Pediatric Hypertrophic Pyloric Stenosis

Hirschsprung wrote the first complete description of hypertrophic pyloric stenosis (HPS) in 1888. He believed the disease was congenital and represented fetal pyloric development failure. In 1907, Ramstedt described an operation to alleviate this condition. He suggested splitting the pyloric muscle and leaving it open to heal secondarily. This procedure has been used to treat infantile hypertrophic pyloric stenosis (IHPS) since that time. Although this curious disease is treated easily with surgery, its etiology remains undetermined. Hypertrophic pyloric stenosis is inherited by a multifactorial threshold model, and the generalized occurrence risk for siblings is 5-9%. Associated congenital anomalies are reported in 6-20% of patients with pyloric stenosis. A rare association with developmental delay has also been reported.[7]

Hypertrophic pyloric stenosis occurs secondary to hypertrophy and hyperplasia of the muscular layers of the pylorus, which cause a functional gastric outlet obstruction. Diffuse hypertrophy and hyperplasia of the smooth muscle of the antrum of the stomach and pylorus proper narrow the channel, which then can become easily obstructed. The antral region is elongated and thickened to as much as twice its normal size. In response to outflow obstruction and vigorous peristalsis, stomach musculature becomes uniformly hypertrophied and dilated. Gastritis may occur after prolonged stasis. Hematemesis is occasionally noted. The patient may become dehydrated as a result of vomiting and develop marked hypochloremic alkalosis.

Researchers have investigated the cause of this muscle hypertrophy for several decades. Many believe the problem is induced by the pyloric musculature failing to relax. Results of studies of pyloric muscle innervation are inconclusive, possibly showing a tendency toward fewer or more immature ganglion cells in affected individuals. 

No definitive cause for hypertrophic pyloric stenosis has been found. However, various environmental and hereditary factors have been implicated. Suspected environmental factors include infantile hypergastrinemia, abnormalities in the myenteric plexus innervation, cow's milk protein allergy, and exposure to macrolide antibiotics. Hereditary factors may also play a role; hypertrophic pyloric stenosis occurs in as many as 7% of infants of affected parents. The etiology is probably multifactorial, with both genetic and environmental factors contributing. Recognition that hypertrophic pyloric stenosis is an acquired disorder and not a congenital disorder is increasing. Recently, genetic studies have identified susceptibility loci for infantile hypertrophic pyloric stenosis and molecular studies have concluded that smooth muscle cells are not properly innervated in infantile HPS.[8]

Researchers who identified a cholesterol-related genetic locus associated with risk for infantile hypertrophic pyloric stenosis have also demonstrated that low serum lipids are a risk factor for this disorder. In a genome-wide association study, Feenstra and colleagues found that the single-nucleotide polymorphism (SNP) most strongly associated with risk for HPS was rs12721025 on the long arm of chromosome 11. In a follow-up study, the researchers compared levels of total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides in plasma obtained prospectively from 46 HPS cases and 189 control patients. Mean total cholesterol levels for cases and controls were 65.2 mg/dL and 75.2 mg/dL, respectively. The risk for IHPS was inversely and significantly associated with total cholesterol level, with an odds ratio of 0.77 per 10 mg/dL.[9, 10, 11]

In a retrospective study of pediatric data from the US military health system (MHS) spanning 11 years, investigators found that administering oral azithromycin to infants in the first 2 weeks of life increased their risk of developing hypertrophic pyloric stenosis by more than 7 fold (P < 0.001); when azithromycin was given at ages 15-42 days, the risk of developing hypertrophic pyloric stenosis was more than 2 fold (P =0.028).[12]  No cases of hypertrophic pyloric stenosis were reported among infants exposed to azithromycin between ages 43 and 90 days.[12, 13]  Further studies have reported this association along with an increased risk of developing infantile hypertrophic pyloric stenosis following the ingestion of erythromycin and azithromycin, especially in the first 14 days of life.[14, 15]  Based on these reports, monitoring for hypertrophic pyloric stenosis in infants receiving erythromycin, azithromycin, or prostaglandin infusion during the first few weeks of life is recommended. 

