The utility of the 24-h delayed film of barium enema for detecting the dysganglionic bowel segment in Hirschsprung's disease.

Background: Preoperative evaluation of the dysganglionic bowel segment is critical for establishing the optimal resection strategy for Hirschsprung's disease (HSCR), which facilitates patient outcomes. Objective: We set out to determine the utility of the 24-h delayed film of barium retention in predicting the length of dysganglionic bowel segment in HSCR. Materials and methods: A retrospective study of patients with clinically suspicious HSCR who underwent a preoperative 24-h delayed film of barium enema and were surgically treated from January 2015 to December 2019 was conducted. Results: Two hundred and 58 patients were enrolled in this study. The sensitivity, specificity, positive and negative predictive values (NPVs) of the 24-h delayed film of barium enema to predict the neuropathological segment were 89.1, 91.5, 91.3, and 89.4%, respectively. The Youden index was 80.6%, with a kappa value of 0.806 (P < 0.001). The correlation rate between barium retention level and pathological results was 72.7% (16/22) when aganglionosis was restricted within the mid-distal rectum (short-segment type), increasing to 92.0% (46/50) and 93.5% (174/186) for patients that had aganglionosis extended beyond the mid-distal rectum (classical type) and sigmoid colon (long-segment type), respectively. Lastly, patients younger than 3 months showed a lower correlation rate (72.2%) compared to patients aged 3-12 months (91.0%) and > 12 months (92.6%). Conclusions: Our investigation of the 24-h delayed film of barium enema performed for patients suspected of having HSCR indicated that the barium retention level remains crucial in predicting dysganglionic bowel segment, which contributes to the decision-making for surgical physicians.

NOX1/4 Inhibitor GKT-137831 Improves Erectile Function in Diabetic Rats by ROS Reduction and Endothelial Nitric Oxide Synthase Reconstitution.

BACKGROUND: Previous studies have shown that oxidative stress contributes to hyperglycemia-induced erectile dysfunction. A preferential direct inhibitor of NOX1 and NOX4, GKT-137831, exhibited a strong anti­oxidative role via blockade of reactive oxygen species (ROS) generation in endothelial cells, but whether GKT-137831 could improve erectile function was not clear. AIM: Our study was designed to investigate the effect of NOX1/4 inhibition on improving diabetic erectile dysfunction (ED) in rats. METHODS: We used streptozotocin to induce type 1 diabetes mellitus (DM) in 32 male Sprague Dawley (SD) rats (8 weeks old). Eight weeks later, type 1 diabetes mellitus-induced erectile dysfunction (DMED) in rats was confirmed using an apomorphine test. Our study consisted of 3 groups: (i) nondiabetic control group (n = 8), (ii) DMED + vehicle group (DMED group; n = 8), and (iii) DMED + GKT-137831 group (n = 9); GKT-137831 was given as a once-daily intraperitoneal injection for 4 weeks. Cavernous nerve electrostimulation was used to evaluate erectile function. Western blot, ELISA, immunohistochemistry, and immunofluorescence were used to measure expression of specific proteins, and DHE fluorescent probe was performed to detect ROS level. OUTCOMES: Intracavernous pressure (ICP), nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway, oxidative stress level, inflammatory response, corporal autophagy, and apoptosis were measured. RESULTS: Erectile function in the DMED group was significantly impaired compared to the nondiabetic control group, whereas this impairment was improved with GKT-137831 treatment by 70%. Similarly, endothelial function and overactivated oxidative stress in the corpus cavernosum (CC) of the DMED + GKT-137831 group were improved. The DMED group showed serious inflammatory responses and excessive autophagy, which were inhibited by GKT-137831 treatment in the DMED + GKT-137831 group. CLINICAL TRANSLATION: Our study showed improvement in erectile function with GKT-137831 in a diabetic rat ED model. STRENGTH AND LIMITATIONS: This study suggested for the first time that GKT-137831, an NOX1/4 inhibitor undergoing clinical trials, is effective in improving erectile function in rats with type 1 DMED. However, we only investigated GKT-137831 treatment of streptozotocin-induced type 1 diabetic rats, and therapeutic evidence in other types of diabetes is lacking. CONCLUSION: GKT-137831 improves erectile function by 70% in type 1 DMED rats and constitutes a promising compound for the treatment of type 1 DMED, likely by inhibition of overactivated oxidative stress, down-regulation of proinflammatory factors, and amelioration of excessive autophagy and endothelial function. B Zhou, Y Chen, H Yuan, et al. NOX1/4 Inhibitor GKT-137831 Improves Erectile Function in Diabetic Rats by ROS Reduction and Endothelial Nitric Oxide Synthase Reconstitution. J Sex Med 2021;18:1970-1983.

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.

Optimal time for single-stage pull-through colectomy in infants with short-segment Hirschsprung disease.

