Laparoscopic Redo Pull-Through for Hirschsprung Disease Due to Innervation Disorders

Abstract

Background:

Reoperations in Hirschsprung disease (HD) may be required due to pathological problems. We conducted this retrospective study to determine the incidence and outcomes of innervation disorders among HD patients following pull-through operation.

Materials and Methods:

We retrospectively reviewed the data of patients who underwent pull-through procedure from 2005 to 2017. Only patients who underwent reoperation due to histological disorders were analyzed. Patients with mechanical obstruction that caused recurrent constipation were excluded.

Results:

There were 836 patients who got treated for HD in our department during the study period, and of these, 72 (8.6%) had redo operation. Thirty-one out of the 72 patients (43.1%) showed abnormal histological findings on full-thickness biopsies. Primary operations included totally transanal endorectal pull-through (18), laparoscopic-assisted Duhamel (5) and Soave (8) techniques. The full-thickness biopsies before the reoperation showed aganglionosis (n = 8, 1 was residual resulted from false-positive intraoperative frozen sections and 7 were acquired aganglionosis), transition-zone (3), intestinal neuronal dysplasia B (IND B, n = 15), and hypoganglionosis (5). The final diagnoses according to the resection specimens of the initial and second operations were HD (11), Hirschsprung-associated IND B (15), and Hirschsprung-associated hypoganglionosis (5). Reoperation consisted of laparoscopic-assisted Duhamel (14) and Soave procedures (17). In these patients, 77.4% had excellent/good bowel function, 16.1% were fair, and 6.5% were poor.

Conclusions:

Innervation disorders are still the underlying causes of recurrent constipation in almost half of all HD patients requiring redo pull-through operation. Most patients have a satisfactory outcome after redoing laparoscopic-assisted Duhamel or Soave operation.

Introduction

Hirschsprung disease (HD) is a very common form of functional obstruction of the bowel, with a higher incidence of 2.8 per 10,000 live births in Asians than any other ethnicities.¹ It is the most common indication for surgical treatment in children with constipation. Since Swenson described the first definitive surgical treatment of HD in the late 1940s, many modifications and advances have been made in technique. Duhamel retrorectal anastomosis and Soave extramucosal dissection were developed immediately after the Swenson operation.^2,3 In 1995 Georgeson et al.⁴ described a minimal invasive procedure, consisting of an initial laparoscopic seromuscular biopsy to identify the transition zone, followed by laparoscopic-assisted colon pull-through and transanal anastomosis 1 cm above the dentate line. Subsequently, De la Torre-Mondragón and Ortega-Salgado⁵ reported a procedure of entirely transanal endorectal pull-through without laparoscopic assistance in 1998.⁵ Currently, transanal endorectal pull-through and laparoscopic-assisted approach such as Soave and Duhamel procedures have become the standard operations for HD.⁶

However, even though significant developments have been made in understanding the pathologic anatomy of HD, and much effort have been devoted to guarantee the ganglionic bowel been pulled down to be anastomosed, the results remain far from perfect.⁷ The recurrent constipation after radical operation is not uncommon. Excluding mechanical obstructions, innervation disorders of the pulled-through colon may also contribute to the recurrence of constipation (Table 1).^7–9 The success of a one-stage pull-through procedure for HD relies highly on the precise identification of the normally innervated colon by intraoperative frozen biopsies.¹⁰ Nevertheless, in some children, normal ganglion cells were clearly identified at the proximal resection margin, but the ganglion cells got “lost” subsequently (Table 2).^11–16 The purpose of this report was to review our experience with laparoscopic reoperation for HD resulting from abnormal innervation of the “neo-rectum.”

Table 1.

Causes of Recurrent Constipation After a Pull-Through for Hirschsprung Disease

Mechanical obstruction

Anastomotic stricture

Twisting of the pull-through bowel

Rolling down of the rectal muscular cuff after a Soave procedure

Soave cuff

Kinking of the anastomosis

Compression by the aganglionic pouch after a Duhamel procedure

Postoperative adhesions

Internal sphincter achalasia

Innervation disorders

Transition zone

Residual aganglionosis

Acquired aganglionosis

Hirschsprung disease related any other intestinal dysganglionosis

Table 2.

