ABSTRACT
PURPOSE: Choroid plexus carcinomas (CPCs) are extremely rare brain tumors and carry a dismal prognosis. Treatment options are limited and there is an urgent need to develop models to further research. In the present study, we established two CPC cell lines and performed multi-omics analyses. These cell lines serve as valuable models to propose new treatments in these rare but deadly brain tumors. METHODS: Multi-omic profiling including, (i) methylation array (EPIC 850 K), (ii) whole genome sequencing (WGS), (iii) CANCERPLEX cancer genome panel testing, (iv) RNA sequencing (RNA-seq), and (v) proteomics analyses were performed in CCHE-45 and NGT131 cell lines. RESULTS: Both cell lines were classified as methylation class B. Both harbored pathogenic TP53 point mutations; CCHE-45 additionally displayed TP53 loss. Furthermore, alterations of the NOTCH and WNT pathways were also detected in both cell lines. Two protein-coding gene fusions, BZW2-URGCP, and CTTNBP2-ERBB4, mutations of two oncodrivers, GBP-4 and KRTAP-12-2, and several copy number alterations were observed in CCHE-45, but not NGT131. Transcriptome and proteome analysis identified shared and unique signatures, suggesting that variability in choroid plexus carcinoma tumors may exist. The discovered difference's importance and implications highlight the possible diversity of choroid plexus carcinoma and call for additional research to fully understand disease pathogenesis. CONCLUSION: Multi-omics analyses revealed that the two choroid plexus carcinoma cell lines shared TP53 mutations and other common pathway alterations and activation of NOTCH and WNT pathways. Noticeable differences were also observed. These cell lines can serve as valuable models to propose new treatments in these rare but deadly brain tumors.
Subject(s)
Carcinoma , Choroid Plexus Neoplasms , Multiomics , Humans , Tumor Suppressor Protein p53/genetics , Choroid Plexus Neoplasms/genetics , Choroid Plexus Neoplasms/pathology , Cell Line , Choroid Plexus/chemistry , Choroid Plexus/metabolism , Choroid Plexus/pathology , DNA-Binding Proteins/metabolismABSTRACT
PURPOSE: Liquid biopsy of cyst fluid in brain tumors has not been extensively studied to date. The present study was performed to see whether diagnostic genetic alterations found in brain tumor tissue DNA could also be detected in cell-free DNA (cfDNA) of cyst fluid in cystic brain tumors. METHODS: Cyst fluid was obtained from 22 patients undergoing surgery for a cystic brain tumor with confirmed genetic alterations in tumor DNA. Pathological diagnoses based on WHO 2021 classification and diagnostic alterations in the tumor DNA, such as IDH1 R132H and TERT promoter mutation for oligodendrogliomas, were detected by Sanger sequencing. The same alterations were analyzed by both droplet digital PCR (ddPCR) and Sanger sequencing in cyst fluid cfDNA. Additionally, multiplex ligation-dependent probe amplification (MLPA) assays were performed to assess 1p/19q status, presence of CDKN2A loss, PTEN loss and EGFR amplification, to assess whether differentiating between astrocytomas and oligodendrogliomas and grading is possible from cyst fluid cfDNA. RESULTS: Twenty-five genetic alterations were found in 22 tumor samples. All (100%) alterations were detected in cyst fluid cfDNA by ddPCR. Twenty of the 25 (80%) alterations were also detected by Sanger sequencing of cyst fluid cfDNA. Variant allele frequency (VAF) in cyst fluid cfDNA was comparable to that of tumor DNA (R = 0.62, Pearson's correlation). MLPA was feasible in 11 out of 17 (65%) diffuse gliomas, with close correlation of results between tumor DNA and cyst fluid cfDNA. CONCLUSION: Cell-free DNA obtained from cyst fluid in cystic brain tumors is a reliable alternative to tumor DNA when diagnosing brain tumors.
