Infantile Hypertrophic Pyloric Stenosis #

Although a few isolated cases of infantile hypertrophic pyloric stenosis (IHPS) had been reported previously, Hirschsprung (l888) is generally regarded as the first author to have recognized it as a separate clinical entity. At that time the tendency was to designate the condition congenital hypertrophic pyloric stenosis. At present, the clinical features and management are well understood, and will not be recapitulated. It may be useful to discuss the images seen during radiographic and ultrasonic examinations, especially in relation to anatomical factors, and to consider some of the theories regarding the etiology and pathogenesis.

Anatomical Localization and Radiographic Features #

Cunningham (1906) studied the morbid anatomical appearances in "a considerable number" of cases of IHPS, and found the muscular hypertrophy to be limited to the anatomical pyloric sphincteric cylinder, which includes the pyloric ring (Chap. 3). The affected area was almost 2.54 cm in length and had the look and feel of a hard, solid cylinder. It was sharply demarcated from the duodenum on its aboral, and from the pyloric vestibule on its oral side. In more severe cases the narrowing was greatest at the two ends, the cylinder in those cases assuming an oval or fusiform shape, somewhat like an olive. In all cases the musculature of the remainder of the stomach was normal. The relative extent to which each of the two muscular layers was involved in the hypertrophy was not the same in every case. While some observers believed that the circular musculature had undergone the greater degree of hypertrophy, Cunningham (1906) found that both layers were involved. Nevertheless the circular layer of the cylinder remained 3 to 4 times as thick as the longitudinal in his cases.

Forssell (l913) emphasized that muscular hypertrophy in cases of IHPS was localized to the canalis egestorius, i.e. the pyloric sphincteric cylinder of Cunningham (1906) (Chap. 3). The radiographic appearances of the contracted canalis in IHPS corresponded exactly to those of a maximal normal contraction of the pyloric sphincteric cylinder (Chap. 13); while the contraction was cyclical and of a fleeting nature in normal subjects, it was constant in IHPS. The muscular hypertrophy was associated with functional abnormalities of the closing mechanism of the canalis egestorius. The autoplastic movements of the mucous membrane were also involved (Chaps. 2, 13).

Meuwissen and Sloof (l932, l934) were the first to state that the purpose of the radiological examination was not to demonstrate the indirect features of the condition, such as gastric hyperperistalsis and retention, but to visualize the lesion itself, i.e. the contracted pyloric canal, in its longest dimension. The average length of the canal in normal infants was only 1.0 to 2.0 mm, while in the majority of cases of IHPS it was very long and narrow, ranging from 12.0 to 24.0 mm in length. In a minority of cases the range was from 3.0 to 11.0 mm. (Owing to magnification factors the actual length was about nine-tenths of that measured on the films). Radiologically the thin, permanently contracted canal, containing a single, central streak of barium in the lumen, resembled a string. These authors were the first to describe the "string sign" of IHPS, and also mentioned concave indentations of the distal stomach on either side of the string, caused by the bulging pyloric musculature, which became known as the "shoulder sign" (Fig. 23.1). There was complete absence of peristalsis in the contracted region. According to Meuwissen and Sloof (l932, l934) the contraction was largely due to spasm, with or without associated muscular hypertrophy.

Fig. 23.1 A-F. More common radiographic signs of infantile hypertrophic pyloric stenosis (after Astley, 1952). A Central "beak". B Beak with adjacent concave indentations (shoulder sign). C Beak, gap and cap. D String sign. E Longitudinal mucosal folds. F Concave indentation base of cap. Pyloric "tit" (arrow)

Frimann-Dahl (l935) reported 3 cases and showed that muscular hypertrophy was not limited to the pyloric ring, as was commonly thought, but that it was up to 20.0 mm in length and involved the entire canalis egestorius. In his cases the musculature of the canalis was hypertrophied and strongly contracted, whereas the ring itself showed little thickening.

Runström (l939), in a study of 107 cases of IHPS, described the main patho- anatomical finding as a tumor as hard as cartilage, 2.0 to 3.0 cm in length and 1.5 cm thick, involving the muscular part of the stomach which had been designated the canalis egestorius by Forssell (l913); the muscular hypertrophy was not localized to the pyloric sphincter (i.e. the pyloric ring), but involved the entire canalis. Radiologically the contracted canalis presented as a tube with a narrow lumen 2.0 to 3.0 cm in length, completely lacking in "peristaltic motility". In contrast, the remainder of the stomach showed increased peristalsis, which invariably stopped at the oral end of the constriction. In addition a change occurred in the autoplastic movements of the mucosa, with mucosal folds filling the narrow passage in the contracted canalis; these factors resulted in a delay in gastric emptying.

