Extracorporeal circulation in neonatal respiratory failure: a prospective randomized study.

A prospective controlled randomized study of the use of extracorporeal membrane oxygenation to treat newborns with respiratory failure was carried out using the "randomized play-the-winner" statistical method. In this method the chance of randomly assigning an infant to one treatment or the other is influenced by the outcome of treatment of each patient in the study. If one treatment is more successful, more patients are randomly assigned to that treatment. A group of 12 infants with birth weight greater than 2 kg met objective criteria for high mortality risk. One patient was randomly assigned to conventional treatment (that patient died); 11 patients were randomly chosen for extracorporeal membrane oxygenation (all survived). Intracerebral hemorrhage occurred in one of 11 surviving children. Extracorporeal membrane oxygenation allows lung rest and improves survival compared to conventional ventilator therapy in newborn infants with severe respiratory failure.

Regenerative healing of incisional wounds in midgestational murine hearts in organ culture.

OBJECTIVE: Using an organ-culture fetal heart repair model, we explored fetal repair in tissues other than dermis. METHODS: Wounded fetal mouse hearts of 14 and 18 days' gestation (term = 20 days), as well as hearts of 22 days' gestation (newborn), were maintained in serum-free medium. Specimens were fixed at 2, 7, and 11 days and then processed for histologic examination. Small fragments of fetal hearts from all time points were cultured as explants. The migration of cells from the periphery of the explants was compared at day 4, and the pattern of microfilaments in these cells was assessed. RESULTS: In 14-day hearts (n = 18), tissue architecture was rapidly reestablished without an inflammatory response or scarring, constituting regenerative repair. In 18-day hearts (n = 18), no reestablishment of muscle fibers or wound closure occurred. In the 22-day explants (n = 12) the wounds closed by scarring. Cell migration from 14-day explants was 4.7 +/- 2.3 ocular units; from 18-day explants, it was 2.6 +/- 1.1 ocular units; and from 22-day explants, it was 0.9 +/- 0.4 ocular units. Microfilaments of 14-day cells were arranged at the periphery of the cell consistent with cardiomyocytes. Microfilaments of 18- and 22-day cells were arranged in parallel arrays (stress fibers) that were consistent with fibroblasts. CONCLUSIONS: We propose that regenerative healing of 14-day fetal hearts is by the migration of cardiomyocytes. At 18 and 22 days, cardiomyocytes are too differentiated and unable to migrate; hence cell migration is limited to resident fibroblasts, which are deficient at 18 days but sufficient at 21 days to be repaired by the scarring process.

Congenital urethral-perineal fistula: diagnosis and new surgical management.

Congenital posterior urethral-perineal fistula is a rare anomaly of which there have been only 6 reported cases to date. This report outlines the clinical presentation of another case and a unique surgical approach to its management, as well as a review of the English literature.

Anatomic and functional abnormalities of the esophagus in infants surviving congenital diaphragmatic hernia.

As more infants with congenital diaphragmatic hernia (CDH) survive by means of extracorporeal membrane oxygenation (ECMO), new clinical observations are being made. We report anatomic and functional abnormalities of the esophagus in these infants. Twenty-two of 30 infants with CDH survived. Three of 7 non-ECMO-treated infants and 14 of 17 ECMO-treated infants had an air- or fluid-filled mediastinal mass that was confirmed by an upper gastrointestinal series as ectatic esophagus. Contrast studies demonstrated severe gastroesophageal reflux. Intra-esophageal pH monitoring confirmed significant reflux (Euler scores greater than 50) in 69% of tested patients. Prolonged acid clearance in most patients implied abnormal peristalsis. Hydramnios was correlated to the observed esophageal abnormalities, being present in 13 of 16 infants with an available amniotic history. All patients had symptomatic gastroesophageal reflux managed without antireflux surgery and were discharged 36 +/- 2 days after initiation of feeding. Follow-up (range: 7 to 56 months; mean: 32 months) showed that weight gain in affected children was slower than in those not affected. All but one are asymptomatic. Repeat upper gastrointestinal series shows persistent ectasia but less gastro-esophageal reflux. Gastroesophageal reflux/ectasia is a new observation with CDH. The associated hydramnios may result from proximal foregut obstruction by kinking the gastroesophageal junction with CDH. The radiographic appearance can be quite unusual. Clinical manifestations of gastro-esophageal reflux are manageable without surgery but may account for the observed compromised growth.

