Pathogenesis of congenital pyloric stenosis: histochemical analyses of pyloric ganglion cells.
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Humans↗
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Single-nucleotide promoter polymorphism alters transcription of neuronal nitric oxide synthase exon 1c in infantile hypertrophic pyloric stenosis.
Infantile hypertrophic pyloric stenosis (IHPS), characterized by enlarged pyloric musculature and gastric-outlet obstruction, is associated with altered expression of neuronal nitric oxide synthase (nNOS). Here we have studied molecular mechanisms by which nNOS gene expression is altered in pyloric tissues of 16 infants with IHPS and 9 controls. A significant decreased expression of total nNOS mRNA was found by quantitative RT-PCR in IHPS after normalization against GAPDH, which predominantly affected exon 1c with a reduction of 88% compared with controls (P < 0.001). After normalization against the neuronal-specific gene PGP9.5, expression of exon 1c was still decreased (P < 0.001), whereas expression of exon 1f was increased significantly (P = 0.001), indicating a compensatory up-regulation of this nNOS mRNA variant. DNA samples of 16 IHPS patients and 81 controls were analyzed for nNOS exon 1c promoter mutations and single-nucleotide polymorphism (SNP). Sequencing of the 5'-flanking region of exon 1c revealed mutations in 3 of 16 IHPS tissues, whereas 81 controls showed the wild-type sequence exclusively. Carriers of the A allele of a previously uncharacterized nNOS exon 1c promoter SNP (-84G --> A) had increased risk for development of IHPS (odds ratio, 8.0; 95% confidence interval, 2.5-25.6). Reporter gene assays revealed an unchanged promoter activity for mutations but a approximately 30% decrease for the -84A SNP (P < 0.001). In summary, our findings indicate that genetic alterations in the nNOS exon 1c regulatory region influence expression of the nNOS gene and may contribute to the pathogenesis of IHPS.
Base Sequence↗
Hyperkalemia and pyloric stenosis.
UNLABELLED: Children presenting with pyloric stenosis have hypochloremic metabolic alkalosis and their serum potassium levels are thought to be low or normal. We reviewed potassium levels in infants with pyloric stenosis. Thirty-six percent of patients with pyloric stenosis had increased serum potassium levels. We conclude that hyperkalemia may be more common in children with pyloric stenosis than previously thought. IMPLICATIONS: A significant number of infants with pyloric stenosis have a serum potassium value above the normal limit.
Anesthesia↗
Increased expression of transforming growth factor-alpha in infantile hypertrophic pyloric stenosis.
Infantile hypertrophic pyloric stenosis (IHPS) is characterized by hypertrophy of the pyloric muscle. The growth of smooth-muscle cells (SMCs) is regulated by several growth factors. Transforming growth factor-alpha (TGF-alpha) is a growth-regulatory peptide found in a wide range of embryonic and adult tissues. It has been recognized that TGF-alpha has growth-promoting effects in vascular and visceral SMCs. The aim of this study was to investigate whether TGF-alpha plays a role in the pyloric-muscle hypertrophy in IHPS. Full-thickness pyloric-muscle biopsy specimens were obtained at the time of pyloromyotomy from 10 IHPS patients (age range 24-76 days). Age-matched control material included 10 pyloric-muscle specimens taken at autopsy in patients without evidence of gastrointestinal disease. Indirect immunohistochemistry was performed using the ABC method with anti-TGF-alpha polyclonal antibody. In-situ hybridization was performed using a digoxigenin-labelled, TGF-alpha-specific oligonucleotide probe. There was a marked increase in TGF-alpha immunoreactivity and messenger RNA (mRNA) expression in SMCs in pyloric circular and longitudinal muscle in IHPS specimens compared to controls. The increased expression of TGF-alpha mRNA together with increased TGF-alpha immunoreactivity in IHPS suggests increased local synthesis of TGF-alpha by pyloric SMCs, causing pyloric-muscle hypertrophy.