Torgersen's (l942) microscopic sections showed that muscular hypertrophy in IHPS involved the two sphincteric loops together with the intervening fibres, i.e. the entire canalis egestorius. As the musculature of the remainder of the stomach was normal, he concluded that it was a pathological process limited to the canalis. Hypertrophy of the muscular wall with resultant narrowing of the lumen gave rise to the radiological picture of a permanently contracted pyloric canal. Torgersen (l942) agreed with Forssell (l913) that the radiological appearance of IHPS conformed to that seen in a maximal or near maximal contraction of the normal canalis. Contraction of the circular fibres of the muscularis externa produced narrowing of the lumen, and contraction of the longitudinal fibres produced shortening; the exact picture seen would depend on which of the two forms of contraction had gained supremacy.

Astley (l952) reiterated that in IHPS the prepyloric portion of the stomach was constantly narrowed and devoid of peristalsis. Radiologically this might present in a number of ways (Fig. 23.1). In some infants in whom no gastric emptying occurred for a considerable time, the distended stomach was seen to end in a small triangular projection or "antral beak". On either side of the beak a concave indentation occurred in the distal stomach due to the bulging pyloric musculature. Whem emptying did take place, the narrowed channel might present as a hair-line of barium, or as 2 or 3 parallel lines (crowded mucosal folds), or as a canal with a width of up to 3.0 mm. The canal was often slightly curved (concave upwards) and its length could vary between 8.0 and 30.0 mm. A concave indentation of the base of the duodenal bulb, again caused by the bulging pyloric muscle mass, might be present, resulting in a mushroom or umbrella-like appearance of the bulb. Incomplete filling of the stenotic area appeared as a gap between the "beak" and the cap.

According to Astley (l952) the following conditions could mimic the radiographic appearances of IHPS, and should be considered in the differential diagnosis:

1. A stage in the normal, cyclical contraction of the region. Referring to Forssell (l913), he mentioned that a maximal normal contraction of the canalis egestorius (Chap. 13) might simulate the contraction of IHPS. While the former is of a fleeting nature, the latter is permanent.

2. Infantile pylorospasm. In a series of 10 vomiting babies Astley (l952) noted that the normal process of widening of the prepyloric channel to its full calibre was considerably delayed in these cases. The narrowing persisted for 10 minutes to over an hour and simulated IHPS. However, continued observation showed that the segment was neither constantly narrowed nor devoid of peristalsis as it was in IHPS. After an interval gradual, or at times a more sudden relaxation occurred. The features were due to pylorospasm (Chap. 20) and were sometimes erroneously diagnosed as IHPS.

3. Gastric inactivity, i.e. failure of barium to leave the stomach due to absence of peristalsis. The retention could simulate that occurring in IHPS.

Shopfner (l964) described an additional radiological sign of IHPS, namely the pyloric tit. This consisted of a sharp projection from the lesser curvature of the filled part of the stomach at the oral end of the constriction (Fig. 23.1). The tit was also seen in 2 cases of pylorospasm, and had exactly the same appearance as in IHPS, but disappeared when the spasm relaxed. The narrowing of pylorospasm resembled IHPS but disappeared within 5 to 10 minutes, enabling a differentiation to be made between the two conditions.

Not all the radiological signs occur in every case. In 14 proved cases of IHPS Haran et al (l966) noted the string sign in 11, the beak sign in 11, the tit sign in 6 and the shoulder sign in 5. These authors also described the doubletrack sign, consisting of 2 parallel linear streaks of barium with an interposed radiolucent band in the constricted channel. (Comment: The sign seems to be similar to one previously described by Astley in l952). While infantile pylorospasm might resemble IHPS radiologically, the "double-track" was not evident in their cases of spasm.

The radiographic features have been reviewed by Shuman et al. (l967), Haller and Cohen (l986) and others.

Swischuk et al. (l980, l989) pointed out that pylorospasm produced an "antral" deformity which was virtually indistinguishable from some forms of true IHPS. However, in spasm the configuration was less permanent, showing slight variations from time to time. The same authors described a number of cases of unusual, atypical or incomplete hypertrophy of the pyloric musculature, in which barium studies led to puzzling "antral" configurations, including funnel antrum, spiculated antrum, pyloric niche, and the lesser curve mass. The spiculated antrum was thought to be due to hypertrophied rings of circular muscularis externa, and the lesser curve mass to selective hypertrophy of the muscle torus (Chap. 25). With ultrasound and its ability to visualize the pyloric musculature directly, the diagnosis of IHPS in these cases left no room for doubt. The following cases illustrate some of the radiological features of IHPS:

Case Reports

Case 23.1. B.G., 21 day old male, was admitted for projectile vomiting. Radiographic examination showed almost total obstruction in the pyloric region with gastric distension. The obstruction presented as a sharp cut-off transverse to the long axis of the stomach, with a tiny central "beak" (Fig 23.2). These appearances are generally accepted to be indicative of IHPS, and in our view can be explained as follows: hypertrophy of the musculature of the pyloric sphincteric cylinder causes a mass which occludes the lumen, preventing its filling with barium (this has sometimes been referred to as "amputation of the antrum"). The tiny "beak" indicates filling of the commencement of the occluded pyloric canal. At operation the diagnosis of IHPS was confirmed.

