Effects of tube voltage and iodine contrast medium on radiation dose of whole-body CT.

BACKGROUND: The low-tube-voltage scan generally needs a higher tube current than the conventional 120 kVp to maintain the image noise. In addition, the low-tube-voltage scan increases the photoelectric effect, which increases the radiation absorption in organs. PURPOSE: To compare the organ radiation dose caused by iodine contrast medium between low tube voltage with low contrast medium and that of conventional 120-kVp protocol with standard contrast medium. MATERIAL AND METHODS: After the propensity-matching analysis, 66 patients were enrolled including 33 patients with 120 kVp and 600 mgI/kg and 33 patients with 80 kVp and 300 mgI/kg (50% iodine reduction). The pre- and post-contrast phases were assessed in all patients. The Monte Carlo simulation tool was used to simulate the radiation dose. The computed tomography (CT) numbers for 10 organs and the organ doses were measured. The organ doses were normalized by the volume CT dose index, and the 120-kVp protocol was compared with the 80-kVp protocol. RESULTS: On contrast-enhanced CT, there were no significant differences in the mean CT numbers of the organs between 80-kVp and 120-kVp protocols except for the pancreas, kidneys, and small intestine. The normalized organ doses at 80 kVp were significantly lower than those of 120 kVp in all organs (e.g. liver, 1.6 vs. 1.9; pancreas, 1.5 vs. 1.8; spleen, 1.7 vs. 2.0) on contrast-enhanced CT. CONCLUSION: The low tube voltage with low-contrast-medium protocol significantly reduces organ doses at the same volume CT dose index setting compared with conventional 120-kVp protocol with standard contrast medium on contrast-enhanced CT.

Usefulness of Contrast-Enhanced 3D-FLAIR MR Imaging for Differentiating Rathke Cleft Cyst from Cystic Craniopharyngioma.

BACKGROUND AND PURPOSE: Because it can be difficult to discriminate between a Rathke cleft cyst and cystic craniopharyngioma by conventional MR imaging alone, we investigated whether contrast-enhanced 3D T2-FLAIR MR imaging at 3T helps to distinguish a Rathke cleft cyst from a cystic craniopharyngioma. MATERIALS AND METHODS: We evaluated pre- and postcontrast T1-weighted and 3D T2-FLAIR images of 17 patients with pathologically confirmed Rathke cleft cyst (n = 10) or cystic craniopharyngioma (n = 7). All underwent 3T MR imaging studies before surgery. Two neuroradiologists independently recorded the enhancement grade of the lesion wall as grade 2 (most of the wall enhanced), grade 1 (some of the wall enhanced), and grade 0 (none of the wall enhanced). One neuroradiologist performed a blinded reading study of conventional MR images with/without 3D T2-FLAIR images. Interobserver agreement was determined by calculating the κ coefficient. Statistical analyses, including receiver operating characteristic curve analysis were performed. RESULTS: Interobserver agreement for postcontrast T1WI and 3D T2-FLAIR images was excellent (κ = 0.824 and κ = 0.867, respectively). Although the difference in the mean enhancement grade of Rathke cleft cysts and cystic craniopharyngiomas was not significant on postcontrast T1WIs, it was significant on postcontrast 3D T2-FLAIR images (P = .0011). The area under the receiver operating characteristic curve of the conventional MR alone and conventional MR with 3D T2-FLAIR readings was 0.879 and 1.0, respectively, though there was no significant difference in the area under the curve between the 2 readings. CONCLUSIONS: Contrast-enhanced 3D T2-FLAIR imaging at 3T helps to distinguish a Rathke cleft cyst from cystic craniopharyngioma.

Three-dimensional reversed fast imaging with steady-state precession diffusion-weighted imaging for the detection of middle ear cholesteatoma.