United States

Pyloric stenosis is the most common cause of gastric outlet obstruction in infants. It is also the most common surgical cause of vomiting in infants. The prevalence of hypertrophic pyloric stenosis ranges from 1.5-4 cases per 1000 live births among whites, although it is less prevalent among blacks and Asian Americans.

Operative therapy for hypertrophic pyloric stenosis has remained unchanged for nearly 100 years. Outcomes have improved through advances in early diagnosis, preoperative resuscitation, operative anesthetics, and nutritional management. Mortality may rarely result from late diagnosis, resulting in dehydration and shock. Mortality is also rare after pyloromyotomy. 

Race

Reported prevalence of hypertrophic pyloric stenosis among whites ranges from 1.5-4 cases 1000 live births; hypertrophic pyloric stenosis is less prevalent among blacks, Asians, and Hispanics.

Sex

Pyloric stenosis has a well-known predilection for occurring more often in males than in females, with reported ratios ranging from 2:1 to 5:1. First-born male children are believed to have the highest risk of developing hypertrophic pyloric stenosis.

Age

Newborns typically develop signs of gastric outlet obstruction at 3-4 weeks. Cases of hypertrophic pyloric stenosis have been documented from the first week of life to 3 months. Approximately 95% of infantile hypertrophic pyloric stenosis cases are diagnosed in those aged 3-12 weeks. Premature infants generally develop symptoms later than full-term infants, which may lead to a delay in diagnosis. Late-onset hypertrophic pyloric stenosis was reported by Wolf et al in a 17-year-old female and by Selzer D et al in a 14-year-old boy who was referred to pediatric surgery for evaluation.[16, 17] The boy in the latter report was diagnosed to have hypertrophic pyloric stenosis. He underwent laparoscopic pyloroplasty with satisfactory outcome.

Typical presentation of an infant with hypertrophic pyloric stenosis (HPS) is onset of initially nonbloody, always nonbilious vomiting at 4-8 weeks. Although vomiting may initially be infrequent, over several days it becomes more predictable, occurring at nearly every feeding. Vomiting intensity also increases until pathognomonic projectile vomiting ensues. Slight hematemesis of either bright red flecks or a coffee-ground appearance is sometimes observed.

Patients are usually not ill-looking or febrile. The baby in the early stage of the disease remains hungry and sucks vigorously after episodes of vomiting.

Prolonged delay in diagnosis can lead to dehydration, poor weight gain, malnutrition, metabolic alterations, and lethargy.

Parents often report trying several different baby formulas because they (or their physicians) assume vomiting is due to intolerance.

Careful physical examination provides a definitive diagnosis for most infants with hypertrophic pyloric stenosis. However, some of the classic signs that would lead to diagnosis may be absent due, in part, to the early diagnosis of hypertrophic pyloric stenosis.

An enlarged pylorus, classically described as an "olive," can be palpated in the right upper quadrant or epigastrium of the abdomen in 60-80% of infants.[2] In order to assess the pylorus, the patient must be calm and cooperative. A pacifier or small amount of dextrose water may help. If the stomach is distended, aspiration using a nasogastric tube is necessary. With the infant supine and the examiner on the child's left side, gently palpate the liver edge near the xiphoid process. Then displace the liver superiorly; downward palpation should reveal the pyloric olive just on or to the right of the midline. To be assured of the diagnosis, the physician should be able to roll the pylorus beneath the examining finger. The tumor (mass) is best felt after vomiting or during, or at the end of, feeding. The diagnosis is easily made if the presenting clinical features are typical, with projectile vomiting, visible peristalsis, and a palpable pyloric tumor.

When diagnosis is delayed, the infant may develop severe constipation associated with signs of dehydration, malnutrition, lethargy, and shock.

