Longitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses.

The utility of patient-derived tumor cell lines as experimental models for glioblastoma has been challenged by limited representation of the in vivo tumor biology and low clinical translatability. Here, we report on longitudinal epigenetic and transcriptional profiling of seven glioblastoma spheroid cell line models cultured over an extended period. Molecular profiles were associated with drug response data obtained for 231 clinically used drugs. We show that the glioblastoma spheroid models remained molecularly stable and displayed reproducible drug responses over prolonged culture times of 30 in vitro passages. Integration of gene expression and drug response data identified predictive gene signatures linked to sensitivity to specific drugs, indicating the potential of gene expression-based prediction of glioblastoma therapy response. Our data thus empowers glioblastoma spheroid disease modeling as a useful preclinical assay that may uncover novel therapeutic vulnerabilities and associated molecular alterations.

Extended approach or usage of nasoseptal flap is a risk factor for olfactory dysfunction after endoscopic anterior skullbase surgery: results from 928 patients in a single tertiary center.

BACKGROUND: The aim of this study was to compare olfactory function change in patients who underwent endoscopic skull-base surgery. METHODOLOGY: A total of 928 patients were included in this retrospective study. Olfactory function was measured using the non- validated Likert scale (0â€"100), the Cross-Cultural Smell Identification Test (CC-SIT) and the butanol threshold test (BTT). Patients were divided into two groups: an endoscopic trans-sellar approach group (ETA, n = 768) and an extended endoscopic endonasal approach group (EEEA, n = 160). The ETA group was sub-divided into Nasoseptal flap (NSF) and no NSF groups. RESULTS: Non-validated olfactory function significantly worsened in the EEEA and ETA-NSF groups compared with that in the ETA- no NSF group for at least 6 months post-operatively. Validated olfactory impairment (BTT and CC-SIT) was also significantly worse in the EEEA and NSF groups compared with that in the ETA-no NSF group 3 months post-operatively. Additionally, the degrees of non-validated and validated olfactory deterioration were not significantly different between the EEEA and ETA-NSF groups. We also found that CC-SIT score changes were significantly impaired in tuberculum sellae meningioma patients than in craniopharyn- gioma patients. CONCLUSIONS: We conclude that NSF was the key factor that led to olfactory impairment after endoscopic skull-base surgery.

Differentiation of Hemangioblastoma from Metastatic Brain Tumor using Dynamic Contrast-enhanced MR Imaging.

PURPOSE: The aim of this study was to differentiate hemangioblastomas from metastatic brain tumors using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and compare the diagnostic performances with diffusion-weighted imaging (DWI) and dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). METHODS: We retrospectively reviewed 7 patients with hemangioblastoma and 15 patients with metastatic adenocarcinoma with magnetic resonance imaging (MRI) including DWI, DSC-MRI, and DCE-MRI. Apparent diffusion coefficient (ADC), relative cerebral blood volume (rCBV), and DCE-MRI parameters (K trans, k ep, v e, and v p) were compared between the two groups. The diagnostic performance of each parameter was evaluated with receiver operating characteristic (ROC) curve analysis. RESULTS: v p, k ep, and rCBV were significantly different between patients with hemangioblastoma and those with metastatic brain tumor (p < 0.001, p = 0.005, and p = 0.017, respectively). A v p cutoff value of 0.012 and a rCBV cutoff value of 8.0 showed the highest accuracy for differentiating hemangioblastoma from metastasis. The area under the ROC curve for v p and rCBV was 0.99 and 0.89, respectively. A v p > 0.012 showed 100 % sensitivity, 93.3 % specificity, and 95.5 % accuracy and a rCBV > 8.0 showed 85.7 % sensitivity, 93.3 % specificity, and 90.9 % accuracy for differentiating hemangioblastoma from metastatic brain tumor. CONCLUSION: DCE-MRI was useful for differentiating hemangioblastoma from metastatic brain tumor.