AIM: To determine the usefulness of three-dimensional reversed fast imaging with steady-state precession diffusion-weighted imaging (3D-PSIF DWI) for the detection of middle ear cholesteatoma. MATERIALS AND METHODS: The study population consisted of 81 patients who underwent 3D-PSIF-DWI at 3 T. They included cholesteatoma in 73 cases, otitis media in five, and cholesterol granuloma in three. Two observers independently performed qualitative evaluations for the detection of cholesteatoma and measured apparent diffusion coefficient (ADC) values and ADC ratios of the lesions. Kappa (κ) statistics, the intraclass correlation coefficient (ICC), the independent t-test, and receiver operating characteristic (ROC) analysis were used for statistical analysis. Pair-wise comparison of the ROC curves was performed using the area under the ROC curve (AUC). RESULTS: Interobserver agreement and ICC for the qualitative and quantitative evaluations were excellent (κ=0.92 and ICC=0.90-0.92, respectively). The ADC value and the ADC ratio were significantly lower for cholesteatoma than non-cholesteatoma lesions (p<0.0001). In <5 mm cholesteatoma group, the diagnostic performance of the ADC value (AUC=0.97) and the ADC ratio (AUC=1) was significantly superior to qualitative 3D-PSIF-DWI (AUC=0.76; p=0.0001 and <0.0001, respectively). For ≥5 mm cholesteatoma group, there were no significant differences in diagnostic performance among the three parameters. CONCLUSION: 3D-PSIF-DWI sequence is useful for the detection of middle ear cholesteatomas, especially <5 mm lesions.

Safety and efficacy of nivolumab in combination with S-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: interim results of a randomized, phase II trial (ATTRACTION-4).

BACKGROUND: Nivolumab is approved as an option for third- or later-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) cancer in several countries after ATTRACTION-2. To further improve the therapeutic efficacy of first-line therapy, exploration of a nivolumab-chemotherapy combination is warranted. In part 1 (phase II) of ATTRACTION-4, the safety and efficacy of nivolumab combined with S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (CapeOX) as first-line therapy for unresectable advanced or recurrent human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer were evaluated. PATIENTS AND METHODS: Patients were randomized (1 : 1) to receive nivolumab (360 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) or CapeOX (capecitabine, 1000 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. RESULTS: Of 40 randomized patients, 39 (nivolumab plus SOX, 21; nivolumab plus CapeOX, 18) and 38 (21 and 17, respectively) comprised the safety and efficacy populations, respectively. Most frequent (>10%) grade 3/4 treatment-related adverse events were neutropenia (14.3%) in the nivolumab plus SOX group, and neutropenia (16.7%), anemia, peripheral sensory neuropathy, decreased appetite, type 1 diabetes mellitus, and nausea (11.1% each) in the nivolumab plus CapeOX group. No treatment-related death occurred. Objective response rate was 57.1% (95% confidence interval 34.0-78.2) with nivolumab plus SOX and 76.5% (50.1-93.2) with nivolumab plus CapeOX. Median overall survival was not reached (NR) in both groups. Median progression-free survival was 9.7 months (5.8-NR) and 10.6 months (5.6-12.5), respectively. CONCLUSION: Nivolumab combined with SOX/CapeOX was well tolerated and demonstrated encouraging efficacy for unresectable advanced or recurrent HER2-negative G/GEJ cancer. ATTRACTION-4 has proceeded to part 2 (phase III) to compare nivolumab plus SOX/CapeOX versus placebo plus SOX/CapeOX. CLINICALTRIALS.GOV ID: NCT02746796.

DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption.

Dendritic cell-specific transmembrane protein (DC-STAMP) plays a key role in the induction of osteoclast (OC) cell fusion, as well as DC-mediated immune regulation. While DC-STAMP gene expression is upregulated in the gingival tissue with periodontitis, its pathophysiological roles in periodontitis remain unclear. To evaluate the effects of DC-STAMP in periodontitis, anti-DC-STAMP-monoclonal antibody (mAb) was tested in a mouse model of ligature-induced periodontitis ( n = 6-7/group) where Pasteurella pneumotropica ( Pp)-reactive immune response activated T cells to produce receptor activator of nuclear factor kappa-B ligand (RANKL), which, in turn, promotes the periodontal bone loss via upregulation of osteoclastogenesis. DC-STAMP was expressed on the cell surface of mature multinuclear OCs, as well as immature mononuclear OCs, in primary cultures of RANKL-stimulated bone marrow cells. Anti-DC-STAMP-mAb suppressed the emergence of large, but not small, multinuclear OCs, suggesting that DC-STAMP is engaged in the late stage of cell fusion. Anti-DC-STAMP-mAb also inhibited pit formation caused by RANKL-stimulated bone marrow cells. Attachment of ligature to a second maxillary molar induced DC-STAMP messenger RNA and protein, along with elevated tartrate-resistant acid phosphatase-positive (TRAP+) OCs and alveolar bone loss. As we expected, systemic administration of anti-DC-STAMP-mAb downregulated the ligature-induced alveolar bone loss. Importantly, local injection of anti-DC-STAMP-mAb also suppressed alveolar bone loss and reduced the total number of multinucleated TRAP+ cells in mice that received ligature attachment. Attachment of ligature induced significantly elevated tumor necrosis factor-α, interleukin-1ß, and RANKL in the gingival tissue compared with the control site without ligature ( P < 0.05), which was unaffected by local injection with either anti-DC-STAMP-mAb or control-mAb. Neither in vivo anti- Pp IgG antibody nor in vitro anti- Pp T-cell response and resultant production of RANKL was affected by anti-DC-STAMP-mAb. This study illustrated the roles of DC-STAMP in promoting local OC cell fusion without affecting adaptive immune responses to oral bacteria. Therefore, it is plausible that a novel therapeutic regimen targeting DC-STAMP could suppress periodontal bone loss.

