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Background/purpose: The progress made in all fields of medicine, including neonatal surgery, has contributed to the rise in healthcare costs. Although neonatal surgery may provide survival gains, these could be at the expense of worse quality of life caused by impairment after surgery. For example, congenital anorectal malformations (CAM) are complex anomalies, and the surgical techniques available have their limitations in achieving continence. It therefore seems justifiable to consider what the effects of treatment are in relation to the costs. Evidence of the cost-effectiveness of neonatal surgery, however, is lacking., Methods: The authors analyzed both direct and indirect, medical and nonmedical costs in patients who had undergone treatment for CAM. Quality-adjusted life years (QALYs) were measured using the EuroQol EQ-5D questionnaire. Descriptive quality-of-life data were collected using a disease-specific questionnaire and a medical consumption questionnaire., Results: Mean costs of treatment are calculated at Euro 31,593. Treated CAM patients suffer stool difficulties and their medical consumption is relatively high. The EQ-5D, however, shows that the quality of life of CAM patients is only slightly lower than that of the general population (0.88 v 0.93). Treatment results in a gain of 12.7 QALYs. Costs per QALY of treatment for CAM amount to Euro 2,482., Conclusions: Treatment for CAM has a favorable cost-effectiveness ratio compared with other evaluated healthcare programs. Bearing in mind the increasing political interest in evidence-based and cost-effective medicine, the results are encouraging., (Copyright 2001 by W.B. Saunders Company.)

Background/purpose: Technological developments have revolutionized both diagnosis and treatment in neonatal surgery. However, it has been increasingly recognized that financial resources might become insufficient to provide all the medical care that is technically feasible or that patients and families might desire. The purpose of this study is to apply the theory of health economics to neonatal surgery and to explore the extent and the kind of economic evaluation done in neonatal surgery., Methods: To explore the work done so far, the authors undertook a literature search aimed at costs and effects of surgical interventions in newborns with Ravitch' surgical index diagnoses of congenital anomalies. Common keywords in cost-effectiveness analysis were used to search Medline., Results: Evidence about the cost effectiveness of neonatal surgery is largely lacking. This is probably because of difficulties in long-term tracking of the patients and to the problem that most generic quality-of-life measures are not applicable in children yet., Conclusions: Further cost-effectiveness research in neonatal surgery is warranted to settle priority discussions in health care when neonatal surgery is part of such discussions. Methodology for generic quality-of-life measurement in children is badly needed.

Background/purpose: Auxiliary liver transplantation is an attractive alternative for orthotopic liver transplantation in patients with certain inborn errors of metabolism of the liver in which complete resection of the liver is unnecessary or even contraindicated. Because in these diseases portal hypertension is mostly absent, finding a balance in portal blood distribution between native liver and graft is complicated. The objective of this study was to investigate requirements for long-term (180 days) graft survival in auxiliary partial heterotopic liver transplantation (APHLT) in a dog model., Methods: A metabolic defect was corrected in 26 dalmation dogs with a 60% beagle heterotopic auxiliary liver graft. Four groups of different portal inflow were studied. In the ligation group the portal vein to the host liver was ligated. In the split-flow group graft and host liver received separate portal inflow. In the banding group the distribution of the portal flow was regulated with an adjustable strapband and in the free-flow group the portal blood was allowed to flow randomly to host or graft liver., Results: Metabolic correction increased in all groups after transplantation from 0.19 +/- 0.02 to 0.70 +/- 0.05 (P< .0001) but remained significantly better in the ligation and split-flow groups (graft survival, 135 +/- 27 and 144 +/- 31 days). In the banding group metabolic correction decreased significantly after 70 days, and although the grafts kept some function for 155 +/- 14 days, in 4 of 6 dogs portal thrombosis was found. In the free-flow group, competition for the portal blood led to reduced correction within 12 days and total loss of function in 96 +/- 14 days. Graft function also was assessed with technetium (Tc) 99m dimethyl-iminodiacetic acid uptake. A good linear association between HIDA uptake and metabolic correction was observed (r = 0.74; P < .0005). Grafts that contributed more than 15% to the total uptake of HIDA showed biochemical correction. This indicates a critical graft mass of about 15% to 20% of the hepatocyte volume to correct this metabolic defect., Conclusion: Auxiliary partial heterotopic liver transplantation can be a valuable alternative treatment for inborn errors of hepatic metabolism if the native liver and the graft receive separate portal blood inflow.

