Infantile Hypertrophic Pyloric Stenosis 1

Transcription

1 Review Radiology Marta Hernanz-Schulman, MD Index terms: Infants, gastrointestinal tract Pylorus, stenosis, Radiography, in infants and children, Review Ultrasound (US), in infants and children, Published online before print /radiol Radiology 2003; 227: Abbreviations: IHPS infantile hypertrophic pyloric stenosis UGI upper gastrointestinal examination 1 From the Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, MCN D-1120, 21st Ave and Garland St, Nashville, TN Received August 6, 2001; revision requested September 25; revision received February 22, 2002; accepted March 14. Address correspondence to the author ( marta.schulman@vanderbilt.edu). RSNA, 2003 Infantile Hypertrophic Pyloric Stenosis 1 Infantile hypertrophic pyloric stenosis is a common condition affecting young infants; despite its frequency, it has been recognized only for a little over a century, and its etiology remains unknown. Nevertheless, understanding of the condition and of effective treatment have undergone a remarkable evolution in the 20th century, reducing the mortality rate from over 50% to nearly 0%. The lesion is characterized by gastric outlet obstruction and multiple anatomic abnormalities of the pyloric antrum. The antropyloric muscle is abnormally thickened and innervated, and the intervening lumen is obstructed by crowded and redundant mucosa. Recognition of the obstructive role of the mucosa led to discovery of effective surgical treatment. Accurate clinical diagnosis in patients in whom a thickened antropyloric muscle is not readily palpable can be difficult, resulting in delayed diagnosis and can lead to emaciation and electrolyte imbalance, making the patient a suboptimal surgical candidate. Current imaging techniques, particularly sonography, are noninvasive and accurate for identification of infantile hypertrophic pyloric stenosis. Successful imaging requires understanding of anatomic changes that occur in patients with this condition and plays an integral role in patient care. Accurate, rapid, noninvasive imaging techniques facilitate rapid referral of vomiting infants and prompt surgical treatment of more suitable surgical candidates. RSNA, 2003 The lyf so short, the craft so long to lerne Thassay so hard, so sharp the conquering. Chaucer (1) Infantile hypertrophic pyloric stenosis (IHPS) is a condition affecting young infants, in which the antropyloric portion of the stomach becomes abnormally thickened and manifests as obstruction to gastric emptying. Typically, infants with IHPS are clinically normal at birth; during the first few weeks of postnatal life, they develop nonbilious forceful vomiting described as projectile. Gastric outlet obstruction leads to emaciation and, if left untreated, may result in death. Surgical treatment is curative. The clinical diagnosis hinges on palpation of the thickened pylorus, or olive. Abdominal palpation is accurate but not always successful, depending on factors such as the experience of the examiner, the presence of gastric distention, and a calm infant. Although its etiology remains unknown, our understanding of the clinical manifestation and treatment of IHPS has undergone a remarkable evolution. In patients in whom clinical examination is unsuccessful, modern imaging techniques are highly accurate in facilitating the diagnosis. The radiologist, therefore, plays a key role in the initial care of these infants and the appropriate surgical referral. It is important that the radiologist understand the anatomic changes of the pyloric channel in affected infants as reflected by imaging techniques. The purposes of this review are to describe the imaging diagnosis of IHPS and to outline the gross and histopathologic correlates of IHPS within the context of its historical evolution and our current understanding of the lesion. HISTORICAL PERSPECTIVE IHPS is familiar to most pediatric practitioners and is the most common condition requiring surgery in infants (2). Despite its frequency among Western populations in the 319

2 northern hemisphere, it was virtually unknown prior to 1627, when a clinical description with survival was reported by Fabricious Hildanus (1). Over the subsequent 2 centuries, only approximately seven additional cases were described, some without pathologic proof and of doubtful origin (Table). At the German Pediatric Congress in Wiesbaden in 1887, Harald Hirschsprung (Fig 1) described two infant girls with pathologically proved IHPS, and his seminal article, published in 1888 (3), triggered a profusion of scientific interest in the condition. By 1910, approximately 2 decades later, 598 cases had been recognized. Nevertheless, even as late as 1905, its existence was still occasionally doubted (1). As we enter the 21st century, the etiology of the condition remains elusive, yet great strides have been made in the diagnosis and treatment of IHPS. Historical Perspective on Diagnosis of IHPS Practitioner and Year Fabricious Hildanus, 1627 Patrick Blair, 1717 Christopher Weber, 1758 George Armstrong, 1777 Hezikiah Beardsley, 1788 Michael Underwood, 1799 Thomas Williamson, 1841 Siemon-Dawosky, 1842 Harald Hirschprung, 1888 Various, 1910 Source. Reference 1. orifice and pyloric ring or sphincter. The pyloric orifice marks the opening of the stomach into the duodenum (Fig 2b). Description First reported clinical description with survival Postmortem description, with lack of omentum, which was believed to be related to cause of lesion Postmortem description Two cases, familial occurrence First account in United States: Child died at age 5 years; most likely a case of antral diaphragm Postmortem description Postmortem description Postmortem description includes hypertrophy of the submucous cellular tissue Rigorous description of two proved cases Descriptions of 598 cases EPIDEMIOLOGY The incidence of IHPS is approximately two to five per 1,000 births per year in most white populations, although it varies with the geographic area and the time period being reviewed (4,5). IHPS is less common in India and among black and Asian populations, with a frequency that is one-third to one-fifth that in the white population (6). The male-to-female ratio is approximately 4:1, with reported ratios ranging from 2.5:1 to 5.5:1 (7). There is a familial link, but a hereditary propensity to the development of IHPS is likely polygenic with no single locus accounting for a greater than fivefold increase in the risk to first-degree relatives (7). Male and female children of affected mothers carry a 20% and 7% risk of