Estrogen receptor-beta genetic variations and overall survival in patients with locally advanced gastric cancer.

Estrogen has been shown not only to reduce the incidence of colorectal cancer but also gastric cancer (GC). Polymorphisms in estrogen receptor ß gene, ESR2, correlate with colorectal cancer survival. To better understand the role of ESR2 in GC, genomic DNA extracted from 169 Japanese patients and 172 patients from Los Angeles County (LAC) was analyzed for association of overall survival (OS) with three ESR2 polymorphisms, which are of biological significance using multivariable Cox proportional hazard regression. ESR2 rs1271572 (C>A) and rs3020443 (T>G) had univariate and multivariable associations with OS in the Japanese cohort, whereas the C allele of ESR2 rs2978381 (T>C) predicted favorable OS in the Japanese cohort but worse OS in the LAC cohort. The interaction term of the ESR2 rs2978381 and cohort group reached statistical significance. Our study provides evidence that genetic variations in ESR2 gene are significantly associated with survival in patients with locally advanced GC.

Genetic variations in immunomodulatory pathways to predict survival in patients with locoregional gastric cancer.

Immunomodulator-targeting therapies are under development in gastric cancer (GC). However, the role of genes modulating anti-tumor immunity in GC remains poorly understood. We investigated the association of variations in genes involved in immunomodulatory pathways with overall survival (OS) in locoregional GC patients. Extracted genomic DNA was analyzed for 35 functional single-nucleotide polymorphisms in genes, PDCD1, CD274, CTLA4, FOXP3, LAG3, ADORA2A, NT5E and IDO1, in 162 Japanese patients as discovery set and 277 US patients as validation set. The C allele of PDCD1 rs10204525 had univariate and multivariable associations with shorter OS in Japanese cohort (P=0.015, P=0.043, respectively). In US cohort the C allele predicted worse OS (P=0.007). Univariate and multivariable analyses revealed IDO1 rs9657182 associated with OS in the Japanese cohort; moreover, the association was confirmed in the US cohort. Genetic predisposition of the host in the immunomodulators may serve as a prognostic biomarker in patients with locoregional GC.

Lateral Asymmetry and Spatial Difference of Iron Deposition in the Substantia Nigra of Patients with Parkinson Disease Measured with Quantitative Susceptibility Mapping.

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping is useful for assessing iron deposition in the substantia nigra of patients with Parkinson disease. We aimed to determine whether quantitative susceptibility mapping is useful for assessing the lateral asymmetry and spatial difference in iron deposits in the substantia nigra of patients with Parkinson disease. MATERIALS AND METHODS: Our study population comprised 24 patients with Parkinson disease and 24 age- and sex-matched healthy controls. They underwent 3T MR imaging by using a 3D multiecho gradient-echo sequence. On reconstructed quantitative susceptibility mapping, we measured the susceptibility values in the anterior, middle, and posterior parts of the substantia nigra, the whole substantia nigra, and other deep gray matter structures in both hemibrains. To identify the more and less affected hemibrains in patients with Parkinson disease, we assessed the severity of movement symptoms for each hemibrain by using the Unified Parkinson's Disease Rating Scale. RESULTS: In the posterior substantia nigra of patients with Parkinson disease, the mean susceptibility value was significantly higher in the more than the less affected hemibrain substantia nigra (P < .05). This value was significantly higher in both the more and less affected hemibrains of patients with Parkinson disease than in controls (P < .05). Asymmetry of the mean susceptibility values was significantly greater for patients than controls (P < .05). Receiver operating characteristic analysis showed that quantitative susceptibility mapping of the posterior substantia nigra in the more affected hemibrain provided the highest power for discriminating patients with Parkinson disease from the controls. CONCLUSIONS: Quantitative susceptibility mapping is useful for assessing the lateral asymmetry and spatial difference of iron deposition in the substantia nigra of patients with Parkinson disease.

