The editors and current author thank and acknowledge the significant contribution of Dr. Kevin Higashigawa, the previous author of this chapter from the 2004 first edition. This current third edition chapter is a revision and update of the original author’s work.

A 4 week old previously healthy term male is brought to the emergency department with a chief complaint of vomiting, starting 5 days ago and occurs after he feeds. Initially his parents thought he was just "spitting up"; however, his vomiting progressively got worse, characterized by increased frequency and volume. Mom describes the vomit as "flying out of his mouth". The vomit is non-bloody and nonbilious. After vomiting, he still appears hungry, and there is no fever, cough, runny nose, or diarrhea. He has had less wet and stool diapers than before. There is no known contact with sick persons.

His past medical history is notable for being a term infant with an uncomplicated delivery. He is healthy without any chronic medical problems. He does not take any medications; however, when he was 1 week old, he was prescribed a course of azithromycin because of exposure to a family member with pertussis. His family history is significant for a maternal cousin who had surgery as a young infant for pyloric stenosis.

Exam: VS T37.1, HR 172, RR 50, BP 82/40, oxygen saturation 99% in room air. Height is 54 cm (50th percentile), weight is 3.6 kg (25th percentile), and head circumference is 37 cm (50th percentile). He fussy but consolable and is in no acute distress. HEENT exam is notable for a sunken fontanelle and tacky mucous membranes. His neck is supple. His heart exam is notable for tachycardia with regular rhythm and normal S1 and S2, and no murmurs. His capillary refill is about 3 seconds. His lungs are clear to auscultation bilaterally. His abdomen exam has active bowel sounds, is soft, nontender, no hepatosplenomegaly, and no masses are palpated, including olive shaped ones. His genitalia are normal, and no inguinal masses palpated.

His laboratory studies show a normal CBC. His electrolytes are remarkable for a Na of 134, K 3.1, Chloride 95 and Bicarb of 30. His total bilirubin is 9 with direct portion of 0.3. An abdominal X-ray shows a nonspecific bowel gas pattern. An ultrasound study confirms the diagnosis of pyloric stenosis and after correction of his metabolic alkalosis, he is taken to the OR for a pyloromyotomy without complications.

Hypertrophic pyloric stenosis (HPS) occurs when the pyloric sphincter is enlarged causing a narrowing of the pyloric canal and thereby causes a partial gastric obstruction. HPS is a common cause of GI obstruction in the young infant and can be seen in about 0.2% to 0.4% of children (1). HPS is approximately 4 to 6 times more common in males (in particular first-born males), than females (2). Although HPS does not follow classic Mendelian genetics, a familial pattern exists such that roughly 17% of infants with HPS have had a family history of HPS (3). 20% of infants with HPS have been found to have a coexisting congenital abnormality, such as a cardiovascular, gastrointestinal, or central nervous system anomaly (3). There is also some association between HPS and syndromes such as Apert syndrome, Zellweger syndrome, trisomy 18, Smith-Lemli-Opitz syndrome, Cornelia de Lange syndrome, and eosinophilic gastroenteritis (2).

The exact etiology of HPS is still unknown but there are genetic and environmental factors that have been associated with HPS. Infants treated with erythromycins, in particular in the first 2 weeks of life, have been shown to be at higher risk for HPS. Additionally, there is some evidence of higher incidence of HPS in babies of pregnant or breastfeeding women treated with macrolide antibiotics; however, this evidence is less clear (4). Other risk factors for HPS include prematurity, young maternal age, and maternal smoking (2).

Clinically, HPS presents with progressive nonbilious vomiting which does not occur until about the 3rd to the 8th week of life (1). HPS presents after several weeks of life because the pylorus is normal at birth and hypertrophies as time progresses (2). The hallmark of gastric outlet obstruction is non-bilious vomiting. The vomiting occurs immediately after feeding and varies in intensity, depending upon the degree of stenosis present. Eventually, the vomiting increases in severity to become projectile and will typically involve the entire volume of the feed. When obtaining a history, it is most useful to ask the parent how far the vomit will go from their baby’s mouth rather than asking them if their child has "projective vomiting", since nearly all vomiting appears to be "projectile" (forceful and intense). If the vomit is said to travel about an arm’s length that would be considered truly "projectile" and highly suspicious for HPS. After vomiting, the infant will remain hungry and want to feed again. Approximately 5% of patients will have some degree of hematemesis related to gastritis or esophagitis (3). Other presenting symptoms can include poor weight gain or weight loss and jaundice (3).

