A patient with POLA1 splice variant expands the yet evolving phenotype of Van Esch O'Driscoll syndrome.

Van Esch-O'Driscoll syndrome (VEODS) is a rare cause of syndromic X-linked intellectual disability characterised by short stature, microcephaly, variable degree of intellectual disability, and hypogonadotropic hypogonadism. To date, heterozygous hypomorphic variants in the gene encoding the DNA Polymerase α subunit, POLA1, have been observed in nine patients from five unrelated families with VEODS. We report a three-year-old child with VEODS having borderline intellectual disability due to a novel splice site variant causing exon 6 skipping and reduced POLA1 expression.

Focal pyloric hypertrophy in adults: a diagnostic pitfall-a case report and review of the literature.

Adult hypertrophic pyloric stenosis in the form of focal pyloric hypertrophy is an uncommon but a well-established lesion. In most cases, clinical findings suggest malignancy, and despite advances in imaging techniques, preoperative diagnosis is difficult. Herein, an example of focal pyloric hypertrophy is presented with a review of the literature to emphasize the clinicopathological characteristics of this lesion. In a 43-year-old man with abdominal discomfort, endoscopy showed a 1.5 cm nodular lesion near the pylorus that necessitated surgery to exclude malignancy. Pathological examination allowed the diagnosis of focal pyloric hypertrophy. The present case and the review revealed that focal pyloric hypertrophy is a male dominant lesion in middle-aged patients. The clinical diagnosis is problematic, and its initial diagnosis depends on a high clinical suspicion in patients with upper gastrointestinal system complaints irrespective of the duration of the symptoms. It is not known whether it is a separate entity from the diffuse form. Although both are similar in a clinical point of view, etiopathogenetic studies are required to clarify their differences completely. Moreover, the rare occurrence of focal pyloric hypertrophy and the lack of diagnostic clinical findings do not exclude its consideration in the differential diagnosis, especially in patients with gastric outlet obstruction.

Milk vomiting or regurgitation in the first 3 months of life: Something old-something new.

The age of presentation of reflux symptoms and their self-cure in babies without a sliding hernia parallel those of mild pyloric stenosis of infancy (PS). It is proposed that this is because PS and, at least some cases of reflux, share the same cause-a temporary hold-up at the pyloric sphincter owing to acid provoked hypertrophy of the pyloric sphincter. In support of this theory, the written observations of John Thomson, Pediatrician from Edinburgh, in 1921 and Isabella Forshall, Pediatric Surgeon from Alder Hey Hospital, Liverpool, in 1958 are revisited. An analysis of both papers provides supportive evidence that, in at least some cases diagnosed as simple reflux, an underlying temporary hold up is present owing to early hypertrophy of the sphincter. It is recommended that sphincter thickness measurements should be made by ultrasonic assessment whenever uncomplicated reflux is diagnosed within the first 3 months of life.

PRIMARY HYPERTROPHIC PYLORIC STENOSIS IN ADULTS.

THE AIM: to present some information-about the rare primary hypertrophy of the pylorus in adults and a clinical case of a patient with this disease. MATERIALS AND METHODS: the patient A., 52 years of age, after which clinical-instrumental and laboratory research was diagnosed with infiltrative form of cancer of the pylorus with decompensated stenosis. The used: videothoracoscopy, fluoroscopy, peripheral computer electrogastrogram, local fluorescence spectroscopy. The General blood and urine tests, biochemical blood tests, PCR for the determination of tumor markers. RESULTS: The resection of 2/3 of the stomach Billroth I. histological examination of the pylorus diagnosed with hypertrophy of circular muscle fibers, to a lesser extent, hypertro- phy of the longitudinal fibers with inflammatory changes. CONCLUSION: in cases of suspected infiltrative form of cancer of the pylorus in adults differential diagnosis it is advisable to include the primary hypertrophy of his.

Investigation of the effects of enteral hormones on the pyloric muscle in newborn rats.