Trophic transfer of nano-TiO2 in a paddy microcosm: A comparison of single-dose versus sequential multi-dose exposures.

In the present study, replicated paddy microcosm systems were used to investigate the environmental fate and trophic transfer of titanium nanoparticles (NPs) over a period of 14 days. Most TiO2 NPs immediately settled down in the sediment, and high accumulations of nano TiO2 in the sandy loam sediment and biofilm were observed. The test organisms (quillworts, water dropworts, duckweeds, biofilms, river snails, and Chinese muddy loaches) and environmental media (freshwater, sandy loam sediment) were exposed to sequential low doses (2 mg/L at 1 h, 4 days, and 9 days) or a single high-dose (6 mg/L) of TiO2 NPs. The bioconcentration factors (BCFs) of nano-TiO2 in biofilms, quillworts, duckweeds, and Chinese muddy loaches were higher in the sequential multi-dose group than in the single-dose group. Chinese muddy loaches showed higher bioaccumulation factors (BAFs) over their prey than river snails. The difference in the carbon isotope ratios between Chinese muddy loaches and river snails was less than 2‰, and an approximately 4‰ difference in the stable nitrogen isotope ratio was observed in the two aquatic predators from their major prey (e.g., biofilms or particulate organic matter). The trophic levels between biofilms and river snails and between biofilms and Chinese muddy loaches were 2.8 and 2.4 levels, respectively. These results indicate that these two predators consumed biofilm and other alternative preys at a higher level than biofilm. Although the trophic transfer rates of TiO2 are generally low, relatively higher biomagnification factors (BMFs) were found in Chinese muddy loaches (0.04-0.05) than in river snails (0.01-0.02). These results suggest that TiO2 NPs show greater movement in the sediment than in the water and that TiO2 NPs can be retained through aquatic food chains more after a sequential low-dose exposure than after a single high-dose exposure.

Transarterial embolisation of renal arteriovenous malformation: safety and efficacy in 24 patients with follow-up.

AIM: To evaluate the efficacy and safety of renal artery embolisation (RAE) for renal arteriovenous malformation (AVM) as well as its outcomes. MATERIALS AND METHODS: The technical and clinical success rates, radiological and laboratory findings, and complications of RAE for 31 renal AVMs in 24 patients (M:F=9:15, mean age 46 years) at two separate medical institutions were retrospectively evaluated. Technical success was defined as complete occlusion of feeding arteries with no residual nidus seen on post-treatment angiography. Clinical failure was defined as recurrence of haematuria, presence of AVM on follow-up ultrasound or computed tomography, repeated RAE or surgery for the control of haematuria. Overall clinical success was defined as resolution haematuria or disappearance of AVM on follow-up imaging after single or multiple sessions of RAE. RESULTS: Types of renal AVM were AVM, arterio-venous fistula (AVF) with intranidal aneurysm, and acquired AVF in 19, 1, and 4 patients, respectively. 18 patients (75%) underwent a single session of RAE, while 6 patients (25%) had two or more sessions of RAE. The level of embolisation was feeder, segmental artery, and main renal artery in 28 (90%), 2 (6%), and 1 (4%) procedures, respectively. Coil, n-butyl 2-cyanoacrylate, and polyvinyl alcohol were the most frequently chosen embolic materials and were used in 19, 14, and 8 procedures, respectively. The clinical success rate after initial RAE was 67% (16/24). Overall clinical success rate, including multisession RAE, was 88% (21/24). The technical success rate of 31 procedures was 65% (20/31). Among 11 technical failures in 10 patients, 4 achieved clinical success without additional RAE, 3 underwent second session RAE to achieve clinical success, and 3 patients underwent nephrectomy due to recurrence. CONCLUSION: RAE is a safe and effective treatment for renal AVM. Technical failure of RAE does not always lead to clinical failure and multiple embolisation sessions may be effective for recurrent renal AVM.

