underwent transsphenoidal surgery alone. Diabetes insipidus was not identified in any patients after the operation. Pasireotide LAR was effective on GH as well as IGF-1 suppression and tumor size decreasing when used as the primary therapy. Future large-population studies to investigate the surgical curative rate after presurgical treatment with somatostatin analogs in patients with acromegaly and macroadenomas close to the cavernous sinus are warranted. However, that hyperglycemia developed following pre-surgical treatment with pasireotide should take into consideration.


Subject(s)
Acromegaly/drug therapy , Octreotide/administration & dosage , Pituitary Neoplasms/complications , Pituitary Neoplasms/diagnostic imaging , Somatostatin/analogs & derivatives , Tumor Burden , Adult , Aged , Double-Blind Method , Female , Follow-Up Studies , Human Growth Hormone/metabolism , Humans , Insulin-Like Growth Factor I/metabolism , Magnetic Resonance Imaging , Male , Middle Aged , Prospective Studies , Somatostatin/administration & dosage , Treatment Outcome
7.
Radiother Oncol ; 118(1): 16-23, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26678342

ABSTRACT

BACKGROUND AND PURPOSE: The subventricular zone (SVZ) and the corpus callosum (CC) invasion status are separately associated with adverse prognosis for glioblastoma. We investigated the prognosis and progression patterns of glioblastoma with and without synchronous SVZ and CC (sSVZCC) invasion. MATERIAL AND METHODS: Glioblastoma patients completing concurrent chemoradiotherapy with temozolomide were retrospectively categorized by the preoperative sSVZCC invasion status. The associations between sSVZCC invasion and the survival and progression patterns were analyzed. RESULTS: In total, 108 patients, including 36 with sSVZCC invasion, were followed for a median period of 60.2 (range 34.2-86.3) months. The median overall survival (OS) of patients with and without sSVZCC were 18.6 and 26.4 months, respectively (p=0.005). Using multivariate analyses with the factors of age, performance, surgery extent, and tumor size, sSVZCC invasion remained significant for a poor OS (hazard ratio, 1.96; 95% confidence interval, 1.19-3.21). The rates of progression at tumor bed, preoperative edematous areas, bilateral hemispheres, and ventricles for tumors with and without sSVZCC invasion were 75% and 63.9% (p=0.282), 41.7% and 9.7% (p<0.001), 47.2% and 13.9% (p<0.001), and 38.9% and 13.9% (p=0.006), respectively. CONCLUSIONS: The sSVZCC invasion status determined the distinct prognosis and progression areas of glioblastoma, which suggests individualized radiotherapy and drug administration strategies.


Subject(s)
Brain Neoplasms/therapy , Cerebral Ventricles/pathology , Chemoradiotherapy , Corpus Callosum/pathology , Disease Progression , Glioblastoma/therapy , Adult , Aged , Aged, 80 and over , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Cerebral Ventriculography , Corpus Callosum/diagnostic imaging , Female , Glioblastoma/diagnostic imaging , Glioblastoma/pathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Invasiveness , Prognosis , Proportional Hazards Models , Retrospective Studies , Tomography, X-Ray Computed , Young Adult
8.
PLoS One ; 10(4): e0123359, 2015.
Article in English | MEDLINE | ID: mdl-25894841

ABSTRACT

INTRODUCTION: The accuracy of radiation delivery is increasingly important as radiotherapy technology continues to develop. The goal of this study was to evaluate intrafractional motion during intracranial radiosurgery and the relationship between motion change and treatment time. METHODS AND MATERIALS: A total of 50 treatment records with 5988 images, all acquired during treatments with the CyberKnife Radiosurgery System, were retrospectively analyzed in this study. We measured translation and rotation motion including superior-inferior (SI), right-left (RL), anterior-posterior (AP), roll, tilt and yaw. All of the data was obtained during the first 45 minutes of treatment. The records were divided into 3 groups based on 15-min time intervals following the beginning of treatment: group A (0-15 min), group B (16-30 min) and group C (31-45 min). The mean deviations, systematic errors, random errors and margin for planning target volume (PTV) were calculated for each group. RESULTS: The mean deviations were less than 0.1 mm in all three translation directions in the first 15 minutes. Greater motion occurred with longer treatment times, especially in the SI direction. For the 3D vector, a time-dependent change was observed, from 0.34 mm to 0.77 mm (p=0.01). There was no significant correlation between the treatment time and deviations in the AP, LR and rotation axes. Longer treatment times were associated with increases in systematic error, but not in random error. The estimated PTV margin for groups A, B and C were 0.86 / 1.14 / 1.31 mm, 0.75 / 1.12 / 1.20 mm, and 0.43 / 0.54 / 0.81 mm in the SI, RL, and AP directions, respectively. CONCLUSIONS: During intracranial radiosurgery, a consistent increase in the positioning deviation over time was observed, especially in the SI direction. If treatment time is greater than 15 minutes, we recommend increasing the PTV margins to ensure treatment precision.


