An improved biologically transparent illumination system that increases the accuracy of detecting the correct position of a nasogastric tube in the stomach.

The aim of this study was to determine whether an improved biologically transparent illumination system results in more reliable detection of the correct position of the nasogastric tube in surgical patients. In total, 102 patients undergoing general surgery were included in this prospective observational study. After general anesthesia, all patients were inserted a nasogastric tube equipped with an improved biologically transparent illumination catheter. Identification of biologically transparent light in the epigastric area indicated successful insertion of the nasogastric tube into the stomach. The position of the tube was confirmed by X-ray examination, and its findings were compared with those of the biologically transparent illumination system. We observed biologically transparent light in epigastric area in 87 of the 102 patients. X-ray examination revealed that the nasogastric tube was placed in the stomach in all of these 87 patients. Light was not observed in the remaining 15 patients; the tube position was confirmed in the stomach in 11 of these patients but not in the other 4 by X-ray examination. Illumination had a sensitivity of 88.8% and a specificity of 100%. Our results suggest that this improved biologically transparent illumination system increased the accuracy of detecting the correct position of a nasogastric tube in the stomach. X-ray examination is required to check the position of the nasogastric tube in patients when biologically transparent illumination light is negative.

High-flow nasal cannula oxygen therapy for respiratory management after postoperative re-intubation/re-extubation in patients with trisomy 18 and trisomy 13: Two case reports.

We present two cases of general anesthesia in children with 18, 13 trisomy. One patient had difficulty with intubation and had to be reintubated postoperatively, another developed postoperative acute respiratory distress syndrome. The use of postoperative high-flow nasal cannula oxygen therapy to avoid reintubation is considered a feasible strategy.

Dural sac shrinkage signs on magnetic resonance imaging at the thoracic level in spontaneous intracranial hypotension-its clinical significance.

BACKGROUND: Spontaneous intracranial hypotension (SIH) is secondary to a cerebrospinal fluid leak at the spinal level without obvious causative events. Several signs on brain and cervical spine magnetic resonance (MR) imaging (MRI) have been associated with SIH but can be equivocal or negative. This retrospective study sought to identify characteristic SIH signs on thoracic spinal MRI. METHODS: Cranial and spinal MR images of 27 consecutive patients with classic SIH symptoms, who eventually received epidural autologous blood patches (EBPs), were analyzed. RESULTS: The most prevalent findings on T2-weighted MRI at the thoracic level were anterior shift of the spinal cord (96.3%) and dorsal dura mater (81.5%), probably caused by dural sac shrinkage. These dural sac shrinkage signs (DSSS) were frequently accompanied by cerebrospinal fluid collection in the posterior epidural space (77.8%) and a prominent epidural venous plexus (77.8%). These findings disappeared in all six patients who underwent post-EBP spinal MRI. Dural enhancement and brain sagging were minimum or absent on the cranial MR images of seven patients, although DSSS were obvious in these seven patients. For 23 patients with SIH and 28 healthy volunteers, a diagnostic test using thoracic MRI was performed by 13 experts to validate the usefulness of DSSS. The median sensitivity, specificity, positive-predictive value, negative-predictive value, and accuracy of the DSSS were high (range, 0.913-0.931). CONCLUSIONS: Detection of DSSS on thoracic MRI facilitates an SIH diagnosis without the use of invasive imaging modalities. The DSSS were positive even in patients in whom classic cranial MRI signs for SIH were equivocal or minimal.

Biologically transparent illumination is a safe, fast, and simple technique for detecting the correct position of the nasogastric tube in surgical patients under general anesthesia.

