Pituitary volume and clinical trajectory in young relatives at risk for schizophrenia.

BACKGROUND: Stress and vulnerability likely interact to play a major role in psychosis. While much has been written about the neural diathesis-stress model in psychosis and its clinical risk states, little is known about HPA axis biomarkers in non-help-seeking individuals at familial high risk (FHR). We sought to prospectively measure pituitary volume (PV) in adolescents and young adults at FHR for schizophrenia and to follow their emerging sub-clinical psychotic symptoms and clinical trajectories. METHOD: Forty healthy controls and 38 relatives of patients with schizophrenia or schizoaffective disorder were identified in Pittsburgh, USA. PV was derived from baseline 1.5 T magnetic resonance imaging. Chapman's schizotypy scales were acquired at baseline, and structured clinical interviews for DSM-IV-TR Axis I diagnoses were attempted annually for up to 3 years. RESULTS: Seven individuals converted to psychosis. PV did not differ between FHR and control groups overall. Within the FHR group, PV was positively correlated with Chapman's positive schizotypy (Magical Ideation and Perceptual Aberration) scores, and there was a significant group × PV interaction with schizotypy. PV was significantly higher in FHR subjects carrying any baseline Axis I diagnosis (p = 0.004), and higher still in individuals who went on to convert to psychosis (p = 0.0007). CONCLUSIONS: Increased PV is a correlate of early positive schizotypy, and may predict trait vulnerability to subsequent psychosis in FHR relatives. These preliminary findings support a model of stress-vulnerability and HPA axis activation in the early phases of psychosis.

Chemotherapy effects on hepatoblastoma. A histological study.

The histopathological features of hepatoblastoma in 17 patients treated with preoperative chemotherapy were compared with those in 11 patients not subjected to chemotherapy during the same 11-year period. Tumor necrosis was more extensive in patients receiving preoperative chemotherapy. Two tumors, however, were apparently unaffected by chemotherapy. There was no obvious correlation between the extent of necrosis and the number of courses of chemotherapy. There also seems to be no evidence of preferential ablation of a particular morphological type of tumor. The most notable feature in cases treated with chemotherapy was the extensive presence of osteoid. Osteoid was present in 36% of untreated cases, occupying < 5% of the surface area, compared with 82% in the treated group. In seven cases, osteoid occupied > 40% of the surface area. This finding raises speculation about the role of chemotherapy in the maturation of tumors that have an inherent ability to differentiate. A long-term study is needed to clarify the prognostic significance of mature heterologous elements in hepatoblastoma.

Biliary atresia splenic malformation syndrome: an etiologic and prognostic subgroup.

BACKGROUND: The polysplenia syndrome is the most common extrahepatic anomaly found in association with extrahepatic biliary atresia. This subgroup may have a different cause and a worse prognosis than do infants with biliary atresia alone, and this hypothesis has been tested by analyzing the King's College Hospital series. METHODS: The case records of 308 infants treated between 1975 and 1991 for biliary atresia were examined for extrahepatic anomalies. RESULTS: Twenty-three (7.5%) infants had polysplenia and biliary atresia. There were also four infants with other types of splenic malformation: two with double spleen and two with asplenia. The presence of other anomalies such as situs inversus and portal vein anomalies in all the categories of splenic malformation suggests that they formed part of a larger association for which we now propose the term biliary atresia splenic malformation (BASM) syndrome. There was no difference in age at presentation and in biochemical test results of liver function before operation between infants with BASM and those with biliary atresia alone. Four (15%) infants with BASM were born to mothers with diabetes (three insulin dependent and one with gestational diabetes treated by diet alone). There were no other cases of maternal diabetes in the series as a whole. Actuarial "survival" (death or transplant) of infants with BASM after initial corrective operation was worse than that in a control group without anatomic anomalies (p < 0.05). CONCLUSIONS: BASM syndrome appears to be a distinct subgroup in infants with biliary atresia. This subgroup may have a different cause and tends to have a worse prognosis than do control subjects. Whether this is caused by the presence of the other anomalies (e.g., cardiovascular anomalies), which are in themselves detrimental, is unclear.

Localized, benign, nontraumatic strictures of the extrahepatic biliary tree in children.