Nonrhabdomyosarcoma soft tissue sarcomas in children.

Nonrhabdomyosarcoma soft tissue sarcomas are very rare tumors in the pediatric population and consist of a heterogeneous collection of subtypes. They can occur anywhere in the body, with the extremities the most common anatomic site. In the initial evaluation of a soft tissue mass, proper radiographic evaluation is best performed with magnetic resonance (MR) imaging, while tissue for diagnosis should be obtained with a well planned incisional biopsy. Complete surgical resection remains the cornerstone of therapy, but it is now recognized that multi-modal strategies incorporating surgery, radiotherapy, and chemotherapy should be studied for incompletely resected tumors and those with poor prognostic indicators.

Pediatric soft tissue infections.

Quite often a soft tissue infection in a child may be the primary reason for seeking medical attention or an incidental finding on examination. To identify those infections that may be serious and require further intervention, all those dedicated to the care of children must be familiar with these illnesses and their complications. This article covers selected bacterial, viral, and fungal infections of the skin, subcutaneous fat, fascia, and muscle. Special considerations for the immunosuppressed child will also be discussed.

Fetal tissue repair and wound healing.

The fibrosis and scar formation that characterize adult wound healing are also the cause of clinical problems; scar contracture, hypertrophic scar, and pulmonary and hepatic fibrosis are only a few examples. Studies of fetal wound healing can provide an insight into the initiation and regulation of a scarless repair process akin to regeneration. Studies of fetal repair have already suggested mechanisms that might favorably alter adult healing. Topical application of hyaluronic acid to wounds in adult diabetic rats leads to enhanced epithelial migration. It has been recognized that the addition of TGF-beta to fetal wounds causes an adultlike healing response with fibrosis and inflammation. A subsequent study using neutralizing antibody to TGF-beta in adult wounds showed enhanced healing with a more normal dermal architecture with fewer macrophages, fewer blood vessels, and less collagen. As our understanding of regenerative tissue repair increases, the opportunities to modulate adult fibrotic conditions should expand.

Newborn surgical emergencies. Gastrointestinal anomalies, abdominal wall defects.

Structural anomalies of the gastrointestinal tract and anterior abdominal wall diagnosed in the perinatal period often require prompt surgical intervention. This article highlights the pathophysiology, evaluation, and management of the more common lesions encountered in the neonate.

Modification of cardiopulmonary hemodynamics and vasoactive mediators by extracorporeal membrane oxygenation in newborn lambs.

We asked if prolonged venoarterial extracorporeal membrane oxygenation (ECMO) causes alterations in cardiopulmonary hemodynamics that might be reflected in arbiters of vascular tone: thromboxane, prostacylin, norepinephrine, and epinephrine. Newborn lambs undergoing ECMO demonstrated significant augmentation of systemic and pulmonary arterial blood pressure that was temporally related to rises in all vasoactive mediators measured. Although the prostanoids returned to baseline within 30 minutes, the catecholamines remained elevated significantly throughout bypass. Long-term bypass, however, was not associated with sustained systemic hypertension. Pulmonary hypertension was achieved only after 6 hours of bypass. These acute and chronic changes may exacerbate a pathological state for which ECMO is indicated.

Extracorporeal membrane oxygenation and congenital diaphragmatic hernia: modification of the pulmonary vasoactive profile.

