The History of Hirschsprung’s Disease: Then and Now

1691 

Although the very first description of megacolon was attributed to Ruysch, Ehrenpreis felt the clinical and autopsy findings did not produce enough evidence to make the definitive diagnosis of Hirschsprung’s disease. Subsequently in the literature, most reported cases involved adults with similar atypical histories and inconclusive autopsy reports.7

1825 

Parry reported the earliest autopsy findings of a narrow rectosigmoid and a dilated, proximal colon. This was in an adult with chronic constipation who died after an acute colonic obstruction.8

1830 

Harald Hirschsprung was born in Copenhagen. As a pediatrician (Fig. 1), he was interested in, and wrote about, a wide range of neonatal problems that became the domain of the pediatric surgeon in the 20th century.9 These lesser known writings were of equal or even greater importance than his description of the disease that now bears his name.

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Figure 1. Harald Hirschsprung, 1830 to 1916. (Courtesy of Elsevier Publishers, Philadelphia, PA, USA and Dr. C. M. Madsen, Odense, Denmark.)

1861 

Hirschsprung described four cases of esophageal atresia with tracheoesophageal fistula: “The disease is of such a nature that therein is contained the seeds of a rapid and inevitable death.”10

1876 

Hirschsprung’s most imposing medical contribution was his report of controlled hydrostatic reduction of an ileocolic intussusception long before the introduction of the barium enema. His results of a 20 to 30% mortality in a condition that was 80% fatal continued into the mid 1900s.11

Before 1886 

Over 20 reports preceded Hirschsprung’s classic description of congenital megacolon.5

January 1886 

Hirschsprung presented a paper on “Constipation in Newborns due to Dilation and Hypertrophy of the Colon” to the prestigious Society of Pediatrics in Berlin.7 He offered no definite opinion as to the etiology or treatment of the disease in his two newborn cases, although the title of his talk indicated his attitude toward this problem. He did believe this was a new, rare, congenital condition in infants and children. He thought it was inconceivable that any other mechanism of origin would or could produce a megacolon so soon after birth, thus, his opinion of the congenital nature of the colonic dilation. This view was also shared by many of the authors of his time and soon became known as the “Malformation Theory.” Although he noted the narrow rectosigmoid, he did not understand its significance and never pursued this observation.12 However, he did focus (as did subsequent authors) on the dilated proximal colon and actually believed the entire colon was congenitally defective.13 Although he failed to recognize that the cause of the proximal megacolon was in the distal, normal-appearing, aganglionic rectosigmoid (which contributed to the delay in the eventual complete understanding of the pathogenesis of this disease for another 60 years), his presentation was really the classic description of the disease that would eventually bear his name.

1887 

Hirschsprung published his classic January 1886 talk.7

1888 

Hirschsprung reported two cases of congenital hypertrophic pyloric stenosis.14

1893 

Osler described two cases in which he thought there was a defect in the innervation and contraction of the colon. One child was successfully treated with a colostomy and the other was successfully treated by a rectal tube and irrigations.15

1894 

The term “Congenital Megacolon” was introduced by Mya.2

1895 

Marfan said a long, redundant sigmoid caused obstruction producing dilation and hypertrophy of the proximal colon and this obstruction could be relieved by passage of a rectal tube.16

1898 to 1902 

Authors writing about congenital megacolon said that symptomatic relief of the colonic obstruction could be obtained by colonic irrigations and/or by colostomy. Ironically, for some patients, both of these treatments still play an important role in today’s preoperative and occasional postoperative management.

1898 

Treves came close to proving the cause of this disease by performing a colostomy in a 5-year-old girl with life-long constipation and obstruction. This relieved her symptoms and signs, although he failed to appreciate the functional rectosigmoid obstruction as the real cause. Later, at a second operation, he cured her by resecting all of the proximal dilated colon, the narrow rectosigmoid, and also the anus. This created an incontinent perineal colostomy. He considered the anus to be at fault.3

Early 1900s 

Case reports of the absence of ganglion cells in this disease started to appear, but were considered rare, medical curiosities. These reports were refuted by as many—if not more—reports of normal ganglion cells in similar cases, possibly from the normal, dilated, proximal colon in cases of both congenital and idiopathic megacolon.

