Application of enhanced recovery after surgery during the perioperative period in infants with Hirschsprung's disease - A multi-center randomized clinical trial.

BACKGROUND & AIMS: Various enhanced recovery after surgery (ERAS) guidelines have been established for several kinds of adult surgeries. While the guidelines for pediatric surgeries remained to be explored. The aim of the study was to prospectively evaluate the safety and efficacy of an ERAS protocol for Hirschsprung's disease (HSCR) infants undergoing pull-through procedures. METHODS: An infant-specific ERAS protocol was developed and implemented at multiple centers from June 1, 2016 to December 31, 2017. The study included 145 consecutive patients who underwent pull-through surgery for HSCR in three Children's hospitals. Patients were primarily divided into three groups based on the clinical classification and surgical methods. Group I included patients with the short segment type who received transanal endorectal pull-through (TEPT) surgery. Group II comprised of patients with the classical type and long segment type who received laparoscopic-assisted pull-through (LAPT) surgery. Group III involved patients with the long segment type (who had received ileostomy or colostomy during the neonatal period) and total colonic aganglionosis who received open pull-through (OPPT) surgery. Patients in the three groups mentioned above were randomly and equally assigned into the ERAS group and traditional (TRAD) group with random number table row randomization. The primary outcome was the length of postoperative hospital stay (LOS). Secondary outcomes of interest included white blood cell (WBC) and C-reactive protein (CRP) on postoperative day 1 (POD 1), the blood glucose at the time of anesthesia and 24 h after surgery, time to first defecation, time to regular diet, plasma markers of nutrition status on POD 5, plasma natrium on POD 5, the mean intraoperative fluid volume, time to discontinuation of intravenous infusion, incidence of postoperative complications, re-admission within 30 days, hospitalization costs, parental satisfaction, and growth from admission to 6 months after surgery. RESULTS: 73 and 75 patients were assigned to the TRAD and ERAS groups, respectively. There were no significant differences in demographic data. The LOS decreased from 9.5 days in the TRAD group to 7.9 days (P < 0.001) in the ERAS group. WBC count on POD 1 showed no significant difference between the two groups. CRP on POD 1 in the ERAS group was significantly lower (P < 0.001). In the ERAS group, the blood glucose was higher at anesthesia compared to the TRAD group (P < 0.001). On the contrary, the blood glucose at 24 h after surgery was significantly lower in the ERAS group (P < 0.001). Intraoperative fluid volume was lower in the EARS group (P < 0.001). ERAS could also reduce the time to first defecation (P < 0.001), discontinuation of intravenous infusion (P < 0.001) and regular diet (P < 0.001). In the ERAS group, the concentrations of prealbumin and retinol conjugated protein on POD 5 were higher than those in the TRAD group (P < 0.001, P < 0.001, respectively). The plasma natrium had no difference in the two groups on POD 5 (P > 0.05). The rate of complications (P > 0.05) and 30-day re-admission (P > 0.05) were not significantly different between the two groups. Hospitalization costs were also reduced (P < 0.001). ERAS group has a higher parental satisfaction rate, although there was no statistical difference (96% vs 89%). There was no difference in growth between the ERAS and the TRAD groups from admission to 6 months after the surgery (weight for age z score: P > 0.05, weight for length z score: P > 0.05). We also found that the shortening of LOS by the application of ERAS protocol was more obvious in the OPPT group (-2.5 ± 1.0) than that in the TEPT (-1.9 ± 1.3) and LAPT (-1.3 ± 0.4) groups. CONCLUSIONS: Implementation of the ERAS protocol in infants undergoing HSCR pull-through operations is safe and efficient. The ERAS protocol is worthy of recommendation. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02776176.

Specific serum microRNA profile in the molecular diagnosis of Hirschsprung's disease.

Hirschsprung's disease (HSCR), a congenital gastrointestinal disorder, is one of the most common causes of neonatal bowel obstruction. Without an early screening and diagnosis, some patients develop serious complications, such as toxic megacolon or acute enterocolitis. We sought to identify specific serum microRNAs (miRNAs) that can serve as novel early, non-invasive screening signature and then to test their specificity and sensitivity in diagnosing Hirschsprung's disease. We obtained serum samples from 95 HSCR cases and 104 matched controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array. The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR arranged in the training and a two-stage validation set. Additional double-blind testing was performed in 23 patients with clinically suspected HSCR to evaluate the diagnostic value and accuracy of the serum miRNA profile in predicting HSCR. Following a multi-stage evaluation approach, five miRNAs were significantly increased in HSCR cases compared with controls. The areas under the receiver operating characteristic (ROC) curve of this five-serum miRNA signature were 0.895, 0.893 and 0.925 in training set and two validation sets, respectively. The accuracy rate of the five-miRNA profile as HSCR signature was 82.6%, which, in the double-blind testing set, was markedly higher than that of contrast enema (70%), the most commonly used test performed to diagnose HSCR. Our results indicate that a five-serum miRNA signature may be linked to HSCR, representing a potential, novel, non-invasive diagnostic approach for early screening of HSCR.

Observation on erythrocyte acetylcholinesterase (AChE) in infants and children with Hirschsprung's disease.

In 31 cases of Hirschsprung's disease, the mean value of erythrocyte AChE activity was discovered to be 91.24 +/- 10.24 u/mL, being significantly higher than that from 127 normal children of 73.51 +/- 9.36 u/mL (P less than 0.001); whereas serum ChE mean value of 14.49 +/- 4.04 u/mL showed no difference from normal control (16.89 +/- 8.86 u/mL, P greater than 0.05). In addition, the erythrocyte AChE activity of six newborns with Hirschsprung's disease was also found to be much higher than its own normal control. It was therefore, concluded that this assay may be of supplementary diagnostic significance in diagnosing neonatal Hirschsprung's disease.