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.

The outcome of the older (> or =100 days) infant with biliary atresia.

BACKGROUND: There is a detrimental effect of increasing age on the results of the Kasai portoenterostomy for biliary atresia (BA), and some centers routinely advocate primary liver transplantation for the older infant, irrespective of other criteria. This perception that such infants are indeed irretrievable was tested by retrospective analysis. METHODS: All infants who had undergone surgery for BA during the period 1980 through 2000 aged > or =100 days were reviewed. Actuarial survival was calculated using 2 end-points (death and transplantation). A retrospective review of their ultrasonography (n = 12) and preoperative liver histology (n = 22) was also undertaken to ascertain possible predictive criteria. RESULTS: A total of 422 infants had BA diagnosed during this period, of which 35 (8.2%) were > or =100 days at surgery (median [interquartile range], 133 [range, 108 to 180] days). Surgery included portoenterostomy (n = 26), hepaticojejunostomy (n = 7), and a resection and end-to-end anastomosis (n = 1). A laparotomy only was performed in 1. Five- and 10-year actuarial survival rate with native liver was 45% and 40%, respectively. Currently, 12 (35%) patients are alive with their native liver (8 are anicteric), 9 (28%) have undergone transplantation, and 13 have died. Although there were some survival advantages for types 1 or 2 BA and "noncirrhosis" at time of surgery, neither reached statistical significance. Individual histologic features (eg, degrees of fibrosis, giant cell transformation, bile duct destruction) in the retrospective review of available material were not discriminatory. The finding of a "heterogeneous" parenchyma on ultrasonography was predictive of poor outcome but lacked sensitivity. CONCLUSIONS: The potential for reasonable medium-term survival is present in about one third of infants 100 days or older coming to primary corrective surgery. In the absence of accurate discrimination, the authors continue to favor this option rather than subject all to transplant simply on the basis of age.

The spectrum of surgical jaundice in infancy.

BACKGROUND: Conjugated jaundice arising during infancy may be caused by a number of different surgical conditions. The aim of this study was to compare clinical features, management, and outcome of all types of surgical jaundice presenting in the first year of life. METHODS: A retrospective review was conducted of all infants born in the United Kingdom with jaundice caused by a surgical cause referred to the authors' institution from January 1992 to December 1999. RESULTS: There were 171 infants who could be separated into 3 specific groups: biliary atresia (BA, n = 137), inspissated bile syndrome (IBS; n = 14), and choledochal malformation (CM; n = 12) together with a group containing various miscellaneous conditions (n = 8). Infants with BA had higher bilirubin (P <.01) and aspartate aminotransferase levels (P <.001) and came to surgery earlier (P <.01) than infants with either IBS or CM. Infants with IBS and CM were more likely to be premature and have other malformations, respectively. Ultrasound scan was the principal investigation in the differentiation of BA from other causes of jaundice. Accurate prelaparotomy diagnosis was made by percutaneous liver biopsy in 87% of cases later shown to be BA. Currently, 88 (64%) of children with BA are alive with their native liver postportoenterostomy, 4 have died, and 45 have undergone liver transplantation (with 1 death postoperatively). A policy of primary portoenterostomy for BA followed by transplantation, if necessary, resulted in a survival rate of over 95%. All children in the other diagnostic groups are alive and anicteric after appropriate surgical intervention. CONCLUSIONS: Approximately 80% of infants presenting with surgical jaundice have biliary atresia, whereas those with inspissated bile syndrome and choledochal malformations make up most of the remainder. Mortality in this age-group is confined to infants with BA, but even on these infants an overall survival rate of greater than 95% is currently expected.

Long-term outcome after gastrectomy for intractable diabetic gastroparesis.

AIMS: To examine the long-term outlook for patients with intractable vomiting from diabetic gastroparesis who underwent major gastric surgery. METHODS: Of 18 patients with problems from vomiting referred to the King's Diabetes Centre during the years 1994-2000, seven were considered to suffer irreversible symptoms not alleviated by protracted periods of medical treatment. They were all Type 1 Caucasian diabetic women, mean age 32 years (range 28-37 years) with multiple symptoms of severe autonomic neuropathy. They underwent major gastric surgery comprising 70% gastric resection including pylorus and antrum, with a 60-cm Roux-en-Y loop of jejunum to prevent reflux gastritis. RESULTS: The vomiting was relieved in six of the seven patients almost immediately after surgery and during review up to more than 6 years post-operatively. There have been no serious relapses, resulting in considerable improvement in quality of life. Unfortunately, three of the patients developed renal failure, two of them needing renal support treatments 2 and 3 years after successful gastrectomy. One patient died suddenly 5 months after successful surgery and one 3 months after starting dialysis. CONCLUSIONS: Major gastric surgery can, after careful patient selection, effectively relieve distressing vomiting from severe gastroparesis and give a greatly improved quality of life to a small group of seriously disadvantaged patients where risk of subsequent renal failure is high and where life expectancy is poor.

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.

Hepatic hemangioendothelioma associated with production of humoral thyrotropin-like factor.

