CD90(+) stromal cells are the major source of IL-6, which supports cancer stem-like cells and inflammation in colorectal cancer.

IL-6 is a pleiotropic cytokine increased in CRC and known to directly promote tumor growth. Colonic myofibroblasts/fibroblasts (CMFs or stromal cells) are CD90(+) innate immune cells representing up to 30% of normal colonic mucosal lamina propria cells. They are expanded in CRC tumor stroma, where they also known as a cancer associated fibroblasts (CAFs). Cells of mesenchymal origin, such as normal myofibroblasts/fibroblasts, are known to secrete IL-6; however, their contribution to the increase in IL-6 in CRC and to tumor-promoting inflammation is not well defined. Using in situ, ex vivo and coculture analyses we have demonstrated that the number of IL-6 producing CMFs is increased in CRC (C-CMFs) and they represent the major source of IL-6 in T2-T3 CRC tumors. Activity/expression of stem cell markers-aldehyde dehydrogenase and LGR5- was significantly up-regulated in colon cancer cells (SW480, Caco-2 or HT29) cultured in the presence of conditioned medium from tumor isolated C-CMFs in an IL-6 dependent manner. C-CMF and its derived condition medium, but not normal CMF isolated from syngeneic normal colons, induced differentiation of tumor promoting inflammatory T helper 17 cells (Th17) cell responses in an IL-6 dependent manner. Our study suggests that CD90(+) fibroblasts/myofibroblasts may be the major source of IL-6 in T2-T3 CRC tumors, which supports the stemness of tumor cells and induces an immune adaptive inflammatory response (a.k.a. Th17) favoring tumor growth. Taken together our data supports the notion that IL-6 producing CAFs (a.k.a. C-CMFs) may provide a useful target for treating or preventing CRCs.

Use of Magnetic Resonance Cholangiopancreatography in Clinical Practice: Not as Good as We Once Thought.

BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is believed to be a useful tool to evaluate the biliary tree and pancreas for stones, tumors, or injuries to the ductile system. The purpose of this study was to compare the accuracy of MRCP to the gold standard, endoscopic retrograde cholangiopancreatography (ERCP), in our institution. STUDY DESIGN: We performed a retrospective review of all MRCP followed by ERCP (follow-on ERCP) at a single institution over a 6-year period. Exam findings from MRCP were compared with findings on the follow-on ERCP and compared. Studies were grouped into 2 main classifications: tests being performed for patients with suspected choledocholithiasis (stone disease) and tests being performed for concerns of malignant strictures or duct injuries (non-stone disease). RESULTS: A total of 81 patients had MRCPs and follow-on ERCPs in this time period. Thirty-six patients had positive findings on MRCP and ERCP for stones in the common duct system, and 14 patients had positive findings on MRCP and subsequent ERCP for masses and strictures of the common duct. Three patients had positive MRCP and ERCP findings for pancreatic duct abnormalities. The specificity and positive predictive value of MRCP were 94% and 98%, respectively. However, 13 of 28 patients had lesions identified on ERCP after a normal MRCP. The sensitivity and negative predictive value were 80% and 54%, respectively. CONCLUSIONS: Magnetic resonance cholangiopancreatography was not useful in the management algorithm of either stone or non-stone disease of the biliary tree or pancreas. It should be abandoned as a diagnostic tool for work-up of biliary duct pathology.

Can education policy be health policy? Implications of research on the social determinants of health.

Research on the social determinants of health has demonstrated robust correlations between several social factors, health status, and life expectancy. Some of these factors could be modified through policy intervention. National-level public policies explicitly based on population health research are in various stages of development in many Western countries, but in spite of evident need, seemingly not at all in the United States. Because research shows such a strong association between education and good health, we offer evidence to show that at least two pressing problems in American society, namely the uneven distribution of educational attainment and health disparities linked to socioeconomic position, may be ameliorated through policy initiatives that link quality early childhood care, child development programs, and parental training in a seamless continuum with strengthened K-12 education.