Esophageal Atresia and Tracheo-Esophageal Fistula...
The Journey

(Ed. Note: So much is involved in the history of esophageal atresia that this has to be a greatly condensed summary, which will provide a foundation from where to begin. Interspersed with the text is a dialogue with Mary Clark, a nutritionist who has been studying the history of esophageal atresia, and Terri Burke, the founder of this organization, Much of the background information comes from Dr. Keith Ashcraft and Dr. Nate Myers, both of whom have written the most extensive histories to date. Myers breaks down the history into three segments: 1)pre-1670 (we know of no literature written before this time); 2) 1670-1930 (pre-surgical/pre-survival era); and 3) 1930's-present day (surgical/survival era).)

Terri: Mary, I had never heard of esophageal atresia before our daughter was born with it. Is it a relatively new birth defect?

MARY: Esophageal atresia and tracheo-esophageal fistula are incredibly complicated. They have been around forever, as have all of the birth defects related to VATER Association.

Terri: How do you know?

MARY: Well, because doctors first started seeing and recording them during the seventeenth century. In the 1600's, Thomas Gibson described a baby who (at autopsy) had esophageal atresia with a distal TE-fistula. Previous to that, Thomas Gibson had written of seeing something that looked like esophageal atresia. These are things they discovered during an autopsy. The problem was not apparent in a live baby.

Terri: How did they find out?

MARY: Autopsies were performed extremely rarely on babies. The physicians were doing them in training. There were very few brave, curious physicians who wanted to know more about what was going on with these babies. Why did they die? I think it is safe to assume that if babies had this kind of birth defect as far back as the 1600's, go back further and babies would have had the same kind of problems, perhaps nobody ever knew. It is logical to assume that defects in people's anatomy have always existed. Whether it was a defect in the way a person's fingers or toes looked or a defect in how their nervous system was formed or a defect in how their gastrointestinal system was formed. The defects have always been there, just nobody knew what they were.

NATE: One has only to review case histories as recent as the past decade to find examples where identical symptoms were attributed to such conditions as prematurity, cerebral birth injury or pulmonary atelectasis (a condition in which the lungs of a fetus remain unexpanded at birth) and no thought was given to the possibility of esophageal obstruction." So, many babies could have been born with esophageal atresia, but because the obvious defect was something else, an autopsy on the baby was not performed, and no one gave thought to esophageal atresia.

During the second era, which spanned nearly 300 years (1670-1930's), there were a number of references of esophageal atresia in the literature. As a parallel, one could say there was a "surgical era" which began in 1888 in which advances and interest in surgery were being made.

Terri: So when did physicians start doing these autopsies?

MARY: An early account by Thomas Gibson, the London physician, who in 1697 wrote "An Anatomy of Humane Bodies Epitomized, a Clinical Account of Esophageal Atresia with Distal Tracheo-oesophageal Fistula." He was sent to see a baby who couldn't swallow. They tried to figure out what was wrong with the baby. The symptom was the baby was very, very hungry and the mother, of course, tried to nurse the baby and the baby couldn't be satisfied, and everything was coming right back up. So they sent for the doctor, who was unable to figure out why the food was coming back up. The baby died. Afterwards, the doctor tried to insert a pipe down the baby's throat so that he could look, but he couldn't see anything, and it looked like a blind pouch. After the baby died the parents agreed to have the baby autopsied, which is a huge sacrifice for a parent to do. When you lose a brand new baby it is really easy to say, "This baby is too perfect and too beautiful. I just don't want him cut open." Maybe the doctor said, "I just want to see what made the baby sick without saying what he was going to really do—but then he got permission to autopsy the baby, and he made a slit in his stomach and looked down from the mouth. Then he saw that the two ends of the gullet, the esophagus, didn't meet. So Thomas Gibson was the first to put it in medical literature. We can assume it happened before this period of time. The disorder seems to be rare enough that few doctors had experience with it, so the body of knowledge grew quite slowly.

Terri: Do you think it was really rare, or they just didn't talk about it? Or maybe if a baby died, they just didn't...