1900 

Fenwick made a strong case for an abnormally tight anal sphincter from a spastic rectal contraction acting as a mechanical obstruction and causing the proximal colon to dilate. However, his therapy did not lead to any improvement in the treatment of megacolon.4

Bayliss and Starling also published a study showing how peristalsis carried material through the colon and described its autonomic nerve supply.17

1901 

Tittel described the first histological report on the absence of intramural ganglion cells in the rectum of a 15-month-old infant who had been constipated since birth.18

1902 to 1924 

During this period of time, many different treatments, procedures, and operations were tried to accommodate the variety of opinions (theories) about the origin of the disease:

Although many of these treatments, procedures, and operations were temporarily successful, after a short period, recurrences were almost inevitable, especially if the diagnosis was Hirschsprung’s disease.19

1904 

Hirschsprung wrote the first textbook chapter on “Congenital Dilation of the Colon.” It was based on his own series of patients, along with his observations of other contemporary publications.20 He retired from practice in the same year.9 Despite some clarity with the disease, Kredel still said: “It is astonishing that it should be possible to put forward so many different opinions on one and the same thing.”21

1907 

Hawkins stated, “The origin of the disease is mysterious.” He believed that a neuromuscular defect caused a rectal spasm producing an obstruction, and he treated this with enemas, a rectal tube, and resection. Unfortunately, the resection was not distal enough, so the result was a failure.22

1916 

Hirschsprung died at age 86. Amazingly, his contributions to pediatric knowledge over his academic lifetime go far beyond the disease named after him. Aside from his writings (some mentioned above), his observations also on biliary and intestinal atresia, hiatus hernia, and spina bifida established him with the rare and unusual reputation of being a pediatrician who became a pioneer in Pediatric Surgery.9, 12

1918 

Wilms tried anal sphincter dilation to treat Hirschsprung’s disease.23

1920 

Dalla Valle was the first to report total absence of ganglion cells from the rectosigmoid. This was seen in two brothers with typical symptoms and signs of Hirschsprung’s disease, with normal ganglion cells being present in the dilated proximal colon.24

1923 to 1944 

Because of the “Spastic (Neuromuscular) Theory,” easier operative procedures (than bowel resection) were tried with lower morbidity and mortality: spinal anesthesia, lumbar sympathectomy with or without excision of the inferior, mesenteric plexus or splanchnic nerves. The results were initially successful, but ultimately failed with longer follow-ups.

1927 

Wade and Royle believed that normal colonic function could be restored by dividing the sympathetic nerve supply of the colon (lumbar sympathectomy).25

Martin and Burden reported rectosigmoid myotomy as the treatment for Hirschsprung’s disease.26

1928 to 1947 

The continuing poor outlook for infants and children with definite Hirschsprung’s disease was best reflected in contemporary Pediatric Surgery textbooks:7

1930 

Ask-Upmark reported 102 cases of Hirschsprung’s disease treated surgically and recommended resection of the dilated colon as the “superior” treatment. He had a mortality rate of 50%.27

1932 

Adamson and Aird concluded that rectosigmoid aganglionosis was a rare, secondary change caused by chronic stasis and dilation of the proximal colon.28 Unfortunately, the converse was true.

1935 

Ross reported that lumbar sympathectomy for congenital megacolon was of questionable value.29

1938 

Robertson and Kernohan (from the Mayo Clinic) reported the absence of ganglion cells in the rectosigmoid and correctly correlated it with proximal colonic obstruction in infancy.30

1940 

Tiffin, Chandler, and Faber (also from the Mayo Clinic) described a case of absent ganglion cells in the resected rectosigmoid and suggested that the proximal megacolon was due to a disturbance of peristalsis in the resected bowel.31

