Esophageal obstruction-prenatal detection rate and outcome.

OBJECTIVE: Prenatal diagnosis of esophageal obstruction is believed to improve the outcome for the affected newborn. However, the prenatal detection rate is only 10-40%, the diagnosis is usually not made before the third trimester and the false-positive rate has been high. This study investigated the prenatal detection rate and time of prenatal diagnosis at our center and its influence on outcome. In addition, incidence, detection rate and accuracy of the diagnosis in a large non-selected population were determined. METHODS: All cases diagnosed pre- or postnatally with esophageal obstruction and examined prenatally by ultrasound at the National Center for Fetal Medicine in Norway during 1987-2004 were evaluated. RESULTS: Of 48 cases with esophageal obstruction, 21 (44%) were diagnosed prenatally (median, 32 + 0 weeks). All 21 had a small or empty stomach, 20/21 (95%) had polyhydramnios and 9/21 (43%) had a visible esophageal pouch. Associated anomalies were present in 38/48 cases (79%). The karyotype was abnormal in 11/48 cases (23%). Ten (21%) pregnancies with lethal fetal conditions were terminated. Two fetuses died in utero. Ten infants with associated anomalies died within 3 months after birth. The 26/48 (54%) survivors included 16/21 cases with a prenatal diagnosis of esophageal obstruction and 9/10 cases with isolated esophageal obstruction. CONCLUSIONS: The clinical signs of polyhydramnios were the most important factors for prenatal detection of esophageal obstruction. Consequently, the time of diagnosis was late and the detection rate was low (44%). An increased awareness of the possibility of esophageal obstruction, leading to targeted examinations whenever the suspicion is raised during pregnancy, might improve the prenatal detection rate and thereby provide a possibility to improve the outcome. Of the cases with isolated esophageal obstruction, 90% survived, irrespective of prenatal diagnosis.

Nordic consensus on treatment of undescended testes.

AIM: To reach consensus among specialists from the Nordic countries on the present state-of-the-art in treatment of undescended testicles. METHODS: A group of specialists in testicular physiology, paediatric surgery/urology, endocrinology, andrology, pathology and anaesthesiology from all the Nordic countries met for two days. Before the meeting, reviews of the literature had been prepared by the participants. RECOMMENDATIONS: The group came to the following unanimous conclusions: (1) In general, hormonal treatment is not recommended, considering the poor immediate results and the possible long term adverse effects on spermatogenesis. Thus, surgery is to be preferred. (2) Orchiopexy should be done between 6 and 12 months of age, or upon diagnosis, if that occurs later. (3) Orchiopexy before age one year should only be done at centres with both paediatric surgeons/urologists and paediatric anaesthesiologists. (4) If a testis is found to be undescended at any age after 6 months, the patient should be referred for surgery--to paediatric rather than general surgeons/urologists if the boy is less than one year old or if he has bilateral or non-palpable testes, or if he has got relapse of cryptorchidism.

Imperforate anus: A relatively common anomaly rarely diagnosed prenatally.

OBJECTIVE: Despite the relatively common occurrence of imperforate anus, prenatal diagnosis is rarely reported. In this study, we investigated the presence and diagnosis of imperforate anus along with strategies for improving prenatal diagnosis of the condition. PATIENTS AND METHODS: Fetuses and infants with imperforate anus who had been examined prenatally by ultrasound at the National Center for Fetal Medicine (NCFM) from 1987 to 2004, were evaluated. RESULTS: Of 69 cases with imperforate anus, only 11 (15.9%) were diagnosed prenatally, at a median gestation of 18 + 4 (range, 15 + 6 to 35 + 6) weeks. In all 11, dilatations of the rectum or lower part of the bowel were seen. Additional anomalies, most of them diagnosed prenatally, were present in 59/69 (85.5%) of the cases. The most frequent additional anomalies were urogenital (53.6%). The karyotype was abnormal in nine cases (13.0%). A retrospective evaluation of available videotapes of 22 cases of imperforate anus that were not diagnosed prenatally revealed that it was possible to suspect the diagnosis in 11/22 (50%) cases. Sixteen infants were born with imperforate anus without prenatal diagnosis of any abnormality. In total, 31/69 (44.9%) cases were terminated, two (2.9%) died in utero and 12 (17.4%) died postnatally. Twenty-four (34.8%) infants survived, including all 10 with isolated imperforate anus and seven of eight cases with only one additional anomaly. CONCLUSIONS: The prenatal detection rate of imperforate anus was only 15.9%. Imperforate anus is often associated with other anomalies; in this study, 85.5% had additional anomalies. Prenatal diagnosis makes prenatal counseling possible and facilitates optimized postnatal care. We believe that the prenatal detection rate of imperforate anus could be improved. Examiners should intensify their search for typical findings of imperforate anus especially when other anomalies that frequently accompany this condition are present.

