In infants with IHPS, the pyloric portion of the stomach becomes abnormally thickened, resulting in narrowing and elongation of the pyloric channel (Fig. 1). A gastric outlet obstruction is produced, with compensatory dilation, hypertrophy, and hyperperistalsis of the stomach. Most infants with IHPS present in the first 2 to 12 weeks of life with forceful or projectile nonbilious vomiting after feeding. The emesis may become blood-tinged because of gastritis. The timing of the presentation is likely related to increasing volumes of enteral feeding acting on abnormal pyloric tissue. Many infants with IHPS are initially believed to have a food allergy or gastroesophageal reflux [2,3]. The narrow window of diagnosis between approximately 2 and 12 weeks may be due to the introduction of enteral feeding, which acts on abnormal pyloric tissue.

Fig. 1 Congenital hypertrophic pyloric stenosis. Sonogram depicting thick-walled pylorus (arrow) in a longitudinal section (A) and cross section (B).

(Reprinted from Maheshwari P, Abograra A, Shamam O. Sonographic evaluation of gastrointestinal obstruction in infants: a pictorial essay. J Pediatr Surg 2009;44(10):2038; with permission.)

As reviewed by Panteli [4], the pyloric sphincter contracts tonically and phasically to effect gastric emptying. Sphincter function is controlled by a complex system involving the enteric nervous system, gastrointestinal hormones, and interstitial cells of Cajal. Abnormalities in hormonal control, extracellular matrix, smooth muscle fibers, growth factors, interstitial cells of Cajal, and pyloric innervations have been implicated in the pathogenesis of IHPS. The muscular layer of the pylorus in IHPS is reportedly characterized by abnormal distribution of nerve terminals [5], reduced intramuscular nerve supporting cells [6], altered peptidergic innervation [7], altered nitric oxide production [8], ultrastructural abnormalities of enteric nerves and the interstitial cells of Cajal [9], and increased insulin-like growth factor production [10]. This constellation of abnormalities leads to failure of the pyloric muscle to relax, increased synthesis of growth factors, and subsequent hypertrophy [11].

Traditionally, the diagnosis of IHPS was based on a history of projectile vomiting and palpation of the hypertrophied pyloric muscle, which is referred to as an olive because of its size and shape. This method, known as palpating the olive, has a 99% positive predictive value [12]. Positive test feeds can also be used diagnostically; however, this approach has unacceptably high false-positive and false-negative rates and is not used extensively [13,14]. Ultrasound imaging is usually used as a substitute or complement to physical examination or test feeds. Although imaging is more costly, it is highly sensitive, with accuracy and sensitivity approaching 100% [2,12,14]. Measurements of canal length and muscle thickness can support the ultrasonographic diagnosis [14].

The increasing reliance on imaging has resulted in diagnoses being made before alkalosis has developed, and in a shorter clinical course, less morbidity, and a shorter postoperative hospital stay [15]. Fluoroscopic upper gastrointestinal contrast studies can also be used for diagnosis, because the pyloric canal in IHPS is outlined by a string of contrast material. However, fluoroscopy is time consuming, involves radiation exposure, and its sensitivity is dependent on the skill of the examiner. Consequently, real-time ultrasonography has supplanted fluoroscopy as the diagnostic procedure of choice [2,3]. Although ultrasonography is the standard diagnostic procedure, the pylorus is difficult to visualize in patients with gastric overdistension because of displacement of the pyloric muscle dorsally by the gas-filled and fluid-filled stomach. This problem can usually be averted by turning the patient to a right lateral decubitus position, which causes the pylorus to rise to an anterior position, thus allowing it to be imaged [16]. Borderline cases can also be problematic, because the muscle typically does not measure more than 3 mm in thickness [16]. Repeating the ultrasound several days later may confirm the diagnosis [17]. Dehydration resulting from the protracted vomiting can also cause a spuriously low measurement of muscle thickness, which may increase after fluid resuscitation [18]. In borderline cases, it may also be helpful to visualize the relaxation of the pyloric canal following introduction of fluid into the stomach; this finding reliably excludes IHPS [16]. Although radiologists most often make the diagnosis, Copeland and colleagues [16] report that surgeons who have undergone focused training can diagnose the condition without confirmatory testing by a radiologist.

Despite the high specificity and sensitivity of diagnostic methods, the current guidelines may not be sufficient for accurate diagnosis of IHPS in infants younger than 3 weeks because of the thin pyloric muscle thickness [19] and equivocal clinical and biochemical variables [14]. Young infants should be observed and reevaluated in 1 to 2 days when the lesion may be more clinically or radiologically evident [20].