Fig. 23.2. Case B.G. Sharp cut-off pyloric region causing obstruction. Presumed extent of pyloric muscular hypertrophy (straight arrows). Central "beak" (curved arrow)

Case 23.2. B.B., 28 day old male, had a history of post-feeds vomiting for the previous 2 weeks. Radiographic examination showed a severe, constant narrowing 2.0cm in length in the pyloric region of the stomach, causing obstruction. The narrowing was string-like in appearance and at its proximal end associated with concave indentations into the stomach (Fig. 23.3). The appearance is compatible with IHPS and can be explained as follows: hypertrophy of the musculature of the entire length of the pyloric sphincteric cylinder causes a pronounced narrowing of the lumen, which is permanent. Muscular hypertrophy surrounding the narrowed lumen indents the stomach, causing concave defects. The diagnosis of IHPS was confirmed at operation.

Fig. 23.3. Case B.B. String-like narrowing 2.0cm in length (arrows) due to pyloric muscular hypertrophy

Case 23.3. M.M., male aged 10 days, was admitted with a history of vomiting since birth. Radiographic examination initially showed total obstruction of the pyloric region ("amputation of the antrum") (Fig. 23.4A). After 15 minutes, barium filled the pyloric canal, which was permanently contracted and approximately 2.0 cm in length (Fig. 23.4B); two longitudinal mucosal folds were seen in the contracted canal. There was a concave indentation of the base of the duodenal bulb. The appearance is that of IHPS and can be explained as follows: muscular hypertrophy of the entire length of the pyloric sphincteric cylinder initially obstructs the lumen; somewhat later filling of the permanently formed pyloric canal occurs. Muscular hypertrophy surrounding the latter indents the base of the duodenal bulb. Ramstedt operation two days later confirmed IHPS.

A	B
Fig. 23.4. A Case M.M. Initial total obstruction pyloric region ("amputation of antrum"). Presumed extent of pyloric muscular hypertrophy (arrows). B Case M.M. Permanently formed pyloric canal, containing longitudinal mucosal folds, due to IHPS (arrows). Concave indentation base of duodenal bulb

Case 23.4. C.V., male aged 15 days, was admitted for projectile vomiting and dehydration. Radiographic examination showed a constant narrowing, 1.5 cm in length, in the pyloric region, with a concave indentation of the base of the duodenal bulb (Fig. 23.5). At times a small dilatation was seen in the centre of the narrowed canal. The appearance is indicative of IHPS and can be explained as follows: the entire length of the musculature of the pyloric sphincteric cylinder is hypertrophied, causing narrowing of the lumen and a permanently contracted pyloric canal, as well as a concave indentation of the base of the duodenal bulb. The dilatation in the centre of the narrowed canal is probably an outward bulge between the right and left pyloric loops. The diagnosis was confirmed at a Ramstedt operation a few days later.

Fig. 23.5. Case C.V. Permanently formed pyloric canal due to IHPS. Concave indentation base of bulb. Small central dilatation in canal

Anatomical Localization and Ultrasonic Features #

Using a grey-scale unit with a 5MHz nonfocused transducer, Teele and Smith (l977) first described the sonographic appearances in 5 babies with IHPS. By passing the transducer transversely over the right lateral abdominal wall at the level of the costal margin, the region of the pylorus was scanned through the liver; the hypertrophied pyloric musculature presented as a round or oval echolucent mass with a central stellate collection of echoes. The average antero-posterior diameter of each mass was 2.3 cm, with a range of 1.8 to 2.8 cm. They were unable to identify a similar soft tissue mass in normal babies. An echolucent mass could also be produced by the gastric "antrum" or duodenal bulb filled with fluid, and by the hepatic flexure of the colon filled with stool, but in those instances the appearance was evanescent and did not have the typical central collection of echoes seen in IHPS.

Subsequently, various authors determined the measurements of the pyloric mass in IHPS by direct viewing during ultrasonic examinations. Strauss et al. (l98l) examined 20 infants aged from 14 to 49 days with IHPS, initially using a static gray-scale B-scan and later a real-time unit with a 5 MHz focused transducer. The pylorus was considered to be abnormally thickened if it measured 1.5 cm or more in its ventral-dorsal diameter. (In surgically controlled cases the pyloric mass of IHPS measured approximately 1.5 cm in diameter). In 16 of the cases the mass measured from 1.5 cm to 3.0 cm. It presented as a round anechoic mass with a central collection of echoes. In addition the pyloric "canal" was seen to be elongated to 20 mm. Real-time scanning showed an absence of movement of gastric contents across the pyloric canal.