developing the condition, respectively, whereas male and female children of affected fathers carry a risk of 5% and 2.5%, respectively. Probandwise concordance in monozygotic twins is , and that in dizygotic twins is (8). ANATOMY Normal Anatomy The incisura angularis divides the stomach into a body to the left and a pyloric portion to the right. The sulcus intermedius further divides the pyloric portion of the stomach: the pyloric vestibule to the left, denoted by an outward convexity of the greater curvature, and the pyloric antrum or pyloric canal to the right (Fig 2a). The pyloric antrum is approximately 2.5 cm in length and terminates at the pyloric IHPS Anatomy In infants with IHPS, the pyloric ring is no longer identifiable as a clearly definable separation between the normally distensible pyloric antrum and the duodenal cap. Instead, a channel of variable length ( cm) corresponding to the pyloric canal separates the normally distensible portion of the antrum from the duodenal cap (Fig 3a). This channel is characterized by thickened muscle, which changes rather abruptly from the normal 1-mm thickness in the distensible portion of the antrum to 3 mm or more in the hypertrophied canal (12). The muscle thickness may be greater than 6 mm, with larger muscle usually being present in larger and older infants (12,13). The diameter of the canal lumen is variable, ranging between 3 and 6 mm; the canal lumen is filled with compressed and redundant mucosa, presenting an obstructed passage to the gastric contents (Fig 3b) (15). The rigid antropyloric canal is unable to accommodate the redundant mucosa, which protrudes into the gastric antrum. When viewed endoscopically, the mucosa protrudes as a nipplelike projection (Fig 3c) (16), likened to a cauliflower by DeBacker et al (17). CLINICAL PRESENTATION The clinical presentation varies with the length of symptoms. The infant presents with a recent onset of forceful nonbilious vomiting, typically described as projectile. The emesis consists of gastric contents, which may become blood tinged Figure 1. Harald Hirschsprung ( ). Dr Hirschsprung s postmortem description of two cases led to the recognition of IHPS by the scientific community and ushered in the interest and research leading to our modern understanding and treatment of the condition. (Reprinted, with permission, from reference 2.) with protracted vomiting, likely related to gastritis. Initially intermittent, the frequency of vomiting increases to follow all feedings. Since the child is unable to achieve adequate nutrition, he or she exhibits a voracious appetite despite distention of the stomach. Starvation can exacerbate diminished hepatic glucoronyl transferase activity, and indirect hyperbilirubinemia may be seen in 1% 2% of affected infants. Vomiting of gastric con- 320 Radiology May 2003 Hernanz-Schulman

3 Figure 2. (a) Schematic of gastric segmental anatomy. (Reprinted, with permission, from reference 9.) (b) Endoscopic photograph of open pyloric sphincter. Arrow open canal. (Reprinted, with permission, from reference 10.) Figure 3. (a) Illustration of pyloric antrum in IHPS. Note circumferentially thickened muscle (arrows). The lumen is shown as a narrowed canal, but the mucosa, which fills and obstructs the lumen, is not illustrated. (Reprinted, with permission, from reference 11.) (b) Close-up view of hypertrophied pylorus from specimen of infant dying of IHPS. Abnormally thickened antropyloric muscle stops abruptly at the duodenal cap (D) and antrum (A). Note thickened mucosa within opened canal lumen curving from the antrum into the pyloric channel (curved arrows) deep to muscle (M). (Reprinted, with permission, from reference 14.) (c) Endoscopic photograph of pyloric sphincter in a patient with IHPS. Note mucosa (M) protruding into normal antrum, occluding and obstructing the pyloric orifice. Compare with Figure 2b. (Reprinted, with permission, from reference 16.) tents leads to depletion of sodium, potassium, and hydrochloric acid, which results in hypochloremic alkalosis and sodium and potassium deficits. Renal mechanisms designed to maintain intravascular volume conserve sodium at the expense of hydrogen ions, leading to paradoxical aciduria. Weight loss may be extensive, and the infant may be below birth weight at the time of presentation to the radiologist. Volume 227 Number 2 Infantile Hypertrophic Pyloric Stenosis 321

4 Weight loss and dehydration coupled with an insatiable appetite lead to a characteristic facies, with a furrowed brow, wrinkled appearance, and prominent sucking pads, resembling an old man crying inconsolably and gnawing at his or her fist. In emaciated infants, the distended stomach may be identifiable in the hypochondrium, with active peristaltic activity visible through the thin abdominal wall (Fig 4). ETIOLOGIC CONSIDERATIONS Despite the frequency of IHPS, our current familiarity with the condition, and the success of modern surgical management, its etiology remains elusive. In the search for an etiologic condition or event, researchers have focused on findings associated with the condition, some of which seem foolish from our more sophisticated perspective. For example, in 1717 the lack of omentum noted at autopsy, which was likely a result of nutritional deprivation, led to a report that this might be related to the cause of the lesion. The identification of three of 11 cases as being children of physicians resulted in the condition being identified as a disease of the intellectual classes in In 1917, Palmer suggested a link to thymic hyperplasia (1,19), which he subsequently recanted. During the past decade, advanced techniques have been applied to examination of the hypertrophied muscle, with some interesting results. It has been found that, when compared with control specimens, the muscular layer is deficient in the quantity of nerve terminals (20), markers for nerve-supporting cells (Fig 5a) (21), peptide-containing nerve fibers (22,23), nitric oxide synthase activity (24), messenger RNA production for nitric oxide synthase (25), and interstitial cells of Cajal (26,27) and that it contains increased insulin-like and platelet-derived growth factors (Fig 5b) (2) and increased expression of insulin-like growth factor I messenger RNA (28). It is postulated that this abnormal innervation of the muscular layer leads to failure of relaxation of the pyloric muscle; increased synthesis of growth factors; and subsequent hypertrophy, hyperplasia, and obstruction (29). An increased incidence of IHPS in neonates receiving erythromycin has been reported (30). The