The vomiting associated with IHPS leads to depletion of sodium, potassium, and hydrochloric acid, resulting in hypokalemic, hypochloremic metabolic acidosis. Because IHPS is not a surgical emergency, fluid and electrolyte losses should be corrected before surgical intervention. This correction typically requires hospitalization and intravenous fluid replacement therapy [2,3].

The practice of evidence-based medicine requires physicians to review evidence to justify medical decisions and treatments. Although general pediatric surgeons perform a great variety of different operations, the number of surgeries performed is small relative to comparable procedures performed in adults. In addition, surgery has lagged behind other disciplines in the conduct of randomized clinical trials. As a result, the evidence base for many pediatric and neonatal surgical procedures is weak [21,22]. There is a paucity of randomized, controlled trials for IHPS treatment, and most are based on collaborations between pediatric surgical units, thus highlighting the importance of creating a network of centers that promote multicenter prospective studies [21].

Extramucosal longitudinal pyloromyotomy, first described in 1908 [23], has been the standard treatment of IHPS for decades. The pyloric muscle is split longitudinally, which allows the submucosal layer to bulge out to the level of the serosa. Most patients have excellent short-term and long-term outcomes, and mortality has been virtually eliminated with the use of appropriate fluid resuscitation, improvements in anesthesia, and a standard surgical approach. Muscle thickness returns to normal within 4 weeks, and is associated with healing of the pyloric muscle and return of function [3].

Laparoscopic pyloromyotomy (LP) was first described in 1990 [24], and it is increasingly the surgical treatment of choice as laparoscopic technology has improved. However, it remains controversial whether LP is superior to open pyloromyotomy. Sola and Neville [25] performed a systematic review and meta-analysis of laparoscopic versus open pyloromyotomy. Six prospective studies with 625 patients (303 laparoscopic, 322 open surgery) met selection criteria. Patients who underwent LP had lower total complication rates (odds ratio [OR] 0.58; 95% CI 0.35, 0.97), mostly because of fewer wound complications, shorter time to full feedings (mean difference −11.52 hours, 95% CI −12.77, −10.27) and shorter postoperative lengths of stay (mean difference −5.71 hours, 95% CI −8.90, −2.52). There were no significant differences in the rates of mucosal perforation, wound infection, postoperative emesis, or operating time. Incomplete pyloromyotomy occurred in 6 patients who underwent LP. As Hall and colleagues [21] point out, major complications such as incomplete pyloromyotomy are rare and individual studies are not powered to detect them. Thus, although rare complications are important, they may not pose a clinically significant risk for individual patients. Because LP is associated with shorter postoperative recovery period and duration of pain, it should be considered a valid technique as long as care and attention are paid to avoiding incomplete pyloromyotomy [21].

Although pyloromyotomy remains the first choice of treatment in Western countries, several investigators, mostly from Asian countries, have reported that some infants respond to intravenous or oral atropine without requiring surgery. The rationale for atropine therapy is that the pathophysiology of IHPS may be due, in part, to impaired function of acetylcholine and muscarinic receptors. Because atropine is an anticholinergic agent with strong antimuscarinic activity, it may decrease intestinal peristalsis by relaxing smooth muscles [26]. In studies conducted in Japan [27–30], Taiwan [31], and India [32], infants with IHPS were treated with intravenous or oral atropine sulfate daily until vomiting ceased, with higher doses given thereafter for varying periods of time. The investigators concluded that medical treatment is a safe and effective treatment option for IHPS, although approximately 10% of patients required pyloromyotomy and prolonged medical treatment was often needed. Meissner and colleagues [33] reported that atropine sulfate was successful in only 25 of 33 IHPS cases treated in Germany, and that clinical improvement was often not observed before the sixth or seventh day of treatment. Because of the persistent vomiting, nearly a quarter of families requested that their child be treated surgically before completing the 7 days of treatment. The investigators conclude that the 75% success rate does not favor atropine in view of the 95% success rate with surgical repair, and that the higher cure rates reported by other investigators were likely caused by prolonged medical therapy. Surgically treated patients are typically discharged within 24 hours of surgery, whereas medical treatment may require 7 days or more of skilled nursing and careful follow-up. Although the investigators conclude that atropine sulfate therapy should not be recommended where standard surgical procedure is available [33], Aspelund and Langer [2] believe it should be considered as an alternative in infants with contraindications to anesthesia or surgery.

The reported prevalence of IHPS has varied considerably by region and time. Although early case reports date from the eighteenth and nineteenth centuries, from the time of Hirschsprung’s initial report (1888) through the mid-twentieth century very few cases were examined in case series reports [34]. More recent reports have been varied both in prevalence estimates and trends over time. The most recent national report on prevalence of birth defects for 2003 to 2007 shows state-level prevalence of IHPS ranging by almost an order of magnitude, from 0.5 to 4.21 per 1000 live births (excluding states with clearly incomplete case ascertainment) [35].