Biomedical subjects
Publications and source records attributed to E R Howard.
Maldescent is a common anomaly. Treatment is recommended at two years of age. Extensive retroperitoneal mobilization may be necessary for the high testis, but treatment may be facilitated by a preoperative course of gonadotrophin injections. This article is based on our management of 405 consecutive orchidopexies.
A postal survey identified 114 infants with biliary atresia (roughly one in 21 000 live births). Biliary operations were performed on 107. Of the 105 infants who were followed up, 35 were free of jaundice at 10 months to 3 1/2 years. Good results occurred most often in those operated on by 12 weeks and were also related to the number of cases operated on in each centre. Only two of 18 infants treated in centres dealing with one case a year were free of jaundice compared with 11 of 38 at centres treating two to five cases a year and 22 of 49 in a centre treating more than five cases a year. Jaundice in an infant of more than 2 weeks associated with yellow urine or pale stools is never physiological and requires urgent investigation to identify causes for which effective treatment may be possible. Identification of suspected cases by 4 weeks of age and a greater concentration of investigative and surgical skills should improve the short term results of surgery and the long term prognosis of biliary atresia.
Esophageal varices in 57 consecutive children were treated by injection sclerotherapy using 5% ethanolamine oleate injection via a fiberoptic endoscope (Olympus P2). Variceal obliteration was achieved with 4.7 and 5.7 injections in the extra- and intrahepatic disease groups. Complications of injections included hemorrhage, esophageal ulceration, and stricture. Thirty two cases were followed from 6 to 60 months after treatment and only five further bleeds were observed (extrahepatic 1: intrahepatic 4). The early results suggest that sclerotherapy is an effective method for the control of esophageal varices in children.
48 hours after oesophagoscopy and injection sclerotherapy of oesophageal varices under general anaesthesia, 11 studies of 6 children with cystic fibrosis and portal hypertension showed a significant deterioration in 4 tests of lung function. The largest falls were seen in Forced Expiration Volume in one second (p less than 0.01) and Forced Expiratory Flow between 25% and 75% of Vital Capacity (p less than 0.02). In 14 studies of 10 children with portal hypertension from other causes a significant fall occurred only in Peak Expiratory Flow Rate (p less than 0.01). The slight falls in Forced Expiratory Volume in one second and Forced Expiratory Flow between 25% and 75% of vital capacity were significantly smaller than those observed in the patients with cystic fibrosis (p less than 0.05; p less than 0.01).
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Full-thickness muscle biopsies have been taken from patients with severe disabling chronic constipation that has not responded to conservative measures. Assessment by neurohistochemical techniques has revealed that a range of neuronal dysplasias of the myenteric plexus are responsible in many cases; these include aganglionosis (Hirschsprung's disease), hypoganglionosis and hyperganglionosis. In cases considered unlikely to be Hirschsprung's disease on clinical grounds, the procedure used has often been anorectal myectomy; this has not only provided tissue for diagnosis but has also been of therapeutic value in most cases of hypoganglionosis and some cases reported as 'normal'.
Macroscopic examination of the extrahepatic bile ducts in infants with biliary atresia reveals fibrous occlusion of variable extent from an inflammatory process of unknown aetiology. Histological studies have shown that bile duct remnants at the porta hepatis frequently contain small epithelium-lined channels which communicate with intrahepatic ducts and through which effective bile drainage may be established by the operation of portoenterostomy. The 4-year survival rate in untreated cases is 2 per cent, but surgical treatment can improve the outlook and recent reports suggest that a 5-year survival rate of over 35 per cent can be achieved with portoenterostomies performed before 10 weeks of age. Complications after surgery include progressive liver disease, ascending bacterial cholangitis and portal hypertension.