Blumhagen and Coombs (l98l) examined 23 proven cases of IHPS between the ages of 2 and 10 weeks, using a B-scanner with a 6.0 mm focused 7.5 MHz transducer. In all cases the hypoechoic single muscle layer was 4.0 mm thick or thicker. The thick hypoechoic ring in the pyloric region was the sole criterion by which IHPS was diagnosed. The fundamental advantage of ultrasonography over other methods of diagnosis was that it visualized the hypertrophied muscle directly. Occasionally a hypoechoic ring might be formed by the muscle layers of the normal "distal antrum" as seen on parasagittal sections near the midline, but in those cases the layer was less than 4.0 mm in thickness. A false positive sonograph might be obtained in pylorospasm, in which there was persistent contraction of the circular musculature of the "distal antrum" and pylorus, creating a cylindrical muscle mass. In those cases the muscle was also less than 4.0 mm in thickness. The length of the hypertrophied muscle in IHPS was found to be variable, with some patients having only a short segment of hypertrophy and others a more elliptical mass. In a larger series of cases Blumhagen and Noble (l983) followed the normal hypoechoic muscle layer of the proximal stomach distally to the gastric outlet. Where the thickness of the muscle layer of the distal antrum and pylorus was 4.0 mm or more, a confident diagnosis of IHPS could be made. (The thickness varied from 3.0 mm to 6.0 mm in IHPS, being approximately 4.5 mm in the majority of cases). It was stated that at sonography the hypertrophied antral and pyloric circular musculature formed a thick, rounded cylinder having the appearance of a hypoechoic ring in cross section, and an ellipse with an echogenic core in sections parallel to the long axis. The best safeguard against making a false positive sonographic diagnosis is to identify the continuity of the thickened pyloric muscular layer with that of the remainder of the stomach, and to measure its thickness, rather than to measure the diameter of the mass, as advocated by previous authors.

Khamapirad and Athey (l983) obtained transverse and longitudinal sonographic images in l8 babies between the ages of one and 6 weeks with IHPS. A constant finding was a hypoechoic mass greater than 1.0 cm in diameter and containing a round or stellate central echogenic area. (The diameter of the mass ranged from 1.2 cm to 2.2 cm, with an average of l.7 cm). This was considered to be one of the main criteria for the diagnosis, the other being the ability to demonstrate a continuation of the hypoechoic mass with the gastric "antrum".

Graif et al. (l984) considered previous sonographic measurements in IHPS to have been inconclusive, especially in borderline cases. In order to increase the diagnostic accuracy of the modality other parameters and features of the hypertrophied muscle were evaluated, using a high resolution real-time unit with a 10 MHz transducer. In 22 infants with IHPS between the ages of 2 and 10 weeks the following measurements were obtained (mean and standard deviations were given respectively): the transverse diameter of the pylorus was 13.4 ± 1.6mm, the single wall thickness 4.5 ± 0.9 mm, and the mean pyloric length was 84 percent longer than that of normals. It was noted that high resolution, high frequency real-time scanning also showed the pressure effects of the hypertrophied muscle on the adjacent "antrum" by direct vision, confirming the fact that the concave indentations were caused by the muscle mass. (Comment: In radiology hypertrophy of the muscular wall is inferred from the configuration of intraluminal barium).

Wilson and Vanhoutte (l984) held that the true pyloric muscle length was the most important criterion for the diagnosis of IHPS. This was obtained by rotating the transducer from a short axis image of the pylorus until a maximum long axis was produced. In 16 proven cases of IHPS the true pyloric muscle length ranged from 2.0 to 2.6 cm. In 17 normal controls the range varied from 12.0 mm to 15.0 mm. It was felt that measurements of the true pyloric muscle length approached more closely the established radiological criterion of an elongated pyloric muscle and that it defined the anatomic abnormality seen at surgery more clearly. It was concluded that a true pyloric muscle length of 2.0 cm or more was a reliable sonographic sign of IHPS.

Stunden et al. (l986) achieved 100 percent accuracy in the ultrasound diagnosis of IHPS in 112 cases. Criteria used included measurements of the pyloric diameter, muscle thickness, canal length, real-time observation of the function of the pylorus and gastric peristalsis. Statistics showed that canal length was the only factor which could discriminate precisely between a normal and an hypertrophied pylorus. The overall diameter of the ring in IHPS was usually more than 11.0 mm (normal 11.0 mm or less) and the thickness of the muscle layer in the wall more than 2.5 mm (normal less than 2.5 mm). The canal length in IHPS was more than 16mm (normal less than 15 mm). When viewing the hypertrophied pylorus in real-time, relaxation of the canal did not occur, little fluid passed through it and gastric peristalsis was increased.

Carver et al. (l988) pointed out that in most of the previous publications where normal and abnormal ranges for length, breadth and muscle thickness were determined, there was often an overlap between the normal and abnormal ranges for all three measurements. By using a 7.5 MHz real-time sector scanner they estimated pyloric muscle volume and correlated this with body weight. In 21 babies with surgically confirmed IHPS, the pyloric muscle index was obtained by dividing the pyloric muscle volume in cubic centimeters by the body weight in kilograms. If this index was less than 0.4 the pylorus was normal, and if more than 0.4 the diagnosis of IHPS could be made with confidence.