Characteristics and outcome of 90 cases of fetal omphalocele.

OBJECTIVE: The aim of this study was to describe the outcome of a case series of fetuses with omphalocele. METHODS: Ninety fetuses with omphalocele at the National Center for Fetal Medicine (NCFM) between January 1985 and January 2004 were followed from the time of prenatal diagnosis. Follow-up times ranged from 6 months to 17 years. Omphaloceles were subdivided into epigastric, central and hypogastric types based on their location on the abdominal wall. RESULTS: There were 58 central and 32 epigastric omphaloceles. Abnormal karyotype was found in 40/58 (69%) of the central and in 4/32 (12.5%) of the epigastric omphaloceles. Trisomy 18 was the most frequent abnormality associated with omphalocele. Among the fetuses with normal karyotype, 89% of the central and 71% of the epigastric cases had other anomalies. 38 (66%) of the fetuses with central omphalocele were terminated and 12 (21%) died during pregnancy or after delivery. 11 (34%) of the fetuses with epigastric omphalocele were terminated and eight (25%) died during pregnancy or after delivery. Of the 90 cases followed from the time of diagnosis there were 21 (23%) survivals. Of eight survivals with central omphalocele, only two were considered healthy while six had other anomalies and/or substantially impaired development. Of 13 survivals with epigastric omphalocele, six were considered healthy and seven had other anomalies and/or substantial impairment. CONCLUSIONS: Fetal central and epigastric omphaloceles may be different entities: central omphaloceles are more strongly associated with abnormal karyotype (69%) than are epigastric omphaloceles (12.5%). The outcome of fetuses with omphalocele is poor irrespective of the type of omphalocele, with only eight of the 90 (9%) being alive and healthy at present. The results emphasize the importance of identifying both those fetuses with a potentially good prognosis and favorable outcome and those which are likely to have a fatal outcome.

Surveillance and outcome of fetuses with gastroschisis.

OBJECTIVES: Infants with gastroschisis have a high survival rate. However, the rate (10-15%) of intrauterine fetal death (IUFD) is considerable, and the association with fetal distress is well known. The aim of this study was to describe the outcome of fetuses with a prenatal diagnosis of gastroschisis. The impact of correct prenatal diagnosis, surveillance and signs of complicating risk factors were evaluated. METHODS: All fetuses with prenatally diagnosed gastroschisis at the National Center for Fetal Medicine from January 1988 to August 2002 were registered and prospectively evaluated with regular ultrasound examinations. From 34-36 completed gestational weeks the fetuses were monitored daily to every second day with cardiotocography (CTG). RESULTS: Gastroschisis was diagnosed in 64 fetuses at a mean gestational age of 19 + 2 weeks. All had normal karyotype. Associated anomalies were found in four cases (6.3%). Three pregnancies (4.7%) were terminated, all for reasons other than gastroschisis. One fetus (1.6%) died in utero. Thirteen fetuses (22%) had abnormal CTG leading to subsequent Cesarean sections. Mean gestational age at delivery was 36 + 1 weeks. Mean birth weight was 2586 g. Thirteen infants (22%) were small for gestational age (SGA). In 15 cases (25%) meconium-stained amniotic fluid was found; 14 of these had abnormal CTG and/or were SGA. Small bowel atresia was found in four infants (6.7%). Four infants died postnatally at the age of 0-9 months. CONCLUSIONS: CTG surveillance of fetuses with gastroschisis may improve the outcome through detection of fetal distress thereby reducing the risk of IUFD. Other clinical situations of importance that are associated with gastroschisis are described and discussed.

Gastric outlet obstruction caused by heterotopic pancreas.

Heterotopic pancreas (HP) in the stomach is a relatively well-known entity, but there are not many symptomatic cases reported in children. We report on a 9-year-old boy presenting with nausea and vomiting. The first gastroscopic examination showed a crater-like lesion in the antrum, but at follow-up gastroscopy a few weeks later the lesion was polypoid, obstructing the pylorus. Endoscopic biopsy was not diagnostic, but histological examination after open excision showed HP. It is unclear why the lesion changed so markedly in appearance in just a few weeks. HP is a rare cause of gastric outlet obstruction in children.