Subject(s)
Operative Time , Patient Positioning , Radiosurgery/methods , Humans , Radiographic Image Interpretation, Computer-Assisted , Radiotherapy Planning, Computer-Assisted , Rotation , Time Factors
9.
PLoS One ; 8(6): e67139, 2013.
Article in English | MEDLINE | ID: mdl-23826216

ABSTRACT

The aim of the present study was to identify genetic and epigenetic alterations involved in the progression of oligodendroglial tumors. We characterized 21 paired, World Health Organization (WHO) grade II and III oligodendroglial tumors from patients who received craniotomies for the partial or complete resection of primary and secondary oligodendroglial tumors. Tumor DNA was analyzed for alterations in selected genetic loci (1p36, 9p22, 10q23-24, 17p13, 19q13, 22q12), isocitrate dehydrogenase 1 (IDH1), isocitrate dehydrogenase 2 (IDH2) and the CpG island methylation status of critical tumor-related genes (MGMT, P16, DAPK, PTEN, RASSF1A, Rb1). Alterations of these markers were common early in the tumorigenesis. In the primary tumors we identified 12 patients (57.1%) with 1p36 deletions, 17 (81.0%) with 19q13 deletions, 9 (42.9%) with 1p36/19q13 codeletions, 11 (52.3%) with 9p22 deletions, and 12 (57.1%) with IDH1 mutation. Epigenetic analysis detected promoter methylation of the MGMT, P16, DAPK, PTEN, RASSF1A, and Rb1 genes in 38.1%, 19.0%, 38.1%, 33.3%, 66.7%, and 14.3% of primary tumors, respectively. After progression, additional losses of 1p, 9p, 10q, 17p, 19q and 22q were observed in 3 (14.3%), 1 (4.8%), 3 (14.3%), 2 (9.5%), 1 (4.8%) and 3 (14.3%) cases, respectively. Additional methylations of the MGMT, P16, DAPK, PTEN, RASSF1A, and RB1 promoters was observed in 4 (19.0%), 2 (9.5%), 0 (0%), 6 (28.6%), 2(9.5%) and 3 (14.3%) cases, respectively. The status of IDH1 mutation remained unchanged in all tumors after progression. The primary tumors of three patients with subsequent progression to high-grade astrocytomas, all had 9p deletion, intact 1p, intact 10q and unmethylated MGMT. Whether this may represent a molecular signature of patients at-risk for the development of aggressive astrocytomas needs further investigation.


Subject(s)
Brain Neoplasms/genetics , Brain Neoplasms/pathology , Disease Progression , Epigenesis, Genetic , Oligodendroglioma/genetics , Oligodendroglioma/pathology , Adult , Aged , Base Sequence , DNA Methylation/genetics , DNA Mutational Analysis , Female , Humans , Isocitrate Dehydrogenase/genetics , Longitudinal Studies , Male , Middle Aged , Molecular Sequence Data , Promoter Regions, Genetic/genetics , Real-Time Polymerase Chain Reaction , Treatment Outcome , Young Adult
10.
Stereotact Funct Neurosurg ; 91(3): 177-85, 2013.
Article in English | MEDLINE | ID: mdl-23446119