PURPOSE: To investigate the effects of enteral hormones on pyloric muscle in order to clarify the etiopathogenesis of hypertrophic pyloric stenosis (HPS). METHODS: Forty-two newborn Wistar-Albino rats were included. No intervention was done in the control group (CG, n=6). In the sham group (SG, n=6) 1ml saline (0.9% NaCl solution), in the Nw-nitro-l-arginine methyl ester hydrochloride (L-NAME) group (LNG, n=6) 100mg/kg/d L-NAME, in the somatostatin group (STG, n=6) 7mcg/kg/d ST, in the cholecystokinin group (CCKG, n=6) 3mcg/kg/d CCK, in the substance P group (SPG, n=6) 5ml/kg/d SP, and in the prostaglandin-E1 group (PGE1G, n=6) a cumulative dose of 360mcg/kg PGE1 was given intraperitoneally for 14days. On the 21st day, histopathological examination and muscle thickness measurements were done. Results were evaluated statistically. RESULTS: Total and circular pyloric muscle thicknesses were significantly increased in the LNG compared to the CG and SG (p<0.05). Circular pyloric muscle thickness was not increased in the STG, CCKG and SPG compared to the CG and SG (p>0.05). In the PGE1G, muscle thickness was significantly decreased in the pylorus and increased in the antrum compared to the CG and SG (p<0.05). CONCLUSION: Nitric oxide synthase (NOS) inhibition with L-NAME seems to be a causative factor in HPS by increasing pyloric muscle thickness. PGE predominantly affects antral gastric muscle and has no profound effect on pyloric muscle.

Hypertrophic pyloric stenosis in twins; genetic or environmental factors.

The etiology of infantile hypertrophic pyloric stenosis (IHPS) remains obscure. Over 120 years after the condition has become a clinical entity the debate whether the cause of IHPS is genetic, environmental or both, has not yet reached a final conclusion. Herein, we present a pair of monozygotic male twins with IHPS together with a review of the literature. We aimed to support genetic pre-disposition in the epidemiology of IHPS, adding a twin data to the literature and to review the associated articles about the pathogenesis and inheritance patterns.

Infantile hypertrophic pyloric stenosis: does size really matter?

Pyloric stenosis is a common infantile disorder typically occurring between 2 weeks and 8 weeks of age. Presentation outside this range and in premature infants is uncommon and often atypical. We present three cases, a pair of premature twins and a 5.5-month-old infant with pyloric stenosis. We highlight that despite their difference in size and weight, ultrasound examination remains a reliable diagnostic tool. However, pyloric measurements should be interpreted in combination with the other dynamic features on ultrasound.

Video capsule endoscopy and CT enterography in diagnosing adult hypertrophic pyloric stenosis.

Primary adult hypertrophic pyloric stenosis is a rare but important cause of gastric outlet obstruction that may be misdiagnosed as idiopathic gastroparesis. Clinically, patients present with early satiety, abdominal fullness, nausea, epigastric discomfort and eructation. Permanent gastric retention of a video capsule endoscope is diagnostic in differentiating between the two diseases, in the absence of an organic gastric outlet obstruction. This case presents the longest video capsule retention in the medical literature to date. It is also the first case report of adult hypertrophic pyloric stenosis diagnosed with video capsule endoscopy or a computed tomography scan. Finally, an unusual "plugging" of the gastric outlet with free floating capsule has an augmented effect on disease physiology and on patient's symptoms.

Evaluation of ultrasonographic parameters in the diagnosis of pyloric stenosis relative to patient age and size.

