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Objective: To evaluate the authors' experience with gastric transposition as a method of esophageal replacement in children with congenital or acquired abnormalities of the esophagus., Summary Background Data: Esophageal replacement in children is almost always done for benign disease and thus requires a conduit that will last more than 70 years. The organ most commonly used in the past has been colon; however, most series have been fraught with major complications and conduit loss. For these reasons, in 1985 the authors switched from using colon interpositions to gastric transpositions for esophageal replacement in infants and children., Methods: The authors retrospectively reviewed the records of 41 patients with the diagnoses of esophageal atresia (n = 26), corrosive injury (n = 8), leiomyomatosis (n = 5), and refractory gastroesophageal reflux (n = 2) who underwent gastric transposition for esophageal replacement., Results: Mean +/- SE age at the time of gastric transposition was 3.3 +/- 0.6 years. All but two transpositions were performed through the posterior mediastinum without mortality or loss of the gastric conduit despite previous surgery on the gastric fundus in 8 (20%), previous esophageal operations in 15 (37%), and previous esophageal perforations in 6 (15%) patients. Complications included esophagogastric anastomotic leak (n = 15, 36%), which uniformly resolved without intervention; stricture formation (n = 20, 49%), all of which no longer require dilation; and feeding intolerance necessitating jejunal feeding (n = 8, 20%) due to delayed gastric emptying (n = 3), feeding aversion related to the underlying anomaly (n = 1), or severe neurological impairment (n = 4). No redo anastomoses were required., Conclusions: Gastric transposition reestablishes effective gastrointestinal continuity with few complications. Oral feeding and appropriate weight gain are achieved in most children. Therefore, gastric transposition is an appropriate alternative for esophageal replacement in infants and children.

Intestinal ischemia-reperfusion is a common clinical event associated with both clinical and experimental distant organ injury. In particular, the pulmonary microvasculature appears to be susceptible to injury resulting from systemic inflammatory mediator activation. This study was designed to evaluate the hypothesis that noncellular humoral factors associated with intestinal ischemia-reperfusion result in pulmonary endothelial cell adenosine triphosphate (ATP) depletion. Male Sprague-Dawley rats had intestinal ischemia induced by microvascular clip occlusion of the superior mesenteric artery (SMA) for 120 minutes. Reperfusion resulted from superior mesenteric artery clip removal. After reperfusion for 0, 15, or 30 minutes, plasma samples were obtained from the portal vein. Monolayers of cultured rat pulmonary artery endothelial cells then were incubated with the plasma samples. Adenosine triphosphate levels were determined using a luciferin-luciferase assay. A 51Cr-release assay using labeled endothelial cells was performed under identical conditions to assess cytotoxicity. Potential mechanisms of ATP depletion were evaluated by analysis of cellular energy charge and assessment of microfilament architecture. Endothelial cell ATP levels decreased from 2.23 +/- 0.16 x 10(-11) moles/microgram DNA in sham preparations to 1.23 +/- 0.09 x 10(-11) moles/microgram DNA (p < 0.001) after 4 hours in plasma from animals undergoing 120 minutes of intestinal ischemia. For plasma obtained after 15 minutes of reperfusion, the decrease in cellular ATP concentration persisted (1.23 +/- 0.27 x 10(-11) moles/microgram DNA, p < 0.001 vs. sham). After 30 minutes' reperfusion, cellular ATP levels increased only slightly after the 4-hour incubation (1.39 +/- 0.26 x 10(-11) moles/microgram DNA, p < 0.005 vs. sham). No significant cytotoxic injury occurred in any group when compared with controls. Cellular energy charge was unchanged, and microfilament architecture was preserved. These data confirm the hypothesis that humoral factors, independent of the neutrophil, result in endothelial cell ATP depletion without metabolic inhibition or cell death. Depletion of energy stores by noncellular humoral factors may represent an early event that predisposes the cell to more severe injury by other mediators of the endogenous inflammatory response.

