Obesity is not associated with disease-free interval, melanoma-specific survival, or overall survival in patients with clinical stage IB-II melanoma after SLNB

BACKGROUND AND OBJECTIVES: Clinicopathologic characteristics have prognostic value in clinical stage IB‐II patients with melanoma. Little is known about the prognostic value of obesity that has been associated with an increased risk for several cancer types and worsened prognosis after diagnosis. This study aims to examine effects of obesity on outcome in patients with clinical stage IB‐II melanoma. METHODS: Prospectively recorded data of patients with clinical stage IB‐II melanoma who underwent sentinel lymph node biopsy (SLNB) between 1995 and 2018 at the University Medical Center of Groningen were collected from medical files and retrospectively analyzed. Cox‐regression analyses were used to determine associations between obesity (body mass index> 30), tumor (location, histology, Breslow‐thickness, ulceration, mitotic rate, SLN‐status) and patient‐related variables (gender, age, and social‐economic‐status [SES]) and disease‐free interval (DFI), melanoma‐specific survival (MSS), and overall survival (OS). RESULTS: Of the 715 patients, 355 (49.7%) were women, median age was 55 (range 18.6‐89) years, 149 (20.8%) were obese. Obesity did not significantly affect DFI (adjusted hazard ratio [HR] = 1.40; 95% confidence interval [CI] = 0.98–2.00; p = 0.06), MSS (adjusted HR = 1.48;95%CI = 0.97–2.25; p = 0.07), and OS (adjusted HR = 1.25; 95% CI = 0.85–1.85; p = 0.25). Increased age, arm location, increased Breslow‐thickness, ulceration, increased mitotic rate, and positive SLN‐status were significantly associated with decreased DFI, MSS, and OS. Histology, sex, and SES were not associated. CONCLUSION: Obesity was not associated with DFI, MSS, or OS in patients with clinical stage IB‐II melanoma who underwent SLNB

Acute-Phase-HDL Remodeling by Heparan Sulfate Generates a Novel Lipoprotein with Exceptional Cholesterol Efflux Activity from Macrophages

During episodes of acute-inflammation high-density lipoproteins (HDL), the carrier of so-called good cholesterol, experiences a major change in apolipoprotein composition and becomes acute-phase HDL (AP-HDL). This altered, but physiologically important, HDL has an increased binding affinity for macrophages that is dependent on cell surface heparan sulfate (HS). While exploring the properties of AP-HDL∶HS interactions we discovered that HS caused significant remodeling of AP-HDL. The physical nature of this change in structure and its potential importance for cholesterol efflux from cholesterol-loaded macrophages was therefore investigated. In the presence of heparin, or HS, AP-HDL solutions at pH 5.2 became turbid within minutes. Analysis by centrifugation and gel electrophoresis indicated that AP-HDL was remodeled generating novel lipid poor particles composed only of apolipoprotein AI, which we designate β2. This remodeling is dependent on pH, glycosaminoglycan type, is promoted by Ca2+ and is independent of protease or lipase activity. Compared to HDL and AP-HDL, remodeled AP-HDL (S-HDL-SAA), containing β2 particles, demonstrated a 3-fold greater cholesterol efflux activity from cholesterol-loaded macrophage. Because the identified conditions causing this change in AP-HDL structure and function can exist physiologically at the surface of the macrophage, or in its endosomes, we postulate that AP-HDL contains latent functionalities that become apparent and active when it associates with macrophage cell surface/endosomal HS. In this way initial steps in the reverse cholesterol transport pathway are focused at sites of injury to mobilize cholesterol from macrophages that are actively participating in the phagocytosis of damaged membranes rich in cholesterol. The mechanism may also be of relevance to aspects of atherogenesis