BACKGROUND: Benign, nontraumatic, inflammatory strictures of the extrahepatic biliary tree are rare in children and have been reported infrequently in the literature. We describe 7 children with this type of stricture and describe the results of their surgical treatment. METHODS: There were 6 girls and 1 boy, aged 2(1/2) to 15 years. The majority, who had no significant medical or surgical history, were first seen with obstructive jaundice. Investigations revealed isolated strictures of the extrahepatic biliary tree and varying degrees of secondary biliary change within the liver. All 7 patients underwent biliary-enteric anastomosis; 5 also had resection of the stricture. RESULTS: No child experienced significant early complications from the operation, although 2 patients with unresectable lesions required further surgical treatment since their initial bypass. All patients are currently well at 1 to 17 years from initial referral without evidence of recurrent biliary disease after resection. CONCLUSIONS: Children who present with benign strictures of the extrahepatic biliary tree can be treated very satisfactorily with resection and hepaticojejunostomy. This rare condition should be considered as part of the differential diagnosis in children who present with obstructive jaundice. The etiology remains unknown.

Congenital hepatoportal arteriovenous fistula.

BACKGROUND: Two children with congenital hepatoportal arteriovenous fistulas have been investigated and treated surgically. These cases have been reviewed with five cases previously reported. METHODS: Two children, 5 months and 14 months of age, presenting with failure to thrive, hepatosplenomegaly, ascites, and recurrent gastrointestinal bleeding with evidence of portal hypertension, were found to have congenital hepatoportal arteriovenous fistulas. RESULTS: Doppler ultrasonographic examination was important in identifying abnormal portal venous flow. Angiogram identified the fistulas, confirming the diagnosis. Both patients had significant portal hypertension (pressure more than 30 mm Hg). Surgical resection in one child was unsuccessful, but surgical ligation of the hepatic artery controlled the symptoms in both patients. CONCLUSIONS: Rapid collateralization of the hepatic arterial blood supply made embolization a short-term therapeutic measure, and surgical ligation of the hepatic artery is the treatment of choice for congenital hepatoportal arteriovenous fistulas.

Liver and gall-bladder imaging with technetium-99m dihydorthioctic acid and technetium-99m pyridoxylidene glutamate-a study in the young pig.

Seventeen scans on ten young pigs were performed after injection of Technetium-99m labelled dihydrothioctic acid (99Tcm-DHT) and Technetium-99m labelled pyridoxylidene glutamate (99Tcm-PG) using a gamma-camera. Sequential images of the liver, gall-bladder and intestine were observed in all healthy animals. 99Tcm-DHT produced the clearer liver images, whereas 99Tcm-PG produced more rapid and intense gall-bladder images. Analysis of hepatic bile in three animals also suggested a more rapid and higher concentration of 99Tcm-PG than 99Tcm-DHT (36% vs. 4% of the injected dose over two hours). Bowel images were not seen in an animal that had undergone exicision of the extrahepatic biliary tract, but scans performed after hepaticojejunostomy demonstrated intestinal transit of isotope. This study shows that the hepatobiliary system can be easily imaged using Technetium-99m labelled compounds which are excreted into bile. These agents may be useful in the diagnosis of obstructive lesions of the extrahepatic biliary tract of adults and infants.

Hepatobiliary imaging: the use of 99Tcm-pyridoxylidene glutamate scanning in jaundiced adults and infants.

99Tcm-pyridoxylidene glutamate (99Tcm-PG) scans have been carried out in 24 jaundiced adults (mean total bilirubin 255 mumol/l and 11 infants with prolonged obstructive jaundice (mean total bilirubin 165 mumol/l). Absence of radioactivity in the gut was interpreted as complete biliary obstruction which was the cause of jaundice in ten adults and six infants. Using this criterion occlusion or patency of the bile ducts was correctly determined in 21 adults and eight infants. False-negative gut images were found in one adult and two infants, and three scans were inconclusive (two adults, one infant). The scan was unable to show details of the site of obstruction or pathology but the technique was simple and atraumatic and was safely performed in patients with serious complications, e.g. renal failure, coagulation defects, septicaemia. In infants the 99Tcm-PG scan compared well with the 131I rose bengal faecal excretion test and with liver biopsy in the investigation of prolonged obstructive jaundice. Repeat scans in infants with biliary atresia were used to assess postoperative bile drainage. It is suggested that 99Tcm-PG scanning is useful screening test in difficult cases of jaundice. It is especially useful in frail patients, and patients with complications.

Hepatobiliary imaging: a comparison of 99Tcm-dihydrothioctic acid and 99Tcm-pyridoxylidene glutamate in the non-jaundiced patient.