ABSTRACT

BACKGROUND: Vestibular assessment in patients with acoustic tumor (so-called vestibular schwannoma, VS) via ocular vestibular-evoked myogenic potential (oVEMP) and cervical VEMP (cVEMP) tests are not often discussed in the neurosurgical literature. OBJECTIVES: This study conducted physiological and morphological assessments for VS patients before and after CyberKnife radiosurgery. METHODS: Twenty patients with unilateral VS underwent a battery of tests comprising facial nerve function test, audiometry, and caloric, oVEMP and cVEMP tests before and 2 years after CyberKnife treatment at a mean dosage of 18 Gy in 3 fractions. RESULTS: The abnormal percentages of caloric, oVEMP and cVEMP tests did not significantly differ before and after Cyberknife treatment, indicating that preservation of the superior and inferior vestibular nerves can be achieved after radiosurgery. Median tumor volumes, 1.49 cm3 before treatment versus 0.97 cm3 at 2 years after treatment, differed significantly. CONCLUSIONS: The use of oVEMP and cVEMP tests in VS patients before stereotactic radiosurgery may help to evaluate the tumor origin from the superior or inferior vestibular nerve. It takes a short time and costs less, and it would be practical to make this a routine examination in VS patients having stereotactic radiosurgery.


Subject(s)
Neuroma, Acoustic/surgery , Radiosurgery/instrumentation , Vestibular Evoked Myogenic Potentials/physiology , Vestibular Nerve/physiopathology , Adult , Aged , Aged, 80 and over , Audiometry , Caloric Tests , Female , Humans , Male , Middle Aged , Neuroma, Acoustic/physiopathology , Outcome Assessment, Health Care , Treatment Outcome
11.
Clin Neurol Neurosurg ; 112(7): 552-6, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20483531

ABSTRACT

OBJECTIVES: Acute subdural hematoma (SDH) normally appears as a panhemispheric collection of blood with a crescent configuration. However, a number of SDH show lentiform appearances, mimicking acute epidural hematoma (EDH). In this study, we reported our experiences with this special disease entity. Radiological features that aided in the accurate localization of the hematoma were also addressed. PATIENTS AND METHODS: From among 51 acute SDH cases who were surgically treated between July 2007 and April 2008, five cases whose SDH had a localized convex appearance were enrolled. Surgical records and CT images were retrospectively reviewed. Important CT features that could differentiate lentiform SDH from EDH were especially analyzed. RESULTS: Subdural adhesions were major causes of localized SDH in four out of five patients, all of whom had previous neurosurgical interventions or radiotherapy. Though those hematomas appeared as biconvex on CT scans, four differential features could be identified in favor of SDH. These included a crescentic tail, an obtuse angle at the margin of the hematoma, a dural line above the hematoma and a direct connection to the underlying intracerebral hematomas. CONCLUSIONS: Biconvex localized SDH might be misinterpreted as acute EDH if the diagnosis is based on the shape of the hematoma alone. This study emphasized that a detailed evaluation of surgical histories and CT features are mandatory in differentiating lentiform SDH and EDH.


Subject(s)
Hematoma, Epidural, Spinal/diagnostic imaging , Hematoma, Subdural, Spinal/diagnostic imaging , Adult , Diagnosis, Differential , Diskectomy , Female , Hematoma, Epidural, Spinal/surgery , Hematoma, Subdural, Spinal/surgery , Humans , Low Back Pain/surgery , Male , Mental Health , Middle Aged , Prospective Studies , Quality of Life , Surveys and Questionnaires , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
12.
Lung Cancer ; 68(3): 484-90, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19740564

ABSTRACT

O(6)-Methylguanine-DNA methyltransferase (MGMT) is critical for repairing pro-mutagenic DNA bases and is correlated with response to alkylating agents in cancers. Since there is great interest in pursuing the potential role of temozolomide, a novel alkylating agent, in the treatment of brain metastases, this study aimed to evaluate MGMT expression as well as its prognostic value in this devastating disease. We studied the expression and methylation status of MGMT in 86 brain metastases of lung cancers. Twenty of them had matched primary lung tumor tissues available for direct comparison. MGMT expression was assessed by immunohistochemistry (IHC); the methylation status of MGMT promoter was analyzed by nested methylation-specific PCR (MSP) and validated by quantitative real-time PCR analysis. Positive nuclear MGMT expression was detected more frequently in brain metastases as compared with primary lung cancers (83% versus 50%, P=0.004). The discordance in MGMT expression persisted in the 20 paired primary and metastatic tumors (P=0.031). MGMT promoter hypermethylation was highly correlated with loss of MGMT expression. Both univariate and multivariate analyses showed that median overall survival was significantly longer in patients with positive MGMT expression in brain metastases (16.5 versus 3.5 months, P<0.001). In conclusion, MGMT expression was enhanced in brain metastases as compared with the primary lung cancers. MGMT expression in brain metastases was significantly correlated with better survival.