Subject(s)
Brain Neoplasms , Cell-Free Nucleic Acids , Oligodendroglioma , Humans , Oligodendroglioma/diagnosis , Oligodendroglioma/genetics , Oligodendroglioma/pathology , Cyst Fluid , Brain Neoplasms/diagnosis , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Mutation , Multiplex Polymerase Chain Reaction , DNAABSTRACT
BACKGROUND: There has been widespread use of short-segment posterior fixation (SSPF) for traumatic thoracolumbar burst fractures. The relationship between the destruction of the vertebral endplate and adjacent disc and postoperative correction loss has been studied in only a few studies. This study investigated the risk factors for correction loss following SSPF. METHODS: Forty-eight patients (mean age 35.0 years) who underwent SSPF for thoracolumbar burst fractures were enrolled. The mean follow-up period was 25.7 months (12-98 months). The neurological status and postoperative back pain were assessed by the medical records. Segmental kyphotic angle (SKA) and anterior vertebral body height ratio (AVBHR) were measured radiographically to assess indirect vertebral body reduction and local kyphosis. Preoperative Sander's traumatic intervertebral disc lesion (TIDL) classification and AO classification were used to evaluate the severity of disc and vertebral endplate injury. The corrective loss was considered present if ΔSKA was ≥10°. A multivariate logistic regression analysis was performed to identify the risk factors associated with postoperative loss of correction. RESULTS: The fracture distribution was as follows: 10 at T12, 17 at L1, 10 at L2, 9 at L3, and 2 at L4. Vertebral fractures were classified in the following way: A3 in 13 patients, A4 in 11, B1 in 11, and B2 in 13. In 47 patients (98%), a union of the fractured vertebrae was achieved. SKA and AVBHR improved significantly after surgery from 11.6° to 3.5° and from 67.2 to 90.0%, respectively. However, the correction loss at follow-up was 10.4° and 9.7%, respectively. Twenty patients (42%) had severe TIDL (grade 3). Postoperative ΔSKA and ΔAVBHR were significantly higher in patients with TIDL grade 3 than with TIDL grade 0-2. The presence of cranial TIDL grade 3 and older age were significant risk factors for ΔSKA ≥10° on multivariate logistic regression analysis. All patients could walk at follow-up. TIDL grade 3 and ΔSKA ≥10° were associated with severe postoperative back pain. CONCLUSIONS: Risk factors for loss of correction after SSPF for thoracolumbar burst fractures were severe disc and endplate destruction at the time of injury and older age.
Subject(s)
Fractures, Bone , Fractures, Comminuted , Intervertebral Disc , Kyphosis , Spinal Fractures , Humans , Adult , Fracture Fixation, Internal/adverse effects , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Lumbar Vertebrae/injuries , Fractures, Bone/complications , Spinal Fractures/diagnostic imaging , Spinal Fractures/etiology , Spinal Fractures/surgery , Intervertebral Disc/diagnostic imaging , Intervertebral Disc/surgery , Intervertebral Disc/injuries , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgery , Thoracic Vertebrae/injuries , Pain, Postoperative/etiology , Kyphosis/diagnostic imaging , Kyphosis/etiology , Kyphosis/surgery , Treatment Outcome , Retrospective StudiesABSTRACT
BACKGROUND: Limitations of gait function persist in some patients with knee osteoarthritis after total knee arthroplasty. This study aimed to identify preoperative muscle composition variables of the operated limb associated with postoperative gait function. METHODS: Longitudinal data from 45 patients who underwent unilateral primary total knee arthroplasty were retrospectively analyzed. Timed Up-and-Go test and gait speed were measured preoperatively and at 3 and 6 months postoperatively. Preoperative muscle composition in the glutei medius and minimus, the quadriceps, the hamstrings, and combination of the hamstrings and quadriceps were evaluated by computed tomography. The area ratio of the individual muscle composition to the total muscle was calculated. The factors associated with Timed Up-and-Go test and gait speed were identified using stepwise regression analysis. RESULTS: Shorter Timed Up-and-Go test and faster gait speed at each time point correlated with higher lean muscle mass area of the total hamstrings, higher area ratio of lean muscle mass to the total hamstrings or to combination of the hamstrings and quadriceps, and lower area ratio of low density lean tissue or intramuscular adipose tissue to the total hamstrings. Shorter Timed Up-and-Go test at each time point also correlated with higher combined area of lean muscle mass of the hamstrings and quadriceps. Faster gait speed at each time point additionally correlated with lower area ratio of intramuscular fat to the total hamstrings and lower area ratio of lean tissue mass or intramuscular adipose tissue to combination of the hamstrings and quadriceps. Regression analysis using the significant muscle composition variables revealed that the area ratio of lean muscle mass to the total hamstrings was the only predictor of Timed Up-and-Go test and gait speed after operation. CONCLUSIONS: Preoperative area ratio of ipsilateral lean muscle mass to the total hamstrings could predict gait function after total knee arthroplasty.
Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Humans , Retrospective Studies , Muscle Strength/physiology , Gait/physiology , Osteoarthritis, Knee/surgery , Lower Extremity , Quadriceps Muscle/physiologyABSTRACT
BACKGROUND: Although the mortality related to hip fracture and osteoporotic vertebral fracture have been reported, few studies have examined the mortality related to atlas and/or axis fractures. The aim of this study was to assess the association between mortality and atlas and/or axis fractures retrospectively and to elucidate the efficacy of surgical treatment. METHODS: A total of 33 elderly patients who were treated for atlas and/or axis fractures at our institution between January 2012 and December 2018 were included in this study. These patients were divided into two groups: surgical treatment and conservative treatment. Fracture types, comorbidities, neurological status, treatment types, and walking ability at follow-up were reviewed. Mortality was assessed using medical records or via phone interviews. RESULTS: The mean age at injury was 79.9 ± 8.0 years, and the mean follow-up period was 2.3 years. The overall mortality rates at 1 and 5 years were 21.4% and 48.4%, respectively. During the observation period, 12 (36%) patients died. Twenty-two patients were treated conservatively (14 were treated with a cervical collar, 8 were treated with a halo vest). Surgical procedures included occipital-cervical fixation, osteosynthesis of C2 fractures, C1-2 fixation, and C1-4 fixation using a posterior approach. Surgical treatment correlated with better survival rates. There was no significant difference between the two groups in terms of ambulatory ability and functional recovery. CONCLUSION: Upper cervical spine fractures appear to have a worse prognosis compared to hip and osteoporotic vertebral fractures. This study indicates the efficacy of surgical treatment for upper cervical spine fractures in the elderly for improving survival prognosis.
Subject(s)
Osteoporotic Fractures , Spinal Fractures , Aged , Cervical Vertebrae/surgery , Fracture Fixation, Internal/methods , Humans , Osteoporotic Fractures/diagnostic imaging , Osteoporotic Fractures/mortality , Osteoporotic Fractures/surgery , Retrospective Studies , Spinal Fractures/diagnostic imaging , Spinal Fractures/mortality , Spinal Fractures/surgery , Treatment OutcomeABSTRACT
There is growing interest in liquid biopsy, the less-invasive detection of circulating tumor DNA(ctDNA)or circulating tumor cells(CTCs)from cerebrospinal fluid(CSF)and/or serum of patients, for the diagnosis of brain tumors. We share our experience of detecting hot spot point mutations using droplet digital PCR(ddPCR)in ctDNA obtained from the CSF of patients with brain tumors. The detection of mutations such as IDH1 R132H, BRAF V600E, and TERT promoter mutations in gliomas can be diagnostic. For optimal detection of ctDNA, which is only seen at very low concentrations, proper handling and storage of CSF, high-yield extraction of ctDNA, and usage of sensitive PCR methods for detection are imperative. We discuss which mutations can be assessed when diagnosing brain tumors, with a specific focus on gliomas. Finally, we look at what the near future holds for liquid biopsy of brain tumor patients, including next-generation sequencing panel analysis and accurate assessment of fusion genes.