The aim of this study was to evaluate the effectiveness of using biologically transparent illumination to detect the correct position of the nasogastric tube in surgical patients. This prospective observational study enrolled 102 patients undergoing general surgeries. In all cases, a nasogastric tube equipped with a biologically transparent illumination catheter was inserted after general anesthesia. The identification of biologically transparent light in the epigastric area either with or without finger pressure indicated that the tube had been successfully inserted into the stomach. X-ray examination was performed to ascertain the tube position and was compared with the findings of the biologically transparent illumination technique. Biologically transparent light was detected in 72 of the 102 patients. In all of these 72 patients, the position of the nasogastric tube in the stomach was confirmed by X-ray examination. The light was not detected in the other 30 patients; X-ray examination showed that the nasogastric tube was positioned in the stomach in 21 of these 30 patients but not in the other 9. The sensitivity and specificity of the illumination were 77.4% and 100%, respectively. The results suggest that biologically transparent illumination is a useful and safe technique for detecting the correct position of the nasogastric tube in surgical patients under general anesthesia. When the BT light cannot be identified, X-ray examination is mandatory to confirm the position of the nasogastric tube.

Roles for hENT1 and dCK in gemcitabine sensitivity and malignancy of meningioma.

BACKGROUND: High-grade meningiomas are aggressive tumors with high morbidity and mortality rates that frequently recur even after surgery and adjuvant radiotherapy. However, limited information is currently available on the biology of these tumors, and no alternative adjuvant treatment options exist. Although we previously demonstrated that high-grade meningioma cells were highly sensitive to gemcitabine in vitro and in vivo, the underlying molecular mechanisms remain unknown. METHODS: We examined the roles of hENT1 (human equilibrative nucleoside transporter 1) and dCK (deoxycytidine kinase) in the gemcitabine sensitivity and growth of meningioma cells in vitro. Tissue samples from meningiomas (26 WHO grade I and 21 WHO grade II/III meningiomas) were immunohistochemically analyzed for hENT1 and dCK as well as for Ki-67 as a marker of proliferative activity. RESULTS: hENT1 and dCK, which play critical roles in the intracellular transport and activation of gemcitabine, respectively, were responsible for the high gemcitabine sensitivity of high-grade meningioma cells and were strongly expressed in high-grade meningiomas. hENT1 expression was required for the proliferation and survival of high-grade meningioma cells and dCK expression. Furthermore, high hENT1 and dCK expression levels correlated with stronger tumor cell proliferative activity and shorter survival in meningioma patients. CONCLUSIONS: The present results suggest that hENT1 is a key molecular factor influencing the growth capacity and gemcitabine sensitivity of meningioma cells and also that hENT1, together with dCK, may be a viable prognostic marker for meningioma patients as well as a predictive marker of their responses to gemcitabine.

Genetic analysis in patients with newly diagnosed glioblastomas treated with interferon-beta plus temozolomide in comparison with temozolomide alone.

PURPOSE: This study aimed to explore the genetic alterations and to identify good responders in the experimental arm in the tumor samples from newly diagnosed glioblastoma (GBM) patients enrolled in JCOG0911; a randomized phase II trial was conducted to compare the efficacy of interferonß (IFNß) plus temozolomide (TMZ) with that of TMZ alone. EXPERIMENTAL: DESIGN: Of 122 tumors, we performed deep targeted sequencing to determine the somatic mutations, copy number variations, and tumor mutation burden; pyrosequencing for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation; Sanger sequencing for the telomerase reverse transcriptase (TERT) promoter; and microsatellite instability (MSI) testing in 95, 91, 91 and 72 tumors, respectively. We performed a multivariable Cox regression analysis using backward stepwise selection of variables including clinical factors (sex, age, performance status, residual tumor after resection, tumor location) and genetic alterations. RESULTS: Deep sequencing detected an IDH1 mutation in 13 tumors (14%). The MGMT promoter methylation by quantitative pyrosequencing was observed in 41% of the tumors. A mutation in the TERT promoter was observed in 69% of the tumors. While high tumor mutation burden (> 10 mutations per megabase) was seen in four tumors, none of the tumors displayed MSI-high. The clinical and genetic factors considered as independent favorable prognostic factors were gross total resection (hazard ratio [HR]: 0.49, 95% confidence interval, 0.30-0.81, P = 0.0049) and MGMT promoter methylation (HR: 0.43, 0.21-0.88, P = 0.023). However, tumor location at the temporal lobe (HR: 1.90, 1.22-2.95, P = 0.0046) was an independent unfavorable prognostic factor. No predictive factors specific to the TMZ + IFNß + Radiotherapy (RT) group were found. CONCLUSION: This additional sub-analytical study of JCOG0911 among patients with newly diagnosed GBM showed that tumor location at the temporal lobe, gross total resection, and MGMT promoter methylation were significant prognostic factors, although no factors specific to IFNß addition were identified.

