Derrame pleural unilateral tras perforación vascular por catéter venoso central de inserción periférica: utilidad del verde de indocianina en el diagnóstico / Unilateral pleural effusion caused by vessel perforation due to peripherally inserted central catheter: Indocyanine green as a diagnostic tool

Varón de 44 años con desnutrición calórico-proteica grave en el contexto de una estenosis pilórica benigna, a quien se decidió colocar un catéter central de inserción periférica (CCIP) para tratamiento con nutrición parenteral. Al quinto día de la inserción del catéter, presentó un derrame pleural derecho masivo de color blanco e insuficiencia respiratoria tras la realización de una endoscopia digestiva alta para el tratamiento de la estenosis pilórica. Ante la sospecha inicial de quilotórax el paciente ingresó en la Unidad de Reanimación. Se administró verde de indocianina a través del CCIP, obteniendo a los 30 min una coloración verdosa del contenido del derrame pleural; este resultado nos hizo sospechar que el derrame pleural era secundario a una perforación vascular por el CCIP con extravasación de la nutrición parenteral al espacio pleural. Se realizó una tomografía computarizada toracoabdominal, que confirmó la existencia de una perforación a nivel de la vena innominada. La colocación de un CCIP puede asociarse a complicaciones graves, como la perforación de una vena central, por tanto, la correcta posición de un catéter central debe ser siempre comprobada. La prueba diagnóstica de elección de perforación vascular a nivel central es la tomografía computarizada con contraste; sin embargo, ante la existencia de derrame pleural en este contexto, es posible emplear un colorante que, administrado de forma intravenosa, oriente su diagnóstico in situ. En este caso se empleó el verde de indocianina con este objetivo (AU)

A peripherally inserted central catheter (PICC) was inserted into a 44-year-old man to provide parenteral nutrition in a protein-calorie malnutrition secondary to a benign pyloric stenosis. On the fifth day while monitoring the catheter, the patient presented with a massive whitish pleural effusion after undergoing gastric endoscopy in order to treat pyloric stenosis. Chylothorax was initially suspected, and the patient was admitted to a recovery unit. Indocyanine green was administered through the PICC, obtaining a greenish discoloration in the pleural effusion 30 min later. This led to the diagnosis of a pleural effusion caused by a vessel perforation due to the PICC, leading to parenteral nutrition extravasation. Thoraco-abdominal computed tomography was performed, which confirmed an innominate vein perforation due to the PICC. PICC insertion may be associated with severe complications, such as central vessel perforation, and therefore the correct position of a central catheter should be always checked. Intravenous computed tomography contrast is the gold standard for central vascular perforation diagnosis. However if a pleural effusion occurs in this context, it is possible to use a dye, which administered intravenously can lead us to the correct diagnosis in situ. Indocyanine green was used for this purpose in this case (AU)

Causa inusual d'obstrucció gàstrica en el lactant: membrana antropilòrica / Causa inusual de obstrucción gástrica en el lactante: membrane antropilórica / Unusual cause of gastric outlet obstruction in infants; antral web

Introducció: la membrana antropilòrica (MA) és una alteració congènita de baixa incidència i difícil diagnòstic per la seva semblança clinicoradiològica amb l'estenosi hipertròfica de pílor (EHP). La MA completa o parcial causa una obstrucció del buidament gàstric que provoca vòmits de repetició no biliosos, deshidratació, pèrdua de pes i alcalosi metabòlica hipoclorèmica. La radiografia d'abdomen mostra una dilatació gàstrica greu, i l'ecografia abdominal ens descarta l'EHP. Aleshores cal plantejar altres causes d'obstrucció a la sortida gàstrica en el lactant, com la MA. Cas clínic: es presenta el cas d'un lactant d'1 mes i 5 dies, sense antecedents obstètrics d'interès, que consulta per vòmits no biliosos, estancament ponderal i hipotonia de 24 hores d'evolució. Les exploracions complementàries fetes van ser normals, tret d'un lleu reflux gastroesofàgic, i es va descartar l'EHP per ecografia abdominal. Davant la sospita d'intolerància a proteïnes de llet de vaca es va fer un canvi de fórmula d'inici a fórmula elemental amb persistència de la clínica i instauració progressiva d'alcalosi metabòlica. Amb la sospita de MA, es va fer un segon estudi ecogràfic dirigit que mostrava un petit ressort antropilòric que es va confirmar en la fibrogastroscòpia, i es va diagnosticar una MA parcial. La resecció quirúrgica de la membrana va re-soldre la clínica. Comentaris: davant d'un lactant amb obstrucció gàstrica, i un cop descartada la causa més comú (EHP), cal pensar en la membrana antral com a possible etiologia, ja que si aquesta es confirma, el seu maneig quirúrgic és definitiu amb resolució clínica posterio

