Expression of B7-H3, a potential factor of tumor immune evasion in combination with the number of regulatory T cells, affects against recurrence-free survival in breast cancer patients.

BACKGROUND: In the tumor microenvironment, factors inhibiting the targeting of cancer cells by activated T cells have recently been noted. B7-H3 belongs to the B7 superfamily of immune regulatory ligands and plays an important role in the adaptive immune response of co-inhibitory/stimulatory factors in regulating T cells. However, the degree to which B7-H3 directly affects tumor immune evasion mechanisms remains unclear, particularly in patients with breast cancer. Regulatory T cells (Tregs) are known as a key player in the inhibition of immune mechanisms. The present study demonstrated that expression of B7-H3 on tumor cells and the number of Tregs in the tumor microenvironment independently affected prognosis in breast cancer patients. METHODS: We immunohistochemically investigated the presence of B7-H3 and forkhead box P3 (Foxp3)-positive Tregs in pathological specimens from 90 patients with breast cancer. RESULTS: Positive B7-H3 expression was associated with shorter recurrence-free survival (RFS) (p = 0.014). A higher percentage of Foxp3-positive cells also correlated with shorter RFS (p = 0.039). Multivariate analysis showed B7-H3 as an independent factor on RFS. Foxp3 expression in tumor-infiltrating lymphocytes (TILs) correlated significantly with larger tumor size (>2 cm), expression of human epidermal growth factor receptor 2 (HER2), and higher nuclear grade (p = 0.003, p < 0.001, p = 0.001, respectively). No correlation was identified between expression of B7-H3 and the percentage of Foxp3-positive TILs. CONCLUSIONS: B7-H3 and Foxp3 can be regarded as markers of poor prognosis in breast cancer. These expressions were not correlated, suggesting that B7-H3 expression plays an independent role in tumor immune evasion, regardless of Tregs.

Interobserver Reliability on Intravoxel Incoherent Motion Imaging in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Noninvasive perfusion-weighted imaging with short scanning time could be advantageous in order to determine presumed penumbral regions and subsequent treatment strategy for acute ischemic stroke (AIS). Our aim was to evaluate interobserver agreement and the clinical utility of intravoxel incoherent motion MR imaging in patients with acute ischemic stroke. MATERIALS AND METHODS: We retrospectively studied 29 patients with AIS (17 men, 12 women; mean age, 75.2 [SD, 12.0 ] years; median, 77 years). Each patient underwent intravoxel incoherent motion MR imaging using a 1.5T MR imaging scanner. Diffusion-sensitizing gradients were applied sequentially in the x, y, and z directions with 6 different b-values (0, 50, 100, 150, 200, and 1000 seconds/mm2). From the intravoxel incoherent motion MR imaging data, diffusion coefficient, perfusion fraction, and pseudodiffusion coefficient maps were obtained using a 2-step fitting algorithm based on the Levenberg-Marquardt method. The presence of decreases in the intravoxel incoherent motion perfusion fraction and pseudodiffusion coefficient values compared with the contralateral normal-appearing brain was graded on a 2-point scale by 2 independent neuroradiologists. Interobserver agreement on the rating scale was evaluated using the κ statistic. Clinical characteristics of patients with a nondecreased intravoxel incoherent motion perfusion fraction and/or pseudodiffusion coefficient rated by the 2 observers were also assessed. RESULTS: Interobserver agreement was shown for the intravoxel incoherent motion perfusion fraction (κ = 0.854) and pseudodiffusion coefficient (κ = 0.789) maps, which indicated almost perfect and substantial agreement, respectively. Patients with a nondecreased intravoxel incoherent motion perfusion fraction tended to show recanalization of the occluded intracranial arteries more frequently than patients with a decreased intravoxel incoherent motion perfusion fraction. CONCLUSIONS: Intravoxel incoherent motion MR imaging could be performed in < 1 minute in addition to routine DWI. Intravoxel incoherent motion parameters noninvasively provide feasible, qualitative perfusion-related information for assessing patients with acute ischemic stroke.

Intravoxel Incoherent Motion MR Imaging of Pediatric Intracranial Tumors: Correlation with Histology and Diagnostic Utility.