Subject(s)
Brain Neoplasms , Circulating Tumor DNA , Glioma , Biomarkers, Tumor/genetics , Brain Neoplasms/diagnosis , Brain Neoplasms/genetics , Circulating Tumor DNA/genetics , Glioma/diagnosis , Glioma/genetics , Humans , Liquid BiopsyABSTRACT
We present the case of an 11-month-old girl with linear nevus sebaceous syndrome who underwent posterior quadrantectomy(PQ)for intractable epilepsy due to cortical dysplasia extending from the temporal, parietal, and occipital lobes in the right hemisphere. Epileptic spasms started at 4 months after birth, and the frequency of her seizures gradually increased to 10 episodes per day. Electroencephalograms in the interictal periods showed hypsarrhythmia. Magnetic resonance imaging(MRI)suggested cortical dysplasia in the right temporal, parietal, and occipital lobes. Ictal single-photon emission computed tomography revealed increased cerebral blood flow in similar areas as the cortical dysplasia suggested on MRI. Several antiepileptic drugs were administered to control the epileptic spasms, without success. In addition, her developmental delay gradually became evident. Because the epileptic foci extended into the posterior region of the right hemisphere, we did not execute a focused resection, but performed a PQ. The epileptic spasms completely disappeared after surgery and her developmental delay gradually improved. Early surgical intervention via PQ is useful in patients with drug-resistant epilepsy in whom the epileptic foci have extended into the temporal, parietal, and occipital lobes. This intervention not only controls intractable seizures but also helps to facilitate normal development.
Subject(s)
Drug Resistant Epilepsy , Epilepsy , Cerebral Cortex , Drug Resistant Epilepsy/surgery , Electroencephalography , Female , Humans , Infant , Magnetic Resonance ImagingABSTRACT
We have previously reported that reliable detection of 2-hydroxyglutarate (2HG) in isocitrate dehydrogenase (IDH)-mutant WHO grade 2 and 3 gliomas is possible utilizing 3.0-T single-voxel magnetic resonance spectroscopy (SVMRS). We set out to determine whether the same method could be applied to detect 2HG in IDH-mutant glioblastoma. Forty-four patients harboring glioblastoma underwent pre-operative MRS evaluation to detect 2HG and other metabolites. Presence of IDH-mutations was determined by IDH1 R132H immunohistochemical analysis and DNA sequencing of surgically obtained tissues. Six out of 44 (13.6%) glioblastomas were IDH-mutant. IDH-mutant glioblastoma exhibited significantly higher accumulation of 2HG (median 3.191 vs. 0.000 mM, p < 0.0001, Mann-Whitney test). A cutoff of 2HG = 0.897 mM achieved high sensitivity (100.0%) and specificity (92.59%) in determining IDH-mutation in glioblastoma. Glioblastoma with high 2HG accumulation did not have significantly longer overall survival than glioblastoma with low 2HG accumulation (p = 0.107, log-rank test). Non-invasive and reliable detection of 2HG in IDH-mutant glioblastoma was possible by 3.0-T SVMRS.
Subject(s)
Brain Neoplasms/diagnosis , Glioblastoma/diagnosis , Glutarates/metabolism , Isocitrate Dehydrogenase/genetics , Magnetic Resonance Spectroscopy , Adolescent , Adult , Aged , Aged, 80 and over , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Child , Female , Glioblastoma/genetics , Glioblastoma/metabolism , Humans , Male , Middle Aged , Mutation/genetics , Reproducibility of Results , Sensitivity and Specificity , Young AdultABSTRACT
Glioblastoma (GBM), one of the most malignant human cancers, frequently recurs despite multimodal treatment with surgery and chemo/radiotherapies. GBM-initiating cells (GICs) are the likely cell-of-origin in recurrences, as they proliferate indefinitely, form tumors in vivo, and are resistant to chemo/radiotherapies. It is therefore crucial to find chemicals that specifically kill GICs. We established temozolomide (the standard medicine for GBM)-resistant GICs (GICRs) and used the cells for chemical screening. Here, we identified 1-(3-C-ethynyl-ß-d-ribopentofuranosyl) uracil (EUrd) as a selective drug for targeting GICRs. EUrd induced the death in GICRs more effectively than their parental GICs, while it was less toxic to normal neural stem cells. We demonstrate that the cytotoxic effect of EUrd on GICRs partly depended on the increased expression of uridine-cytidine kinase-like 1 (UCKL1) and the decreased one of 5'-nucleotidase cytosolic III (NT5C3), which regulate uridine-monophosphate synthesis positively and negatively respectively. Together, these findings suggest that EUrd can be used as a new therapeutic drug for GBM with the expression of surrogate markers UCKL1 and NT5C3. Stem Cells 2016;34:2016-2025.