Closed reduction of displaced or dislocated mandibular condyle fractures in children using threaded Kirschner wire and external rubber traction.

Most surgeons agree that closed treatment provides the best results for condylar fractures in children. Nevertheless, treatment of the paediatric mandibular condyle fracture that is severely displaced or dislocated is controversial. The purpose of this study was to investigate the long-term clinical and radiological outcomes following the treatment of displaced or dislocated condylar fractures in children using threaded Kirschner wire and external rubber traction. This procedure can strengthen the advantage of closed reduction and make up for the shortcomings of open reduction. From March 1, 2005 to December 25, 2011, 11 children aged between 4 and 12 years with displaced or dislocated mandibular condyle fractures were treated using threaded Kirschner wire and external rubber traction under portable C-arm fluoroscopy. All patients had unilateral displaced or dislocated condylar fractures. The follow-up period ranged from 24 to 42 months (mean 29.3 months). Normal occlusion and pain-free function of the temporomandibular joint, without deviation or limitation of jaw opening, was achieved in all patients. This closed reduction technique in displaced or dislocated condylar fractures in children offers a reliable solution in preventing the unfavourable sequelae of closed treatment and the open technique, such as altered morphology, functional disturbances, and facial nerve damage.

Increased protein oxidation and decreased expression of nuclear factor E2-related factor 2 protein in skin tissue of patients with diabetes.

BACKGROUND: Reactive oxygen species (ROS) contribute to the cell dysfunction and tissue damage that result from glucolipotoxicity in diabetes. ROS formation in cells causes oxidative stress, thereby activating oxidative damage-inducing genes. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to play an essential role in the vital defence mechanisms that help cells cope with oxidative stress. AIM: To compare Nrf2 protein expression in nondiabetic skin tissue with that in diabetic skin tissue. METHODS: Nrf2 expression was evaluated by Western blotting, reverse transcription (RT)-PCR, and immunohistochemical staining in diabetic and nondiabetic skin tissues. Dinitrophenylhydrazone derivatives of protein carbonyls in the oxidized proteins were measured by oxyblotting analysis. Cytoplasmic and nuclear Nrf2 protein expression was determined to identify the activity and level of Nrf2. RESULTS: Protein oxidation, a marker of oxidative stress, was found to be increased in diabetic skin tissue. In subcellular fraction analysis, Nrf2 protein was detected in the nuclei and cytoplasm of nondiabetic skin tissues, and the Nrf2 protein band was identified from among the multiple bands detected, using small interfering RNA-mediated Nrf2 gene silencing. Compared with nondiabetic tissue, diabetic skin tissue showed simultaneous downregulation of Nrf2 at both the mRNA and protein levels. Nuclear condensation, loss of nuclei, and vacuolization were seen in some parts of the specimen by haematoxylin and eosin staining of diabetic skin tissue. Immunohistochemical staining of Nrf2 confirmed the RT-PCR and Western blotting results. CONCLUSIONS: Collectively, our data show that expression of Nrf2 is clearly downregulated in diabetic skin tissue, and suggest that Nrf2 may be necessary for protection against glucose-induced oxidative stress.

Differentiation of tumor progression from pseudoprogression in patients with posttreatment glioblastoma using multiparametric histogram analysis.