Characteristics of Japanese patients with pustulotic arthro-osteitis associated with palmoplantar pustulosis: a multicenter study.

BACKGROUND: Pustulotic arthro-osteitis (PAO) is a major comorbidity of palmoplantar pustulosis (PPP), which is frequently seen in Japanese patients. To determine the characteristics of Japanese patients with PAO, we conducted a multicenter, retrospective epidemiologic survey at four university hospitals. METHODS: Clinical features including age, gender, duration of disease, extrapalmoplantar lesion, smoking habit, focal infection, site of joint pain, bone scintigraphy with Technetium99 , and therapies were retrospectively evaluated. RESULTS: In total, 165 patients with PAO were identified among 576 patients with PPP (28.6%). The male to female ratio was 1 : 3.7, and the mean age was 50.2 years. The mean disease duration of PAO was 6.0 years. Smoking habit was observed in 104 patients. Focal infection was detected in 74 patients, who developed tonsillar infection (n = 41), sinusitis (8), odontogenic infection (40), and others (2). Fifteen patients had multifocal infection. Technetium bone scintigraphy was performed in 97 cases. Increased uptake was most frequently observed in the sternocostoclavicular regions, followed by wrist and ankle, sacroiliac joint, knee and elbow, finger and toe, lumbar spine, thoracic spine, scapula, and thigh. Patients were mainly treated with nonsteroidal anti-inflammatory drugs, methotrexate, cyclosporine, antibiotics, and biologics, as well as tonsillectomy and dental treatment. CONCLUSION: PAO frequently involves the anterior chest wall of middle-aged women with smoking habit and is closely associated with focal infection.

Formin-like 1 (FMNL1) Is Associated with Glioblastoma Multiforme Mesenchymal Subtype and Independently Predicts Poor Prognosis.

Glioblastoma multiforme (GBM), the most common primary malignant brain tumor in adults, is characterized by rapid proliferation, aggressive migration, and invasion into normal brain tissue. Formin proteins have been implicated in these processes. However, the role of formin-like 1 (FMNL1) in cancer remains unclear. We studied FMNL1 expression in glioblastoma samples using immunohistochemistry. We sought to analyze the correlation between FMNL1 expression, clinicopathologic variables, and patient survival. Migration and invasion assays were used to verify the effect of FMNL1 on glioblastoma cell lines. Microarray data were downloaded from The Cancer Genome Atlas and analyzed using gene set enrichment analysis (GSEA). FMNL1 was an independent predictor of poor prognosis in a cohort of 217 glioblastoma multiforme cases (p < 0.001). FMNL1 expression was significantly higher in the mesenchymal subtype. FMNL1 upregulation and downregulation were associated with mesenchymal and proneural markers in the GSEA, respectively. These data highlight the important role of FMNL1 in the neural-to-mesenchymal transition. Conversely, FMNL1 downregulation suppressed glioblastoma multiforme cell migration and invasion via DIAPH1 and GOLGA2, respectively. FMNL1 downregulation also suppressed actin fiber assembly, induced morphological changes, and diminished filamentous actin. FMNL1 is a promising therapeutic target and a useful biomarker for GBM progression.