Subject(s)
Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Dacarbazine/analogs & derivatives , Drug Evaluation, Preclinical , Glioblastoma/drug therapy , Glioblastoma/pathology , Uracil/therapeutic use , Uridine/analogs & derivatives , 5'-Nucleotidase/metabolism , Animals , Carcinogenesis/metabolism , Carcinogenesis/pathology , Cell Cycle Checkpoints/drug effects , Cell Death/drug effects , Cell Line, Tumor , Dacarbazine/pharmacology , Dacarbazine/therapeutic use , Drug Resistance, Neoplasm/drug effects , Glycoproteins/metabolism , Humans , Mice, SCID , Temozolomide , Uracil/pharmacology , Uridine/pharmacology , Uridine/therapeutic useABSTRACT
Objective: In this study, we provide long-term outcome data of patients with primary central nervous system lymphoma. Methods: The long-term outcomes of PCNSL patients diagnosed between 1982 and 2006 were reviewed. Neurological late neurotoxicity symptoms, neuroradiological brain atrophy and leukoencephalopathy were evaluated. Surviving patients completed the Quality of Life Questionnaire-30 and Brain Cancer Module-20. The differences in overall survival were assessed using the Kaplan-Meier method and log-rank test. The differences between groups in terms of each investigated parameter were analyzed using the Wilcoxon signed-rank test. Results: Among 112 PCNSL patients, there were 33 (29.4%) long-term (> 5 years) survivors. The median survival of all long-term survivors was 105.7 months; of these, 8 (7.1%) were alive at the latest follow-up, with a mean survival time of 170.2 months (range, 121.8286.4). Clinical assessment revealed severe neurotoxicity in 14 patients (42.4%), moderate neurotoxicity in 5 (15.1%), and normal status in 14 (42.4%). Correlations were seen between the neuroradiological imaging score changes and neurocognitive condition (P=0.0001), neurocognitive condition and the whole brain irradiation dose (P=0.0004), and atrophy and the whole brain irradiation dose (P=0.0035). Conclusions: A more severe clinical condition was found to be associated with increasing age and whole brain irradiation dose in long-term survivors with PCNSL.
Subject(s)
Central Nervous System Neoplasms/physiopathology , Lymphoma, Non-Hodgkin/physiopathology , Central Nervous System Neoplasms/drug therapy , Central Nervous System Neoplasms/mortality , Central Nervous System Neoplasms/psychology , Female , Humans , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/psychology , Male , Middle Aged , Prognosis , Quality of Life , SurvivorsABSTRACT
Although primary diffuse large B-cell lymphomas of the CNS are designated as primary CNS lymphomas according to the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue in 2008, a variety of other lymphomas (Burkitt lymphomas, EBV-positive diffuse large B-cell lymphoma of the elderly) and related diseases (lymphomatoid granulomatosis) that are also found in the CNS have been spotlighted in recent years. The histopathology of primary CNS Burkitt lymphomas mimics that of primary diffuse large B-cell lymphomas of the CNS after steroid administration. Therefore, for correct diagnosis of the involved lymphoma, comprehensive fluorescent in situ hybridization analysis for c-MYC and BCL2 is recommended in all primary CNS lymphoma cases with aggressive clinical course, multifocal involvement of the CNS, and a high proliferation index. The pathological characteristics of primary CNS EBV-positive diffuse large B-cell lymphoma of the elderly have similarities with those of the latency phenotype III, EBV lymphoproliferative disorders that arise in the setting of immunodeficiency. These age-related lymphomas usually occur in elderly immunocompetent patients, and the incidence of this disease was estimated to range from 4.0% to 13.6% of all primary CNS lymphomas. Shorter overall survival has been reported for patients with this disease. Lymphomatoid granulomatosis (LYG) is a systemic, EBV-driven, angiocentric and angiodestructive lymphoproliferative disorder. Primary LYG that shows distinct clinicopathological features compared with systemic LYG was recently reported. Finally, this review focuses on the relationship between primary CNS lymphomas and demyelinating diseases, and the concomitant use of intraoperative cytology and frozen sections that are helpful in rapid intraoperative diagnosis.
