Metabolomic profiles of ovariectomized mice and their associations with body composition and frailty-related parameters in postmenopausal women.

BACKGROUND: Menopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women's health. PURPOSE: To investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women. METHODS AND RESULTS: Untargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36:6, and PC ae C42:3 in plasma as well as PC aa 34:1, PC aa C34:3, PC aa C36:5, PC aa C32:1, PC aa C36:2, and sphingosine in muscle as top featured metabolites that differentiate the OVX mice from the sham-operated group. When circulating levels of AKG, arginine, and carnosine, which showed the most significant changes in OVX mice blood, were measured in postmenopausal women, higher plasma AKG levels were associated with lower bone mass, weak grip strength, poor physical performance, and increased frailty risk. CONCLUSIONS: Metabolomics- and ML-based methods identified the key metabolites of blood and muscle that were significantly changed after ovariectomy in mice, and the clinical implication of several metabolites was investigated by looking at their correlation with body composition and frailty-related parameters in postmenopausal women. These findings provide crucial context for understanding the diverse physiological alterations caused by estrogen deficiency in women.

CRISPR-Cas9 and beyond: identifying target genes for developing disease-resistant plants.

Throughout the history of crop domestication, desirable traits have been selected in agricultural products. However, such selection often leads to crops and vegetables with weaker vitality and viability than their wild ancestors when exposed to adverse environmental conditions. Considering the increasing human population and climate change challenges, it is crucial to enhance crop quality and quantity. Accordingly, the identification and utilization of diverse genetic resources are imperative for developing disease-resistant plants that can withstand unexpected epidemics of plant diseases. In this review, we provide a brief overview of recent progress in genome-editing technologies, including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) technologies. In particular, we classify disease-resistant mutants of Arabidopsis thaliana and several crop plants based on the roles or functions of the mutated genes in plant immunity and suggest potential target genes for molecular breeding of genome-edited disease-resistant plants. Genome-editing technologies are resilient tools for sustainable development and promising solutions for coping with climate change and population increases.

Relationship between radiological characteristics and combined 1p and 19q deletion in World Health Organization grade III oligodendroglial tumours.

OBJECTIVE: The radiological characteristics of World Health Organization grade III oligodendroglial tumours in relation to chromosome 1p and 19q deletions were analysed. METHODS: 56 patients recently diagnosed with anaplastic oligodendroglioma (AO, n=49) or anaplastic oligoastrocytoma (AOA, n=7) were studied. Their preoperative magnetic resonance images were examined. Deletions of chromosome 1p and 19q were determined using the fluorescence in situ hybridisation method. Both 1p and 19q chromosomes had deletions (1p19q codeletion) in 39 patients (36 AO and 3 AOA). RESULTS: Tumors associated with the 1p19q codeletion were predominantly located in the frontal lobe (p=0.044). The magnetic resonance image characteristics of indistinct tumour borders (p=0.005 on T1, p=0.036 on T2) and a heterogeneous intratumoural signal intensity (p=0.033 on T1, p=0.041 on T2) were significantly correlated with the 1p19q codeletion. Analysis of patient survival showed those with the 1p19q-co-deleted tumours survived significantly longer than those lacking the 1p19q codeletion (p=0.042). The presence of a heterogeneous signal intensity in T2-weighted images, a characteristic significantly related to the 1p19q codeletion, indicated a favourable prognosis for patients' survival (HR; 0.125, 95% CI, 0.016 to 0.963, p=0.046) based on multivariate analysis. CONCLUSION: A relationship between radiological characteristics and molecular signatures in AO/AOAs was shown. It is believed that radiological characteristics have prognostic value as a surrogate marker for molecular characteristics.

Combination treatment with corticosteroid, cyclosporine A, and mycophenolate in refractory nephrotic syndrome.