High filamin-C expression predicts enhanced invasiveness and poor outcome in glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM), the most common brain malignancy in adults, is generally aggressive and incurable, even with multiple treatment modalities and agents. Filamins (FLNs) are a group of actin-binding proteins that regulate the actin cytoskeleton in cells. However, the role of FLNs in malignancies-particularly in GBM-is unclear. METHODS: The relation between FLNC expression and overall survival in GBM was evaluated by the Kaplan-Meier analysis using GBM patients from the Kagoshima University Hospital (n = 90) and data from the Cancer Genome Atlas (TCGA) (n = 153). To assess FLNC function in GBM, cell migration and invasion were examined with Transwell and Matrigel invasion assays using FLNC-overexpressing U251MG and LN299 GBM cells, and ShRNA-mediated FLNC knocked-down KNS81 and U87MG cells. The gelatin zymography assay was used to estimate matrix metalloproteinase (MMP) 2 activity. RESULTS: In silico analysis of GBM patient data from TCGA and immunohistochemical analyses of clinical GBM specimens revealed that increased FLNC expression was associated with poor patient prognosis. FLNC overexpression in GBM cell lines was positively correlated with enhanced invasiveness, but not migration, and was accompanied by upregulation of MMP2. CONCLUSIONS: FLNC is a potential therapeutic target and biomarker for GBM progression.

Histogram analysis of amide proton transfer-weighted imaging: comparison of glioblastoma and solitary brain metastasis in enhancing tumors and peritumoral regions.

OBJECTIVES: Differentiation of glioblastomas (GBMs) and solitary brain metastases (SBMs) is an important clinical problem. The aim of this study was to determine whether amide proton transfer-weighted (APTW) imaging is useful for distinguishing GBMs from SBMs. METHODS: We examined 31 patients with GBM and 17 with SBM. For each tumor, enhancing areas (EAs) and surrounding non-enhancing areas with T2-prolongation (peritumoral high signal intensity areas, PHAs) were manually segmented using fusion images of the post-contrast T1-weighted and T2-weighted images. The mean amide proton transfer signal intensities (APTSIs) were compared among the EAs, PHAs, and contralateral normal appearing white matter (NAWM) within each tumor type. Furthermore, we analyzed APTSI histograms to compare the EAs and PHAs of GBMs and SBMs. RESULTS: In GBMs, the mean APTSI in EAs (2.92 ± 0.74%) was the highest, followed by that in PHAs (1.64 ± 0.83%, p < 0.001) and NAWM (0.43 ± 0.83%, p < 0.001). In SBMs, the mean APTSI in EAs (1.85 ± 0.99%) and PHAs (1.42 ± 0.45%) were significantly higher than that in NAWM (0.42 ± 0.30%, p < 0.001), whereas no significant difference was found between EAs and PHAs. The mean and 10th, 25th, 50th, 75th, and 90th percentiles for APT in EAs of GBMs were significantly higher than those of SBMs. However, no significant difference was found between GBMs and SBMs in any histogram parameters for PHA. CONCLUSIONS: APTSI in EAs, but not PHAs, is useful for differentiation between GBMs and SBMs. KEY POINTS: • Amide proton transfer-weighted imaging and histogram analysis in the enhancing tumor can provide useful information for differentiation between glioblastomas and solitary brain metastasis. • Amide proton transfer signal intensity histogram parameters from peritumoral areas showed no significant difference between glioblastomas and solitary brain metastasis. • Vasogenic edema alone can substantially increase amide proton transfer signal intensity which may mimic tumor invasion.

A Clinical Rule for Preoperative Prediction of BRAF Mutation Status in Craniopharyngiomas.

