Eur J Pediatr Surg 2006; 16(6): 380-384
DOI: 10.1055/s-2006-924729
Original Article

Georg Thieme Verlag KG Stuttgart, New York · Masson Editeur Paris

Duhamel Lecture: The Incurability of Hirschsprung's Disease

K. (N) M. A. Bax1
  • 1Department of Pediatric Surgery, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, The Netherlands
Further Information

Publication History

Received: May 10, 2006

Accepted after Revision: May 13, 2006

Publication Date:
08 January 2007 (online)

It is a tremendous honor for me that EUPSA has invited me to deliver this year's Bernard Duhamel lecture.

Bernard Duhamel (1917 - 1996) was a great man. He established the first neonatal surgical unit in France at the Hôpital des Enfants Malades in Paris in 1947. In 1956 he moved to the Centre Hospitalier in Saint Denis, a suburb of Paris, where he remained until his retirement in 1982 [[40]]. Bernard Duhamel was one of the founders of pediatric surgery in France and a founding member of the Société Française de Chirurgie Infantile. He was the first editor of the Annales de Chirurgie Infantile, which merged in 1991 with the Zeitschrift für Kinderchirurgie to become the European Journal of Pediatric Surgery. He wrote more than 60 articles indexed in PubMed and several books on pediatric surgery in the French language.

Duhamel was particularly interested in congenital malformations. He believed that, in order to understand congenital malformations, one must know about embryology and he called himself an “embryologiste de chambre” as he got his knowledge by reading. It was Duhamel who introduced the concept of caudal regression syndrome in 1961 [[10]]. The name of Duhamel is particularly linked to the surgical treatment of Hirschsprung's disease [[8]]. In 1956 he published his method of a retrorectal pullthrough. We described a laparoscopic variation of the technique in 1994 [[2]]. The technique has been adapted over the years and is now as follows: a laparoscopic biopsy is taken proximal to the hypertrophied bowel. Next, the rectum is mobilized circumferentially close to the bowel wall until just under the peritoneal reflection. The dissection is continued posteriorly until the pelvic floor is reached. The bowel is then everted and amputated close to the anus. The aganglionic part of the bowel is resected, and the proximal bowel is closed and reintroduced into the abdomen together with the everted rectum. A transverse incision is made in the posterior rectum, half a centimeter above the dentate line. The retrorectal space is entered and the proximal ganglionic bowel is pulled through and anastomosed circumferentially to the posterior rectum. A wide side-to-side anastomosis is then made between the anterior aganglionic rectum and the posterior pulled-through bowel using an endolinear stapler. Finally, the upper rectum is closed laparoscopically with a running suture. However, today I do not intend to talk much more about laparoscopy.

Too often, too good results of surgery are reported, while I feel that all Hirschsprung's disease is incurable. In many papers it is stated that only a minority of patients have residual problems.

I would like to go back in history, as surgeons have thought for a long time that they could cure the disease. The first description of a child with a megacolon is said to date back to the Dutch anatomist Frederik Ruysch [[44]]. Apparently he described in 1691 the postmortem findings in a 5-year-old girl who died with a megacolon. But it was Hirschsprung who described it as a disease and called it congenital dilatation of the colon [[20]]. In 1901 Karl von Tittel, a registrar in pediatrics in Vienna, was the first to describe an absence of ganglion cells in the colon and to correlate it to disturbed peristalsis [[55]]. He believed, however, that the colon was ectatic from birth and felt that there was no place for surgery. The significance of the absence of ganglion cells was not clear for a long time. In 1946 Ehrenpreis wrote that he thought that the aganglionosis was a secondary event [[13]]. Bypassing the discussion on the absence of ganglion cells, Swenson together with his radiologist Neuhauser came in 1948 to the conclusion that it was the narrow distal segment which was responsible for the manifestations of the disease [[51]]. That same year Swenson and Bill proved that resection of the distal narrow segment could be therapeutic [[52]]. In the historical review given in the book “Hirschsprung's disease and allied disorders” published in 2000, Swenson wrote: “In May that same year [1948] the author [Swenson] reported to the society of Pediatric Research the same curative operation on 23 children with excellent results and no complications” [[53]]. Swenson apparently believed that he could cure the disease.