Subject(s)
Central Nervous System Neoplasms/diagnostic imaging , Central Nervous System Neoplasms/pathology , Lymphoma/diagnostic imaging , Lymphoma/pathology , Adult , Aged , Aged, 80 and over , Demyelinating Diseases/diagnostic imaging , Demyelinating Diseases/pathology , Diagnosis, Differential , Female , Humans , Lymphoma, B-Cell/diagnostic imaging , Lymphoma, B-Cell/pathology , Male , Middle AgedABSTRACT
Genetic and epigenetic status, including mutations of isocitrate dehydrogenase (IDH) and TP53 and methylation of O(6) -methylguanine-DNA methyltransferase (MGMT), are associated with the development of various types of glioma and are useful for prognostication. Here, using routinely available histology sections from 312 patients with diffuse gliomas, we performed immunohistochemistry using antibodies specific for IDH1 mutation, MGMT methylation status, and aberrant p53 expression to evaluate the possible prognostic significance of these features. With regard to overall survival (OS), univariate analysis indicated that an IDH1-positive profile in patients with glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligoastrocytoma and oligodendroglioma, or a MGMT-negative profile in patients with GBM and AA were significantly associated with a favorable outcome. Multivariate analysis revealed that both profiles were independent factors influencing prognosis. The OS of patients with IDH1-positive/MGMT-negative profiles was significantly longer than that of patients with negative/negative and negative/positive profiles. A p53 profile was not an independent prognostic factor. However, for GBM/AA patients with IDH1-negative/MGMT-negative profiles, p53 overexpression was significantly associated with an unfavorable outcome. Thus, the immunohistochemical profiles of IDH1 and MGMT are of considerable significance in gliomas, and a combination of IDH1, MGMT and p53 profiles may be useful for prognostication of GBM/AA.
Subject(s)
Brain Neoplasms/metabolism , Brain Neoplasms/pathology , DNA Modification Methylases/metabolism , DNA Repair Enzymes/metabolism , Glioma/metabolism , Glioma/pathology , Isocitrate Dehydrogenase/metabolism , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Proteins/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Brain Neoplasms/mortality , Female , Glioma/mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Young AdultABSTRACT
CASE: (1) A 69-year-old man sustained a proximal humeral fracture-dislocation. During emergency surgery, copious bleeding occurred. A pseudoaneurysm was identified 30 days postoperatively. (2) A 69-year-old man sustained a proximal humeral fracture and axillary artery injury. Physical examination demonstrated a cold but pink hand. Hemiarthroplasty and bypass vein grafting were performed. (3) An 86-year-old woman sustained a proximal humeral fracture and axillary artery injury. Her hand had turned cold and pale. Reverse shoulder arthroplasty and bypass vein grafting were performed. CONCLUSION: In cases of proximal humeral fractures with significant displacement, concomitant axillary artery injury must be assessed and if there is a high index of suspicion, prompt advanced imaging is necessary.