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The diagnostic accuracy of laboratory investigations in the prelaparotomy differentiation between extrahepatic biliary atresia (EHBA) and intrahepatic disease (IHD) was assessed in 86 consecutive infants presenting with conjugated hyperbilirubinaemia. Forty five infants had EHBA and 41 IHD. The mean serum bilirubin concentration, gamma-glutamyltranspeptidase (GGT) activity, and the GGT/aspartate transaminase (AST) ratio were appreciably higher in infants with EHBA than in those with IHD. In infants with IHD, however, serum bilirubin concentrations were in the EHBA range in 19 (47%), as were GGT values in 29 (71%), and GGT/AST ratios in 33 (80%). In individual patients neither increasing nor decreasing GGT values were of diagnostic importance. Failure of biliary excretion of 99Tcm-p-Butyl-ida occurred in 29 of 30 (97%) patients with EHBA but also in 22 of 23 (67%) with IHD. In all 5 patients with IHD associated with alpha 1 antitrypsin deficiency these 4 investigations gave results in the EHBA range. Liver biopsy specimen interpretation, correct in 38 of 42 infants with EHBA, gave an overall accuracy of diagnosis of 86%: the results of 3 further biopsies were equivocal. In 33 of 40 infants with IHD bile duct obstruction was excluded; the remaining 7, including 4 with alpha 1 antitrypsin deficiency, showed equivocal changes. Faecal excretion of 131I rose bengal faecal excretion was less than 10% in 36 of 37 patients with EHBA and in 9 of 26 with IHD, giving an overall accuracy of diagnosis of 84%. In patients in whom genetic disorders, such as alpha 1 antitrypsin deficiency had been excluded, interpretation of liver biopsy specimens together with 131I rose bengal faecal excretion remain the most accurate means of identifying those who need surgery for EHBA and of avoiding unnecessary laparotomy in infants with IHD.
Oesophageal varices in 21 children with portal hypertension (intrahepatic 13, extrahepatic 8) were treated with sclerotherapy using ethanolamine oleate injected via a fibreoptic endoscope. Repeat endoscopy confirmed variceal obliteration in 18 children with a mean of 3.5 (range 1-8) injections. No patient has bled since obliteration of varices. Complications were oesophageal stricture (2 patients), oesophageal ulcer (5 patients) and haemorrhage within 3 days of injection (5 patients). The early results suggest that this is a satisfactory method for the treatment of oesophageal varices in children.
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Of 88 cases of extrahepatic biliary atresia, satisfactory bile flow has been established in 46% of the patients who have undergone portoenterostomies and in 25% of patients with hepaticojejunostomies. Histological analysis of the extrahepatic biliary tissue has not shown a consistent correlation with outcome of operation, except that the patients with one or two large residual ducts lined with columnar epithelium have a better chance of developing bile flow. Cholangitis developed in 43% of the cases, and co-trimoxazole was not shown to have any beneficial effect in a small prospective trial in 18 patients. Severe haemorrhage from oesophageal varices has occurred in 4 jaundice-free survivors. Seventeen patients are now over 3 years of age and thriving but many show persistent elevation of liver enzymes.
74 patients with cystic fibrosis aged 1-19 years were assessed prospectively for 1-7 years for evidence of liver involvement. 20 of these patients were referred primarily because of hepatic problems. 3 of 4 with neonatal hepatitis recovered. Chronic active hepatitis developed in a further child but resolved spontaneously. 6 patients had abnormal liver-function tests without clinical evidence of liver disease. In 18 cirrhosis was detected at age 4-13 years. Liver disease was stable in these except terminally in 3 with cor pulmonale. The principal hepatic problem was variceal bleeding, which occurred in 6 patients. 50% of bleeds followed aspirin ingestion. This drug therefore should be avoided in such patients. 13 had hypersplenism. 2 had severe splenic pain necessitating splenectomy with lienorenal shunt, which was performed also in 2 patients who had bled. 3 remain well up to 5 years later. In 3 patients seen in the past 3 years injection sclerotherapy has controlled bleeding. This technique was well tolerated without the pain associated with, or intensive physiotherapy necessary after, shunt surgery; and this may be the method of choice for controlling variceal bleeding in cystic fibrosis.