Association of variants in genes encoding for macrophage-related functions with clinical outcome in patients with locoregional gastric cancer.

BACKGROUND: Nuclear factor-kappaB (NF-κB) and CCL2/CCR2 chemokine axis play a central role in tumor progression such as stimulation of angiogenesis, acceleration of tumor invasion and migration, and suppression of innate immunosurveillance in the macrophage-related functions. There have been few reports regarding association of the macrophage function-related genes with the clinical outcome in gastric cancer. We hypothesized that variants in genes encoding for NF-κB and CCL2/CCR2 axis may predict prognosis in gastric cancer and tested whether the functional single-nucleotide polymorphisms (SNPs) will be associated with clinical outcome in patients with gastric cancer across two independent groups. PATIENTS AND METHODS: This study enrolled two cohorts which consisted of 160 Japanese patients and 104 US patients with locoregional gastric cancer. Genomic DNA was analyzed for association of 11 SNPs in NFKB1, RELA, CCL2, and CCR2 with clinical outcome using PCR-based direct DNA sequencing. RESULTS: The univariable analysis showed four SNPs had significant association with clinical outcome in the Japanese cohort, NFKB1 rs230510 remained significant upon multivariable analysis. The patients with the A allele of the NFKB1 rs230510 had significantly longer overall survival (OS) compared with those with the T/T genotype in both the Japanese and US cohort in the univariable analysis. In contrast, genotypes with the T allele of CCL2 rs4586 were significantly associated with shorter OS compared with the C/C genotype in the US cohort [hazard ratio (HR) 2.43; P = 0.015] but longer OS in the Japanese cohort (HR 0.58; P = 0.021), resulting in the statistically significant opposite impact on OS (P = 0.001). CONCLUSIONS: Our study provides the first evidence that the NFKB1 rs230510 and CCL2 rs4586 are significantly associated with the clinical outcome in patients with locoregional gastric cancer. These results also suggest that the genetic predisposition of the host may dictate the immune-related component of the tumor for progression in gastric cancer.

Distinguishing imaging features between spinal hyperplastic hematopoietic bone marrow and bone metastasis.

BACKGROUND AND PURPOSE: Systematic investigations of the distinguishing imaging features between spinal hyperplastic hematopoietic bone marrow and bone metastasis have not been reported, to our knowledge. The purpose of this study was to determine the distinguishing imaging features of the 2 entities. MATERIALS AND METHODS: We retrospectively reviewed the radiologic images of 8 consecutive male patients (age range, 52-78 years; mean, 64 years) with suspected spinal metastasis on MR imaging and FDG-PET, which was later confirmed as hyperplastic hematopoietic bone marrow. MR imaging, FDG-PET, CT, and bone scintigraphy images were qualitatively and/or quantitatively evaluated. Imaging findings in 24 patients with spinal metastasis were compared, and differences were statistically analyzed. RESULTS: All 8 vertebral hyperplastic hematopoietic bone marrow lesions were hypointense on T1- and T2-weighted images; lesions contiguous with the adjacent vertebra were significantly more often seen in hyperplastic hematopoietic bone marrow than in metastasis (P = .035). T2 signal intensity of the lesion was significantly different between the 2 entities (P = .033). FDG-PET showed slightly higher uptake in all hyperplastic hematopoietic bone marrow lesions; their maximum standard uptake value was significantly lower than that of metastatic lesions (P = .037). CT attenuation of hyperplastic hematopoietic bone marrow was equal to or slightly higher than that of adjacent normal-appearing vertebra; the CT appearances of hyperplastic hematopoietic bone marrow and metastasis were significantly different (P < .01). Bone scintigraphy showed normal uptake for all vertebrae with hyperplastic hematopoietic bone marrow; the uptake was significantly different from that of metastasis (P < .01). CONCLUSIONS: If a lesion was isointense to hyperintense to normal-appearing marrow on MR imaging or had a maximum standard uptake value of >3.6, the lesion was considered metastatic. A normal appearance on CT or bone scintigraphy excluded metastasis.