In many instances Bowen (l988) was unable to identify the normal pyloric muscles with 5 MHz mechanical sector transducers; the normal pyloric muscle was much easier to demonstrate with computed sonography using a 5 MHz linear transducer. Normally pyloric dimensions might vary during real-time ultrasonic scanning, probably related to peristaltic contractions involving the pyloric muscle itself; the contracted gastric antrum might simulate an elongated pyloric channel of IHPS.

Pathogenesis and Etiology #

Meuwissen and Sloof (l932, l934) were of the opinion that the condition was entirely due to spasm of the pyloric muscle, causing a permanent contraction. This might or might not be associated with muscular hypertrophy.

Torgersen (l942) thought the simplest explanation would be that the circular musculature of the canalis egestorius had developed disproportionately strongly in comparison with the longitudinal musculature. During foetal life the circular musculature was laid down earlier and reached considerable thickness before the longitudinal layer was differentiated (Chap. 3). It seemed possible that regressive changes in the powerful circular musculature, which normally occurred at or near birth, had not taken place. Torgersen (l949) later also pointed out that the pyloric sulcus had an asymmetrical position in relation to the axis of the transverse part of the stomach, being closer to the angulus on the lesser curvature side. In IHPS genetic causes might lead to excessive asymmetry with consequent hypertrophy of the musculature of the canalis (i.e. the sphincteric cylinder).

Meeker and De Nicola (l948) described IHPS in a newborn infant; it had caused gastric outlet obstruction on the 2nd day of life and required operation on the 4th day. The etiology was unclear, and the question was whether muscular hypertrophy had preceded or followed pylorospasm. As the condition appeared to be congenital in their case, it was thought that it had occurred too early in life for spasm to have caused hypertrophy. By means of light microscopy Belding and Kernohan (l953) studied the myenteric plexuses and thickness of the muscle layers in normal controls, in 9 cases of IHPS and in 5 cases of adult hypertrophic pyloric stenosis (AHPS). In both IHPS and AHPS the number of myenteric ganglion cells and myenteric nerve fibre tracts per unit area of muscle tissue showed a real decrease in the pyloric region, while it remained quantitatively normal in the remainder of the stomach and in the duodenum. A constant finding was that the majority of myenteric ganglion cells in the pyloric region also showed degenerative changes, consisting of indistinct nuclear membranes, fragmentation or disintegration of the nucleolus, and disintegration of the cytoplasm with loss of cell membranes. Such changes were not present in the myenteric ganglion cells in the remainder of the stomach and in the duodenum, nor were they evident in normal controls. These pathological changes could be due to exhaustion caused by excessive vagal stimulation. According to these authors thickening of the muscularis externa in the normal stomach commences at a point just below the gastric incisura, extends to the pyloro-duodenal junction, and consists mainly of an increase in thickness of the circular musculature. In IHPS and AHPS the circular muscle of the pylorus was 2 to 4 times as thick as in normal controls, while it remained normal, or showed only a slight increase in thickness, in the remainder of the stomach and the duodenum. Microscopically the hypertrophied circular muscle of IHPS and AHPS had an irregular pattern with muscle fibres running in all directions, resembling a leiomyoma. The disorganization of muscle fibres was not evident in the stomach above the stenosed area and in the duodenum, neither was it seen in the normal stomach. It was unlikely that the ganglionic changes were secondary to the muscle hypertrophy and there appeared to be primary changes in both the myenteric ganglia and the musculature.

Carter and Powell (l954) recorded 12 examples of pyloric stenosis in parent and child, and drew attention to the increased risk of the disease in offspring of parents who were themselves affected. It was thought that genetic predisposition was a strong probability in the pathogenesis. However, environmental factors also had to be considered.

McKeown and MacMahon (l955) traced 112 adults who had been operated upon for IHPS in infancy. They had 29 children, none of whom exhibited pyloric stenosis. This and several other series examined by these authors, led them to conclude that a simple genetic hypothesis was unlikely. The condition could more plausibly be attributed to early postnatal environmental factors.

Friesen et al (l956) also using light microscopy, studied the myenteric nerve plexuses in normal controls and in l9 infants with IHPS. In the normal foetus at 12 weeks' gestation, the myenteric nerve layer of the pylorus appeared as an almost continuous layer of immature, completely undifferentiated nerve cells with little, if any segmentation into nests or plexuses. At 14 to 16 weeks there was a tendency towards elongated plexuses of cells which were still undifferentiated. At 26 weeks the myenteric layer showed organization into definite plexuses which contained, in addition to the undifferentiated cells, some cells with vesicular nuclei. Shortly after birth more mature cells appeared in the plexuses. Mature ganglion cells with abundant cytoplasm, prominent cell and nuclear membranes with nucleoli first appeared between the second and the fourth week after full-term gestation. The shift was toward differentiation so that recognizable mature ganglion cells were present in the normal pylorus from one to 5 months, with only a few undifferentiated cells being visible. In IHPS, at 4 to 8 weeks after birth, the plexuses contained no mature ganglion cells, having a cellular development similar to that of a normal pylorus several weeks earlier in age. It was concluded that failure of development or maturation of the ganglion cells was present, rather than degeneration of the cells as had been postulated by previous authors. The "degenerated" or "disintegrated" appearances previously described were probably cells which had never developed completely.

