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The intestinal epithelium has one of the greatest regenerative capacities in the body; however, neither stem nor progenitor cells have been successfully cultivated from the intestine. In this study, we applied an "artificial niche" of mouse embryonic fibroblasts to derive multipotent cells from the intestinal epithelium. Cocultivation of adult mouse and human intestinal epithelium with fibroblast feeder cells led to the generation of a novel type of nestin-positive cells (intestinal epithelium-derived nestin-positive cells [INPs]). Transcriptome analyses demonstrated that mouse embryonic fibroblasts expressed relatively high levels of Wnt/bone morphogenetic protein (BMP) transcripts, and the formation of INPs was specifically associated with an increase in Lef1, Wnt4, Wnt5a, and Wnt/BMP-responsive factors, but a decrease of BMP4 transcript abundance. In vitro, INPs showed a high but finite proliferative capacity and readily differentiated into cells expressing neural, pancreatic, and hepatic transcripts and proteins; however, these derivatives did not show functional properties. In vivo, INPs failed to form chimeras following injection into mouse blastocysts but integrated into hippocampal brain slice cultures in situ. We conclude that the use of embryonic fibroblasts seems to reprogram adult intestinal epithelial cells by modulation of Wnt/BMP signaling to a cell type with a more primitive embryonic-like stage of development that has a high degree of flexibility and plasticity.

Histopathological tumor regression grade (TRG) has been shown to be a prognostic factor in patients with esophageal cancer after neoadjuvant radiochemotherapy (RCT). The system introduced by Mandard to group TRG (Cancer 1994;73:2680-2686) has been used to analyse and discuss its prognostic significance on survival in a single institution retrospective analysis: TRG 1 (complete regression) - TRG 5 (absence of regressive changes). Sixty patients with locally advanced (T3/4 or N1) adenocarcinoma or squamous cell carcinoma received cisplatin-based RCT. Three to four weeks later operation for curative intent was performed. Median follow-up was 17.7 months. Histopathological tumor stages were stage 0 in 17%, stage I in 10%, stage II in 60%, stage III in 12% and stage IVA in 1%. The 5-year overall survival (OS) rate was 35%. In univariate analysis, ypN-status and TRG correlated significantly with OS (P = 0.004, P = 0.0008, respectively). While OS of TRG 1 differed significantly from all other groups, no differences in OS between the other TRG groups were seen. Patients with complete tumor regression after neoadjuvant RCT showed a much better survival than patients with tumors that responded less to induction therapy. Further qualitative subdivision of tumor regression could not identify patient groups with significant differences in prognosis. After comparing our data with the literature, it is reasonable to consider classifying all patients into 'Complete tumor regression' and 'Incomplete tumor regression'.

Background: The aim of this study was to determine the accuracy of prediction of the surgeon's 'gut-feeling' in estimating postoperative outcome., Methods: A prospective series of 1077 consecutive patients undergoing major hepatobiliary or gastrointestinal surgery were studied. Patients having elective (n = 827) and emergency (n = 250) procedures were included. The surgeon predicted the development of postoperative complications immediately after completion of surgery on a scale from 0 to 100 percent. These predictions were compared with the actual outcome and with predictions made using the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM). The Portsmouth predictor equation (P-POSSUM) was applied for the estimation of mortality., Results: The observed morbidity and mortality rates were 29.5 and 3.4 percent respectively. POSSUM predicted a morbidity rate of 46.4 percent and P-POSSUM a mortality rate of 6.9 percent. The surgeon's gut-feeling was more accurate in the prediction of morbidity at 32.1 percent. On the basis of gut-feeling, surgeons overpredicted morbidity in elective surgery, but underestimated the risk of complications in the emergency setting. The (P)-POSSUM scoring system overpredicted morbidity and mortality for elective and emergency operations., Conclusion: The surgeon's gut-feeling is a good predictor of postoperative outcome, especially after elective surgery. (P)-POSSUM overpredicted morbidity and mortality in this series of major gastrointestinal and hepatobiliary operations.