IgG4: not only for allergists.

We describe herein a case of IgG4-related disease with the isolated clinical presentation of malabsorption due to pancreatic failure. Histology of an abdominal lymph node was critical for diagnosis. IgG4-related disease is increasingly recognized as an immunological disorder that can mimic various clinical entities.

Prevention of relapse by mesalazine (Pentasa) in pediatric Crohn's disease: a multicenter, double-blind, randomized, placebo-controlled trial.

AIM: This study aimed to test the efficacy of mesalazine in maintaining remission in pediatric Crohn's disease (CD) following successful flare-up treatment. METHODS: In this double-blind, randomized, placebo-controlled trial, 122 patients received either mesalazine 50mg/kg per day (n=60) or placebo (n=62) for one year. Treatment allocation was stratified according to flare-up treatment (nutrition or medication alone). Recruitment was carried out over two periods, as the first period's results showed a trend favoring mesalazine. Relapse was defined as a Harvey-Bradshaw score more than or equal to 5. Time to relapse was analyzed using the Cox model. RESULTS: The one-year relapse rate was 57% (n=29) and 63% (n=35) in the mesalazine and placebo groups, respectively. We demonstrated a twofold lower relapse risk (P<0.02) in patients taking mesalazine in the medication stratum (first recruitment period), and a twofold higher risk in patients taking mesalazine in the nutrition stratum (second recruitment period), compared with the other groups. None of the children's characteristics, which differed across the two recruitment periods, accounted for the between-period variation in mesalazine efficacy. One serious adverse event was reported in each treatment group. CONCLUSION: Overall, mesalazine does not appear to be an effective maintenance treatment in pediatric CD.

Recurring enteric peritonitis associated with non-perforating colon carcinoma.

Peritonitis of enteric origin may occur during treatment with peritoneal dialysis due to visceral perforation or injury or, in the absence of perforation, due to transmural migration of enteric bacteria across the bowel wall into the peritoneal cavity. To the best of our knowledge, peritonitis has not previously been reported associated with carcinomatous colon polyp in the absence of bowel wall perforation. We describe the case of a 31-year-old female who experienced recurring episodes of enteric peritonitis associated with a clinically occult adenocarcinoma of the colon, without having any other known risk factors for peritonitis. A 15 mm carcinomatous polyp was not visible on CT scan but was found at colonoscopy with polypectomy. She proceeded to transverse colectomy; the resected colon showed no evidence of bowel wall perforation. This case demonstrates that a non-perforating carcinomatous polyp of the colon may predispose to enteric peritonitis in the setting of peritoneal dialysis, and it emphasizes the importance of making an aggressive search for underlying pathology, in patients who present with recurring enteric peritonitis or unusual presentations of enteric peritonitis.

[How to deal with gastroesophageal reflux in childhood]. / Le reflux gastro-oesophagien: attitude pratique.

Gastroesophageal reflux is frequent source of consultation at the paediatrician's room, although most GER resolve spontaneously in infancy. In most cases, after a thorough anamnesis and a full physical examination prokinetic and anti-acid medications are started, as well as postural change, without the assistance of a specialist. When reflux is complicated by either oesophagitis, respiratory symptoms, failure to thrive or when the above treatment fail, further investigations need to be undertaken. Their option will depend on the clinical presentation. Rarely GER will lead to surgery.

Selective hepatic artery ligation for hepatic haemangioendothelioma: case report and review of the literature.

Although benign, hepatic haemangioendotheliomas (HHE) are rare vascular tumours of the infant which have a high mortality rate secondary to high output congestive heart failure. The management of these tumours is still controversial and none of the different medical or surgical options has been unanimously accepted. We report the case of a neonate with congestive heart failure (CHF) due to a localized HHE, treated successfully by selective ligation of the left hepatic artery branch irrigating the tumour, under perioperative ultrasound Doppler control. A review of the literature showed 35 cases of HHE treated by hepatic artery ligation (HAL) with a survival rate of 80 %.

Biliary atresia and orthotopic liver transplantation. 11 years of experience in Geneva.