Roberts (l959) studied normal controls and biopsy specimens obtained at pyloromyotomy in 25 cases of IHPS. True hypertrophy of both longitudinal and circular muscle layers was evident, which he ascribed to overwork. The myenteric plexuses were examined for the quality and quantity of neural elements, i.e. nerve cells, supporting cells of Schwann and nerve fibrils. In IHPS the constituent cells had less cytoplasm and were more tightly packed than in normal controls, with fewer well-differentiated nerve cells in evidence. The size of ganglia tended to be smaller and the intervals between them greater than in normal specimens. The large continuous sheets of ganglia seen in the normal pylorus were absent, and it was concluded that there were quantitative as well as qualitative changes in the myenteric ganglia in IHPS.

Rintoul and Kirkman (l961) studied the morphological appearance of the myenteric ganglion cells and the structure of the nerve fibre tracts in biopsy specimens in 38 infants with IHPS. With silver staining two distinct ganglion cell types were recognized: (1) Type I Dogiel cells, showing a marked affinity for silver. While they were present in the control specimens, they were absent or virtually absent from the pyloric ganglia in cases of IHPS; this suggested that these cells were either congenitally absent, or that they had degenerated. (2) Type II Dogiel cells, which were less argentophylic. These were present and uniformly distributed throughout the myenteric ganglia in both the control and biopsy material. No clear evidence of degeneration of ganglion cells, such as had been described earlier, was found. However, it was admitted that early degenerative changes might not have been revealed by the silver staining process.

Friesen and Pearse (l963) studied the histological and histochemical features of the pyloric ganglion cells in biopsy material in 15 cases of IHPS; post-mortem studies were done in 2 additional cases. In IHPS the ganglion cells in the pylorus were not arranged in an evenly dispersed layer between the longitudinal and circular musculature. Cells were present in clumps within the thin longitudinal musculature, with infrequent extensions into the underlying circular layer. While numerous cells were present, few were large, mature cells, the majority being small and immature; these cells were enzymatically active and the histological appearances were not those of degenerated or dead cells. However, there was lack of mitochondrial and other oxidative enzymes characteristic of the mature cell. The features suggested arrest of the normal development of ganglion cells in the pyloric area. Mature ganglion cells containing numerous mitochondria were present in large numbers in the gastric wall above the pylorus in cases of IHPS, as well as in the pylorus in normal stomachs. The results supported the theory that motor acitivity such as pylorospasm preceded the development of hypertrophy of the pyloric circular musculature. According to Heinisch (l967) the etiology and pathogenesis of IHPS and AHPS remained obscure. Macroscopically and microscopically these conditions could not be differentiated from each other. As the pathological process was not limited to the pyloric ring, but also encompassed the immediate prepyloric area, Heinisch suggested that it should be termed "antrumhypertrophy" instead of pyloric hypertrophy. In his experimental work on rabbits, Heinisch attached glass spheres to the interior of the gastric fundus through a gastrostomy. This caused an "impairment of the functional unity" of the stomach; after 4 weeks a definite pyloric muscular thickening, which could not be distinguished from pyloric hypertrophy, occurred. Heinisch (l967) thought that the muscular hypertrophy was a compensatory mechanism due to the functional impairment of the proximal part of the stomach.

Smith (1970) noted that hypertrophic pyloric stenosis could occur in Chagas disease, in which myenteric plexus damage occurs. The general effect of this is loss of co-ordinated muscle contractions which propel the bolus analwards, leading to local hypertrophy and hyperplasia of smooth muscle.

Dodge (l970) found that pentagastrin injections of 3 pregnant bitches produced pyloric muscle hypertrophy and duodenal ulceration in some of the offspring.

Keet and Heydenrych (l97l) showed that electrical and mechanical stimulation of the vagal nerve trunks in the oesophageal hiatus of the diaphragm in canines, produced a temporary, tubular contraction of the pyloric sphincteric cylinder, approximately 3.0cm in length and exactly resembling hypertrophic pyloric stenosis. Increasing the stimulus caused the contraction to become firmer, until it became a rubbery hard cylinder simulating the "olive" of IHPS. It lasted as long as the stimulus was applied, while the remainder of the stomach remained flaccid. A similar result was obtained with mechanical stimulation (Chap. 32).

Dodge (l973), in a wide ranging review of the genetics of the condition, concluded that IHPS had a familial distribution but that this did not obey simple Mendelian laws. A single X-linked gene whose effects were greatly modified by other genetic and/or environmental factors would explain the increased risk to male relatives of female probands, but the excess of males with IHPS could not be accounted for by X-linkage, as male to male transmission occurred with greater frequency than expected. The most likely explanation for the distribution pattern was that multiple genetic and environmental factors, including a modifying effect of sex, operated together to produce IHPS. Female patients carried a heavier genetic load and were more likely to have affected male relatives. Suggested environmental factors were the maternal blood group, primogeniture, and the occurrence of stress shortly before birth.