BACKGROUND: Papillary craniopharyngiomas are characterized by BRAFV600E mutations. Targeted therapy can elicit a dramatic radiographic regression of these tumors. Therefore, prediction of BRAF mutation status before definitive surgery could enable neoadjuvant treatment strategies. OBJECTIVE: To establish preoperative prediction criteria to identify patients with a BRAF mutant craniopharyngioma. METHODS: Sixty-four patients with craniopharyngioma were included in this study. We determined BRAF mutation status by targeted sequencing. After scoring interobserver variability between presurgical clinical data and radiographic features, we established a diagnostic rule for BRAF mutation in our discovery cohort. We then validated the rule in an independent cohort. RESULTS: The BRAFV600E mutation was detected in 12 of 42 patients in the discovery cohort. There were no patients under age 18 with BRAF mutation. Calcification was rare in tumors with BRAF mutation (P < .001), and 92% of them were supradiaphragmatic in location. Combining these 3 features-older than 18 years, absence of calcification, and supradiaphragmatic tumor location-we established a rule for predicting BRAF mutation. In cases where all 3 criteria were fulfilled, the sensitivity and specificity for the presence of BRAF mutation were 83% and 93%, respectively. In the validation cohort (n = 22), the sensitivity was 100% and specificity was 89%. CONCLUSION: We propose predictive criteria for a BRAF mutation in craniopharyngioma using preoperative clinical and radiographic data. This rule may be useful in identifying patients who could potentially benefit from neoadjuvant BRAFV600E-targeted systemic therapies.

Evaluation of the efficacy of granulocyte and monocyte adsorption apheresis on skin manifestation and joint symptoms of patients with pustulotic arthro-osteitis.

Pustulotic arthro-osteitis, occasionally complicated with palmoplantar pustulosis, affects patients' activities of daily living. Granulocyte and monocyte adsorption apheresis selectively removes activated granulocytes and monocytes by means of extracorporeal circulation. Although the efficacy of granulocyte and monocyte adsorption apheresis in the treatment of generalized pustular psoriasis has been proved, very few reports have assessed its efficacy in the treatment of palmoplantar pustulosis and pustulotic arthro-osteitis. Ten pustulotic arthro-osteitis patients with five palmoplantar skin manifestations were treated with weekly granulocyte and monocyte adsorption apheresis over 5 weeks. Skin manifestations were assessed using palmoplantar pustulosis area and severity index, and joint symptoms were assessed using a visual analog scale of joint pain, tender joint count, swollen joint count and C-reactive protein immediately before, after and at the 3-month follow up of the five granulocyte and monocyte adsorption apheresis sessions. Two out of five patients with skin manifestations achieved more than 50% improvement in their score (remarkably improved). However, in two patients, deterioration was noted, in one of whom the skin manifestations remained unchanged at the 3-month follow up. In five out of the 10 patients, the joint symptoms were assessed as better than improved at the 3-month follow up. No deterioration was noted at the 3-month follow up. In three patients, reduction or cessation of medication for arthralgia was possible. We concluded that granulocyte and monocyte adsorption apheresis is a therapeutic option to consider when pustulotic arthro-osteitis is recalcitrant to conventional therapy.

JCOG0911 INTEGRA study: a randomized screening phase II trial of interferonß plus temozolomide in comparison with temozolomide alone for newly diagnosed glioblastoma.

PURPOSE: This study explored the superiority of temozolomide (TMZ) + interferonß (IFNß) to standard TMZ as treatment for newly diagnosed glioblastoma (GBM) via randomized phase II screening design. EXPERIMENTAL DESIGN: Eligibility criteria included histologically proven GBM, with 50% of the tumor located in supratentorial areas, without involvement of the optic, olfactory nerves, and pituitary gland and without multiple lesions and dissemination. Patients in the TMZ + radiotherapy (RT) arm received RT (2.0 Gy/fr/day, 30 fr) with TMZ (75 mg/m2, daily) followed by TMZ maintenance (100-200 mg/m2/day, days 1-5, every 4 weeks) for 2 years. Patients in the TMZ + IFNß + RT arm intravenously received IFNß (3 MU/body, alternative days during RT and day 1, every 4 weeks during maintenance period) and TMZ + RT. The primary endpoint was overall survival (OS). The planned sample size was 120 (one-sided alpha 0.2; power 0.8). RESULTS: Between Apr 2010 and Jan 2012, 122 patients were randomized. The median OS with TMZ + RT and TMZ + IFNß + RT was 20.3 and 24.0 months (HR 1.00, 95% CI 0.65-1.55; one-sided log rank P = 0.51). The median progression-free survival times were 10.1 and 8.5 months (HR 1.25, 95% CI 0.85-1.84). The incidence of neutropenia with the TMZ + RT and the TMZ + IFNß + RT (grade 3-4, CTCAE version 3.0) was 12.7 versus 20.7% during concomitant period and was 3.6 versus 9.3% during maintenance period. The incidence of lymphopenia was 54.0 versus 63.8% and 34.5 versus 41.9%. CONCLUSIONS: TMZ + IFNß + RT is not considered as a candidate for the following phase III trial, and TMZ + RT remained to be a most promising treatment. This trial was registered with the UMIN Clinical Trials Registry: UMIN000003466.