BACKGROUND AND PURPOSE: The multiparametric imaging can show us different aspects of tumor behavior and may help differentiation of tumor recurrence from treatment related change. Our aim was to differentiate tumor progression from pseudoprogression in patients with glioblastoma by using multiparametric histogram analysis of 2 consecutive MR imaging studies with relative cerebral blood volume and ADC values. MATERIALS AND METHODS: Thirty-five consecutive patients with glioblastoma with new or increased size of enhancing lesions after concomitant chemoradiation therapy following surgical resection were included. Combined histograms were made by using the relative cerebral blood volume and ADC values of enhancing areas for initial and follow-up MR imaging, and subtracted histograms were also prepared. The histogram parameters between groups were compared. The diagnostic accuracy of tumor progression based on the histogram parameters of initial and follow-up MR imaging and subtracted histograms was compared and correlated with overall survival. RESULTS: Twenty-four pseudoprogressions and 11 tumor progressions were determined. Diagnosis based on the subtracted histogram mode with a multiparametric approach was more accurate than the diagnosis based on the uniparametric approach (area under the receiver operating characteristic curve of 0.877 versus 0.801), with 81.8% sensitivity and 100% specificity. A high mode of relative cerebral blood volume on the subtracted histogram by using a multiparametric approach (relative cerebral blood volume ×ADC) was the best predictor of true tumor progression (P < .001) and worse survival (P = .003). CONCLUSIONS: Multiparametric histogram analysis of posttreatment glioblastoma was useful to predict true tumor progression and worse survival.

Fibroblast growth factor 21 improves insulin resistance and ameliorates renal injury in db/db mice.

Despite the emerging importance of fibroblast growth factor 21 (FGF21) as a metabolic hormone regulating energy balance, its direct effects on renal function remain unexplored. FGF21 was injected ip daily for 12 weeks into db/db mice. Compared with control vehicle injection, FGF21 treatment significantly improved lipid profiles and insulin resistance and resulted in significantly higher serum adiponectin levels. In contrast, serum insulin and 8-isoprostane levels were significantly decreased. Interestingly, FGF21 and its receptor components in the kidneys were found to be significantly up-regulated in db/db mice, which suggests an FGF21-resistant state. FGF21 treatment significantly down-regulated FGF21 receptor components and activated ERK phosphorylation. FGF21 administration also markedly decreased urinary albumin excretion and mesangial expansion and suppressed profibrotic molecule synthesis. Furthermore, FGF21 improved renal lipid metabolism and oxidative stress injury. In cultured renal cells, FGF21 was mainly expressed in mesangial cells, and knockdown of FGF21 expression by stealth small interfering RNA further aggravated high-glucose-induced profibrotic cytokine synthesis in mesangial cells. Our results suggest that FGF21 improves insulin resistance and protects against renal injury through both improvement of systemic metabolic alterations and antifibrotic effects in type 2 diabetic nephropathy. Targeting FGF21 could therefore provide a potential candidate approach for a therapeutic strategy in type 2 diabetic nephropathy.

Renal protective effects of toll-like receptor 4 signaling blockade in type 2 diabetic mice.

Chronic inflammation caused by high glucose and high free fatty acid (FFA) concentrations is a major contributor to the pathogenesis of type 2 diabetes. Recent evidence suggests that activation of Toll-like receptor (TLR) signaling induces peripheral insulin resistance and mediates central insulin and leptin resistance. In this study, we investigated the renal effects of TLR4 signaling blockade in type 2 diabetic mice. Eight-week-old db/db mice were treated for 12 weeks with (S,R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid (GIT27), which targets macrophages through the inhibition of TLR4- and TLR2/6-mediated signaling pathways. Although GIT27 treatment improved glycemic control and insulin tolerance, which is associated with a lower lipid profile, it did not impact body weight or food consumption. GIT27 treatment also markedly decreased urinary albumin excretion, decreased proinflammatory cytokine synthesis, improved tissue lipid metabolism, induced oxidative stress, and improved glomerulosclerosis compared with the control db/db group. In cultured podocytes and adipocytes, high glucose levels with FFA stimulation increased TLR4 expression and proinflammatory cytokine synthesis, but the effects were abolished by GIT27 treatment. In addition, knockdown of TLR4 expression by stealth small interfering RNA abolished FFA-induced proinflammatory cytokine synthesis in cultured podocytes. In conclusion, our results suggest that GIT27 treatment improves insulin resistance and protects against the renal injury that occurs in type 2 diabetic nephropathy through both metabolic and antiglomerulosclerotic mechanisms. These results suggest that TLR pathway inhibition might play a direct protective role in diabetic kidney disease.