INTRODUCTION: Pyloric thickness of 3 mm or higher and length of 15 mm or higher by ultrasonography (US) is widely accepted as diagnostic criteria for pyloric stenosis (PS). However, infants presenting at earlier ages are held to this same criteria, which may not be applicable. METHODS: Retrospective review was conducted on patients evaluated with pyloric US to rule out PS from May 2010 through December 2010. Pearson correlation was used to detect an association between weight and age with pyloric thickness and length. Sensitivity and specificity for US parameters were determined. RESULTS: Three hundred four patients underwent 318 ultrasounds, of which 67 had PS. Of those with PS, age and weight had a positive correlation with thickness (P < .007), and age positively correlated with length (P < .001). In patients with and without PS, there was a negative correlation for both age and weight with thickness (P < .02). Those who did not have PS held a stronger negative correlation between age and thickness (P = .002). Overall, US had a 100% sensitivity and specificity for PS. Thickness of 3 mm or higher was 100% sensitive and 99% specific, and pyloric length of 15 mm or higher was 100% sensitive and 97% specific. CONCLUSIONS: Although significant associations between age and weight with pyloric thickness and length may exist, our data indicate that this does not have an impact on the diagnostic criteria for PS.

Spectral changes in electrical activity of pylorus due to L-NAME induced hypertrophic pyloric stenosis.

OBJECTIVES: To investigate the relation between hypertrophic pyloric stenosis (HPS) and the changes in the myoelectrical activity of the pyloric and gastric areas. METHODS: Three pregnant females, at 14 days of gestation two of which were named as D14n (NOS inhibitor group) and one was named as D14c (control). From the beginning of the study until the end of gestation, rats in D14n group received nitric oxide synthase inhibitor L-NAME for administrating their pups, and the rat in D14c group was drinking water for 21 days. The pups of each group underwent laparotomy at 42 days of their life and myoelectrical signals of their pyloric and gastric regions were recorded via bipolar electrodes and then evaluated through signal processing. RESULTS: Signal analysis showed that HPS induced pyloric segment reveals a suppressed spectral component that was detected in normal pyloric segment. The HPS induced pyloric segment also revealed higher power/ min and +/- SD compared to that of normal and gastric areas. In the pyloric segment, while the number of interstitial cells of Cajal (ICC) was lesser, the number of smooth muscle cells was higher than in the pyloric segment of controls. CONCLUSIONS: The spectral differentials depend on the type, population and condition of locally specialized muscular mechanism which can be affected from HPS. The HPS also has a relation to specific cells, such as ICC that generates NO, provoke the spontaneous pacemakers and biological slow waves (Tab. 1, Fig. 1, Ref. 19).

Interstitial cells of Cajal in the gut--a gastroenterologist's point of view.

Alterations of normal function of interstitial cells of Cajal (ICC) are reported in many intestinal disorders. Diagnosis of their involvement is rare (infrequent), but necessary to propose a specific treatment. This article reviews the place of ICC in the pathogenesis of achalasia, gastroesophageal reflux disease, infantile hypertrophic pyloric stenosis, chronic intestinal pseudo-obstruction and slow transit constipation. Moreover we discuss the role of the Cajal cells in the development of stromal tumors of the gastrointestinal tract.

Hypertrophic pyloric stenosis in newborns younger than 21 days: remodeling the path of surgical intervention.

BACKGROUND: According to currently accepted diagnostic criteria, ultrasonography confirms hypertrophic pyloric stenosis (HPS) when the pyloric muscle thickness (MT) is greater than 4 mm and the pyloric channel length (CL) is greater than 15 mm. Hypertrophic pyloric stenosis frequently presents in newborns younger than 21 days; yet, the diagnostic criteria in this younger population remain poorly defined. We, therefore, sought to define the diagnostic criteria for HPS in newborns younger than 21 days. METHODS: Ultrasonographic measures of pyloric MT and CL were obtained by retrospective chart review (2000-2006) at a single institution for all newborns (aged 10 days to 6 weeks) with an intraoperatively proven diagnosis of HPS. Demographic characteristics and ultrasonographic measurements were collected, and features differentiating younger (21 days or younger) from older newborns were assessed. Measures of pyloric MT and CL were analyzed in 7-day increments, and comparisons were made between newborns aged 21 days or less and newborns 22 to 42 days of age. Based upon these features, a set of ultrasonographic parameters to establish the diagnosis of HPS in younger patients was defined. RESULTS: Three hundred fourteen newborns (83% male) underwent pyloromyotomy of whom 64% (n = 200) had a preoperative pyloric ultrasound. Sixty newborns (19%) were younger than 21 days, of whom 51 (85%) had preoperative ultrasonography. The ultrasound measurement of HPS was significantly decreased in younger vs older newborns: (MT, 3.7 +/- 0.65 vs 4.6 +/- 0.82 mm, P < .05; CL, 16.9 +/- 2.8 vs 18.2 +/- 3.4 mm, P < .05). Importantly, the mean ultrasound measurement for young newborns with HPS typically fell within the currently defined "normal" or "borderline" range. A linear relationship was determined to exist between pyloric MT and CL and patient age, suggesting the use of 3.5 mm as a "cutoff" in younger patients. CONCLUSIONS: These findings suggest that current guidelines to diagnose HPS do not accurately diagnose HPS in children younger than 3 weeks, and these findings raise the need to evaluate the decision analysis algorithm using prospective studies.