reason for this remains unclear, although a prokinetic effect on gastric muscle contraction is postulated. Figure 4. Infant with IHPS. Note protruding rib cage and scaphoid abdomen through which the distended stomach and prominent peristaltic activity can be seen. (Reprinted, with permission, from reference 18.) Figure 5. (a) Photomicrographs show immunocytochemical localization of D7, a marker for peripheral Schwann cells, in pyloric muscle of a healthy patient (left) and of a patient with IHPS (right). Staining of myenteric plexus (large arrow) is similar in both; however, there is a striking reduction in the intramuscular nerve fibers (small arrows) in the patient with IHPS. cm circular muscle layer, lm longitudinal muscle layer. (Peroxidase technique; original magnification, 100.) (Reprinted, with permission, from reference 21.) (b) Photomicrographs show immunohistochemical peroxidase staining for platelet-derived growth factor receptor in a healthy patient (left) and in a patient with IHPS (right). The muscle of the healthy patient shows no evidence of immunoreactivity, whereas there is abundant staining in the muscle of the patient with IHPS. (Original magnification, 400.) (Reprinted, with permission, from reference 1.) 322 Radiology May 2003 Hernanz-Schulman

5 Figure 6. Longitudinal sonogram of the normal stomach, pyloric ring (cursors), and duodenum outlining the open pyloric ring in an infant without IHPS. The distance between cursors is 3.1 mm. A variable degree of thickening of the mucosa within the canal leading to obstruction of the lumen has also been described (15). The lumen of the canal is wider than the normal pyloric ring (Fig 6), but it is obstructed and filled with redundant mucosa. The mucosa filling the canal typically equals or exceeds the muscle thickness but at times may far exceed it (Fig 7). In histologic descriptions of the mucosa, submucosal edema and cellular infiltrates have been reported (15,31). Foveolar hyperplasia after administration of prostaglandins has been implicated in the development of this condition (32). The hypergastrinemia hypothesis proposes that an inherited increase in the number of parietal cells initiates a cycle of increased acid production, repeated pyloric contraction, and delayed gastric emptying (33). Development of IHPS after initiation of feedings, increased postprandial gastrin levels, markedly increased gastric acid secretion in infants with IHPS, and the induction of IHPS in puppies by means of pentagastrin infusion (34) support this hypothesis. However, which if any of these associated muscular and mucosal phenomena hold the key to initiation or development of the lesion remains uncertain. Certain intriguing characteristics of the development and resolution of IHPS Figure 7. Imaging-histopathologic correlation of exaggerated mucosal thickening that occurs in some infants with IHPS. Top left: Image from upper gastrointestinal tract examination (UGI) shows a markedly widened pyloric channel with intervening mucosal filling defect (arrows). Top right: Sonogram in same patient shows hypertrophied mucosa (straight arrows) measuring approximately 8 mm protruding into the gastric antrum (curved arrow). Arrowheads thickened pyloric muscle. (Reprinted, with permission, from reference 15.) Bottom: Histopathologic full-thickness biopsy specimen from another patient shows thickened, hypertrophied, and edematous mucosa (muc) and its relationship to the underlying hypertrophied musculature (MUS). (Reprinted, with permission, from reference 31.) likely hold a key to the etiologic event(s) in the initiation of IHPS. The condition is seldom present at birth, but rather the functional obstruction typically develops in the first 2 12 weeks of life. Sonographic evaluation indicates that the anatomy is also normal at birth (35). Relief of the obstruction by means of incision of the muscular layer leads to a relatively rapid involution of the muscle and return of the anatomy to normal. As early as 4 months after surgical treatment, assay results for nerve growth factor, interstitial cells of Cajal, and nitric oxide synthase have returned to normal levels, coincident with anatomic resolution of the lesion (27). Resuturing of the muscle does not relieve the obstruction and may result in surgical failure, as recognized by Ramstedt in If failure to relieve the obstruction does not result in death, the condition eventually resolves. On the other hand, bypassing the obstruction may result in persistence of the hypertrophied muscle for many years (36). Thus, it is difficult to postulate that the undeniable abnormalities of the muscular layer are congenital, given their rapid resolution after relief of obstruction and the absence of functional or anatomic abnormalities at birth. These facts suggest that an obstructing event at the gastric outlet may initiate a feedback cycle, resulting in obstruction that resolves once the obstruction is relieved and normal gastric activity resumes. At present, the etiologic events underlying the development of IHPS remain difficult to extricate from the multiplicity of associated findings. Further investigation is necessary to identify the pathophysiology of IHPS, which could result in prevention of the condition or identification of an effective nonsurgical treatment. Volume 227 Number 2 Infantile Hypertrophic Pyloric Stenosis 323

6 Figure 8. Fluoroscopic image from UGI in a patient with IHPS. Contrast material courses through the mucosal interstices of the canal, forming the double-track sign (large arrowheads), with an additional central channel along the distal portion (small arrowhead). Mass impression on the gastric antrum (arrow), best seen during peristaltic activity, is termed the shoulder sign. DIAGNOSIS Figure 9. Sonograms demonstrate transducer sweep from esophagus to pylorus in a patient with IHPS. Left: Transducer is placed transversely, below the xiphoid, allowing identification of the esophagus (E) anterior to the aorta (A) at the gastroesophageal junction. Middle: Transducer is swept in caudal direction to outline a distended, albeit gas-filled, stomach (S). Right: Gastroduodenal junction is shown bridged by the hypertrophied pylorus, with fluid-filled duodenal cap (arrow). In this case, the pyloric mucosa is of the same echogenicity as gastric contents, which could lead to a false impression of unimpeded gastric emptying. A antrum. The diagnosis of IHPS is initially suggested by the typical clinical presentation. Palpation of the hard muscle mass, or olive, is diagnostic but is often challenging and time