Postoperative Changes in Metabolic Parameters of Patients with Surgically Controlled Acromegaly: Assessment of New Stringent Cure Criteria.

The criteria for surgical cure of acromegaly have become more stringent during the past decades and a change from Cortina to new consensus criteria has recently been proposed. However, the superiority of the new consensus over Cortina criteria with respect to postoperative metabolic parameters remains to be ascertained. We retrospectively assessed metabolic parameters, the body habitus, and other health-related parameters of 48 patients with surgically controlled acromegaly who met the Cortina criteria [normalized insulin-like growth factor-1 (IGF-1) level and nadir growth hormone (GH) level <1.0 ng/ml during postoperative oral glucose tolerance test]. The 48 patients were divided into two groups. Group A (n = 33) met the new consensus criteria (normalized IGF-1 and nadir GH level <0.4 ng/ml). Group B (n = 15) met Cortina criteria, but their nadir GH ranged from 0.4 to 1.0 ng/ml. In both groups, the level of triglyceride and homeostasis model assessment-insulin resistance (HOMA-IR) was significantly decreased 1 year after the operation (P < 0.05). High-density lipoprotein cholesterol showed a significant increase only in group B (P = 0.02). However, the two groups did not differ with respect to the postoperative improvement rate of these parameters and the other health-related parameters including body mass index, blood pressure, anterior pituitary function, and self-estimated quality of life scale. In conclusion, our findings show that with respect to changes in metabolic parameters and the body habitus assessed 1 year after surgery, the stricter consensus criteria seemed not to be superior to Cortina criteria.

Bilateral lateral ventricular subependymoma with extensive multiplicity presenting with hemorrhage.

This 48-year-old-man who had undergone right thyroid lobectomy for undifferentiated thyroid carcinoma nine years earlier developed generalized seizures. His cerebrospinal fluid was xanthochromic with elevation of total protein. Computed tomography (CT) showed mixed-density bilateral ventricular masses. Magnetic resonance imaging (MRI) revealed multiple nodules in both lateral ventricles; they were heterogeneously enhanced by gadolinium. Diffuse hyperintensity in the right medial temporal lobe and bilateral subependymal area was noted on fluid-attenuated inversion recovery images. Susceptibility-weighted imaging showed low intensity in the masses and cerebellar sulci suggesting hemorrhage and hemosiderin deposition. The preoperative diagnosis was disseminated malignant tumor with recurring hemorrhage. Histological examination of biopsy specimens showed clusters of cells with small uniform nuclei embedded in a dense fibrillary matrix of glial cells and microcystic degeneration. Pseudo-rosettes indicating ependymoma were absent. Microhemorrhages and hemosiderin deposits were noted. Immunohistochemically, the background fibrillary matrix and neoplastic cells were positive for glial fibrillary acidic protein. Mutated isocitrate dehydrogenase-1 was negative. The MIB-1 index was 1.5%. The tumor was pathologically diagnosed as subependymoma containing microhemorrhages and hemosiderin deposits. The extensive multiplicity and hemorrhage encountered in this case have rarely been reported in patients with subependymoma.

Antitumor activity of gemcitabine against high-grade meningioma in vitro and in vivo.