Introducción. La membrana antropilórica (MA) es una alteración de baja incidencia y difícil diagnóstico por el parecido clínico-radiológico con la estenosis hipertrófica de píloro (EHP). La MA completa o parcial causa una obstrucción en la salida gástrica produciendo vómitos de repetición no biliosos, deshidratación, pérdida de peso y alcalosis metabólica hipoclorémica. La radiografía de abdomen muestra una dilatación gástrica severa y la ecografía abdominal descarta la EHP. Es entonces cuando hemos de plantear otras causas de obstrucción de la salida gástrica en el lactante, como la MA. Caso clínico. Se presenta el caso de un lactante de 1 mes y 5 días, sin antecedentes obstétricos de interés, que consulta por vómitos no biliosos, estancamiento ponderal e hipotonía de 24 horas de evolución. Las exploraciones complementarias realizadas fueron normales, excepto un leve reflujo gastroesofágico, y se descartó la EHP por ecografía abdominal. Ante la sospecha de intolerancia a proteínas de leche de vaca se realizó un cambio de fórmula de inicio a fórmula elemental, con persistencia de la clínica e instauración progresiva de alcalosis metabólica. Con la sospecha de MA, se realizó un segundo estudio ecográfico dirigido que mostraba un pequeño resorte antropilórico que se confirmaba en la fibrogastroscopia, y se diagnosticó una MA parcial. Con la resección quirúrgica de la membrana se resolvió la clínica. Comentarios. Ante un lactante con obstrucción gástrica, y una vez descartada la causa más común (EHP), se ha de pensar en la membrana antral como posible etiología, ya que si esta se confirma, su manejo quirúrgico es definitivo con la resolución clínica posterior (AU)

Introduction. The antral web (AW) is a disorder of low incidence and difficult diagnosis despite its similar clinical and radiological findings to hypertrophic pyloric stenosis (HPS). Complete or partial AW cause gastric outlet obstruction with persistent non-bilious vomiting, dehydration, weight loss, and hypochloremic metabolic alkalosis. Abdominal radiograph shows severe gastric dilatation; however, the normal abdominal ultrasound ruling out HPS should raise the suspicion of other causes of gastric outlet obstruction, such as AW. Case report. We report a case of a one-month and five days-old infant with no relevant obstetric history, who presented with a 24- hour history of non-bilious vomiting, lack of weight gain and hypotonia. Diagnostic studies suggested mild gastroesophageal reflux, and an abdominal ultrasound ruled out HPS. The diagnosis of intolerance to cow’s milk protein was first considered, and elemental formula was started without improvement. Suspecting AW, a repeat abdominal ultrasound showed a small prepyloric spring. Gastroscopy confirmed the diagnosis of partial AW, and surgical resection of the membrane resulted in resolution of the symptoms. Comments. In the presence of an infant with gastric outlet obstruction syndrome, and after the most common cause (HPS) has been ruled out, the diagnosis of AW should be considered. Surgery is curative (AU)

Enhanced gastric ghrelin production and secretion in rats with gastric outlet obstruction.

