Background and aims: Endoscopic submucosal dissection (ESD) was developed in Japan and has been performed on many patients with early stage esophageal cancer; however quality of life in patients with postoperative stricture is drastically decreased and repeat, periodic endoscopic balloon dilatation (EBD) is usually required over long periods. In this study, we evaluate the efficacy of short period, low dose oral prednisolone in controlling post-procedural esophageal stricture. Patients and methods: In total, 33 patients who underwent semicircular or complete circular ESD for esophageal superficial squamous cell carcinoma were included in this study. They were divided into two groups: those who underwent large-circumference ESD with no preventative treatment for stricture (ESD alone group) and those who received systemic steroid treatment for stricture (oral prednisolone group). We compared the two groups in terms of stricture rate and total number of EBD sessions. The ESD alone group underwent no preventative treatment. The oral prednisolone group started with 30 mg/day prednisolone on the second day post-ESD, and continued with a gradually tapering prednisolone dose, finally discontinuing systemic steroid administration 3 weeks later. Results: The stricture rate after ESD was significantly lower in the oral prednisolone group (3 of 17 patients; 17.6 %) than in the ESD alone group (11 of 16 patients; 68.7 %) (P < 0.01). The number of EBD sessions was significantly lower in the oral prednisolone group than in the ESD alone group (median 4.6, range 2 – 10 vs. median 8.1, range 1 – 18; P < 0.01). Conclusion: Short period, low dose oral prednisolone showed promising results for the prevention of stricture after ESD for early stage esophageal cancers.

BackgroundIntestinal stem cells (ISCs) play indispensable roles in the maintenance of homeostasis, and also in the regeneration of the damaged intestinal epithelia. However, whether the inflammatory environment of Crohn’s disease (CD) affects properties of resident small intestinal stem cells remain uncertain.MethodsCD patient-derived small intestinal organoids were established from enteroscopic biopsy specimens taken from active lesions (aCD-SIO), or from mucosa under remission (rCD-SIO). Expression of ISC-marker genes in those organoids was examined by immunohistochemistry, and also by microfluid-based single-cell multiplex gene expression analysis. The ISC-specific function of organoid cells was evaluated using a single-cell organoid reformation assay.ResultsISC-marker genes, OLFM4 and SLC12A2, were expressed by an increased number of small intestinal epithelial cells in the active lesion of CD. aCD-SIOs, rCD-SIOs or those of non-IBD controls (NI-SIOs) were successfully established from 9 patients. Immunohistochemistry showed a comparable level of OLFM4 and SLC12A2 expression in all organoids. Single-cell gene expression data of 12 ISC-markers were acquired from a total of 1215 cells. t-distributed stochastic neighbor embedding analysis identified clusters of candidate ISCs, and also revealed a distinct expression pattern of SMOC2 and LGR5 in ISC-cluster classified cells derived from aCD-SIOs. Single-cell organoid reformation assays showed significantly higher reformation efficiency by the cells of the aCD-SIOs compared with that of cells from NI-SIOs.ConclusionsaCD-SIOs harbor ISCs with modified marker expression profiles, and also with high organoid reformation ability. Results suggest modification of small intestinal stem cell properties by unidentified factors in the inflammatory environment of CD.Electronic supplementary materialThe online version of this article (10.1007/s00535-018-1437-3) contains supplementary material, which is available to authorized users.

SummaryATOH1 is a master transcription factor for the secretory lineage differentiation of intestinal epithelial cells (IECs). However, the comprehensive contribution of ATOH1+ secretory lineage IECs to the homeostasis, repair, and tumorigenesis of the intestinal epithelium remains uncertain. Through our ATOH1+ cell-lineage tracing, we show here that a definite number of ATOH1+ IECs retain stem cell properties and can form ATOH1+IEC-derived clonal ribbons (ATOH1+ICRs) under completely homeostatic conditions. Interestingly, colonic ATOH1+ IECs appeared to exhibit their stem cell function more frequently compared with those of the small intestine. Consistently, the formation of ATOH1+ICRs was significantly enhanced upon dextran sodium sulfate colitis-induced mucosal damage. In addition, colonic ATOH1+ IECs acquired tumor stem cell-like properties in the azoxymethane-DSS tumor model. Our results reveal an unexpected contribution of colonic ATOH1+ IECs to maintaining the stem cell population under both homeostatic and pathologic conditions and further illustrate the high plasticity of the crypt-intrinsic stem cell hierarchy.

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