Subject(s)
Adenocarcinoma/diagnosis , Brain Neoplasms/diagnosis , DNA Modification Methylases/metabolism , DNA Repair Enzymes/metabolism , Lung Neoplasms/diagnosis , Tumor Suppressor Proteins/metabolism , Adenocarcinoma/drug therapy , Adenocarcinoma/enzymology , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/adverse effects , Brain Neoplasms/drug therapy , Brain Neoplasms/enzymology , Brain Neoplasms/genetics , Brain Neoplasms/mortality , Brain Neoplasms/secondary , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Dacarbazine/administration & dosage , Dacarbazine/adverse effects , Dacarbazine/analogs & derivatives , Female , Humans , Immunohistochemistry , Lung Neoplasms/drug therapy , Lung Neoplasms/enzymology , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Methylation , Middle Aged , Predictive Value of Tests , Prognosis , Promoter Regions, Genetic/genetics , Reverse Transcriptase Polymerase Chain Reaction , Survival Analysis , Temozolomide , Tumor Suppressor Proteins/genetics
13.
Int J Cancer ; 124(12): 2872-9, 2009 Jun 15.
Article in English | MEDLINE | ID: mdl-19330828

ABSTRACT

Recent studies have revealed a correlation between specific genetic changes, such as loss of chromosome 1p and 19q, and sensitivity of oligodendroglial neoplasm to radiotherapy and chemotherapy; epigenetic changes also play an important role in some tumors. In this retrospective study, we analyzed chromosomal alterations in 17 loci and promoter methylation status of 8 tumor-related genes in 49 oligodendroglial tumors (29 WHO grade II and 11 WHO grade III oligodendrogliomas; 7 WHO grade II and 2 WHO grade III oligoastrocytomas) using quantitative microsatellite analysis and methylation-specific polymerase chain reaction and correlated this information with clinical data. We also performed immunohistochemical stains for Ki-67 and O (6)-methyl guanine-DNA methyl transferase. Our results showed that the frequency of deletions in regions on 1p, 9p, 10q, 17p and 19q were 71.4%, 26.5%, 6.1%, 69.4% and 89.8%, respectively. Promoter methylation was detected in p14, p15, p16, p53, p73, PTEN, MGMT and RASSF1A genes in 24.5%, 6.1%, 46.9%, 0%, 6.1%, 42.9%, 53.1% and 77.6% of tumors, respectively. Statistical analysis identified that 9p22 loss, p73 methylation and p15 methylation were independently associated with reduced overall survival, and Ki-67 labeling index (LI) > or = 5%, 9p22 loss, no loss of 19q, p73 methylation, p14 methylation and unmethylated MGMT predicted shorter progression-free survival. Our findings suggest that the frequent deletion and hypermethylation of tumor-related genes may represent a mechanism of tumor development and progression and emphasize the importance of defining new molecular markers for predicting prognosis, tumor recurrence and therapeutic response in cancer management.


Subject(s)
Brain Neoplasms/genetics , Chromosome Aberrations , Chromosomes, Human/genetics , Epigenesis, Genetic , Neoplasm Proteins/genetics , Oligodendroglioma/genetics , Oligodendroglioma/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Brain Neoplasms/pathology , Cell Proliferation , Child , Child, Preschool , DNA Methylation , DNA Modification Methylases/genetics , DNA Modification Methylases/metabolism , DNA Repair Enzymes/genetics , DNA Repair Enzymes/metabolism , DNA, Neoplasm/genetics , Female , Humans , Immunoenzyme Techniques , Ki-67 Antigen/metabolism , Male , Microsatellite Repeats , Middle Aged , Neoplasm Proteins/metabolism , Neoplasm Staging , Polymerase Chain Reaction , Promoter Regions, Genetic/genetics , Retrospective Studies , Survival Rate , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Young Adult
14.
Surg Neurol ; 70 Suppl 1: S1:34-8; discussion S1:38-9, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18423539

