Prognostic significance of NT5E/CD73 in neuroblastoma and its function in CSC stemness maintenance.

Cluster of differentiation 73 (CD73), a cell surface enzyme that catalyzes adenosine monophosphate (AMP) breakdown to adenosine, is differentially expressed in cancers and has prognostic significance. We investigated its expression profile in neuroblastoma (NB), its association with NB clinical outcomes, and its influence in the regulation of cancer stem cells' (CSCs) stemness maintenance. RNA-Seq data mining (22 independent study cohorts, total n = 3836) indicated that high CD73 can predict good NB prognosis. CD73 expression (immunohistochemistry) gauged in an NB patient cohort (n = 87) showed a positive correlation with longer overall survival (OS, P = 0.0239) and relapse-free survival (RFS, P = 0.0242). Similarly, high CD73 correlated with longer OS and RFS in advanced disease stages, MYCN non-amplified (MYCN-na), and Stage-4-MYCN-na subsets. Despite no definite association in children < 2 years old (2Y), high CD73 correlated with longer OS (P = 0.0294) and RFS (P = 0.0315) in children > 2Y. Consistently, high CD73 was associated with better OS in MYCN-na, high-risk, and stage-4 subsets of children > 2Y. Multivariate analysis identified CD73 as an independent (P = 0.001) prognostic factor for NB. Silencing CD73 in patient-derived (stage 4, progressive disease) CHLA-171 and CHLA-172 cells revealed cell-line-independent activation of 58 CSC stemness maintenance molecules (QPCR profiling). Overexpressing CD73 in CHLA-20 and CHLA-90 cells with low CD73 and silencing in CHLA-171 and CHLA-172 cells with high CD73 showed that CD73 regulates epithelial to mesenchymal transition (E-Cadherin, N-Cadherin, Vimentin), stemness maintenance (Sox2, Nanog, Oct3/4), self-renewal capacity (Notch), and differentiation inhibition (leukemia inhibitory factor, LIF) proteins (confocal-immunofluorescence). These results demonstrate that high CD73 can predict good prognosis in NB, and further suggest that CD73 regulates stemness maintenance in cells that defy clinical therapy.

An analysis of sexual dimorphism in the tumor microenvironment of colorectal cancer.

Women with colorectal cancer (CRC) have survival advantages over men, yet the underlying mechanisms are unclear. T cell infiltration within the CRC tumor microenvironment (TME) correlates strongly with survival. We hypothesized that women with CRC have increased T cell infiltration and differential gene expression in the TME compared to men. Tissue microarrays comprising primary tumor, tumor infiltrated lymph nodes, and uninvolved colon were created from CRC patients. Proportions of CD4 positive (CD4+) and CD8 positive (CD8+) T cells were identified using immunohistochemistry. TME immune- and cancer-related genetic expression from primary and metastatic CRC tumor were also evaluated via the NanoStringIO360 panel and The Cancer Genome Atlas Project database. CD4+ was higher in tumor samples from women compared to men (22.04% vs. 10.26%, p=0.002) and also in lymph node samples (39.54% vs. 8.56%, p=0.001). CD8+ was increased in uninvolved colon from women compared to men (59.40% vs. 43.61%, p=0.015), and in stage I/II tumors compared to III/IV in all patients (37.01% vs. 23.91%, p=0.009). Top CD8+ tertile patients survived longer compared to the bottom (43.9 months vs. 25.3 months, p=0.007). Differential gene expression was observed in pathways related to Treg function, T cell activity, and T cell exhaustion, amongst several others, in women compared to men. Thus, significant sexual dimorphism exists in the TME that could contribute to survival advantages observed in female patients with CRC.

Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma With Extraintestinal Areas of Peripheral T-Cell Lymphoma Involvement.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a primary intestinal T-cell lymphoma, previously known as enteropathy-associated T-cell lymphoma (EATL) type II. Its clinical, morphologic, and immunophenotypic features distinguishing it from the more common EATL (previously EATL type I) made it a separate entity. Unlike EATL, MEITL typically is noted in Asian, Hispanic, and indigenous populations; it is rarer in native European and Caucasian populations. Due to its poor prognosis, it needs to be distinguished from inflammatory diseases and less aggressive T-cell lymphomas. We present an unusual case of MEITL in a Caucasian patient who developed nonspecific GI symptoms and was diagnosed with MEITL of the jejunum, mesenteric lymph nodes, and multiple extraintestinal sites based on histology, immunophenotype, molecular testing, and imaging. Despite aggressive treatment, he expired about seven months after the definitive diagnosis.

Histopathology of sabra dermatitis: A case report.

Sabra dermatitis (SD) is a form of irritant contact dermatitis caused by penetration of small, hair-like glochids from Opuntia cactus into the skin. SD is a common problem among the farmers who are in close contact with prickly pears; however, the histopathologic criteria for this condition are not well defined. The purpose of this article is to present a well-documented case of SD and to acquaint pathologists with the entity.

Integrative model of leukocyte genomics and organ dysfunction in heart failure patients requiring mechanical circulatory support: a prospective observational study.