Thirty-four infants with biliary atresia were primarily treated at our institution between 1974 and 1987. The mean age at diagnosis was 8.8 weeks. The Kasai portoenterostomy was used in 11 patients (32%) and the Sawaguchi modification in 23 infants (68%). Overall survival was 47% (16/34), with a mean follow-up of 45 months. Fifteen survivors (94%) are jaundice free, with two having undergone liver transplantation. Survival was not influenced by earlier age at operation, size of ductal remnants, or the use of an external biliary vent. Good bile flow was predictive of a favorable outcome. The incidence of cholangitis was increased in the Kasai (87%) versus the Sawaguchi groups (45%) (p less than 0.05), but 1-year survival rates were similar (55% vs 64%). The authors conclude that portoenterostomy offers a reasonable chance for success and should be the initial procedure for biliary atresia.

Noninfectious obliterative cholangitis results from biliary tract inflammation in clinical conditions such as biliary atresia and sclerosing cholangitis. The purpose of this study was to develop an animal model of noninfectious biliary tract inflammation and fibrosis. An implantable osmotic pump was connected to a catheter placed into the gallbladder of hamsters. Phorbol myristate acetate (PMA) was infused into the biliary tract for periods of 6 hours to 28 days. After 7 days the animals developed neutrophil infiltration, cellular necrosis, and edema of the biliary ducts. After 14 days, the animals demonstrated intrahepatic cholestasis with bile duct fibrosis and acute and chronic inflammatory cell infiltration. By 28 days pronounced portal fibrosis was present, some of which created an early bridging cirrhosis pattern. In addition there was evidence of neocholangiogenesis. We conclude that long-term PMA infusion into the biliary tract generates an inflammatory response characterized by obliterative cholangitis and fibrosis, sharing many of the histologic features of human biliary atresia. This model may provide a relatively simple technique for investigating the process of nonpyogenic biliary tract inflammation.

Acute lung injury characterized by increased microvascular permeability is one feature of multiple-organ system failure and the adult respiratory distress syndrome. Intestinal ischemia-reperfusion injury has been linked to this type of acute lung injury. The purpose of these experiments was to examine the pathogenic mediators that link the two processes, with particular emphasis on the roles of endotoxin and tumor necrosis factor alpha (TNF alpha). Previously described characteristics of the acute lung injury in this rat model of intestinal ischemia-reperfusion include pulmonary neutrophil sequestration, depletion of lung tissue ATP, alveolar endothelial cell disruption, and increased microvascular permeability. Plasma levels of TNF in the systemic circulation of sham-operated animals and those with intestinal ischemic injury less than 60 minutes in duration were very low or undetectable. Intestinal ischemia for 120 minutes was associated with TNF elevation to 1.19 +/- 0.50 U/mL. Reperfusion for periods of 15 and 30 minutes generated 5- to 10-fold increases in circulating TNF levels (6.61 +/- 3.11 U/mL, p greater than 0.05 and 10.41 +/- 5.41 U/mL, p = 0.004 compared to sham); however this increase in circulating TNF was transient and largely cleared within 60 minutes after initiating reperfusion. Portal vein endotoxin levels were found to increase significantly before the appearance of TNF in systemic plasma, suggesting that gut-derived endotoxin may induce TNF release from hepatic macrophages into the systemic circulation. Anti-TNF antibody attenuated the increase in pulmonary microvascular permeability in this preparation but did not prevent pulmonary neutrophil sequestration. These observations suggest that endotoxin and TNF have pathogenic roles in this acute lung injury, but that mechanisms of adherence of neutrophils to endothelial cells independent of TNF may be involved. The accumulation of neutrophils in the lung but the prevention of a vascular permeability increase in the presence of antibody to TNF may imply an in vivo role for TNF in the process of neutrophil activation. These studies provide additional evidence of the importance of the endogenous inflammatory mediators in the development of systemic injury in response to local tissue injury.