ABSTRACT

BACKGROUND: Dumbbell-shaped schwannomas of the hypoglossal nerve are very rare. This report concerns a case with an extradural, dumbbell-shaped hypoglossal schwannoma extending both intra- and extracranially. CASE DESCRIPTION: A 25-year-old woman presented with a right hypoglossal palsy. Imaging revealed a dumbbell-shaped tumor with considerable compression and medial displacement of the medulla oblongata, diagnosed as a hypoglossal schwannoma. The tumor mass extended extracranially to the parapharyngeal space through the enlarged hypoglossal canal. The tumor was partially excised by a right far-lateral suboccipital approach and the tumor was found to be predominantly extradural with minimal intradural extension. A histopathologic diagnosis of schwannoma was made. CONCLUSIONS: This case emphasizes the importance of recognizing this extradural variant of schwannoma. Staged extracranial and intracranial approaches to these tumors may be necessary.


Subject(s)
Cranial Nerve Neoplasms/pathology , Cranial Nerve Neoplasms/surgery , Hypoglossal Nerve Diseases/pathology , Hypoglossal Nerve Diseases/surgery , Neurilemmoma/pathology , Neurilemmoma/surgery , Adult , Female , Humans , Magnetic Resonance Imaging , Medulla Oblongata/pathology
15.
Surg Neurol ; 68 Suppl 1: S43-50; discussion S50-1, 2007.
Article in English | MEDLINE | ID: mdl-17963922

ABSTRACT

BACKGROUND: Unilateral subthalamotomy has been reported to be effective in the treatment of rigidity, bradykinesia, and tremor of the contralateral limb. However, gait, clinical fluctuation, and postural stability are not significantly improved by unilateral lesioning of the STN in the long term. We sought to determine if bilateral surgery of the STN offers more benefits in the treatment of advanced PD. METHODS: Radiofrequency thermal coagulation was performed bilaterally in the STN in 10 patients. Under microelectrode and stereotactic guidance, surgery was directed at the dorsolateral portion of the STN in stages and followed by MRI in each patient to confirm lesion location. Patients have been followed for a median duration of 26 months as measured from the date of first surgery (range, 6-48 months) with UPDRS before and after surgery. RESULTS: Bilateral subthalamotomy demonstrated persistent benefits in bradykinesia, rigidity of the limbs, and consequently the improvement in activities of daily living, motor function, Schwab and England scales. In addition, significant improvement in axial motor features, gait, postural stability, and clinical fluctuation were present with bilateral STN surgeries. The benefits were sustained at the last evaluation period of 36 months. Tremor and drug-induced dyskinesia improved in early postoperative period, but the benefits declined over time. The reduction of daily l-dopa equivalent was 34%. No speech impairment was observed. Mild choreic movement occurred in 2 of 20 procedures that resolved spontaneously in 4 to 8 weeks. CONCLUSION: For advanced PD present with bilateral symptoms, axial motor impairment, or clinical fluctuation, staged bilateral subthalamotomy appears as a safe and effective treatment in the long term.


Subject(s)
Catheter Ablation/methods , Functional Laterality/physiology , Parkinson Disease/surgery , Radiosurgery/methods , Subthalamic Nucleus/surgery , Aged , Dyskinesia, Drug-Induced/physiopathology , Dyskinesia, Drug-Induced/surgery , Female , Follow-Up Studies , Humans , Hypokinesia/etiology , Hypokinesia/physiopathology , Hypokinesia/surgery , Levodopa/administration & dosage , Male , Microelectrodes/standards , Middle Aged , Muscle Rigidity/etiology , Muscle Rigidity/physiopathology , Muscle Rigidity/surgery , Neural Pathways/physiopathology , Neural Pathways/surgery , Parkinson Disease/physiopathology , Subthalamic Nucleus/physiopathology , Time , Treatment Outcome , Tremor/etiology , Tremor/physiopathology , Tremor/surgery
16.
Head Neck ; 29(8): 793-8, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17252587

ABSTRACT

BACKGROUND: Meningiomas involving the jugular foramen and parapharyngeal space are extremely rare. They most commonly occur intracranially and then extend to the extracranial region through the foramen of the skull base, such as jugular foramen. Clinically, these tumors mimic the more common glomus jugulare tumor. Preoperative diagnosis can be correct on the basis of the characteristic imaging findings. METHODS: A 52-year-old woman was seen with a left neck mass and mixed-type hearing loss. She underwent physical examination, MRI, high-resolution CT, and angiography. RESULTS: Physical examination revealed a retro-tympanic, pulsatile red mass in the left ear, and mild bulging of the left oropharyngeal wall. The patient was found to have the spreading, carpet-like, meningioma with extracranial extensions via jugular foramen to parapharyngeal space. Preoperative imaging strategy allowing accurate preoperative diagnosis is discussed. CONCLUSIONS: Accurate distinction between meningioma and glomus tumor or schwannoma is possible in most cases, with attention to fine radiologic detail.