Dental pulp dendritic cells migrate to regional lymph nodes.

Dendritic cell (DC) migration to regional lymph nodes (RLNs) is an essential step in adaptive immunity, and cell-surface antigens on migrating DCs greatly affect the quality and quantity of subsequent immune responses. Although MHC class II(+) DC-like cells exist in the dental pulp, the lineage and function of these cells remain unknown. Here, we identified migratory DCs from the dental pulp after cusp trimming and acid etching in KikGR mice, in which the photoconvertible fluorescent protein changed from green to red upon violet light exposure. Two major cell fractions from the dental pulp had migrated to the RLNs at 16 hrs after cusp treatment, which showed the following lineage markers in the main and second fractions: CD11c(high)CD11b(++)Ly6C(low) Ly6G(low) F4/80(+) and CD11c(med)CD11b(+++)Ly6C(++)Ly6G(+++)F4/80(-), respectively. These lineage markers indicate that the former cells were DCs that had migrated through afferent lymphoid vessels, and the latter were granulocytes recruited via blood circulation. Migratory dental pulp DCs were mature, expressing the highest levels of CD273 (B7-DC) and CD86 co-stimulators and MHC class II. Our results suggest that cariogenic-bacteria-exposed dental pulp DCs migrate to RLNs and there trigger adaptive immune responses.

The role of IL-6 on apical periodontitis: a systematic review.

The aim of this review was to examine current knowledge of the role of interleukin-6 (IL-6) in apical periodontitis (AP) pathogenesis as an inflammatory or pro-inflammatory cytokine. It also looked at whether IL-6 could serve as a measure for differential diagnosis or as a biomarker that can further predict the progression of bone resorption. A systematic review relating to AP and IL-6 was made via PubMed, BIOSIS, Cochrane, EMBASE and Web of Science databases using keywords and controlled vocabulary. Two independent reviewers first screened titles and abstracts and then the full texts. The reference lists of the identified publications were examined for additional titles. Eighteen papers were studied in total. In vitro studies (n = 6) revealed that IL-6 is present in AP, and its levels are proportional to the size of the periapical lesions. Neutrophils and macrophages resident in these lesions can produce IL-6 in vitro after a bacterial stimulus. Animal studies (n = 5) showed that IL-6 is present in AP and that osteoblasts can produce IL-6 in vivo. On the other hand, two studies using IL-6 knockout mice revealed larger periapical lesions when compared with control groups, demonstrating IL-6's role as an anti-inflammatory cytokine. In human studies (n = 7), IL-6 was identified in AP, and its levels were higher in symptomatic, epithelialized and large lesions than in asymptomatic and small lesions. These data lead to the conclusion that IL-6 may play a pro-inflammatory role, increasing its levels and reabsorbing bone in the presence of infections. When IL-6 is not present, other cytokines such as IL-1 and TNF-α induce bone resorption. Further studies about the relationship between AP development and the cytokine network must be performed to establish the exact role of each cytokine in the inflammatory process.

Factors associated with the presence of multiple Lugol-voiding lesions in patients with esophageal squamous-cell carcinoma.

