Muh-Lii Liang

Endoscopic transnasal transclival odontoidectomy: a new approach to decompression: technical case report.

OBJECTIVE Endoscopic transnasal transclival resection of the odontoid process is less invasive than the standard transoral odontoidectomy. In this article, we describe our techniques, which are less invasive but provide successful decompression. CLINICAL PRESENTATION From September 2004 to April 2007, three consecutive patients with basilar invagination and instability in the craniovertebral junction were enrolled. The causes for the invagination and instability included rheumatoid arthritis in two patients and trauma in one patient, and all patients presented with myelopathy and quadriparesis before intervention. INTERVENTION All three patients underwent an endoscopic transnasal transclival approach for anterior decompression and resection of the displaced odontoid process and pannus to decompress the underlying medulla. Subsequently, they received occipitocervical fixation by lateral mass screws and bone fusion to ensure stability. Remarkable neurological recovery was observed after surgery in all patients, and no adverse effects were noted. CONCLUSION Compared with the standard transoral approach, the transnasal transclival endoscopic approach for decompressing basilar invagination is a feasible and effective alternative that avoids common disadvantages like prolonged intubation, excessive tongue retraction, and the need for palatal incision.

YM500: a small RNA sequencing (smRNA-seq) database for microRNA research

MicroRNAs (miRNAs) are small RNAs ∼22 nt in length that are involved in the regulation of a variety of physiological and pathological processes. Advances in high-throughput small RNA sequencing (smRNA-seq), one of the next-generation sequencing applications, have reshaped the miRNA research landscape. In this study, we established an integrative database, the YM500 (http://ngs.ym.edu.tw/ym500/), containing analysis pipelines and analysis results for 609 human and mice smRNA-seq results, including public data from the Gene Expression Omnibus (GEO) and some private sources. YM500 collects analysis results for miRNA quantification, for isomiR identification (incl. RNA editing), for arm switching discovery, and, more importantly, for novel miRNA predictions. Wetlab validation on >100 miRNAs confirmed high correlation between miRNA profiling and RT-qPCR results (R = 0.84). This database allows researchers to search these four different types of analysis results via our interactive web interface. YM500 allows researchers to define the criteria of isomiRs, and also integrates the information of dbSNP to help researchers distinguish isomiRs from SNPs. A user-friendly interface is provided to integrate miRNA-related information and existing evidence from hundreds of sequencing datasets. The identified novel miRNAs and isomiRs hold the potential for both basic research and biotech applications.

ENDOSCOPIC TRANSNASAL TRANSCLIVAL ODONTOIDECTOMY: A NEW APPROACH TO DECOMPRESSION

OBJECTIVE Endoscopic transnasal transclival resection of the odontoid process is less invasive than the standard transoral odontoidectomy. In this article, we describe our techniques, which are less invasive but provide successful decompression. CLINICAL PRESENTATION From September 2004 to April 2007, three consecutive patients with basilar invagination and instability in the craniovertebral junction were enrolled. The causes for the invagination and instability included rheumatoid arthritis in two patients and trauma in one patient, and all patients presented with myelopathy and quadriparesis before intervention. INTERVENTION All three patients underwent an endoscopic transnasal transclival approach for anterior decompression and resection of the displaced odontoid process and pannus to decompress the underlying medulla. Subsequently, they received occipitocervical fixation by lateral mass screws and bone fusion to ensure stability. Remarkable neurological recovery was observed after surgery in all patients, and no adverse effects were noted. CONCLUSION Compared with the standard transoral approach, the transnasal transclival endoscopic approach for decompressing basilar invagination is a feasible and effective alternative that avoids common disadvantages like prolonged intubation, excessive tongue retraction, and the need for palatal incision.

Change in treatment strategy for intracranial germinoma: Long-term follow-up experience at a single institute

Previous intracranial germinoma (IG) studies have investigated the effect of different radiotherapy (RT) volumes and the necessity for adjunctive chemotherapy, but there is currently no consensus on the best treatment for this tumor.

Pediatric primary central nervous system germ cell tumors of different prognosis groups show characteristic miRNome traits and chromosome copy number variations