Sarcoglycan immunoreactivity is lacking in infantile hypertrophic pyloric stenosis. A confocal laser scanning microscopic study.

OBJECTIVES: The Dystrophin-Glycoprotein Complex (DGC) is a large multisubunit complex that plays a crucial role in maintaining the structural integrity and physiology of muscle fibers. Dystrophin has been reported to be absent in the pyloric muscle of infantile hypertrophic pyloric stenosis (IHPS) patients. The present study was designed to investigate the other two patterns of DGC (dystroglycan and sarcoglycan complexes) in normal pyloric muscle and their possible modifications in IHPS patients. METHODS: Ten pyloric muscle biopsies were obtained from babies operated for IHPS and five control pylorus biopsy taken at autopsy from cases without gastrointestinal disease. The DGC sub-complexes (beta-dystroglican and beta, delta- sarcoglycans) were localized immunohistochemically using specific monoclonal antibodies. The results were evaluated using a confocal laser scanning microscope. RESULTS: Positive immunolocalization of the two DGC sub complexes was demonstrated in the smooth muscle cells (SMCs) of the pyloric region of control patients. Similarly, a positive immune expression of beta-dystroglican was observed in the pyloric SMCs of IHPS patients. On the other hand a negative immunoreaction for sarcoglycans was recorded within the full thickness of the pyloric SMCs of these patients. CONCLUSIONS: The absence of sarcoglycans within the hypertrophied pyloric muscle may be a predisposing factor in the pathogenesis of IHPS since it could alter the normal physiology of SMCs through the modifications of structural integrity of sarcolemma and signaling between the extracellular and intracellular compartment.

Piloromiotomía laparoscópica: tratamiento de estenosis hipertrófica del píloro / Laparoscopic pyloromyotomy treatment of hipertrophic pyloric stenosis

Introducción: la estenosis hipertrófica del píloro es una condición común de la infancia. El tratamiento convencional consiste en realizar una piloromiotomía a través de una incisión en el cuadrante superior derecho del abdomen. El desarrollo de la cirugía videolaparoscópica nos ha permitido realizar este procedimiento, ofreciendo los mismos resultados que la técnica tradicional. Material y métodos: en la Sección de Cirugía Pediátrica del Hospital Roosevelt se han realizado 10 piloromiotomías videolaparoscópicas en los últimos tres meses. El procedimietno se realiza a través de tres puertos de cinco milímetros, localizados en el ombligo...

Low plasma nitrite in infantile hypertrophic pyloric stenosis patients.