Short bowel syndrome (SBS) in the newborn results in limited intestinal absorptive capacity, leading especially to fatty acid (FA) malabsorption. It is unknown whether adaptation occurs in time in FA absorption, and whether this adaptation is chain-length dependent. The aid of the present study was to prospectively evaluate FA absorption and excretion during SBS in the newborn. Twenty-one neonates who underwent small bowel resection (of variable length) for various reasons (necrotizing enterocolitis, intestinal atresia, meconium peritonitis, cloacal extrophy, etc) were studied. Eight neonates had SBS, defined as a small bowel remnant of less than 50% of the original small bowel length related to gestational age. The mean remaining small bowel length in the SBS group was 34% (24% to 42%). The non-SBS control group consisted of 13 neonates who had only minor small bowel resections. The mean remaining bowel length for the non-SBS group was 95% (70% to 100%). The results show that the total fractional excretion of FA (FE-FA) at 2 weeks and 1, 2, 3, and 4 months postsurgery was 51% +/- 37%, 33% +/- 24%, 51% +/- 65%, 53% +/- 27%, and 7% +/- 2% in patients with SBS, versus 12% +/- 8%, 24% +/- 10%, 9% +/- 3%, 8% +/- 3% and 17% +/- 14% in the non-SBS controls, respectively (P < .05 by ANOVA). There appeared to be an amelioration in time in FA absorption, especially in the SBS group, after 3 months. FE-FA was chain-length related, being considerably less for C10 and C12 than for C14 and longer amounts. An amelioration of absorption occurred in the SBS patients, especially with the longer-chain FA. On the basis of the study data, the authors conclude that in the initial adaptation phase shorter chain lengths are better absorbed than longer chain lengths; however, in the latter FA group, substantial adaptation occurs with time.

The authors report their experience with hepatic artery ligation in two newborns, as well as relevant findings from a literature review. A 2-day-old boy had progressive cardiac and respiratory difficulty. A firm liver was palpable, with an overlying thrill. Sonography and arteriography showed diffuse arteriovenous shunting in both liver lobes. Hepatic artery ligation provided remarkable hemodynamic and clinical improvement. Another boy was admitted 3 weeks after birth because of bilious vomiting with abdominal distension and bloody stools. Abdominal examination showed a large liver with a systolic bruit and thrill. X-rays showed cardiac enlargement and dilated bowel loops with air-fluid levels. Arteriography and sonography showed arteriovenous and arterioportal venous shunting. Laparotomy was performed, and a large vascular malformation was palpated in both liver lobes. The entire bowel was congested and cyanotic, but there were no signs of obstruction. This patient had acute portal hypertension imitating intestinal obstruction. Ligation of the hepatic artery improved the color of the bowel, and the thrill disappeared. Five and nearly 4 years after the operation, both boys are growing normally without medication or diet. Sonography showed almost complete resolution of the hemangiomas.

This study was undertaken to investigate whether two-stage segmental small bowel allotransplantation can maintain growth and development of young dogs (16 weeks, 5 to 6 kg) with surgically created short bowel syndrome (SBS). After near-total small bowel resection (group 1; n = 3), irreversible weight loss was noted. After a sham operation (group 2; n = 3), no growth disturbances were found. Major histocompatibility matched small bowel transplantation (SBT) with cyclosporine A as immunosuppressant, was performed in two stages (group 3; n = 7). During the first stage, one meter of jejunoileum from an adult donor was placed as a Roux loop. Four weeks later, the native small bowel was removed and replaced by the graft. Only one dog survived long-term; the dogs died from infectious complications. The addition of selective decontamination of the digestive tract and early gastrostomy feeding (group 4; n = 10) resulted in long-term survival in 60%. Follow-up at 4 months showed that their growth was about 20% compromised compared with that of the sham-operated animals. Functional analysis showed that electrolytes, urea, and D-xylose were normal, but there was an increase in the lactulose:mannitol ratio, fecal fat excretion, and postheparin diamine oxidase release. These results show that under the conditions described, segmental SBT functions sufficiently to treat SBS but does not maintain normal growth.

The outcome after major bowel resection in the neonatal period depends primarily on the time needed for bowel adaptation. A prospective study was begun in neonates after small bowel resection to evaluate the absorptive capacity of the bowel and growth parameters as a result of adaptation of the bowel. Twenty-four neonates who underwent bowel resection were included. The underlying diagnoses were necrotising enterocolitis (12), jejunal atresia (3), meconium peritonitis (3), and other (6). During the study, a standardized treatment with respect to nutrition was followed. At predetermined times, enterostomy fluid or faeces were collected for analysis of carbohydrate content, fat content, and fatty acids, together with a xylose test and a hydrogen breath test. Growth parameters included weight and height. The 24 patients were divided into two groups. Group A consisted of eight patients with short bowel syndrome (defined as loss of more than 50% of the original small bowel length related to gestational age). The mean remaining small bowel length in this group was 34.0% (24% to 42%). Group B consisted of 16 patients who had only minor bowel resections. Retarded growth was observed in four group A patients. Low levels of carbohydrate absorption were found 2 and 4 weeks after the initial operation in group A, and 2 weeks after the initial operation in group B. Low levels of fat absorption were found 4 and 8 weeks after the initial operation in group A. The coefficient of absorption of the different fatty acids showed complete absorption of caprylic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracorporeal membrane oxygenation (ECMO) is a commonly used treatment modality for severe neonatal respiratory failure. The aim of the present study was to evaluate the relationship between ECMO blood flow and gas exchange across the native lungs and the extracorporeal membrane. In three healthy pigs, the ECMO flow correlated significantly with oxygen transfer (VO2) across the membrane (n = 12, r = .90, P < .001) and inversely with VO2 across the lungs (n = 12, r = -.75, p < .005). In three pigs with acute respiratory distress syndrome induced by repeated bronchoalveolar lavage, flow also significantly correlated with VO2 across the membrane (n = 9, r = .93, P < .001) and inversely with VO2 across the lungs (n = 9, r = -.97, P < .001). Eight neonates had measurements taken at different time intervals and different flow rates during ECMO. The ECMO flow correlated significantly with VO2 across the membrane (n = 45, r = .61, P < .001) and inversely with VO2 across the lungs (n = 15, r = -.54, P < .05). The relationship between carbon dioxide transfer (VCO2) and ECMO flow rates had the same trend as VO2 on all occasions. It is concluded that the ECMO flow rate is one of the main determinants of gas exchange across the lungs and the membrane.