BACKGROUND/AIMS: Refractory nephrotic syndrome (NS) is problematic because the optimal therapy for this disease is unclear and because persistent NS progresses eventually to end-stage renal disease. We report our experience using a combination of corticosteroid, cyclosporine A (CsA), and mycophenolate mofetil (MMF) to treat 10 refractory NS patients. METHODS: Ten refractory NS patients, who showed resistance to corticosteroid and CsA, were treated with triple immunosuppressive therapy. Cyclophosphamide and MMF had been used previously in 6 patients, but had failed to induce remission. RESULTS: Triple immunosuppressive therapy was discontinued after 4 months in 1 patient because of progressive azotemia. Partial remission was achieved in 9 of the 10 patients after 10 months, and remission was maintained during the treatment (urine protein to creatinine ratio, mg/mg, baseline vs. 12th month; 5.7 ± 1.8 vs. 1.4 ± 0.7). Renal function was preserved in these 9 patients (estimated GFR, ml/min/1.73 m2, baseline vs. 12th month; 71.4 ± 29.1 vs. 68.9 ± 31.5). Of the 7 patients who discontinued triple immunosuppressive therapy, remission and renal function were maintained in 4 patients. CONCLUSION: Triple immunosuppressive therapy significantly reduced proteinuria and preserved renal function in refractory NS patients, indicating a promising role of this therapy for refractory NS.

Atypical and anaplastic meningiomas: prognostic implications of clinicopathological features.

OBJECTIVES: To evaluate patient outcome and investigate the prognostic factors of high-grade meningiomas by adopting the 2000 World Health Organization (WHO) classification system. METHODS: Between 1986 and 2004, 74 patients were diagnosed with high-grade meningioma: 33 with atypical and 41 with anaplastic meningioma. The mean follow-up was 58.5 months. We reclassified all surgical specimens, according to the 2000 WHO classification system, using two expert neuropathologists. RESULTS: Forty of 74 meningiomas were reclassified as atypical meningioma and 24 as anaplastic meningioma. Overall and recurrence-free survivals were significantly longer in patients with atypical than in those with anaplastic meningioma: 142.5 versus 39.8 months and 138.5 versus 32.2 months, respectively (p<0.001). In patients with atypical meningiomas, brain invasion and adjuvant radiotherapy were not associated with survival; however, in the brain invasion subgroup, adjuvant radiotherapy improved patients' survival. In patients with anaplastic meningioma, the prognostic factors were brain invasion, adjuvant radiotherapy, malignant progression, p53 overexpression and extent of resection. The p53 overexpression was the only factor associated with malignant progression (p = 0.009). CONCLUSIONS: The 2000 WHO classification has identified the truly aggressive meningiomas better than did the previous criteria. A precise meningioma grading system may help to avoid over-treatment of patients with an atypical meningioma as, once the tumour has "declared itself" by recurrence and histological features, it becomes a tumour that is poorly amenable to current therapies.

Evaluation of tumour response after gamma knife radiosurgery for residual vestibular schwannomas based on MRI morphological features.

OBJECTIVE: To evaluate tumour response after gamma knife (GK) radiosurgery for residual vestibular schwannoma (VS) based on MRI morphological features. METHODS: Sixty-one patients with histopathologically confirmed VS underwent GK radiosurgery with marginal tumour doses of 9.0-14.0 Gy (mean, 12.5). Mean tumour volume at GK radiosurgery was 3.65 ml (range, 0.52-15.50). GK radiosurgery was performed 0.3-95.7 months (median, 5.8) after microsurgery. Tumour volumes and half-reduction time were calculated using serial MRI. The morphological features of VS were documented by pre-microsurgical MRI. Histopathological investigation included Antoni-type dominance, the proliferation marker Ki-67 and tumour vascularity. RESULTS: Median duration of radiological follow-up was 53.7 months (range, 24.1-102.2) and the 8-year actuarial tumour control rate was 93.5%. No factor was associated with tumour control, although a cystic VS had borderline significance (p = 0.089). Mean tumour half-reduction time was 8.70 years (range, 0.57-79.89) and tumour half-reduction time in cystic VS proved to be significantly shorter than those in solid VS (p = 0.006). Thrombotic vessels (p = 0.015) and abnormal vessel proliferation (p = 0.003) were significantly more prominent in cystic VS than those in solid VS. CONCLUSIONS: GK radiosurgery appeared to be an effective treatment modality for residual tumour control after microsurgery. Owing to having relatively abundant tumour vascularity, residual solid portions of cystic VS resulted in efficient shrinkage after GK radiosurgery. Therefore, GK radiosurgery was found to be a rewarding therapeutic approach to the residual solid portions of cystic VS.

