Gastroesophageal Reflux and Other Disorders of Esophageal Function

Fundoplication is currently either the first or the second most commonly performed intra-abdominal procedure in infants and children in most pediatric surgical centers. Since the 1970s, surgical correction for gastroesophageal reflux (GER) has been performed by wrapping the upper stomach around the esophagus either a partial (Thal, Boix-Ochoa, Dor, Toupet) or complete (Nissen) fundoplication. In general, it seems that the Nissen fundoplication is more effective in preventing GER, but it may lead to difficulty swallowing and troublesome bloating in some patients compared with a partial fundoplication, which seems not as effective in preventing reflux. These symptoms after the Nissen procedure seem to be minimized with use of an appropriate-sized esophageal tube used as a “sizer” and division of the blood vessels that attach the stomach to the spleen for sufficient mobilization of the stomach.

PATHOPHYSIOLOGY
Physiologic vomiting is a benign variant of vomiting and is seen early in life, usually after burping or feeding or when the infant is placed in a lying down position. Physiologic vomiting in infancy does not interfere with normal growth or development and rarely leads to other complications. It is a self-limited process with symptoms resolving by 18 to 24 months of age in most patients. Usually, there is no treatment indicated for these symptoms, and diagnostic evaluation rarely is required.

In contrast to physiologic vomiting, GER can present as a single or as multiple clinical conditions resulting in significant problems and even near-fatal events. Many barriers exist to protect the patient against reflux of gastric juice into the esophagus. The two most important anatomic factors preventing GER appear to be the length of the intra-abdominal esophagus and the angle at which the esophagus enters into the stomach. Although no absolute effective intra-abdominal esophageal length that prevents GER has been identified, there is correlation between increased intra-abdominal esophageal length and lack of GER.

It seems that an intra-abdominal length of 3 to 4.5cm in adults with normal intra-abdominal pressure provides sufficient protection against reflux most of the time. A length of 3cm seems sufficient in preventing reflux in approximately half of adult patients, whereas a length of less than 1cm results in reflux in most patients.

When the usual sharp angle at which the esophagus enters into the stomach becomes flatter, GER is more prone to develop. On the other hand, increase of this angle seems to inhibit reflux. The ability of this angle to participate in prevention of GER may be diminished as a result of abnormal development or may occur after gastrostomy tube placement.

Components working against this barrier to reflux include the lower esophageal muscles; the difference between abdominal and chest pressures; and various naturally occurring substances which alter the tone of the esophageal and stomach muscles. The lower esophagus has an inner muscle layer, which is thickened. This thickened muscle layer creates a high-pressure zone that can be measured. This muscular thickening extends onto the stomach. This acts as a valve in the lowest portion of the esophagus. The ability to prevent GER is directly proportional to this valve effect and the length of this lower musculature, provided that the muscle relaxes normally.

If relaxation of this muscle is excessive, GER can develop. Also, malposition of the muscle, which can occur with a hiatal hernia in which the area where the esophagus joins the stomach is up in the chest instead of in the abdomen, or with abnormal development, results in loss of the valve effect and contributes to development of GER. Lower esophageal muscle relaxation occurs when the upper esophagus tries to push food down towards the stomach, which is initiated by the swallowing mechanism. If this normal relaxation is exaggerated and is unassociated with swallowing, GER results.

Although the valve function is sometimes imperfect, it is usually highly effective. Short muscle length, abnormal muscle function, increased frequency of muscle relaxation, and muscle location within the chest can contribute individually or in combination to GER. There are many ways that infants and children present with GER. Persistent regurgitation is the most common clinical symptom of GER, especially in young children and in neurologically impaired patients. This excessive vomiting can result in inadequate nutritional intake and can lead to growth failure.

Respiratory symptoms also are seen commonly in infants and children secondary to GER. Identifying that GER is the reason for ongoing respiratory symptoms can be difficult because the symptoms may be the same as those often seen with other lung diseases. Chronic cough, wheezing, choking, or near sudden infant death syndrome (SIDS) all can be attributed to GER.

Acid within the esophagus causes the vocal cords and the small airways of the lung to spasm, which clinically presents as apnea or choking and can be mistaken for asthma. Irritation of the esophagus, likely enhances this mechanism. Although major bleeding is a rare presenting symptom, slow blood loss with iron deficiency anemia can occur occasionally.