consuming. In experienced hands and with adequate time and preparation, abdominal palpation can be successful in 85% 100% of infants (37). However, increased reliance on rapid and accurate imaging techniques has led to a decline in this rate. For example, in a study by Macdessi and Oates (38), palpation was successful in 87% of infants between 1974 and 1977 but in only 49% between 1988 and Further, this is not construed as being necessarily counterproductive, since the desired outcome is rapid and accurate diagnosis (39). Palpation requires a calm infant with relaxed abdominal musculature, which is a difficult accomplishment in these hungry babies. Sedation of infants has been suggested to facilitate the examination (18); given the ease of sonographic diagnosis, this does not seem indicated in a child who may vomit while sedated. The distended stomach may rise anterior to the pylorus, rendering the examination nondiagnostic unless the stomach is evacuated by means of nasogastric drainage. In cases in which physical examination is unsuccessful, other methods must be used to establish the diagnosis. Several techniques involving insertion of a nasogastric tube have been proposed over the years. In 1913, Ramstedt indicated that exploratory laparotomy was preferable to undue delay in surgery in infants in whom the diagnosis was uncertain (1). Hessa in 1912 and Howard in 1917 suggested insertion of a duodenal catheter to help determine the degree of gastric obstruction (1). Insertion of a nasogastric tube for assessment of the volume in the stomach is still occasionally advocated today (40). The roentgen ray was first applied to the diagnosis of IHPS in 1903 by Ibrahim, without success. Fluoroscopic techniques were proposed by Abram and Strauss in By 1942, however, Mack (1) reported that there is no universal agreement on the reliability of x-ray studies. Over the subsequent 4 decades, improvements in fluoroscopic equipment and greater familiarity of radiologists with the condition permitted the UGI ( barium meal ) to become widely used in cases in which palpation of the olive was unsuccessful at clinical examination. In 1977, Teele and Smith (41) published a report on five cases in which a correct diagnosis was rendered after using articulated-arm B-mode sonography; this initiated a proliferation of articles on the sonographic diagnosis of IHPS. These articles, coincident with the introduction of realtime capability and improvements in equipment resolution aimed at defining the measurements of the abnormal canal, generated controversy regarding normal and abnormal values and suggestions regarding various indices and signs to help establish the diagnosis (42 45). In 1988, the author of an editorial (46) suggested that the diagnosis should be made clinically by means of repeated attempts to palpate the olive, eschewing imaging techniques as time consuming and often inaccurate. Authors of subsequent publications (40,47,48) have addressed the issue of cost-effectiveness, suggesting that the use of sonography does not justify the cost, as compared with the cost of UGI. In 1994, De Backer et al (17) proposed endoscopy as the most expeditious and accurate method for the diagnosis of IHPS. CURRENT CONSIDERATIONS It is clear that for a diagnostic study to become the imaging modality of choice, it must be demonstrated to be, above all, accurate; further, the procedure should be noninvasive and should be able to be performed quickly so that results will be available immediately, without delay in diagnosis. The examination must allow unequivocal differentiation between normal 324 Radiology May 2003 Hernanz-Schulman

7 Figure 10. Sonograms demonstrate transducer sweep from esophagus to pylorus in a patient without IHPS. Left: The esophagus (E) is seen anterior to the aorta (A), allowing identification of the caudal gas-filled viscus to the left as the stomach (S). Right: Normal empty antrum (A) is seen adjacent to the duodenal cap (D). Figure 11. Sonograms in a patient with IHPS. (a) Longitudinal sonogram shows anterior thickened muscle (cursors). Double layer of crowded and redundant mucosa fills the channel and protrudes into fluid-filled antrum (arrow). D fluid-filled duodenal cap. (b) Cross-sectional sonogram shows circumferential muscular thickening (cursors) surrounding the central channel and filled with mucosa (M). and abnormal conditions. At present, there are two valid and successful methods for the imaging diagnosis of IHPS, the UGI and sonography. Technique and Imaging Findings UGI Studies Abnormal study. In patients with IHPS, there is failure of relaxation of the prepyloric antrum, typically described as elongation of the pyloric canal. The canal is outlined by a string of contrast material coursing through the mucosal interstices, termed the string sign; or by several linear tracts of contrast material separated by the intervening mucosa (Fig 8). The latter is termed the double-track sign. This sign demonstrates the intervening redundant mucosa outlined as a filling defect by the contrast material; it was reported as specific for IHPS by Haran et al in 1966 (49) and, therefore, may aid in differentiation from pylorospasm. Interestingly, the fact that the redundant mucosa in the canal is responsible for the filling defect between the channels of contrast material was not recognized by the authors in the illustration included in the original article. UGI is performed with the infant in the right anterior oblique position, to facilitate gastric emptying. The examination can be successfully accomplished with the child drinking from a bottle; these infants are usually very hungry and will drink with little effort. Insertion of a nasogastric tube is not necessary; however, emptying of an overdistended stomach may help to prevent vomiting, if needed. Fluoroscopic observations include vigorous active peristalsis resembling a caterpillar and coming to an abrupt stop at the pyloric antrum, outlining the external thickened muscle as an extrinsic impression, termed the shoulder sign. Luminal barium may be transiently trapped between the peristaltic wave and the muscle, and this is termed the tit sign. Eventual success of gastric peristaltic activity will propel contrast material through the pyloric mucosal interstices, with the appearance as either the string sign or the double-track sign, although at times more than one layer of contrast material may be appreciated in the mucosal filling defect (Fig 8). Normal study. On the normal study, the prepyloric antrum is widely distensible between normal peristaltic waves, and the thin pyloric ring can be seen bridging the prepyloric antrum and duodenal cap. Fluoroscopic observations are important, since antral peristalsis may transiently simulate an elongated and abnormal canal. Volume 227 Number 2 Infantile Hypertrophic Pyloric Stenosis 325