Subject(s)
Axillary Artery , Shoulder Fractures , Humans , Axillary Artery/injuries , Axillary Artery/surgery , Axillary Artery/diagnostic imaging , Shoulder Fractures/surgery , Shoulder Fractures/diagnostic imaging , Shoulder Fractures/complications , Aged , Male , Female , Aged, 80 and over , Aneurysm, False/diagnostic imaging , Aneurysm, False/surgery , Aneurysm, False/etiology , Shoulder Dislocation/surgery , Shoulder Dislocation/diagnostic imagingABSTRACT
Genetic testing has improved the accuracy of diagnosis of brain tumors, and treatment is now tailored to the type of brain tumor. In contrast, the factors that influence the improvement in independence in activities of daily living (ADLs) following rehabilitation have not been clarified, particularly the role of tumor type. In this retrospective cohort study of 358 participants, we analyzed changes in the Functional Independence Measure (FIM) from pre-rehabilitation to post-rehabilitation provided in an acute care hospital. Multiple regression was used to determine whether FIM gain is associated with age, gender, preadmission Karnofsky Performance Status (KPS), number of rehabilitation days, average duration of daily therapy (min/day), and tumor recurrence and type (WHO grade 1, 2, 3, and 4 gliomas; primary central nervous system lymphomas; and metastatic brain tumors). The results showed that older age (ß -0.183), tumor recurrence (ß -0.137), preadmission KPSâ <â 80 (ß -0.180), and higher baseline total FIM score (ß -0.470) were associated with lower FIM gain whereas the average duration of daily therapy (ß 0.153) was associated with higher FIM gain. Brain tumor type was not associated with FIM gain. Improved independence in ADLs is more influenced by demographic, functional status, and treatment factors than differences in brain tumor type.
ABSTRACT
Neurocutaneous melanosis (NCM) is a rare congenital neurocutaneous syndrome characterized by congenital melanocytic nevus of skin and abnormal proliferation of leptomeningeal melanocytes. Early acquisition of post-zygotic somatic mutations has been postulated to underlie the pathogenesis of NCM. The pathogenesis of NCM remains to be fully elucidated, and treatment options have not been established. Here, we report for the first time, multiregional genomic analyses in a 3-year-old autopsied girl with leptomeningeal melanomatosis associated with NCM, in which a ventriculo-peritoneal (VP) shunt was inserted for the treatment of hydrocephalus. The patient expired six months after the onset due to respiratory failure caused by abdominal dissemination via VP shunt. We performed multiregional exome sequencing to identify genomic differences among brain and abdominal tumors, nevus, and normal tissues. A total of 87 somatic mutations were found in 71 genes, with a significantly large number of gene mutations found in the tumor site. The genetic alterations detected in the nevus were only few and not shared with other sites. Three mutations, namely GNAQ R183Q, S1PR3 G89S and NRAS G12V, considered pathogenic, were found, although S1PR3 mutations have not been previously reported in melanocytic tumors. GNAQ and S1PR3 mutations were shared in both tumor and normal sites. Moreover, the mutant allele frequencies of the two mutations were markedly higher in tumor sites than in normal sites, with copy-neutral loss-of-heterozygosity (CN-LOH) occurring in tumor. NRAS mutation was found only in the abdominal tumor and was thought to be responsible for malignant progression in the present case. Multiregional comprehensive genetic analysis may lead to discovering novel driver mutations associated with tumorigenesis and targeted therapy.
Subject(s)
Melanosis , Neurocutaneous Syndromes , Nevus , Skin Neoplasms , Female , Humans , Child, Preschool , Neurocutaneous Syndromes/genetics , Mutation, Missense , Skin Neoplasms/genetics , Membrane Proteins/genetics , GTP Phosphohydrolases/geneticsABSTRACT
Surgical biopsy is the gold standard for diagnosing central nervous system (CNS) lymphomas. However, reliable liquid biopsy methods for diagnosing CNS lymphomas have quickly developed and have been implicated in clinical decision-making. In the current report, we introduce two patients for whom liquid biopsy was essential for diagnosing CNS lymphomas and discuss the rapidly growing applications of this technology.
Subject(s)
Central Nervous System Neoplasms , Aged , Female , Humans , Male , Central Nervous System Neoplasms/diagnosis , Central Nervous System Neoplasms/pathology , Liquid Biopsy/methods , Lymphoma/diagnosis , Lymphoma/pathologyABSTRACT
Molecular analysis of the growing teratoma syndrome has not been extensively studied. Here, we report a 14-year-old boy with a growing mass during treatment for a mixed germ cell tumor of the pineal region. Tumor markers were negative; thus, growing teratoma syndrome was suspected. A radical resection via the occipital transtentorial approach was performed, and histopathological examination revealed a teratoma with malignant features. Methylation classifier analysis confirmed the diagnosis of teratoma, and DMRT1 loss and 12p gain were identified by copy number variation analysis, potentially elucidating the cause of growth and malignant transformation of the teratoma. The patient remains in remission after intense chemoradiation treatment as a high-risk germ cell tumor.