Currently, there is no established therapeutic option for high-grade meningioma recurring after surgery and radiotherapy, and few chemotherapeutic agents are in development for the treatment of high-grade meningioma. Here in this study, we screened a panel of chemotherapeutic agents for their possible antitumor activity in high-grade meningioma and discovered that high-grade meningioma cells show a preferential sensitivity to antimetabolites, in particular, to gemcitabine. In vitro, gemcitabine inhibited the growth of high-grade meningioma cells effectively by inducing S-phase arrest and apoptotic cell death. In vivo, systemic gemcitabine chemotherapy suppressed not only tumor initiation but also inhibited the growth and achieved a long-term control of established tumors in xenograft models of high-grade meningioma. Histological analysis indicated that systemic gemcitabine blocks cell cycle progression and promotes apoptotic cell death in tumor cells in vivo. Together, our data demonstrate that gemcitabine exerts potent antitumor activity against high-grade meningioma through cytostatic and cytotoxic mechanisms. We therefore propose gemcitabine is a promising chemotherapeutic agent that warrants further investigation as a treatment option for high-grade meningioma.

ATP7B expression in human glioblastoma is related to temozolomide resistance.

Glioblastoma multiforme (GBM) is one of the most aggressive types of brain malignancy, with resistance to chemotherapy being a primary treatment obstacle. ATPase copper transporting ß (ATP7B) is involved in multidrug resistance; however, its expression in GBM remains to be evaluated. In the present study, GBM specimens from 79 patients who underwent gross total tumor removal followed by concomitant temozolomide (TMZ) chemotherapy and radiotherapy were assessed immunohistochemically. The association between the overall survival times of patients and the expression of ATP7B in neoplastic cells was evaluated. In 12/79 tumors (15.2%) >10% of neoplastic cells were immunohistochemically-positive for ATP7B, and categorized as high-ATP7B GBM. In the remaining 67 tumors (84.8%) the rate of ATP7B-positive cells was <10% and recorded as low-ATP7B GBM. The median overall survival times of patients with high- and low-ATP7B GBM were 14.6, and 24.7 months, respectively. High expression of ATP7B was identified to be associated with shorter overall survival times (hazard ratio, 0.452; 95% confidence interval, 0.206-0.994; P=0.048). Of the 79 patients, 12 underwent a second operation due to recurrence. These tissue samples were also subjected to immunohistochemical study. The ATP7B positivity rate of tumor cells obtained during the second surgery was significantly higher compared with that in the first surgery (9.17±2.56 vs. 2.75±0.55%; P=0.008). In addition, two ATP7B-transfected GBM cell lines were identified to be significantly resistant (3.8- and 1.7-fold, respectively) to TMZ compared with the control cell line. The findings of the present study suggest that ATP7B influences GBM resistance to TMZ.

[Affinity of Luliconazole for Human Nail Derived Keratin].

Affinity of Luliconazole (LLCZ), an antifungal drug used for topical treatment of onychomycosis in Japan, to nail keratin was demonstrated. Efinaconazole (EFCZ) was used as a reference drug. Drugs at fixed concentrations were added to 4 ml of buffer solution containing 40 mg of nail keratin powder prepared from healthy volunteers or from tinea unguium patients. The mixtures were shaken at 37℃, and adsorption and desorption rates of the drug in nail keratin were measured. Theoretical analysis using the Freundlich adsorption isotherm was applied to eliminate effects of testing conditions on the results. Results showed that compared with EFCZ, LLCZ exhibited high adsorption rates and low desorption rates in nail keratins. These results were verified by Freundlich analysis, in which adsorption coefficient (KadsF) and desorption coefficient (KadsF) of LLCZ were 5-7 times and about 2 times higher than EFCZ, respectively. In addition, antifungal activity against Trichophyton rubrum of the desorbed LLCZ samples was determined using disk diffusion assay. In conclusion, LLCZ is considered to possess high affinity to nail keratin. LLCZ, therefore, can be retained in the nail as a reservoir and continuously desorbed at the infection site to exhibit antifungal activity against pathogenic fungi. The pharmacokinetics of LLCZ in the nail is believed to differ from that of EFCZ. As adsorption and desorption rates of the two drugs in nail keratin tended to be different between healthy volunteers and patients, further detailed study is needed.