BACKGROUND AND AIM: Ghrelin has distinct effects on gastrointestinal motility through the vagus nerve and gastric excitatory neural plexus. The objectives of this study were to investigate the dynamics of ghrelin and expression of neuromuscular markers in a newly established surgically manipulated rat model of gastric outlet obstruction (GOO), akin to the pyloric stricture associated with duodenal ulcer, advanced gastric cancer, and other conditions, in the clinical setting. MATERIAL AND METHODS: The rats were divided into two groups, a control group (sham operation) and the GOO group (proximal duodenal stricture). The animals were sacrificed 2 weeks after the operation. Plasma and gastric ghrelin were measured by radioimmunoassay. mRNA expression in the stomach of neural choline acetyltransferase (ChAT), c-kit, and membrane-bound stem cell factor (SCF) were analyzed by quantitative RT-PCR. In addition, gastric mRNA expression of the aforementioned were also evaluated 60 min after intraperitoneal administration of a synthetic GHS-R1a antagonist ([D: -Lys3] GHRP-6 6.0 mg/kg). RESULTS: Mechanical GOO induced increases of fasting plasma ghrelin levels and hyperplasia of the gastric muscle layers, with enhanced expression of the gastric neuromuscular markers. Administration of [D: -Lys3] GHRP-6 normalized the enhanced expression of c-kit and SCF. CONCLUSION: GOO stimulates ghrelin dynamics and then enhances the mechanistic expression of gastric cellular communication network molecules between nerves and smooth muscle cells.

Salt-wasting 21-hydroxylase deficiency congenital adrenal hyperplasia and pyloric stenosis in two Hispanic brothers.

The differential diagnosis of vomiting and dehydration in the first month of life includes congenital adrenal hyperplasia (CAH) and pyloric stenosis (PS). Each diagnosis may mask the presence of the other, requiring careful evaluation and follow-up. We document the occurrence of CAH and PS in two Hispanic siblings.

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.

[Immunohistochemical study of hypertrophic pyloric stenosis]. / Estudio inmunohistoquímico en la estenosis hipertrófica del píloro.

INTRODUCTION: In spite of the clinical experience about infantil Hypertrophic Pyloric Stenosis (IHPS), its etiopathology remains unknown. Recent studies have been focussed in immunohistochemistry techniques for valuing the neuronal development in the pyloric muscle. MATERIAL AND METHODS: We took biopsy from 10 babies diagnosed of IHPS and 10 babies with similar age, died because of other causes. Immunohistochemical study was performed using monoclonal antibodies: S100 protein, GFAP, enolasa and neurofilaments NF. The results were showed semi-quantitativement as strong (++), moderate (+) and absent (-). Immunotinction of the myenteric plexus (ganglion cells and satellite) and nervous fibers of the muscle layer, were done. RESULTS: We observed a poor immunoreactivity in the muscle layer (longitudinal and circular) in the 60-70% of specimens of pyloric muscle in babies with IHPS. GFAP were absent in the 80% in the myenteric plexus. This poor innervation may be related to the etiopathogenesis of pyloric stenosis and hypertrophy.

Streamlining the care of patients with hypertrophic pyloric stenosis: application of a clinical pathway.

PURPOSE: The purpose of this study was to evaluate the impact of a clinical pathway on infants admitted to a pediatric tertiary care center with the diagnosis of hypertrophic pyloric stenosis (HPS). METHODS: The records of 132 HPS patients were evaluated before and after implementation of a clinical pathway. Infants were excluded for prematurity, admission to nonsurgical services, or multiple diagnoses requiring prolonged hospitalization, resulting in 83 patients for analysis. Group I (prepathway, n = 40) and group II (postpathway, n = 43) infants were analyzed for time from admission to operation, operation to first feeding, operation to discharge, total length of stay, hospital charges, metabolic status at time of admission, and postoperative complications. The Mann-Whitney test was performed (statistical significance at P <.05). RESULTS: There was no significant difference between group I and group II patients in the length of preoperative hospitalization or metabolic status at the time of hospital admission. In comparison with group I patients, there was a significant reduction in time to resumption of oral feedings (4.6 +/- 1.9 hours v 7.5 +/- 3.2 hours; P <.001) for group II infants and a significantly earlier discharge (26.7 +/- 6.8 hours v 38.0 +/- 11.7 hours; P <.001). This resulted in a shortened length of stay (41.8 +/- 9.7 hours v 57.8 +/- 14.3 hours; P <.001) with an associated decrease in hospital charges ($4,555 +/- $464 v $5,400 +/- $1,017; P <.001). CONCLUSIONS: Elimination of practice variability by the use of a clinical pathway for HPS resulted in significant reduction of hospital stay and related charges. The impact of the pathway occurred in the postoperative period and is a consequence of a rapid and systematic return to oral feedings.