We studied the vasoactive profile of a term infant with congenital diaphragmatic hernia and intractable pulmonary hypertension who was refractory to conventional medical management despite an early stable period. Plasma prostanoid vasoconstrictor thromboxane A2 (TxB2) levels were elevated prior to ECMO at 150pg/mL, rose to 310pg/mL with the first hour of bypass and remained elevated until 72 hours by which time they fell to less than 50pg/mL. This coincided with the decreased extracorporeal circulatory support needed to maintain systemic arterial pO2 between 70 to 90 torr. Pulmonary vasodilator prostacyclin (6-keto-PGF1 alpha) was minimally elevated prior to bypass a 50pg/mL and became undetectable. Catecholamine levels were markedly elevated prior to ECMO at 4,000pg/mL with no demonstrable pulmonary extraction of norepinephrine. Though catecholamine levels remained nonspecifically elevated, pulmonary metabolism of norepinephrine improved with bypass time to 48% at 96 hours and coincided with the overall improvement of the infant's respiratory function. These data suggest pulmonary hypertension associated with congenital diaphragmatic hernia is at least partially precipitated by alterations in prostanoid homeostasis as selective activation of thromboxane synthetase pathways rather than nonspecific activation of the entire archidonate cascade. While ECMO per se may have no lasting effect on prostanoid homeostasis, ECMO can allow a period of cardiopulmonary rest during which more physiologic prostanoid levels are established. Although activation of the sympatho-adrenal axis may contribute to pulmonary hypertension, the role of catecholamines in this infant is not clear. Return of the lungs ability to clear norepinephrine may be an additional marker of biologic lung recovery.

Endoscopic sphincterotomy in the management of posttraumatic biliary fistula.

Complications after nonoperative management of hepatic trauma are rare but include persistent biliary fistula in 4% of cases. Therapy usually involves surgical drainage or hepatic resection to control the fistula. The authors present a case of hepatic biliary fistula treated nonoperatively with percutaneous drainage and endoscopic sphincterotomy. A 16-year-old girl suffered a grade III parenchymal liver fracture to the right lobe in an automobile accident. She was hemodynamically stable with no coexistent injuries and was treated nonoperatively. Over 2 weeks her total bilirubin rose to 3.2 mg/dL, and alkaline phosphatase was 463 U/L. Ultrasound showed free intraperitoneal fluid, and 2 L of bilious fluid were retrieved by paracentesis. A radionuclide scan confirmed massive extravasation of isotope from the right lobe. Two drains percutaneously placed over the parenchymal fracture produced 500 to 600 mL of bile daily. Endoscopic retrograde cholangiopancreatography (ERCP) 1 week later showed a normal extrahepatic biliary system. A 1-cm sphincterotomy was performed without difficulty. Within 72 hours, percutaneous drains produced only 35 mL per day. The follow-up radionuclide scan showed no evidence of extrahepatic biliary extravasation, and 3 weeks later the drains were removed. Six months after the accident, results of the computerized tomography scan and liver function tests were normal. It was believed that endoscopic sphincterotomy reduced fistula output by decreasing the intrabiliary pressure caused by the ampulla, thus favoring internal drainage. This case demonstrates the effectiveness of endoscopic sphincterotomy as an alternative to direct surgical intervention for the management of posttraumatic biliary fistula.

Isolated fetal mouse limbs: gestational effects on tissue repair in an unperfused system.

While it is known that adult tissue repair is tightly regulated through local effects in the wound environment mediated by circulating blood elements such as platelets, white cells, cytokines, and hormones, the degree to which each is required in fetal tissue repair is uncertain. This raises the following questions regarding regulation of fetal tissue repair: (1) is the local wound matrix alone sufficient to sustain fetal tissue repair in the same regenerative manner seen in previous in vivo whole animal studies? (2) Will it occur only during the period of rapid fetal growth and development in early and mid gestation? To address these fundamental questions, an organ culture system has been designed to grow isolated, unperfused, developing fetal mouse limbs in a chemically defined, serum-free media. Amputated fetal mouse forelimbs (n > or = 10) were wounded with linear incisions at gestational days 14, 16, and 18 (term = 19); the wounds were closed primarily. These amputated and wounded limbs were placed on steel grids in organ culture petri dishes, then partially submerged in a chemically defined, serum-free media. The limbs were grown at 37 degrees C in humidified 95% air/5% CO2 for 1 week. These wounded limbs were examined histologically at days 0, 3, and 7 postwounding to determine their viability and whether or not tissue repair occurred. In the 14-day group, limb growth and differentiation was evident during the incubation period. Normal dermal and epidermal architecture was restored at the wound site without abundant collagen deposition by day 7 postwounding.(ABSTRACT TRUNCATED AT 250 WORDS)

The potential role of the lymphocyte in fetal wound healing.