Biopsy↗
Abnormalities of elastin and elastic fibers in infantile hypertrophic pyloric stenosis.
Infantile hypertrophic pyloric stenosis (IHPS) is characterized by hypertrophy of the pyloric muscle, causing pyloric-channel narrowing and elongation. The rigidity of the muscle is increased, which is characterized as an "olive." Elastin is an insoluble protein that forms the major structural component of the elastic fibers and maintains the tensile strength of the tissues. To understand the possible histologic and molecular basis of the elasticity of the hypertrophic muscle in IHPS, we determined the distribution of the elastic fibers and elastin expression using Victoria blue van Gieson (VVG) staining and immunohistochemistry. In IHPS, the number of elastic fibers in the connective tissue was significantly increased in the thickened connective-tissue septa (CTS) compared with normal control specimens. In normal pyloric muscle, weak to moderate elastin immunoreactivity was observed in the CTS while no immunoreactivity was observed among the muscle fibers. In IHPS, strong immunoreactivity of elastin was observed in the CTS and moderate immunoreactivity among the hypertrophic smooth-muscle fibers. Our findings suggest that the increase on elastic fibers and elastin expression in the pyloric muscle in IHPS may play an important role in the development of pyloric-muscle rigidity, causing pyloric-canal obstruction.
Elasticity↗
Smooth muscle cell hypertrophy versus hyperplasia in infantile hypertrophic pyloric stenosis.
Infantile hypertrophic pyloric stenosis (IHPS) is characterized by hypertrophy of the pyloric muscle. It is not clearly understood whether pyloric muscle enlargement is due to hypertrophy (increase in cell size) or hyperplasia (increase in cell number). In the present study, we investigated proliferative activity as well as size and number of smooth muscle cells to understand the mechanism of pyloric muscle enlargement in IHPS. Full thickness muscle biopsy specimens were obtained from 18 IHPS patients at pyloromyotomy and from 11 age-matched controls. Formalin-fixed paraffin sections were immunostained with MAb MIB-1, which stains cells in the proliferating phase of the cell cycle. The proliferative index (PI) was calculated as the percentage of positive cell nuclei. Smooth muscle cell number per bundle and cell size were measured with an image analyzer. The mean PI in IHPS (9.6 +/- 5.7%) was significantly higher than that of controls (1.3 +/- 1.2%) (p < 0.01). There was a significant inverse correlation between PI and age at operation. Smooth muscle cell number per bundle in IHPS (240.6 +/- 129.4) was significantly greater than that of the controls (134.1 +/- 49.8) (p < 0.05). Smooth muscle cell size in IHPS (298.5 +/- 59.0 microm2) was also significantly greater than that of controls (154.3 +/- 21.5 microm2) (p < 0.01). Our findings suggest that hypertrophy-and hyperplasia as well-play important roles in increasing pyloric smooth muscle mass in IHPS.
Case-Control Studies↗
Increased local synthesis of epidermal growth factors in infantile hypertrophic pyloric stenosis.
Infantile hypertrophic pyloric stenosis (IHPS) is characterized by hypertrophy of the pyloric muscle. The growth of smooth muscle cells is regulated by several growth factors. Epidermal growth factor (EGF) and heparin-binding EGF-like growth factor are potent mitogens for smooth muscle cells. In the present study, we investigated immunohistochemical localization of EGF and EGF-related peptides and EGF mRNA expression in pyloric smooth muscle cells to determine whether the EGF family is involved in the process of pyloric muscle hypertrophy in IHPS. Pyloric muscle biopsy specimens were obtained at the time of pyloromyotomy from 10 patients with IHPS. Control material included 10 pyloric muscle specimens taken at autopsy from age-matched cases without evidence of gastrointestinal disease. Indirect immunohistochemistry was performed using the avidin-biotin-peroxidase complex method with anti-EGF, anti-EGF receptor, and anti-heparin-binding EGF-like growth factor antibody. In situ hybridization was performed using digoxigenin-labeled EGF-specific oligonucleotide probe. The pattern of immunoreactivity in pyloric muscle with EGF, EGF receptor, and heparin-binding EGF-like growth factor was similar in all specimens. There was a marked increase in EGF, EGF receptor, and heparin-binding EGF-like growth factor immunoreactivity and EGF mRNA expression in smooth muscle cells in pyloric circular and longitudinal muscle from patients with IHPS compared with control specimens. These data suggest that the upregulated local synthesis of EGF and EGF-related peptides in pyloric muscle may play a critical role in the development of pyloric muscle hypertrophy in IHPS.