Patients with congenital diaphragmatic hernia (CDH) have unilateral or bilateral hypoplasia of the lungs including delayed maturation of the terminal air sacs. Because these lungs are highly susceptible to barotrauma and oxygen toxicity, even in full-term newborns, continued research into optimal ventilatory regimen is essential to improve survival rate and to prevent ongoing lung damage. Against this background, the effect of exogenous surfactant application is evaluated. In newborn rats, CDH was induced after a single dose of 2,4 dichloro-4'-nitrophenyl (Nitrofen) (400 mg/kg) on day 10 of gestation. The newborn rats were intubated immediately after hysterotomy, transferred to a heated multichambered body plethysmograph, and artificially ventilated. Inspiratory peak pressures were initially set at 17 cm H2O, with positive end-expiratory pressure at 0 cm H2O and FIO2 at 1.0. The pressure was raised in steps of 5 cm H2O, from 5 to 30 cm H2O, to obtain pressure-volume diagrams at 0, 1, and 6 hours of artificial ventilation. These measurements were obtained in controls and in CDH rats with and without endotracheal installation of bovine surfactant (n = 4 to 10 in each group). Significant differences in lung volume between CDH and control rats were observed at all time-points. Surfactant application had a positive effect on lung volume, especially in control rats at t = 1 hour. No significant differences were observed between the CDH groups at t = 1 or t = 6 hours. In this animal model, the effect of artificial ventilation as well as the beneficial short-term effect of exogenous surfactant application have been evaluated. A continued positive effect on lung volume in CDH lungs could not be determined. Routine administration of exogenous surfactant in human CDH patients is not supported by these experimental results.

Three newborn boys presented with features suggestive of classic low anorectal abnormality. However, during surgery they were found to have an intermediate anorectal abnormality and a rectoperineal fistula rather than an anocutaneous fistula. The surgical treatment of these infants is discussed.

For more than 10 years the authors have been using ultrasonography to confirm clinically suspected intussusception without performing a contrast enema. The aim of this study is to review this diagnostic policy. Between 1980 and 1989, 163 children who, on clinical examination and plain abdominal radiographs were suspected of having intussusception, underwent ultrasonography to confirm the diagnosis. In 33 children, ultrasonography did not show intussusception; of the remaining 130 children, intussusception was diagnosed in 128. In two children in whom intussusception was noted subsequently, the diagnosis was not established on ultrasound. Thus, ultrasonography had a sensitivity of 98.5% and a specificity of 100% in the diagnosis of intussusception. It is a quick, simple, noninvasive method to diagnose intussusception, with high accuracy. The role of contrast enema is limited to therapeutic application.

Survival of congenital diaphragmatic hernia patients depends on the gravity of pulmonary hypoplasia and persistent pulmonary hypertension (PPH). Many vasoactive drugs have been used in the treatment of PPH, but often they also lower peripheral resistance, leading to a significant drop in arterial blood pressure. The incidence of PPH in 52 high-risk diaphragmatic hernia patients and the results of treatment with tolazoline and prostacyclin were evaluated in a study lasting 52 months and involving 52 patients. High-risk patients require ventilatory support within 6 hours after birth. Study parameters were alveolar-arterial oxygenation difference (AaDO2), oxygenation index (OI), and mean arterial blood pressure (MABP), measured at set times before and after administration of tolazoline or prostacyclin. Twenty-one patients had documented episodes of PPH (46%), and 18 of them died. Tolazoline did not lower AaDO2 and OI values, but MABP dropped significantly. Prostacyclin caused a significant decrease of AaDO2 and OI values without an effect on MABP. We concluded: (1) PPH presented in 46% of our patients, associated with a high mortality rate; (2) tolazoline is not an effective dilator of the pulmonary vascular bed and lowers MABP; and (3) prostacyclin is an effective pulmonary vasodilator as reflected by ventilation parameters without systemic side effects; it does not affect overall outcome but can used as a "bridge" to extracorporeal membrane oxygenation.