A comparison of two hepatobiliary imaging agents, 99Tcm-dihydrothioctic acid (99Tcm-DHT) and (99Tcm-pyridoxylidene glutamate (99Tcm-PG) has been carried out in 44 non-jaundiced patients. Thirty-one patients were admitted for investigation of upper abdominal pain and 13 patients were volunteers who were undergoing treatment for unrelated conditions. Satisfactory liver images were obtained with both agents in patients without liver disease, but they were inferior to those seen after 99Tcm-sulphur colloid. 99Tcm-PG produced clearer images of the gall-bladder and bile ducts than 99Tcm-DHT. Non-visualization of the gall-bladder was interpreted as gall-bladder disease; in patients with inflammatory gall-bladder disease no gall-bladder image was seen (nine 99Tcm-DHT, nine 99Tcm-PG). The gall-bladder was also not demonstrated in two of the volunteers' group (one 99Tcm-DHT, one 99Tcm-PG), nor was a gall-bladder seen in five patients whose abdominal pain was not due to acute cholecystitis. Despite this, there was agreement between the results of imaging and oral cholecystography in 21 out of 22 subjects. 99Tcm-PG is non-toxic, cheap and rapidly excreted by the liver into the bile. A 99Tcm-PG scan would be useful when rapid diagnosis is required in suspected acute cholecystitis when conventional contrast radiology is unlikely to be of value.

Extrahepatic biliary atresia and twinning.

1. Four pairs of discordant twins were observed in a series of 237 extrahepatic biliary atresia patients ascertained in London. 2. The twinning prevalence (1.7%) was as expected considering the ethnic composition of the sample. 3. Out of a total of 17 other twin pairs reported in the literature, only one was concordant for the disease. Since only 17 instances of familial cases have been described, the conclusion is that any influence of genetic factors in this condition is likely to be manifested indirectly, possibly in the form of increased susceptibility of the biliary epithelium to infectious or toxic agents.

The relative importance of familial, reproductive and environmental factors in biliary atresia: etiological implications and effect on patient survival.

1. The clinical records of 237 patients with extrahepatic biliary atresia (EHBA) attending King's College Hospital, London, between March 1973 and October 1985 were analyzed in terms of familial and reproductive factors, as well as of their possible effect on patient survival. 2. The male:female ratio was 0.93, and the ages of the patients' mothers and fathers were significantly higher than would have been expected from sibship data. Similarly, the number of first-born children having EHBA was less than expected. 3. In a subsample of 189 mothers, the obstetrical histories of women who had children with associated EHBA (20% of the total) showed: 1) a higher frequency of illness before and during pregnancy; 2) a higher level of pharmaceutical drug consumption during pregnancy, and 3) more fetal losses, especially in the gestation immediately preceding the patient's birth. 4. Age at death (average 15.1 +/- 13.2 months) and survival rates depend critically on surgical intervention and were not related to the presence or absence of extrahepatic malformations or to the type of atresia. 5. The present observations, taken together with those of others, indicate that problems in the reproductive process or exposure to noxious environmental agents may be etiological factors in associated EHBA.

Macroscopic appearance at portoenterostomy--a prognostic variable in biliary atresia.

UNLABELLED: A number of features (eg, age at time of surgery, size of microscopic biliary ductules) have been suggested to be useful predictors of the efficacy of portoenterostomy in the treatment of biliary atresia. However, no previous study has attempted to quantify the macroscopic appearance of the degree of hepatobiliary damage found during initial surgery. METHODS: A macroscopic appearance at portoenterostomy (MAP) score was calculated for 30 infants treated consecutively at King's College Hospital, London. The MAP score was summated from four features (liver consistency, size of portal remnants, degree of portal hypertension, and associated extrahepatic anomalies), with the possible range being from 0 to 6. The infants had follow-up prospectively for a median of 32 months. RESULTS: Twenty infants were anicteric at the time of analysis; their median time to clear jaundice was 48 days (Success group; n = 20). Of the remaining infants, eight had undergone transplantation, one had died awaiting transplantation, and one was still jaundiced (Failure group; n = 10). There was a significant correlation between the MAP score and the age at time of surgery (rB = .57, P = .0005), but only the MAP score was significantly different between the Success and Failure groups (P = .02). Component analysis showed that the portal-remnant subscore contributed most to discrimination (P = .007). The time until clearance of jaundice for the Success group was related to liver consistency (P = .01) and portal remnants (P = .02). CONCLUSION: Simple observation by an experienced surgeon (quantified as the MAP score) was a useful indicator of the success of this procedure and may be as valuable as the more sophisticated histological or biochemical tests.