[Increase of the chondroitin-sulfate proteoglycan, fibronectin and fibroblasts in infantile hypertrophic pyloric stenosis]. / Aumento de la expresión del proteoglicano condroitín-sulfato, fibronectina y fibroblastos en la estenosis hipertrófica de píloro.

INTRODUCTION: Infantile hypertrophic pyloric stenosis (IHPS) consists of hypertrophy of the muscular layer of the pylorus. Its etiology is still unknown. In the last years only few jobs that studied the extracellular matrix (ECM) in the muscular layer in the IHPS have been reported. Our aim was to investigate the expression of two ECM molecules: chondroitin-sulfate proteoglycan (CSPG) and fibronectin (FN), and fibroblasts. MATERIAL AND METHODS: Full-thickness muscle biopsy specimens were obtained from 33 IHPS patients at pyloromyotomy and 12 controls. Indirect immunohistochemistry was performed using CSPG, FN and fibroblasts monoclonal antibodies. The results were showed by a semiquantitative scale as follows: strong (++), moderate (+), weak (+/-), and absent (-). RESULTS: We demonstrated that the CSPG immunoreactivity was localized in the connective tissue septa and the expression of FN molecules in the pericellular space. Both molecules were significantly the increased in the muscle layer of the pylorus with IHPS in relation to control pylorus. We also demonstrated a marked increased expression in the number of fibroblasts in the muscle layer of the pylorus with IHPS. Even-though the most striking increase was localized in the septa, we also observed great number of fibroblasts amongst the smooth muscle cells. CONCLUSIONS: We suggest that IHPS is characterized, not only by the muscle layer hypertrophy, but also by the increase of several ECM molecules, such as CSPG and FN. We also think that the increase of fibroblast could explain the higher expression of both ECM molecules in the muscle layer of pylorus in IHPS.

Selective neurotrophin deficiency in infantile hypertrophic pyloric stenosis.

BACKGROUND/PURPOSE: Increasing evidence suggests that the enteric nervous system is under the control of neurotrophins. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), promote differentiation, growth, and survival of various central and peripheral nervous system neurons. The biological effects of neurotrophins are mediated by the interactions with high-affinity tyrosine kinase receptors (TrkA, TrkB, TrkC). Recently, abnormalities of intramuscular innervation have been reported in infantile hypertrophic pyloric stenosis (IHPS). To further understand the reported abnormalities in pyloric innervation in IHPS, the authors analyzed the expression of Trk receptors and the neurotrophins content in IHPS. METHODS: Full-thickness muscle biopsy specimens were obtained from 8 IHPS patients (age range, 23 to 41 days) at pyloromyotomy and from 8 age-matched controls without gastrointestinal disease at autopsy performed within 12 hours after death. Indirect immunohistochemistry was performed using ABC (Avidin Biotin peroxidase Complex) method with anti-Trk specific antibodies (A,B,C). Quantitative analysis was performed using sandwich-type ELISA for NGF, BDNF, NT-3, and NT-4/5. RESULTS: The intensity of staining of the myenteric plexus for TrkA, TrkB, and TrkC was similar among IHPS and controls. There was a lack of TrkA-positive nerve fibers in IHPS compared with controls. The quantity of total NGF, NT-3, and BDNF in IHPS was significantly lower than in controls. CONCLUSIONS: The reduced production of neurotrophins in IHPS may be responsible for the delay in the functional and structural maturation of pyloric innervation in IHPS. The lack of TrkA-positive nerve fibers in pyloric muscle may explain the abnormal intramuscular innervation in IHPS.

