The incidence of left-sided colon and rectal cancer in young people are increasing worldwide, but its causes are poorly understood. It is not clear if the tumor microenvironment is dependent on age of onset, and little is known about the composition of tumor-infiltrating T cells in early-onset colorectal cancer (EOCRC). To address this, we investigated T-cell subsets and performed gene expression immune profiling in sporadic EOCRC tumors and matched average-onset colorectal cancer (AOCRC) tumors. Left-sided colon and rectal tumors from 40 cases were analyzed; 20 EOCRC (<45 years) patients were matched 1:1 to AOCRC (70–75 years) patients by gender, tumor location, and stage. Cases with germline pathogenic variants, inflammatory bowel disease or neoadjuvant-treated tumors were excluded. For T cells in tumors and stroma, a multiplex immunofluorescence assay combined with digital image analysis and machine learning algorithms was used. Immunological mediators in the tumor microenvironment were assessed by NanoString gene expression profiling of mRNA. Immunofluorescence revealed no significant difference between EOCRC and AOCRC with regard to infiltration of total T cells, conventional CD4+ and CD8+ T cells, regulatory T cells, or γδ T cells. Most T cells were located in the stroma in both EOCRC and AOCRC. Immune profiling by gene expression revealed higher expression in AOCRC of the immunoregulatory cytokine IL-10, the inhibitory NK cell receptors KIR3DL3 and KLRB1 (CD161), and IFN-a7 (IFNA7). In contrast, the interferon-induced gene IFIT2 was more highly expressed in EOCRC. However, in a global analysis of 770 tumor immunity genes, no significant differences could be detected. T-cell infiltration and expression of inflammatory mediators are similar in EOCRC and AOCRC. This may indicate that the immune response to cancer in left colon and rectum is not related to age of onset and that EOCRC is likely not driven by immune response deficiency.
Traditionally considered a disease common in the older population, colorectal cancer is increasing in incidence among younger demographics. Evidence suggests that populational- and generational-level shifts in the composition of the human gut microbiome may be tied to the recent trends in gastrointestinal carcinogenesis. This review provides an overview of current research and putative mechanisms behind the rising incidence of colorectal cancer in the younger population, with insight into future interventions that may prevent or reverse the rate of early-onset colorectal carcinoma.
Background: Anatomical variations of the sternal angle and anomalies of the sternum are unique happenings of major clinical significance. It is known that misplaced sternal angles may lead to inaccurate counting of ribs and create challenges with intercostal nerve blocks and needle thoracostomies. Sternal foramina may pose a great hazard during sternal puncture, due to inadvertent cardiac or great vessel injury. These sternal variations and anomalies are rarely reported among Africans. The aim of this study was to determine the anatomical variations of the sternal angle and anomalies of the sternum among adult dry human sterna at the Galloway osteological collection, Makerere University, Uganda. Materials and methods: This was a descriptive cross sectional study in which quantitative and qualitative data were collected. The study examined 85 adult human sterna at the Department of Anatomy, Makerere University. Univariate and bivariate analyses were done using SPSS 21.0 for Windows. Results: Over 40% (36/85) of the specimens had variations in size, location and fusion of the sternal angle. There was no significant difference in the mean size of the sternal angle in males at 163.4 ± 6.7o compared with 165.0 ± 6.4o in females (p = 0.481). Of the 85 specimens examined, only 21 (24.7%) had a xiphoid process. The most frequent sternal anomalies were bifid xiphoid process 42.9% (9/21) and sternal foramen 12.9% (11/85). Conclusions: Sternal variations and anomalies are prevalent in the Galloway osteological collection and there is need for increased awareness of these findings as they may determine the accuracy of clinical and other procedures in the thoracic region. Background: Anatomical variations of the sternal angle and anomalies of the sternum are unique happenings of major clinical significance. It is known that misplaced sternal angles may lead to inaccurate counting of ribs and create challenges with intercostal nerve blocks and needle thoracostomies. Sternal foramina may pose a great hazard during sternal puncture, due to inadvertent cardiac or great vessel injury. These sternal variations and anomalies are rarely reported among Africans. The aim of this study was to determine the anatomical variations of the sternal angle and anomalies of the sternum among adult dry human sterna at the Galloway osteological collection, Makerere University, Uganda. Materials and methods: This was a descriptive cross sectional study in which quantitative and qualitative data were collected. The study examined 85 adult human sterna at the Department of Anatomy, Makerere University. Univariate and bivariate analyses were done using SPSS 21.0 for Windows. Results: Over 40% (36/85) of the specimens had variations in size, location and fusion of the sternal angle. There was no significant difference in the mean size of the sternal angle in males at 163.4 ± 6.7o compared with 165.0 ± 6.4o in females (p = 0.481). Of the 85 specimens examined, only 21 (24.7%) had a xiphoid process. The most frequent sternal anomalies were bifid xiphoid process 42.9% (9/21) and sternal foramen 12.9% (11/85). Conclusions: Sternal variations and anomalies are prevalent in the Galloway osteological collection and there is need for increased awareness of these findings as they may determine the accuracy of clinical and other procedures in the thoracic region.