Early History of the Therapy of Hirschsprung’s Disease:
Early History of the Therapy of Hirschsprung’s Disease: Facts and Personal Observations Over 50 Years
by Orvar Swenson
Reprinted from the Journal of Paediatric Surgery, August 1996, Vol. 31, No. 8
Congenital megacolon is perhaps the most studied of all congenital anomalies. Let us travel back through medical history and note the twists and turns that took place in the treatment of this disease. Even more fascinating is how close, at one point, investigators came to proving the cause of this obscure condition. In 1886, a Danish physician named Harald Hirschsprung, with a discerning eye and skill, described two patients whom he cared for until their death, with a presentation of his findings at autopsy. Both patients were boys who had a history of severe constipation since birth. He began his presentation to the Society of Paediatrics in Berlin by demonstrating the colon from his first patients, who died at 11 months of age. There was massive dilatation of the descending and sigmoid portions. No mention was made of the rectosigmoid and rectum, therefore it has been assumed that these parts of the colon were not enlarged. He described the mucosal erosions and ulceration's, none of which penetrated through more than the mucosa, leaving the deeper layers and serosal coat unaffected. Hirschsprung then related his struggles to induce evacuations with cathartics, washouts, and enemas. A large elastic tube 1 ft in length could be inserted through the anal canal.
This allowed the passage of intestinal contents, provided evidence that no stricture existed. This seemed to him to indicate an atonic state in the lowest part of the intestinal tract. The second patient died at about 8 months of age. He was treated during one of his acute bouts of obstruction by the insertion of a needle through the abdominal wall and into the colon, which resulted in great relief of his distension. This patient had an empty rectum (the first patient did not). Hirschsprung then described the second child’s massive colon, which had mucosal erosions and ulceration's. In this case the ulcers penetrated all the way to the serosal surface. He ended the presentation by stating that he was convinced that the primary abnormality was either a congenital anomaly or a defect within the bowel wall that had developed during foetal life. Overlooked in subsequent studies as the most interesting statement of the presentation: that Hirschsprung considered the possibility of an atonic state in the lowest portion of the intestinal tract. Unfortunately, this information was not pursued — it could have led to a solution to the problem.
Hirschsprung encouraged his colleagues to be on alert for this condition and to report such cases. In this respect he could not have been disappointed. From the time of the first report until 1948, when we were fortunate enough to have discovered the etiology of the disease, there were at least 200 case reports and some speculation about the etiology of the disease. In his 1907 paper, Hawkins wrote that "the origin of this disease is mysterious." This is not surprising because the surgical and postmortem findings were always the same: massive dilation of the colon or parts of it. From this, the physician would inevitably suspect a mechanical obstruction, yet none was ever found.
In 1895, Marfan insisted that the etiology was an elongated colon that was prone to kinking and that was the site of inspissated material producing mechanical obstruction. This was supported by other publications, particularly from France, wherein some investigators referred to the condition as Mya’s disease. Walker and Griffith, in 1893, described a fatal case that they considered to be caused by colonic inflammation. In 1900, Finwick made a strong case for an abnormally tight anus as the cause. He stated that in general the colon in these cases was similar to the intestine above a mechanical obstruction and that the condition might result from a spastic contraction in the lower end of the bowel. These postulations did not lead to any improvement in the therapy of megacolon. At about this time a number of reports appeared in which the narrow segment of colon distal to the dilated intestine was described. Hawkins, in 1907, believed that a ring of spasm in the distal segment of the colon in these patients resisted the passage of intestinal contents, and to overcome this an anastomosis was made between the dilated descending colon and the rectosigmoid. In light of what we know today, this did not help the patient. However, it was a step in the right direction. In the literature, Pennato is credited with the idea that paralysis of a distal segment of colon produced the disease. However, it is not clear in the conclusion of his report that this is the case. It is correct that he mentions paralysis, but he does not indicate that this lack of function is localised in the narrow distal segment. Treves came close to proving the etiology of the disease in 1898. He performed a colostomy on a 5 year old girl, which relieved her symptoms. He failed to appreciate that this was evidence of a physiological obstruction that produced dilatation of the proximal colon. During the second operation, the colon from the hepatic flexure, including the dilated portion, the narrow segment and the anus, was removed and a perineal colostomy established. There is no doubt that the child was helped by this because she lived at least until age 67, when she was seen in a clinic by Johnson et al. These investigators described her perineal colostomy and found her to be in good health. However, in the final analysis, Treves did not precisely locate the etiology of the disease because he removed the dilated portion of colon, the narrow segment, and the anus.
