Factors Influencing the Use of Sentinel Lymph Node Biopsy in the Netherlands

Background

In the US, whether a sentinel lymph node biopsy (SLNB) is performed depends on tumor and patient factors, including socioeconomic status (SES) and type of health care insurance. We analyzed which patient and tumor characteristics influenced the use of SLNB in a country where every patient has equal access to healthcare.

Methods

Patients diagnosed with a cutaneous invasive melanoma of ≥1 mm between 2004 and 2011 and living in the northeastern part of the Netherlands were selected from the Netherlands Cancer Registry. Regression analysis was performed to assess the association of patient and tumor characteristics and SLNB use.

Results

SLNB was performed in 42 % of the 2,413 included patients. The frequency of performing SLNB increased between 2004 and 2011 from 24 to 55 % (p < 0.001). Patients were less likely to undergo SLNB if they had a melanoma located in the head and neck area (p < 0.001), when they were over 55 years (p = 0.001), and if they had a low SES (p = 0.03). SLNB use was more likely when the diagnosis of melanoma was made in the university hospital (p = 0.045) or when the Breslow thickness was 2.01–4.0 mm (p = 0.03).

Conclusions

The use of SLNB has increased significantly between 2004 and 2011. However, in 2011 it was still performed in only 55 % of the Dutch patients with a melanoma ≥1 mm. In patients with head and neck melanoma, older patients, and patients with low SES, SLNB was less frequently performed. Patients with T3 melanomas and a diagnosis made in the university hospital more often had an SLNB performed.     

Adiposity and Fat Metabolism in Lactating and Fasting Northern Elephant Seals

Several taxa of animals fast completely from food and water during energy-intensive periods such as lactation, breeding, and development. In elephant seals, these behaviors are sustained by high adiposity, high rates of fat mobilization, and reduced oxidation of carbohydrates and proteins. Adiposity and the regulation of lipolysis directly affect lactation energetics, milk composition, and mating success. Long-term fasting induces changes in regulation of lipolysis and lipid metabolism that influence fatty acid (FA) availability and the onset of insulin resistance. Hypoinsulinemia and elevated circulating FAs are also associated with several unique features of carbohydrate metabolism, including elevated plasma glucose, gluconeogenesis, and Cori cycle activity as well as high rates of pyruvate and tricarboxylic acid cycling. Glucose-lactate pools and triacylglycerol-FA cycles may be linked via glyceroneogenesis and this may be an important pathway influencing both fat and carbohydrate metabolism. Together, these features allow a sustained, high intensity, fat-based metabolism without substantial accumulation of ketoacids.     

Gastritis Promotes an Activated Bone Marrow-Derived Mesenchymal Stem Cell with a Phenotype Reminiscent of a Cancer-Promoting Cell

Background

Bone marrow-derived mesenchymal stem cells (BM-MSCs) promote gastric cancer in response to gastritis. In culture, BM-MSCs are prone to mutation with continued passage but it is unknown whether a similar process occurs in vivo in response to gastritis.

Aim

The purpose of this study was to identify the role of chronic gastritis in the transformation of BM-MSCs leading to an activated cancer-promoting phenotype.

Methods

Age matched C57BL/6 (BL/6) and gastrin deficient (GKO) mice were used for isolation of stomach, serum and mesenchymal stem cells (MSCs) at 3 and 6 months of age. MSC activation was assessed by growth curve analysis, fluorescence-activated cell sorting and xenograft assays. To allow for the isolation of bone marrow-derived stromal cells and assay in response to chronic gastritis, IRG/Vav-1^Cre mice that expressed both enhanced green fluorescent protein-expressing hematopoietic cells and red fluorescent protein-expressing stromal cells were generated. In a parabiosis experiment, IRG/Vav-1^Cre mice were paired to either an uninfected Vav-1^Cre littermate or a BL/6 mouse inoculated with Helicobacter pylori.

Results

GKO mice displayed severe atrophic gastritis accompanied by elevated gastric tissue and circulating transforming growth factor beta (TGFβ) by 3 months of age. Compared to BM-MSCs isolated from uninflamed BL/6 mice, BM-MSCs isolated from GKO mice displayed an increased proliferative rate and elevated phosphorylated-Smad3 suggesting active TGFβ signaling. In xenograft assays, mice injected with BM-MSCs from 6-month-old GKO animals displayed tumor growth. RFP+ stromal cells were rapidly recruited to the gastric mucosa of H. pylori parabionts and exhibited changes in gene expression.

Conclusions

Gastritis promotes the in vivo activation of BM-MSCs to a phenotype reminiscent of a cancer-promoting cell.