Fetal duodenal obstructions: increased risk of prenatal sudden death.

OBJECTIVES: The aim of this study was to describe the outcome of fetuses with duodenal obstruction diagnosed prenatally and to compare the outcome with the results of studies of newborns. METHODS: All fetuses with a prenatal diagnosis of duodenal obstruction were registered and evaluated prospectively from January 1985 to December 2000. RESULTS: Duodenal obstruction was found in 29 fetuses at a mean gestational age of 29+2 weeks. Polyhydramnios was found in 24 cases (83%). Six fetuses (21%) had trisomy 21. Associated anomalies, including trisomy 21, were found in 18 cases (62%). Four fetuses with normal karyotype died in utero at 31-35 gestational weeks. Two of them had associated anomalies, but the anomalies could not explain the prenatal deaths and the deaths occurred suddenly and unexpectedly. Three infants died postnatally; all three had associated anomalies. Four infants with normal karyotype had neurological impairment suggesting that they might have had intrauterine asphyxia. CONCLUSIONS: The present study indicates that duodenal obstruction is a more serious condition than previously believed, with an increased risk of prenatal asphyxia and death, even when the karyotype is normal and no associated anomalies are present. We consider the possibility that it could be caused by bradycardia/asystole following vagal overactivity due to distension of the upper gastrointestinal tract.

[Laparoscopic examination of non-palpable testis]. / Laparoskopisk undersøkelse ved ikke-palpabel testikkel.

BACKGROUND: Approximately 20% of undescended testes are impalpable. They can be located intraabdominally, in the inguinal canal, in ectopic position, or they can be missing. Traditionally, surgical groin exploration has been carried out in such cases, sometimes followed by laparotomy if no testis or spermatic cord could be found in the groin. This approach often involves unnecessary and sometimes too extensive surgery. Laparoscopy facilitates the identification of the testicle or proves the lack of it in a less invasive way. MATERIAL AND METHODS: From 1986 to 1999, 77 boys aged one year five months to 13 years 7 months underwent laparoscopy for unilateral or bilateral nonpalpable testis in our department. RESULTS: In 72 boys (94%), the findings were conclusive in the form of intraabdominal testis in 26, an intact intraabdominal spermatic cord entering the deep inguinal ring in 27, and a missing testis in 19 boys. INTERPRETATION: Laparoscopy identified the boys who did not require further surgery because the testis was missing, Furthermore, when a testis was found, laparoscopy was helpful in choosing the most appropriate method of orchiopexy. It is concluded that at present, laparoscopy is the preferred method of investigation in boys older than one year of age with nonpalpable testis.

Glucocorticoid and ACTH regulation of rat peritoneal phagocyte chemiluminescence and nitric oxide production in culture.

In order to study the adrenocortical regulation of monocyte/macrophage functions further, leucocytes from the rat peritoneum were incubated in vitro with glucocorticoid concentrations up to 10 mumol L-1 and with adrenocorticotropic hormone (ACTH) up to 100 micrograms mL-1. The monocyte/macrophage production of reactive oxygen molecules was measured by luminol amplified chemiluminescence, and the production of nitric oxide (NO) was measured as nitrite (NO2-). Dexamethasone in vitro in nanomolar concentrations inhibited monocyte/macrophage chemiluminescence and also nitric oxide production; the potency was dexamethasone > methylprodnisolone > prednisolone. ACTH enhanced both activated chemiluminescence and endotoxin-induced nitric oxide production, but only at concentrations about 20-100 micrograms mL-1, and there was no significant effect of physiological concentrations. In summary, the results of the present study further confirm and substantiate that glucocorticoids in low pharmacological concentrations have a general inhibitory effect on monocyte/ macrophage production of reactive oxygen molecules through the specific glucocorticoid receptors, while the stimulatory effect of ACTH is only observed by very high, non-physiological concentrations. Furthermore, since low concentrations of glucocorticoids inhibited the production of these reactive oxygen molecules in vitro, indirect mechanisms involving hormones and other elements outside the immune system are not essential for the effect of glucocorticoids on monocytes/macrophages.

[Duplication of the small intestine. Unusual cause of abdominal pain]. / Duplikasjon av tynntarm. Uvanlig årsak til magesmerter.