Despite numerous hypotheses, the exact etiology of hypertrophic pyloric stenosis is not fully understood. Genetic, extrinsic and hormonal factors have been implicated. In addition, abnormalities of various components of the pyloric muscle, such as smooth muscle cells, growth factors, extracellular matrix elements, nerve and ganglion cells, neurotransmitters, and interstitial cells of Cajal, have been reported. Genetic studies have identified susceptibility loci, and molecular studies have concluded that smooth muscle cells are not properly innervated in this condition.[18]  Kundal et al reported a rare case of dizygotic twins who were bottle fed and were affected with infantile hypertrophic pyloric stenosis.[19]

Bottle-feeding was associated with an increased risk for hypertrophic pyloric stenosis in a population-based case-control study of 714 infants.[20, 21] After adjustment for sex, race, maternal smoking status, and other factors, bottle-feeding was associated with an increased risk for hypertrophic pyloric stenosis (odds ratio [OR], 2.31; 95% confidence interval, 1.81-2.95) compared with breast feeding. This effect was most pronounced in the children of older and multiparous mothers.[20, 21]

Infant and maternal use of macrolides also appears to increase the risk of infantile hypertrophic pyloric stenosis. In an analysis of 999,378 live-born Danish singletons from a nationwide, register-based cohort (1996-2011), Lund et al found that infantile HPS appeared to be associated with the use of macrolide antibiotics in young infants, pregnant women in late pregnancy, and early postpartum (≤2 wk) women.[22, 23] Because macrolide antibiotic treatment of young infants was strongly associated with infantile hypertrophic pyloric stenosis, the investigators cautioned to only administer these agents if the potential treatment benefits outweigh the risk.[22, 23]

Infants with severe vomiting can develop profound hypochloremia and hypokalemia. The classic biochemical abnormality in hypertrophic pyloric stenosis (HPS) is hypochloremic, hypokalemic metabolic alkalosis.

Ultrasonography has become the criterion standard imaging technique for diagnosing hypertrophic pyloric stenosis. It is reliable, highly sensitive, highly specific, and easily performed. An experienced ultrasonographer increases the test's predictive value. Necessary measurements include pyloric muscle thickness and pyloric channel length. Muscle wall thickness 3 mm or greater and pyloric channel length 14 mm or greater are considered abnormal in infants younger than 30 days.

Barium upper GI (UGI) study is an effective means of diagnosing hypertrophic pyloric stenosis when ultrasonography is not diagnostic. It should demonstrate an elongated pylorus with antral indentation from the hypertrophied muscle. The UGI may demonstrate the "double track" sign when thin tracks of barium are compressed between thickened pyloric mucosa or the "shoulder" sign when barium collects in the dilated prepyloric antrum. After UGI barium study, irrigating and removing any residual barium from the stomach is advisable to avoid aspiration.

Although UGI endoscopy would demonstrate pyloric obstruction, physicians would find it difficult to differentiate accurately between hypertrophic pyloric stenosis and pylorospasm. Endoscopy is reserved for patients with atypical clinical signs when ultrasonography and UGI studies are nondiagnostic. Endoscopic dilatation has rarely been used as a method of treatment. This treatment is not standard for hypertrophic pyloric stenosis; endoscopy should be used rarely, if ever.

Surgical repair of hypertrophic pyloric stenosis (HPS) is fairly straightforward and without many complications, yet properly preparing the infant for this procedure is vitally important. Most infants with hypertrophic pyloric stenosis do not have complete gastric outlet obstruction and can tolerate their inherent gastric secretions.

Repeated episodes of vomiting following attempts to feed the infant cause progressive dehydration and loss of hydrogen chloride from the gastric juices. Preoperative management is directed at correcting the fluid deficiency and electrolyte imbalance. Base fluid resuscitation on the infant's degree of dehydration. Most infants can have their fluid status corrected within 24 hours; however, severely dehydrated children sometimes require several days for correction. If necessary, administer an initial fluid bolus of 10 mL/kg with lactated Ringer solution or 0.45 isotonic sodium chloride solution. Continue intravenous (IV) therapy at an initial rate of 1.25-2 times the normal maintenance rate until adequate fluid status is achieved.