1943 

Whitehouse, Bargan, and Dixon (again from the Mayo Clinic) reviewed the results of all the various medical and surgical treatments including neurogenic ablation and found them all to be failures. They felt the absent ganglion findings in the narrow rectosigmoid were secondary, and therefore, once again, advocated segmental resection of the dilated proximal colon as the best treatment.32 This was despite their mortality rate of 24% and the fact that their Mayo Clinic colleagues (Robertson and Kernohan) had also reported the absence of ganglion cells in a case of megacolon.30 “The literature related to the therapy of congenital megacolon is rather chaotic and difficult to evaluate.”32

1943 

Ehrenpreis said: “A critical review of the evidence offered previously as support for the different theories on pathogenesis satisfied us that none of this material was conclusive.” As a result, he defined Hirschsprung’s disease as “a dysfunction of evacuation of the colon of as yet unknown origin, occurring in the absence of morphological and mechanical causations and giving rise secondarily to a characteristic dilation of the colon.”7

1945 

Grimson, Vandergrift, and Datz proposed subtotal colectomy and ileosigmoidostomy as the best treatment for Hirschsprung’s disease, after observing failures of segmental resection of the dilated proximal colon. Their procedure also failed.33

1946 

After 60 years (1886 to 1946) of confusion, the solution finally came quickly. Classical articles focusing on clinical, radiological, surgical, and histological aspects of Hirschsprung’s disease appeared in rapid succession and formed the basis of diagnosis and treatment as we practice it today.6 Ehrenpreis best summed up the prevailing opinions regarding ganglion cells in megacolon. He wrote that several authors (Tittel 1901, Brentano 1904, Cameron 1928) showed that the aganglionic changes in Auerbach’s plexus in the rectosigmoid did indeed have pathologic significance. He noted that other authors (Smith 1908, Retzlaff 1920, Passler 1938) could never confirm these findings, and therefore, considered them as probable secondary changes.34 Ehrenpreis was the first to appreciate that the proximal colon became dilated because of a distal obstruction. Unfortunately, the narrow rectosigmoid, seen in some of his cases, also failed to impress him, because he did not mention this finding as a cause of the disease. His clinical investigations tried to prove that Hirschsprung’s original theory that the congenital nature of megacolon was incorrect; he pointed out that this problem developed shortly after birth, could be diagnosed in a neonate, and did not involve the entire colon.

From Hirschsprung’s first report in 1886 until Orvar Swenson and his colleagues in Boston entered the picture, there had been about 200 case reports of megacolon, with an equal amount of speculation about the etiology: “At the time we began our work … there was no consensus regarding the absence of Auerbach’s plexus in congenital megacolon … and no new therapy had evolved from these findings.”35 Confusion about the cause of this disorder continued because some children with idiopathic megacolon were included in the mix with those who indeed had congenital megacolon.36 At this time, confusion also continued about different treatments. Ladd (at Boston Children’s Hospital) treated several children by resecting the dilated colon, only to find the disease recurred. Swenson also reported that a few other Boston patients treated by sympathectomy “had (also) not been helped.”35 Initially, Swenson and Bill proved the cause of Hirschsprung’s disease by careful clinical observation, without concern about the ongoing debate of ganglion cells.37 They established for the first time that the narrow rectosigmoid was the cause of the disease. Swenson subsequently felt that the finding of no ganglion cells in this narrow rectosigmoid in pediatric patients of all ages with congenital megacolon supported their concept that the treatment of choice for Hirschsprung’s disease was indeed the resection of this aganglionic segment.38 Finally!

January 1948 

Swenson and Bill presented their work at the Society of University Surgeons. They reported that radiographic and balloon manometry demonstrated an area of spasm and lack of peristalsis in the rectosigmoid. It was “the first absolute concrete evidence that the etiology of the disease was the defective narrow distal segment,” and it explained why removal of the dilated proximal colon did not cure the disease.37 They presented a curative operative technique (plus a temporary colostomy). Before this, they had previously developed an operation experimentally on dogs, whereby the entire rectum and appropriate lengths of dilated, proximal bowel were removed, preserving the anal internal sphincter for continence.35 This anal, pull-through procedure was then used successfully in a child with Hirschsprung’s disease.37