Series of Patients with Acquired Aganglionosis Following a Pull-Through Procedure

Author	Year	Country	No. of case	Initial surgical procedure	Recurrent symptoms	Treatment	Outcome
Ehrenpreis¹⁶	1965	Sweden	1	Swenson	Constipation	Modification of the Swenson and Duhamel procedures	Successfully treated
Towne et al.¹⁵	1979	America	1	Swenson	Constipation	Colostomy followed by a Soave procedure	Successfully treated
Cogbill and Lilly ¹⁴	1982	America	1	Soave	Constipation	Posterior myomectomy	Successfully treated
West et al.¹³	1990	America	5	Soave: 2 Duhamel: 2 Swenson: 1	Abdominal distention, obstipation, enterocolitis, and failure to thrive	Swenson: 2 Extended posterior anomyomectomy procedures: 2 A preliminary colostomy: 1	4 were successfully treated; 1 was awaiting a second procedure
Cohen et al.¹²	1993	South Africa	5	Soave: 4 Swenson: 1	Constipation, abdominal pain and distension, enterocolitis, and soiling	Rectal myectomy: 3 Repeat anal dilation: 1 Refuse treatment: 1	3 were successfully managed by rectal myectomy; 1 improved following repeated anal dilatation
Langer¹¹	2004	Canada	10	Soave: 8 Swenson: 1 Duhamel: 1	Severe chronic constipation, fulminant bowel obstruction, and enterocolitis	Duhamel: 8 Refused further surgery: 2	6 done very well; 2 have persistent obstructive systems

Materials and Methods

Patients

The medical records of all patients who received a redo pull-through procedure for HD from January 2005 until December 2017 were retrospectively reviewed. This was approved by the Research Ethics Board of the Union Hospital of Huazhong University of Science and Technology. The research has been registered at the Chinese Clinical Trial Registry (Registration No.: ChiCTR-OOC-17010670).

We focused on the following patients: (1) patients were confirmed as HD before the first operation; (2) ganglion cells were presented in the intraoperative frozen sections (IOFS) taken from the surgical margin of the removed bowel from the first operation; and (3) full-thickness biopsies above the level of the initial anastomosis before the repeat surgery indicated the abnormal microscopic features in the pulled-through bowel, including aganglionosis and dysganglionosis. For children who underwent a previous Duhamel procedure, biopsies were taken at the posterior wall of the pulled-through colon. Patients with any other mechanical problems listed in Table 1 were excluded. The total number of patients treated for HD and the total number of patients with recurrent constipation who need reoperation during the study period were also recorded.

Surgical technique for reoperation

The reoperation consisted of a modified laparoscopic Duhamel procedure^17,18 or a Soave operation¹⁹ as mentioned in our previous publications, which was determined due to the length of the residual colon. At first, multi-points intraoperative frozen biopsies were employed to confirm the extent of the innervation disorders. According to our experience, increased defecation frequency and soiling were common complications after subtotal or total colectomy. However, the short rectal pouch after a Duhamel pull-through can achieve adequate balance between soiling and constipation after the surgery. Thus, if the residual colon ≤15 cm, a Duhamel procedure was selected; otherwise, Soave operation was chosen if the residual colon >15 cm.

Before the first operation, all patients were evaluated with a contrast enema, an anorectal manometry, and a rectal suction biopsy. Reoperation was indicated only when the constipation failed to improve after 6–12 months' conservative treatments that included enema, oral paraffin oil, high dose lactulose, and colonic irrigation. Before the reoperation, after a history and physical examination, we performed full-thickness biopsy under general anesthesia to verify the histopathological changes for every child. Full-thickness slides stained by immunostaining of calretinin were reviewed for a comprehensive diagnosis of these cases.²⁰

The type of initial and repeat operation, age at primary and redo surgery, the results of original IOFS, and the final pathological sections taken from the primary and second operation were analyzed.

