Long-term outcome of children with patent processus vaginalis incidentally diagnosed by laparoscopy.

INTRODUCTION: Patent processus vaginalis (PPV) might be incidentally diagnosed during laparoscopy. The aims of this study were to determine the prevalence and the natural history of PPV, i.e. its possible development into symptomatic inguinal hernia. INCLUSION CRITERIA: children <16years undergoing laparoscopy for pathologies other than processus vaginalis (PV) related, from 10/2000-10/2005. EXCLUSION CRITERIA: past or present history of PV-related pathologies. The internal inguinal rings were documented during laparoscopy. Follow-up was provided by phone inquiry and clinical examination if needed. Median follow-up was 10.5years (range 7.1-12.8). RESULTS: 416 patients were included. Median age at laparoscopy was 12.4years (range 3days-18.1years). Forty-three PPV (33 unilateral, 5 bilateral) were found in 38 patients (9.1%). Four children with PPV presented later with an ipsilateral inguinal hernia (10.5%, 95%CI [3%; 25%]), at a median age of 16.0years (range 11.8-17.3), at a median of 22.5months (range 12-50) after initial laparoscopy, as compared to no patient in the population with obliterated PV (0%, 95%CI [0%; 1%]). CONCLUSION: 9.1% of the observed pediatric population showed an asymptomatic PPV, and 10.5% of these children later developed an inguinal hernia. None of the children with obliterated PV developed a hernia.

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.

Intestinal obstruction caused by an ectopic fallopian tube in a child: case report and literature review.

The authors present the case of a prepubertal 14-year-old girl who was admitted for an acute abdominal pain, fever, and vomiting. She was in a poor general state, having recently suffered a weight loss of 5 kg. A plain abdominal x-ray disclosed signs of mechanical ileus. An abdominal ultrasound scan showed a normal uterus, a normal right-sided ovary, but no left ovary. An emergency laparoscopy found a normal uterus with complete absence of the left ovary and salpinx, the upper left dome of the uterus being smooth with no visible horn. The right ovary and salpinx were normal. Intestinal obstruction was caused by a strangulating cordlike structure of unclear origin. After converting to a laparotomy, we found an abnormal fallopian tube inserted in the left parieto-colic groove. The tube extended next on the lateral sigmoïd mesentery and wrapped itself around the ileum, provoking a local strangulation and an ischemic covered bowel perforation. The bowel perforation was treated by a segmental bowel resection. Careful dissection of the cordlike structure disclosed a true rudimentary fallopian tube with hypotrophic fimbriae and a small distal round structure containing ovarian tissue. These structures were removed entirely. A review of the literature on this rare situation is presented and discussed.

Improvement of the effect of hepatocyte isograft in the Gunn rat by cotransplantation of islets of Langerhans.

PURPOSE: Hepatocyte transplantation (HcTX) has been investigated for many years as an alternative therapy to orthotopic liver transplantation to treat hepatic congenital enzymatic deficiency disease. The animal model most used is the Gunn rat, which presents a hyperbilirubinemia caused by the lack of uridine-diphosphate-glucuronyl-transferase. Some investigators have clearly described a hepatotrophic effect mediated by islets of Langerhans (IL) when transplanted with hepatocytes (Hc). In this study, the functional effect of cotransplanted IL on hepatocytes (co-HcTX) in Gunn rats in an isograft model is assessed. METHODS: Two groups are compared: group 1 (n = 6), HcTX to group 2 (n = 6), co-HcTX. Cells isolated by enzymatic digestion are transplanted directly into the splenic parenchyma. Blood samples are taken regularly until day 100 to measure the unconjugated bilirubin (UB). Histological examination of the spleen is performed at the end of the experiment. RESULTS: Both groups show a significant decrease of the UB: group 1, 47%; group 2, 65%. The decrease is statistically more pronounced with co-HcTX. The histological analysis shows a trophic effect of the IL on the grafted hepatocytes in the co-HcTX group. CONCLUSIONS: The HcTX and the co-HcTX correct partially the hyperbilirubinemia of the Gunn rat. A functional assessment has been performed to evaluate the effect of cotransplanted IL on HcTX.

Effects of glucose on chemically induced acute hepatic failure in rats.