8 Sonography Figure 12. Longitudinal sonograms obtained within a few minutes of each other show peristaltic activity and changes in pyloric anatomy in a patient with IHPS. Note the shorter canal in image on left and subsequent elongation coincident with peristaltic activity in image on right. There is failure of relaxation of the pyloric channel, and persistent obliteration of the lumen. Also note that on the left image, the gastric contents and pyloric mucosa have similar echogenicity, falsely suggestive of unimpeded passage of gastric contents through the canal. A antrum, D duodenal cap, arrows outer muscular layer. Equipment. The examination should be performed with high-frequency transducers. We use a linear transducer operating between 6 and 10 MHz, adjusted to the size of the infant and the depth of the pylorus. Because the pylorus rises anteriorly with positioning of the patient, the transducer frequency may be adjusted for greater detail while achieving adequate penetration to the pyloric channel. A sector transducer may be helpful in certain cases, as discussed later. Abnormal study. Sonographic examination demonstrates the thickened prepyloric antrum bridging the duodenal bulb and distended stomach. In infants with IHPS, the stomach is distended to a variable degree. This gastric distention in a vomiting infant is the first sign available to the examiner that there is a gastric outlet obstruction. Positioning of the patient by using gravity allows the examination to proceed, with the focus on identifying the duodenal cap and its connection to the stomach. Because the variable gastric distension is likely to displace the gastroduodenal junction, the search for the pylorus may prove difficult. It is, therefore, best to begin at a specific site of constant location. We begin by placing the transducer transversely below the xiphoid process, identifying the esophagus as it enters the abdomen anterior to the aorta at the diaphragmatic crus. Caudal movement of the transducer allows identification of the gastric fundus, and continued caudal motion subsequently allows definition of the gastric body, antrum, and duodenal cap, regardless of displacement or position and whether or not IHPS is present (Figs 9, 10). If the stomach is filled with gas, placement of the patient in a right anterior oblique position permits fluid to gravitate to the antrum for adequate evaluation. On the other hand, if the stomach is markedly distended the duodenal cap may be displaced caudally and medially, rendering the pylorus extremely difficult to access. In such cases, if the patient is slowly moved toward the supine and even the left posterior oblique position, the pylorus will be able to rise anteriorly for optimal examination. Use of these simple gravity-aided maneuvers eliminates the need for placement of nasogastric tubes to evacuate the stomach or for additional drinking of fluid to further distend an already overtaxed system, thus markedly shortening the duration of the examination. Demonstration of the pylorus is achieved by identifying the duodenal cap, distended stomach, and intervening pyloric channel. In patients with IHPS, the muscle is hypertrophied to a variable degree, and the intervening mucosa is crowded, thickened to a variable degree, and protrudes into the distended portion of the antrum (the nipple sign; Fig 11a) (12,16,50) and can be seen filling the lumen on transverse sections (Fig 11b). The length of the hypertrophied canal is variable and may range from as little as 14 mm to more than 20 mm. The numeric value for the lower limit of muscle thickness has varied in reports in the literature, ranging between 3.0 and 4.5 mm. In our experience and in that of others (51), the actual numeric value is less important than the overall morphology of the canal and the real-time observations. The antropyloric canal, as part of the stomach, is a dynamic structure, and it is seen undergoing changes in both length and width during many examinations (Fig 12). The intervening mucosa can often be observed sliding within the canal, usually as a wave of gastric peristalsis washes over the hypertrophied channel. The unequivocal diagnosis of IHPS is made by identifying the hypertrophied pylorus; in these patients, the muscle thickness, although variable during the examination, will be 3 mm or more throughout the examination. The intervening lumen is filled with crowded and redundant mucosa, best seen on transverse sections or on longitudinal sections through the center of canal (Fig 13), and gastric peristaltic activity at all times fails to distend this preduodenal portion of the stomach. Normal study. A negative study hinges on an unequivocal diagnosis of a normal pyloric ring and a distensible antropyloric portion of the stomach, which rule out IHPS. The examination is similar to that described for an abnormal study, with identification of the esophagus, body, and antrum of the stomach and hence the duodenal bulb (Fig 10). The duodenal bulb is separated from the gastric antrum by the pyloric ring, and the appearance is analogous to that seen at a normal UGI (Fig 14). There is, therefore, no overlap between the length and dimensions of the normal pyloric ring and those of the abnormal hypertrophied 326 Radiology May 2003 Hernanz-Schulman

9 Figure 13. Longitudinal sonograms of hypertrophied pylorus in a patient with IHPS. Left: On image obtained off center, the maximum width of the canal lumen and intervening mucosa (arrowheads) cannot be identified. Right: Image obtained through the central portion of the canal outlines full diameter of channel (arrowheads). 