Multicentric squamous dysplasia of the esophagus is characterized by multiple Lugol-voiding lesions (LVLs) on Lugol chromoendoscopy. Multiple LVLs are associated with a very high risk of multiple cancers arising in the esophagus as well as the head and neck. To gain insight into the pathogenesis of multiple LVLs of the esophageal mucosa, we studied risk factors for the development of such lesions in 76 patients who had a current or previous diagnosis of esophageal squamous cell carcinoma. All patients underwent Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Polymorphisms of the aldehyde dehydrogenase type 2 (ALDH2) gene were identified by polymerase chain reaction using sequence-specific primers. Clinical factors related to multiple LVLs were analyzed. All patients with multiple LVLs were drinkers. On univariate analysis, male sex (odds ratio [OR] 15, 95% confidence interval [CI] 1.84-122.45: P = 0.011), presence of the ALDH2-2 allele (OR 4.5, 95% CI 1.55-13.24: P = 0.006), and smoking index ≥1000 (OR 2.6, 95% CI 1.02-6.6: P = 0.045) were associated with multiple LVLs. On multivariate analysis, male sex (OR 10.02, 95% CI 1.13-88.44: P = 0.038) and presence of the ALDH2-2 allele (OR 4.56, 95% CI 1.4-14.82: P = 0.012) were associated with multiple LVLs. Among drinkers, a daily alcohol intake of ≥100 g pure ethanol with the ALDH2-2 allele (OR 17.5, 95% CI 1.97-155.59: P = 0.01) and a daily alcohol intake of <100 g pure ethanol with the ALDH2-2 allele (OR 8.85, 95% CI 1.68-46.69: P = 0.01) more strongly correlated with multiple LVLs than did a daily alcohol intake of <100 g pure ethanol without the ALDH2-2 allele, whereas a daily alcohol intake of ≥100 g pure ethanol without the ALDH2-2 allele (OR 4.0, 95% CI 0.54-29.81: P = 0.18) did not. In conclusion, male sex and the ALDH2-2 allele are associated with an increased risk for multiple LVLs of the esophageal mucosa in patients with esophageal squamous cell carcinoma. Among drinkers with the ALDH2-2 allele, the risk of multiple LVLs increased in parallel to the daily alcohol intake.

Intratumoral expression profiling of genes involved in angiogenesis in colorectal cancer patients treated with chemotherapy plus the VEGFR inhibitor PTK787/ZK 222584 (vatalanib).

The phase III CONFIRM clinical trials demonstrated that metastatic colorectal cancer patients with elevated serum lactate dehydrogenase (LDH) had improved outcome when the vascular endothelial growth factor receptor (VEGFR) inhibitor PTK/ZK (Vatalanib) was added to FOLFOX4 chemotherapy. We investigated the hypothesis that high intratumoral expression of genes regulated by hypoxia-inducible factor-1 alpha (HIF1α), namely LDHA, glucose transporter-1 (GLUT-1), VEGFA, VEGFR1, and VEGFR2, were predictive of outcome in CONFIRM-1. Tumor tissue was isolated by laser-capture microdissection from 85 CONFIRM-1 tumor specimens; FOLFOX4/placebo n=42, FOLFOX4/PTK/ZK n=43. Gene expression was analyzed using quantitative RT-PCR. In univariate analyses, elevated mRNA expression of LDHA, GLUT-1, and VEGFR1 were associated with response to FOLFOX4/PTK/ZK. In univariate and multivariate analyses, elevated LDHA and VEGFR1 mRNA levels were associated with improved progression-free survival in FOLFOX4/PTK/ZK patients. Furthermore, increased HIF1α and VEGFR2 mRNA levels were associated with decreased survival in FOLFOX/placebo patients but not in patients who received FOLFOX4/PTK/ZK. These are the first data suggesting intratumoral mRNA expression of genes involved in angiogenesis/HIF pathway may predict outcome to VEGFR-inhibitors. Biomarkers that assist in directing VEGFR-inhibitors toward patients with an increased likelihood of benefit will improve the cost-effectiveness of these promising agents.

Can 3T MR angiography replace DSA for the identification of arteries feeding intracranial meningiomas?

BACKGROUND AND PURPOSE: For identifying the arterial feeders of meningiomas, the usefulness of 3D TOF MRA at 3T has not been systematically investigated. This study was intended to assess whether unenhanced 3D TOF MRA at 3T can replace DSA for the identification of arteries feeding intracranial meningiomas and whether it is useful for assessing their dural attachment. MATERIALS AND METHODS: Twenty-one consecutive patients with intracranial meningiomas (18 women, 3 men; aged 42-77 years, mean 57 years) underwent DSA, conventional MR imaging, and 3D TOF MRA. Two neuroradiologists independently evaluated the primary and secondary feeders of each tumor on maximum-intensity-projection and source MRA images. They also identified the location of dural attachments based on information from MR imaging/MRA images. Interobserver and intermodality agreement was determined by calculating the κ coefficient. RESULTS: For the identification of primary and secondary feeders on MRA images, interobserver agreement was very good (κ=0.83; 95% CI, 0.66-1.00) and moderate (κ=0.58; 95% CI, 0.34-0.82) and intermodality agreement (consensus reading of MRA versus DSA findings) was excellent (κ=0.94; 95% CI, 0.84-1.00) and good (κ=0.72; 95% CI, 0.51-0.93), respectively. With respect to the dural attachment of meningiomas, interobserver agreement was very good (κ=0.95; 95% CI, 0.84-1.00). The agreement in the diagnosis between MR imaging/MRA and surgery was excellent (κ=1.00). CONCLUSIONS: Unenhanced 3D TOF MRA at 3T cannot at present supplant DSA for the identification of the feeding arteries of intracranial meningiomas. This information may be useful for evaluating their dural attachment.