TOPIC: Acute hepatic failure (AHF) is a physiopathological entity difficult to reproduce experimentally but necessary to evaluate new therapies such as bioartificial liver (BAL) or hepatocyte transplantation (HcTX). Two main animal models are available: surgical or chemical induction of an AHF. Many authors have assessed BAL or HcTX with such models and observed increased survival rate in the treated groups. However, during AHF, severe hypoglycemia takes place. Some authors have shown that adjunction of glucose in beverage after surgically induced AHF may induce by itself an improvement of survival rate. METHOD: The purpose of the present study is to test if the adjunction of glucose leads to the same effect in an AHF chemically induced by D-Galactosamine (D-Gal). A group of animals (rats) receiving glucose 20% as beverage immediately after intoxication (Group 1), is compared with a control group receiving tap water (Group 2). RESULTS: The required dose to achieve AHF is 2.75 g/kg body weight (Gr. 0). Survival rates are as follows: Gr. 1: Day 3:20%; day 5: 10%; day 8: 0%. Gr. 2: Day 3: 0%. The difference in survival rate is not statistically significant between the two groups. Liver enzymes peak at 24 hours, then return to normal values; blood sugar levels show no difference between groups. Histological examination of Gr. 0 animals surviving and sacrificed on day 28 shows restitutio ad integrum of hepatic structure. CONCLUSION: Glucose adjunction does not alter survival rate. We can conclude that this particular model of AHF is reliable.

Does hepatocyte transplantation in a chemically induced acute hepatic failure make sense?

PURPOSE: Acute hepatic insufficiency (AHF) is one of the major challenges of intensive care medicine. Liver transplantation is the current solution to unsuccessful medical management. Owing to the lack of organ donors, other methods such as hepatocyte transplantation (HcTX) and bioartificial livers need to be explored. The aim of our experimental study is to evaluate the effect of hepatocyte transplantation on the survival in AHF animals intoxicated with D-Galactosamine (D-Gal). METHODS: The first step consists of the determination of the dose of D-Gal needed to induce at least 80% mortality between 48 and 72 hours. Two groups of a single strain of male Wistar rats are then compared, one being intoxicated with D-Gal (control group), the other receiving and HcTX in the splenic parenchyma 48 hours after intoxication. RESULTS: The required dose to achieve AHF is 3 gr/kg body weight (Gr. 0). Survival rates are as follow: Gr. 1: D0: 93%; from D1 to D28: 13%. Gr. 2: D0: 80%; D1 and D2: 33%; D3: 20%; D4: 13%, from D5 to D28: 6%. (D0 = Day of transplantation). Liver enzymes show a peak of deterioration at 24 hours, then return to normal values in both groups. Histological examination of those animals still alive and sacrificed on day 28 demonstrates a restitutio ad integrum of hepatic structure. In Group 2, it is possible to observe remaining living hepatocytes in the splenic parenchyma. CONCLUSIONS: When HcTX is performed 48 hours after D-Gal intoxication, i.e., when the animals begin to develop AHF symptoms, animal survival only significantly improves between days 0 and 3. Unlike other trials, we cannot demonstrate an improvement in long-term survival. Thus, according to this particular experimental model, HcTX is not an alternative for the treatment of AHF.

A silicone-coated nylon dressing reduces healing time in burned paediatric patients in comparison with standard sulfadiazine treatment: a prospective randomized trial.

Mepitel is a new grid like silicone coated nylon dressing containing no additional biological compounds. We describe a prospective randomized pilot study comparing Mepitel to the standard silver sulfadiazine cream (Flamazine) dressing for the topical treatment of paediatric burns. Seventy-six children presenting within 24 h of injury with a non previously treated burn were randomly assigned to Mepitel treatment (group M) or Flamazine treatment (group F). Age, sex, surface area of burn and causal agent were noted at admission. The depth of the burn, cumulative number of dressings, presence or absence of a complete epithelial cover, infection, bleeding and allergy were noted at each dressing change. There were 41 children in group M and 35 children in group F. Five children were subsequently withdrawn from each group because they required skin grafting. Analysis of the above mentioned criteria showed no statistical difference between the two groups except for the healing time (group M: 7.58+/-3.12, group F: 11.26+/-6.02, p < 0.01) and the number of dressings (group M: 3.64+/-1.5, group F: 5.13+/-2.9, p < 0.05). Mepitel has proved to be an easy-to-remove dressing, adhering only to intact skin. The faster healing time found in the Mepitel group may be related to a direct effect of silicone on epithelial growth or to a decrease in surface-cell damage compared to the silver sulfadiazine group. This attractive product will be further assessed on a larger scale trial to confirm our observations.