MARY: Well, consider that babies were almost always born at home with midwives, and even later with physicians in the home. After the birth, the doctor packed up and went away, and the mother and the baby were left there. If something happened to the baby in the days following birth, it wasn't that unusual for a family to see death back then.

NATE: The first documented case of esophageal atresia in Siamese ( conjoined) twin girls was written by William Durston in 1670, and the first account of esophageal atresia with a tracheo-esophageal fistula was written by Thomas Gibson in 1697. These are both classic contributions, although many would refer to Gibson's account as the purest. The baby that Durston saw was a very unusual and rare case, being a Siamese twin. Gibson's experience involved a distal (closer to the stomach) esophageal atresia, which is now considered the most common type.

No references of esophageal atresia have been found during the 1700's. However, another seemingly unrelated incident provided a solution which was later adapted to care for these babies. In 1793, John Hunter suggested providing a substitute for "deglutition"; paralysis of the muscles of deglutition (the act of swallowing), something that could happen to "normal" children as well as adults, in which they lose the motility of the esophagus. He says of a patient who acquired the disease of being unable to swallow, "It becomes our duty to put some artificial mode of conveying food into the stomach by which the patient may be kept alive while the disease continues." Although John Hunter was not referring specifically to esophageal atresia, it is important to see that the method he suggested and ended up adopting, ultimately became a vital part of the treatment for esophageal atresia...tube feeding.

More was written in the 1800's usually of an esophageal atresia with a fistula connection to the trachea. It seems that more people were independently writing about these anomalies without ever realizing that anyone had seen it before.

The first mention of VATER Association, as we know it today, was written by Thomas Hill in 1840 in the Boston Medical and Surgical Journal. "His patient, the newborn infant of Dr. and Mrs. Webster, also had rectal agenesis (failure of an organ or body part to develop or grow) with a recto-urinary fistula." Hill is given credit for the first description of a combination of anomalies which has recently been encountered since and is presently referred as VATER or VACTERL Association. Hill's clinical description says, "The infant had been noted to salivate excessively since birth, and with each feeding it would cough, become cyanotic (blue), and regurgitate all its food." His diagnosis was 'spasmodic stricture' of the oesophagus (British spelling), and he suggested a warm enema might relieve the spasm. When the nurse attempted to give the enema, she found not even a trace or mark of an anus. The baby died, and autopsy subsequently revealed esophageal atresia with a distal tracheo-esophageal fistula and an imperforate (without an opening) anus with a fistula to the bladder neck.

MARY: Many doctors didn't know why a child died. If a baby died of pneumonia, a well-known problem for children with TEF, then they would put "pneumonia" on the death certificate. If the babies had some other problem, such as a cardiac defect, which caused death, the physicians might never have known about esophageal atresia or some of the other anomalies that sometimes accompany it.

Dr. Hirschsprung, a well-known doctor in 1861, found 10 cases that had been written about and then added four cases of his own. What was interesting about Hirschsprung is that he personally observed four cases in less than seven months in a town of only 108,000 inhabitants. And then within three weeks a Dr. Ilott met with two cases in a county district near London. "There is the possibility that if more babies had been autopsied, malformations of the esophagus would be found of more frequent occurrence than the small numbers of recorded (ed. italics) cases would lead us to suppose."

Terri: I have questioned that, too. I hear how rare the defect is, and then I hear of four cases within a month of each other in the same hospital. In fact, in 1942 there were eight babies born at Children's Hospital of Boston. (see photo)