Population declines and heavy metal exposure of Swinhoe's Storm Petrels (Oceanodroma monorhis) breeding on the southwest coast of Korea.

We investigated the population dynamics of globally near-threatened Swinhoe's Storm Petrels on Kugul and Chilbal islets where >90% of the world breeding population have resided for >25 years. We also determined the levels of six heavy metals in the seabird species as a possible factor affecting reproduction. Of the 892 and 307 marked burrows since 1986, the breeding density of Swinhoe's Storm Petrels has changed significantly, based on a 55% decline at Kugul islet, and a 39% decline at Chilbal islet, suggesting that this species has suffered an extensive population decline. Of the individuals studied, five Swinhoe's Storm Petrels and two Streaked Shearwaters had >8.0 µg/g Pb in tissues, which is a potentially lethal level in avian species. Given that substantial changes in their breeding populations may occur in a limited breeding colony, ecological threats including environmental pollutants warrant attention for global conservation of these birds.

Blockade of cannabinoid receptor 1 improves insulin resistance, lipid metabolism, and diabetic nephropathy in db/db mice.

The endocannabinoid system is important in the pathogenesis of obesity-related metabolic disorders. However, the effect of inhibiting the endocannabinoid system in type 2 diabetic nephropathy is unclear. Therefore, we examined the effect of the cannabinoid (CB)1 receptor antagonist, SR141716, on insulin resistance and diabetic nephropathy in db/db mice. Six-week-old db/db mice were treated with the CB1-specific antagonist SR141716 (10 mg/kg · d) for 3 months. Treatment with SR141716 significantly improved insulin resistance and lipid abnormalities. Concomitantly, CB1 antagonism improved cardiac functional and morphological abnormality, hepatic steatosis, and phenotypic changes of adipocytes into small differentiated forms, associated with increased adiponectin expression and decreased lipid hydroperoxide levels. CB1 receptor was overexpressed in diabetic kidneys, especially in podocytes. Treatment with the SR141716 markedly decreased urinary albumin excretion and mesangial expansion and suppressed profibrotic and proinflammatory cytokine synthesis. Furthermore, SR141716 improved renal lipid metabolism and decreased urinary 8-isoprostane levels, renal lipid hydroperoxide content, and renal lipid content. In cultured podocytes, high-glucose stimulation increased CB1 receptor expression, and SR141716 treatment abolished high-glucose-induced up-regulation of collagen and plasminogen activator inhibitor-1 synthesis. Additionally, knockdown of CB1 receptor expression by stealth small interfering RNA abolished high-glucose-induced sterol-regulatory element-binding protein-1 expression in podocytes. These findings suggest that CB1 blockade improves insulin resistance and protect against renal injury through both metabolic and antifibrotic effects in type 2 diabetic nephropathy. Targeting CB1 blockade could therefore provide a new therapeutic target to prevent type 2 diabetic nephropathy.

Time-resolved MR angiography for detecting and grading ovarian venous reflux: comparison with conventional venography.

OBJECTIVE: The purpose of this study was to compare the diagnostic accuracy of time-resolved MR angiography (TR-MRA) with that of conventional venography for the detection and grading of ovarian venous reflux, which aid in the diagnosis of pelvic venous congestion. METHODS: We performed a retrospective analysis of 19 consecutive patients who underwent TR-MRA and conventional venography. The images were analysed by two radiologists in a randomised "blinded" manner. With the use of conventional venography as a gold standard, the images were reviewed to determine if differences in the detection and grading of ovarian venous reflux were seen between TR-MRA and conventional venography; the sensitivity, specificity and accuracy of TR-MRA compared with that of conventional venography were evaluated. The McNemar test was performed to determine the significance of any differences. Interobserver agreement was analysed using generalised κ statistics. RESULTS: There was no significant difference between TR-MRA and conventional venography for grading ovarian venous reflux (p>0.05). The sensitivity, specificity and diagnostic accuracy of TR-MRA were found to be 66.7%, 100% and 78.9%, and 75%, 100% and 84.2%, respectively, for the two observers. The weighted κ-values indicated excellent agreement between the two observers for grading ovarian venous reflux on TR-MRA (κ = 0.894). CONCLUSION: TR-MRA is an accurate method for accessing pelvic venous congestion.