Biliary atresia (BA) is a congenital malformation or an evolutive inflammatory process which, without treatment, leads to cirrhosis, hepatic failure and death within two years of birth. The literature gives a survival rate of 60% at five years and 25% to adulthood after an initial operation performed for BA. 30% of children do not survive beyond two years of age. BA has become the most frequent indication for liver transplantation (LT) in children. With LT, survival expectancy is 90%. Results of the operation designed for BA remain unsatisfactory, and seem to depend on the age of the infants, as well as on other factors such as liver histology, and centre experience. Since 1989, onset of the paediatric hepatic transplantation program in Geneva, to July 2000, 20 children have been referred for initial treatment of BA, and 26 for possible hepatic transplantation after initial treatment done in another centre. The aim of the current study is to analyse our own results of the initial operation and to present the results of liver transplantation in this particular group of patients. All the patients with a BA are included in this study. The initial operation for BA yielded 43% favourable outcome at five years and the survival in this group following LT reached 91.3% survival. The importance of the age of the patient at time of initial operation is underlined.

Etiology and management of pediatric chylothorax.

OBJECTIVES: To determine the incidence and etiology of chylothorax and to assess our therapeutic management approach. STUDY DESIGN: We reviewed 51 patients diagnosed with chylothorax over a 12-year period. Cause, interval between operation and diagnosis, duration of chylothorax, and total volume loss per weight were recorded. RESULTS: Chylothorax was diagnosed in 46 children after cardiothoracic surgery, giving an incidence of 2.5% (46/1842); in 1 child chylothorax occurred after chest trauma, and in 4 the chylothorax was congenital or a manifestation of lymph angiomatosis. Three etiologic groups were identified: group 1, direct injury to the thoracic duct (33/51 = 65%); group 2, thrombosis and/or high venous pressure in the superior vena cava (14/51 = 27%); and group 3, congenital (4/51 = 8%). Conservative treatment was the only treatment in 80% of the patients. Surgical procedures consisted of 4 ligations of the thoracic duct, placement of 7 pleurodesis shunts, and placement of 2 pleuroperitoneal shunts. Patients in groups 2 and 3 were at higher risk for failure of conservative treatment (P <. 005). Longer duration of chylothorax and higher volume of drainage were present in group 2 compared with group 1 (P <.01). CONCLUSION: Conservative treatment was successful in 80% of the patients with our management approach. Prevention, early recognition, and treatment of potential complications, such as superior vena cava thrombosis or obstruction, may further improve success of conservative treatment. Congenital chylothorax seems different and may require a specific approach.

[Results of a combined adult-child liver transplantation in Switzerland]. / Résultats d'un programme de transplantation hépatique combiné adultes-enfants en Suisse.

Between July 1987 and August 1998, 173 orthotopic liver transplantations (OLT) were performed in Geneva. We studied a homogeneous group of 114 OLT performed during the 6 years between 1992 and 1997 on 107 patients (89 adults and 18 children; 7 retransplantations). Although Geneva has the largest transplantation programme in Switzerland and is the only centre performing paediatric liver transplantation, the mean number of procedures per year was 19, corresponding to only a small transplantation programme in Europe. It could be reasonably questioned, therefore, whether Swiss patients are not at a disadvantage as compared with patients from European countries with larger liver transplantation centres. Although the perioperative morbidity was still considerable, the results of this series -90% of actuarial patient survival at 1 and 2 years and 84% at 5 years-compare favourably with the results of the European Liver Transplantation Registry: 76% of actuarial patient survival at 1 year and 65% at 5 years. In this series, 95 patients (89%) were alive on January 1, 1998. As no patient was refused on the severity of the liver disease and as more than 10% of OLT were performed as emergencies, a bias due to the selection of the best cases cannot explain the good results. This series demonstrates that a small liver transplantation centre may obtain results that compare favourably with the results of large European centres, and that Swiss patients are not at a disadvantage as compared with patients of other European countries.

Chemotactic factors in bronchial secretions of cystic fibrosis patients.

To understand chronic neutrophil attraction into cystic fibrosis airways, both global chemotactic activity and individual chemotactic factors were studied in bronchial secretions. Bronchial secretions of 8 cystic fibrosis patients, collected on the first day of admission for antibiotic treatment, showed a high chemotactic index (19.4 +/- 5.7, n = 8). Fractionation by gel filtration of bronchial secretions resulted in three chemotactic fractions. The first factor corresponded to interleukin-8, and the second activated neutrophils via the FMLP receptor. The third factor, which was of lower molecular weight, did not activate FMLP or leukotriene B4 receptors, and its nature is still under investigation. Treating patients with antibiotics reduced global chemotactic activity, mainly by reducing the activity due to stimulation of the FMLP receptor.

Liver transplantation in children: past, present and future.