BACKGROUND: The implantation of mechanical circulatory support devices in heart failure patients is associated with a systemic inflammatory response, potentially leading to death from multiple organ dysfunction syndrome. Previous studies point to the involvement of many mechanisms, but an integrative hypothesis does not yet exist. Using time-dependent whole-genome mRNA expression in circulating leukocytes, we constructed a systems-model to improve mechanistic understanding and prediction of adverse outcomes. METHODS: We sampled peripheral blood mononuclear cells from 22 consecutive patients undergoing mechanical circulatory support device (MCS) surgery, at 5 timepoints: day -1 preoperative, and postoperative days 1, 3, 5, and 8. Clinical phenotyping was performed using 12 clinical parameters, 2 organ dysfunction scoring systems, and survival outcomes. We constructed a strictly phenotype-driven time-dependent non-supervised systems-representation using weighted gene co-expression network analysis, and annotated eigengenes using gene ontology, pathway, and transcription factor binding site enrichment analyses. Genes and eigengenes were mapped to the clinical phenotype using a linear mixed-effect model, with Cox models also fit at each timepoint to survival outcomes. RESULTS: We inferred a 19-module network, in which most module eigengenes correlated with at least one aspect of the clinical phenotype. We observed a response of advanced heart failure patients to surgery orchestrated into stages: first, activation of the innate immune response, followed by anti-inflammation, and finally reparative processes such as mitosis, coagulation, and apoptosis. Eigengenes related to red blood cell production and extracellular matrix degradation became predictors of survival late in the timecourse corresponding to multiorgan dysfunction and disseminated intravascular coagulation. CONCLUSIONS: Our model provides an integrative representation of leukocyte biology during the systemic inflammatory response following MCS device implantation. It demonstrates consistency with previous hypotheses, identifying a number of known mechanisms. At the same time, it suggests novel hypotheses about time-specific targets.

High-resolution computed tomography analysis of variations of the sphenoid sinus.

Purpose The sphenoid sinus is a complex structure with key variations that are important for endoscopic parasellar approaches. In this study, high-resolution computed tomography (HRCT) scans were analyzed for the frequency of these variations. Methods A retrospective radiographic analysis was conducted on patients undergoing HRCT between July 2008 and September 2010. Results Sphenoid sinus pneumatization was defined as conchal, presellar, sellar, and postsellar based on pneumatization relative to the anterior and posterior face of the sella. The distribution ranged from 1.8%, 7.3%, 47.6%, and 43.3%, respectively. We found a greater preponderance of sellar and postsellar variation than previously reported. No differences were found in regard to age, gender, and ethnicity (African American, Caucasian, Asian, and Hispanic) (p > 0.05). The prevalence of optic nerve, maxillary nerve, and internal carotid artery protrusion was 26.1%, 25.9%, and 28.2%, respectively, and dehiscence was 2.1%, 7.4%, and 2.9%, respectively. Accessory septae were present in 43.5% of cases. A lateral recess was identified in 72.4% and clinoid pneumatization in 20% of patients. Conclusion This study demonstrates a greater prevalence of sphenoid sinus pneumatization and variations than previously reported. This has important implications in terms of preparation and anticipation of possible variations to avoid complications.

High-resolution computed tomography analysis of the prevalence of Onodi cells.

OBJECTIVES/HYPOTHESIS: Onodi cells are the posterior-most ethmoid air cells that lie superior to the sphenoid sinus. Identification of these cells is essential prior to endoscopic sinus and skull base surgery due to their intricate relationship with the optic nerves and carotid arteries, which may lead to deleterious complications. In this study, high-resolution computed tomography (HRCT) scans from 170 adult-patients were analyzed by two independent observers for the presence of Onodi cells. STUDY DESIGN: Radiographic analysis at a tertiary care medical center. METHODS: A retrospective analysis was performed on patients undergoing HRCT between July 2008 and September 2010. Incidence of Onodi cells and demographic data were collected. RESULTS: The overall prevalence of Onodi cells in this cohort was 65.3%. Subgroup analysis based on ethnicity showed a rate of Onodi cells of 83.3% in Asians, 73.1% in whites, 57.0% in African Americans, and 62.7% in Hispanics. The prevalence of Onodi cells was not significantly different among the different ethnicities (P > .05). However, this was limited by a small sample size in some ethnic groups. Onodi cell prevalence was equivalent among males and females: 62.2% and 63.5% respectively (P > .05). Overall, our results show a greater prevalence of Onodi cells than previously reported. CONCLUSIONS: We found a higher prevalence of Onodi cells in our cohort than previously reported in the literature. Therefore, it is important for surgeons to anticipate the presence of these cells during endoscopic sinus and skull base procedures to prevent potential complications.

Incomplete deployment of the Vena Tech LP filter--case series and concerns.

The Vena Tech LP vena cava filter (B Braun, Evanston, Illinois) has been FDA approved since 2001 and is a permanent vena cava filtration device. It replaced the previous Vena tech LGM filter also manufactured by B Braun. The LGM filter had 2 case series reporting a high incidence of incomplete deployment of the filter, especially when placed from a jugular approach. Design changes were made to this device and the LP filter introduced. The LP filter has also been reported to have incompletely deployed both in peer reviewed literature as well as the FDA MAUDE website. We present here 3 cases of incomplete deployment of the Vena Tech LP filter and review the cases previously described as well as attempt to present possible etiologies for incomplete deployment.

Imaging techniques for the in vivo diagnosis of melanoma.

The ability to detect early melanoma remains of paramount importance in our efforts to curtail deaths related to this malignancy. Fortunately, our clinical skills at recognizing the varied clinical presentation of early melanomas are continuously improving. Our enhanced clinical acumen together with improved awareness of the danger signs of melanoma has resulted in a greater proportion of thin melanomas being diagnosed today as compared to the past. The implementation and utilization of in vivo imaging technologies in clinical practice promises to further enhance our ability to detect melanoma while this cancer is still thin and easily curable. This article describes the utility and application of the in vivo imaging technologies that are currently in clinical use today including dermoscopy, total body photography, individual lesion photography, and reflectance confocal microscopy.