Differential diagnosis of idiopathic normal pressure hydrocephalus from other dementias using diffusion tensor imaging.

BACKGROUND AND PURPOSE: Because DTI can provide good markers of white matter pathology, it could be useful in differentiating white matter changes of INPH from those of other dementias. The aim of this study was, by using DTI, to compare the characteristic white matter changes in INPH with those in AD, subcortical vascular dementia, and healthy control subjects. MATERIALS AND METHODS: Sixteen patients with presurgical INPH, 10 with AD, 10 with subcortical vascular dementia, and 20 healthy control subjects underwent DTI. All patients with INPH showed clinical improvement after shunt surgery, and 9 of them also underwent postshunting DTI. Regions of interest were selected at the periventricular white matter, the anterior limb of the internal capsule, the posterior limb of the internal capsule, the genu and the splenium of the corpus callosum, the superior longitudinal fasciculus, and the inferior longitudinal fasciculus. FA and MD were obtained from each region of interest and were compared among the groups. RESULTS: Presurgical INPH showed significantly higher FA than all the other groups in the posterior limb of the internal capsule, which was decreased after shunt surgery. Presurgical MD of the INPH group was higher than that in the AD and healthy control groups but lower than that in the subcortical vascular dementia group in the anterior periventricular white matter, the anterior limb of the internal capsule, and the superior longitudinal fasciculus. In differentiating INPH, the sensitivity and specificity of FA in the posterior limb of the internal capsule was 87.5% and 95.0%, respectively. CONCLUSIONS: Patients with shunt-responsive INPH showed higher FA in the posterior limb of the internal capsule compared with healthy controls and those in other groups of dementia that was reversible with shunt surgery. With this parameter, shunt-responsive INPH could be distinguished from AD, subcortical vascular dementia, and healthy conditions with high diagnostic accuracy.

Diagnostic dilemma of pseudoprogression in the treatment of newly diagnosed glioblastomas: the role of assessing relative cerebral blood flow volume and oxygen-6-methylguanine-DNA methyltransferase promoter methylation status.

BACKGROUND AND PURPOSE: Methylation of the MGMT gene promoter is associated with a favorable prognosis in adult patients with GBM treated with TMZ. We determined the incidence of pseudoprogression according to the MGMT methylation status and the potential value of DSC perfusion MR images for predicting pseudoprogression. MATERIALS AND METHODS: New or enlarged enhancing lesions after CCRT in adult patients with newly diagnosed GBMs were prospectively assessed by measuring their rCBV by using DSC perfusion MR images. Tumor tissue was assayed to determine MGMT promoter methylation status. All patients were regularly followed up at an interval of 2 months by MR images, including DSC perfusion MR images. RESULTS: Ninety eligible patients were enrolled in this study. After CCRT, new or enlarged enhanced lesions were found in 59 of 90 patients, which were subsequently classified as pseudoprogression (26 patients, 28.9%) and real progression (33 patients, 36.7%). Overall, there was a significant difference in the mean rCBV between pseudoprogression and real tumor progression (P = .003). The ROC curve revealed that an rCBV ratio >1.47 had an 81.5% sensitivity and a 77.8% specificity. The unmethylated MGMT promoter group had a significant difference of mean rCBV between pseudoprogression and real progression (P = .009), though the methylated MGMT promoter group had no significant difference (P = .258). CONCLUSIONS: The current study suggests that rCBV measured by DSC perfusion MR images has a differential impact on the predictability of pseudoprogression in patients with GBM.