We report on 7 patients referred for treatment of hepatic hemangioendothelioma with increased thyrotropin levels. The serum thyroxine level was decreased in 4 and increased in 2. Immunohistochemistry showed positive staining of tumor, but not of normal liver tissue, for thyrotropin. We propose secretion by the tumor of a thyrotropin-like factor.

Immunohistochemistry of the liver and biliary tree in extrahepatic biliary atresia.

BACKGROUND: Progressive destruction of intrahepatic bile ducts may determine outcome in extrahepatic biliary atresia (EHBA) despite successful portoenterostomy. The aim of this study was to characterize the inflammatory infiltrate of a large series of cases of biliary atresia and relate these findings to clinical outcome. METHODS: Immunohistochemical analysis was performed on frozen tissue sections of extrahepatic biliary tree and liver biopsies obtained (August 1996 to March 1998) from 28 infants with EHBA and 8 liver biopsy specimens from age-matched controls with other cholestatic liver disorders. A semiquantitative scoring system was designed to evaluate the staining with a panel of antibodies to the CD4, CD8, CD25, CD56, CD68, CD71 antigens and to HLA-DR, ICAM-1, VCAM-1, E-selectin and LFA-1. The infants then underwent followup prospectively and divided into 2 prognostic groups at 12 months postoperatively: those who had cleared their jaundice (graded as a good outcome [n = 19]), and those who required liver transplantation or who had failed to clear their jaundice (defined as > 50 micromol/L; graded as poor outcome [n = 9]). RESULTS: CD4(+) lymphocytes and CD56(+) (NK cells) predominated in the liver of infants with EHBA as compared with controls. The infiltrating cells exhibited marked proliferation (CD71 expression) and activation (particularly LFA-1 but also CD25 expression). A smaller subpopulation of the cells also expressed VCAM and E-selectin. HLA-DR was strongly expressed on Kupffer cells and to a lesser extent on proliferating bile ducts and sinusoidal endothelium. Expression of the majority of markers was lower in the remnant bile duct tissue than in the liver of EHBA (P <.05) with only HLA-DR and LFA-1 (on infiltrating cells) and ICAM (on endothelium) expressed strongly in the remnant bile duct tissue. Although quantitatively less pronounced, all of these immunohistochemical features also were noted in non-EHBA cholestatic liver tissue. A good outcome at 12 months was associated with lower CD68 (macrophage) expression in both the liver (P <.05) and biliary tree (P <.05) and with reduced expression of ICAM-1 (P =.05) on infiltrating cells in the biliary remnant. CONCLUSIONS: Immunohistochemical patterns of immune-mediated liver injury and inflammation were prevalent features at the time of portoenterostomy. They were neither exclusive to nor characteristic of EHBA. A reduction in the expression of the macrophage marker (CD68) within the liver and biliary remnants and reduction of ICAM-1 expression on infiltrating cells in the biliary remnants appear to be associated with a better postoperative prognosis.

Survival patterns in biliary atresia and comparison of quality of life of long-term survivors in Japan and England.

BACKGROUND/PURPOSE: Portoenterostomy is an accepted method of achieving bile drainage in biliary atresia, but there is a paucity of data, including formal quality-of-life (QoL) studies, on long-term survivors. This report includes survival analysis and QoL studies from the world's largest series of cases treated in Japan (1951 to 1998). The Japanese QoL results are compared with a matched group of UK patients from King's College Hospital, London. METHODS: One hundred fifteen Japanese surviving portoenterostomy patients were studied and comparison of trends in survival calculated from 6-year period cohorts. Liver function and hematologic status in a group of 30 long-term survivors (14 to 24 years) were compared with 25 patients from England, (14 to 23 years). Twenty-five Japanese and 21 UK patients (SF-36) completed a QoL questionnaire. RESULTS: Median survival times in Japanese patients before 1975 were less than 1 year but increased to 18 years after 1975. Hematologic and liver function test results did not show any significant differences between the Japanese and UK patients. QoL studies in the UK patients showed no significant difference from normative, general population data. Japanese patients underperformed in general health (P = .01), role emotional (P = .05) and role physical (P = .07) but, overall, there was no significant difference between the Japanese and UK patients except for marginal differences in indices of general health and vitality (P = .06 and .04, respectively). CONCLUSIONS: Long-term survival rate in the Japanese patients increased dramatically from 1 year to 17 years after 1975. The QoL of survivors was comparable in Japan and England. The satisfactory comparison with normative population data suggests that we should continue to use portoenterostomy as the primary treatment for biliary atresia. J Pediatr Surg 36:892-897.

Serum hyaluronic acid as an early prognostic marker in biliary atresia.

PURPOSE: The aim of this study was to assess whether serum concentrations of hyaluronic acid (HA), measured at diagnosis is an early biochemical marker of prognosis in biliary atresia. METHODS: Serum HA was measured at diagnosis using a radiometric assay in 84 infants with biliary atresia (BA), and related to outcome by 5 years of age. RESULTS: Serum HA was higher in the 29 patients who died or required liver transplant by 5 years of age compared with the 56 who survived to 5 years without transplant (490 +/- 216 microg/L v 262 +/- 163 microg/L; P <.001, 95% confidence intervals of the difference 145 to 311 microg/L). CONCLUSION: High serum concentrations of HA at diagnosis may help to identify at an early stage those patients with BA who have a poor prognosis and will require liver transplant by 5 years of age.