Congenital extrahepatic portocaval shunts--the Abernethy malformation.

The first account of an absent portal vein and a congenital mesenterico-caval shunt was given by John Abernethy in 1793. Five new cases of congenital extrahepatic portocaval shunts are described in this report. One end-to-side shunt with congenital absence of the portal vein (type 1 shunt) is the 13th case in the literature. Four are side-to-side (type 2) shunts of which there have been only two previous reports. Type 1 shunts are associated with other congenital abnormalities and have only been recognized in girls. Five of these cases developed liver tumours. Type 2 shunts are rarer, and four of five have been boys. They are not usually associated with other anomalies. Encephalopathy may be associated with these shunts in adults, and surgical closure of the side-to-side shunts is therefore recommended. End-to-side shunts are not correctable but the abnormal anatomy may create a problem for hepatic transplantation, should this be necessary for associated disorders such as biliary atresia. "The Abernethy Malformation" would seem to be a suitable eponym for congenital extrahepatic portocaval shunts.

Gastric volvulus in childhood.

Gastric volvulus is a rare surgical emergency in infancy and childhood. Only 51 cases have been reported. We describe four new cases. The classical features of the condition are discussed.

Progressive biliary pathology associated with common pancreato-biliary channel.

A female infant who presented with transient obstructive jaundice and who was shown to have mild fusiform dilatation of the common bile duct at the age of 18 months was followed up with hepatobiliary ultrasound scans over a period of 17 years. Enlarging gallbladder polyps were identified during the last 2 years of follow-up, and endoscopic retrograde cholangio-pancreatography (ERCP) showed a common pancreato-biliary channel with minimal bile duct dilatation. A high concentration of pancreatic amylase was detected in the bile. Hepaticojejunostomy and cholecystectomy were performed. Histologically, the resected common bile duct showed fibrous thickening of the wall and loss of surface epithelium. Muscular hypertrophy and polypoid lesions, which were foci of cholesterosis, were identified in the gallbladder. There was a minimal lymphocytic infiltrate in the subepithelial connective tissue. This report documents a progressive change in the ultrasound appearances of the gallbladder and histological changes in the extrahepatic ducts secondary to a common pancreato-biliary channel and pancreato-biliary reflux.

Biliary amylase and congenital choledochal dilatation.

The relationship between levels of biliary amylase measured at operation and clinical features was studied in a series of 55 children with congenital biliary dilatation (choledochal cyst) who presented between 1976 and 1993. There were 36 cystic and 19 fusiforms dilatations in the series. The most common modes of presentation were painless jaundice (n = 23) and pancreatitis (n = 22). Five infants presented with abnormal antenatal ultrasound examinations. Children with pancreatitis were older than those with painless jaundice (4.2 versus 1.5 years; P = .005), and a higher proportion had raised levels of biliary amylase (100% versus 44%; P < .0001). There was no difference in the age at presentation (P = .32), clinical mode of presentation (P = .3), or the level of biliary amylase (P = .25) between cystic and fusiform dilatations. A correlation was found between age at surgery and biliary amylase in the cystic (rs = 0.55; P = .001) but not in the fusiform group (P = .22). All infants with antenatal diagnoses were cystic dilatations. Choledochal cystic dilatations that were diagnosed antenatally did not have significant amylase reflux, suggesting that the aetiology of this subgroup is truly congenital. Children who present at a later age with pancreatitis invariably have high levels of biliary amylase, which is presumed to occur because of a common channel and reflux of biliary and pancreatic secretions.

Antenatal diagnosis of congenital anomalies of the biliary tract.