German cancer statistics 2004

Background: For years the Robert Koch Institute (RKI) has been annually pooling and reviewing the data from the German population-based cancer registries and evaluating them together with the cause-of-death statistics provided by the statistical offices. Traditionally, the RKI periodically estimates the number of new cancer cases in Germany on the basis of the available data from the regional cancer registries in which registration is complete; this figure, in turn, forms the basis for further important indicators. Methods: This article gives a brief overview of current indicators - such as incidence, prevalence, mortality, survival rates - on the most common types of cancer, as well as important ratios on the risks of developing and dying of cancer in Germany. Results: According to the latest estimate, there were a total of 436,500 new cancer cases in Germany in 2004. The most common cancer in men is prostate cancer with over 58,000 new cases per annum, followed by colorectal and lung cancer. In women, breast cancer remains the most common cancer with an estimated 57,000 new cases every year, also followed by colorectal cancer. These and further findings on selected cancer sites can be found in the current brochure on “Cancer in Germany”, which is regularly published by the RKI together with the Association of Population-based Cancer Registries in Germany (GEKID). In addition, the RKI made cancer-prevalence estimates and calculated current morbidity and mortality risks at the federal level for the first time. According to these figures, the 5-year partial prevalence - i.e. the total number of cancer patients diagnosed over the past five years who are currently still living - exceeds 600,000 in men; the figure is about the same among women. Here, too, the most common cancers are prostate cancer in men and breast cancer in women. The lifetime risk of developing cancer, which is more related to the individual, is estimated to be higher among men (48.5%) than among women (40.3%). In roughly rounded figures, therefore, about every second person in Germany develops cancer in the course of their lives. One in four men and one in five women die of cancer. Conclusions: In recent years, population-based cancer registration in Germany has come significantly closer to the aim of the complete, nationwide coverage of cancer. The continuous improvements in the data situation help describe cancer development in Germany

Increase in mammography detected breast cancer over time at a community based regional cancer center: a longitudinal cohort study 1990–2005

Background: Coincident with the advent of mammography screening, breast carcinoma in situ has increased in the US population. Methods: We conducted a prospective cohort study of all women presenting with primary breast cancer, aged 21-94, and biopsy confirmed Stage 0-IV from 1990-2005 identified and tracked by our registry. Clinical presentation characteristics including age, race, TNM stage, family and pregnancy history, histologic type and method of detection by patient (PtD), physician (PhysD) or mammography (MgD) were chart abstracted at time of diagnosis. Cases with unknown or other method of detection (n = 84), or unusual cell types (n = 26) were removed (n = 6074). Results: From 1990 to 1998 the percentage of PtD and MgD cases was roughly equivalent. In 1999 the percentage of MgD cases increased to 56% and PtD dropped to 37%, a significant 20% differential, constant to 2005 (Pearson chi square = 120.99, p less than .001). Overall, percent TNM stage 0 (breast carcinoma in situ) cases increased after 1990, percent stage I and III cases declined, and stage II and IV cases remained constant (Pearson chi square = 218.36, p less than .001). Increase in MgD over time differed by age group with an 8.5% increase among women age 40-49 and 12% increase among women age 50-95. Women age 21-39 rarely had MgD BC. In forward stepwise logistic regression modeling, significant predictors of MgD BC by order of entry were TNM stage, age at diagnosis, diagnosis year, and race (chi square = 1867.56, p less than .001). Conclusion: In our cohort the relative proportion of mammography detected breast cancer increased over time with a higher increase among women age 50+ and an increase of breast carcinoma in situ exclusively among MgD cases. The increase among women currently targeted by mammography screening programs (age = 50) combined with an increase of breast carcinoma in situ most often detected by mammography screening indicates a possible incidence shift to lower stage breast cancer as a result of mammographic detection.Kaplan Research Fun

Numerical study of chemical reaction effects in magnetohydrodynamic Oldroyd B oblique stagnation flow with a non-Fourier heat flux model

Reactive magnetohydrodynamic (MHD) flows arise in many areas of nuclear reactor transport. Working fluids in such systems may be either Newtonian or non-Newtonian. Motivated by these applications, in the current study, a mathematical model is developed for electrically-conducting viscoelastic oblique flow impinging on stretching wall under transverse magnetic field. A non-Fourier Cattaneo-Christov model is employed to simulate thermal relaxation effects which cannot be simulated with the classical Fourier heat conduction approach. The Oldroyd-B non-Newtonian model is employed which allows relaxation and retardation effects to be included. A convective boundary condition is imposed at the wall invoking Biot number effects. The fluid is assumed to be chemically reactive and both homogeneous-heterogeneous reactions are studied. The conservation equations for mass, momentum, energy and species (concentration) are altered with applicable similarity variables and the emerging strongly coupled, nonlinear non-dimensional boundary value problem is solved with robust well-tested Runge-Kutta-Fehlberg numerical quadrature and a shooting technique with tolerance level of 10−4. Validation with the Adomian decomposition method (ADM) is included. The influence of selected thermal (Biot number, Prandtl number), viscoelastic hydrodynamic (Deborah relaxation number), Schmidt number, magnetic parameter and chemical reaction parameters, on velocity, temperature and concentration distributions are plotted for fixed values of geometric (stretching rate, obliqueness) and thermal relaxation parameter. Wall heat transfer rate (local heat flux) and wall species transfer rate (local mass flux) are also computed and it is observed that local mass flux increases with strength of heterogeneous reactions whereas it decreases with strength of homogeneous reactions. The results provide interesting insights into certain nuclear reactor transport phenomena and furthermore a benchmark for more general CFD simulations