Duplications of the alimentary tract are rare. Since 1982 only three patients with such anomalies have been treated in the Department of Paediatric Surgery at the University Hospital in Trondheim, Norway. We describe the last patient treated, where duplication of the ileum was found upon laparotomy, performed because of exaggerated recurrent abdominal pain. Duplications may be found anywhere along the alimentary tract and diagnosis can be difficult. The duplications can be found upon laparotomy for suspected appendicitis or bowel obstruction. The condition may also be suspected upon antenatal ultrasonography and in the event of abdominal symptoms after birth.

Congenital diaphragmatic hernia: determination of the optimal time for operation by echocardiographic monitoring of the pulmonary arterial pressure.

Preoperative stabilization and delayed operation rather than emergency repair of congenital diaphragmatic hernia (CDH) may improve survival, but there are no clear criteria for how long operation should be delayed. Because increased pulmonary vascular resistance (PVR) may be an important risk factor, we used Doppler echocardiography to study patients with CDH presenting with respiratory distress immediately after birth. During the study period 10 patients were admitted, but 2 were moribund on admission and died shortly thereafter. In the remaining patients the pulmonary arterial pressure (PAP) and direction of ductal shunt were estimated by Doppler echocardiography. Initial PAPs were in the range of 45 to 90 mm Hg, with bidirectional or right-to-left shunt through the ductus arteriosus. Reduction of pressure to 25 to 55 mm Hg, or reversal of shunt to left-to-right, reflecting decreased PVR, occurred after ventilation for 3 to 20 days (mean, 8 days). Patients underwent operation after there was evidence of reduced PVR. None developed persistent fetal circulation, and all 8 patients survived. We conclude that postponing operation until PVR has decreased seems to improve survival in patients with CDH presenting within hours of birth.

Bioactivity studies on new gastrin analogues.

Gastrin antagonists may be useful in the treatment of peptic ulcer disease and gastrointestinal malignancies. The aim of the present study was to synthesize gastrin analogues and test them for their ability to inhibit gastrin-stimulated acid secretion. Five peptides were synthesized: peptide [2], in which methionine was replaced by leucine, and the COOH-terminal amide was replaced by the thiomethylamide; peptide [3], in which the COOH-terminal phenylalanine was removed, and the aspartic acid thioamidated; peptide [5], in which methionine was replaced by leucine, and the peptide bond between leucine and aspartic acid was replaced by a thioamide; peptide [7], in which the bond between leucine and aspartic acid was replaced by a ketomethylene amino bond; and, finally, peptide [8], in which a beta-bend was induced in the COOH-terminal region by the introduction of a D-phenylalanine in place of glycine. The biologic effect of the peptides was tested in the totally isolated, vascularly perfused rat stomach. The peptides were tested in concentrations of 10(-9), 10(-7), and 10(-5) M for agonist activity and together with gastrin 1-17, 5.2 X 10(-10) M, at a concentration of 10(-5) M for antagonist activity. Peptide [2] had full biologic activity but greatly reduced potency, and peptide [7] had a faint biologic activity. None of the peptides showed any antagonist activity.

Free periosteal grafts in tracheal reconstruction: an experimental study.

If resection followed by end-to-end anastomosis is not possible in obstructive lesions of the trachea other methods of reconstruction must be used. The ability of a periosteal graft to induce bone or cartilage formation when transplanted to cover a tracheal defect was confirmed in a previous experimental study. In this study free tibial periosteal grafts were used for repair of tracheal defects created in rabbits. The graft was placed circumferentially around the trachea. It is concluded that there is a high risk of development of severe osseous tracheal stenosis when periosteal grafts are placed circumferentially around the trachea.

Effect of pentagastrin on gastric acid secretion in the totally isolated vascularly perfused rat stomach stimulated with the phosphodiesterase inhibitor isobutyl methylxanthine.