The detection and discrimination of malignant and benign focal hepatic lesions: T2 weighted vs diffusion-weighted MRI.

OBJECTIVE: The purpose of this study was to evaluate the use of diffusion-weighted imaging (DWI) for the detection and characterisation of focal hepatic lesions compared with the use of T(2) weighted imaging. METHOD: 45 patients with 97 hepatic lesions (51 malignant lesions and 46 benign lesions) were included in this retrospective study. Malignant hepatic lesions included 12 hepatocellular carcinomas, 26 metastases and 13 intrahepatic cholangiocarcinomas. Benign hepatic lesions included 19 haemangiomas and 27 cysts. The MRI protocol for the upper abdomen included T(2) weighted images, in- and opposed-phase T(1) weighted images and dynamic T(1) weighted images. Breath-hold fat-suppressed single-shot echo planar DWI was performed with the following parameters: 1338/66; b factors, 0, 50 and 800 s mm(-2). Two independent observers reviewed the T(2) weighted images and the DWI to detect and to characterise the hepatic lesions. RESULTS: For detection of malignant hepatic lesions, the use of DWI showed a significantly higher detection rate than the use of T(2) weighted images (p<0.05). However, there was no significant difference between the use of DWI and T(2) weighted images for benign hepatic lesions. For the differentiation between malignant and benign hepatic lesions, there was no significant difference in sensitivity, specificity and accuracy between the use of T(2) weighted images and the use of DWI. CONCLUSION: The use of DWI was better for the detection of malignant hepatic lesions than the use of T(2) weighted images. However, for detection of benign hepatic lesions and characterisation of hepatic lesions, the use of DWI was equivalent to the use of T(2) weighted images.

Acute appendicitis: relationships between CT-determined severities and serum white blood cell counts and C-reactive protein levels.

OBJECTIVES: The aim of this study was to evaluate the relationships between the severity of appendicitis as depicted on CT and blood inflammatory markers of serum white blood cell (WBC) count and C-reactive protein (CRP). METHODS: CT images in 128 patients (109 surgically proven and 19 with clinically excluded appendicitis) were retrospectively reviewed. Two radiologists by consensus evaluated and scored (using a 0, 1 or 2 point scale) severities based on CT-determined appendiceal diameters, appendiceal wall changes, caecal changes, periappendiceal inflammatory stranding and phlegmon or abscess formation. We investigated whether CT findings were significantly related to elevated WBC counts or CRP levels and performed the correlations of WBC counts and CRP levels with CT severity scores. Patients were also subjectively classified using four grades from normal (Grade I) to perforated appendicitis (Grade IV) on the basis of CT findings to evaluate differences in WBC counts and CRP levels between grades. RESULTS: Only appendiceal wall changes and the phlegmon or abscess formation were related to elevated WBC counts and CRP levels, respectively (p<0.05). CT severity scores were found to be more strongly correlated with CRP levels (r = 0.669) than with WBC counts (r = 0.222). On the basis of CT grades, the WBC counts in Grade I were significantly lower than in other grades (p<0.001), whereas CRP levels in Grade IV were significantly higher than in other grades (p<0.001). CONCLUSION: CRP levels were found to correlate with CT-determined acute appendicitis severity and could be a useful predictor for perforated appendicitis, whereas WBC counts might be useful to detect early acute appendicitis.

Mercury and selenium content of Taiwanese seafood.