Karim, Morrison and Parks (l974) administered daily pentagastrin injections to 12 bitches during the second half of pregnancy. Among 59 offspring 14 developed pyloric muscle hypertrophy, and 8 others pyloroduodenal ulcers. No muscle hypertrophy was seen in the controls.

Rogers et al. (l975) found no difference in circulating plasma gastrin levels in babies with and without IHPS, and concluded that gastrin stimulation was an unlikely cause of the muscle hypertrophy. An alternative hypothesis could be an abnormal response to intermittent milk feeding. This would release cholecystokinin and secretin from the duodenal mucosa, causing contraction, and ultimately hypertrophy, of the pylorus.

Dodge and Karim (l976) again found that pentagastrin administered to pregnant bitches produced typical pyloric muscular hypertrophy in some of their offspring. This occurred in 16 out of 56 puppies; some had duodenal ulceration. The findings indicated a variation in the response, with some pups showing no pathological changes while others were markedly affected. It suggested that individual inherent susceptibilities, such as genetic and environmental factors, were important determinants of the response.

In electron microscopic studies of the pyloric parasympathetic ganglia in IHPS, Jona (l978) found no abnormalities in the neurons and interstitial cells of the nerve plexuses; the maturation process of the ganglia proceeded normally. A small number of large axons, the significance of which was unclear, was present. While there was a marked increase in the overall thickness of the circular musculature, the individual muscle cells appeared normal. In view of the essentially normal morphology, Jona suggested that a "functional" etiology should be considered.

According to Swischuk (l980) evidence was accumulating to suggest that prolonged spasm or overactivity of the "antropyloric muscle" was the primary problem in infants with IHPS. It was probable that multiple causes of the muscular spasm could be operating.

While numerous factors had been proposed as the cause of IHPS, Haller and Cohen (l986) reiterated that the precise etiology remained uncertain.

Discussion #

In the radiological examination, here as elsewhere, only the barium suspension in the lumen is visible, and from the luminal appearances the alterations in the walls are inferred (Chap. 13). With ultrasonography the actual muscle mass causing narrowing of the lumen can usually be demonstrated. Consequently ultrasound has become the investigation of choice for suspected IHPS in many centers. Pilling (l983) discussed the relative sensitivity of radiology and ultrasound in the diagnosis. Of 26 cases with palpable pyloric tumors the mass was not detected by ultrasound in 2; in these cases, as well as in cases without palpable masses, an upper gastrointestinal radiological series was deemed necessary.

Pathogenesis #

In considering the pathogenesis, it should be noted that many authors held the view that the pyloric canal was elongated in IHPS (Shopfner l964; Shuman et al. l967; Teele and Smith l977; Strauss et al. l98l; Graif et al. l984; Stunden et al. l986; Bowen l988). The same was implied by Meuwissen and Sloof (l932, l934) and by Jenkinson (l955). While terminological uncertainties have to be taken into account, it is clear that in all these instances the "pyloric canal" was equated with the pyloric ring, which was considered to be the sphincter. Meuwissen and Sloof, for instance, stated that the average length of the pyloric canal was 1.0 to 2.0 mm in normal infants, which tallies with the width of the ring. According to these authors the essential factor in the pathogenesis was hypertrophy and elongation of the pyloric ring or "sphincter".

However, in dissections of morbid anatomical specimens of IHPS, Cunningham (l906) had shown previously that muscular hypertrophy involved the entire length of the sphincteric cylinder; it included, but was not limited to, the ring. Forssell (1913) and Torgersen (l942) showed convincingly that the musculature of the entire canalis egestorius (the sphincteric cylinder) was involved in the hypertrophy; the findings were subsequently confirmed by Frimann-Dahl (l935), Runstr"m (l939) and Astley (l952). Although he did not refer to the anatomical findings of Cunningham (l906), Forssell (l913) and Torgersen (l942), Heinisch (l967) noted that muscular hypertrophy was not confined to the pyloric ring but also involved the prepyloric region, which led him to suggest the term "antrumhypertrophy" for the condition. Analysis of our own cases also shows that the pyloric sphincteric cylinder in its entirety, is involved.

The premise that the pyloric canal is hypertrophied and elongated in IHPS (where "canal" is equated with the pyloric ring or sphincter), is difficult to accept. In view of the evidence quoted it appears much more likely that the entire pyloric sphincteric cylinder is involved in the hypertrophy, causing a permanently formed pyloric canal with concomitant motility disturbances. Normally the canal is a fleeting, physiological structure, being fully formed at the end of a maximal, cyclical contraction of the sphincteric cylinder (Chap. 13); in IHPS it is permanent, due to muscular hypertrophy of the entire cylinder.