Wound healing is a complex process involving a number of different cell populations. Since fetal wounds contain only a small number of mononuclear cells and no fibrosis immunohistochemical techniques using monoclonal antibodies specific to T and B lymphocytes, as well as macrophages, were used to identify the mononuclear cells in fetal wounds and to compare the lymphocyte response with the adult wound healing response. Polyvinyl alcohol sponges were placed subcutaneously in fetal rabbits on day 24 of gestation (then 31 days). Adult rabbits underwent similar implantation. Implants (8 to 14 per group) were harvested 5 days later and examined by H&E and trichrome staining as well as immunohistochemical staining with monoclonal antibody (Mab) specific for rabbit T and B lymphocytes. The sponges in one group of fetal rabbits were impregnated with the polypeptide growth factor, transforming growth factor-beta (TGF-beta), a known regulator of adult tissue repair. Adult wounds showed an intense inflammatory response with extensive collagen deposition; 80% of the infiltrating cellular elements were T lymphocytes. Fetal wounds were less cellular with minimal collagen deposition; 40% of the cells were T lymphocytes. The fetal wounds treated with TGF-beta were intensely cellular and fibrotic with 71% of the cellular infiltrate comprised of T lymphocytes. The increased cellularity of the TGF-beta wounds appears to be primarily the result of increased numbers of T lymphocytes. These findings demonstrate that the fetus mounts an attenuated T lymphocyte response compared to the adult. The increased response of T lymphocytes with TGF-beta suggests that the specific growth factor milieu may account for the fetal response to wounding.(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant tissue plasminogen activator for neonatal and pediatric vascular thrombolytic therapy.

Thrombotic vascular occlusion may complicate the clinical course of many neonatal and pediatric pathologic processes. Systemic thrombolytic therapy with heparin, urokinase, or streptokinase may not be appropriate in the critically ill neonate because these agents generate a diffuse coagulopathic state. Direct surgical intervention for repair may be precluded by the small size of the vessels involved. Recombinant tissue plasminogen activator (rTPA) induces only a minimal proteolytic state while inducing thrombolysis within the local environment of the clot. We report our experience with regional rTPA infusion in four critically ill patients with venous and arterial thrombotic disorders. there were two brachial artery occlusive lesions--a neonate with iatrogenic occlusion due to a misplaced intravenous catheter and a 2-year-old child with inadvertent arterial ligation during an attempted venous cutdown. Two venous lesions consisted of a full-term neonate with renal vein/inferior vena caval thrombosis and a 32-week infant with partial superior vena caval thrombosis due to a Broviac catheter. Systemic thrombolytic therapy was contraindicated in these patients because of underlying illnesses. Pretherapy vascular evaluation included Doppler examination and angiography. The rTPA infusion was continued until there was evidence of clot lysis by ultrasound, angiogram, or venogram. Infusion rate of rTPA was adjusted according to fibrinogen levels. All three neonates responded successfully to rTPA therapy. Two neonates required only bolus administration and one responded to combined bolus and continuous infusion therapy after 58 hours. rTPA failed to reverse brachial artery occlusion in the 2-year-old child with purpura fulminans.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitric oxide reversal of recurrent pulmonary hypertension and respiratory failure in an infant with CDH after successful ECMO therapy.

Nitric oxide (NO) represents a new therapeutic modality for treating neonatal pulmonary hypertension and may obviate the need for extracorporeal membrane oxygenation (ECMO) in a number of cases of neonatal respiratory failure. Recently, the authors treated an infant with a congenital diaphragmatic hernia and pulmonary hypertension with NO on two separate occassions. During the initial period of stabilization, NO failed to reverse the pulmonary hypertension and prevent the development of progressive respiratory failure. After a successful course of ECMO, recurrent pulmonary hypertension developed that was successfully treated with continuous low-dose NO therapy for over 1 month. Prolonged administration of NO in varying doses titrated to clinical and echocardiographic parameters was well tolerated by the infant and prevented the need for a second run of ECMO.

Long-term outcome for infants and children with sacrococcygeal teratoma: a report from the Childrens Cancer Group.