Prevalence of Antiphospholipid Antibody Positivity and Association of Pretransplant Lupus Anticoagulant Positivity With Early Allograft Dysfunction in Liver Transplantation.

BACKGROUND: Antiphospholipid antibodies (aPL), including anticardiolipin (aCL), anti-ß2-glycoprotein I (anti-ß2GPI), and lupus anticoagulant (LA) antibodies, are frequently found in liver cirrhosis and associated with splanchnic vein thrombosis. Although the risk factors of early allograft dysfunction (EAD) are known, the association between EAD and aPL has been poorly investigated. We hypothesized that LA, potent aPL with thrombotic potential, may be associated with EAD development after living donor liver transplantation (LDLT). METHODS: Data of 719 patients who underwent LDLT from February 2014 to June 2016 at our center were retrospectively collected and analyzed. Patients were divided into 2 groups according to the positivity of LA screening test (LA group [n = 148] vs no-LA group [n = 571]). Risk factors for EAD were investigated using multivariable regression analysis and inverse probability of treatment weighting (IPTW) of propensity scores. RESULTS: The prevalence of LA screening positivity, confirmatory test positivity, and EAD was 20.6%, 1.1%, and 11.3%, respectively. aCL positivity rate was 7.5% and anti-ß2GPI positivity rate was 7.0%. The EAD prevalence in LA and no-LA group was 25.7% and 7.5%, respectively. However, multivariable and IPTW analyses showed no association between EAD and LA screening positivity (P = .263 and P = .825, respectively), although a significant association was found in univariate analysis (odds ratio, 4.242; P < .001). Model for End-stage Liver Disease score, operation time, and C-reactive protein level remained significant after multivariable analysis. CONCLUSION: A positive LA screening test result was associated with EAD only in the univariate analysis. Inflammation, based on C-reactive protein level, was more important for EAD development.

Determining the Cut-off Values for Sarcopenia in the Korean Elderly Population Using Bioimpedance Analysis.

BACKGROUND: Bioimpedance analysis (BIA) is known to be a useful method for assessing sarcopenia because cost-effective and not involving radiation exposure. However, the cut-off values for sarcopenia using BIA have not yet been determined in the Korean population. OBJECTIVES: To establish the cut-off values for sarcopenia in the Korean elderly population with the use of BIA. METHODS: Body composition assessed by BIA was obtained in 7,641 participants aged 20-34 years and 3,902 participants aged ≥65 years from data routinely collected during health examinations at Seoul National University Gangnam Center. Appendicular skeletal muscle mass was adjusted for height and weight. Gender-specific cut-points for class I and class II sarcopenia were defined as 1 and 2 standard deviations below the mean in the reference group aged 20-34 years, respectively. In addition, the gender-specific, lowest 20th percentile cut-offs for muscle mass in participants aged ≥65 years were determined. RESULTS: The cut-offs for class I and class II sarcopenia in men for height-adjusted appendicular skeletal mass were 6.74 kg/m2 and 5.96 kg/m2 and for weight-adjusted appendicular skeletal mass were 29.4% and 27.4%, respectively; those in women for height-adjusted appendicular skeletal mass were 4.93 kg/m2 and 4.35 kg/m2, and for weight-adjusted appendicular skeletal mass were 25.6% and 23.9%, respectively. The lowest 20th percentile cut-offs for height-adjusted and weight-adjusted appendicular skeletal mass were 6.69 kg/m2 and 28.9% in men, and 5.76 kg/m2 and 24.5% in women, respectively. Based on the derived cut-offs, prevalence of class II sarcopenia in participants ≥65 years of age for height-adjusted and weight-adjusted appendicular skeletal mass was 3.7% and 3.5% in men, and 0.2% and 11.2% in women, respectively. Among the above-mentioned definitions, sarcopenia by height-adjusted appendicular skeletal mass was significantly associated with 2-year mortality in older participants. CONCLUSIONS: Muscle mass deficit in the Korean population can be assessed based on the cut-offs determined in this study using BIA.