NATE: In the 1800's Dr. Morell MacKenzie made a substantial contribution not only with his own literature on this subject, but also from the fact that he researched the topic so thoroughly that he "dug up" names that rarely appear anywhere else in literature. MacKenzie's assessment of the situation was "the most generally accepted view of the immediate cause of oesophageal malformations is that they depend on arrested development." This view is probably correct, but it does not go far enough; it does not explain the cause of the arrested development. The most common form of atresia is when the upper part of the esophagus usually ends in a dilated pouch about half an inch above the bifurcation (separation or branching into two parts) of the trachea, while the lower portion generally originates from the trachea still closer to the bifurcation, and passing downward enters the stomach in the usual way. The portion of the esophagus immediately proceeding from the trachea is generally very narrow, but as it descends, it acquires its normal size. The upper portion, or pouch, is always much dilated, and its walls considerably thickened. In regards to the associated deformities, in one instance there was spina bifida, absence of an anus, and a single horseshoe kidney placed over the spine. The diagnosis of the deformity is easy—in fact, there is no disease for which it can be mistaken...the inability to swallow, which cannot fail to be observed from the first time the infant attempts to suckle, is characteristic. The diagnosis can be further verified by the attempted passage of a catheter. If a catheter of suitable size cannot be passed the distance indicated, it may be presumed that there is a congenital (born with) obstruction. Morell MacKenzie's writings are valuable for all who are interested in the early diagnosis and assessment of congenital anomalies of the esophagus.

Terri: When was the first attempt made to join the ends of the esophagus together?

MARY: It wasn't until 1869 that a brave doctor tried to do a surgical repair of esophageal atresia. And in some of the very first attempts they simply felt if they could put a gastrostomy tube into the baby's stomach, at least they could feed the baby and keep the baby alive. But it didn't work. Every time they tried this the babies would die because usually it was an esophageal atresia with a fistula—they were more likely being fed into the stomach, and the stomach contents were going up through the little part of the esophagus, into the distal fistula (lower end and most common), into the trachea, and then into the lungs.

Terri: At that point, did they know about the fistula yet?

MARY: I think they speculated on it by that time. Thomas Gibson, when he did that first autopsy, had written about a distal TEF. So, the literature mentions the existence of that disorder. At that time doctors began to have the idea that maybe a primary anastomosis or could be done. In other words, it occurred to them that, hey, maybe these two ends could be hooked together. But the technical ability to do it just wasn't there yet. It seems like there was a lot of growth in the knowledge of anatomy that was happening simultaneously. They were learning more about the vascular system and the gastrointestinal system. If they needed to transport a piece of tissue from one part of the body to the next, like taking part of the intestine to put between the two ends of the esophagus, they needed to make sure there was a blood supply available to that section so that that part of the tissue wouldn't just die. That causes problems in itself. So, there was tremendous growth happening at the same time in these different fields...in abdominal surgery, in thoracic surgery. In the days before antibiotics, many surgeons were reluctant to enter into the pleural cavity, which is where the lungs are, because they knew that it would subject a child to terrible infection.

NATE: The true surgical era for esophageal atresia began a little under 100 years ago on October 20, 1888, when Charles Steele of London operated on a baby. He decided that there was most likely a membrane across the esophagus or that it ended in blind "terminations," and possibly they could perforate the membrane. However, if there was a distance between the two ends of the esophagus, they could do no more, but the parents would know they had tried everything possible to save their baby's life. The father willingly gave his permission to the operation. They did try passing a bougie down through the oesophagus and another upward from the stomach, but the two ends didn't meet, by what they guessed to be an inch and a half. After trying another type of probe, they realized it was useless, so they closed the stomach and abdomen. The infant slept for some time and died twenty-four hours later.

Nothing much was reported again until the 1930's when an acceleration in the number of reports, climaxing in the classic contribution of Drs. N. H. Levin, W. E. Ladd, and Cameron Haight.

MARY: Harry Richter seems to have done quite a lot. All the literature goes back to the surgeries and research that he began in 1913. He managed to describe a way that the babies could be kept alive until they could work out the technical aspects of anastomosis. They said he did very well with the people he worked with, but he simply didn't have enough babies to work with. One of Richter's babies only lived two days. A third one seen by Richter lived 5 days, but he wasn't even operated on because he was in such poor shape before the surgery. Now this was another complicating factor...sometimes these babies were so sick that by the time they were able to see a doctor that knew anything about this problem, it was dangerous to try and operate on them. They were too sick with things like pneumonia. Today, because we have antibiotics, they'll operate if it's a life threatening situation at the time, such as repair on a brand new baby with a fistula. If they don't try to repair it quickly, more "gunk" is going to the lungs. Richter did his best, but his only problem was that he just didn't see the anomaly anymore in his career.