Adequate amounts of both chloride and potassium are necessary to correct metabolic alkalosis. Unless renal insufficiency is a concern, initially add 2-4 mEq of KCL per 100 mL of IV fluid. Adequate chloride for resuscitation can usually be provided by 5% dextrose in 0.4% sodium chloride solution. Before induction of anesthesia, aspirate the infant's stomach with a large-caliber suction tube to remove any residual gastric fluid or barium. Saline irrigation is occasionally necessary to remove a large quantity of barium.

Pyloromyotomy remains the standard of treatment, and outcome is excellent.[24] The best surgical outcome and lowest complications are more likely when the surgeon has specialist pediatric surgical training.

Ramstedt pyloromyotomy remains the standard procedure of choice for hypertrophic pyloric stenosis because it is easily performed and is associated with minimal complications. The usual approach is via a right upper quadrant transverse incision that splits the rectus muscle and fascia.

Some authorities report that laparoscopic pyloromyotomy has a significantly shorter recovery time compared with open pyloromyotomy but that open pyloromyotomy has higher efficacy and fewer complications. While complication rates were similar between the 2 groups, significantly superior long-term cosmetic results were noted in the laparoscopic group.[25] A systematic review of 502 patients echoed these results, finding laparoscopic pyloromyotomy does not lead to significant postoperative complications compared to open pyloromyotomy.[26]

Endoscopic pyloromyotomy is a simple procedure and can be performed as an outpatient procedure. Recently, endoscopic balloon dilatation of hypertrophic pyloric stenosis after failed pyloromyotomy has been used with greater frequency. Several other approaches have been described. A supraumbilical curvilinear approach has gained popularity with good cosmetic results.

Postoperative management

Continue IV maintenance fluid until the infant is able to tolerate enteral feedings. In most instances, feedings can begin within 8 hours following surgery. Graded feedings can usually be initiated every 3 hours, starting with Pedialyte and progressing to full-strength formula.

Addition of a histamine 2 (H2) receptor blocker sometimes can be beneficial.

Treat persistent vomiting expectantly because it usually resolves within 1-2 days.

Avoid the temptation to repeat ultrasonography or UGI barium study; these invariably demonstrate a deformed pylorus and results are difficult to interpret.

Early consultation with a surgeon familiar with neonatal care is warranted because treatment is essentially surgical. Early consults facilitate decisions for diagnostic studies, fluid resuscitation, and scheduling the operative procedure. This is especially important if the child requires transfer to another facility for surgical care. The American Pediatric Surgical Association offers guidelines for appropriate consultation and transfer of small infants. Good outcome has been shown to depend on the quality of preoperative correction of fluid and electrolyte abnormalities, availability of a pediatric anesthetist, and training level of the surgeon.

Feedings are usually resumed 6-8 hours after operation.[27] In most instances, gradually increasing the volume and strength of feedings is recommended (see Surgical Care).

Medication is not currently a component of care in hypertrophic pyloric stenosis (HPS). See Treatment.

Infants generally recover rapidly after operative correction of hypertrophic pyloric stenosis. Advise parents to increase food volume in the days after discharge. A single postoperative visit 1-2 weeks after surgery is often all that is necessary to document weight gain. Long-term sequelae from pyloromyotomy are virtually unheard of. Studies have documented normal function returns in months to years after surgery.

Infants can be discharged from hospital care once they can remain hydrated and have adequate enteral intake.

Postoperative analgesics are used as with any other surgical patient. Once oral intake has resumed, acetaminophen usually suffices.

The following complications are noted:

• Undetected mucosal perforation: Perform a diligent search for mucosal transgressions at the time of operation and examine the infant again before initiating feedings. In those rare cases where a perforation was not detected, the infant develops fever, tenderness in the abdomen, and abdominal distention. Return to the operating room if perforation is suspected.

• Bleeding: In most instances, venous oozing from the myotomy site is self-limited and is not a concern in the postoperative period. Reports of continued bleeding are exceedingly rare but can occur, especially in children with undetected coagulopathy.

• Persistent vomiting: Incomplete pyloromyotomy is rare in the hands of an experienced pediatric surgeon and usually presents as persistent vomiting until after the second week postsurgery. This problem is confounded when repeat studies performed after surgery provide a confusing picture. Patient observation resolves the problem in most cases.