Isolation, partial sequencing, and expression of pathogenesis-related cDNA genes from pepper leaves infected by Xanthomonas campestris pv. vesicatoria.

Specific cDNAs showing differential expression in bacteria-infected pepper leaves as opposed to healthy leaves were isolated from a pepper cDNA library from hypersensitive response (HR) lesions of leaves infected with an avirulent strain of Xanthomonas campestris pv. vesicatoria. Among a total of 282 cDNA clones tested, 36 individual cDNA genes (13%) hybridized strongly or differentially to the cDNA probes from bacteria-infected leaves. Ten Capsicum Annuum-Induced (CAI) genes encoding putative thionin, lipid transfer protein I and II, osmotin (PR-5), class I chitinase, beta-1,3-glucanase, SAR 8.2, stellacyanin, leucine-rich repeat protein, and auxin-repressed protein were identified. Two CAI genes showed little or no sequence homology to the previously sequenced plant genes. Transcripts of the CAI genes were strongly or preferentially induced in pepper tissues by infection with X. campestris pv. vesicatoria or Phytophthora capsici, and by abiotic elicitor treatment. In particular, most of the CAI genes were strongly induced in pepper tissues by ethephon and methyl jasmonate.

Prevalence of Gs alpha mutations in Korean patients with pituitary adenomas.

The reported frequencies of Gs alpha mutations (gsp mutations) in growth hormone (GH)-secreting pituitary adenomas are variable (ranging from 4.4 to 43%), and the presence of these mutations in the other pituitary adenomas is still a matter of controversy. Previous clinical and biochemical analyses of patients with GH-secreting pituitary adenomas and gsp mutations produced conflicting results and did not demonstrate obvious characteristics. Therefore, we investigated the prevalence of gsp mutations in Korean patients with pituitary adenomas and elucidated the characteristics of these patients. Forty-four GH-secreting adenomas, 7 prolactin (PRL)-secreting adenomas and 32 clinically non-functioning adenomas were examined for the presence of point mutations in codon 201 and 227 of the Gs alpha gene using a nested PCR and direct sequencing of DNA extracted from fresh tissue or paraffin-embedded pituitary adenoma samples. Seven of the 44 GH-secreting pituitary adenomas had point mutations at codon 201 or 227; of these, five mutations were in codon 201 and two were in codon 227. In patients with gsp mutations, mean tumor size was significantly smaller than in patients without gsp mutations (15.9+/-8.7 mm vs. 24.9+/-14.9 mm, P<0.05). Age, sex, basal GH levels, GH response to oral glucose loading, GH response to octreotide and surgical outcome were not different in the two groups. One of the 32 clinically non-functioning pituitary adenomas had a point mutation at codon 201; none of the seven prolactinomas had these mutations. These results show that gsp mutations are not rare in Korean acromegalic patients and mean tumor size is significantly smaller in acromegalic patients with gsp mutations. Our results also confirm the low frequency of gsp mutations in clinically non-functioning pituitary adenomas and the absence of gsp mutations in prolactinoma.

Cell behaviour on polymer surfaces with different functional groups.