Terri: How many do you think he saw?

MARY: Enough that he did make some important advances but not enough to keep the advances going continuously. So what happened here was a gap in the knowledge and technique, and then the other surgeons started taking it up again.

NATE: In 1913 a Dr. Bennemann wrote of his experience: "Congenital atresia of the oesophagus is everywhere considered one of the rare anomalies. Shukowsky, with a hospital experience of 50,000 newborn babies, saw only one case. And yet within a period of one year three of these cases came under my observation. While many different kinds of congenital anomalies of the oesophagus are described, one type is the most common. This is the...type in which the upper end of the oesophagus ends in a free dilated pouch, while the lower end passes from the stomach into the trachea.

Terri: Where did it go after him?

MARY: Other doctors were attempting surgery, but the babies didn't live. One of the problems they had was all the mucous and saliva that accumulates in that little pouch up near the neck. It would just spill over into the trachea, and for a long time that was a real big problem, even during surgery.

They didn't have a good way to control keeping the secretions out of the trachea, and the babies would aspirate them and maybe even die on the operating table. It was always a risk they were taking. And postoperatively, they didn't have a good way to suction out the mucous and all those little bubbly secretions that accumulate in the top part of the esophagus. The babies could accidentally breathe in those secretions, which would go right down their tracheas.

NATE: There is a very famous contribution from Richter written in 1913, in which he wrote an article entitled Congenital Atresia of the Oesophagus; an Operation Designed for its Cure—with a Report of Two Cases Operated Upon by the Author. This contribution presented two particularly important aspects of the problem. First, he drew attention to basic problems, "The essentially fatal factor in the anatomy consists of a communication between the upper end of the distal segment and the trachea or bronchus, allowing of free communication between lungs, gullet, and stomach (if the infant with a fistula cries, air from the lungs fills up the stomach, distending (pushing it out so it blows up like a balloon) it. If the infant vomits, stomach contents go into the lungs causing drowning)," and second, he was very near to finding a solution. In addition, he attempted an operative technique which was, 50 years later, to become standard practice for the poor-risk baby in many centers.

This classic paragraph has been quoted and requoted in the medical world and indicates Richter's clear thinking at a time when thoracic and neonatal surgery had not really entered its infancy.

Direct anastomosis, or connection, of the ends, with closure of the trachea, in an infant less than a week old, is certainly a hazardous proceeding. I am not certain, however, that it may not prove impossible, and, if so, would be the ideal operation. The technical difficulties would be rather greater than that of the operation here suggested. The greatest obstacle would be the danger of infection. The present problem seems to be to close the communication (fistula) with the trachea, do a gastrostomy, and so feed the child.

Many years later Cameron Haight said it was unfortunate that Richter had no further experience with these problems. He believed that if Richter had been able to see more infants with TEF, he might have figured out an operable solution much earlier. In fact, an article from the more recent past by C. Everett Koop and James Hamilton, Atresia of the Esophagus: Increased Survival with Staged Procedure in the Poor Risk Infant, mentions that in a series of 41 patients 13 were initially managed by the Richter technique, i.e. the upper esophageal pouch was left intact, the tracheo-esophageal fistula closed, and a gastrostomy performed.

"The remaining years of the presurvival era were marked by despair and hope, and isolated examples of babies living for varying periods—sometimes several months—following various surgical measures. Advance in pediatric medicine, particularly in the care of the newborn, anesthesia, and in due course the introduction of chemotherapeutic agents and antibiotics, were all parallel surgical advances and play their part in the success which would ultimately be achieved."

MARY: To me, it's incredible that for thousands of years all babies with this condition died, and then just in recent history, between about 1939 and now—50 years or so—suddenly children are being kept alive, and survival rates are improving. With the introduction of antibiotics, pneumonia could be cured. When they finally figured out how to maintain people's electrolytes and fluid levels...that happened later on in the 40's...more babies could be maintained.