In their investigations of IHPS many authors (Teele and Smith l977; Strauss et al. l98l; Blumhagen and Coombs l98l; Blumhagen and Noble l983; Khamapirad and Athey l983; Graif et al. l984) failed to consider the fundamental anatomical findings of Cunningham (l906), Forssell (l913) and Torgersen (l942); this may account for much of the uncertainty surrounding the pathogenesis.

Etiology #

In considering the etiology, it has to be pointed out that numerous theories have been formulated (some of which will be mentioned or recapitulated briefly). Most authors agree that the cause remains obscure. Freeman (l929) pointed out that the gizzard in graminivorous birds was situated in exactly the same location as the pyloric mass in IHPS. Normally in birds, food is mixed with gastric juice in the proventriculus or glandular stomach, and ground in the gizzard or muscular stomach. Similarly, in some higher mammals such as the coloured anteater, the gastric outlet is occupied by a heavy muscular mass in the same situation as the "tumor" in IHPS. It was thought that the condition could be of an atavistic nature, a reversion to a more primitive form.

According to Torgersen (l942, 1949) the most likely explanation was a genetic disturbance associated with excessive asymmetry; this could delay or impede regressive changes in the circular musculature of the sphincteric cylinder, normally occurring at or near birth.

Prolonged pylorospasm was suggested as a possible cause by Meeker and De Nicola (l948). A genetic defect was also postulated by Carter and Powell (l954) and by Rintoul and Kirkman (l96l). McKeown and MacMahon (l955) mentioned the possibility of environmental factors. Belding and Kernohan (l953) demonstrated degeneration of neurons in the myenteric ganglia of the affected region; Rintoul and Kirkman (l96l) were unable to substantiate these findings, but postulated an absence of argyrophilic Type I Dogiel cells from pyloric myenteric ganglia in IHPS.

Friesen et al. (l956) suggested delay in maturation of myenteric ganglion cells; this statement was questioned by Roberts (l959), as premature infants did not have an increased incidence of IHPS. Skoryna et al (l959) thought a congenital neuro-muscular dysfunction of the pyloric sphincteric cylinder could be responsible for both the infantile and adult forms. Friesen and Pearse (l963) found the ganglion cells in the affected region to be present in clumps and not arranged in evenly dispersed layers; many cells were small and immature, suggesting failure or arrest of normal development.

Heinisch (l967) produced hypertrophic pyloric stenosis in rabbits by suturing glass spheres to the interior of the fornix. Keet and Heydenrych (l97l) found that electrical and mechanical stimulation of the vagal trunks in the oesophageal hiatus of the diaphragm (in canines), produced temporary muscular contraction of the pyloric sphincteric cylinder, indistinguishable from IHPS.

Dodge (l970, l973, l976) as well as Karim et al. (l974) produced IHPS in some newborn pups by administration of pentagastrin to the mothers (other probands developed pyloroduodenal ulcers).

Rogers et al. (l975) and Moazam et al (l978) found no difference in plasma gastrin levels in infants with and without IHPS, concluding that gastrin stimulation was an unlikely cause of the muscular hypertrophy.

In view of the fact that the pyloric parasympathetic ganglia and individual muscle cells appeared normal at electron microscopy, Jona (l978) suggested a "functional" etiology. Swischuk (l980) thought that prolonged spasm of the "antropyloric muscle" (which could be due to a variety of causes) was the primary event.

Conclusion #

It has been shown that the pyloric sphincteric cylinder is a specialized muscular region of the stomach (Chap. 3), normally lined by pyloric mucosa (Chap. 5). In the vast majority of subjects its vagal supply occurs exclusively via the hepatic branch or branches (Chap. 8). Its motility is unique (as far as the stomach is concerned) in that it contracts cyclically in a "segmental" or "systolic", rather than a peristaltic way (Chap. 13). The contractions depend on and are triggered by underlying myoelectric activity (Chap. 16). In our view any one, or a combination of these factors, may have a bearing on the pathogenesis.

The contraction of the hypertrophied musculature in IHPS closely resembles a normal maximal or near-maximal contraction of the pyloric sphincteric cylinder (Chap. 13). In the former the contraction is permanent, in the latter of a fleeting nature, occurring in cycles with a frequency of approximately 3 per minute during active gastric emptying of solids. Normally when the cylinder is fully contracted, its lumen is obliterated by closely packed longitudinal mucosal folds; barium-filling of furrows between the folds may resemble lines or strings (Chap.13). A similar appearance of the mucosa is seen in IHPS, where barium-filling of longitudinal mucosal furrows in the hypertrophied and contracted cylinder gives rise to the "string sign" (Fig. 23.0). In a sense IHPS can be looked upon as the pathological counterpart of a maximal normal, physiological contraction of the sphincteric cylinder.

Radiologically and ultrasonically the narrowing of pylorospasm resembles that of IHPS in many respects (Meuwissen and Sloof l932; Torgersen l942; Astley l952; Shopfner l964; Haran et al. l966; Swischuk l980; Blumhagen and Coombs l98l; Bowen l988), showing that pylorospasm is not limited to the pyloric ring, but involves the entire pyloric sphincteric cylinder.

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