There is now substantial evidence that reduced expression of neuronal nitric oxide synthase (nNOS) is implicated in the pathogenesis of infantile hypertrophic pyloric stenosis (IHPS). This study aimed to investigate the role of plasma nitric oxide (NO) in patients with IHPS. Blood and pylorous biopsies of 13 IHPS patients were examined. The control group consisted of 19 age-matched healthy infants and 22 age-matched acute gastroenteritis patients. Plasma nitrite (NO(2-)) and nitrate (NO(3-)) levels were detected with an NO analyzer. Pylorus biopsies of 13 IHPS patients were examined for nitric oxide synthase isoform expression. Plasma nitrite levels in the 13 IHPS patients were significantly lower than in the age-matched healthy controls (0.97 +/- 0.19 vs. 3.53 +/- 0.79 microM; P < 0.001) and the acute gastroenteritis controls (0.97 +/- 0.19 vs.1.39 +/- 0.45 microM; P = 0.006). Decreased expression of nNOS in the nerve fibers of the pylorus circular muscle was found in the 13 IHPS patients. The decreased plasma nitrite levels rose to the normal range (3.27 +/- 0.77 M) after pyloromyotomy. There was no significant correlation between plasma nitrite levels and muscle wall thickness in IHPS patients. We conclude that NO is implicated in the occurrence of IHPS and the plasma nitrite level is valuable for the diagnosis of IHPS.

Helicobacter pylori and infantile hypertrophic pyloric stenosis: is there a possible relationship?

BACKGROUND: Recently, it has been suggested that Helicobacter pylori might be a cause of some cases of infantile hypertrophic pyloric stenosis (IHPS) in infancy on the basis of its epidemiologic and clinical features. We performed this study to evaluate the possible relationship between IHPS and H. pylori. DESIGN: In consecutive infants with IHPS, we performed upper gastrointestinal endoscopy with biopsy before pyloromyotomy. The endoscopic appearance of the pylorus was noted to validate endoscopic features of IHPS. RESULTS: Sixteen infants, 15 male, 14 white, mean age 42 days, range 21 to 104 days, were studied. The index case had chronic active gastritis on biopsy with organisms suspicious for H. pylori. Four others had chronic active gastritis, six more had focal or mild chronic gastritis, five were normal, and none had H. pylori on histology or immune histochemical staining in selected cases. All patients had negative rapid urease test. Most common endoscopic findings of IHPS were thickened prominent asymmetric pyloric folds and pin-hole pylorus that could not be intubated by the pediatric endoscope. CONCLUSION: H. pylori was not specifically identified in our patients with IHPS. The presence of H. pylori-like organisms in the gastric mucosa in our index case and finding of chronic active gastritis in several others may indicate the possibility of an acquired infectious etiology for IHPS.

Study of insulin-like growth factor-1 (IGF-1) and platelet-derived endothelial cell growth factor (PDEGF) expression in children with infantile hypertrophic pyloric stenosis.

BACKGROUND: The pathogenesis of infantile hypertrophic pyloric stenosis (IHPS) is not fully understood. Hypertrophy of the pyloric muscle is probably regulated by growth factors. Recent studies reported an increase in the local synthesis of insulin-like growth factor-1 (IGF-1). There are no reports concerning platelet-derived endothelial cell growth factor (PDEGF) playing an important role in the pathological angiogenesis. The aim of this study was to analyze the expressions of IGF-1 and PDEGF by immunohistochemistry (IHC) in the muscularis propria of the pyloric muscle in children with IHPS. MATERIAL/METHODS: Twenty-two muscle biopsies were obtained at the time of pyloromyotomy. The control group consisted of seven children. Specimens were evaluated by routine histopathological methods and by immunohistochemistry using monoclonal mouse anti-PDEGF or -IGF-1 antibodies. Cells showing positive reaction were counted in five random 200x high-power fields. Values were expressed as the mean +/-SD of the real expression area of the analyzed marker to the total analyzed area. RESULTS: In children with IHPS the average area of PDEGF expression was 62+/-52.5, whereas in the control group it was 15+/-12.1. The average area of IGF-1 expression was 1037+/-491.9) in study group and 259+/-221.44 in the controls. Statistically significant differences were found. CONCLUSIONS: These results show a local increase in the expressions of IGF-1 and PDEGF in the muscularis propria of the pyloric muscle in children with IHPS, which may have implications to the pathogenesis of the disease.