On physical exam, the infant may exhibit poor weight gain or even weight loss. Jaundice is observed in approximately 5% of infants (2). Traditionally, the diagnosis of HPS has been made after palpating the hypertrophied pylorus, also referred to as the palpable "olive" (2). This "olive" is described as a firm, mobile, olive shaped mass that is found to the right of the umbilicus beneath the liver edge. A palpable "olive" is pathognomonic of HPS, but it is very difficult to feel in practice. Additionally, studies have shown a decrease in HPS patients presenting with this palpable olive mass from >50% to 13%, likely secondary to earlier diagnoses of HPS (3). Another finding described in HPS is the gastric peristaltic wave that can be seen after feeding. It is a wave traversing the abdomen from left to right, representing intense contractions against an obstruction. Abdominal distention may be a late finding, as is usually the case with proximal GI obstructions.

The diagnostic test of choice is the ultrasound, which has approximately 95% sensitivity (2). Criteria for diagnosis include an elongated pyloric channel (longer than 15 to 19 mm), an enlarged pyloric diameter (greater than 10 to 14 mm), and a thickened muscle wall (greater than 3 to 4 mm) (1,2). Some have used the number pi (3.14) to help remember these numbers 3 and 14 mm. Point-of-care ultrasound (POCUS) in the emergency room setting has also shown to accurately diagnose HPS (5). If an ultrasound is non-diagnostic but clinical suspicion remains high, an upper gastrointestinal (GI) series may be helpful. On contrast studies, signs of HPS include a bulge of the pyloric muscle into the antrum, known as the "shoulder sign" and streaks of barium flowing through the stenosed channel, producing either a single "string sign" or a "double track sign" (if there are parallel streaks) (2). A "caterpillar sign" has also been described on plain films or upper GI of patient’s with HPS where the stomach appears dilated and air filled with undulating borders secondary to vigorous peristaltic gastric waves (6). This gives the appearance of a caterpillar.

The laboratory finding of HPS is a hypochloremic, hypokalemic metabolic alkalosis, related to the ongoing loss of HCl with persistent vomiting. The patient is likely dehydrated from repeated GI loss and poor oral intake. Due to more expedient diagnosis and treatment; however, fewer patients are presenting with electrolyte disturbances and one study showed 30% present with hypochloremia, 8% with metabolic alkalosis, and 7% with hypokalemia (3). An indirect hyperbilirubinemia can be seen in HPS in a small percentage of infants due to decreased levels of glucuronyl transferase when the liver is deprived of substrate from poor caloric intake.

The differential diagnosis of HPS is extensive; however, the classic hallmark of HPS is nonbilious vomiting. Nonbilious vomiting in a young infant can also be due to gastroesophageal reflux disease, gastroenteritis, metabolic disorders, adrenal insufficiency, or rarer abnormalities of the pyloric anatomy including pyloric membrane or pyloric duplication.

Management of HPS initially consists of fluid replacement and management of electrolyte abnormalities to stabilize the patient. It is important to initially correct the metabolic alkalosis otherwise there is an increased risk of postoperative apnea due to decreased respiratory drive (1,2,3). The treatment of choice for HPS is pyloromyotomy. The mortality rate for pyloromyotomy is less than 0.5% and the laparoscopic technique has become the standard approach (1,2). Post-operative vomiting may occur secondary to edema of the pylorus at the incision site in up to 50% of patients (3). There is evidence that supports ad-libitum feeds for patients after surgery from pyloromyotomy (1). Atropine sulfate, which induces smooth muscle relaxation has potential to relax the hypertrophied pylorus. It has been shown to be successful in up to 80% in some studies and can be considered when surgical expertise is not available or for patients who are not good surgical candidates (2). The infant’s heart rate should be continuously monitored during atropine sulfate administration.

