No abstract

Intestinal atresia (IA), a common cause of neonatal intestinal obstruction, is a developmental defect, which disrupts the luminal continuity of the intestine. Here, we investigated (i) the process of lumen formation in human embryos; and (ii) how a defective lumen formation led to IA. We performed histological and histochemical study on 6–10 gestation week human embryos and on IA septal regions. To investigate the topology of embryonic intestine development, we conducted 3D reconstruction. We showed that a 6–7th gestation week embryonic gut has no lumen, but filled with mesenchyme cells and vacuoles of a monolayer of epithelial cells. A narrow gut lumen was formed by gestation week-9, the gut was filled with numerous vacuoles of different sizes, some vacuoles were merging with the developing embryonic gut wall. At gestation week-10, a prominent lumen was developed, only few vacuoles were present and were merging with the intestine wall. At IA septal regions, vacuoles were located in the submucous layer, covered by a single layer of epithelium without glandular structure, and surrounded with fibrous tissue. The mucosal epithelium was developed with lamina propria and basement membrane, but the submucosa and the longitudinal smooth muscle layers were not properly developed. Hence, the vacuoles in IA septum could represent a remnant of vacuoles of embryonic gut. In conclusion, the fusion of vacuoles with the developing intestine wall associates with the disappearance of vacuoles and gut lumen formation in human embryos, and perturbation of these developmental events could lead to IA.

BACKGROUND: Brain metastasis (BM) is one of the main causes of high morbidity and mortality in cancer patients. OBJECTIVE: To evaluate the factors that influenced the survival time of patients with primary cancer and survival time after BM. METHODS: Ninety patients with BM diagnosed by magnetic resonance imaging (MRI) were included in the study. We retrospectively analyzed the time to brain metastasis (TTB), overall survival time (OS1) and survival time after BM (OS2). The Kaplan-Meier method and Cox regression analysis were used for survival analyses. RESULTS: The median TTB was 12.0 (95% CI: 9.2–14.8 months), the median OS1 was 31.0 (95% CI: 25.8–35.2 months) and the median OS2 was 14.0 (95% CI: 10.9–17.1 months). Surgical excision of the primary tumor was an independent factor for a prolonged TTB (p< 0.000) and prolonged OS1 (p< 0.000). A single intracranial metastatic lesion was an independent protective factor for prolonged OS1 (p= 0.011) and prolonged OS2 (p= 0.050). TTB, OS1 and OS2 were analyzed with Gender (p< 0.000, < 0.000, and = 0.017, respectively). CONCLUSIONS: It suggests that TTB can be prolonged by primary tumor resection. Furthermore, women with a prolonged TTB and single intracranial metastasis are associated with high OS. These were helpful for the clinical treatment of BM patients before brain metastasis.