In pediatric patients, another presenting symptom is irritability owing to pain. This discomfort can lead to crying in infants despite consoling measures. Although small volumes of feedings in infants can alleviate this discomfort briefly, it is not a lasting benefit. Pain is a presenting symptom often in older children as well. As in adults, the pain is usually located under the breast bone and is described as heartburn. Whether in infants or older children, long-standing GER with inflammation or irritation of the esophagus can lead to scarring and narrowing of the esophagus. When a stricture (narrowing) develops, pain and trouble swallowing are the two most commonly associated symptoms.

Barrett’s esophagitis is a precancerous condition in which the lining of the distal esophagus changes. In adults, it is believed to be the result of chronic esophageal injury from gastric acid reflux. This condition is rare in infants and children. When it does develop, however, serious complications often result. In addition to the increased risk for cancer in adults, approximately 50% of these patients develop an esophageal stricture, and many develop ulcerations. Barrett’s esophagitis can be seen in the older child and teenager as a result of long-standing GER. For this reason, looking into the esophagus and sampling the lower lining may be more appropriate in the evaluation of the older patient when compared with the infant. When Barrett’s esophagitis is documented in the child, it usually can be managed successfully with an anti-reflux operation. When GER has been entertained as the cause of the patient’s symptoms, diagnostic evaluation should be initiated. Among the possible studies used for evaluation of GER are the upper gastrointestinal (GI) contrast study, 24-hour pH monitoring, esophageal manometry (pressure monitoring), upper GI endoscopy (direct telescopic visualization), and nuclear medicine gastric emptying studies.

The use of these studies varies according to the medical center in which the patient is seen. Although some surgeons and gastroenterologists believe that all patients should undergo a gastric emptying study preoperatively, many do not because gastric emptying is thought to improve with anti-reflux surgery owing to a decrease in the capacity of the stomach. For this reason, it can be difficult to interpret which patient with delayed gastric emptying on a preoperative study is benefited by a gastric emptying operation at the time of anti-reflux surgery. Esophageal manometry is not used routinely in children but is beneficial when there is concern about a motility problem in the esophagus or abnormally high pressure at the bottom of the esophagus (achalasia).

The 24-hour pH monitoring test is an objective way to document the presence or absence of GER. This test can be particularly helpful in patients in whom the history is unclear or confusing, such as a patient presenting with respiratory symptoms only. For an accurate result, it is important to cease all anti-reflux medication before the study. Proton-pump inhibitors should be withheld for 7 days, and histamine receptor blockers should not be given for 72 hours before the examination. The patient often needs to be admitted for this test.

An upper GI contrast study is the most frequently used study for initial evaluation of GER. Although not as sensitive as 24-hour pH monitoring, it can be performed on an outpatient basis. In addition, if reflux is documented on this study, and if the patient’s symptoms are consistent with this diagnosis, 24-hour pH monitoring may not be necessary in all circumstances.

If the upper GI series is normal, however, and the suspicion of reflux persists, 24-hour pH monitoring is recommended. In centers where the upper GI series and 24-hour pH monitoring are employed routinely for diagnosis, the upper GI series is used primarily to document anatomic abnormalities of the stomach and first part of the intestine or gastric outlet obstruction (blockage of the outlet of the stomach) that might be contributing to the patient’s symptoms. The upper GI series provides a crude evaluation of whether or not there is normal or delayed gastric emptying.

Direct visualization of the esophagus and stomach is used in some centers for the routine evaluation of infants and children with suspected GER. When endoscopy is used, biopsy is performed to document inflammation or irritation of the esophagus and to exclude cancer or precancerous lesions in older children. Symptoms of bloody vomiting or irritability in infants or trouble swallowing with or without heartburn in infants and children should prompt a direct look into the esophagus and stomach with a telescope (endoscopy).

The presence of delayed gastric emptying is assessed best preoperatively using a nuclear scan with radioactive eggs or milk. Neurologically impaired children with GER have been shown to have delayed gastric emptying more often than neurologically normal children. The benefit and complication rates for these patients undergoing emptying procedures at the time of anti-reflux surgery are unclear. In addition to assessing delayed gastric emptying, the technetium scan is able to help evaluate possible aspiration into the lungs.Initial treatment for “garden variety” GER is usually medical. Initial non-operative treatment in infants includes upright positioning and thickened feedings with or without the addition of medicine that helps the stomach empty (Reglan). Most infants respond to medical treatment and do not require a surgical procedure. H 2-blockers, such as cimetidine or ranitidine, also may improve the success of non-operative therapy. A proton-pump inhibitor (e.g., omeprazole) has revolutionized medical therapy and is the most effective agent for non-operative treatment of this disorder.