Hunterian Lecture. The ontogeny of the peptide innervation of the human pylorus with special reference to understanding the aetiology and pathogenesis of infantile hypertrophic pyloric stenosis.

Infantile hypertrophic pyloric stenosis is the most common cause for urgent abdominal surgery in infancy. The aetiology of the condition is unknown. The ontogeny of the innervation and structure of the normal infant pylorus is unknown. A variety of differing histological features have been attributed to this condition and a number of animal models have been described. The histological changes in the human condition and those in the animal models have not been quantified and statistically verified. Thus, precise comparisons cannot be made. Immunohistochemistry was the principal technique employed in this study. Using this technique, the ontogeny and structure of the normal infant pylorus have been documented. The morphological and immunohistochemical changes underlying infantile hypertrophic pyloric stenosis have been quantified for the first time and compared with the quantified changes in natural and experimental animal models of this condition.

Structural immaturity of the pylorus muscle in infantile hypertrophic pyloric stenosis.

Recent reports indicate that extracellular matrix and cytoskeleton plasmalemmal elements are altered in infantile hypertrophic pyloric stenosis (IHPS). Desmin is a cytoskeletal protein that is important for the organization and function of muscular fibers. It has been found to be increased in the smooth muscle in chronic intestinal pseudo-obstruction and in skeletal muscle in some forms of myopathies as well as in unexplained hypertrophic cardiomyopathies. The aim of this study was to analyze the expression of desmin in IHPS. Full-thickness muscle-biopsy specimens were obtained from 8 IHPS patients (age range 23 to 41 days) at pyloromyotomy, from 8 age-matched controls without evidence of gastrointestinal (GI) disease at autopsy, and from 2 stillborns who died at 27 and 30 weeks of gestation without evidence of GI disease. Indirect immunohistochemistry was performed using the avidin-biotin-peroxidase complex method with anti-desmin and visualized by development with 3-diaminobenzidine tetrahydrochloride. Pyloric muscle in IHPS demonstrated strong desmin immunoreactivity. The expression of desmin was also strong in the muscular layers of fetal pylorus. In the age-matched controls absent or weak desmin immunoreactivity was seen in the pyloric muscle layer. The increased amount of desmin in hypertrophied pyloric muscle in IHPS may result in inco-ordination of contraction and relaxation of the pylorus, thus causing motility dysfunction. The similar pattern of desmin expression in IHPS and fetal pylorus suggests that the organization of intermediate filaments in IHPS is in a fetal stage of development.

Glial-derived growth factor signaling pathway in infantile hypertrophic pyloric stenosis.

BACKGROUND/PURPOSE: Glial-derived growth factor (GDNF), which is the ligand of RET is reported to be essential for the development of enteric nervous system. A GDNF knockout mouse model has shown that the gastric region is a critical passing site between GDNF-RET-independent neuroblasts (colonizing the esophagus) and GDNF-RET-dependent neuroblasts (colonizing the small and large bowel). The earliest GDNF site of production is the mesenchyme and the outer smooth muscle cell (SMC) layer of the developing bowel. In the mature gastrointestinal tract the presence of GDNF is restricted to enteric glial cells. The aim of this study was to investigate the expression of GDNF and RET in infantile hypertrophic pyloric stenosis (IHPS). METHODS: Full-thickness muscle biopsy specimens were obtained from 8 IHPS patients at pyloromyotomy and from 8 age-matched controls without gastrointestinal disease. Indirect immunohistochemistry was performed using avidin-biotin-peroxidase complex method with anti-GDNF and anti-RET antibodies. Quantitative analysis was performed using sandwich-type enzyme-linked immunosorbent assay (ELISA) for GDNF. RESULTS: GDNF- and RET-positive nerve fibers were absent or markedly reduced in IHPS compared with controls. GDNF was expressed strongly by smooth muscle cells of both muscular layers in IHPS, whereas no GDNF expression was detected in pyloric muscle of controls. The quantity of total GDNF in IHPS was significantly higher than in controls (P < .01). CONCLUSIONS: The lack or markedly decreased number of GDNF-positive nerve fibers in IHPS supports the hypothesis of a selective immaturity of the enteric glia in the muscular layers in IHPS. The strong expression of GDNF in smooth muscle cells in IHPS and the increased levels of GDNF in IHPS suggest a compensatory mechanism by which the smooth muscle cells continue to produce GDNF until maturation of the enteric glial cells occurs.