Subject(s)
Glomus Jugulare Tumor/diagnosis , Meningeal Neoplasms/diagnosis , Meningioma/diagnosis , Neurilemmoma/diagnosis , Paraganglioma/diagnosis , Angiography , Diagnosis, Differential , Female , Glomus Jugulare/diagnostic imaging , Glomus Jugulare Tumor/diagnostic imaging , Glomus Jugulare Tumor/surgery , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/surgery , Hearing Loss/etiology , Humans , Magnetic Resonance Imaging , Meningeal Neoplasms/complications , Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/surgery , Meningioma/complications , Meningioma/diagnostic imaging , Meningioma/surgery , Middle Aged , Neurilemmoma/diagnostic imaging , Paraganglioma/diagnostic imaging , Tomography, X-Ray Computed , Treatment Outcome
17.
Laryngoscope ; 116(9): 1678-81, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16955003

ABSTRACT

OBJECTIVE/HYPOTHESIS: This retrospective study presents our experience on the posterior cranial fossa tumors in young adults during the past 15 years. METHODS: From 1991 to 2005, 16 (0.8%) of 2,091 young adults (range, 16-29 years) with dizziness/vertigo, hearing loss, or tinnitus were diagnosed with posterior fossa tumor. Each patient underwent a battery of audiovestibular tests and image study. RESULTS: Audiometry revealed sensorineural hearing loss in 12 patients (75%). Spontaneous nystagmus was disclosed in eight patients (50%), consisting of bilateral gaze nystagmus in five, unilateral gaze nystagmus in two, and downbeat nystagmus in one. Electronystagmographic examination displayed abnormal eye tracking test in 75% and abnormal optokinetic nystagmus test in 81% of cases. Magnetic resonance imaging scan demonstrated space-occupying lesions at the cerebellopontine angle in 11, cerebellum in two, brainstem in two, and jugular fossa in one. Diagnoses consisted of vestibular schwannoma and neurofibromatosis II in eight patients (50%), glial neoplasm (including astrocytoma, ependymoma, glioma) in four patients (25%), epidermoid cyst in three patients, and glomus jugulare tumor in one patient. At study close, excluding one lost patient, three patients died as a result of recurrent or residual tumor at the primary site. Restated, 12 of 15 (80%) patients were alive. CONCLUSIONS: Unlike predominant medulloblastoma in children, the most frequent posterior fossa tumor in young adults is vestibular schwannoma and neurofibroma. However, the second most frequent one in young adults is glial neoplasm as opposed to meningioma in adults.


Subject(s)
Cranial Fossa, Posterior/pathology , Infratentorial Neoplasms/complications , Adolescent , Adult , Audiometry , Electronystagmography , Female , Hearing Loss, Sensorineural/etiology , Humans , Infratentorial Neoplasms/therapy , Male , Nystagmus, Pathologic/etiology , Retrospective Studies , Vertigo/etiology
18.
Eur Arch Otorhinolaryngol ; 263(7): 614-7, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16612611

ABSTRACT

Primary myxoma in the head and neck region occurs mostly in the maxilla and mandible, and rarely in the temporal bone. A 32-year-old female patient with temporal bone myxoma manifested as acute vertigo, headache, and tinnitus on the right ear. Audiometry and auditory brainstem response revealed normal responses, bilaterally. Vestibular function test displayed spontaneous nystagmus beating toward the left side. Absent ice water caloric response was disclosed on the right ear, whereas vestibular evoked myogenic potential test showed normal responses, bilaterally. MRI scan demonstrated a well-enhanced mass at the anterior middle portion of the right temporal bone with intracranial extension. Tumor excision via craniotomy was performed, and the histopathological study confirmed as myxoma. One year after operation, follow-up audiovestibular function tests revealed normal responses, except for 23 dB conductive hearing loss on the right ear.