The octadecaneuropeptide stimulates somatolactin release from cultured goldfish pituitary cells.

The present study aimed to investigate the distribution of the octadecaneuropeptide (ODN) in the goldfish brain and to look for a possible effect of ODN on somatolactin (SL) release from pituitary cells. A discrete population of ODN-immunoreactive neurones was localised in the lateral part of the nucleus lateralis tuberis. These neurones sent projections through the neurohypophyseal tract towards the neurohypophysis, and nerve fibres were seen in the close vicinity of SL-producing cells in the pars intermedia. Incubation of cultured goldfish pituitary cells with graded concentrations of ODN (10(-9) -10(-5 ) m) induced a dose-dependent stimulation of SL-ß, but not SL-α, release. ODN-evoked SL release was blocked by the metabotrophic endozepine receptor antagonist cyclo(1-8) [DLeu(5) ]OP but was not affected by the central-type benzodiazepine receptor antagonist flumazenil. ODN-induced SL release was suppressed by treatment with the phospholipase C (PLC) inhibitor U-73122 but not with the protein kinase A (PKA) inhibitor H-89. These results indicate that, in fish, ODN produced by hypothalamic neurones acts as a hypophysiotrophic neuropeptide stimulating SL release. The effect of ODN is mediated through a metabotrophic endozepine receptor positively coupled to the PLC/inositol 1,4,5-trisphosphate/protein kinase C-signalling pathway.

Propofol sedation with bispectral index monitoring is useful for endoscopic submucosal dissection: a randomized prospective phase II clinical trial.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) has become a standard treatment. However, the treatment time tends to be relatively long and insufflation and manipulation of the endoscope can increase pain and discomfort. We aimed to find an optimal method for sedation during ESD. PATIENTS AND METHODS: Patients scheduled to undergo ESD for early gastric cancer or adenoma were randomly assigned to sedation with midazolam or propofol, and consciousness level was evaluated by bispectral index (BIS) monitoring. Primary end points of effectiveness (three parameters) and secondary end points of safety during ESD and after return to the ward were compared between the groups. Study registration was in the UMIN Clinical Trial Registry (UMIN 000001497), and the institutional trial number was KDOG 0801. RESULTS: From June 2008 through June 2009, we enrolled 178 patients (90 midazolam, 88 propofol). Regarding safety after ESD, recovery was significantly better in the propofol group immediately after and at 1 hour and 2 hours after return to the ward (P < 0.001). The number of patients who required a continuous supply of oxygen 2 hours after returning to the ward was significantly lower in the propofol group (midazolam 18; propofol 6; P = 0.010). Though propofol seemed to be better for effectiveness and safety, there were no statistically significant differences for all three primary end points and the safety parameters (hypotension, hypoxia, bradycardia). CONCLUSIONS: Propofol with BIS monitoring improved recovery of patients after ESD, though this study was underpowered to prove the effectiveness and safety of propofol.

Tissue rinse liquid-based cytology: a feasible tool for the intraoperative pathological evaluation of sentinel lymph nodes in breast cancer patients.