11% have been reported (12). As with sonography, the experience and skill of the examiner are important to achieve the most accurate results (54). Sonography provides direct information on the anatomy of the pyloric canal; there is no need to wait for gastric contents to exit through the narrowed channel; therefore, the diagnosis can be made rapidly, without the need for the patient to drink additional contrast material and for the examiner to await gastric emptying. There is no radiation exposure. Use of gravity-aided maneuvers permits rapid examination in all infants, without manipulation of gastric contents. Identification of the pylorus, whether the study proves to be positive or negative and regardless of gastric distention, can be made rapidly by following the stomach from the gastroesophageal junction to the duodenal cap during one transverse sweep of the transducer. The examination can be performed accurately in a very short time with an accuracy approaching 100% (12). Sonography is operator dependent, and the learning curve is steep. However, once technical proficiency has been achieved, sonography is the most expedient diagnostic examination for this condition. Figure 14. Normal correlative anatomy. Sonogram (left), illustration (middle), and fluoroscopic image from UGI (right) show the normal pyloric ring (arrows) and the proximity of the duodenal cap (D) to the relaxed antropyloric portion of the stomach, bridged by the pyloric ring. See also Figure 2a. A antrum. (Middle image adapted and reprinted, with permission, from reference 52.) antropyloric canal. As in the UGI, realtime observations are important (53) since antral peristalsis may transiently simulate IHPS (Fig 15). Comments There are several options for evaluation of a vomiting infant. The first option is to perform a clinical examination. In a calm infant and with experienced hands, this is successful in the majority of cases, the findings are diagnostic of IHPS, and no further imaging is required. In patients in whom the olive is not readily palpable, however, maneuvers such as placement of nasogastric tubes to evacuate the stomach and sedation of the infant do not seem justifiable when noninvasive and successful diagnostic tools are available. Endoscopy has been advocated by some investigators (17) as a successful tool in the diagnosis of IHPS. Demonstration of the cauliflower- or nipplelike projection of the mucosa is characteristic in patients with IHPS (Fig 3c). However, the invasiveness and expense of this procedure do not seem to justify its use when other diagnostic methods are available. The UGI provides indirect information regarding the status of the antropyloric canal based on the morphology of the canal lumen as outlined by contrast material. Because of this fact, failure of relaxation of the antropyloric canal, also known as pylorospasm, may be difficult to differentiate from IHPS. The examination may be time consuming, particularly in infants with high-grade obstruction, because it necessitates awaiting the passage of contrast material through the obstructed canal. Fluoroscopy time and, therefore, radiation exposure may be prolonged. The reported sensitivity of UGI for the diagnosis of IHPS is approximately 95%, but error rates as high as Pitfalls Inability to visualize the pylorus. In patients with IHPS, the most common reason for inability to visualize the pylorus is gastric overdistention. As discussed earlier, this leads to displacement of the pylorus dorsally by the overdistended stomach. By following the course of the stomach from the esophagus and slowly turning the patient supine and toward the left, the pylorus can rise anteriorly. The junction of stomach and duodenum can then be identified, and the hypertrophied pylorus can be recognized. In patients without IHPS, an excessive amount of gas may be present distal to the stomach and may obscure the gastric antrum, particularly when the stomach is decompressed and overlaid by the transverse colon. In these patients, imaging with a sector transducer, with caudal angulation toward the stomach through the left lobe of the liver, allows access to the antroduodenal junction. Placement of the infant in the right side down position permits fluid in the stomach to enter the antrum and definition of the normal pyloric ring bridging the distensible antrum and duodenal cap. Borderline measurements. Thickening of the antropyloric canal may be a tran- Volume 227 Number 2 Infantile Hypertrophic Pyloric Stenosis 327

10 sient phenomenon due to peristaltic activity or to pylorospasm. Typically, in patients without IHPS the muscle does not measure more than 3 mm in thickness at any given point in time. Relaxation of the antropyloric canal is denoted by a change from the rigid linear morphology of the canal to areas of relaxation that permit pockets of fluid within the lumen. In some patients without IHPS, the stomach is empty and the antrum is collapsed. If documentation of an open distended antrum is desired, a small amount of fluid may be fed to these infants. Within a few minutes, the normal fluid-filled antrum can be documented (Fig 16). As is the case on UGI images, real-time observation for a few minutes usually clarifies the problem (53). Patients in whom the antropyloric canal relaxes to a normal morphology do not have IHPS. Patients in whom the muscle is 2 3 mm thick and does not relax throughout the examination warrant careful monitoring and follow-up examination, particularly if they are at the younger end of the age spectrum at the time of presentation (12,43). UGI in these patients will not help clarify the diagnosis further, and the results may erroneously suggest fully developed IHPS (12). At present, however, neither the cause nor the evolution of IHPS are known. It is, therefore, uncertain whether a young infant in whom the antropyloric canal fails to relax completely will go on to develop IHPS requiring surgery or whether these changes will be arrested and resolve without sequelae. In our experience (12) and that of others (43), these patients in whom measurements are equivocal form a small minority of infants at presentation, and the condition in few of them advances to fully developed IHPS. VOMITING INFANT: DIFFERENTIAL DIAGNOSIS AND IMAGING ALGORITHM Figure 15. Peristaltic changes in antropyloric anatomy on normal sonographic study. Left: Antropyloric channel is closed during peristaltic activity. Right: Distal antrum (A) is fully relaxed. Arrows pyloric ring, D duodenal cap. Figure 16. Sonogram of normal pylorus before (left) and after (right) ingestion of a small amount of fluid. Left: The stomach is empty. Note that the pyloric channel and stomach have a similar appearance and the anatomy of the pylorus is difficult to delineate. Right: The infant has been given a small amount of fluid to fill the stomach. Prepyloric antrum (A) distends normally and is immediately adjacent to the duodenal cap. D duodenum. Patients with bilious vomiting do not have IHPS and are not directed to an initial sonographic evaluation. UGI is the study of choice in a child with bilious vomiting. In patients with malrotation, inversion of the normal relationship of the superior mesenteric artery and vein may be observed at sonography. This finding