Non-familial small bowel carcinomas in Crohn's disease: clinico-pathological, molecular and prognostic features

Background Primary non-ampullary small bowel adenocarcinoma (SBAs) is a remarkably rare tumor in the general population. Celiac disease (CD) is associated with an increased risk of developing SBA. Published data on the morphologic, phenotypic and molecular features of CD-associated SBAs (CD-SBAs) are very limited. Design We analyzed 11 SBAs arisen in the setting of CD collected from four different Italian Institutions. Immunoreactions for intestinal markers (MUC2, CDX2, CD10) and for gastric markers (MUC5AC, MUC6) were performed on representative sections of each SBA. In all cases, non-tumoral small intestinal mucosa was also examined. Additionally, we investigated the frequency of KRAS, NRAS, and BRAF somatic mutations in 9 out of 11 cases. Results The average age of patients was 56 years (rang 38-72) with predilection of females (9 females and 2 males). Three tumors were at stage III or IV and 1 patient died of disease after 6 months from diagnosis. One tumor was localized in the duodenum (second part), the remaining ten were in the jejunum. On histologic examination, three neoplasms were high grade poorly differentiated carcinomas (grade 3), one of which showing a poorly cohesive component with signet ring cells, while 8 were low-grade intestinal-type tubular adenocarcinomas. Ten cases were positive for CDX2, 7 for MUC2 and 7 for CD10. One case showed >5% MUC5AC-positive cells. No case had MUC6. Sequencing analysis of KRAS, NRAS, and BRAF hot spot regions revealed the presence of mutations only at codon 12 in exon 2 of KRAS in X of 9 cases. We found no mutations in the hot spot regions of NRAS (exons 2, 3, 4) or BRAF (exon 15). Conclusion CD-SBAs appear to have a predilection for younger people (especially female) than other SBAs and may behave aggressively. Most CD-SBAs express structural and phenotypic patterns of intestinal differentiation, including CD10 (a marker of the enterocyte brush border). In about 30% of cases they can show a high grade histology. Unlike SBAs associated with Crohn’s disease, CD-SBAs seem to rarely express gastric markers

The Arrival of Homo sapiens into the Southern Cone at 14,000 Years Ago.

The Arroyo Seco 2 site contains a rich archaeological record, exceptional for South America, to explain the expansion of Homo sapiens into the Americas and their interaction with extinct Pleistocene mammals. The following paper provides a detailed overview of material remains found in the earliest cultural episodes at this multi-component site, dated between ca. 12,170 14C yrs B.P. (ca. 14,064 cal yrs B.P.) and 11,180 14C yrs B.P. (ca. 13,068 cal yrs B.P.). Evidence of early occupations includes the presence of lithic tools, a concentration of Pleistocene species remains, human-induced fractured animal bones, and a selection of skeletal parts of extinct fauna. The occurrence of hunter-gatherers in the Southern Cone at ca. 14,000 cal yrs B.P. is added to the growing list of American sites that indicate a human occupation earlier than the Clovis dispersal episode, but posterior to the onset of the deglaciation of the Last Glacial Maximum (LGM) in the North America