Each of these previously had been postulated to cause the disease. In 1886, Morris reported the use of what could be considered as a myotomy of the anal structures and the lower rectum. He described the case of a 24 year old woman with massive impactions that were removed after cutting the anal structures and lower rectum back to the coccyx. The divided structures were sutured together, and the patient recovered and regained faecal control. Unfortunately, these important leads were not pursued. They too could have led to a solution to the problem. Instead, surgeons began to excise the dilated portion of the colon. Finney published a long historical report in which he described in detail his treatment of a 9-year old boy. He performed a colostomy at the hepatic flexure, above where the dilated colon began and persisted, down to the rectosigmoid beyond which the colon was not enlarged.
During the second operation an anastomosis was performed between the ascending colon and the rectosigmoid, leaving the colostomy in place. The patient improved; however, after 5 months, symptoms returned and during the third operation the dilated colon from beyond the colostomy to the rectosigmoid was removed. Subsequently the colostomy was closed and the child was reported to be in good health. The follow-up period is not specified. In the proceedings of the Johns Hopkins Medical Society of April 1893, Osler discussed a typical case of megacolon in which Halsted performed a colostomy in the dilated colon, and there was great relief of the child’s symptoms. Neither of them appreciated the significance of what the colostomy indicated regarding the etiology of the disease. Finney reported that two of the 11 patients seen at Johns Hopkins Hospital were treated with a colostomy, but no details were provided regarding the placement of the colostomies. Finney was able to find 21 case reports of patients with megacolon who had been treated with a colostomy. Again, no information was given regarding where in the colon the colostomies were placed or how the patients fared. If the colostomy had been placed in the distal part of the dilated colon and had functioned well, this would have been evidence of partial obstruction.
A number of reports appeared that espoused the idea that the etiology was a neurogenic imbalance. In 1900, Bayliss and Starling published a study of colonic function and innervation. They demonstrated how peristalsis carried material through the colon and described its autonomic nerve supply. Adamson and Aird performed experiments that produced some colonic dilatation by dividing the parasympathetic supply. Their problem was that this had such a profound affect on urinary bladder function that the animals died of renal failure in a short time. A few survived long enough for some colonic dilatation to develop. Operations involving excision of various portions of the pelvic autonomic system preceded these laboratory observations by several years. Wade and Royal performed lumbar sympathectomies on several patients.
They based their operation on the behaviour of one adult who was treated with a sympathectomy for spastic paralysis, which produced relief from severe constipation. It is noteworthy that although they claimed good results, they prepared their patients with purgatives, enemas, and washouts for several weeks before the operation and continued some part of the regimen indefinitely afterward. The first patient described is of particular interest. A colectomy was performed with an ileorectal anastomosis, and follow-up showed the development of ileal dilatation. These investigators failed to see the significance of this development. A somewhat different ablation of the sympathetic system was performed by Rankin and Learmounth, and they claimed good results. These operations became popular, and a large number were performed. Ross examined several patients some time after operation and failed to find uniformly good results. At Boston Children’s Hospital we had the opportunity to observe a few patients treated in this manner, and they had not been helped.