is not constant, and, when encountered, UGI is necessary for confirmation of the diagnosis (55). Patients with nonbilious vomiting typically have IHPS or reflux. Other conditions that can manifest with nonbilious vomiting include pylorospasm, hiatal hernia, and preampullary duodenal stenosis. IHPS can be diagnosed or excluded by using sonography. Pylorospasm is more easily demonstrated with sonography than with UGI because of the ability with the former to detect and measure the muscle thickness (12). Hiatal hernia is uncommon in infants and can be detected easily at UGI (56). However, herniation of the gastric fundus can also be identified along the esophageal hiatus during sonography. Preampullary duodenal stenosis is rare among the population of infants with nonbilious vomiting. At sonography, a normal pyloric ring bridges the distensible antrum to a dilated duodenal cap. In these patients, UGI may be performed for confirmation of this diagnosis (Fig 17). Thus, infants presenting with nonbilious vomiting should be directed to undergo sonography if IHPS is a consid- 328 Radiology May 2003 Hernanz-Schulman

11 Figure 17. Preampullary duodenal stenosis. (a) Sonogram in vomiting infant demonstrates a distensible antropyloric canal (A). However, there is a consistent gas shadow to the right of the pyloric ring, resembling a very dilated duodenal cap (D). This led to suspicion of preampullary duodenal stenosis and referral for UGI. (b) Initial UGI image of stomach shows gas-filled dilated duodenum (D). (c) UGI image obtained with patient prone shows normal pylorus (arrow) and dilated proximal duodenum (D). Figure 18. Surgical photograph of Ramstedt pyloromyotomy. Thickened pyloric muscle has been divided, and forceps outlines the internal bulging mucosal lining. (Photograph courtesy of R. Cywes, MD.) eration. If the patient has IHPS, the appropriate surgical referral is made rapidly and accurately. If the sonogram delineates a normal pylorus, a search for other causes, as described above, may allow identification of preampullary duodenal stenosis or hiatal hernia. UGI may be performed if further evaluation for these conditions is warranted. UGI or scintigraphy can be performed to assess reflux if documentation is clinically needed prior to institution of appropriate therapy. TREATMENT The treatment of IHPS has undergone an impressive evolution punctuated by landmark surgical innovations and paralleled by remarkable decline in patient mortality. Nonsurgical treatment has been directed toward maintenance of adequate nutrition until the condition is overcome, manipulations directed at the pylorus, and pharmacologic agents. In 1627, Hildanus advocated nutrient enemas consisting of broth, egg yolk, and sugar. In the late 19th and early 20th centuries, enema solutes included breast milk and Ringer solution. In 1880, gastric lavage was advocated as the first standard treatment in infants with gastric dilatation ; lavage was believed to help by reducing gastric acidity. In 1901, irradiation of the thymus was advocated, with few adherents; in 1929, irradiation of the pylorus was recommended. Local applications of heat and various types of poultices were also attempted. Pharmacologic management was begun in 1904 and included administration of atropine, belladonna, opium, and cocaine. Thickened foods were also advocated by many, probably because of their success in the treatment of vomiting patients with severe reflux but who were unlikely to have had IHPS. Contemporary explanations for the success of this form of medical management included the belief that the hypertrophied stomach would more successfully propel the thickened food across the obstruction, that it was more difficult to vomit this material, and that it had a protective effect on the gastric mucosa (1). Surgical management was begun in Initial curative attempts consisted of gastroenterostomy, with the first survival reported in Lobker would admit the mother to the hospital and insist that she lie in bed with the lower part of her body uncovered, cradling the infant through the surgical and postoperative period. The initial surgical attempt directed at the pylorus itself was attempted by Nicoll and consisted of crude forceps dilatation of the lumen, accessed via a gastric incision, to burst up the thickened pyloric ring by forcible overstretching with a screwing motion with forceps (57). Although the initial operation performed in 1899 was successful, subsequent complications included hemorrhage and perforation. Pyloroplasty became the procedure of choice in the 1st decade of the 20th century and was applied by Dent, Heineke, Mikulicz, Nicoll, Fredet, and Weber, with variations on the theme of incising and resuturing the pyloric muscle (1). In 1911, Conrad Ramstedt performed his first operation for IHPS, and, having difficulty resuturing the muscle, did not complete the process. The operation was successful but not without a protracted course of continued vomiting. In his next patient, Ramstedt decided not to suture the muscle, because one gained the impression that the stenosis had not entirely been overcome, and that the mucosa, perhaps as a result of the transverse closure, was folded in the pylorus, causing additional obstruction (58). The Ramstedt procedure divides the hypertrophied muscle, leaving the intact mucosa bulging through the incision (Fig 18) and, whether performed via abdominal incision or at laparoscopy (59), remains the standard of surgical treatment today. Mortality for patients with IHPS re- Volume 227 Number 2 Infantile Hypertrophic Pyloric Stenosis 329