That Hirschsprung's disease is definitively caused by an absence of ganglion cells in the distal part of the colon was also detected in 1948, namely by Whitehouse and Kernohan [[58]]. They looked not only at patients with Hirschsprung's disease but also at colonic specimens from non-Hirschsprung patients. In the control specimens they did not find any hypertrophied nerve bundles. Moreover, they found that dilatation of the colon had little effect on the myenteric plexus except for creating a somewhat wider separation of the ganglia. Finally they found that inflammatory changes had little effect on the plexus. They concluded therefore that aganglionosis is not an acquired but a congenital anomaly. In the Hirschsprung patients they especially studied the myenteric plexus, but they wrote that the findings in the submucosal plexus seemed to parallel those of the myenteric plexus.

The gold standard for the diagnosis of Hirschsprung's disease is still histology. It was Swenson et al. who, in 1955, proposed taking a full thickness rectal biopsy in order to make the diagnosis [[54]]. In 1960 Gherardi demonstrated that aganglionosis of the myenteric plexus goes together with aganglionosis of the submucosal plexus, which is the basis for taking submucosal biopsies [[17]]. It was Bodian who, in 1960, suggested taking a surgical submucosal biopsy under general anesthesia to make the diagnosis [[3]]. The technique of taking submucosal biopsies by suction was first published by Dobbins and Bill in 1965 and was developed further by Noblett in 1969 [[7], [38]]. Another major contribution to making the diagnosis was the utilization of the acetylcholinesterase staining method of Karnovsky and Roots for the detection of hypertrophied parasympathetic nerve bundles in rectal suction biopsies by Meier-Ruge in 1972 [[25], [29]]. This test has remained one of the cornerstones in the diagnostic process [[29]]. Unfortunately the classic staining method as described by Meier-Ruge takes about two hours and is therefore not suitable for perioperative use. A rapid acetylcholinesterase staining test which takes less than 10 minutes was introduced in 1994 by Kobayashi et al. [[26]]. Other staining techniques have been described as well, but as I am a pathologist “de chambre”, I will not elaborate on these.

In 1967, Okamato and Ueda confirmed in human embryos that neuroblasts migrate in a craniocaudal way along the gastrointestinal tract, but they did not describe the distal distribution of ganglion cells in the rectum in any detail [[39]]. In 1968, Aldridge and Campbell described in detail the distribution of ganglion cells in the normal rectum in different age groups [[1]]. They found that the region below the dentate line is aganglionic, while the area above the dentate line is hypoganglionic for about 2 cm. Interestingly, they found no difference in the length of this zone for four different age groups: premature babies, full-term babies from birth up to 28 days, infants between 1 month and 1 year and children between 1 and 15 years. They concluded that biopsies looking for ganglion cells should be taken at least 2 cm above the dentate line.

As you all know, 4 main surgical techniques are used to deal with Hirschsprung's disease [[9], [43], [49], [52]]. They all have the resection of the distal aganglionic bowel as their basic principle, leaving the lowermost part in place in order to preserve continence. In the Rehbein procedure a bit more distal bowel is left, but the Rehbein procedure starts with forceful dilation of the distal rectum.

Now how far should we go proximally and how far distally? Contrast enemas have been used extensively to determine the upper border for the dissection. However, Jamieson et al. found that such an enema is only a good predictor in 60 % of cases with classic Hirschsprung's disease and in 25 % of cases with long-segment disease [[23]]. The two reviewing radiologists gave a concordant opinion in 90 % of the cases. Proctor et al. had a better rate, but they were still wrong in 1 out of 10 patients with classic disease and in 2 out 3 patients with long-segment extension [[42]].

At present, the gold standard for determining a good proximal place of dissection is undoubtedly histology. Biopsies can be taken transabdominally, either through the umbilicus or laparoscopically [[16], [47]]. Taking a full thickness laparoscopic biopsy in a well prepared colon is no problem as there will be no leakage. Of course, the biopsy site has to be closed. Alternatively, the biopsy can be taken through the anus either after transanal pull through or before mobilization by suction under laparoscopic control and marking, as described by Yamataka et al. [[28], [60]]. As I am a pathologist “de chambre”, I will not elaborate on what should be looked for in the biopsies. It is sufficient to say that one should look at ganglion cells, nerve bundles or acetylcholinesterase staining, of course using the rapid method [[26]].