NATE: After stumbling through many dismal experiences and failures, a new ray of light dawned when in 1939 Ladd in Boston and simultaneously Levin in St. Paul, Minnesota, the activity of each being unknown to the other (ed. ital), developed a multistage attack for treatment of esophageal atresia and tracheo-esophageal fistula. These were:

To provide a means for nourishing the child
To prevent regurgitation of food by reconstructing the esophagus; and
The prevention of pulmonary complications by re-establishment of the continuity of the gastrointestinal tract. Later Drs. Levin and Ladd were able to obtain survival using this multi-stage approach. It is interesting that about this same time a Dr. Belsey wrote a paper on gastro-oesophageal reflux, "a condition which emerged as a very significant problem in the follow-up of patients with repaired esophageal atresia."
In 1940 Dr. Ladd did fistula surgery. Later he performed a cervical esophagostomy (the esophagus is brought to the outside of the neck to drain). He wrote in 1944, "At the present time primary anastomosis of the esophagus appears to be the operation of choice when the two ends of the esophagus can be approximated without too much tension. In other cases, where the ends of the esophagus are far apart, the three stage operation with the ultimate construction of an anterior thoracic esophagus is a safer operation." The important factor is that their patients were the first babies to be born with esophageal atresia and to survive. (Ed. note: See stories on pages 6 and 7 as well as Robert Linsig's story on page 2. Dr. George Humphreys performed surgery on Robert Linsig who was born in 1935 and was 16 years old at the time of his repair. He was born before both Levin's and Ladd's patients).

Some years later Dr. Robert Gross summarized this progress by saying, "In recent years there has been no more dramatic advance in surgery than that which has taken place in the treatment of congenital atresia of the esophagus. In spite of innumerable attempts by many surgeons to correct the malformation by operative means, the abnormality was uniformly fatal throughout the world prior to 1939. In the decade following this, improvement in the surgical handling of babies with this anomaly have been so remarkable that in many centres a high proportion of these children now can be saved and can be provided with a satisfactory pathway for the transport of food to the stomach."

Cameron Haight became the first surgeon to achieve long-term survival with preservation of the esophagus. He writes: "With knowledge of the 10 unsuccessful attempts to obtain a primary anastomosis ...we could not manifest undue encouragement when our next patient arrived on March 14, 1941, twelve days after her birth. This infant was unusually robust, weighing 8 lbs. and 4 oz. upon admission. Roentgenogram (x-rays) obtained before admission had demonstrated a blind upper esophagus. The presence of air in the stomach indicated the existence of a communication between the trachea and the lower esophagus. Since penicillin was not then available, the only antimicrobial agent used post-operatively was sulfathiazole, administered rectally. Fortunately, the patient survived in spite of the fact that generalized edema had appeared on the third post-operative day as a result of excessive use of physiologic saline solution; and leakage of the anastomosis into the extra pleural wound had occurred on the seventh day after the operation. In the interim, a gastrostomy to make feedings possible was performed on the tenth post-operative day...A stricture developed at the site of the two joined ends or anastomosis. As a result of this, accumulation of mucous in the pharynx and upper esophagus interfered greatly with the ability of the patient to swallow, and necessitated a prolonged period of convalescence in the hospital. Eventually, a single dilation of the stricture was performed 17 months after the operation, and the patient was allowed to return home 20 months following the operation. She continued to improve and has developed normally.

Terri: This could really be a history of surgery...

MARY: Even though they have these nice, little, tidy pictures in the medical and surgical journals and these are the way the doctors learn what kind of surgeries to do, all babies don't fit into those nice, little, tidy classifications. A surgeon can get inside when he is doing the surgery, and the baby just has different variation that he's never heard of before. Like different blood vessels that can be in the way and make it a very difficult procedure to connect the two ends of the esophagus. Sometimes the esophagus can be fused to the trachea and potentially cause serious problems.