Fish consumption is avid in Taiwan (and other Asian nations), but little is known about the mercury and selenium content in local seafood. This paper reports on total mercury, methylmercury and selenium levels from 14 commonly consumed seafood items obtained from Taichung, Taiwan. Mean total mercury concentrations varied nearly 100-fold across species. Fifty per cent of the marlins sampled and 35% of the sharks exceeded the 0.3 µg g(-1) US Environmental Protection Agency (USEPA) guideline. Methylmercury comprised a majority of the total mercury in all species. In all species studied there was a molar excess of selenium over mercury. The rank order of mean selenium-mercury molar ratios was red tilapia (166.8) > abura (87.9) > river prawn (82.4) > whiteleg shrimp (64.2) > butterfish (44.6) > milkfish (37.0) > tuna (15.6) > grouper (13.9) > ayu (13.4) > coral hind (13.0) > weever (11.8) > saury (9.0) > shark (7.8) > marlin (4.2).

Gliomatosis cerebri: clinicopathologic study of 33 cases and comparison of mass forming and diffuse types.

OBJECTIVE: Gliomatosis cerebri (GC) is defined as a diffuse neoplastic glial cell infiltration of the brain with the preservation of anatomical architecture and the sparing of neurons and can be classified into Type 1 (diffuse) and Type 2 (mass forming) GCs macroscopically. There is little information on subtypes of GC. The aim of this study was to evaluate the clinicopathologic findings of GCs and to compare the clinicopathologic findings between Type 1 and Type 2 GCs. MATERIAL: A total of 33 cases of GC were obtained from pathology file of Samsung Medical Center. The diagnosis was based on magnetic resonance imaging findings and histological confirmation for all patients. Fifteen cases were classified into Type 1 and 18 were Type 2 based on the MR images. METHODS: Clinical information included patients' age, sex, tumor extent, treatment modality and survival. Pathologic features included the amount of rod cells and cytologic anaplasia such as multinucleated tumor giant cells, endothelial cell proliferation, or mitosis. Immunohistochemical study was performed for GFAP, O1, Gal-C, Ki-67, and p53. Clinicopathologic comparison between subtypes and statistical analysis were performed. RESULTS: Median age at diagnosis was older (56 years) in Type 1 than in Type 2 (44 years). Male to female ratio was about 1.54:1. Mean survival time was shorter (21 months) in Type 2 than in Type 1 GCs (24 months) (p = 0.0447). Histologically, 33 cases of GC were classified into two histologic grades (low and high grade) by cytologic anaplasia. High-grade GC was more common in Type 2 than Type 1 (p = 0.027). Immunohistochemical results demonstrated that the infiltrating tumor cells were undifferentiated cells with astrocytic or oligodendroglial differentiation. Ki-67 labeling index was correlated with subtypes (p = 0.0096). Pathologic features were not correlated with survival. CONCLUSIONS: Type 1 and 2 GCs are somewhat different in clinical presentation and pathologic features. The age group, survival time, histologic grade, and Ki-67 labeling index were significantly correlated with subtypes ofGCs. Type 2 GC was correlated with poor survival but histologic grade was not.

Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients.

In patients with human epidermal growth factor receptor-2 (HER2)-overexpressing breast cancer, treatment with trastuzumab has been shown to markedly improve the outcome. We investigated the role of trastuzumab on brain metastasis (BM) in HER2-positive breast cancer patients. From 1999 to 2006, 251 patients were treated with palliative chemotherapy for HER2-positive metastatic breast cancer at Samsung Medical Center. The medical records of these patients were analysed to study the effects of trastuzumab on BM prevalence and outcomes. Patients were grouped according to trastuzumab therapy: pre-T (no trastuzumab therapy) vs post-T (trastuzumab therapy). The development of BM between the two treatment groups was significantly different (37.8% for post-T vs 25.0% for pre-T, P=0.028). Patients who had received trastuzumab had longer times to BM compared with patients who were not treated with trastuzumab (median 15 months for post-T group vs 10 months for pre-T group, P=0.035). Time to death (TTD) from BM was significantly longer in the post-T group than in the pre-T group (median 14.9 vs 4.0 months, P=0.0005). Extracranial disease control at the time of BM, 12 months or more of progression-free survival of extracranial disease and treatment with lapatinib were independent prognostic factors for TTD from BM.