BACKGROUND: The accuracy of the technique of antenatal ultrasonography in the diagnosis of congenital bile duct lesions is unknown. METHODS: Thirteen patients with proven biliary disease who had abnormal antenatal scans were reviewed. Two infants had type I cystic biliary atresia and one had a noncommunicating segmental dilatation of the bile duct in a type 3 biliary atresia. The remainder had choledochal cysts and included two patients with intrahepatic cysts. The correct diagnosis was made antenatally in only two (15%) cases. Of the remaining patients, seven received a diagnosis of intraabdominal cysts of unknown etiology, three of duodenal atresia, and one ovarian cyst. The median gestational age at the antenatal diagnosis was 20 weeks. RESULTS: Jaundice developed in 11 infants, and dilatation of intrahepatic biliary radicals was noted in four of the choledochal cysts. Obstructive jaundice and increasing cyst size were indications for early surgery, and twelve infants underwent a laparotomy at a median age of 4 weeks. During the median follow-up period of 2 years, 12 of the 13 patients have lost their jaundice or remained anicteric. Antenatal diagnosis offers the possibility of early definitive surgery for uncomplicated choledochal dilatation and the chance of improved outcome for surgically treated biliary atresia. An algorithm is suggested for the management of antenatally detected cystic biliary lesions.

Symptomatic hemorrhoids and anorectal varices in children with portal hypertension.

There have been few reports of the anorectal problems encountered in children with portal hypertension. We report the incidence of anorectal symptoms in a retrospective study of 189 children treated by injection sclerotherapy for esophageal varices secondary to portal hypertension. Anorectal symptoms, proctoscopic findings and treatment have been recorded in this group. The incidence of symptomatic hemorrhoids and rectal varices was 4.2%. Hemorrhoids are rare in children and the increased incidence can be assumed to be secondary to portal hypertension. Treatment is advised only for symptomatic patients and injection sclerotherapy is satisfactory for the majority.

Hepatic histology and the development of esophageal varices in biliary atresia.

Histological features in liver biopsy specimens taken from 71 infants at the time of surgery for biliary atresia (portoenterostomy) were analyzed using a scoring system and compared with an endoscopic grading of esophageal varices performed at a mean age of 3.4 years. The analysis showed no correlation between a "global" score, which represented the severity of all histological changes in the original biopsy specimen, and the severity of esophageal varices. Further analysis also showed no correlation with any individual histological feature (eg, fibrosis). These findings failed to confirm a previous study, which suggested a relationship between liver changes at surgery and the later development of esophageal varices in children with biliary atresia.

Does the morphology of the extrahepatic biliary remnants in biliary atresia influence survival? A review of 205 cases.

Resected extrahepatic remnants taken at the time of portoenterostomy were examined in a single-center review of 205 cases of biliary atresia. The morphological features of the size and number of residual ducts at the porta hepatis and the degree of inflammation at the porta hepatis were analyzed using a semiquantitative scoring system. The morphology of the common hepatic and common bile duct was classified into seven types. These features were then related to age at time of initial surgery and to survival. This showed that few or absent ductal remnants at the porta hepatis and absence of portal inflammation were predictors of poor prognosis. These histological features may represent the "burnt out" end result of the disease process. There was no correlation between age at time of portoenterostomy and either portal duct patency or portal inflammation. The common hepatic and common bile duct were variably involved in the sclerosing process, but the patterns of obliteration were not indicative of prognosis. The severity of intrahepatic biliary cholangiopathy and the extent of liver damage may ultimately be more important to survival in the long term.

Extrahepatic biliary atresia: a first-trimester event? Clues from light microscopy and immunohistochemistry.

Biliary atresia is an obliterative disorder of the bile ducts, causing obstructive jaundice in neonates. In this study, the developing biliary system of normal human embryos and fetuses was examined and compared with the resected extrahepatic biliary remnants from 205 cases of biliary atresia. At the porta hepatis level, it was found that the primary biliary ductal plate undergoes a specific sequence of remodelling, resulting in the formation of large tubular bile ducts surrounded by thick mesenchyme, between 11 and 13 weeks postfertilisation. These developing ducts are in luminal continuity with the extrahepatic biliary tree throughout gestation. Contrary to long-held belief, no "solid phase" was observed in the development of the extrahepatic bile duct. Examination of the biliary remnants in biliary atresia showed that the porta hepatis is encased in fibrous tissue, and a variable pattern of obliteration of the common hepatic and common bile ducts was observed. Anticytokeratin immunostaining showed similarities between the abnormal ductules within the porta hepatis in biliary atresia, and the developing bile ducts in the first trimester. Biliary atresia may be caused by failure of the remodelling process at the hepatic hilum, with persistence of fetal bile ducts poorly supported by mesenchyme. As bile flow increases perinatally, bile leakage from these abnormal ducts may trigger an intense inflammatory reaction, with subsequent obliteration of the biliary tree.