Surfaces with differently chargeable functional groups were prepared on low density polyethylene sheets by corona discharge treatment, followed by graft copolymerization of acrylic acid (-COOH, negatively chargeable) and a subsequent substitution reaction of carboxylic acid groups to hydroxyl (-CH2OH, neutral) or amide (-CONH2, neutral) groups. The amide groups grafted on the surface were further converted to amine groups (-CH2NH2, positively chargeable). The prepared surfaces were characterized by measuring the water contact angle, electron spectroscopy for chemical analysis and Fourier-transform infrared spectroscopy in the attenuated total reflectance mode. It was observed that the wettability of the different functional group-grafted surfaces largely increases compared with the control surface but is not much affected by the kind of functional groups grafted. The interaction of Chinese hamster ovary cells with the functional group-grafted surfaces was investigated. The cells adhered and grown on the surfaces were counted using an electronic cell counter and observed by a scanning electron microscope. The surface grafted with amine groups was best for cell adhesion, spreading and growth probably owing to the positively chargeable character in aqueous cell culture medium. For surfaces grafted with neutral functional groups, the surface grafted with hydroxyl groups showed better cell spreading than that grafted with amide groups.

In vivo single-voxel proton MR spectroscopy in intracranial cystic masses.

PURPOSE: Our objective was to evaluate the proton MR spectroscopic pattern of the cystic contents of various intracranial masses and to report characteristic spectral patterns that may be helpful in the differential diagnosis of these lesions. METHODS: We evaluated 40 proton MR spectra obtained from cystic contents of various intracranial cystic masses in 39 patients, including gliomas (n = 14), metastases (n = 3), abscesses (n = 8), cysticercosis (n = 4), epidermoids (n = 3), and others (n = 7). Proton MR spectroscopy was performed on a 1.5-T MR unit using a point-resolved spectroscopic sequence with a 2 x 2 x 2 cm3 volume of interest. Assignment of the resonance peaks was based on previous studies. RESULTS: Adequate proton MR spectroscopic data were obtained in 35 cases (88%). In most gliomas and metastases, only a lactate resonance was observed. There was a trend toward a higher lactate peak in high-grade gliomas. A few tumors, including malignant gliomas and metastases, showed lipid signal combined with lactate signal. In abscesses, there were various combinations of lactate, acetate, succinate, amino acids (including valine, alanine, and/or leucine), and/or unassigned resonances. In cysticercosis, resonances of lactate, succinate, alanine, acetate, and/or unassigned resonances were observed. Three epidermoid cysts showed only lactate signal. There were no identifiable resonances from the arachnoid and porencephalic cysts. CONCLUSION: Only lactate is commonly observed in a variety of intracranial cystic masses, except for abscess and cysticercosis, in which resonances of acetate, succinate, amino acids, and/or unassigned metabolites can be seen in addition to a lactate peak.

Long-term outcome and growth rate of subtotally resected petroclival meningiomas: experience with 38 cases.

OBJECTIVE: To evaluate the long-term outcome of a subtotally resected residual tumor and to assess its growth rate, we analyzed the records of 38 patients with residual petroclival meningioma. METHODS: Clinical records and radiological findings of 38 cases of petroclival meningioma that were diagnosed and subtotally resected at Seoul National University Hospital between 1981 and 1997 were carefully reviewed. Follow-up imaging studies were reviewed, and Karnofsky performance scale scores at the last follow-up were recorded. The duration of follow-up ranged from 6 to 141 months (mean, 47.5 mo; median, 30 mo). Tumor progression and progression-free survival rates were assessed. The growth rate of a residual tumor was evaluated by measuring the equivalent diameter and the tumor volume serially; the tumor doubling time was calculated, and the predictive factors for determining the growth pattern in residual tumors and the prognosis were analyzed. RESULTS: In 33 (87%) of the 38 patients, Karnofsky performance scale scores at the last follow-up were 80 or above. The median progression-free survival time among patients with subtotally resected tumors was 66 months, and the 5-year progression-free survival rate was 60%. The growth rate of residual tumors was low (volume increase, 4.94 cc/yr; diameter increase, 0.37 cm/yr). The mean tumor doubling time was 8 years. Although there were no significant predictive factors, age and extent of tumor resection seemed to influence the progression-free survival rate. Significant factors affecting the growth rate were age and occurrence of menopause. CONCLUSION: Subtotal resection with or without radiation or radiosurgery should be considered as a suitable treatment option for patients with petroclival meningiomas, especially the elderly, because the growth rate of residual tumors is low.