Long-term outcome after endovascular treatment of cavernous sinus dural arteriovenous fistula and a literature review.

BACKGROUND: The long-term efficacy of endovascular treatment (EVT) for cavernous sinus dural arteriovenous fistulae (CS-dAVF) was assessed with a special focus on residual shunts after initial EVT. PATIENTS AND METHODS: This retrospective survey included 50 patients who had undergone EVT and were followed for 1 month or longer (median follow-up 56 months). RESULTS: Common preoperative symptoms were chemosis (78%), extra-ocular motor palsy (72%), exophthalmos (66%), and tinnitus (26%). CS-dAVF were addressed by transvenous embolization (tVE, n = 48), tVE only was used in 43 instances and tVE plus transarterial embolization (tAE) in five. Two patients underwent tAE only. Procedure-related morbidity (brainstem infarction) was recorded in one patient (2%) and transient symptom exacerbation (paradoxical worsening) in 12 patients (24%). Postoperative digital subtraction angiography showed no major retrograde shunt or cortical venous reflux in any of the 50 patients. Anterograde or minor retrograde residual shunt was observed in 17 patients (34%); three of these underwent additional tVE and four had Gamma Knife surgery. The shunt flow disappeared in all 17 patients 12.6 ± 13.4 (mean ± SD) months after initial EVT. At the latest follow-up, 65.7 ± 52.6 months after the initial operation, no shunt flow was observed in any of the 50 patients. None had remaining or newly developed chemosis or tinnitus on follow-up. The rate of persistent cavernous sinus symptoms at the latest follow-up was higher in patients with than without post-procedural paradoxical worsening (5/12, 41.7% vs. 2/38, 5.3%, p = 0.0059 by Fisher's exact test). CONCLUSIONS: Long-term follow-up showed that EVT, especially tVE, is an efficient and safe treatment for CS-dAVF. It resulted in the eventual disappearance of shunt flow. Residual shunt without major retrograde flow or cortical venous reflux can be monitored without additional treatment.

Preoperative and Postoperative Pituitary Function in Patients with Tuberculum Sellae Meningioma -Based on Pituitary Provocation Tests.

Given the anatomical proximity of tuberculum sellae meningioma (TSM) to the hypothalamo-pituitary system, pituitary function impairments are of great concern. We retrospectively investigated pituitary function changes following surgery in patients with TSM using pituitary provocation tests (PPTs). Thirty-one patients (27 females and 4 males) with TSM underwent initial transcranial surgery (29 patients) or transsphenoidal surgery (two patients); surgeries were performed carefully to avoid injuring the pituitary stalk. In 24 patients, the PPTs were performed via a triple bolus injection with regular insulin, thyrotropin-releasing hormone (TRH), and luteinizing hormone releasing hormone (LH-RH). Seven patients underwent a quadruple test (growth-hormone-releasing factor, corticotrophin-releasing hormone, TRH, and LH-RH). The preoperative and postoperative target hormone levels of the anterior pituitary were normal in 93.5% and 96.8% of patients, respectively. At least one hormonal axis demonstrated impaired PPT responses in two patients (6.5%) preoperatively and in one patient (3.2%) postoperatively. The growth hormone (GH) response was also well preserved. A compromised GH peak level was only observed in one patient (3.2%) preoperatively. Postoperatively, transient diabetes insipidus and transient hyponatremia were observed in four (12.9%) and eight (25.8%) patients, respectively. No patients needed permanent postoperative hormone replacement. The preoperative pituitary function was well preserved in most patients, including those with large tumors pushing against the pituitary stalk considerably or embedded in it. After careful surgery to avoid damaging the pituitary stalk, pituitary function was preserved. However, transient postoperative hyponatremia occurred in 25.8% of patients; thus, surgeons should pay careful attention to this issue.