BACKGROUND/PURPOSE: Sacrococcygeal teratomas (SCT) are a relatively uncommon tumor affecting neonates, infants, and children. This study was designed to determine the effect of therapy on the long-term outcome of neonates and children with sacrococcygeal teratomas (SCT). METHODS: The authors conducted a retrospective review of children with SCT treated at 15 Childrens Cancer Group institutions from 1972 to 1994. RESULTS: One hundred twenty-six children presented with SCT diagnosed prenatally (n = 32), at birth (n = 79), or later in infancy (n = 15). For neonates, complete resection was performed except in two babies with lethal associated defects. All others (n = 15) underwent resection at the age of diagnosis. Six had a sacral mass identified at birth but had delayed surgery (1.5 to 11 months) and of these, two were malignant. Resection was via sacral (n = 96) or abdominosacral (n = 28) approach. Histology showed mature teratoma (MT, 69%), immature teratoma (IT, 20%), or endodermal sinus tumor (EST, 11%) at presentation. Seven neonates (5.6%) died of perioperative complications, whereas the remaining 117 were available for long-term follow-up. Between 6 and 34 months postresection, recurrent disease developed in 9 of 80 MT patients (11%) followed-up for a mean of 5 years. Recurrent disease was MT (n = 2) and EST (n = 7). The recurrent EST patients were treated with adjuvant chemotherapy. Six are alive with mean follow-up of 114 months, whereas one with metastatic disease was lost to follow-up. Recurrence (MT) developed in only 1 of 24 IT patients, and all are alive and well at mean follow-up of 39 months. Patients presenting with EST (n = 13) underwent excision, with two dying from non-EST causes. Six EST patients received no chemotherapy, with two of the six (33%) experiencing recurrence within 11 months and both disease free after salvage chemotherapy. The remaining five EST patients received adjuvant chemotherapy; four are alive and one died of metastatic disease. Of the 18 EST patients followed-up after resection (presentation, 11, recurrent teratoma, 7), 16 (89%) are free of disease with a mean follow-up of 91 months. CONCLUSIONS: (1) Benign teratomas have a significant recurrence rate mandating close follow-up for more than 3 years. (2) Surgical resection alone is adequate therapy for nonmetastatic malignant tumors. (3) Survival for malignant lesions with metastases is excellent with modern chemotherapy.

Postnatal pulmonary hypertension after repair of congenital diaphragmatic hernia: predicting risk and outcome.

BACKGROUND: Pulmonary hypertension (PH) after congenital diaphragmatic hernia (CDH) repair remains a significant cause of morbidity and mortality. Although treatment advances have improved overall survival, a new cohort of patients is surviving with PH beyond the postnatal period. Because the clinical entity of postnatal persistent pulmonary hypertension (PPHTN) in CDH patients has not been published, the authors undertook a retrospective study of our neonatal CDH experience to characterize this group of infants. METHODS: Charts of all infants with CDH treated at this institution from January 1991 to June 1997 were reviewed (n = 51). Persistent pulmonary hypertension by echocardiographic (Echo) measurements at the time of discharge identified PPHTN patients. Control survivors had normal pulmonary artery pressures at discharge. Physiological parameters and the results of therapeutic interventions were analyzed to predict PPHTN. RESULTS: Seven infants (four boys, three girls) had PPHTN at discharge. Significant differences with the control group were noted in length of stay, duration of intubation, and duration of nitric oxide therapy. Extracorporeal membrane oxygenation (ECMO) duration was not significantly different between the groups. By 12 months of age, PPHTN resolved in six patients (87%), and one died at 13 months. Regardless of therapy, two parameters showed 100% positive predictive value for identifying patients with PPHTN (P < .001): an Echo demonstrating PH at 2 months of age or continued oxygen requirement at 3 months. Oxygen requirement at 2 months had a 67% predictive value of PPHTN. CONCLUSIONS: With current treatment strategies for CDH, infants can survive with persistent pulmonary hypertension beyond the newborn period. The long-term survival rate is excellent, and normalization of pulmonary artery pressures can be expected. PPHTN can be predicted in those infants with Echo-defined pulmonary hypertension at 2 months.