We evaluated why and how life support was withheld or withdrawn in surgical neonates. During the study period, January 1988 through December 1991, 529 neonates were admitted, 52 of whom died (10%). Twenty-eight deaths were due to the underlying disease. The other 24 patients died because treatment was withheld or withdrawn. In 15 of 24 (group A, mean stay 9.2 +/- 9.1 days) treatment was initially started but later withdrawn (13/15) because of the severity of congenital anomalies alone (7/12) or congenital anomalies associated with chromosomal anomalies (5/12). In 9 of 24 (group B, mean stay 20.3 +/- 17.3 days) treatment was withdrawn because of serious complications. In all cases often lengthy discussions have led the doctors and nurses together with the parents to chose unanimously for withdrawal of treatment. Mechanical ventilation was the intervention most frequently withdrawn (10/15 group A, 9/9 group B). Vasoactive and other drugs were withheld in 5 patients of group A. Sedatives and analgetics were administrated as supportive care permitting the child to die in a humane way, 17 in the lap of a parent and 7 in the lap of a nurse. We conclude that life-sustaining care is withheld or withdrawn relatively frequently from patients at our ICU. Such decisions are ethical ones, taken in the light of professional and technical expertise. Evaluation of withholding or withdrawal of treatment is difficult but necessary to evolve appropriate decision-making procedures and to formulate humane standards of intensive care.(ABSTRACT TRUNCATED AT 250 WORDS)

During an 8-year period, 71 neonates with congenital diaphragmatic hernia were admitted to the Sophia Children's Hospital. Seventeen patients died before surgery. The other 54 patients underwent either direct suture (18) or patch closure with lyophylized dura (36), depending on the size of the defect. Forty patients survived. In 16 of them the defect was closed by direct suturing. In the other 24 patients a patch was used. Five recurrences of the defect occurred, all of them among the latter group.

During a period of 6 years, 31 of 54 infants with congenital diaphragmatic hernia survived and were evaluated to study incidence and management of gastroesophageal reflux. At 6 months' follow-up 16 patients had gastroesophageal reflux proven by upper gastrointestinal series; at 12 months' follow-up 11 patients. Three patients having gastroesophageal reflux did not respond to medical treatment and underwent Nissen fundoplication. We conclude that after successful treatment, congenital diaphragmatic hernia is likely to be complicated by gastroesophageal reflux. We could not define a predictive feature for gastroesophageal reflux in the individual patient surviving congenital diaphragmatic hernia.

This study explores the development of the enteric nervous system in avian embryos. Particular emphasis was given to colonization characteristics of neural crest cells present in primitive enteric ganglia. By coculturing neuronal and aneuronal gut of quail and chicken embryos, we investigated if and when neural crest cells in primitive enteric ganglia could detach from these ganglia, migrate, and colonize adjacent chicken gut. Quail neural crest cells were identified using the quail nucleolar marker and the HNK-1 antibody. Enteric neurons were identified using three monoclonal antibodies directed against neurofilament proteins. We found that neural crest cells detached from primitive ganglia in neuronal quail gut from E6 till E9, whereas neural crest cells did not leave enteric ganglia from E10 gut. These observations show that there is a transient phase during which enteric neural crest cells can leave the gut. To determine whether neural crest cells could colonize neuronal gut we cocultured neuronal gut or the neural primordium and neuronal chicken gut (E11). We found that quail neural crest cells do not colonize neuronal E11 gut, whereas they do colonize aneuronal gut of the same age. We suggest that aneuronal gut attracts neural crest cells by diffusing factors.

In infants with congenital diaphragmatic hernia (CDH), abnormalities of the pulmonary arteries are present consisting of increased medial wall thickness and decreased external diameter. This forms the morphological substrate for persistent pulmonary hypertension, one of the leading causes of the high mortality in these patients. To elucidate the significance of these abnormalities, experimental models are required that mimic as close as possible the human situation. In our rat model we are able to study the hypoplastic CDH lungs extensively. In this study we performed a histological evaluation of the pulmonary arterial bed in the control group and the nitrofen-treated group in which the latter was divided into two subgroups, CDH and normal diaphragm. We examined the newborn rats after perfusion of the pulmonary arteries with barium gelatine and subsequent fixation. At the level of the respiratory bronchioles significant differences in the vessels were found consisting of decreased external diameter and increased wall thickness as percentage of the external thickness in CDH lungs compared with controls. Abnormal muscularization of the peripheral branches of the CDH pulmonary arteries was also found. We concluded that the rat model strongly resembles the human situation concerning the arterial bed in the lungs.