Circulating levels of IL-11 and leukaemia inhibitory factor (LIF) do not significantly participate in the production of acute-phase proteins by the liver.

To investigate the contribution of IL-11 and LIF to acute-phase protein (APP) production, we first analysed the effects of IL-11 and LIF on production of C-reactive protein (CRP), fibrinogen, and haptoglobin by human primary hepatocytes. We also measured the serum levels of IL-11, LIF, and CRP in serum from patients with inflammatory rheumatic diseases to assess the role of these cytokines in the APP response in vivo. We included patients with conditions associated with a high APP response such as rheumatoid arthritis (RA) or spondylarthropathy (SpA), and others usually associated with a weak APP response such as systemic lupus erythematosus (SLE), in order to investigate whether these cytokines could account for the differences in APP responses. Our results showed that IL-11 and LIF induced only minimal stimulation on production of APP by human primary hepatocytes compared with IL-6, known as the major inducer. Serum levels of CRP were elevated in RA and SpA, and significantly higher than in SLE patients. Despite the presence of a high APP response in some of our patients and despite the fact that we used sensitive assays to measure IL-11 and LIF, serum levels of both cytokines were not detected in any of the tested sera. In conclusion, our results show that circulating levels of IL-11 or LIF do not contribute significantly to the production of APP in vivo, and that they do not account for the difference in APP response between SLE and other inflammatory rheumatic diseases.

Skin harvesting on the scalp in children: utopia or reality.

UNLABELLED: Since 1990 we have used systematically the scalp as donor site for split skin graft in children. The aim of this retrospective and prospective study is to analyse the results, advantages, disadvantages, complications and problems of this method. MATERIAL AND METHODS: The series includes 43 children, age: 9 months to 15 years 6 months (mean age 5 years 9 months) who presented burns or other lesions. The surface to be grafted was 0.5% to 35% of the body surface (mean surface: 6.6% TBS). The follow-up was 25 to 1086 days (mean: 304 days). The donor site is prepared by marking of the hair-limit, shaving, disinfection and infiltration with normal saline under the galea of the surface to be harvested. Skin harvesting is done with an electrical dermatome. The donor site is covered with sponges soaked in adrenaline (1/500,000). RESULTS: 1 child required harvesting twice in 2 weeks, another one 3 times in 3 months. All the other children required only one procedure. 4 children needed a meshing of the graft. They required also harvesting from other donor sites. The surface to be grafted represented more than 15% TBS. 5 children with a surface to be grafted between 10 and 15% TBS could be covered in one session, without meshing, taking only the scalp. The healing of the scalp was complete after 7 to 14 days (mean: 9.5 days). There was no mortality in our series. We were not confronted with any infection. No hypertrophic scars or retractions were encountered. 3 children presented zones of alopecia, one had sequelae and needed two surgical procedures. The two other cases were minor cases and did not require further treatment. A certain sparseness of hair was noticed in a black girl, after the third harvesting. The blood losses were estimated as a total and have also to be attributed to the tangential excision of the burn area. CONCLUSION: Skin harvesting from the scalp in children can be recommended as first choice. The advantages, especially the rapid epithelialisation and the lack of visible scars, overcome the problems and the risks.

Soluble interleukin-6 receptor strongly increases the production of acute-phase protein by hepatoma cells but exerts minimal changes on human primary hepatocytes.