It all seems easy, but reality is different. Clinically, a varying number of patients do not do well after surgery. They are constipated, they have recurrent bouts of enterocolitis, and they soil. Looking at the histology after resection, Farrugia et al. found that in 18.8 % of cases transitional bowel had been left in situ [[14]]. It has been reported over and over again that the length of the transitional zone may vary widely. The discussion of neuronal intestinal dysplasia in conjunction with Hirschsprung's disease has not made things easier [[30], [31]]. More recently, abnormalities in the interstitial cells of Cajal have been described, not only in the aganglionic segment but also in the ganglionic part [[44], [59]]. Miele et al. looked at gastric emptying and total gastrointestinal transit time in children operated on for Hirschsprung's disease [[32]]. They found delayed gastric emptying in the Hirschsprung group and a correlation between delayed gastric emptying and total gastrointestinal transit time. Although the colon was emptied preoperatively, a factor of obstruction can not be excluded. Now how do we surgeons deal with this? Georgeson at the recent IPEG congress in Dallas said that he resects up to 20 cm more, proximal to the site of a good biopsy, depending on age. Surgeons may be reluctant, however, to resect more left colon, as this may imply that the right colon may have to be turned down for a pull-through. At the recent IPEG congress in Dallas, Frinkman et al. presented a paper on intraoperative spectrometry in a mouse model with Hirschsprung's disease with promising results [[15]]. They were able to differentiate ganglionic from aganglionic bowel spectrometrically. I hope this method will give us the answer as to how far we should go proximally.

Let us now turn to the distal extent of the resection. The absence of ganglion cells in the internal sphincter has misled many pediatric surgeons. It looked as though the aganglionosis in the distal rectum was normal both in normal and in Hirschsprung's disease. Thus, resection of the colon up to just above the physiologic aganglionic zone would be curative. Duhamel initially saw the internal sphincter as just a thickening of the circular muscle layer of the bowel and proposed turning the distal muscle layer back after taking off a few centimeters of mucosa [[12]]. There are big differences, however, between the internal sphincter under normal conditions and in Hirschsprung's disease, first at all from the manometric point of view. In Hirschsprung's disease the rectoanal inhibition reflex is absent, and this reflex remains absent whatever kind of surgery is performed [[4], [21], [35], [61]]. When in the adult the rectoanal inhibition reflex becomes absent for whatever reason, e.g. diabetes, surgery or scleroderma, incontinence is the result [[6], [19], [46]]. We also know now that the internal sphincter in Hirschsprung's disease is strongly abnormal histologically with loss of the non-adrenergic non-cholinergic nerves, abnormal nitric oxide NO synthetase, and insensitivity to NO [[56]]. Furthermore, the interstitial cells of Cajal are sparse and disrupted [[41]]. When Duhamel developed his operation, he initially cut the internal sphincter completely, with a high incidence of soiling as a result. Later on, he modified his operation by cutting the internal sphincter 1 cm proximal to the pectinate line [[8], [11]].