The development of a very sensitive stomach biomodel, using the totally isolated rat stomach, is reported. Pentagastrin-stimulated acid secretion in anesthetized and conscious rats was also studied, and the capacity to produce acid and the sensitivity towards pentagastrin in the different rat stomach models were compared. The secretory capacity and the sensitivity were evaluated by means of the maximal acid output (MAO) and threshold dose (TD), respectively. Conscious rats provided with gastric fistulas had a MAO of 48 +/- 6.3 mu eq/10 min and a TD of 6 micrograms/kg-h. In anesthetized rats with luminally perfused stomach MAO was reduced to 11.6 +/- 1.2 mu eq/10 min, whereas the sensitivity was increased, as indicated by a TD of 0.5 micrograms/kg-h. Totally isolated vascularly perfused rat stomachs without isobutyl methylxanthine (IMX) produced even less acid (MAO, 2.2 +/- 0.4 mu eq/10 min) without any change in demand for stimulant (TD, 0.25 micrograms/stomach-h). Addition of IMX to the vascular perfusate in the isolated stomach preparation increased the MAO to 8.0 +/- 1.0 mu eq/10 min and induced a remarkable reduction in demand for stimulant, with a TD obtained already at a pentagastrin dose of 0.008 micrograms/stomach-h, corresponding to a concentration of pentagastrin in the vascular perfusate medium of 84.5 pM. Accordingly, the totally isolated vascularly perfused rat stomach stimulated with IMX is the most sensitive bioassay for (penta)gastrin so far reported.

The effect of pentagastrin on the gastric secretion by the totally isolated vascularly perfused rat stomach.

Gastric acid and pepsin secretion by the totally isolated vascularly perfused rat stomach was studied. Rat stomachs were vascularly perfused with Krebs-Ringer buffer gassed with 96% O2-4% CO2 and containing 5 mM glucose, 5 mM pyruvate, 4% bovine serum albumin, 10% ovine erythrocytes, and various concentrations of pentagastrin. The gastric lumen was perfused with distilled water gassed with 100% O2. To remove preformed juice and to enable preformed pepsin to be washed out, the initial 20-min gastric juice was discarded. The gastric effluent was then collected continuously for six 10-min periods, and the H+ concentration was determined by titration and the pepsin concentration estimated by a hemoglobin digestion method. Inclusion of pentagastrin in the perfusion buffer increased the acid output dose-dependently from 2.3 +/- 0.4 mueq/h during the control perfusion to a maximum of 12.7 +/- 2.1 mueq/h (p less than 0.01). With the higher doses of pentagastrin and concomitant high acid secretion, gastric acid secretion faded during the collection period. In contrast, gastric pepsin secretion was virtually unaffected by pentagastrin. The present model should be useful for studying the regulation of gastric acid and pepsin secretion.

The preparation of bioactive 125I-gastrin, using Iodo-gen as oxidizing agent, and the use of this tracer in receptor studies.

The preparation of 125I-labelled gastrin 1-17, using Iodo-gen as oxidizing agent, is described. Mono-125I-gastrin was purified from the iodination mixture by gel chromatography, followed by ion-exchange chromatography. The Iodo-gen-labelled 125I-gastrin tracer showed a slightly higher immunoreactivity than a similarly purified tracer produced by a gentle chloramine-T method (50% binding of 0.45 fmol tracer at an antibody dilution of 945,000 versus 780,000, respectively). The Iodo-gen-labelled 125I-gastrin, which had the same biological activity as native gastrin when tested in conscious gastric fistula rats, was tested for specific binding at 30 degrees C in pronase-isolated rat gastric fundic cells and plasma membranes from the same area. A specific binding with a Kd of 4.5 X 10(-9) M was found to isolated fundic cells. This binding was rapid and reached equilibrium within 40 min. The dissociation induced by a 10-fold dilution of the incubation medium was biphasic, with a rapid initial phase and a slow late phase, indicating two different binding sites. On the other hand, no reproducible specific binding of the tracer to plasma membranes was obtained. This study shows that Iodo-gen is suitable as an oxidizing agent in iodination of gastrin without loss of biological activity. The tracer produced may be used in receptor studies for isolated cells, whereas the use of plasma membranes for studying gastrin receptors needs reevaluation.

To the management of the solitary thyroid nodule.

Excisional biopsy with peroperative frozen section and later paraffin section examination was performed in 107 consecutive cases of solitary thyroid nodules. Frozen section gave a correct diagnosis in 99 cases (92%). A false benign diagnosis was made in 6 cases, one was inconclusive and one was false malignant (Hürthle cell tumor). Technetium scintigraphy was of no definite diagnostic value. Malignancy was found in 25 cases (23%) in which the whole gland was removed. Multicentric bilateral lobe involvement was encountered in 7 patients. Lack of reliable preoperative diagnostic methods makes liberal excisional biopsy of all solitary thyroid nodules advisable.