February 1948 

Zuelzer and Wilson reported a series of 11 infants who had the classic clinical, roentgenological, and pathological findings typical of Hirschsprung’s disease. There was no mechanical cause for the obstruction found. Microscopic examination of the myenteric plexus of the narrow rectosigmoid showed no ganglion cells. All 11 infants died. They initially suggested that their patients be treated by temporary enterostomy “at the lowest level of normal intestinal motility … to decide whether resection of part or all of the nonmobile portion of the intestine is a desirable and practical procedure.” The authors thought this bowel obstruction was functional and due to a congenital neurogenic cause, but they did not call it “congenital megacolon.” Nonetheless they had really made the correct diagnosis.39

July 1948 

Whitehouse and Kernohan reported on the postmortem examinations of 11 children who had also died of megacolon. They conclusively established the pathology of the narrow, spastic rectosigmoid to be “an absence of the ganglions of the myenteric plexus … (and) the presence of (hypertrophied) nonmyelinated nerve trunks between the longitudinal and circular (Auerbach) muscle layers.”40

Swenson and Pickett (along with their radiological colleague Neuhauser) first published a barium enema technique demonstrating the narrow rectum, sigmoid, and distal colon and a transition zone on the way to the dilated proximal colon. This X-ray finding became the standard, diagnostic test for Hirschsprung’s disease, until supplanted by rectal biopsy.42

1949 

Swenson, Rheinlander, and Diamond showed that the narrow rectosigmoid had no peristalsis, had abnormally high intraluminal pressure, and was aganglionic. All of these findings combined to form a physiological functional obstruction resulting in a dilated, proximal megacolon. In 1934 Cannon’s Law had stated that smooth muscle contracts when denervated. They concluded, therefore, that patients with Hirschsprung’s disease could be cured by removal of this defective rectosigmoid.41

Bodian, Stephens, and Ward analyzed 73 cases of megacolon and distinguished between congenital and idiopathic, based on the presence or absence of a narrow, spastic, aganglionic rectosigmoid. Fifty percent of their cases belonged to each group and the prognosis was very different between them: Hirschsprung’s disease carried a high mortality rate, while no children with idiopathic megacolon died.43

After the 1950s 

After the Swenson pull-through procedure was introduced, there were several procedures and/or modifications, but all agreed with the concept of the defective rectosigmoid as the cause of the disease. Essentially, these new operations represented modifications (variations) of the anastomotic method used, following removal or bypass of the aganglionic rectosigmoid.

1951 

Hiatt also showed by manometric studies that the rectum (and maybe some proximal sigmoid and colon) was the pathological site of Hirschsprung’s disease. This segment of bowel was narrow, spastic, contracted, and devoid of peristalsis, but still able to have a mass contraction. He also noted a lack of the normal, reflex relaxation of the internal anal sphincter. He described very short segments of aganglionosis. He demonstrated that an inadequate resection of the distal, aganglionic rectosigmoid initially had an excellent result, but with time, the same, functional, distal obstruction returned.44

1952 

State described a low, anterior resection as his answer to the treatment of Hirschsprung’s disease. However, after a long follow-up, it became obvious that leaving more then a few centimeters of aganglionic rectum was not curative.45

1955 

Swenson, Fisher, and MacMahon introduced the rectal biopsy as a precise, complication-free test to establish the diagnosis of Hirschsprung’s disease. They reported it as superior to the barium enema. Their biopsy was done under general anesthesia and consisted of removing a 0.5 × 1 cm full-thickness section of the posterior, rectal wall 3 cm from the mucocutaneous junction (the pectinate line). It also needed a two-layered closure. The specimen required a search for ganglion cells in the intermuscular nerve plexuses; the presence of ganglion cells ruled out the diagnosis of Hirschsprung’s disease.46

1956 

Duhamel described a posterior, colorectal, side-to-side anastomosis just above the internal sphincter, with crushing of the colorectal septum (spur, common wall) using two Kocher clamps (with their handles sticking out of the rectum) to cut through the septum and to fall out in 10 to 14 days. This procedure was done to leave rectal mucosa, believed to be important in sensation, anteriorly and to decrease injury to the pelvic nerves from the perirectal dissection.47