Results

There were 836 patients who got treated for HD in our department during the study period, and of these, 72 (8.6%) had redo operation. Thirty-one out of the 72 patients (43.1%) showed abnormal histological findings on full-thickness biopsies. The patients' age at the primary operation ranged from 1 month to 6 years, with an average of 5 months. Twenty-two were male and 9 were female. The original pull-through procedures included totally transanal endorectal pull-through (18), laparoscopic-assisted Duhamel (5) and Soave (8) operations. The interval between initial and redo operation varied from 12 months to 5 years (mean, 3 years). During the first operation, the proximal ganglionated segment was recognized by means of intraoperative biopsy. We routinely resected 5–10 cm of the bowel proximal to the positive biopsy to prevent the transition zone and retained segments being used in the anastomosis in the original operation.

Subsequently, we explored the discrepancies between the diagnoses of IOFS and the final pathological findings of the initial operation. In 1 case the IOFS suggested the presence of ganglion cells, but this was not confirmed by the pathological examination of the resected bowel. For this patient, residual aganglionosis was verified by the repeat surgery. As for the rest 30 cases, the IOFS indicated that ganglion cells were positive, and sections taken from the surgical margin of the pulled-through segment confirmed the findings.

Then, we reviewed the full-thickness biopsies taken before the reoperation. They showed aganglionosis (1 was residual aganglionosis due to false-positive IOFS mentioned above and 7 were acquired aganglionosis), transition-zone (n = 3), intestinal neuronal dysplasia B (IND B, n = 15), and hypoganglionosis (n = 5). Compared with normal intestine (Fig. 1a), the characteristics of IND B consist of hyperganglionosis of the submucous and myenteric plexuses, giant ganglia and ectopic ganglion cells, and increased acetylcholinesterase activity in the lamina propria and around submucosal blood vessels (Fig. 1b).²¹ The characteristic histologic features of hypoganglionosis include reduced per longitudinal centimeter number of ganglion cells and plexus area, and double distances between ganglions (Fig. 1c).²² The final diagnoses for the 31 patients in the context of the entire case were HD (n = 11), Hirschsprung-associated IND B (n = 15), and Hirschsprung-associated hypoganglionosis (n = 5). The patients' information was summarized in Table 3.

FIG. 1.

Calretinin immunostaining of full-thickness biopsies taken before the reoperation: (a) normal intestine (× 40), (b) intestinal neuronal dysplasia B (× 40), and (c) hypoganglionosis (× 40).

Table 3.

The Clinical Features of the Patients with Recurrent Pathology-Related Constipation

Main characteristics of the included patients	Case No.
Gender distribution
Male	22
Female	9
Initial operation
Totally transanal endorectal pull-through	18
Laparoscopic-assisted Duhamel	5
Laparoscopic-assisted Soave	8
Histopathologic indications for reoperation
Aganglionosis	8
Residual aganglionosis	1
Acquired aganglionosis	7
Transition-zone	3
IND B	15
Hypoganglionosis	5
Redo operation
Laparoscopic-assisted Duhamel	14
Laparoscopic-assisted Soave	17
Final diagnosis in the context of the entire case
Hirschsprung disease	11
Hirschsprung-associated IND B	15
Hirschsprung-associated hypoganglionosis	5

IND B, intestinal neuronal dysplasia B.

At the initial operation, the dilated portion of the colon was removed for all patients, and the IND B was not identified at this site. For the initial pathologic specimens, we directed special attention to the pathological findings in the proximal segment. Histological characterization of the proximal segment revealed IND B in 11 cases. However, aganglionosis of the proximal segment was diagnosed in the rest 4 cases who were diagnosed as IND B finally. At the time of redo operation, we resected the whole affected colon, which had been proved by the final histopathological findings of the removed specimens.