OBJECTIVES: A unique diagnostic method was designed for the intraoperative pathological evaluation of sentinel lymph nodes (SLNs) in breast cancer patients, and the results were verified with 2 years of experience. METHODS: Excised lymph nodes were cut into 2-mm-thick slices and rinsed thoroughly in CytoRich Red(®). The sliced tissues were embedded in a paraffin block. Three cytological glass slides of the cells exfoliated in CytoRich Red(®) were prepared by the SurePath(®) liquid-based cytology (LBC) technique. Two slides were stained by the Papanicolaou method, and the remaining slide was immunostained with an anti-keratin antibody. This process is called tissue rinse liquid-based cytology (TRLBC). The results of TRLBC were compared with those of the final pathological diagnoses, including immunostaining with an anti-keratin antibody on paraffin blocks (PB). RESULTS: This study analysed 444 SLNs from 247 consecutive breast cancer patients. It required 35 minutes to complete the intraoperative diagnosis on a single node, and it took an additional 5 minutes per node if more than one node was submitted. When the results of PB were assumed to be the gold standard, the sensitivity and specificity of TRLBC were 81.9% and 96.1%, respectively. TRLBC detected all nodes with macrometastasis and 23 of 24 nodes with micrometastasis. Fifteen false-negative TRLBC results were 'isolated tumour cell clusters' on PB, but there was one with micrometastasis histologically. Four of 14 false-positive TRLBC results were proven to be true positive by supplementary examination using step sectioning of the paraffin blocks of the nodes. CONCLUSION: TRLBC is a feasible and promising intraoperative cytopathological tool showing a comparable efficacy to PB while still allowing the conventional postoperative histological examination.

The octadecaneuropeptide exerts an anxiogenic-like action in goldfish.

I.c.v. administration of the octadecaneuropeptide (ODN), a peptide derived from diazepam-binding inhibitor (DBI), induces anorexigenic and anxiogenic-like actions in rodents. We have recently shown that, in goldfish, i.c.v. injection of ODN also reduces food consumption via the metabotropic endozepine receptor. However, there is little information regarding the structure of DBI and the psychophysiological roles of endozepines in fish. Therefore, in the present study, we isolated and cloned a cDNA encoding goldfish DBI. The deduced sequence exhibits high similarity with non-mammalian DBIs, and we investigated the effect of homologous ODN on psychomotor activity in goldfish. i.c.v. injection of synthetic goldfish ODN at 10 pmol/g body weight (BW) stimulated locomotor activity. Since intact goldfish placed in a tank with both black and white background areas prefers the black compartment, we developed a method for measuring the time taken for fish to move from the black to the white area. I.c.v. administration of diazepam (35 and 350 pmol/g BW) decreased, whereas i.c.v. administration of ODN (10 pmol/g BW) or the central-type benzodiazepine receptor inverse agonist FG-7142 (9 pmol/g BW) increased the time taken to move from the black to the white background area. The anxiogenic-like effect of ODN was blocked by the central-type benzodiazepine receptor antagonist flumazenil (100 pmol/g BW), but was not affected by the metabotropic endozepine receptor antagonist cyclo1-8[d-Leu(5)]octapeptide (100 pmol/g BW). These data indicate that ODN can potently affect locomotor and psychomotor activities in goldfish and that this action is mediated via the central-type benzodiazepine receptor-signaling pathway.

Blockade of Th1 chemokine receptors ameliorates pulmonary granulomatosis in mice.

Sarcoidosis is a granulomatous disease of unknown aetiology. We identified immunological targets for the treatment of pulmonary granulomatosis using a murine model generated with Propionibacterium acnes. Sensitisation and challenge using heat-killed P. acnes and dendritic cells (DCs) were performed to produce pulmonary granulomatosis in C57BL/6 mice. Immunological analyses using ELISA as well as cDNA microarray analysis were used to search for cytokines or chemokines associated with the formation of granulomas in the lungs. Co-administration of P. acnes and DCs reproducibly induced the formation of pulmonary granulomas, which resembled sarcoid granulomas. The cDNA microarray assay demonstrated that the gene expression of CXCL9 and CXCL10, ligands for CXCR3, and of CCL4, a ligand for CCR5, was strongly upregulated during granulomatosis. ELISA confirmed that levels of CXCL9 and CXCL10 as well as T-helper (Th)1 cytokines and chemokines including tumour necrosis factor-α and interferon-γ were elevated in bronchoalveolar lavage fluid (BALF). The blockade of Th1 chemokine receptors using TAK-779, a dual blocker for CXCR3 and CCR5, led to reduced numbers of CXCR3+CD4+ and CCR5+CD4+ T-cells in BALF. Furthermore, administration of TAK-779 ameliorated the granulomatosis. The targeted inhibition of Th1 chemokines might be useful for inhibiting Th1-biased granulomatous diseases, including sarcoidosis.