Extracorporeal Membrane Oxygenation (ECMO) has been available to neonates with respiratory failure at the University of Michigan School of Medicine since June 1981. In order to evaluate the impact of this type of pulmonary support, a retrospective analysis of 50 neonates with posterolateral congenital diaphragmatic hernia (CDH) who were symptomatic during the first hour of life and were treated between June 1974 and December 1987 was carried out. The patients were divided into two groups, those treated before June 1981 (16 patients) and those treated after June 1981 (34 patients). Overall survival improved from 50% (eight of 16 patients) during the pre-ECMO era to 76% (26 of 34 patients) during the post-ECMO period (p = 0.06). During the period after June 1981, 21 neonates were unresponsive to conventional therapy and were therefore considered for ECMO. Failure of conventional therapy was defined as acute clinical deterioration with an expected mortality of greater than 80% based on an objective formula previously reported. Six patients were excluded on the basis of specific contraindications to ECMO. Thirteen of 15 infants (87%) supported with ECMO survived. Three patients treated before 1981 met criteria for ECMO; all three died while receiving treatment using conventional therapy. These survival differences are significant (p less than 0.01). In addition, the survival of 87% for the infants treated with ECMO versus the expected mortality of greater than 80% for these same patients when treated with conventional therapy is highly significant (p less than 0.005). Based on this data, ECMO appears to be a successful, reliable, and safe method of respiratory support for selected, critically ill infants with CDH.

Cerulein-induced acute pancreatitis in rats is associated with acute lung injury characterized by increased pulmonary microvascular permeability, increased wet lung weights, and histologic features of alveolar capillary endothelial cell and pulmonary parenchymal injury. The alveolar capillary permeability index is increased 1.8-fold after a 3-hour injury (0.30 to 0.54, p less than 0.05). Gravimetric analysis shows a similar 1.5-fold increase in wet lung weights at 3 hours (0.35% vs. 0.51% of total body weight, p less than 0.05). Histologic features assessed by quantitative morphometric analysis include significant intra-alveolar hemorrhage (0.57 +/- 0.08 vs. 0.12 +/- 0.02 RBC/alveolus at 6 hours, p less than 0.001); endothelial cell disruption (28.11% vs. 4.3%, p less than 0.001); and marked, early neutrophil infiltration (7.45 +/- 0.53 vs. 0.83 +/- 0.18 PMN/hpf at 3 hours, p less than 0.001). The cerulein peptide itself, a cholecystokinin (CCK) analog, is naturally occurring and is not toxic and in several in vitro settings including exposure to pulmonary artery endothelial cells, Type II epithelial cells, and an ex vivo perfused lung preparation. The occurrence of this ARDS-like acute lung injury with acute pancreatitis provides an excellent experimental model to investigate mechanisms and mediators involved in the pathogenesis of ARDS.

Cerulein-induced acute pancreatitis in rats is associated with a reversible lung injury that is characterized by alveolar capillary endothelial-cell injury, increased microvascular permeability, interstitial edema formation, and intraalveolar hemorrhage and fibrin deposition. The role of mediators in this injury was analyzed using gravimetric data, microvascular permeability indices, electron microscopy, and a quantitative morphometric analysis. Neutrophil depletion induced by a specific antibody was highly protective against lung injury. Interruption of the complement pathway (using low dose Naja naja cobra venom factor) also protected against lung injury. Catalase and superoxide dismutase were also protective. The iron chelator deferoxamine and the hydroxyl radical scavenger, dimethylsulfoxide, were not protective against acute lung injury. These data suggest that complement, neutrophils, and neutrophil-derived (H2O2-dependent) oxygen products mediate lung injury that occurs secondary to cerulein-induced pancreatitis. In contrast to other models of neutrophil-dependent, oxygen-radical-mediated lung injury, this lung injury does not appear to be an iron-dependent and hydroxyl-radical mediated injury. We postulate that the process of acute pancreatitis leads to complement activation followed by neutrophil recruitment, sequestration, and adherence to alveolar capillary endothelial cells. Ultimately lung injury appears to result from local endothelial-cell injury secondary to neutrophil-generated oxygen products that may be myeloperoxidase dependent.