The tremendous progress accomplished during the last twenty years in liver transplantation has permitted the treatment of infants and children who can now benefit from a new organ before an and stage liver disease. The main indications in paediatrics are congenital biliary obstructions, metabolic disorders leading to cirrhosis and fulminant hepatitis. Nevertheless, in the future, other treatments for metabolic and viral diseases will be possible. The shortage of paediatric donors has been partially alleviated by the method of reduced liver, however the general shortage of organs has led to the use of split livers and living-related donors. Overall survival in children can be expected above 80%. In Geneva, 15 paediatric patients were transplanted, 3 twice, over a 6-year period with a survival rate of 86%. The indications were the same as in other centers. Acute rejection was often noted, but easily treated, mainly by steroid bolus. 13 patients have been followed up for more than 1 year and have had satisfactory growth and normal liver function tests. Whenever a liver transplantation is performed, paediatricians have hopes and fears; hope of an improvement of growth and neuro-psychological developments and fears of side effects of immunosuppressive drugs, such as renal function impairment or lymphoproliferative syndrome. The future in the field of liver transplantation will require new methods, with the aim of decreasing the necessity of whole organ transplantation. This includes alternative treatments for metabolic disorders, transplantation of isolated hepatocytes, possibly after gene therapy, and the use of an artificial liver. Some of this future is already present.

A new device for in vivo measurement of nasal transepithelial potential difference in cystic fibrosis patients and normal subjects.

Measurement of transepithelial potential difference (PD) on the nasal mucosa has been proposed to test for defective ion transport in cystic fibrosis (CF), and its possible correction after gene therapy or other treatments. The "classical" method records nasal PD under the inferior turbinate, with the disadvantage that the tip of the electrode is not seen by the operator. We have developed a purpose-designed perfusion electrode for PD recording on the visible, medial/posterior aspect of the turbinate. We wanted to determine whether such PD recordings adequately discriminate between CF patients and normal subjects. Measurements of baseline PD and response to a standardized perfusion protocol were performed in 20 normal subjects and 12 CF patients. Solutions of amiloride, with or without low chloride buffer were applied for 3 min. Increased baseline PD and depolarization after amiloride discriminated CF patients from normal subjects. Only one CF patient overlapped with the normal range. Superfusion of low chloride buffer with amiloride and terbutaline caused repolarization in 18 out of 20 normal subjects (90%), consistent with physiological Cl- secretion process, but in none of the CF patients. We conclude that measurements of potential difference on the medial/posterior aspect of the turbinate can discriminate between cystic fibrosis patients and normal subjects. At this site, visual control of the measurement is possible, and the mucosa is easily accessible for subsequent cytological sampling or biopsy.

A critical appraisal of current management practices for infant regurgitation--recommendations of a working party.

Regurgitation is a common manifestation in infants below the age of 1 year and a frequent reason of counselling of general practitioners and paediatricians. Current management starts with postural and dietary measures, followed by antacids and prokinetics. Recent issues such as an increased risk of sudden infant death in the prone sleeping position and persistent occult gastro-oesophageal reflux in a subset of infants receiving milk thickeners or thickened "anti-regurgitation formula" challenge the established approach. Therefore, the clinical practices for management of infant regurgitation have been critically evaluated with respect to their efficacy, safety and practical implications. The updated recommendations reached by the working party on the management of infant regurgitation contain five phases: (1 A) parental reassurance; (1 B) milk-thickening agents; (2) prokinetics; (3) positional therapy as an adjuvant therapy; (4 A) H2-blockers; (4 B) proton pump inhibitors; (5) surgery.

Aerosolized rhDNase in cystic fibrosis: effect on leucocyte proteases in sputum.

In cystic fibrosis (CF), large amounts of free leucocyte proteases are present in bronchial secretions, contributing to progressive lung damage. Recombinant, human deoxyribonuclease (rhDNase) is a new therapeutic agent that decreases sputum viscosity. However, deoxyribonuclease has been shown, in vitro, to release cationic enzymes from complexes with deoxyribonucleic acid (DNA). The present study was conducted to assess this effect in vivo. Free human leucocyte elastase (HLE), human leucocyte cathepsin G (HCG), total chemotactic activity, and interleukin-8 (IL-8) were determined in sputum from eight patients before, during and after rhDNase treatment. After 15 days of treatment, HLE activity increased by 81+/-44% (NS), and HCG by 189+/-70% (p<0.05). One week after stopping a 4-6 months treatment, HLE activity decreased by 35+/-18% (p<0.05), and HCG by 43+/-11% (p<0.05). Sputum bacterial density, chemotactic activity, and IL-8 concentration did not change. Thus, treatment with rhDNase can indeed increase the activity of HLE and HCG in the bronchial secretions of CF patients, and this effect is still detectable after several months of treatment. If this can be shown to be clinically relevant, combination therapy of recombinant human deoxyribonuclease with protease inhibitors should be considered as an approach to the problem.