Subject(s)
Evoked Potentials, Auditory , Myxoma/surgery , Skull Neoplasms/surgery , Temporal Bone/surgery , Adult , Audiometry, Pure-Tone , Caloric Tests , Craniotomy , Electronystagmography , Evaluation Studies as Topic , Evoked Potentials, Auditory, Brain Stem , Female , Follow-Up Studies , Headache , Humans , Magnetic Resonance Imaging , Myxoma/pathology , Myxoma/physiopathology , Nystagmus, Pathologic , Skull Neoplasms/pathology , Skull Neoplasms/physiopathology , Temporal Bone/pathology , Tinnitus , Tomography, X-Ray Computed , Treatment Outcome , Vertigo
19.
Neuroimage ; 31(1): 301-7, 2006 May 15.
Article in English | MEDLINE | ID: mdl-16466936

ABSTRACT

Deep brain stimulation of the subthalamic nucleus (STN DBS) has become an accepted tool for the treatment of Parkinson's disease (PD). Although the precise mechanism of action of this intervention is unknown, its effectiveness has been attributed to the modulation of pathological network activity. We examined this notion using positron emission tomography (PET) to quantify stimulation-induced changes in the expression of a PD-related covariance pattern (PDRP) of regional metabolism. These metabolic changes were also compared with those observed in a similar cohort of patients undergoing STN lesioning. We found that PDRP activity declined significantly (P < 0.02) with STN stimulation. The degree of network modulation with DBS did not differ from that measured following lesioning (P = 0.58). Statistical parametric mapping (SPM) revealed that metabolic reductions in the internal globus pallidus (GPi) and caudal midbrain were common to both STN interventions (P < 0.01), although declines in GPi were more pronounced with lesion. By contrast, elevations in posterior parietal metabolism were common to the two procedures, albeit more pronounced with stimulation. These findings indicate that suppression of abnormal network activity is a feature of both STN stimulation and lesioning. Nonetheless, these two interventions may differ metabolically at a regional level.


Subject(s)
Deep Brain Stimulation , Energy Metabolism/physiology , Image Processing, Computer-Assisted , Nerve Net/physiopathology , Parkinson Disease/rehabilitation , Positron-Emission Tomography , Subthalamic Nucleus/physiopathology , Aged , Analysis of Variance , Blood Glucose/metabolism , Brain Mapping , Cerebellum/diagnostic imaging , Cerebellum/physiopathology , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/physiopathology , Corpus Striatum/diagnostic imaging , Corpus Striatum/physiopathology , Female , Fluorodeoxyglucose F18 , Globus Pallidus/diagnostic imaging , Globus Pallidus/physiopathology , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/physiopathology , Humans , Male , Middle Aged , Nerve Net/diagnostic imaging , Neural Pathways/diagnostic imaging , Neural Pathways/physiopathology , Parkinson Disease/diagnostic imaging , Parkinson Disease/physiopathology , Subthalamic Nucleus/diagnostic imaging , Thalamus/diagnostic imaging , Thalamus/physiopathology
20.
Eur Arch Otorhinolaryngol ; 263(6): 548-51, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16477440

ABSTRACT

The aim of this study was to investigate the audiovestibular deficits in those with posterior fossa epidermoid cyst including cerebellopontine angle in two patients and cerebellum in one patient. Prior to operation, all three patients showed bilateral gaze nystagmus. Audiometry revealed mild hearing loss in two patients, and caloric test displayed canal paresis in two patients. After operation, subsidence of gaze nystagmus and recovery of caloric responses were disclosed in all patients. Two patients had both hearing and vestibular evoked myogenic potential (VEMP) results recovered to normal. In contrast, the only one who underwent craniotomy twice displayed bilateral mild hearing loss and delayed VEMPs, possibly due to operation sequela. Hence, bilateral gaze nystagmus may present as an initial sign for posterior fossa epidermoid cyst. Audiovestibular deficits in cases of epidermoid cyst are attributable to compression neuropathy, which may resolve and return to normal responses after surgery.


Subject(s)
Cerebellar Diseases/diagnosis , Epidermal Cyst/diagnosis , Adult , Audiometry , Cerebellar Diseases/surgery , Epidermal Cyst/surgery , Evoked Potentials, Auditory , Female , Hearing Disorders/etiology , Humans , Magnetic Resonance Imaging , Middle Aged , Nystagmus, Pathologic/etiology , Vestibular Function Tests
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