The reoperation consisted of laparoscopic-assisted Duhamel (n = 14) and Soave (n = 17) procedures. The median length of colon removed during reoperation was 12 (5–26) cm. Median follow-up period was 40 months (10 months–8 years). The bowel function of the 31 patients was analyzed according to the Windspread score. The results were divided into four groups based on the follow-up time after reoperation: <1 year, 1–3 years, 3–5 years, and >5 years (Table 4). Overall, excellent to good bowel function was achieved by 77.4% of patients (24 of 31 patients), fair result was 16.1%, and poor result occurred in 6.5%. There were 8 episodes of enterocolitis, 3 died, and the other 5 thrived with weight gain.

Table 4.

Functional Results (Windspread Score) of Patients After Reoperation

Surgical procedure	Follow-up time	Total case	Excellent/good, n (%)	Fair, n (%)	Poor, n (%)
Duhamel (14)	<1 year	2	1 (50)	1 (50)	0 (0)
	1–3 years	5	4 (80)	0 (0)	1 (20)
	3–5 years	4	3 (75)	1 (25)	0 (0)
	>5 years	3	3 (100)	0 (0)	0 (0)
	Mean		11 (78.6)	2 (14.3)	1 (7.1)
Soave (17)	<1 year	4	2 (50)	1 (25)	1 (25)
	1–3 years	2	2 (100)	0 (0)	0 (0)
	3–5 years	6	4 (66.7)	2 (33.3)	0 (0)
	>5 years	5	5 (100)	0 (0)	0 (0)
	Mean		13 (76.5)	3 (17.6)	1 (5.9)
Over all (31)			24 (77.4)	5 (16.1)	2 (6.5)

Discussion

Most operations for HD result in satisfactory bowel function. However, a small group of children still experience severe obstructive symptoms, including abdominal distension, bloating, vomiting, or refractory constipation.²³ The incidence of postoperative constipation was reported to be 8%–30%.²⁴ Apart from mechanical problems, pathological disorders should also be paid full attention.²⁵ For the former, digital rectal examination combined with contrast enema can easily give us the diagnosis. Whereas the identification of the histopathological abnormality is totally dependent on the typical neuronal malformation found in the sections.

Residual aganglionosis as indication for reoperation for HD has been reported in several publications.^25–27 Recently, a meta-analysis demonstrated that in 555 patients with redo pull-through operations, 144 (26%) patients showed residual aganglionosis.²⁸ We deem that this complication is preventable, for intraoperative biopsy has been extensively employed to recognize the proximal extent of aganglionosis. However, this is well established by the preparation of adequate biopsies and accurate interpretation of the frozen sections, otherwise pathologist error may occur. Shayan et al.¹⁰ reviewed 304 patients with 700 IOFS during surgery for HD, 9 cases (3%) had a discrepancy between IOFS and the final diagnoses. In 2 cases ganglion cells were incorrectly reported (false-positive) and a second operation was required as a result of this error.¹⁰ This also happened to one of our cases. Yamataka et al.²⁹ introduced an intraoperative rapid acetylcholinesterase staining for laparoscopy-assisted HD operation, which provided accurate identification of the level of aganglionosis. This is a superior method than traditional hematoxylin and eosin (H&E) staining of frozen sections that can facilitate the identification of normal ganglionated intestine. In some circumstances, if IOFS were not conclusive, we recommend that delayed radical operation should be performed after the final diagnosis of the paraffin sections.

There is a spectrum of other diseases, such as IND and hypoganglionosis, which frequently coexist with aganglionosis.^30,31 For these patients the distal colon presented as HD but the proximal colon characterized as IND or hypoganglionosis. It is estimated that in 25% of all cases of HD, patients have a segment of IND proximal to the aganglionic segment.³² Due to the difficulty in determining the type and number of ganglion cells, IOFS usually cannot give us an accurate diagnosis when IND or hypoganglionosis coexisted with HD.³³ That is why we took full-thickness biopsies under general anesthesia and performed immunostaining of paraffin sections to get a definitive pathological diagnosis before the reoperation.