Influence of severe underlying pathology and hypovolemic shock on the development of acute pancreatitis in children.

Acute pancreatitis in children is a little known and poorly defined disease, and thus rarely considered in the diagnosis of pediatric abdominal pain. In the past 14 years, the authors treated 21 children who had acute pancreatitis. Trauma was the cause of the disease in 29% of the patients. One third (33%) had hypovolemic shock-related pancreatitis (mostly after either cardiopulmonary bypass or severe gastrointestinal bleeding). Furthermore, a major proportion (38%) had severe underlying organic disease. The clinical presentation was unremarkable; most patients (83%) had abdominal pain, especially in the epigastrium, and vomiting was the only other clinical sign exhibited by more than 50%. The Glasgow score (a severity grading system based on eight laboratory values and calculated within the first 48 hours after admission) had good specificity but poor sensitivity. Amylasemia had no predictive value. More than half our patients (57%) had complications, mainly pseudocysts (24%) and relapse (14%), and about one quarter (24%) had severe pancreatitis. There were two deaths (10%), and all surviving children (90%) eventually were symptom-free. Treatment was conservative in the majority of cases; eight patients (38%) required surgery. Hypovolemic shock and a severe underlying pathology were identified as risk factors for the occurrence of severe pancreatitis (P < .005) or death (P < .001), but not for the development of complications.

Multiloculated epidermoid cyst of the liver.

Epidermoid cysts of the liver are extremely rare and have been described in both children and adults. Their etiology remains an enigma, and several theories have been suggested as to their origin. Due to their possible malignant potential, early detection and resection are mandatory whether the cysts are unilocular or multilocular.

[Results of liver transplantations in Geneva or 32 consecutive transplantations without mortality in 2 years]. / Résultats de la transplantation hépatique à Genève ou 32 transplantations consécutives sans mortalité sur 2 ans.

Between 1 january 1992 and 31 december 1993, 32 liver transplantations were performed in 29 patients (5 transplants in 3 children and 27 transplants in 26 adults) at Geneva University Hospital. Despite 5 super-urgent transplantations (3 fulminant hepatitis, 1 end-stage Wilson disease and 1 primary nonfunction), all patients are still alive and all have lived more than 10 months. On 1 october 1994, all patients were at home and 93% were in good general condition. No patient of this series had been transplanted for cancer and all patients positive for hepatitis B surface antigen receive long-term administration of anti-HBs immune globulin: in this respect, the long-term mortality risk of the present series of patients seems to be very low. Although these results highlight that liver transplantation can be performed safely by a competent medico-surgical team, two significant difficulties have to be outlined. First, patients are likely to die on the waiting list due to unavailable grafts, especially in emergency cases. Second, the postoperative period of patients with decompensated end-stage liver disease at the time of liver transplantation is still one of high morbidity. These facts underline that chronic liver disease patient should be evaluated for liver transplantation prior to the terminal decompensated stage of the disease, when the candidate's invariably poor general condition precludes successful liver transplantation.

Body composition analysis by dual-energy x-ray absorptiometry in adults with cystic fibrosis.

Assessment of nutritional status is important in cystic fibrosis (CF). We performed body composition analysis by dual-energy x-ray absorptiometry (DXA) in 12 adults with CF, 7 of them with malnutrition as defined by percentage of ideal body weight (IBW) lower than 90. The DXA allowed for determination of bone body mass (BBM), lean body mass (LBM), and fat body mass (FBM). A deficit in BBM and LBM was found to be present in all seven patients with malnutrition when compared with a group of young normal adults. By contrast, deficit in FBM was inconstant. Deficits in bone and lean were associated with each other. They did not depend on the severity of steatorrhea, but were highly correlated to ventilatory impairment. In conclusion, DXA provides new and potentially useful information on the nutritional status of these patients. In addition, it confirms the close association of malnutrition and lung disease in CF.