In Silico Ascription of Gene Expression Differences to Tumor and Stromal Cells in a Model to Study Impact on Breast Cancer Outcome

Breast tumors consist of several different tissue components. Despite the heterogeneity, most gene expression analyses have traditionally been performed without prior microdissection of the tissue sample. Thus, the gene expression profiles obtained reflect the mRNA contribution from the various tissue components. We utilized histopathological estimations of area fractions of tumor and stromal tissue components in 198 fresh-frozen breast tumor tissue samples for a cell type-associated gene expression analysis associated with distant metastasis. Sets of differentially expressed gene-probes were identified in tumors from patients who developed distant metastasis compared with those who did not, by weighing the contribution from each tumor with the relative content of stromal and tumor epithelial cells in their individual tumor specimen. The analyses were performed under various assumptions of mRNA transcription level from tumor epithelial cells compared with stromal cells. A set of 30 differentially expressed gene-probes was ascribed solely to carcinoma cells. Furthermore, two sets of 38 and five differentially expressed gene-probes were mostly associated to tumor epithelial and stromal cells, respectively. Finally, a set of 26 differentially expressed gene-probes was identified independently of cell type focus. The differentially expressed genes were validated in independent gene expression data from a set of laser capture microdissected invasive ductal carcinomas. We present a method for identifying and ascribing differentially expressed genes to tumor epithelial and/or stromal cells, by utilizing pathologic information and weighted t-statistics. Although a transcriptional contribution from the stromal cell fraction is detectable in microarray experiments performed on bulk tumor, the gene expression differences between the distant metastasis and no distant metastasis group were mostly ascribed to the tumor epithelial cells of the primary breast tumors. However, the gene PIP5K2A was found significantly elevated in stroma cells in distant metastasis group, compared to stroma in no distant metastasis group. These findings were confirmed in gene expression data from the representative compartments from microdissected breast tissue. The method described was also found to be robust to different histopathological procedures

Slip and hall current effects on Jeffrey fluid suspension flow in a peristaltic hydromagnetic blood micropump

The magnetic properties of blood allow it to be manipulated with an electromagnetic field. Electromagnetic blood flow pumps are a robust technology which provide more elegant and sustainable performance compared with conventional medical pumps. Blood is a complex multi-phase suspension with non-Newtonian characteristics which are significant in micro-scale transport. Motivated by such applications, in the present article a mathematical model is developed for magnetohydrodynamic (MHD) pumping of blood in a deformable channel with peristaltic waves. A Jeffery’s viscoelastic formulation is employed for the rheology of blood. A twophase fluid-particle (“dusty”) model is utilized to better simulate suspension characteristics (plasma and erythrocytes). Hall current and wall slip effects are incorporated to achieve more realistic representation of actual systems. A two-dimensional asymmetric channel with dissimilar peristaltic wave trains propagating along the walls is considered. The governing conservation equations for mass, fluid and particle momentum are formulated with appropriate boundary conditions. The model is simplified using of long wavelength and creeping flow approximations. The model is also transformed from the fixed frame to the wave frame and rendered non-dimensional. Analytical solutions are derived. The resulting boundary value problem is solved analytically and exact expressions are derived for the fluid velocity, particulate velocity, fluid/particle fluid and particulate volumetric flow rates, axial pressure gradient, pressure rise and skin friction distributions are evaluated in detail. Increasing Hall current parameter reduces bolus growth in the channel, particle phase velocity and pressure difference in the augmented pumping region whereas it increases fluid phase velocity, axial pressure gradient and pressure difference in the pumping region. Increasing the hydrodynamic slip parameter accelerates both particulate and fluid phase flow at and close to the channel walls, enhances wall skin friction, boosts pressure difference in the augmented pumping region and increases bolus magnitudes. Increasing viscoelastic parameter (stress relaxation time to retardation time ratio) decelerates the fluid phase flow, accelerates the particle phase flow, decreases axial pressure gradient, elevates pressure difference in the augmented pumping region and reduces pressure difference in the pumping region. Increasing drag particulate suspension parameter decelerates the particle phase velocity, accelerates the fluid phase velocity, strongly elevates axial pressure gradient and reduces pressure difference (across one wavelength) in the augmented pumping region. Increasing particulate volume fraction density enhances bolus magnitudes in both the upper and lower zones of the channel and elevates pressure rise in the augmented pumping region