In 1943, Whitehouse et al published a review of the experience with the surgical treatment of megacolon at the Mayo Clinic, and they wrote "The literature related to the therapy of congenital megacolon is rather chaotic and difficult to evaluate." They noted that among 29 cases treated by resection of the dilated portion of the colon, the mortality rate was 24%; and with a follow-up period ranging from 3 to 32 years (for 12 patients), they claimed no poor results. Their conclusion was that removal of the dilated portion of the colon was the treatment of choice. A number of reports of patients treated in this manner can be found in the literature. The largest study is by Ask-Upmark, who reported 102 cases treated surgically. Forty-seven of these had a partial colectomy, and the mortality rate was almost 50%. He recommended resection of the dilated segment of colon as the superior treatment. Dr. Ladd, at Boston Children’s Hospital, had treated several children in this manner, only to find that the disease recurred.
The most comprehensive review of the subject was published as a monograph in 1946 by Ehrenpreis. The study included the author’s clinical investigations by which he set out to prove that Hirschsprung’s idea of megacolon as a congenital lesion was incorrect. Ehrenpreis contended that the megacolon developed after birth, and he attempted to prove this by performing barium enemas on newborns and monitoring them by repeated examinations. He succeeded very well in this regard. Some of the examination films were reproduced in his monograph, and although they are of poor quality, it is possible to suspect a narrow distal segment in some of the cases. These changed failed to impress him for he never mentioned this finding as playing a role in causing the disease. In his summary he defines megacolon disease as "a dysfunction of the colon of as yet unknown origin." In spite of this definitive statement, Cass stated in his historical review that Ehrenpreis demonstrated the "cause of the problem was a failure of the terminal colon to allow the passage of faeces."
There has been confusion concerning the importance of a defect of Auerbach’s plexus in congenital megacolon. In 1920, Dalla Valle was among the first to report the absence of these cells in twins who died of megacolon. Ehrenpreis, in his 1946 monograph, concluded:
Changes in Auerbach’s plexus were demonstrated in megacolon cases and awared pathologic significance by Tittle in 1901, Brentano in 1904, Cameron in 1928 and Tiffin, Chandler and Faber in 1940. Smith in 1908, Retzlaff in 1920, and Passler in 1938 could not however corroborate these findings which by Adamson and Arid were considered as probably secondary changes.
Whitehouse, et al, in their 1943 report, mentioned the publication of Robertson and Kernohan in which they noted the absence of ganglion cells in a case of megacolon. However, this recognition did not alter their conclusion that the best therapy was resection of the dilated portion of the colon. It is clear that at the time we began our work, in 1946, there was no consensus regarding the importance of the absence of Auerbach’s plexus in congenital megacolon. Certainly no new therapy had evolved from these findings.
It is interesting to speculate about the long delay in proving the cause of this disease. The idea of a functional defect in the distal part of the colon was speculated about by a number of authors. Unfortunately, there was no proof that such a condition ever existed in the intestinal tract. We made a number of observations that could only be explained by a physiological defect in the distal colon. Our investigations were based on several patients’ response to colostomy. In our work at Boston Children’s Hospital, the first child treated, J.M., had rectosigmoid colostomy at 5 years of age. Much to everyone’s surprise, he made a rapid recovery, with adequate colostomy function, which indicated to us that there must be partial obstruction beyond the colostomy. A recording balloon placed in the proximal limb of the colostomy recorded regular forceful contractions. Obviously the next step was to determine the status of peristalsis in the distal limb. Here there were no contractions - only slight changes in pressure. Instillation of barium showed a narrow irregular lumen. Injection of a thick paste also was done, and this failed to be expelled. Our physiology consultants rightfully maintained that this absence of peristalsis could be explained by the fact that the colon had been divided at the colostomy. The radiologist suggested that the narrowness of the colon distal to the colostomy probably was attributable to disuse. My increasing concern about the rectosigmoid led us to examine old barium enema films of patients with megacolon, and in 20 instances we were suspicious that the rectosigmoid was considerably smaller than the massive proximal colon.