Anaesthesia, perioperative management and outcome of correction of extrahepatic biliary atresia in the infant: a review of 50 cases in the King's College Hospital series.

Extrahepatic biliary atresia (EHBA) is an uncommon condition presenting in the first few weeks of life. It has an incidence of 0. 5-1 per 10 000 live births and is the end result of a destructive inflammatory process involving the extrahepatic biliary system of unknown aetiology occurring in utero. The net result is neonatal jaundice due to bile stasis, with subsequent hepatocellular damage and cirrhosis. In the untreated, patient death is inevitable within 2 years. Precise diagnosis (or exclusion) of EHBA in the persistently jaundiced infant must be made urgently and major surgery (hepatic portoenterostomy: Kasai procedure) carried out as soon as possible, preferably before 6-8 weeks of age. This review is concerned with anaesthesia for correction of EHBA in 50 consecutive patients and also outlines the experience gained in the largest European centre for correction of EHBA where the number of cases now approaches 500.

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.

Novel surgical treatment and gastric pathology in diabetic gastroparesis.

AIMS: Observations are made on four Type 1 diabetic patients with the rare syndrome of intractable vomiting from confirmed gastroparesis, to determine whether radical surgery would alleviate their symptoms and subsequently to examine in detail the gastric histopathology. METHODS: The surgical approach consisted of an approximate 70% resection of the stomach, including the antrum and pylorus, with closure of the duodenum and restoration of gastrointestinal continuity with a 60-cm Roux-en-Y jejunal loop. Four longstanding Type 1 diabetic patients were examined and treated as described. They were all women in the age range 2741 years with grossly abnormal autonomic function tests in whom other causes for gastric paresis had been excluded. RESULTS: Vomiting episodes leading to multiple hospital admissions (6-8) in the year preceding surgery were eliminated in three of the four patients, while in the fourth initial success was followed by the need for dialysis for renal failure. Gastric histopathology showed evidence of smooth muscle degeneration and fibrosis, with eosinophilic inclusion bodies (M-bodies) which appear to be unique to this condition. The findings suggest the presence of a gastromyopathy. CONCLUSIONS: Satisfactory relief of intractable vomiting from diabetic gastroparesis was achieved by a novel radical surgical procedure. Histopathological findings suggest that gastromyopathy may contribute to the production of this syndrome.

Pulmonary lymphangitis carcinomatosa and acute pancreatitis: a rare presentation of choledochal cyst.

Pulmonary lymphangitis carcinomatosa is an unusual cause of death in a young adult. This case describes an apparently healthy young woman who presented with severe acute pancreatitis, which is a recognized complication of a choledochal cyst. Autopsy examination revealed advanced malignancy with poorly differentiated adenocarcinoma penetrating the wall of the choledochal cyst and metastatic adenocarcinoma in the lymph nodes, lungs and kidneys. This case emphasises the unusual presentation of a choledochal cyst with acute pancreatitis and the aggressive nature of malignancy associated with this congenital anomaly.

Association of oesophageal atresia and cholecystohepatic duct.

A rare hepatobiliary malformation in which the common hepatic duct drains directly into the gallbladder or the cystic duct (cholecystohepatic duct) is described in two children born with oesophageal atresia. Attention is drawn to the rarity of this combination. A brief review of the literature of cholecystohepatic and accessory hepatic ducts is also presented.

Arterioportal hypertension: a rare complication of partial hepatectomy.

An arterioportal fistula (APF) with arterialisation of the portal-venous system is a rare cause of portal hypertension (PH) in children. The condition may be a congenital isolated fistula or occur as part of a more generalised haemangiomatous malformation. We report a case of PH secondary to an APF, which presented with bleeding gastric varices 6 years after partial hepatectomy for hepatoblastoma. The diagnosis was established by angiography and the fistula occluded by embolisation.

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.

Spontaneous rupture of a malignant rhabdoid tumour of the liver.

Malignant rhabdoid tumours (MRT) of the liver are rare. The criteria for pathological diagnosis are clearly defined, but the clinical behaviour of these tumours is still emerging. We report a MRT of the liver with the rare clinical presentation of spontaneous rupture.

Incarceration of umbilical hernias in children: a rare but important complication.

Umbilical hernia (UH) is a common condition in infants and young children, especially in those of Afro-Caribbean origin. Spontaneous closure occurs in a majority of cases before the age of 4 years unless the neck of the sac is greater than 2 cm in diameter. Complications are rare, and conservative management is therefore advised during this time. We present three cases of incarcerated UH in boys under 4 years old, all of whom presented with small-bowel obstruction. Interestingly, in two of them undigested vegetable matter in the small bowel appeared to have precipitated the obstruction. A survey of the literature suggests that the incidence of this complication is approximately 1:1,500 UHs. We conclude that the present policy of expectant management is safe for the vast majority of children, but parents and general practitioners should be aware of the small risk and early symptoms of incarceration.