It has previously been observed that more than 90% of HD patients show symptoms such as abdominal distention and vomiting during the neonatal period(Bradnock et al., 2017). In our study, all children had symptoms of incomplete obstruction and needed to be hospitalized.
In the past, some researchers believed that the enteric nervous system is immature and is still developing in neonates, so they suggested that conservative management, including anal dilation and colon enema, could be provided first, and then biopsies and surgical treatment could be performed when the infants were older(Nakao et al., 2001). However, in recent years, many studies have demonstrated that this conclusion might not be reliable. For example, even in premature infants, the incidence of HD is the same as that of full-term infants(Downey et al., 2015; Duess et al., 2014). The impression above may be related to the difficulty in identifying ganglion cells in newborns or premature infants because immature ganglion cells or ganglion cells in the neonatal period are similar to inflammatory cells (Ambartsumyan et al., 2020). In addition, multiple submucosal hypertrophic nerves (> 40 µm) are not usually present in SRB from the aganglionic distal rectum of neonates with HD(Knowles et al., 2009). Therefore, it increases the difficulty of the pathological diagnosis in the neonatal period. To diagnose neonatal HD, auxiliary diagnostic methods such as immunohistochemistry and consultations with experienced pathologists are needed.
In our study, rectal mucosal biopsies that gained more than 2 specimens and had adequate submucosa were performed in all children before the operation. The surgical specimens were confirmed to have the absence of ganglion cells and/or had hypertrophic nerve fibers again in the final pathological examination. No misdiagnosis was found in any of the patients. Therefore, we recommend that TEPT be performed for HD in the neonatal period when using the expertise of experienced pathologists.
A contrast enema examination could be used to identify the level of aganglionosis, which generally describes a transitional zone including proximal dilatation with a spastic distal segment, but this is often not apparent in patients within the first few weeks after birth. In our study, the positive rate of contrast enema examination was 72.93%, which was similar to previous studies(Zhu et al., 2019). However, in our experience, surgeons could improve the diagnosis rate of HD by combining the medical history and clinical manifestations with the imaging results. If the aganglionosis level cannot be confirmed before the operation, the operation will be more complicated; that is, a laparotomy or a laparoscopic-assisted seromuscular biopsy may be required to determine the extent of the intestinal excision. In 174 short-segments, the contrast enema examination results of 48 patient showed no transitional zone before the operation, but only 11 patients needed an abdominal approach or laparoscopic assistance during surgery. In the long-segment and TCA groups, no patients were diagnosed as having lower rectum or sigmoid colon disease before the operation, and all patients underwent seromuscular biopsy by laparoscopy or laparotomy and then radical surgery.
The patients in this study had an average operation age of 17 days and an average operation weight of 3375 g, of which 76% of the patients had diseases of the lower rectum and sigmoid colon, which was consistent with the general distribution of HD(Langer, 2013).
The TEPT procedure was first reported by Torre et al. in 1998(Torre-Mondragón and Ortega-Salgado, 1998). They described making a circumferential incision 10 mm above the dentate line in the rectal mucosa as the first step in a transanal mucosectomy. At the same time, Langer et al. described the transanal one-stage Soave procedure in 1999  and started rectal mucosectomy from 5 mm proximal to the dentate line. All of the them retained a long muscular rectal cuff from the incision position to the peritoneal reflex. However, some researchers thought that long muscular cuffs might be associated with obstruction, constipation, and enterocolitis(Arts et al., 2016), and some reports showed better results with a short muscle cuff or even no cuff, such as the Swenson procedure(Levitt et al., 2013; Rintala, 2003; Stensrud et al., 2015). Therefore, a muscular rectal cuff < 2–3 cm has been recommended by ERNICA(Kyrklund et al., 2020).
Since the advent of the TEPT procedure, our department has adopted and optimized the surgical methods based on our own experience. The mucosal incision is made 5 mm proximal to the dental line, and the submucosal dissection is continued proximally. The rectal muscular cuff used is 2.5-3 cm long. Then, it is separated upward along the rectum wall to the level of the peritoneal reflection and proximally. Because the operation is relatively simple, the operation time is shorter, and the impact on patients is less. We usually chose the colon that is close to the normal colon diameter and texture to excise (intraoperative frozen pathology confirmed the presence of ganglion cells). In the decision to select the extent of colon resection, to avoid the residue of the transitional segment, ERNICA recommends that in rectosigmoid HD, the colon should be transected at least 5 to 10 cm proximal to the first normal biopsy(Kyrklund et al., 2020). Then, we found that the compensatory dilatation of the proximal colon was mild, and the transitional segment was short in neonatal HD. This can avoid excessively excising the colon and thus affecting the long-term colonic function, which is especially advantageous in HD with a long level of aganglionosis.