In our series, 15 of the 31 cases turned out to be Hirschsprung-associated IND B, which was also reported as causative factor for the recurrent constipation after an HD pull-through in some other publications.^30,34 In 2000, Schulte et al. conducted a research to investigate the association between the histology of resected proximal bowel and postoperative bowel function.⁸ In their series, there were 28 IND presented at the proximal margin of resected intestine, however, they did not observe significant difference regarding postoperative outcome compared to 38 cases with regular histological patterns. The finding was in line with another study conducted by Hanimann et al.³⁵ Yet in Kobayashi's study 10 out of 31 patients were demonstrated to be Hirschsprung-associated IND and all of them suffered from postoperative constipation.³⁰ The varied prognosis of patients with HD and concomitant IND might be attributed to the different length of residual bowel affected by IND. We have noticed a phenomenon that the dilated segment was longer for Hirschsprung-associated IND than classic HD, and for most of these cases subtotal colectomy was needed.

As for HD combined with hypoganglionosis, more difficult postoperative course was observed.⁸ The 2 children in our study with poor bowel function during the follow-up were Hirschsprung-associated hypoganglionosis. It is challenging to determine the level of normal innervated intestine by frozen sections when hypoganglionosis coexisted with HD.²² For usually the laparoscopic-assisted intraoperative biopsies were taken as seromuscular, but for hypoganglionosis full-thickness biopsy and adequate specimens were imperative.

Transition zone is another common cause for recurrent constipation, since it is highly dependent on the experience of the pathologist to recognize its histopathological features in H&E-stained sections. For some patients the residual transition-zone pathology in HD might be misinterpreted as IND.³⁶ The most prominent characteristics of transition zone included partial circumferential aganglionosis, myenteric hypoganglionosis, and submucosal nerve hypertrophy (a × 400 field with 2 or more nerve trunks >40 μm in diameter).³⁷ Thus, for the IOFS, both the absence or presence of the ganglion cells and the thickness of the nerve trunks should be reported to the surgeon.

Acquired aganglionosis following pull-through procedures for HD is a rare form of colonic aganglionosis, we encountered 7 cases. As is shown in Table 2, this phenomenon could happen following the Swenson, Duhamel, and Soave procedures. The etiology and pathogenesis of acquired aganglionosis after pull-through procedures remain unclear. The poor blood supply at the point of anastomosis, attributed to twisting or excessive stretching, may account for the “loss” of ganglion cells.¹³ Ehrenpreis described the first case of this condition in 1965,¹⁶ and it had been postulated since then that degeneration of the ganglion cells resulted from impairment of vascular supply of the colon during operation. In this case and another 2 cases reported by Cohen et al.¹² hyaline fibrosis were observed in some of the vascular walls, which lends support to the hypothesis that regional hypoxia may have contributed to the recurrent aganglionosis. However, in Cohen's study hyaline fibrosis of blood vessels were not found in the other 3 cases. Additionally, animal model of ischemia on the sigmoid colon did not lead to aganglionosis, but resulted in reduced number of ganglion cells,³⁸ suggesting that other pathogenesis might exist. In 2006 Stefan introduced a case of acquired aganglionosis after varicella-zoster virus infection.³⁹ Furthermore, circulating autoantibodies were also reported to be responsible for the degeneration of the ganglion cells.⁴⁰ Although no consensus has been reached about the etiology and pathogenesis of acquired aganglionosis, what we should currently do during operations is to protect the blood supply, and to make sure the “neo-rectum” has proper anorectal angle.

In conclusion, children after surgical correction of HD might still have innervation disorders, including residual or acquired aganglionosis, transition-zone, and Hirschsprung-associated IND or hypoganglionosis, which might lead to recurrent intractable constipation, even though intraoperative frozen biopsies have confirmed the presence of ganglion cells in the initial operation. Laparoscopic-assisted Duhamel and Soave operations are all safe and effective techniques for redo pull-through to deal with such patients.

Footnotes

Acknowledgments

This study was supported by the Public Welfare Research and special funds were received from the National Health and Family Planning of China (Grant No. 201402007).

Disclosure Statement

No competing financial interests exist.

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