BACKGROUND AND PURPOSE: Intravoxel incoherent motion imaging, which simultaneously measures diffusion and perfusion parameters, is promising for brain tumor grading. However, intravoxel incoherent motion imaging has not been tested in children. The purpose of this study was to evaluate the correlation between intravoxel incoherent motion parameters and histology to assess the accuracy of intravoxel incoherent motion imaging for pediatric intracranial tumor grading. MATERIALS AND METHODS: Between April 2013 and September 2015, 17 children (11 boys, 6 girls; 2 months to 15 years of age) with intracranial tumors were included in this retrospective study. Intravoxel incoherent motion parameters were fitted using 13 b-values for a biexponential model. The perfusion-free diffusion coefficient, pseudodiffusion coefficient, and perfusion fraction were measured in high- and low-grade tumors. These intravoxel incoherent motion parameters and the ADC were compared using the unpaired t test. The correlations between the intravoxel incoherent motion parameters and microvessel density or the MIB-1 index were analyzed using the Spearman correlation test. Receiver operating characteristic analysis was used to evaluate diagnostic performance. RESULTS: The perfusion-free diffusion coefficient and ADC were lower in high-grade than in low-grade tumors (perfusion-free diffusion coefficient, 0.85 ± 0.40 versus 1.53 ± 0.21 × 10-3 mm2/s, P < .001; ADC, 1.04 ± 0.33 versus 1.60 ± 0.21 × 10-3 mm2/s, P < .001). The pseudodiffusion coefficient showed no difference between the groups. The perfusion fraction was higher in high-grade than in low-grade tumors (21.7 ± 8.2% versus 7.6 ± 4.3%, P < .001). Receiver operating characteristic analysis found that the combined perfusion-free diffusion coefficient and perfusion fraction had the best diagnostic performance for tumor differentiation (area under the curve = 0.986). CONCLUSIONS: Intravoxel incoherent motion imaging reflects tumor histology and may be a helpful, noninvasive method for pediatric intracranial tumor grading.

Unusual familial lipoprotein C-III associated with apolipoprotein C-III-O preponderance.

Among 256 consecutive subjects so far studied in our laboratory, we found one subject (a 63-year-old female) whose very low density lipoprotein (VLDL) and high density lipoprotein (HDL) contained unusually high amounts of apolipoprotein C-III-O among apolipoprotein C-III polymorphic forms. Identification of apolipoprotein C-III-O was achieved by a combination of basic polyacrylamide gel electrophoresis, isoelectric focusing and sialidase treatment of plasma apolipoproteins. This unusual lipoprotein was inherited by two of her four children without the manifestation of clinical symptoms. Triacylglycerols and cholesterol concentrations of VLDL, low density lipoprotein (LDL) and HDL fractions, and serum apolipoprotein C-III levels of the three subjects with apolipoprotein C-III-O were within the normal range, as estimated by rocket immunoelectrophoresis. Our results clearly demonstrated that the unusual lipoproteins with the preponderance of apolipoprotein C-III-O among apolipoprotein C-III polymorphic forms were genetically determined. These cases may be a new type of genetic lipoprotein disorder.

Chronic cough in children.

Chronic cough in children is a frequent complaint seen by the primary health care provider. Although many of these coughs spontaneously resolve, some are caused by a more serious process and require further attention. Selecting those patients who will benefit from a more extensive evaluation can be a difficult challenge. An overview is provided that emphasizes a systematic approach to the diagnosis and management of chronic cough.

Neonatal Job's syndrome featuring a vesicular eruption.

A newborn infant who developed a vesicular eruption, clinically indistinguishable from herpetic lesions, eventually developed the classic features of Job's syndrome. The initial ares of involvement included the hands and feet, then the scalp, face, and suprapubic skin. The clear, tense vesicles varied only slightly in size and appeared as isolated, grouped, or confluent lesions on inflamed skin. Many eventually became umbilicated. The more typical eczematous component appeared over the course of the next several months. Although the child initially had an elevated white blood cell count and eosinophilia, his IgE level did not become dramatically elevated until after 1 year of age. Job's syndrome should be considered as part of the differential diagnosis of a vesicular eruption in the newborn.

Histiocytosis X resembling cherry angiomas.

Histiocytosis X is a disorder of histiocytes of the Langerhans' cell lineage. As the initial feature is often cutaneous, recognition of these skin changes is important. Several cutaneous manifestations have been described, most commonly, seborrheic dermatitis with a hemorrhagic component. We saw two patients with histiocytosis X with cutaneous manifestations resembling cherry angiomas.