Hirschsprung's disease is characterized by the absence of enteric neurons in the myenteric and submucosal plexus and the presence of many unmyelinated axons, visible in ganglion like structures, in the aganglionic part of the bowel. In previous studies we showed that the immunoreactivity of a monoclonal antibody (2F11) specific for neurofilament proteins is increased in aganglionic bowel segments. We now investigated whether the increased neurofilament protein staining results from an increase in neurofilament protein immunoreactivity in the aganglionic segment or if it is also related to differences in the phosphorylation state of neurofilament proteins. Bowel resection specimens of patients with Hirschsprung's disease and control patients were investigated by immunohistochemical techniques using a panel of different monoclonal antibodies that are specific for neurofilament proteins and have well known reaction patterns against different phosphorylated epitopes present on two neurofilament proteins, the middle (NF-M) and the high (NF-H) molecular weight subunit. For comparison the specimens were also stained for acetylcholinesterase, neuron-specific enolase (NSE), S-100, and glial fibrillary acidic protein (GFAP). Immunostaining with this panel of antineurofilament-antibodies showed differences in the phosphorylation state of neurofilament proteins in the aganglionic and the ganglionic bowel segments of patients with Hirschsprung's disease. These changes involved the phosphorylation state of these proteins and the ratio of NF-H and NF-M in neurofilament proteins. Staining with NSE and S-100 showed no significant differences between Hirschsprung's disease patients and control patients. We surmise that during the ingrowth and differentiation of hypertrophic axons the composition of neurofilament proteins formed in the aganglionic bowel segment differs from the neurofilament proteins formed in the ganglionic and control bowel segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Auxiliary heterotopic liver transplantation (HLT) was used to achieve functional repair in a dog model with an inborn error of metabolism. For the interpretation of the results, information on separate liver function is essential when a normal host liver is also present. We developed a radionuclear method to quantitate the relative contribution of each liver to the total uptake of intravenously (IV) injected 99mTc-HIDA. The HLT was performed between 20 mismatched pairs of dogs from two different strains. Four surgical procedures were used. After autopsy the outcome of the premortem HIDA-scan was compared with the wet weight of the graft and the host liver. A good linear correlation was noted between the relative contribution of the uptake and weight of the graft to the total HIDA uptake and total liver weight. Therefore, the relative contribution of an auxiliary heterotopic liver graft to the total liver function can be quantitated with a 99mTc-HIDA scan. With this technique, changes in relative function after an HLT under various flow conditions can be sequentially followed.

The mortality pattern and causes of death in surgical neonates were evaluated over the period of 1980 through 1990 in order to assess whether any deaths might have been prevented. In the study period 1,010 neonates were admitted, 104 of whom died (10%). These 104 neonates formed our study population. The Clinical Classification System (CCS) and the Therapeutic Intervention Scoring System (TISS) were used to assess the severity of illness. All 104 nonsurvivors were seriously ill (CCS 3 and 4; TISS greater than 20). The mortality pattern was classified in three groups. Group A (nonpreventable death) included 56 deaths, 48 of which were due to the underlying disease. The other 8 patients died of a nonpreventable complication of treatment. Eleven of the patients in group B (permissible death) had (multiple) congenital anomalies associated with chromosomal anomalies. Three of them were not treated and in the other 8 treatment was initially started but later withdrawn. In most of the other 14 patients further treatment was withdrawn because of serious postoperative complications or inoperable cardiac anomalies. Group C (preventable death) consisted of 23 patients. Six of 10 had irreversible brain damage due to prolonged hypoxemia. In the other 13 patients of group C, death was due to sepsis acquired in the postoperative period and treated inadequately. Staphylococcus epidermidis was the most frequent isolated pathogen (7/13).

Intestinal transplantation (ITx) has potential applications for the treatment of short-bowel syndrome (SBS). A major obstacle to its clinical use is rejection, which may partly be overcome by major histocompatibility complex (MHC) matching. At present, it is impossible to predict accurately the early onset of rejection. The aim of this study was to assess the value of in vivo measurements of transepithelial potential difference (PD) for the determination of rejection in MHC-matched and -mismatched canine ITx. A heterotopic ITx was performed in MHC tissue-typed Beagle dogs. Two ileostomies were created for PD monitoring and histology. Via one ileostomy, a well-defined segment of the IT, was isolated by a double balloon catheter and the intraluminal PD was measured in reference to a subcutaneous electrode. The PD responses during perfusion of a theophylline solution (crypt cell stimulation, PD theophylline) and during perfusion of a glucose solution (villus cell stimulation, PD glucose) were assessed. The results of in vivo PD measurements were compared with simultaneously obtained histology specimens. Four groups of dogs were studied: group 1 (controls, n = 10) ileal autotransplants; group 2 (n = 6) ileal allotransplants, fully mismatched; group 3 (n = 3) ileal allotransplants, 1 haplotype identical; and group 4 (n = 5), ileal allotransplants, fully matched. No immunosuppression was given. All dogs of group 1 survived indefinitely and both PD and histology showed no abnormalities. In group 2, 3, and 4 the onset of histological changes related to rejection corresponded well with decreased PD responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Posterior sagittal anorectoplasty (PSARP) was introduced in 1982 by Peña and De Vries as a new operation for patients with a high anorectal malformation. The degree of postoperative continence is reported to be high. During the past decade, too, new insights have been gained into the embryology of anorectal malformations. Evaluation of PSARP in relation to current understanding of the development and anatomy of the anorectum and the pelvic floor has led us to conclude that optimal continence cannot be expected. Fifty patients with a high anorectal malformation underwent PSARP between June 1983 and May 1990. Postoperative follow-up consisted of anamnesis (subjective) and electrostimulation, defecography, and anorectal manometry (objective). All patients are alive, and all but one are being evaluated regularly. Subjectively, the majority of patients were more or less incontinent, with soiling of pants at least once a day. On the basis of objective criteria, virtually all patients appeared to be incontinent, and in only one patient was the mechanism of defecation almost unimpaired after PSARP. From this study, we conclude that although PSARP provides a good aesthetic result, patients will never acquire normal continence.

Since 1969, reports of 16 patients presenting with the congenital short bowel and malrotation syndrome have been published. The prognosis of this malformation is poor; only two patients survived. We present the history of a third patient, successfully treated with long-term survival.