Indications for operation without initially attempting medical therapy include the presence of precancerous lesions, narrowings or strictures, a near-fatal (SIDS) event, and, in some centers, infants who stop breathing momentarily enough times to lower their heart rates. If medical therapy is employed, failure of medical therapy constitutes an indication for an operation. It is unclear what is the appropriate time between initiation of medical therapy and consideration of surgical intervention for failure of medical therapy. In infants, it seems reasonable to use medical therapy for several months before operation. In older children, the risk of complications is greater, and medical therapy probably should not be employed more than 6 to 8 weeks.

Surgical Procedures
As previously mentioned, many operations have been used in the surgical management of infants and children with GER, including the Nissen fundoplication, the anterior (Thal) fundoplication, the Boix-Ochoa procedure, and the posterior (Toupet) fundoplication. The Nissen procedure is the most commonly used fundoplication in the United States.

The Nissen fundoplication is a full 360-degree wrap, whereas the Thal fundoplication is an anterior 270-degree partial wrap. Cited disadvantages of the Nissen procedure are the inability to vomit, trouble with swallowing, and the development of stomach gas bloating. Potential gas bloat seems to occur less frequently in children than in adults. Although the Thal fundoplication has a higher incidence of recurrent reflux compared with the Nissen fundoplication, it does not have the associated postoperative problems of swallowing difficulties and bloating. The Nissen fundoplication lends itself best to the laparoscopic approach and is the most commonly performed laparoscopic fundoplication in the world.

When either the Nissen or the Thal operation is performed open or laparoscopically, the results are good, especially in the short-term. Because the laparoscopic approach for either operation has not been used extensively for more than 5 years as of this writing, long-term results with the laparoscopic approach are not known. A recurrence rate of 10% for the Nissen procedure and 15% to 20% for the Thal operation has been found in most large series performed in the open fashion. The most common cause for recurrence with the Nissen fundoplication is migration of the wrap up into the chest from the abdomen followed by breakdown of the wrap. Symptoms of recurrent reflux are more common in patients with neurologic impairment than in patients who are neurologically normal. Postoperative intestinal obstruction, which may occur in 15% to 25% of cases after an open fundoplication, is rare following the laparoscopic operation.

A common scenario for pediatric surgeons is a child, usually neurologically impaired, in need of a gastrostomy for feeding and nutrition. Decisions of whether or not to perform an evaluation for GER and how to perform this evaluation vary from surgeon to surgeon. At the least, most surgeons obtain an upper GI series to evaluate for the presence or absence of GER. In a patient with symptoms of reflux, a fundoplication should probably be performed. In a patient without clinical symptoms of reflux and a normal upper GI series and a normal pH probe, gastrostomy alone may be an option. However it should be recognized that placement of a gastrostomy to be likely increases the incidence of GER. If reflux is noted on either the upper GI series or the pH study, and especially if the patient is neurologically impaired, a fundoplication in addition to the gastrostomy is recommended. In neurologically impaired patients, some surgeons also routinely order a gastric emptying study to evaluate whether or not delayed gastric emptying is present and, if so, perform a gastric emptying procedure.

Some neurologically impaired patients with GER are managed initially by radiographic placement of a nasojejunal tube for enteral alimentation. If a gastrostomy has been created previously, and GER has developed, a gastrojejunal tube placed via the gastrostomy stoma also can be used. The main disadvantage of this approach is the frequent dislodgment of these tubes and recurrent trips to the fluoroscopy suite for reinsertion. In addition, underlying reflux and the basic pathologic conditions remain untreated.

Two special circumstances that merit thoughtful evaluation before fundoplication are the patient who previously has required repair of esophageal atresia and the patient, usually neurologically impaired, who has failed two or three prior fundoplications. In the patient with previous esophageal atresia, there is underlying esophageal motility problems, and this may be aggravated by a 360-degree wrap. For this reason, a partial wrap may be recommended in these patients. In the patient who already has failed two or three previous fundoplications mechanically separating the esophagus and stomach is an attractive alternative approach.