Sometimes there can be a fistula, and that can be an unusual repair in itself because the trachea and the esophagus, have to be separated, and then those holes have to be closed, and that can be difficult. Sometimes another piece of tissue has to be put between them so they don't hook back together and have the hole open up again. So each surgery is unique, although a surgeon is thoroughly prepared for what he is doing. Just because he has operated on fifty children with esophageal atresia, he's still going to come across different varieties, and his solution to each child is going to be a little bit different. One child the ends can be pulled together and just stitched up, another child the gap might be so tight, there's no way to do a primary repair, (connecting the neck end and the stomach end of the esophagus together), a piece is used to go between the two ends, either a part of the intestine, or sometimes a tube made from the stomach. Sometimes the stomach is pulled up to the proximal end. They've tried different kinds of surgeries over the years. I wish I could explain it more. I feel I'm only just learning how complicated it really is. Sometimes you see a child or even an adult going for a surgery, and it seems cut and dry. Or they're going to go in and open up my little child and just hook the two ends of the esophagus together, and that's that. But when you start reading how they really have to perform the surgery, it suddenly seems a lot more complicated—watching out for all those blood vessels and nerves and other major organs—all of which are so tiny in babies.

Terri: I remember when we had our surgery. A nerve was nicked, and our daughter's eye drooped. It was a nerve in her neck that ran next to her esophagus.

MARY: Everything is microscopic, and a lot of "stuff" runs right next to each other. It's covered by all this fascia, and sometimes things inside look the same. The doctors have to be exceedingly careful, diligent and very slow, when they're dissecting all the little parts that are hooked together. I was visualizing it while reading, and I thought, "This is incredible—the aorta, the biggest artery in your body that carries all that good oxygenated blood away from the heart, is right there near where a lot of these problems are happening—and it would be so easy to nick it." The aorta can also press on the trachea and cause complications. Sometimes it's like the aorta shouldn't be anywhere close by where this is happening, but what if this is just one child where everything is all tangled up there together.

NATE: Dr. Nate Myers believes that perhaps the "team" approach, more than anything, has improved the survival figures. The mortality rate has gone from 100% to almost zero. This, of course, has required technical expertise, but in addition, the surgeon has found it necessary to seek help from pediatricians, radiologists, pathologists, biochemists, hematologists, bacteriologists, and anesthesiologists, to name a few. Skilled nursing, 24 hours a day, perhaps for weeks and months, has been required. This is the only way that satisfactory results have been achieved in these seriously ill babies.

MARY: In the early surgeries, some were successful, but the baby may have gotten too much IV fluid because it was difficult to monitor how much fluid or electrolytes a person should have. So lab technologies have advanced, which helps to maintain the very sick child. Because not only did they have a child that needed to have surgery, they frequently had one that was quite ill...You know, at one time there were no such things as NICUs (Neonatal Intensive Care Units). The ability did not yet exist to care for critically ill babies.

Terri: So when did things change?

NATE: With Cameron Haight's success in 1941 a new era had commenced, and the technique of removal of the tracheo-esophageal fistula and primary end-to-end oesophageal anastomosis has remained the cornerstone of treatment from that day on.

MARY: There's such a huge range of esophageal atresia. I didn't realize that sometimes they're very closely approximated and can be fairly easily hooked together shortly after birth (anastomosis) or that other times the ends are a centimeter ( a little less than half an inch) or two or three or varying lengths apart; and a lot of times the gap can be very, very long, especially if it's just pure esophageal atresia without a fistula; and sometimes they can't pull the two ends together if there's too long a gap—sometimes it's the distance from the baby's stomach to the baby's neck. And something that occurred to me while I was reading this literature is that even though they have those four classifications of esophageal atresia and tracheo-esophageal fistula, it can be almost infinite. Esophageal atresia and tracheo-esophageal fistula are as individual as the child is.

NATE: Atresia of the oesophagus, with or without trachea-oesophageal fistula, has been a baffling problem for the surgeon. If there is any surgeon who has attempted to save the lives of patients suffering from these malformations who has not had any disappointments and numerous trials and tribulations, I have not heard of him.

MARY: I think that the one doctor in 1939 inspired more doctors...they just kept plugging away. There were always doctors who were trying to continue operating and kept trying and trying to help babies to live.