Dr. Neuhauser re-examined some of these patients and confirmed that distal to the dilated colon the lumen narrowed abruptly. This configuration of the distal colon in Hirschsprung’s disease became the standard diagnostic test for this entity. It was first published by Swenson and Bill in 1948. These x-ray findings supported our belief that the etiology of the disease was a physiological defect in the narrow segment, which served as a partial obstruction, and that removal of this segment of colon with reestablishment of intestinal continuity would absolutely prove for the first time what caused the disease as well as how to cure the patient. Early in 1946 we tested such a procedure in animals. We removed the rectum down to the anus, and the animals remained continent.
The senior surgeons at Boston Children’s Hospital did not accept this radical view, and when the boy, J.M. had recovered completely, his colostomy was closed and he was treated with mecholyl. The use of this treatment was based on Law’s assertion that megacolon could be cured by the administration of mecholyl bromide. The program worked well for several weeks, after which his symptoms returned. He was subjected to a barium enema because it had been claimed that patients with megacolon could be helped by this treatment. It proved of no value, and the child’s illness became sufficiently severe to warrant a colostomy. Again, there was complete relief of the symptoms. This confirmed that there must be partial physiological obstruction in the rectosigmoid. Two additional patients were observed whose clinical courses were identical. When their colostomy was closed, the obstipation recurred and a new colostomy became necessary.
There was now such a preponderance of evidence that permission was granted for us to proceed with this radical new treatment that involved removing the normal-appearing distal segment of colon and leaving in place the massively dilated colon. In June 1947, J.M. had resection in the manner we had worked out in the laboratory. He did well, and 3 months later his colostomy was closed. In the early postoperative period he began to have regular bowel movements. Forty years after the operation, when he was last seen, he was a normal, healthy married man with four children.
This 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 segment did not cure the disease. Our work was presented at the January 1948 meeting of the Society of University Surgeons. This organisation requires that before a paper is read, a manuscript must be in the secretary’s hand. Consequently, it was impossible to include Wilson and Zuelzer’s report (published in February) or Whitehouse and Kernohan’s report (which appeared in June 1948). Both of these groups reported absence of Auerbach’s plexus in small series of patients. In May 1948, our work was presented to the Society for Paediatric Research.
Before our work, there had been suggestions that the absence of Auerbach’s plexus was the pathology of congenital megacolon: however, no concrete evidence existed to prove what its role was or whether it had any part to play at all. We conducted an investigation to define what the nature of the abnormality was in the defective segment. For five patients with megacolon who had transverse colostomies, we obtained recordings from two positions: the dilated colon and the narrow segment. We found that regular contractions were present in the dilated colon but that none existed in the narrow segment, except for small changes that were entirely different from those in the dilated colon. In addition, the intraluminal pressure was higher in the narrow segment than could be demonstrated in the normal colon. This is in accordance with Cannon’s law that smooth muscle contracts when denervated. To be sure that these changes were not normal, two patient with a transverse colostomy and a normal left colon had recordings obtained in the same manner.
Both had regular progressive contractions from all three recording positions. When distal resections were performed on the patients with megacolon, strips of tissue were removed from the specimens and ganglion cells were not present. Thus, it was established that the narrow segment was devoid of peristalsis, that it was aganglionic, and that its intraluminal pressure was higher than normal, indicating a failure of relaxation. All of these combined to form a physiological partial obstruction leading to the proximal megacolon; and most important of all, resection of the narrow segment cured the patients.
In 1989, Sherman et al reported that the operation we had devised had been used in seven different centres, on 880 patients, with a mortality rate of 2.4%, which had been reduced to 1.25% in the last 20 years of the study. Follow-up, which extended to 40 years, showed that 96% of the patients were normal.