OBJECTIVE: Short-segment Hirschsprung disease (HSCR) is the predominant type of HSCR that affects approximately 75% of patients. Whether single-stage endorectal pull-through (ERPT) surgery is appropriate for neonatal patients with HSCR has not been definitively determined. This retrospective cohort study concerning infants with short-segment HSCR investigated the optimal age for single-stage ERPT surgery, regardless of the operative approach. METHODS: The 198 patients were stratified by operative age ≤ 3 or > 3 months (groups A or B, respectively, n = 62 and 136, respectively). Diagnoses of short-segment HSCR were conducted by preoperative contrast enema and rectal suction biopsy with acetylcholinesterase immunohistochemical staining. The perioperative clinical course for all patients was reviewed and the accuracy rate of the preoperative diagnoses and postoperative short- and midterm outcomes were assessed. RESULTS: The rates of diagnostic accuracy, according to the results of the preoperative contrast enema or rectal suction biopsy, were lower in group A (67.2 and 93.5%, respectively) than in group B (81.4 and 94.9%, respectively). In groups A and B, 49 (79.1%) and 108 (79.4%) infants, respectively, completed follow-up examinations. The short-term outcomes were postoperative HSCR-associated enterocolitis, adhesive bowel obstruction, anastomosis leakage, and anal stenosis during the first 12 months after surgery. The midterm outcomes were incontinence and constipation at ~24 months after surgery. Compared with group B, group A experienced more incidences of anastomotic leakage in the short-term and more soiling in the midterm. In groups A and B, the rates of constipation recurrence were nil and 1.9%, respectively. CONCLUSION: Infants with HSCR ≤3 months old at the time of single-stage ERPT surgery showed lower rates of accurate and conclusive diagnostic results and poorer postoperative outcomes. Waiting to perform this surgery until infants are older might be more beneficial.

Diagnostic value of the preoperatively detected radiological transition zone in Hirschsprung's disease.

BACKGROUND AND OBJECTIVE: The cardinal diagnostic sign of congenital aganglionic megacolon, or Hirschsprung's disease (HD), is an aganglionic segment of the distal colon or rectum. To determine the surgical planning of a radiological transition zone (TZ) in HD, this study investigated the association between a radiological TZ and the bowel resection length. METHODS: A prospective observational study was conducted in children (n = 192) with suspected HD determined by radiological TZ on contrast barium enema, and who underwent pull-through operations. The bowel resection length was ≥10 cm above the proximal radiological TZ levels and confirmed by intraoperative frozen sections. In the contrast enema, the presence and level of a radiological TZ were recorded. Correlation of the TZ features with ganglion cells assessed by immunostaining of neuronal nuclei (NeuN) and the odds ratio were calculated. RESULTS: The sensitivity and specificity for diagnosing HD by the presence of a radiological TZ were 86.9 and 92.1%, respectively; Youden's index was 79.0%. The positive and negative predictive values were 91.7 and 87.6%. The kappa value indicating an association between TZ and HD was 0.776 (P < 0.05). The correlation rate between a radiological TZ and the pathological results was 88.5% in the rectosigmoid colon and 44.4% in the descending colon, and was higher in children older than 3 months (85.3%) than in infants (69.0%). CONCLUSION: A preoperatively determined radiological TZ has potential value to identify the length of resected bowel in patients with HD, and it also has a high predictive value for diagnosis of HD.

Pathological changes of interstitial cells of Cajal and ganglion cells in the segment of resected bowel in Hirschsprung's disease.

OBJECTIVES: This study was conducted to investigate the pathological changes which occur in interstitial cells of Cajal (ICCs) and ganglion cells found in segments of resected bowel obtained from patients with Hirschsprung's disease (HD), as well as to explore the benefits of using a contrast enema (CE) with 24-h delayed X-ray films to predict the length of resected bowel. METHODS: We performed a retrospective analysis of 58 children with HD who had undergone the pull-through procedure. After each operation, the ICCs and ganglion cells present in the proximal ends of the barium residue (Level A) and resected proximal bowel segment (Level B) were analyzed using immunohistochemical staining methods. Each patient was followed up for 1 year to record their stool frequency, defecation control ability, and post-surgical complications which may have occurred. RESULTS: Immunohistochemical staining detected fewer ICCs in Level A than in Level B (p < 0.05). However, the density of ganglion cells in the two levels was not significantly different (p > 0.05). One patient had anastomotic stricture, and five patients suffered from enterocolitis. CONCLUSIONS: The density of ICCs was significantly lower in the bowel segments that displayed barium retention. A CE may be a valuable tool for predicting the length of bowel resection in patients with HD.

Nursing Intervention for Outpatient Rehabilitation in Pediatric Patients with Hirschsprung Disease after Colectomy.