It’s interesting that a non-surgical treatment approach for HPS with atropine, IV fluids, parenteral nutrition, and/or enteral tube feedings that bypass the pylorus, can often be successful. Atropine might suppress gastrointestinal peristalsis, which potentially reduces pyloric muscular hypertrophy. This approach can avoid surgery, but it requires a prolonged hospitalization in the range of 2 to 6 weeks and there are some treatment failures that eventually require surgery. Pyloromyotomy results in a faster recovery, a shorter hospital stay, and less weight loss. The non-surgical approach might be favored in neonates with very high surgical risk or in parts of the world that lack the surgical skill to safely perform a pyloromyotomy (7).

Questions
1. What is the classic presentation of HPS?

2. How is HPS diagnosed?

3. What is the initial step in management?

4. Comment on whether HPS is a congenital condition.

5. A 5 week old infant presents with progressive, projectile, nonbilious vomiting. He has a palpable "olive" on exam. Which of the following laboratory findings best fit this patient?
   a. hyperchloremia, hyperkalemia, metabolic alkalosis
   b. hyperchloremia, hypokalemia, metabolic alkalosis
   c. hypochloremia, hypokalemia, metabolic acidosis
   d. hypochloremia, hypokalemia, metabolic alkalosis
   e. hypochloremia, hyperkalemia, metabolic alkalosis

References
1. Rich BS, Dolgin SE. Hypertrophic Pyloric Stenosis. Pediatr Rev. 2021;42(10):539-545.
2. Kilegman RM, St Geme JW, Blum NJ, Shah SS, Tasker RC, Wilson KM. Chapter 355. Pyloric Stenosis and Other Congenital Abnormalities of the Stomach. In: Behrman RE, St Geme JW, et al (eds). Nelson Textbook of Pediatrics, 21st edition. 2020, Elsevier, Philadelphia pp. 1946-1950.e1.
3. Galea R, Said E. Infantile Hypertrophic Pyloric Stenosis: An Epidemiological Review. Neonatal Netw. 2018;37(4):197-204. doi: 10.1891/0730-0832.37.4.197.
4. Abdellatif M, Ghozy S, Kamel MG, Elawady SS, Ghorab MME, Attia AW, Le Huyen TT, Duy DTV, Hirayama K, Huy NT. Association Between Exposure to Macrolides and the Development of Infantile Hypertrophic Pyloric Stenosis: A Systematic Review and Meta-analysis. Eur J Pediatr. 2019;178(3):301-314. doi: 10.1007/s00431-018-3287-7.
5. Park JS, Byun YH, Choi SJ, Lee JS, Ryu JM, Lee JY. Feasibility of Point-of-Care Ultrasound for Diagnosing Hypertrophic Pyloric Stenosis in the Emergency Department. Pediatr Emerg Care 2021;37(11):550-554.
6. Chen F, Cernigliaro J, Bhatt S. The Caterpillar Sign. Abdom Radiol. 2021;46:394–395. doi.org/10.1007/s00261-020-02611-6
7. Jobson M, Hall NJ. Contemporary management of pyloric stenosis. Sem Pediatr Surg. 2016;25:219-224. http://dx.doi.org/10.1053/j.sempedsurg.2016.05.004

Answers to questions
1. A 4 to 5 week old male infant who presents with progressive, nonbilious projectile vomiting. The vomiting occurs immediately after feeding, after which the infant is still hungry and wants to feed again. On physical exam, the infant may display signs of dehydration. Visible waves of peristalsis may be seen and an "olive" may be palpable.
2. An ultrasound is the diagnostic method of choice and has a 95% sensitivity to diagnose HPS. Point-of-care ultrasound can also be considered in the initial evaluation of patients with suspected HPS.
3. The initial step in management involves fluid resuscitation and correction of any metabolic abnormalities. HPS is not a surgical emergency, and any fluid deficits or alkalosis should be corrected prior to surgery to decrease anesthetic risks
4. HPS is sometimes called congenital hypertrophic pyloric stenosis, but symptoms aren’t present at birth. There seems to be a genetic predisposition and the pyloric hypertrophy must develop over time resulting in symptomatic HPS. Erythromycins increase the risk of HPS suggesting that HPS is an acquired condition. HPS can resolve without surgery suggesting that this is often a transient condition that does not necessarily require surgical correction. These clinical characteristics aren’t typical for a truly congenital condition.
5. d. If HPS is diagnosed early, there may be no electrolyte abnormalities. But if a patient presents later in their course after days of persistent vomiting, you may see a hypokalemic, hypochloremic metabolic alkalosis.