12 flects one of the great success stories in modern medicine. The mortality rate in patients undergoing gastroenterostomy was 53%; that for pyloroplasty was 40%. In the United States prior to 1904, the mortality rate was 100%. Within 10 years of the advent of the Ramstedt procedure, published mortality rates for this operation had decreased to 10%; this rate further diminished to 2% by 1931 and is well below that value today (1). These declining numbers are no doubt the result not only of a successful operation but also of increased acceptance of the operation by the medical community, leading to earlier surgical referral, and of earlier diagnosis with successful imaging techniques. In the initial years of experimental surgical treatment, medical management was not considered a failure until the child had lost over 30% of his or her body weight. The question was Should the child be saved by surgery or from surgery? (60). Today, IHPS is not considered to be a life-threatening disease. However, when discussing a mortality rate of 2%, Harold Mack (1) defined it as nothing short of a miracle. SUMMARY This discussion has focused on a review of the detailed anatomic changes that result in the development of IHPS within the historical perspective of the evolution of our understanding and treatment of the lesion. Particular emphasis has been placed on successful imaging techniques. Imaging findings have been correlated to the anatomic, histologic, endoscopic, and surgical anatomy. The recognition, diagnosis and treatment of IHPS has culminated in remarkable diagnostic and therapeutic success, in which radiologists have played an important role. Radiologists are in a unique position to observe the changes that occur in the antropyloric junction in vivo and to contribute to the eventual unraveling of the etiology of this complex entity. References 1. Mack H. A history of hypertrophic pyloric stenosis and its treatment. Bull Hist Med 1942; XII: Ohshiro K, Puri P. Increased insulin-like growth factor and platelet-derived growth factor system in the pyloric muscle in infantile hypertrophic pyloric stenosis. J Pediatr Surg 1998; 33: Hirschsprung H. Falle von angeborener pylorusstenose, beobachtet bei sauglingen. Jahrb der Kinderh 1888; 27: Applegate MS, Druschel CM. The epidemiology of infantile hypertrophic pyloric stenosis in New York State, 1983 to Arch Pediatr Adolesc Med 1995; 149: Jedd M, Melton JI, Griffin M, et al. Factors associated with infantile hypertrophic pyloric stenosis. Am J Dis Child 1988; 142: Schechter R, Torfs CP, Bateson TF. The epidemiology of infantile hypertrophic pyloric stenosis. Paediatr Perinat Epidemiol 1997; 11: Mitchell LE, Risch N. The genetics of infantile hypertrophic pyloric stenosis: a reanalysis. Am J Dis Child 1993; 147: Carter CO, Evans KA. Inheritance of congenital pyloric stenosis. J Med Genet 1969; 6: Gray H. The digestive system. In: Goss CM, ed. Anatomy of the human body. 29th ed. Philadelphia, Pa: Lea & Febiger, 1973; Tytgat G. Upper gastrointestinal endoscopy. In: Yamada T, ed. Atlas of gastroenterology. Philadelphia, Pa: Lippincott, Netter F. The digestive system, part I. Summit, NJ: Ciba-Geigy, Hernanz-Schulman M, Sells LL, Ambrosino MM, Heller RM, Stein SM, Neblett WW III. Hypertrophic pyloric stenosis in the infant without a palpable olive: accuracy of sonographic diagnosis. Radiology 1994; 193: McKeown T, MacMahon B, Record R. Size of tumor in infantile pyloric stenosis related to age at operation. Lancet 1951; 1: Kissane J. Stomach and duodenum. In: Pathology of infancy and childhood. St Louis, Mo: Mosby, 1975; Hernanz-Schulman M, Lowe LH, Johnson J, et al. In vivo visualization of pyloric mucosal hypertrophy in infants with hypertrophic pyloric stenosis: is there an etiologic role? AJR Am J Roentgenol 2001; 177: Hernanz-Schulman M, Dinauer P, Ambrosino MM, Polk DB, Neblett WW III. The antral nipple sign of pyloric mucosal prolapse: endoscopic correlation of a new sonographic observation in patients with pyloric stenosis. J Ultrasound Med 1995; 14: De Backer A, Bove T, Vandenplas Y, Peeters S, Deconinck P. Contribution of endoscopy to early diagnosis of hypertrophic pyloric stenosis. J Pediatr Gastroenterol Nutr 1994; 18: Wyllie R. Pyloric stenosis and other congenital anomalies of the stomach. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson textbook of pediatrics. 16th ed. Philadelphia, Pa: Saunders, Palmer D. Hyperplastic pyloric stenosis. Ann Surg 1917; 66: Okazaki T, Atsuyuki Y, Fijiwara T, Nishiye H, Fujimoto T, Miyano T. Abnormal distribution of nerve terminals in infantile hypertrophic pyloric stenosis. J Ped Surg 1994; 29: Kobayashi H, O Briain D, Puri P. Selective reduction in intramuscular nerve supporting cells in infantile hypertrophic pyloric stenosis. J Ped Surg 1994; 29: Malmfors G, Sundler F. Peptidergic innervation in infantile hypertrophic pyloric stenosis. J Pediatr Surg 1986; 21: Wattchow D, Cass D, Furness J, et al. Abnormalities of peptide-containing nerve fibers in infantile hypertrophic pyloric stenosis. Gastroenterology 1987; 92: Vanderwinden J, Mailleux P, Shiffmann S, Vanderhaeghen J, DeLaet M. Nitric oxide synthase activity in infantile hypertrophic pyloric stenosis. N Engl J Med 1992; 327: Kusafuka T, Puri P. Altered messenger RNA expression of the neuronal nitric oxide synthase gene in infantile hypertrophic pyloric stenosis. Pediatr Surg Int 1997; 12: Langer JC, Berezin I, Daniel EE. Hypertrophic pyloric stenosis: ultrastructural abnormalities of enteric nerves and the interstitial cells of Cajal. J Pediatr Surg 1995; 30: Vanderwinden JM, Liu H, De Laet MH, Vanderhaeghen JJ. Study of the interstitial cells of Cajal in infantile hypertrophic pyloric stenosis. Gastroenterology 1996; 111: [Erratum: Gastroenterology 1996; 111:1403.] 28. Ohshiro K, Puri P. Increased insulin-like growth factor-i mrna expression in pyloric muscle in infantile hypertrophic pyloric stenosis. Pediatr Surg Int 1998; 13: Oue T, Puri P. Smooth muscle cell hypertrophy versus hyperplasia in infantile hypertrophic pyloric stenosis. Pediatr Res 1999; 45: Honein MA, Paulozzi LJ, Himelright IM, et al. Infantile hypertrophic pyloric stenosis after pertussis prophylaxis with erythromycin: a case review and cohort study. Lancet 1999; 354: [Erratum: Lancet 2000; 355:758.] 31. Markowitz RI, Wolfson BJ, Huff DS, Capitanio MA. Infantile hypertrophic pyloric stenosis: congenital or acquired? J Clin Gastroenterol 1982; 4: Callahan MJ, McCauley RG, Patel H, Hijazi ZM. The development of hypertrophic pyloric stenosis in a patient with prostaglandin-induced foveolar hyperplasia. Pediatr Radiol 1999; 29: Rogers IM. The enigma of pyloric stenosis: some thoughts on the aetiology. Acta Paediatr 1997; 86: Dodge JA, Karim AA. Induction of pyloric hypertrophy by pentagastrin: an animal model for infantile hypertrophic pyloric stenosis. Gut 1976; 17: Rollins MD, Shields MD, Quinn RJ, Wooldridge MA. Pyloric stenosis: congenital or acquired? Arch Dis Child 1989; 64: Armitage G, Rhind J. The fate of the tumour in infantile hypertrophic pyloric stenosis. Br J Surg 1951; 39: Irish M, Pearl R, Caty M, Glick P. Pediatric surgery for the primary care pediatrician. I. The approach to common abdominal diagnoses in infants and children. Pediatr Clin North Am 1998; 45: Macdessi J, Oates R. Clinical diagnosis of pyloric stenosis: a declining art. BMJ 1993; 306: Chen E, Luks F, Gilchrist B, Wesselhoeft CJ, DeLuca F. Pyloric stenosis in the age of ultrasonography: fading skills, better patients? J Pediatr Surg 1996; 31: Radiology May 2003 Hernanz-Schulman