Despite some progress in the treatment of congenital malformations of the enteric nervous system, there is no knowledge about the pathogenesis. The study of the normal formation of the enteric nervous system is hampered by the difficulty of manipulating and culturing mammalian embryos and their organs. Three methods to culture bowel explants of murine embryos, (chorioallantoic membrane grafting, organotypic tissue culture, and renal subcapsular space grafting) were compared. The three-dimensional cytoarchitecture of the bowel developed almost normally in the renal subcapsular space cultures. Using this culture system, it was found that neural crest cells colonize the murine bowel in distinct phases. The distal bowel was colonized at the 13th day of development. In a spontaneous mouse mutant model for intestinal aganglionosis, the lethal spotted mouse, the colonization of the distal 2 mm of the bowel did not occur at E13.

Experiments to induce congenital diaphragmatic hernia (CDH) in rats, by means of administering a single dose of 2,4-dichlorophenyl-P-nitrophenyl (Nitrofen) on the 10th day of gestation, are reported here. Previously, congenital diaphragmatic hernia has been induced in sheep late in fetal development, and in mice early in gestation. The rat model, including a control group, was used to evaluate lung development and the presence of lung hypoplasia by morphometrical analysis. It was found that the single dose of Nitrofen, given 5 days before the normal closure of the diaphragm in the rat, leads to a high incidence of diaphragmatic hernia, mainly on the right side, and highly abnormal lung development (hypoplasia) comparable to the human situation. Both the lung weight/body weight index as well as the radial alveolar count were significantly lower in animals with CDH (P less than .05). This animal model offers a good opportunity to study abnormal lung development in relation to ventilatory capacity and pulmonary vascular reactivity.

Carnitine plays a key role in the oxidation of fatty acids. Most solutions for parenteral nutrition do not contain carnitine. Because endogenous carnitine synthesis is insufficient in newborns, they are prone to developing a carnitine deficiency when they are dependent on total parenteral nutrition (TPN). Stimulated by the clinical observation of manifest clinical symptoms of carnitine deficiency in one patient, a study of 13 consecutive neonates who received TPN for over 2 weeks was begun. Their plasma carnitine levels before and during carnitine supplementation were determined. All patients had a carnitine intake far below the recommended minimal need of 11 mumol/kg per day. Although only three of them clearly showed clinical symptoms described as carnitine deficiency, carnitine supplementation for all neonates receiving TPN for over 2 weeks is recommended.

In chick embryos we studied the effect on intestinal development of an experimentally induced perforation and a vascular lesion performed at an early developmental stage. The results show that an intestinal perforation will heal, but may lead to intestinal atresia with microscopic signs of meconium peritonitis. Conversely, a vascular lesion induced at an early stage of development does not lead to intestinal atresia, while a vascular lesion performed at a late stage of development does result in intestinal atresia, but without any signs of meconium peritonitis.

A gastroschisis model was successfully developed in the chicken embryo. The embryologic anatomy of this laboratory animal enabled the inducement of an abdominal wall defect, whereby the eviscerated abdominal contents were not exposed to fetal urine. A total of 999 embryos underwent a surgical intervention at an early developmental stage, from the 5th-8th day of the incubation period. Twenty-four hour mortality was 7%. Surgery carried out on the 5th day resulted in the largest number of survivors, 25% of the induced lesions had healed and gastroschisis did not occur. The characteristic picture of gastroschisis only evolved when the herniated bowel was exposed to urine components. Histologic studies were carried out with the aid of various staining techniques to determine the development and distribution of the enteric ganglia in experimental gastroschisis. Contrary to similar studies that would point to damage of enteric ganglion cells as being responsible for the delay in intestinal motility, no ganglionic injury was noted in our bowel studies.

The diagnostic properties of two monoclonal, antineurofilament antibodies were tested in a retrospective investigation of bowel specimens of 24 cases of Hirschsprung's disease, eight cases of long-segment aganglionosis, eight cases of pseudo-obstruction, and six cases of chronic constipation. Immunohistochemical staining with the antibodies in combination with hematoxylin counterstaining revealed six distinctive and divergent pictures, demonstrating innervation disturbances in all cases. Apart from Hirschsprung's disease and long-segment aganglionosis, characteristic pictures also appeared for pseudo-obstruction and, diversely, for chronic constipation. In addition, anomalies were revealed in the ganglionic, proximal bowel of five patients with Hirschsprung's and two with long-segment aganglionosis, who had all suffered from chronic constipation postoperatively.

Six patients with total colonic aganglionosis (TCA) with ileal involvement were treated with a total colectomy and ileorectal anastomosis according to Rehbein. Follow-up lasted from 1 to 7 years and showed no mortality. Postoperative management consisted of total parenteral nutrition initially, followed by gradual introduction of oral feeding beginning with a low-osmolarity low-residue diet, the use of loperamide, an adequate oral intake of salt, and regular bowel deflation. Major postoperative complications disappeared and all patients demonstrated weight gain by the end of the first postoperative year, with normal feeding and two to three soft stools per day.