Intraluminal pressure studies on patients with congenital aganglionosis showed that the aganglionic rectum contracted in an uncoordinated manner and failed to relax. Histochemical assessment of the innervation helped to explain the variable severity of the symptoms in this condition. It is concluded that (1) absence of ganglia prevents normal coordinated peristalsis and creates an obstructive element; (2) absence of reflex relaxation adds to the obstruction; (3) the degree of uncoordinated motor activity in distal aganglionic bowel probably relates to the number of cholinesterase-positive nerves in the circular muscle and adds another variable obstructive element; and (4) deficient innervation of distal ganglionic bowel probably creates a poor propulsive force and so accentuates more distal obstructive factors. Neurohistochemical and functional studies in the anorectum of cats reveal a somewhat different innervation pattern from that in humans but show that sphincteric tone is mainly due to alpha-adrenergic neural activity. Reflex relaxation of the internal anal sphincter is a complex function in which inhibitory responses override motor responses, and it involves an important non-adrenergic non-cholinergic component. The role of cholinergic nerves in the sphincter remains uncertain. Neurohistochemical assessment of full thickness biopsy specimens of rectal muscle from patients with disabling constipation shows that developmental neuronal dysplasias of the hind-gut may be divided into three main categories: (1) aganglionosis (Hirschsprung's disease), (2) hypoganglionosis and (3) hyperganglionosis, and that the different neuronal elements may be affected to differing degrees in individuals within each group. Resection of the aganglionic bowel is required in congenital aganglionosis but the combined diagnostic-therapeutic procedure of anorectal myotomy has been found beneficial in patients with hypoganglionosis.
Five cases of hepatic haemangioma are described, and a sixth (previously reported) is reviewed. Clinical features, investigation, and management are described to show the great variability of the complications and prognosis. Five children presented in the first 10 weeks of life with hepatomegaly; 4 developed congestive cardiac failure; 3 had cutaneous haemangiomata. One child presented at age 4 years with hepatomegaly and anaemia, and on investigation had features of chronic disseminated intravascular coagulation. Focal decrease or patchiness in hepatic uptake of technetium-99m colloid, and abnormal intrahepatic circulation was shown in all cases. In 3 children liver biopsy was performed to exclude malignant disease. In one patient there was spontaneous regression of the tumour by age 3 years. In 3 cases hepatic artery ligation was necessary to control congestive cardiac failure which had persisted despite treatment with digoxin, diuretics, and oral corticosteroids, a procedure which was without complications after up to 8 years. One infant with intractable portal hypertension, hepatic vein obstruction, and severe cholestasis died with persisting alimentary haemorrhage and intra-abdominal sepsis. One child aged 4 years showed no immediate response to hepatic artery ligation but the size of her tumour got smaller and the clinical features diminished after irradiation. These tumours cause considerable morbidity and have a high reported mortality. If congestive cardiac failure is not rapidly controlled, hepatic artery ligation should be performed.
Specimens of excised tissue from the porta hepatis in 26 infants with extrahepatic biliary atresia undergoing hepatic portoenterostomy were analysed histologically for the presence and size of biliary ductules. No correlation could be found between the establishment of effective biliary drainage and the number or size of biliary ductules. it is suggested that prognosis after surgery may be related to the intrahepatic lesion and age of the child at operation rather than to the histology of the extrahepatic bile duct remnants.
Three patients with congenital hepatic fibrosis and childhood-type autosomal recessive polycystic kidney disease are reported. Portal hypertension in two of the children was decompressed surgically by lieno-renal shunting, and the renal failure in two children has been successfully treated with renal transplantation. Prophylactic porta-caval shunting followed by renal transplantation is ideally suited to the sequence of events occurring clinically in the intermediate form of this condition, preventing complications of bleeding from oesophageal varices and hyperplenism. The relationship of congenital hepatic fibrosis with the various forms of polycystic kidney disease is discussed and classified.