1958 

Rehbein adopted State’s anterior, resection technique, but improved it significantly by doing a lower resection and anastomosis within 3 to 4 cm of the mucocutaneous line.48 Rehbein’s modification was limited only to patients about 3 months of age and was the classic, low, anterior resection, which (unlike the Swenson pull-through procedure) was done entirely within the pelvis. The internal sphincter was also dilated to overcome the obstructive tendency of the remaining, aganglionic rectum.52

1959 

Duhamel originally incised the posterior, anorectal wall less than 1 cm above the mucocutaneous line for his posterior anastomosis. However, he either destroyed or bypassed the internal sphincter, resulting in partial incontinence for gas and liquids. Therefore Grob, Genton, and VonTobel raised the posterior, anastomotic incision to 2 to 2.5 cm above the mucocutaneous line, thus preserving the entire, internal sphincter, but the patients suffered constipation, often with fecaloma formation in the residual blind anterior rectal pouch.49

1960 

Bodian said the diagnosis of Hirschsprung’s disease could be made by examination of a smaller rectal biopsy including only mucosa and submucosa and searching for ganglion cells in Meissner’s submucosal nerve plexus.50

Grob again modified the Duhamel operation by shortening the anterior, rectal pouch, minimizing the occurrence of a postoperative fecaloma.51

1961 

Shandling improved the biopsy technique by using a laryngeal, biopsy forceps and doing only submucosal (punch) biopsies of a valve of Houston. Later, this was modified so that the biopsies were taken from the posterior rectal wall. No anesthesia was necessary in newborns, infants, and some older children, and no closure of the biopsy site was required.53

1964 

Swenson published a review of his first few 100 cases and reported a number of patients with postoperative enterocolitis who required a sphincterotomy. He felt this occurred because his original pull-through procedure left too much distal rectum (3 to 4 cm above the mucocutaneous line), much like ultrashort disease. When this was converted to 2 cm anteriorly and 0.5 to 1 cm posteriorly (thus removing a bit of the posterior internal sphincter), the incidence of postoperative enterocolitis requiring a sphincterotomy virtually disappeared and continence was still maintained.54

Soave also modified the original Swenson procedure by a submucosal dissection, removing the mucosa of the aganglionic rectosigmoid, starting 8 cm above the peritoneal reflection and descending to 1 cm above the mucocutaneous line. Then he did an endorectal pull-through of the proximal colon, through the residual, rectosigmoid, muscular cuff and left the bowel protruding (telescoping) 5 to 10 cm out from the anus, so that adhesions developed between the two, after which the prolapsed bowel was amputated by cautery in 15 to 20 days. The severed end spontaneously withdrew into the anal canal after a few hours or immediately with slight finger pressure. The principal advantages were technical ease and minimal pelvic dissection.55, 56

Boley modified Soave’s original, endorectal pull-through with protruding pulled-through colon by trimming the proximal colon at the original operation and performing a primary anorectal anastomosis.57

1965 

Dobbins and Bill reported that rectal suction biopsy was a reliable method of diagnosing Hirschsprung’s disease, especially when the absence of ganglion cells was combined with histochemical staining for excess acetylcholinesterase that is associated with an increased number of hypertrophied nerve trunks.58

1967 

Schnaufer and coauthors reported that the absence of the internal sphincter relaxation was the most important criterion in the manometric diagnosis of Hirschsprung’s disease.59

1968 

Soper and Miller modified the Duhamel procedure to eliminate a common, postoperative anatomic and functional problem: the residual, colorectal septum causing an anterior, rectal, pouch fecaloma. This was simply done by opening the top of the residual, anterior rectum from the abdomen to make sure the two Kocher (crushing) clamps had completely eliminated the colorectal septum. This rectal opening was then closed and placed below the peritoneal reflection.60