Interleukin-6 (IL-6) interacts with a system of receptors, which include a 80-kDa IL-6-binding subunit (IL-6R) and a transducing element (gp130). The soluble form of IL-6R (sIL-6R) can bind its ligand and induce cellular responses by association with gp130, thus acting as an IL-6 agonist. We and others have previously shown that the responsiveness to IL-6 is different in hepatoma and human primary hepatocytes. We therefore compared the effects of sIL-6R on the two types of cells, and on the B9 hybridoma, another IL-6-sensitive cell line. Human primary hepatocytes, hepatoma cells PLC/PRF/5, and B9 cells were incubated with different concentrations of IL-6, sIL-6-R, or both. The hepatocyte culture supernatants were tested for their content of acute-phase proteins (APP). The proliferation of B9 cells was assessed by a colorimetric method. Results showed that sIL-6R alone markedly increased the production of APP by hepatoma cells in a dose-dependent manner, but affects only minimally primary hepatocytes and the proliferation of B9 cells. The combinations of IL-6R and its ligand enhanced the effects of Il-6 alone in both PLC/PRF/5 and B9 cells, but had no effect on primary hepatocytes. An immunohistochemical study indicated that the cell-surface expression of IL-6R was dramatically lower in hepatoma cells than in primary hepatocytes. In conclusion, our results show that the expression of IL-6R is low in the hepatoma cell PLC/PRF/5 when compared with primary hepatocytes and that this difference can, at least partly, explain their deficient responsiveness to IL-6. On the other hand, it appears that IL-6R expression by primary hepatocytes is sufficient and that circulating sIL-6R is unlikely to play a significant role in the modulation of IL6 effects.

IL-1 receptor antagonist (IL-1Ra) does not inhibit the production of C-reactive protein or serum amyloid A protein by human primary hepatocytes. Differential regulation in normal and tumour cells.

The synthesis of some class 1 acute-phase proteins (APP), including C-reactive protein (CRP) and serum amyloid A (SAA) protein is completely blocked by the IL-1 receptor antagonist (IL-1Ra), whereas the production of fibrinogen, a class 2 APP, is increased by IL-1Ra in hepatoma cells, but this has never been tested in human hepatocytes in primary culture. Since previous studies on the contributions of cytokine inhibitors in connective tissues diseases suggested that IL-1 and tumour necrosis factor-alpha (TNF-alpha) might play an important role in the regulation of CRP, we decided to examine in more detail the respective roles of IL-1 beta, IL-6, and TNF-alpha and their inhibitors in the production of APP by human primary hepatocytes versus the hepatoma cell line PLC/PRF/5. In the hepatoma cell line, IL-1 beta and/or TNF-alpha had synergistic effects with IL-6 on the production of CRP and SAA. In contrast, these cytokines were devoid of effect in normal hepatocytes. The production of fibrinogen was increased by IL-6 and decreased by IL-1 (and TNF-alpha) in both cell types. The secretion of CRP and SAA by primary hepatocytes incubated with a cytokine-rich mononuclear cell-conditioned medium was totally unaffected by IL-1Ra or anti-TNF-alpha antibodies. In contrast, the addition of IL-1Ra increased the production of fibrinogen by both hepatoma cells and primary hepatocytes incubated with the mononuclear cell-conditioned medium. We therefore conclude that IL-1 beta and TNF-alpha do not exert any significant effect on the synthesis of CRP and SAA by human primary hepatocytes.

Glucokinase and cytosolic phosphoenolpyruvate carboxykinase (GTP) in the human liver. Regulation of gene expression in cultured hepatocytes.

Glucokinase and phosphoenolpyruvate carboxykinase are key enzymes of glucose metabolism in the rat liver. The former is considered to be instrumental in regulating glucose hepatic release/uptake according to the glycaemia level, and cytosolic phosphoenolpyruvate carboxykinase is a major flux-generating enzyme for gluconeogenesis. The level of expression of both enzymes and the regulation of their mRNAs in the human liver cell were investigated. Surgical biopsies of liver from patients undergoing partial hepatectomies and parenchymal hepatocytes derived from the biopsies were used to assay glucokinase, hexokinase and phosphoenolpyruvate carboxykinase activities. Hepatocytes were placed in culture and the actions of insulin, glucagon and cAMP on glucokinase and phosphoenolpyruvate carboxykinase mRNAs were studied. The main results are: (a) glucokinase accounts for 95% of the glucose phosphorylation activity of human hepatocytes, although this fact is masked in assays of total liver tissue; (b) glucokinase activity is set at a lower level in human hepatocytes than in rat hepatocytes, and vice-versa for the gluconeogenic enzyme phosphoenolpyruvate carboxykinase; and (c) as previously shown in rat liver, glucokinase and phosphoenolpyruvate carboxykinase mRNAs are regulated in a reciprocal fashion in human hepatocytes, insulin inducing the first enzyme and repressing the latter, whereas glucagon has opposite effects. These data have interesting implications with respect to metabolic regulation and intracellular hormone signaling in the human liver.