Subject(s)
Teratoma , Humans , Male , Teratoma/therapy , Teratoma/pathology , Adolescent , Brain Neoplasms/therapy , Combined Modality TherapyABSTRACT
This study aimed to identify preoperative lower-limb muscle predictors for gait speed improvement after total hip arthroplasty (THA) with hip osteoarthritis. Gait speed improvement was evaluated as the subtraction of preoperative speed from postoperative speed. The preoperative muscle composition of ipsilateral hip abductors was evaluated using computed tomography. The females (n = 45) showed smaller total cross-sectional areas of the gluteal muscles than the males (n = 13). The gluteus maximus in the females showed lower lean muscle mass area (LMM) and higher ratios of the intramuscular fat area and the intramuscular adipose tissue area to the total muscle area (TM) than the males. Regression analysis revealed that LMM/TM of the glutei medius and minimus may correlate negatively with postoperative improvement in gait speed. Receiver operating characteristic curve analysis for prediction of minimum clinically important improvement in gait speed at ≥0.32 m/s resulted in the highest area under the curve for TM in the upper portion of the gluteus maximus with negative correlation. The explanatory variables of hip abductor muscle composition predicted gait speed improvement after THA more precisely in the females compared with the total group of both sexes. Preoperative muscle composition should be evaluated separately based on sex for the achievement of clinically important improvement in gait speed after THA.
ABSTRACT
Background The volar lip of the distal radius is the key structure for wrist joint stability. Rigid fixation of the volar lunate facet (VLF) fragment is difficult because of its unique anatomy, and a high rate of postoperative displacement was demonstrated. Purposes The aim of the study is to identify risk factors for VLF in distal radius fractures (DRFs) and to reconsider the important point for primary fixation. Patients and Methods One hundred fifty-five patients who underwent open reduction and internal fixation for an DRF were included and classified into one of the following two groups: VLF(+)or VLF(-). Demographic data, including age, sex, body mass index (BMI), laterality, trauma mechanism, and AO Foundation/Orthopaedic Trauma Association (AO/OTA) classification were recorded. Several parameters were investigated using wrist radiographs of the uninjured side and computed tomography scans of the injured side. Univariate and multivariate logistic regression analyses were performed to evaluate the risk factors for VLF. Results There were 25 patients in the VLF(+) group and 130 patients in the VLF(-) group. The incidence of VLF was 16.1%. The VLF(+) group tended to have a higher BMI and higher energy trauma mechanism. The odds ratio for the sigmoid notch angle (SNA), volar tilt (VT), and lunate facet curvature radius (LFCR) were 0.84, 1.32, and 0.70, respectively, with multivariate analysis, which was significant. A smaller SNA, larger VT, and smaller LFCR are potential risk factors for VLF. Conclusion Over-reduction of the VT at primary fixation should be avoided because it could place an excess burden on the VLF and cause subsequent postoperative fixation failure and volar carpal subluxation. Level of Evidence IV.
ABSTRACT
BACKGROUND: Cerebellopontine angle (CPA) lipoma-associated hemifacial spasm (HFS) is rare. As the removal of CPA lipomas has a high risk of worsening the neurological symptoms, surgical exploration is warranted only in selected patients. Preoperative identification of the lipoma affected site of the facial nerve, and offending artery are crucial for patient selection and successful microvascular decompression (MVD). OBSERVATIONS: Presurgical simulation using three-dimensional (3D) multifusion imaging showed a tiny CPA lipoma wedged between the facial and auditory nerves, as well as an affected facial nerve by the anterior inferior cerebellar artery (AICA) at the cisternal segment. Although a recurrent perforating artery from the AICA anchored the AICA to the lipoma, successful MVD was achieved without lipoma removal. LESSONS: The presurgical simulation using 3D multifusion imaging could identify the CPA lipoma, affected site of the facial nerve, and offending artery. It was helpful for patient selection and successful MVD.