The 16th case in our series was a failure because of inadequate resection. The patient’s condition did not improve, and a repeat barium enema showed a persistent narrow segment above the anastamosis site, proving that in young patients we could not rely on the barium enema to precisely identify the proximal extent of agangloinosis. The solution was to perform a biopsy to identify normal colon. This led to the recommendation of rectal biopsy to establish the diagnosis more definitively than was possible with our previously published barium enema technique. We were cautioned by our chief surgeon, Dr. Gross, that this probably result in troublesome rectal infections. In 1955, however, we overcame our fears and tested rectal biopsy, and found it virtually free of complications. It is a precise test to establish the diagnosis of Hirschsprung’s disease and is greatly superior to the previously used barium enema test.
Several modifications have been made to our original operation. Duhamel changed the method of anastomosis from and end-to-end procedure to a side-to-side method to simplify the operation. He did not acknowledge our work, yet he used our method of removing the defective distal segment. This is the crucial step in curing the patient. He stated that his operation was based on Ehrenpreis’s discovery of the etiology of the megacolon. Four years later, Soave modified our operation by using a telescoping type of anastomosis. Rehbein, who limited his operations to patients of approximately 3 months of age, removed the defective colon and made the anastomosis deep in the pelvis. When we began our work, the etiology of this disease was unknown.
Before we could devise an effective treatment, this difficult problem had to be and was resolved. Duhamel, Soave and Rehbein had this crucial information provided to them. Their contributions consisted of technical changes in the manner intestinal continuity was achieved. They claim their operations are new. Actually, they are modifications of our original procedure that differ only with respect to the anastamosis. Because these procedures involve removing the dysfunctional segment, good results can be obtained. Patients are cured by removal of the defective narrow segment - not by the type of anastamosis used to reestablish intestinal continuity. Because there are no detailed reports of complications and long-term results comparable to Sherman’s 40 year follow-up study of patients treated by the original operation, it is impossible to determine at this time whether the modifications result in fewer complications and similar long-term findings. All these modifications have a potential flaw in that more defective tissue is left in place than with the original resection procedure.
The various methods of reporting demonstrate how difficult it is to make comparisons regarding complications between the various techniques. For instance, Soave, in his report of 20 years’ experience, states that he operated on 271 patients, but he excludes from the report the five adults. Sherman et al include adult cases, which increases the complication rate. Only through a carefully prepared protocol used on patients treated by all these methods can we determine which procedure has the fewest complications and the best long-term results.
Unfortunately, some problems remain concerning the treatment of megacolon. The management of children with total aganglionosis is not uniformly satisfactory. Attempts to salvage part of the defective colon in the hope of improving water absorption have not proven universally successful. Sherman, in his 1989 follow-up article, reports the treatment of 19 cases in which the ileum was anastomosed to the rectum, as in our original procedure; there were no deaths. These patients had difficulty adjusting to their abnormal intestinal arrangement; however, in time they did well. One patient became a husky boy, able to play on his high school football team. There has been one disturbing development. Our first patient treated in this manner reported 30 years after the operation that he was anemic because of intestinal blood loss, and protoscopy showed inflammation of the small intestine. An ileostomy has restored the intestinal mucosa to normal and has corrected the anemia. Whether the small intestine can be made to substitute for the colon for a lifetime is in question. Perhaps at some later time in the future, when intestinal transplantation becomes safer and permanent, the technique may be used to help these patients.
The second problem is so-called enterocolitis. I believe that this is a misnomer because the condition is inflammatory bowel disease related to ulcerative colitis. Sherman reported that this disease developed in nine of our patients, which represents a higher incidence that in the normal population. One study has shown that tissue immunity in megacolon patients with inflammatory bowel disease has the same defect found in patients with ulcerative colitis. To my knowledge, there is no confirmation of this finding. I believe that some patients with megacolon have this potential defect. Therefore, it is incorrect to list this as a postoperative complication. This would suggest that patients with this disease might well be treated with colonic instillations of cortisone, before or after the operation, in addition to the irrigations now used. It might be advisable to treat these patients in conjunction with gastroenterologists experienced in the treatment of other forms of inflammatory bowel disease.