BackgroundIntracranial pediatric germ cell tumors (GCTs) are rare and heterogeneous neoplasms and vary in histological differentiation, prognosis and clinical behavior. Germinoma and mature teratoma are GCTs that have a good prognosis, while other types of GCTs, termed nongerminomatous malignant germ cell tumors (NGMGCTs), are tumors with an intermediate or poor prognosis. The second group of tumors requires more extensive drug and irradiation treatment regimens. The mechanisms underlying the differences in incidence and prognosis of the various GCT subgroups are unclear.ResultsWe identified a distinct mRNA profile correlating with GCT histological differentiation and prognosis, and also present in this study the first miRNA profile of pediatric primary intracranial GCTs. Most of the differentially expressed miRNAs were downregulated in germinomas, but miR-142-5p and miR-146a were upregulated. Genes responsible for self-renewal (such as POU5F1 (OCT4), NANOG and KLF4) and the immune response were abundant in germinomas, while genes associated with neuron differentiation, Wnt/β-catenin pathway, invasiveness and epithelial-mesenchymal transition (including SNAI2 (SLUG) and TWIST2) were abundant in NGMGCTs. Clear transcriptome segregation based on patient survival was observed, with malignant NGMGCTs being closest to embryonic stem cells. Chromosome copy number variations (CNVs) at cytobands 4q13.3-4q28.3 and 9p11.2-9q13 correlated with GCT malignancy and clinical risk. Six genes (BANK1, CXCL9, CXCL11, DDIT4L, ELOVL6 and HERC5) within 4q13.3-4q28.3 were more abundant in germinomas.ConclusionsOur results integrate molecular profiles with clinical observations and provide insights into the underlying mechanisms causing GCT malignancy. The genes, pathways and microRNAs identified have the potential to be novel therapeutic targets.

Intact INI1 gene region with paradoxical loss of protein expression in AT/RT: implications for a possible novel mechanism associated with absence of INI1 protein immunoreactivity.

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system tumor often misdiagnosed as some other type of pediatric embryonal tumor, such as medulloblastoma (MB). Distinguishing AT/RT from primitive neuroectodermal tumor/MB is of clinical significance, as the reported survival rate of patients with AT/RT is much lower than that of patients with average-risk primitive neuroectodermal tumor/MB. The diagnosis of AT/RT currently relies primarily on the morphologic assessment and immunostaining of a few known markers, such as the lack of INI1 protein expression. Immunohistochemical staining of INI1 is considered very sensitive and is highly specific for the detection of INI1 genetic defects. Genetic studies have shown that deletion or mutation of the INI1 gene, which is located on 22q11.2, occurs in AT/RT lesions. During our gene expression microarray analysis, we unexpectedly found a subgroup of AT/RT patients still expressing INI1 mRNA, even though INI1 proteins were negative by immunohistochemistry in those cases. Direct DNA sequencing showed no INI1 sequence alternation in 3 of 4 AT/RTs. Point mutation was found in only 1 allele of the fourth case, which would result in a frameshift mutation and generate a new INI1 protein with an extra 100-aa tail. Global array comparative genomic hybridization analysis confirmed no aberration around the INI1 gene at 22q11.2. It also extended our knowledge on the chromosomal aberration situations in our series. This study reveals that a novel yet unidentified posttranscriptional regulatory mechanism(s) for INI1 protein synthesis exists in AT/RT tumor cells.

Endoscopic transnasal odontoidectomy without resection of nasal turbinates: clinical outcomes of 13 patients

Object The goal of the study was to report a series of consecutive patients who underwent endoscopic transnasal odontoidectomy (ETO) without resection of nasal turbinates. The techniques for this minimally invasive approach are described in detail. Methods The authors conducted a retrospective review of consecutive patients who underwent ETO for basilar invagination. All the patients had myelopathy caused by compression at the cervicomedullary junction, which required surgical decompression. Preoperative and postoperative data, including those from radiographic and clinical evaluations, were compared. Morbidity and mortality rates for the procedure are also reported in detail. Results Thirteen patients (6 men and 7 women) with a mean age of 52.7 years (range 24-72 years) were enrolled. The basilar invagination etiologies were rheumatoid arthritis (n = 5), trauma (n = 4), os odontoideum (n = 2), ankylosing spondylitis (n = 1), and postinfectious deformity (n = 1). The average follow-up duration was 51.2 months (range 0.3-105 months). One patient died 10 days after the operation as a result of meningitis caused by CSF leakage. Among the other 12 patients, the average postoperative Nurick grade (3.2) was significantly improved over that before the operation (4.1, p = 0.004). The mean (± SD) duration of postoperative intubation was 1.5 ± 2.1 days, and there was no need for perioperative tracheostomy or nasogastric tube feeding. There also was no postoperative velopharyngeal insufficiency. There were 6 (46%) intraoperative and 2 (15%) postoperative CSF leaks in the 13 patients in this series. Conclusions ETO is a viable and effective option for decompression at the ventral cervicomedullary junction. This approach is minimally invasive and causes little velopharyngeal insufficiency. The pitfall of this approach is the difficulty in repairing dural defects and subsequent CSF leakage.