On the other hand, in 40 patients who had sigmoid colon disease, the level of aganglionosis was located in the proximal sigmoid colon, near the junction of the sigmoid colon and descending colon. However, all of them underwent transanal surgery without laparotomy or laparoscopy, which might be related to the shallowness of the pelvic cavity, the small volume of the abdominal cavity and the relaxation of the mesocolon in newborns. During the transanal surgery, the longest length of the colon pulled out through the anus was 28.5 cm. In our opinion, the majority of lower rectum and sigmoid colon HD patients, whose level of aganglionosis is below the junction of the sigmoid colon and descending colon, could undergo TEPT without a laparotomy or a laparoscopy in the neonatal period, and this technique is simple and efficient.
Almost as remarkably, in the long-segment and TCA, when the intestinal morphology might not be typical, we require a seromuscular biopsy to determine the transitional segment. Furthermore, the atypical pathology of some patients, such as patients who have immature ganglion cells and a normal nerve fiber plexus, makes the intraoperative pathological diagnosis more difficult. At this time, the surgeon needs to analyze the clinical manifestation and morphology of the intestine during the operation and verify the results repeatedly with the pathologist. We had experience in the long-segment, we took biopsy sections from the normal colon during the operation, but the results showed that there were no ganglion cells. After repeated confirmation by multipoint biopsies, it was finally confirmed that there were ganglion cells, which avoided excessively excising the colon, as well as a poor outcome.
As our study is a retrospective study, patients with long segment and TCA who underwent one-stage surgery in the neonatal period were selected, and they were in good condition. Therefore, for more serious patients, we need to choose the corresponding treatment plan according to the specific situation. In our patients, routine placement of an anal draining tube through the anastomosis was unnecessary, and anal dilation was performed for 1–3 months on an outpatient basis.
The incidence of complications within 6 months after operation was 11.8% (27/229), which was lower than the 15.6% complication rate found within one month after surgery in 182 patients in the neonatal period (< 31 days) noted by Mollie et al(Freedman-Weiss et al., 2019). Compared with other scholars' reports, the proportion of complications in our group was low. It has been reported that the incidence of postoperative enterocolitis in the neonatal period is 40.2%(Lu et al., 2017), which was not consistent with our experience. We believe that this may be related to the long preoperative colon enema time (5–7 days) in our hospital and the short muscular cuff we preserved, and more research is needed to support this view.
A total of 165 patients were followed up in this study, of which 106 children older than four years old took part in an interview about bowel function, and they were divided into two groups according to their age. There is no unified evaluation method for bowel function after surgery in HD. In the pediatric literature, several different questionnaires have been used, and only the BFS questionnaire has data from the normal population(Jarvi et al., 2010), so we chose the BFS and compared it with the literature using the same scoring criteria. In the lower rectum and sigmoid colon patients, the BFS was at a good level and increased with age. Although there was no significant difference, this might suggest that the defecation function may improve with age. Kristin et al. reported a survey of long-term bowel function after TEPT in 200 patients with rectosigmoid HD, and the mean BFS in nonsyndromic patients was 15.7. In contrast, the BFS of our group was better. The bowel movements of most healthy infants changed from more frequent and loose stool to less frequent and formed stool. We hypothesize that this may be because infants undergoing surgery as newborns also went through that process, and the defecation system, the nervous system and muscular system were well developed, as well as the coordination between systems. This is our speculation, and more research evidence is needed.
In contrast, the BFS was lower in the long-segment patients. Among the 3 patients with TCA, 2 patients had fine bowel function (BFS = 18), and 1 patient had poor bowel function (BFS = 13), which was consistent with other reports(Kawaguchi et al., 2021). However, the number of children in our group was relatively small, and long-term follow-up is needed.
The frequency of fecal incontinence after TEPT varies considerably in the literature. In a recent retrospective population-based study of 103 patients with rectosigmoid aganglionosis who underwent TEPT, 29% reported fecal incontinence episodes of variable degree more than once a week after a median follow-up time of 15 years(Neuvonen et al., 2015). On the other hand, fecal incontinence was reported in only 12% of 281 patients who underwent endorectal pull-through after a mean follow-up time of 36 months(Kim et al., 2010), and in another study of patients undergoing endorectal pull-through, none reported fecal incontinence(Mattioli et al., 2008). In our study, soiling and fecal incontinence were also the main problems of long-term follow-up after the operation. A total of 73.6% (78/106) of the patients had no soiling or fecal incontinence during the follow-up, and the rest had a few of problems that occurred with a frequency of less than 1/week. Constipation only occurred in 2 long-segment patients, which was less than the proportion previously reported in the literature(Lu et al., 2017). We considered that constipation in the long-segment might be related to poor bowel function, which leads to insufficient intestinal peristalsis, resulting in stool retention.
Among all the follow-up patients, 6 children were poor in growth and development, and 22 children were above the normal level, which seemed to be basically consistent with the normal population distribution. Therefore, the one-stage TEPT in the neonatal period had no significant effect on the growth and development of HD children.