The long-term results after Duhamel are not good when one looks critically. Heij et al. reported good long-term results only in 29 % of patients [[18]]. The results of Catto-Smith et al. are no better [[5]]. With the more modern approach of transanal laparoscopically-assisted pull-through, the results do not seem ideal either, and when the Duhamel procedure is compared with the transanal technique, I am not sure that there is much difference [[22], [33]]. After so many years of pediatric surgery I still do not know the real difference between incontinence and soiling. Ishihara et al. report normal continence in 25 %, good continence in 50 %, but soiling in 60 % of the patients [[51]]. Snyder et al., reviewing a collected series of all four main surgical procedures, which included thousands of cases, reported a constipation incidence of 8.2 %, an incontinence incidence of 8.2 % and an enterocolitis incidence of 12.3 % [[50]]. They concluded that the uniformity of the results is more striking than any differences between major procedures. As I said earlier, in Utrecht we have been performing a laparoscopic variant of the Duhamel technique. We compared our open technique with our laparoscopic experience for the period from January 1987 to July 2003. We excluded patients who received a colostomy preoperatively, patients with extended aganglionosis, patients with trisomy 21, patients with Waardenburg syndrome and patients with severe associated congenital anomalies. We looked at perioperative complications, postoperative factors such as fever, leakage, abscess, stenosis, ileus, first feeding, and hospital stay. We also looked at readmission for enterocolitis, constipation and at enuresis and fecal incontinence. Twenty-five patients had an open Duhamel, 30 a laparoscopic one. No statistically significant differences were found between the open group and the laparoscopic group, except for earlier first feeding and an earlier discharge in the laparoscopic group, which is undoubtedly due to historical bias. In the study we did not look at postoperative pain and cosmesis.

The ultimate goal of treatment is to relieve the obstruction and to preserve or obtain continence. I would like to remind you that normal continence is the ability to hold on when necessary and to pass completely when the individual wants, at a convenient time. But is this attainable in Hirschsprung's disease? Complete resection of the abnormal bowel means creating incontinence. Resection of all aganglionic bowel except for the most distal internal sphincter means that the obstruction is not completely relieved. An important question is, how much internal sphincter should be spared? I would like to remind you that the distance between the dentate line and the lower edge of the internal sphincter measures 1.2 to 8.8 mm depending on age in the study of Aldridge and Campbell [[1]]. Not much is required to damage this small ring by retraction during transanal surgery or by dilatation. In all types of operations for Hirschsprung's disease, except for the Rehbein procedure, an important part of the internal sphincter is cut. I have little doubt that differences in outcome are related to an absence of standardization of the sphincterotomy, and I doubt that this will ever be possible.

Now what should we do when the patient remains subobstructed and something has to be done? Apart from so-called bowel management programs, there are a few surgical options such as dilatation. Dilatation of the anus in adults causes incontinence in a significant number of adult patients, and there is no reason to believe that this will be less in children treated for Hirschsprung's disease [[27], [37], [48]]. In most procedures for Hirschsprung's disease, part of the internal sphincter is already cut at the initial procedure.

What about myotomy or myectomy? Why should this be effective? And if so, how should it be standardized? In a series of 348 patients treated by Wildhaber et al., 9.1 % received a myotomy or myectomy later on [[59]]. Of 29 patients 12 had pure constipation and 6 of them had residual aganglionosis. 17 had recurrent enterocolitis with only one residual aganglionosis. Of the patients with residual aganglionosis, 83 % had a poor result. If there was no residual aganglionosis, 25 % had poor results. They concluded that sphincterotomy was moderately effective.

What about isosorbide ointment, which delivers nitric oxide locally? It has been shown now that nitric oxide has no effect on aganglionic bowel [[55]]. The effect described may be the results of relaxation of the pelvic floor. One should also be aware that this type of treatment may give headaches.

What about botulinum toxin? Injections with botulinum toxin are temporarily active. They destroy the synaptic junction but within two days new synapses are made. Moreover, antibodies may be created [[24], [34]].

I would like to conclude that definitive surgery in the sense of a cure for Hirschsprung's disease does not exist. So let us stop talking about perfect results. I do not want to finish this talk on a negative note. The good news is that the patient can learn to deal with his handicap. Today, we do understand the genetics better, and mortality for enterocolitis has dropped significantly [[36]]; we are better able to diagnose normal proximal bowel using suction biopsies in combination with rapid acetylcholinesterase staining, and perhaps soon with spectrometry, and we have become less invasive. We operate earlier, we try to avoid ostomies, we operate transanally or laparoscopically and we try to treat the internal sphincter with respect.

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M.D., Ph.D., FRCS (Ed), Professor and Chief of Pediatric Surgery Klaas (N) M. A. Bax

Department of Pediatric Surgery
Sophia Children's Hospital
Erasmus Medical Center Rotterdam

P. O. Box 2060

3000 CB Rotterdam

The Netherlands

Email: n.bax@erasmusmc.nl