Biopsy↗
[Atypical infantile hypertrophic pyloric stenosis].
Infantile hypertrophic pyloric stenosis (IHPS) is the most common reason for nonbilious vomiting in infants. Its cause is unknown. Hypertrophy of pyloric muscle can progress after birth and reach complete gastric outlet obstruction. Usually symptoms start after the age of 3 weeks. In the past diagnosis was based on history of projectile, nonbilious vomiting and palpation of a pyloric mass. Greater awareness of IHPS and increased use of imaging modalities, mainly abdominal ultrasonography, have resulted in a change in the clinical condition at presentation. The length of illness before admission has decreased and weight loss, dehydration and metabolic abnormalities have become less common. We describe an atypical clinical manifestation of IHPS: bilious vomiting. This atypical presentation may be due to earlier diagnosis.
Humans↗
Ultrasonographic follow-up of the healing process of medically treated hypertrophic pyloric stenosis.
In hypertrophic pyloric stenosis (HPS), prompt pyloromyotomy is, in general, the treatment of choice. There has been no information available as to the natural history of the pyloric tumour. We present four infants with medically treated HPS who were followed by sonography to observe the anatomical changes that occur with atropine sulfate. The initial change was shortening of the pyloric canal, followed by thinning of the muscular layer as clinical symptoms improved.
Atropine↗
Increased insulin-like growth factor and platelet-derived growth factor system in the pyloric muscle in infantile hypertrophic pyloric stenosis.
BACKGROUND: Infantile hypertrophic pyloric stenosis (IHPS) is characterized by hypertrophy of the pyloric muscle. The etiology of IHPS is unknown. The growth of smooth muscle cells (SMC) is regulated by several growth factors. Insulin-like growth factor (IGF) and platelet-derived growth factor (PDGF) act synergistically to stimulate SMC proliferation. The effects of IGF-I and PDGF are mediated via their receptors. METHODS: Full-thickness muscle biopsy specimens were obtained from eight IHPS patients (age range, 14 to 46 days) at pyloromyotomy and from eight age-matched controls without gastrointestinal disease at autopsy performed within 4 hours after death. Indirect three-step immunohistochemistry was performed using anti-IGF-I, IGF-I receptor alpha (IGF-IR alpha), IGF-IR beta, PDGF-BB and PDGF receptor (PDGF-R) antibodies and visualized by peroxidase staining. RESULTS: The most striking difference between tissues from IHPS patients and controls was the marked increase in IGF-I, IGF-IR alpha, IGF-IR beta and PDGF-R in the hypertrophic circular muscle layer, and, to a lesser degree, in the longitudinal muscle in pyloric stenosis. CONCLUSION: The findings suggest that the upregulated local IGF and PDGF systems may play a role in the development of pyloric muscle hypertrophy in IHPS.
Becaplermin↗
Current management of infantile hypertrophic pyloric stenosis.
Infantile hypertrophic pyloric stenosis is a relatively common paediatric condition effectively cured by Ramstedt's pyloromyotomy. Nevertheless, published results demonstrate a residual perioperative morbidity indicating a need for improved management. While technological advances in diagnosis and treatment may contribute to this, attention to the details of perioperative care coupled with a meticulous surgical approach are likely to have a much greater impact.
Humans↗
[Clinical experience of infantile hypertrophic pyloric stenosis].