A three-dimensional micro-organ culture system optimized for in vitro growth of human malignant brain tumors.

A brain tumor is composed not only of tumor cells, but also of normal glial, mesenchymal, endothelial, and microglial cells, as well as lymphocytes and macrophages. Therefore, homogeneous cultures of tumor cells, currently used for chemosensitivity testing, do not accurately model in situ tumors. We have developed an in vitro growth assay for brain tumors that includes normal host cells and is potentially useful for studies of chemotherapy and biological response modifiers. Human glioblastoma xenografts (U251-MG) were resected from mice, minced, and explanted into agarose-coated culture wells. After 5 to 7 days, microtumors emerged as expanding spheroids, which grew most efficiently in minimum essential medium supplemented with 20% fetal calf serum, 90% of which was replaced on alternate days. The growth rate and bromodeoxyuridine labeling index were similar in the microtumors and the xenografts, and light microscopy revealed highly cellular, pleomorphic tumors with high mitotic activity in both. Immunohistochemical studies also demonstrated the persistence of macrophages in both xenografts and microtumors. Microtumors treated for 2 hours with 75 mumol/L 1,3-bis-(2-chloroethyl)-1-nitrosourea showed a growth delay of 1.5 days; no effects were observed after treatment with lower doses. This in vitro system for brain tumor culture may provide a useful technique for the study of new therapies as an alternative to in vivo xenograft studies using immunodeficient animals.

In vivo proton magnetic resonance spectroscopy of central neurocytomas.

OBJECTIVE: The authors report on the metabolic features of central neurocytomas observed during in vivo single-voxel proton magnetic resonance spectroscopy. METHODS: Volume-selective single-voxel proton magnetic resonance spectroscopy was performed with a 1.5-T unit using a point-resolved spectroscopy sequence (TR/TE = 2000 ms/135 and 270 ms) to obtain spectra of a single 8-cc voxel. The subjects were five patients in the Department of Neurosurgery of Seoul National University Hospital whose central neurocytomas had been diagnosed histologically. The peak intensities of compounds containing choline (Cho), N-acetylaspartate, creatine/phosphocreatine, and lactate were analyzed. RESULTS: The ratios of Cho to creatine/phosphocreatine and Cho to N-acetylaspartate were significantly higher than ratios in normal brains. A lactate signal was present, and an unidentified signal was also observed at 3.55 ppm, which might have been produced by inositol or glycine. CONCLUSION: A combination of the signal at 3.55 ppm and a prominent Cho peak seems to be a characteristic feature of central neurocytomas. Volume-selective single-voxel proton magnetic resonance spectroscopy could provide additional information to aid in diagnosing this condition.

Chordoid meningioma with polyclonal gammopathy. Case report.

The authors present a case of chordoid meningioma in a 55-year-old woman who manifested headache and personality change. Magnetic resonance imaging of the brain and cerebral angiography demonstrated a mass in the right frontal lobe that resembled a typical convexity meningioma. However, the pathological diagnosis was chordoid meningioma, a rare subtype of this tumor that usually occurs in adolescence and is known to be associated with Castleman syndrome. A meningothelial meningiomatous pattern suggestive of a meningothelial origin was focally present, and cytokeratin-positive squamoid cells were noted in the tumor. The lesion lacked dense infiltration of lymphocytes and plasma cells. Polyclonal gammopathy was the only sign of Castleman syndrome and hypochromic microcytic anemia was absent in this case. Polyclonal gammopathy resolved completely 6 months after total removal of the mass.

Malignant triton tumor of the acoustic nerve. Case report.

The authors present the clinical, radiological, pathological features, and autopsy findings of a patient with malignant triton tumor of the acoustic nerve, which probably arose from a pre-existing acoustic schwannoma. The term "malignant triton tumor" is applied to malignant schwannomas with rhabdomyoblastic differentiation. A cerebellopontine angle tumor with spinal drop metastasis occurred in this patient 10 months after near-total removal of the original tumor.

Gamma knife radiosurgery for brain metastases: prognostic factors for survival and local control.