In 11 puppies, 8-12 wk old, with an average weight of 9.3 kg, a short segment of the thoracic esophagus was replaced by a revascularized autologous ileum segment. Four dogs died: 1 as a result of an untreated hemorrhagic shock, 3 due to thrombonecrosis of the transplant. Seven dogs were subjected to a follow-up program consisting of weekly weighing, swallow cinematography and angiography, endoscopic tests, and taking biopsies of the mucous membrane for histologic examination. The management of these puppies over a period of 1 yr is described. It proved possible in rapidly growing puppies to replace a segment of the thoracic esophagus with an autologous revascularized ileum segment, without this being a detterent for these puppies to grow into normal well-nourished adults.

It is generally accepted that a circulatory disorder of the bowel during the embryonic stage of development plays an important part in the occurrence of atresias of the small bowel and colon, with the exception of the septal types of atresia. In most cases, the cause of this disorder is not known. An experimental study, making use of chick embryos, is presented and the results are discussed. Two sets of experiments were conducted. In the first set the bowel of the chick embryo was subjected to temporary ischemia. In the second one the chick embryo was subjected to a period of general hypoxia. Temporary ischemia of the bowel frequently resulted in stenosis or atresia. The duration of the vascular occlusion was significant factor. Temporary general hypoxia resulted in serious morphologic changes of the bowel and the liver. Stenosis or atresia did not occur in this case, but there was a strong resemblance to the histopathological picture of neonatal necrotizing enterocolitis.

The influence of the size of the recipient upon posttransplantation renal function was investigated in an experimental study of inbred rats as well as in a retrospective analysis of juvenile recipients of adult donor kidneys. The experimental study revealed either augmentation of the compensatory response, in case of a juvenile donor kidney transplanted into an adult recipient, or attenuation of this response, in case of an adult donor kidney transplanted into a juvenile recipient. Various workers have reported an augmentation of renal function in humans in case of adult recipients of juvenile donor kidneys. In contrast, attenuation of renal function in case of adult donor kidneys transplanted into juvenile recipients, has not been reported. This attenuation was substantiated in our retrospective clinical study. We found that 3 weeks after transplantation, the absolute creatinine clearance (mL/min) was lower in a group of recipients under 12 years old than in a group of recipients older than 12 years. The experimental as well as the clinical investigation indicated that the size of the recipient plays an important part in the functional outcome after renal transplantation. It appeared that the transplanted kidney behaves like a single organ pertaining to the recipient.

Extensive studies in the chicken embryo have recently supplied more insights into the development of the enteric nervous system, which mainly derives from the vagal neural crest (i.e., the neural crest opposite somites 1 to 7). Crest cells migrate from this region to and via the developing gut. By means of a double labeling technique of both neural crest cells and cells in the S-phase of the cell cycle, we found that these migrating crest cells still proliferate in the gut. Some cells even go through cell division after the formation of a nerve plexus. Some implications for the pathogenesis of congenital innervation abnormalities such as hyperganglionosis and the aganglionosis of Hirschsprung's disease are discussed.

An experimental study was carried out investigating the feasibility of using only a portion of a donor liver in orthotopic, nonauxiliary transplantation, establishing a canine model. After being totally hepatectomized, 20 immunosuppressed adult beagles received a 60% donor liver graft, derived from tissue-typed identical littermates. Preservation time was 5 hr. In control experiments, 10 beagles, only half of them immunosuppressed, underwent an operation involving complete liver mobilization, vascular exclusion, cooling of the liver in situ, and a 40% partial hepatectomy with biliary anastomosis. The surgical procedure, including the method of cooling and preservation, is described in detail. Survival rate amounted to 90% for the control group and 50% for the transplanted group, while all surviving dogs were sacrificed 24 wk postoperatively. At sacrifice, the liver weight amounted to the weight of the total native liver at operation. Body weight profiles reflect good general condition of the surviving dogs. No major differences were noted between the immunosuppressed and the nonimmunosuppressed control dogs. No complications were related to the fact that only a partial liver was grafted or left in situ.

After a short literature a review a comparison is made between the development of the human digestive tract during the second trimester of gestation and that of the chick embryo (Gallus domesticus) during the last week of incubation. The surgical procedure for chick embryosis is discussed in connection with the the study of the pathogenesis of small bowel atresia and meconium peritonitis. The results corroborate that the chick embryo is a valuable laboratory animal in experimental fetal surgery.

Perforation of the appendix in the neonatal period may be a complication of neonatal necrotizing enterocolitis and should be differentiated from perforating appendicitis in later life. A patient is presented together with a review of the literature to illustrate this concept. Perforation of the appendix occurred in a 12-day-old preterm baby. Th cause of this perforation is assumed to be localized full thickness necrosis of the appendiceal wall, a form of neonatal necrotizing enterocolitis. The similarity between the clinical histories of neonates with so called "appendicitis" and those with necrotizing enterocolitis is pointed out. It is argued that "idiopathic primary peritonitis" probably does not exist, but that the peritonitis may be secondary to similar small perforations of the bowel. The importance of a thorough search for such a perforation is stressed.