Infantile hypertrophic pyloric stenosis (IHPS) is a relatively common disease. We report our experience with 24 IHPS infants admitted to the Departments of Pediatrics and Pediatric Surgery of Chang Gung Memorial Hospital in Kaohsiung over 4 years, from 1986 to 1989. Analysis disclosed a high male to female ratio (11:1) and a heavy preponderance of firstborn male (46%). Fifty per cent of our cases had symptoms beginning between the ages of 2-4 weeks. The fact that 67% of the patients had duration of symptoms longer than 2 weeks prior to admission, with a mean interval of 25 days of progressive symptoms, represented that there was delay in diagnosis and treatment in most of our cases. The major clinical manifestations were projectile vomiting (100%), palpable pyloric mass (66.7%) and visible gastric peristaltic waves (41.7%). Of the 18 cases receiving plain supine abdominal roentgenogram, 17 (94.4%) demonstrated typical pictures. A gastric air outline extending below L2 vertebra is the most helpful criteria. Preoperative sonography suggested that the determination of pyloric muscle wall thickness predicted IHPS more accurately than that of pyloric muscle length. All 24 cases received Fredet-Ramstedt pyloromyotomy, with no mortality and short hospitalizations.
Female↗
Congenital hypertrophic pyloric stenosis.
Congenital hypertrophic pyloric stenosis, an important cause of intractable vomiting in infants is diagnosed clinically and confirmed ultrasonographically. Other useful interventions are plain radiography and barium study. Differential diagnosis includes pylorospasm and gastroesophageal reflux. Management protocol includes correction of dehydration and electrolyte imbalance and either Fredet Ramstedt pyloromyotomy or medical treatment with atropine sulphate. Atropine is initially given intravenously till vomiting is controlled and then orally at double the effective i.v. done for another 3 weeks. Atropine sulphate is generally well tolerated and side effects are few like tachycardia, raised SGPT and hyperthermia. Atropine sulphate is very effective, cheap, safe and perhaps more acceptable treatment option for CHPS.
Atropine↗
[Factors related to the olive size in patients with hypertrophic pyloric stenosis].
INTRODUCTION: The pyloric "olive" (PO) is the result of the anomalous growth of the pyloric muscle among patients with pyloric stenosis (PS). It frequently is unexpectedly large, or some other times surprisingly small, and those variations in size have been difficult to explain. MATERIALS AND METHODS: We measured the PO in 145 consecutive patients with PS during the operation, and then we classified them as small if their length was less than 20 mm, medium if 20 to 30 mm, or large if more than 30 mm; several variables were analyzed by mean of the chi square or Spearman rho tests. RESULTS: Six cases were excluded due to an unclear total length record of the PO. The PO size was classified as small in 19 (13.7%), medium in 71 (51%) and large in 49 (35.3%). The PO size did not associate with gender, way of birth, the presence of jaundice, constipation or any specific blood group or Rh factor, and it did not correlate with birth weight or month and gestational order either. Medium and large PO were more frequently palpated than smaller (94-100% vs. 83%, p = 0.009); PO size correlated with the duration of the history of vomiting (CQ 0.267, p = 0.002), child's age (CQ 0.243, p = 0.005) and weight at operation (CQ 0.190, p = 0.048). A daily weight loss surpassing 5 g was more commonly found among small PO (p = 0.038). CONCLUSIONS: In more than a third of the PS patients, PO is unexpectedly large, and in one of every seven it is surprisingly small. The bigger PO size associates with a longer disease, and with older and heavier patients, which probably is explained by a slighter clinical course. A small PO is more difficult to palpate during clinical evaluation.
Female↗
The changing presentation of pyloric stenosis.