Salvage Treatment for Recurrent Intracranial Germinoma After Reduced-Volume Radiotherapy: A Single-Institution Experience and Review of the Literature

PURPOSE Intracranial germinomas (IGs) are highly curable with radiotherapy (RT). However, recurrence still occurs, especially when limited-field RT is applied, and the optimal salvage therapy remains controversial. METHODS AND MATERIALS Between January 1989 and December 2010, 14 patients with clinically or pathologically diagnosed recurrent IGs after RT were reviewed at our institution. Of these, 11 received focal-field RT, and the other 3 received whole-brain irradiation, whole-ventricle irradiation, and Gamma Knife radiosurgery as the respective first course of RT. In addition, we identified from the literature 88 patients with recurrent IGs after reduced-volume RT, in whom the details of salvage therapy were recorded. RESULTS The median time to recurrence was 30.3 months (range, 3.8-134.9 months). One patient did not receive further treatment and was lost during follow-up. Of the patients, 7 underwent salvage with craniospinal irradiation (CSI) plus chemotherapy (CT), 4 with CSI alone, 1 with whole-brain irradiation plus CT, and 1 with Gamma Knife radiosurgery. The median follow-up time was 105.1 months (range, 24.2-180.9 months). Three patients died without evidence of disease progression: two from second malignancies and one from unknown cause. The others remained disease free. The 3-year survival rate after recurrence was 83.3%. A total of 102 patients from our study and the literature review were analyzed to determine the factors affecting prognosis and outcomes. After recurrence, the 5-year survival rates were 71% and 92.9% for all patients and for those receiving salvage CSI, respectively. Univariate analysis showed that initial RT volume, initial RT dose, initial CT, and salvage RT type were significant prognostic predictors of survival. On multivariable analysis, salvage CSI was the most significant factor (p = 0.03). CONCLUSIONS Protracted follow-up is recommended because late recurrence is not uncommon. CSI with or without CT is an effective salvage treatment for recurrence after reduced-volume RT.

Posterior transarticular screw fixation for chronic atlanto-axial instability.

Treatment for chronic atlanto-axial instability remains problematic despite recent innovations in new surgical techniques and instrumentation. Our team reviewed a series of 23 cases of patients with chronic atlanto-axial instability who underwent posterior transarticular screw fixation operations between May 1998 and September 2002. Etiologies of these patients included failed prior surgery, rheumatoid arthritis, congenital anomalies and old odontoid fractures. The clinical presentations were nuchal pain and cervical myelopathy or radiculopathy, with sensory and/or motor deficits that persisted for more than 3 months. We routinely used external reduction to realign the C1-C2 axis prior to operating, and operated on patients using halo-vest fixation. After surgery, the halo-vest was replaced by a collar. In the post-operative follow-up, 22 of the 23 patients (96%) were found to have achieved solid, bony or fibrous union of the C1-C2 axis. Eleven of the 14 (79%) patients with pre-operative neck pain experienced immediate relief or significant improvement. Thirteen of the 20 patients (65%) with myelo-radiculopathy demonstrated improvement of previous motor deficits. Major morbidity included a vertebral artery (VA) injury and a malpositioned screw. No cases of mortality or neurological complications occurred in this series. Posterior transarticular C1-C2 screw fixation results in a high fusion rate without the additional need for rigid external immobilization. It allows good neurological recovery in cases of chronic atlanto-axial instability. Judicious pre-surgical planning and meticulous operative technique may avoid neurological complications and vertebral artery injury.

Neuropsychological functions and quality of life in survived patients with intracranial germ cell tumors after treatment

BACKGROUND The notable survival chances of intracranial germ cell tumors (icGCTs) lead to a rising concern over long-term neurocognitive outcome. Yet, prior evidence related to this issue fails to provide a comprehensive examination of the effects of tumor location and radiotherapy. We attempt to explore their impacts on the neuropsychological functions and life quality in children with icGCT after multimodality treatments. METHODS A retrospective review of 56 patients diagnosed with icGCTs at age <20 and treated at the Taipei Veterans General Hospital was provided. Intelligence, memory, visual organization, attention, and executive function were assessed by neurocognitive tests; adaptation to life, emotional and behavioral changes, interpersonal relationships, and impact on the family were evaluated by parent-report instruments. Effects of tumor locations (germinomas and nongerminomatous malignant germ cell tumors in the pineal, suprasellar, and basal ganglia) and irradiation on these measurements were examined. RESULTS Patients with tumors in the basal ganglia region had lower full-scale IQs than those with tumors in the pineal or suprasellar regions. Subscores of intelligence scale and short-term retention of verbal and visual stimuli showed evident group differences, as did the quality of life and adaptive skills, particularly in psychosocial domains. Patients treated with whole-ventricular irradiation had better outcomes. Extensive irradiation field and high irradiation dosage influenced intellectual functions, concept crystallization, executive function, and memory. CONCLUSIONS Tumor location and irradiation field/dosage appear to be the crucial factors related to certain neuropsychological, emotional, and behavioral dysfunctions that in turn alter the quality of life in children with icGCTs who survive after treatment.