Steichen, Talbert, and Ravitch modified the original Duhamel operation by using disposable, sterile, preloaded staples (instead of the Kocher clamps) that allowed a fast, safe anastomosis with immediate cutting between the two rows of metallic clips to eliminate the septum between the anterior rectum and posterior colon. This ended the inconvenient and potentially dangerous waiting period (of up to 2 weeks) for the septum-crushing instrument to fall off. These staple cartridges were long enough to be placed in one or two bites, only from below, and not leave any residual septum at the top of the pouch,61 which no longer had to be opened (see Soper modification).60

1970 

Ehrenpreis reported that the principal complication in all of the operative procedures of that era related to the internal sphincter. If too much sphincter was damaged, incontinence resulted; if more than the sphincter remained, constipation and other obstructive symptoms and signs (often with enterocolitis) returned.7

Pagès and Duhamel (both of whom understood the role of the internal sphincter in the physiology of fecal continence) placed their retrorectal incision in the middle of the internal sphincter 1 to 1.5 cm above the mucocutaneous line. This preserved some of the internal sphincter posteriorly and with it normal fecal continence.62

1971 

Kasai, Suzuki, and Watanabe modified the original Soave operation by doing both a longitudinal myotomy of the aganglionic, rectosigmoid, muscular cuff and a higher, anorectal anastomosis to eliminate some of the cuff stenosis problems.63

By using special, staining techniques, Meier-Ruge described pathognomonic criteria for diseases mimicking Hirschsprung’s disease (like Intestinal Neuronal Dysplasia).64

1979 

Kleinhaus and coauthors surveyed the members of the Surgical Section of the American Academy of Pediatrics and found that satisfactory results could be obtained with the Swenson pull-through, subsequent procedures, and/or their modifications.65

1982 

Holschneider reported that, although there were subsequent procedures and/or their modifications to the Swenson pull-through operation for Hirschsprung’s disease, each still had its own, peculiar, postoperative problem.66

1980 to 1990 

Several case reports and small series of successful one-stage “pull-through” operations are presented. Except in cases of infants with enterocolitis, all forego the diverting colostomy. Within the decade, this approach quickly gains favor as its efficacy and safety are proven.

During this period two prevailing theories emerged that attempted to explain the pathogenesis of Hirschsprung’s disease. Both theories focused on the neural crest stem cell. The first theory hypothesizes that the stem cells fail to migrate effectively from their neural crest niche.67 The second theory postulated that the stem cells either involute or fail to differentiate, once they have arrived at their terminal location.68, 69

Martucciello and colleagues identified the first Hirschsprung’s specific genetic defect for a sporadic case of Hirschsprung’s disease. They reported an interstitial deletion in the long arm of chromosome 10 in a child who presented with total colonic aganglionosis but did not have a familial history. These investigators along with others narrowed the location of this mutation to the region between 10q11.2 and 10q21.2.70, 71

1985 

The first laparoscopic cholecystectomy is reported in 1985 and the first large series involving 157 patients was reported in 1990.73 Laparoscopic equipment is quickly tailored to the needs of the surgeon for use in many operations.

1990s 

Laparoscopic surgery becomes a dependable approach to many surgical problems. Minimally invasive surgery is quickly adopted by the pediatric surgical community and proves to be an ideal application in many surgical diseases of children. Georgeson and colleagues first describe a new “gold standard” laparoscopic approach for endorectal colon pull-through (Soave) in 1999.74 He and his colleagues provide evidence that laparoscopy reduces perioperative complications and postoperative recovery time. This procedure starts like all others; a pathological diagnosis of the “transition zone” is confirmed and mesenteric dissection begins after a pathologist confirms the presence of ganglion cells in the proximal, dilated bowel. Proponents of this approach describe the ease with which the transition zone is identified and the mesenteric dissection is performed.