OBJECT: The authors conducted an analysis of prognostic factors for patient survival and local control of brain metastases after gamma knife radiosurgery. METHODS: In the survival analysis, 53 consecutive patients with 121 lesions treated in the last 2 years were examined. Common primary sites were lung (26 patients), kidney (seven), breast (three), and colon (three). Patient age ranged from 28 to 75 years (median 58 years) and the female/male ratio was 1:0.9. The median tumor volume was 2.1 cm3 (range 0.02-45.5 cm3) and the average prescription dose was 15.4 Gy to the 50% isodose. The median follow up was 12 months (range 1-23 months) and the median survival was 46 weeks. Six-month and 1-year survival rates were 63% and 39%, respectively. Karnofsky Performance Scale score, tumor volume, and presence of extracranial disease were statistically significant prognostic factors (p < 0.05) for survival in multivariate analysis. Number of lesions, patient age, and adjuvant whole-brain radiation therapy were not statistically significant. Ninety-one of 121 lesions with follow-up images were included in the local control analysis. The 1-year actuarial local control rate was 48%. In multivariate analysis smaller volume was associated with better control (p = 0.0043), and, control period of renal cell carcinoma was shorter than that of the other tumor types (p = 0.0070). CONCLUSIONS: Karnofsky Performance Scale score, tumor volume, controlled primary cancer, and absence of extracranial metastases were associated with longer survival in the present study. For local control, tumor volume was a statistically significant factor.

Postoperative spinal seeding of craniopharyngioma. Case report.

The authors present a case of postoperative spinal seeding of papillary craniopharyngioma. This 27-year-old man who had previously undergone subtotal removal of a suprasellar craniopharyngioma was admitted because of low-back and right leg pain. Results of neurological examination showed a limitation in straight-leg raising in the right side with no sensorimotor changes. Magnetic resonance imaging of the lumbar spine demonstrated multiple enhanced intradural extramedullary masses causing spinal cord compression. Pathological examination of the tumor tissue obtained via laminectomy revealed papillary craniopharyngioma, which had the same histological features as those of the previous suprasellar tumor. Several ectopic recurrences of craniopharyngioma have been reported; however, the authors believe that this is the first published report of the spinal seeding of craniopharyngioma.

Central neurocytoma: proliferative potential and biological behavior.

The authors analyzed 13 central neurocytomas diagnosed at Seoul National University Hospital between January 1982 and December 1993 to clarify the proliferative potential and biological behavior of these tumors. The tumor was confined to the lateral and third ventricles in 12 cases and in one case extended from the posterior thalamus to the body and trigone area of the lateral ventricle. In all 13 cases, typical clinical and radiological findings were observed, and histological diagnosis was performed via craniotomy. The diagnosis was made using light microscopic examination, immunohistochemical staining for neuronal markers, and electron microscopic findings of neuronal differentiation. One patient died due to tumor progression with recurrence 26 months after subtotal removal plus radiation therapy. Another patient had a recurrence 18 months after total tumor removal. The remaining 11 patients are free of recurrent tumor after a follow-up period that ranged from 14 to 109 months (median 50 months). To predict the proliferative potential, immunoreactivity to proliferating cell nuclear antigen (PCNA), silver colloid staining for nucleolar organizing regions (AgNORs), and DNA flow cytometry were performed in 10 of the 13 cases. The proportion of PCNA-positive cells was less than 1% in all cases and the AgNORs score ranged from 1.11 to 2.0 (mean 1.67). The DNA flow cytometry revealed diploidy in all cases and the calculated proliferation index ranged from 5.1% to 9.6% (mean 7.8%). The one case of tumor recurrence, in which the authors performed the study of proliferative potential, and another case that demonstrated mild nuclear pleomorphism also showed low percentages of PCNA-positive cells, low AgNORs scores, and diploidy in DNA flow cytometry. It is suggested that most central neurocytomas follow a benign clinical course with low proliferative potential assessed by PCNA, AgNORs, and DNA flow cytometry; however, recurrence is possible within a relatively short time period.