We investigated the ability of neural crest (NC) cells to colonize hindgut, which had remained aneuronal due to bowel transection in ovo at an early stage. The fact that the bowel remained aneuronal proved that the "sacral" NC does not provide precursor cells for enteric neurons in the hindgut. HNK-1 immunostaining of aneuronal hindgut revealed cell-free, ganglionic structures at the site of the myenteric plexus and a sub-population of mesenchymal cells in the submucosa. We cocultured this particular type of aneuronal bowel with the vagal neural anlage of either quail or chick embryos on the chick chorioallantoic membrane. After 1 week coculture, it appeared that NC cell colonisation of the hindgut had taken place, although there was a difference between the quail-chick and chick-chick model. Quail NC cells had given rise to submucous plexuses and some myenteric plexuses. Chick NC cells had only colonised the submucous region. These findings indicate that the cell-free ganglionic structures hamper neural crest cell colonization in the myenteric region.

The development of gastroschisis was studied experimentally as well as clinically, particularly concerning the characteristic fibrous coating of the protruding bowel loops, associated intestinal atresia, and postoperative hypoperistalsis without intestinal obstruction. Experimental investigation was carried out in the chicken embryo. The clinical study was a joint one, involving a total of 50 patients with gastroschisis seen at the Sophia Children's Hospital, Rotterdam, and the Royal Hospital for Sick Children, Glasgow, between 1972 and 1985. Some patients were followed antenatally. The results, correlating with previous experiments, were compared with data from the literature. The fibrous coating of the protruding bowel loops appeared to be a late occurrence and directly related to changes of the amniotic fluid secondary to the onset of renal function. Associated intestinal atresia and postoperative hypoperistalsis in the absence of an obstruction both appeared to be due to another late gestational event, consisting of ischemic changes of the bowel wall secondary to the compression of bowel loops and mesentery in the small abdominal wall defect.

Ten boys with a fistula between the rectum and the urinary tract are presented. Six resulted from complications of imperforate anus surgery, three were various congenital abnormalities, and one was associated with an inflammatory pelvic mass. The management of these patients is described and the problems are discussed.

In case of congenital diaphragmatic hernia (CDH), survival generally depends not on prenatal diagnosis, planned delivery, and immediate postnatal operation, but on the gravity of pulmonary hypoplasia and persistent hypertension (PPH). Many vasoactive drugs have become available for lowering PPH, but the mortality rate for CDH still amounts to 40% to 70%. Preoperative stabilization might prevent or at least reduce the risk of PPH. This method was evaluated in a pilot study lasting 15 months and involving 13 patients. All were admitted to the pediatric surgical intensive care unit within six hours of birth, all requiring mechanical ventilation. Continuous suction of the stomach and bowel proved successful in reducing the mediastinal shift. Study parameters were alveolar-arterial oxygenation differences ((A-a)DO2), mean airway pressure (MAP), oxygenation index (OI), and ventilation index (VI), measured on admission and at set times before and after surgery. Eight patients did not survive, but in two cases death was not directly related to CDH. The following conclusions were reached: (1) satisfactory ventilation parameters on admission will remain good during the preoperative stabilization phase and will not be affected by its duration or by subsequent surgery, spelling survival; (2) unsatisfactory ventilation parameters on admission may improve with preoperative stabilization, giving these patients a better chance of survival; and (3) poor ventilation parameters on admission that fail to improve with preoperative stabilization will not improve with surgery or postoperatively, spelling death.

Experience with 108 neonates treated for aganglionosis at the Sophia Children's Hospital, Rotterdam, between 1975 and 1983 has been reviewed. Twenty two of them suffered from disturbed defecation postoperatively, involving 16 cases of classical Hirschsprung's, 4 long-segment aganglionosis, 1 case of aganglionosis up to the cecum, and 1 total aganglionosis. The monoclonal antineurofilament antibody NF2F11 was used to investigate ganglionated as well as aganglionic bowel specimens of these patients as well as 17 patients from the remainder without postoperative constipation serving as controls. The original diagnosis was confirmed in all cases. Proximal ganglionated bowel of all 17 controls appeared normal, while the antibody revealed normal bowel in only 4 out of the 22 patients with postoperative constipation. In 18 cases this new staining technique revealed the picture of pseudo-obstruction. Early recognition of pseudo-obstruction in proximal ganglionated bowel would provide early warning of postoperative complications.

Two courses of LHRH nasal spray (400 micrograms three times a day for 28 days), partly administered in a double-blind placebo-controlled study, resulted in the descent of 48 of 281 testes (18%) in 237 prepuberal boys. Logistic regression analysis confirmed the clinical observation that pretreatment testicular position was the major factor influencing treatment results: the lower the pretreatment testicular position, the better the result. Of the unsuccessfully treated boys, 170 with 196 undescended testes subsequently underwent orchiopexy revealing anatomic anomalies that accounted for failure of hormonal treatment in 80% of the cases. Most frequent finding amounted to an underdeveloped processus vaginalis, extending no further than the level of the pubic bone, often associated with major epididymal deformities and a lack of obliteration of the processus vaginalis (107 of 196 operations). Obstruction of the scrotal entrance due to abnormal Scarpa's fascia or abnormal gubernacular remnant was found in 35 and testicular absence in 15 cases. LHRH nasal spray might be effective when the testis can be manipulated to at least the scrotal entrance before treatment, but in view of our surgical findings, LHRH nasal spray will not replace orchiopexy.