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.

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.

Correlation of prostaglandin E2 production and gastric acid secretion in infants with hypertrophic pyloric stenosis.

PURPOSE: The aim of this study was to evaluate the relationship between gastric acid secretion and prostaglandin E2 (PGE2) generation in gastric mucosa and the role of PGE2 in the pathogenesis of hypertrophic pyloric stenosis (HPS). METHODS: The authors measured the levels of PGE2 and gastric acidity in the gastric juice of HPS patients before and after a Ramstedt operation. RESULTS: The PGE2 concentration in the gastric juice of nine HPS patients before the Ramstedt operation was significantly higher than that of eight controls, and the concentration significantly decreased after the operation. A significant inverse correlation between the PGE2 concentration and the pH level in the gastric juice was shown in HPS patients before and after the operation. CONCLUSION: These results suggest that the enhanced generation of PGE2 in gastric mucosa in cases of HPS is a secondary phenomenon caused by hyperacidity and is not responsible for the pathogenesis of HPS.

Active collagen synthesis in infantile hypertrophic pyloric stenosis.

M-57 antibody, which is capable of distinguishing newly-synthesized type I procollagen from fully-processed, mature collagen, was used to examine the expression of collagen synthesis in hypertrophic pyloric muscle from patients with infantile hypertrophic pyloric stenosis (IHPS). Seven specimens from IHPS patients were removed at the time of operation; age-matched normal pyloric tissue of 5 post-mortem cases was obtained as controls. Immunohistochemistry was performed using antibody of the amino-terminal end of the procollagen type I propeptide (M-57). Newly-synthesized procollagen (M-57) was strongly detected in both the connective tissue septa between circular muscle bundles, and among the circular-muscle fibers in patients with IHPS. No M-57 staining was observed among the circular-muscle fibers in controls. Our findings show that the hypertrophic circular muscle in IHPS is actively synthesizing collagen, and this may be responsible for the characteristic "firm" nature of the pyloric tumor.

Increased insulin-like growth factor-I mRNA expression in pyloric muscle in infantile hypertrophic pyloric stenosis.

The etiology of infantile hypertrophic pyloric stenosis (IHPS) is unknown. Insulin-like growth factor-I (IGF-I) is a polypeptide hormone that elicits various biological activities (cellular growth, replication, and differentiation) by binding to its receptors. IGF-I has been suggested to play an important role in both gastrointestinal (GI) maturation and smooth-muscle-cell (SMC) hypertrophy. Full-thickness muscle biopsy specimens were obtained from 8 IHPS patients (age range 14-64 days, mean 28.1 days) at pyloromyotomy and from 8 age-matched controls (15-60 days, mean 33.8 days) without GI disease at autopsy. In-situ hybridization was performed using an IGF-I-specific and digoxigenin (DIG)-labeled oligonucleotide probe and visualized by nitroblue tetrazolium staining. In normal controls, IGF-I mRNA expression was absent or weak in both circular and longitudinal smooth-muscle layers of pyloric muscle. In contrast, the pyloric muscle in IHPS patients demonstrated strong IGF-I mRNA expression in the circular smooth-muscle layer and moderate expression in the longitudinal smooth-muscle layer. The increase in IGF-I mRNA in pyloric muscle in IHPS suggests that SMCs are actively synthesizing IGF-I, contributing to the development of pyloric muscle hypertrophy.

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.