OBJECTIVE: The present study was designed to evaluate the effectiveness of a nursing intervention program for outpatient rehabilitation of children with Hirschsprung-associated enterocolitis (HAEC) after radical colectomy for Hirschsprung disease (HD). BACKGROUND: Postoperative outcomes severely affect the quality of life in pediatric HD patients after operation. The improvement in defecation function is regarded as one of the most useful parameters to evaluate the quality of life in HD patients after radical intestinal resection. A close attention should also be paid to the patients' ability of social adaptation. METHODS: This prospective, randomized control trial enrolled 85 pediatric patients with HAEC after colectomy. They were randomly divided into the control and intervention groups. All the patients were followed up for 6 to 12 months after initial HAEC treatment. RESULTS: The intervention group had a lower enterocolitis recurrence rate than the control group, with a better ability to control defecation and their parents had better rehabilitation nursing knowledge (p < 0.05). The degree of parents' satisfaction regarding the outcome was significantly better in the intervention group than that in the control group (p < 0.05). CONCLUSION: A systemic rehabilitation nursing program could decrease enterocolitis recurrence, improve the recovery of anorectal functions, and enhance the quality of life in the pediatric patients after radical colectomy.

A new diagnostic scoring system to differentiate Hirschsprung's disease from Hirschsprung's disease-allied disorders in patients with suspected intestinal dysganglionosis.

PURPOSE: To create a simple diagnostic scoring system to differentiate Hirschsprung's disease (HD) from Hirschsprung's disease-allied disorders (HAD) in patients with suspected intestinal dysganglionosis (IDs). METHODS: Between 1998 and 2008, 967 patients with suspected intestinal dysganglionosis underwent surgical treatment at the pediatric surgery department of Tongji Hospital. The diagnosis of HD or HAD was confirmed by postoperative pathological examination. All patients underwent preoperative work-up including barium enema, anorectal manometry, and histochemical acetylcholinesterase staining of rectal mucosa. Known risk factors for IDs were recorded. The predicting score was calculated by summing the scores of the risk factors and three preoperative tests. The sensitivity, specificity, accuracy, positive predictive values, negative predictive values, positive likelihood ratios, and negative likelihood ratios of the predicting score were calculated. The cutoff score for predicting HD was determined using receiver operating characteristic (ROC) analysis. The accuracy of the predicting score was measured by the area under the ROC curve. RESULTS: Failed or delayed passage of meconium, age <3 years and male gender were risk factors associated with HD. The area under the ROC curve of the predicting score was 0.927 (95 % confidence interval, 0.910-0.944). A predicting score of more than 5 was used as a cutoff for predicting HD. The scoring system achieved 83.1 % sensitivity, 89.5 % specificity, and 85.9 % accuracy in predicting HD. CONCLUSION: Patients with a predicting score of more than 5 are more likely to be diagnosed with HD, whereas a score less than 5 are mostly indicative of HAD.

Diagnosis and surgical treatment of isolated hypoganglionosis.

BACKGROUND: Some patients suspected with Hirschsprung's disease (HD), however, were diagnosed as having isolated hypoganglionosis according to the updated pathohistologic methods. This study was undertaken to investigate the diagnostic methods and the therapeutic results of isolated hypoganglionosis in children. METHODS: A retrospective analysis was made on 17 patients with isolated hypoganglionosis (hypoganglionosis group) identified pathologically after operation. The data included clinical presentations, barium enema, anorectal manometry, histochemical staining for acetylcholinesterase (AChE) before operation, histological results after operation and follow-up outcomes. The data of hypoganglionosis with HD (HD group) were compared retrospectively. RESULTS: Common complaint of the patients with hypoganglionosis and HD was intractable constipation. Barium enema showed typical narrowing and distended segment of the colon in 9 patients in the hypoganglionosis group (9/16) and in 15 patients in the HD group (15/18). In the hypoganglionosis group, in 15 patients who underwent anorectal manometry only 5 showed absent rectal anal inhibitory reflex, significantly lower than the rate in the HD group (17/18) (P<0.05). From 16 patients in hypoganglionosis group, positive staining for AChE was noted in 3 patients (3/16, 18.8%), significantly lower than that in the HD group (16/18, 88.9%) (P<0.05). Thirteen patients in the hypoganglionosis group received subtotal colectomy, while only 5 patients needed subtotal colectomy in the HD group. In the hypoganglionosis group, except 2 patients who suffered from mild enterocolitis after operation and recovered after conservative therapy, all patients recovered uneventfully without wound dehiscence, intestinal fistula, fecal incontinence or constipation recurrence. In the HD group, one patient suffered from anastomotic leak and got secondary operation, one patient had anastomotic stricture at 1 year after operation and recovered by dilatation, and other three patients suffered from mild enterocolitis after operation and recovered after conservative therapy. CONCLUSIONS: Hypoganglionosis is a common disease, and could be finally confirmed by full-thickness biopsies in different bowel segments. The resection range can be estimated according to barium enema and 24-hour delayed X-ray findings, by which the satisfactory result in short-term follow-up can be obtained.