Metabolic abnormalities described in pyloric stenosis are now rare, probably because of prompter recognition of the disease. This report reviews the trend in presentation over three decades. All infants treated for pyloric stenosis during three mid-decade target periods were reviewed. Comparison between the 1975 group and the 1985 group and between the 1995 group and previous decades were designed to identify the impact of ultrasonography, since this modality has only been available in the last decade. Parameters included age at diagnosis and incidence of water and electrolyte imbalance as measures of delay in presentation. Two hundred eighty-three patients were reviewed. Mean age (weeks) at presentation was 5.4+/-3.0 in 1975, 4.6+/-2.0 in 1985, and 3.4+/-1.3 in 1995 (P < .05, ANOVA). Overall, 88% had no electrolyte anomalies on admission. There was no statistical difference in frequency of abnormal results between the three decades. Total and postoperative hospitalization was significantly shorter in the recent period: in 1985, 5.34 and 4.36 days; in 1985, 4.48 and 3.4 days; and in 1995, 3.8 and 2.8 days. These data show that pyloric stenosis is now recognized earlier than in previous decades. The availability of ultrasonography cannot solely be credited for earlier diagnosis, since this trend was already apparent before its introduction. The "classic" metabolic derangements associated with pyloric stenosis have been highly uncommon for the past three decades.
Age Distribution↗
The true cause of pyloric stenosis is hyperacidity.
UNLABELLED: Pyloric stenosis (PS) has no known cause. A testable theory of cause is proposed, based on the inheritance of a parietal cell mass (PCM) at the upper end of the normal range. It is proposed that, until 3-4 wk of age, the obligatory high fasting gastrins are at maximal levels and not able to be diminished by increasing antral acidity. Hence, rising acidity is not reduced by a lowered gastrin during this time, and very high acidity occurs. CONCLUSION: Persisting duodenal hyperacidity is created by an inherited high PCM and loss of gastrin control. These two factors produce pyloric stenosis through work hypertrophy from repeated pyloric contraction in response to hyperacidity.
Gastric Acid↗
Nitric oxide synthase is absent in only a subset of cases of pyloric stenosis.
PURPOSE: The aim of this study was to study nitric oxide synthase (NOS) immunohistochemistry in the pyloric muscle and establish the role of nitric oxide in pyloric stenosis. METHODS: Pyloric muscle biopsy specimens were obtained from 20 patients with pyloric stenosis during pyloromyotomy. Ten control specimens without pyloric disease were obtained from autopsy performed less than 4 hours after death on age-matched babies who died of other causes. Tissues were fixed in 4% paraformaldehyde immediately. A monoclonal antibody against the neuronal form of NOS (bNOS) was used for immunohistochemistry. RESULTS: Immunohistochemistry showed activity of bNOS in the control specimens and some pyloric stenosis specimens. This shows that NOS is present in the pylorus in normal cases as well as in a few cases of pyloric stenosis. CONCLUSIONS: NOS deficiency leading to lack of locally available nitric oxide causes a failure of smooth muscle relaxation. This may account for the cause of pyloric stenosis in infants. However, this study shows that this is true probably only in a subset of cases. The etiology of pyloric stenosis may still be multifactorial. Further investigations are required regarding the etiology of pyloric stenosis. J Pediatr Surg 36:616-619.
Biopsy, Needle↗
Comparison of preoperative sonography with intraoperative findings in congenital hypertrophic pyloric stenosis.
In 17 infants with hypertrophic pyloric stenosis, the pyloric diameter was measured preoperatively by ultrasound. The mean pyloric diameter was 15.12 +/- 2.11 mm (mean +/- SD), range 11 to 19 mm. During pyloromyotomy, the hypertrophic pylorus was precisely measured craniocaudally and dorsoventrally, and measurements were obtained concerning muscular thickness and length of the pylorus. The preoperative and intraoperative measurements were subsequently compared. Differences of 0.76 +/- 1.68 mm and 1.24 +/- 2.04 mm were found for the dorsoventral and craniocaudal diameters, respectively. The intraoperative measurements were consistently greater than the sonographic findings. The length of the pylorus averaged 22.0 +/- 2.66 mm, the muscular thickness 6.53 +/- 1.68 mm, respectively. This prospective study confirms the diagnostic value of sonography in congenital hypertrophic pyloric stenosis.
Female↗