1998 

The first animal models of aganglionosis were developed in 1966.75 These mice are found to exhibit megacolon and die from presumed enterocolitis within the first few months of life. The genome of the spotting lethal rat, a naturally occurring rodent model of Hirschsprung disease, is found to contain a deletion mutation in the endothelin-B receptor (EDNRB) gene. A mutation in endothelin-B receptor gene causes myenteric aganglionosis and coat color spotting in rats.76 Rats that are homozygous for this mutation exhibit congenital intestinal aganglionosis, a result of failure of the neural crest-derived enteric nervous system stem cells to effectively colonize the intestine. Gariepy and colleagues demonstrate the “dosage” of a single gene mutation may be responsible for the disease and the variety of constellations with which it presents.77 Concomitantly, others found a link between dermal pigmentation and intestinal aganglionosis. Lethal White Foal Syndrome is a disease of horses that produces foals that are all white or nearly all white; these animals die shortly after birth of severe intestinal blockage and have total colonic aganglionosis, mimicking human Hirschsprung’s disease.78 Investigators separately report a role for EDNRB in Lethal White Foal Syndrome.79

1998/1999 

Two essentially simultaneous manuscripts were presented,80, 81 which described a novel and completely transanal approach. This approach (or modification of existing techniques) utilizes an anal approach through which the rectal mucosectomy, distal aganglionic colectomy, and pull-through are performed. The group led by Jacob Langer postulated that the benefits of staying out of the peritoneum has potential advantages that included lower cost, less risk of damage to pelvic structures, a lower incidence of intraperitoneal bleeding and adhesion formation, and the absence of any abdominal scars.

Since their original reports, Langer, Durrant, and De la Torre together with other investigators presented a multicenter review of 141 patients undergoing transanal pull-through operations.82 They reported comparable morbidity to the open approaches, less analgesia requirements, and shorter time to feed and discharge. Although there was no comparison group, the large sample size and multiple centers supported the authors’ claim that this procedure can be done safely and with good results. A separate study presented information comparing the open Soave approach to the transanal Soave approach. In fact, the analgesia requirements were lower, the time to feed and the hospital stay were shorter, and the cost was lower in the transanal cohort.

Although the benefits in performing the surgery transanally are well documented, there are some clear disadvantages that have been reported for this approach. There was an increased incidence of stricture formation and enterocolitis in the transanal pull-through group. It is unclear why this occurs, but it may be due to the retraction that is required when operating through the anus of a small infant. Finally, although it is not clear, there may be an increased incidence of incontinence associated with the transanal operation.

2000 

The American Pediatric Surgical Association reports that mortality in the newborn period declined from 70% in 1954 to as little as 1% in 2000. This has been attributed to a more precise and earlier diagnosis, as well as aggressive and more effective surgical management of this disease.

2000 to 2003 

Many genes and mutations have since been identified to have a possible link to Hirschsprung’s disease. These are reviewed in exhaustive detail.83 Although it is unclear what role genes play in the development of the disease, several candidate genes that have been implicated as the cause of Hirschsprung’s disease include the RET proto-oncogene, cell-derived neurotrophic factor,84 SOX-10,85 and the Smad interactive protein 1.86, 87 In 2003, Iwashita and colleagues provided the strongest evidence that Hirschsprung’s disease is linked to dysfunctional neural crest stem cells and that the likely candidate gene is identified (RET) which is thought to be necessary for neural crest stem cell migration.88 Results presented in 2004 suggest that at least 10 genes are associated with Hirschsprung’s disease; these are reviewed by Puri and Shinkai.89 However, scientific focus remains on loss of function due to RET mutations.

2003 

Procter and colleagues present information that warns against performing any pull-through armed only with radiological information (barium enema).90 The authors found that, although there was good correlation between preoperative contrast enemas and intraoperative pathology in cases involving the distal colon, in 10% of patients with long segment disease, the level of aganglionosis was not correctly predicted by barium enema. They cautioned surgeons that proper planning for surgery should included a biopsy to confirm the level (transition zone) where ganglion cells are present.

2005 

As the transanal pull-through gained favor over the last decade, concerns were raised about its use in infants with long segment disease. Some believe that this approach is relatively contraindicated when the transition zone is in the proximal colon, when the infant presents with enterocolitis or significant abdominal distension. Some surgeons, to confirm the transition zone and to establish the diagnosis of distal disease, use laparoscopy.74 Still others have described an umbilical incision to do the same and to fashion a leveling ostomy if this is needed.91 Most surgeons continue to believe that the Duhamel procedure gives better functional results when long segment disease exists.