Immunosuppression as adjuvant therapy for biliary atresia.

BACKGROUND/PURPOSE: Despite improvements in the surgical management of biliary atresia, the long-term incidence of progressive liver failure remains high. Because chronic inflammation involving both bile ducts and liver parenchyma contributes to the pathology, the authors have hypothesized that the liver damage may be altered using immunosuppressive therapy. The aim of this study was to examine the safety and efficacy of long-term steroid therapy in patients with biliary atresia. METHODS: A retrospective analysis of all patients with biliary atresia treated with an hepatoportoenterostomy and postoperative steroid therapy at our 3 institutions was undertaken. Patients were treated uniformly with immunosuppressive doses of oral steroids for a minimum of 6 weeks after surgery. RESULTS: Twenty-five infants with biliary atresia were treated with steroid therapy. Overall survival rate was 22 patients (88%) with a mean follow-up period of 50 months. Nineteen patients (76%) became jaundice free with native liver function. Four patients (16%) did not respond to treatment and required transplantation. Age less than 12 weeks was a crucial predictor of success of adjuvant steroid therapy. Cholangitis developed in 8 patients (32%). There were no complications caused by steroid therapy. CONCLUSIONS: Steroid administration at immunosuppressive doses markedly improves the clinical outcome within the first 5 years after surgery as measured by jaundice-free status and survival without liver transplantation when compared with concurrent reports. These results suggest that immunosuppressive therapy is safe and has a positive impact on the clinical course of this disease. However, a randomized study is needed to ultimately prove such an hypothesis.

Diagnosis, management, and outcome of cervicofacial teratomas in neonates: a Childrens Cancer Group study.

The management of cervicofacial teratomas in neonates is often complicated and may result in significant morbidity and death. A Childrens Cancer Group (CCG) retrospective study was conducted to evaluate a multiinstitutional experience with the treatment of these extremely rare neoplasms. Twenty neonates with cervicofacial teratomas, presenting from 1971 to 1994, were identified from nine CCG institutions. Fourteen neonates had cervical teratomas, and six had orofacial teratomas. There were 12 males and eight females. A diagnostic prenatal ultrasound examination was performed in six cases. Life-threatening airway obstruction occurred in seven infants (35%) in the early postnatal period. Two neonates died in the delivery room without ever having their airway secured. Two other infants with a prenatal diagnosis survived only because tracheostomies were performed by pediatric surgeons who were in the delivery room. Three other patients were orally intubated, one after sustaining hypoxic cardiac arrest. Eighteen infants had their primary tumor excised. Three patients required tracheostomy. After resection, two patients had evidence of unilateral recurrent laryngeal nerve injury, and two required prolonged thyroid hormone replacement. Histological examination showed eight mature and seven immature teratomas. Four infants (20%) clearly had malignant lesions. Pulmonary metastases occurred in two patients and contributed to one late death at 6 months of age. The overall survival rate was 85%, and the mean follow-up period was 5 years (range, 2 months to 16 years). Twelve of 17 surviving patients (70%) have had an excellent functional and cosmetic outcome. Four children have varying degrees of developmental delay and mental retardation. Hypoxia at birth was believed to have contributed to these problems in two cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal soft tissue sarcomas: the influence of pathology on treatment and survival. Children's Cancer Group Surgical Committee.

INTRODUCTION: A multi-institutional study was conducted by the Children's Cancer Group (CCG) to evaluate all soft tissue sarcomas diagnosed within the first month of life. METHODS: A retrospective study by 11 CCG institutions of patient records from 1971 to 1991 were reviewed for demographic data, pathology, therapy, and outcome. RESULTS: 32 neonates with soft tissue sarcomas were identified. There were 21 boys and 11 girls. Pathology was equally divided into three groups: Congenital fibrosarcoma (CFS) (12), rhabdomyosarcoma (RMS) (11), and non-RMS soft tissue sarcomas (NRSTS) (9). Anatomic sites consisted of head/neck (11), extremity (9), trunk (8), pelvis (3), and unknown (2). Overall survival rate was 59% (19/32). CONCLUSION: Soft tissue sarcomas in the neonate comprise three general groups with survival rates dependent on pathology and extent of disease.