In vitro analysis of esophageal atresia using a whole-embryo culture system.

BACKGROUND/PURPOSE: Administration of Adriamycin to pregnant rats leads to the development of esophageal atresia with tracheo-esophageal fistula. This defect arises from failure of the trachea to develop normally from the primitive foregut; instead,the upper foregut differentiates into trachea, then continues to the lower esophageal segment as a tracheo-esophageal fistula. Our aim was to explore the possibility of growing Adriamycin-exposed embryos using a whole-embryo culture technique and to determine whether or not esophageal atresia with tracheo-esophageal fistula could be prevented in an Adriamycin-treated rat model. METHODS: Rat embryos were exposed to Adriamycin in utero on days 6 - 9 of gestation, removed on day 10 and grown in vitro as described by New (11) for 48 hours using 100% serum from animals not exposed to Adriamycin. RESULTS: Thirty Adriamycin-exposed embryos were grown in vitro using normal serum. Histologic assessment of tracheo-esophageal development showed that 14 embryos had normal development, while 16 developed esophageal atresia. CONCLUSIONS: Growth of Adriamycin-exposed embryos was successful using "whole-embryo culture technique"; abnormal tracheo-esophageal development could in some cases be altered by removing the embryos at day 10 and exposing them to normal serum for 48 hours.

Embryogenesis of tracheal atresia.

A spectrum of tracheo-esophageal anomalies has been described in an adriamycin-treated model with common features to the human pattern. Tracheal agenesis was part of this spectrum. It is a rare congenital anomaly that has not been described in embryos. Virgin timed-pregnant Sprague-Dawley rats were injected with adriamycin i.p. at a dose of 2 mg/Kg on days 6-9 of gestation (plug day = day 0). Fetuses were recovered at term and histologic assessment of tracheo-esophageal anomalies was made. Also, embryos were removed on different gestational days and the embryology of these defects was analysed. Two out of sixty-two fetuses and nine out of 180 embryos were identified with tracheal atresia. Type III tracheal atresia was seen in the full-term fetuses with a tracheo-esophageal fistula arising from the origin of the left main bronchus. Day 13 embryos did not show normal tracheal development; instead, the lung buds developed from the ventral aspect of the foregut which continued to the stomach as a lower esophageal segment. A blind ending pouch was seen on the ventral aspect of the upper part of the foregut. The embryogenesis of tracheal atresia was similar to that of esophageal atresia except that the blind upper foregut pouch developed ventrally rather than dorsally.

Timing and embryology of esophageal atresia and tracheo-esophageal fistula.

BACKGROUND: The embryology of tracheo-esophageal anomalies is controversial. The development of an adriamycin-treated animal model has enabled improved understanding of the embryogenesis of these anomalies. Using this model, we aimed to describe the events leading to esophageal atresia and tracheo-esophageal fistula. METHODS: Timed-pregnant Sprague-Dawley rats were injected daily with adriamycin intraperitoneally at a dose of 2 mg/Kg on days 6-9 of gestation. Histological sections were prepared from 96 experimental and 34 control rat embryos at 11-14 days gestation (plug day = day 0). RESULTS: The tracheal bud failed to develop normally from the foregut, leaving the foregut to give origin to both bronchi and differentiate into the respiratory system, and then continue as a fistula to the lower esophageal segment. Dorsal pouching of the proximal foregut, which is seen clearly on day 13, is responsible for the development of the upper esophageal segment. CONCLUSIONS: We conclude that failure of the tracheal bud to develop normally from the primitive foregut is the main event which leads to the tracheo-esophageal anomalies. As the proximal part of the primitive foregut develops primarily into a trachea rather than an esophagus, the anomaly of the esophagus could be described as agenesis instead of atresia.

A prospective evaluation of the modified Alvarado score for acute appendicitis in children.

The accuracy of the modified Alvarado score was assessed prospectively in the preoperative diagnosis of acute appendicitis in children. A consecutive series of 118 patients (54 boys, 64 girls) with acute abdominal pain was studied prospectively over a 6 month period. Appendicitis was confirmed in 38 of 43 children undergoing appendicectomy, giving a false-positive appendicectomy rate of 11.6%. No child under active observation was subsequently found to have a perforated appendix. The overall sensitivity of a modified Alvarado score of > or = 7 was 76.3% and its specificity was 78.8%. Current clinical practice is more accurate than the modified Alvarado score in the diagnosis of acute appendicitis in children.