Technique
Nissen Fundoplication
The Nissen fundoplication can be performed either laparoscopically or open. The laparoscopic approach is being used more frequently because of its perceived advantages of reduced discomfort and length of hospitalization and earlier return to routine activities, such as school or sports in older children. Whether performed laparoscopically or open, the operation is done in a similar fashion. In the open operation, either an incision from the bottom of the breast bone toward the belly button or an incision below the left ribs is used. With the laparoscopic operation, five small (3 or 5 mm) incisions are employed Whether performed in an open or laparoscopic fashion, the blood vessels connecting the stomach and spleen are divided. After division of these blood vessels, the esophagus is identified and an adequate length of intra-abdominal esophagus is obtained. A hiatal hernia (a “too large” opening in the diaphragm through which the esophagus passes) may be present that requires one or two sutures for closure. If used, an appropriate-sized dilator is directed through the mouth and into the stomach to help make sure that the wrap is not too tight. Anatomically, the esophagus is made up of two types of muscle fibers: the upper one third of the esophagus is composed of striated muscle, and the remaining lower portion is composed of smooth muscle. Functionally, there are three zones to the esophagus: the upper esophageal sphincter (UES), the body, and the lower esophageal sphincter (LES). Swallowing is a complex series of coordinated contractions and relaxations of these muscle fibers in these physiologic areas. When this does not occur in a coordinated fashion an esophageal motility disorder occurs.

Compared with GER, esophageal motility disorders are rare in children. These disorders include achalasia, diffuse esophageal spasm, and scleroderma. The diagnosis of these disorders is based on clinical suspicion, upper GI contrast study, manometry, and, occasionally, pH monitoring. Dysphagia or difficulty swallowing is usually a prominent symptom with these esophageal motor disorders.

Achalasia
Achalasia is a motor disorder usually affecting the entire length of the esophagus. Although the cause of achalasia is unclear, approximately 10% of cases occur in children. Even though this disease is relatively uncommon in children, it seems to be increasing in frequency. Two thirds of affected children are boys. Whether the condition is being diagnosed at an earlier age or there is a true increase in its incidence is unclear. This disorder is caused by failure of the LES to relax and failure of the esophagus to advance food into the stomach. Most children with achalasia present with symptoms of several months’ to several years’ duration consisting typically of vomiting of undigested food, severe bad breath, and significant dysphagia (difficulty swallowing). These children also may have prolonged coughing spells after meals. Weight loss is common because the nutritional status is affected. Children often complain of pain behind their breastbone or burning secondary to esophageal irritation from food that is stuck. Usually there is a delay in establishing a diagnosis. A chest x-ray may show a widening in the middle of the chest and a fluid level in the esophagus when the child is sitting or standing. (Figure 6A).

The diagnosis usually is suspected after an upper GI series shows narrowing at the LES with a large esophagus above it (bird beak deformity) (Figure 6B)

In addition, there is no relaxation of the LES on UGI study. The diagnosis is confirmed by manometric (pressure) evaluation revealing an elevated resting pressure in the esophagus without evidence of relaxation of the LES There also is absence of coordinated contractions in the esophagus.The ideal treatment of patients with achalasia is controversial. In 1971, Van Trapp introduced the concept of balloon dilation of the narrowed LES for adult patients. Balloon dilation is used in children but seems to be less successful in relieving symptoms than in adults. The incidence of post-dilation GER may be higher in children, and the procedure is technically more difficult in younger patients. Other approaches for relief of symptoms include injection of botulinum toxin into the LES. Although this technique has gained popularity in more recent years, its effectiveness usually lasts only a few months. Medical management is also not successful. Because non-operative therapy is rarely successful, especially for a prolonged period, most children with achalasia require an operation for long-term relief.

In 1913, Heller described an operation for relief of symptoms of achalasia. With advancements in minimally invasive surgery, this procedure has become an attractive approach for surgical management. Although esophagomyotomy (Heller’s procedure) has been reported using either the laparoscopic (through the abdomen) or the thorascopic (through the chest) route, the laparoscopic route is now favored. There are many reports in adults describing the effectiveness of a laparoscopic Heller myotomy for relief of symptoms resulting from achalasia, but the experience in the pediatric literature is not nearly as large.

The most controversial aspect of performing a laparoscopic esophagomyotomy in a child is whether or not an anti-reflux procedure should be added. This controversy also exists in the adult literature. Most adult surgeons favor the performance of an anti-reflux operation because it is relatively easy to accomplish and prevents the need for a second procedure if GER develops. In most children a fundoplication is not performed.