Management of major pancreatic duct injuries in children.

BACKGROUND: The operative versus nonoperative management of major pancreatic ductal injuries in children remains controversial. The computed tomographic (CT) scan may not be accurate for determination of location and type of injury. We report our experience with ductal injury including the recent use of acute endoscopic retrograde cholangiopancreatography (ERCP) for definitive imaging, and an endoscopically placed stent as definitive treatment. This has not been reported in children. METHODS: In review of 14,245 admissions to a regional pediatric trauma center over a 14-year period, 18 patients with major ductal injuries from blunt trauma were noted. Records were reviewed for mechanism of injury, method of diagnosis, management, and outcome. RESULTS: There were 10 girls and 8 boys, ranging in age from 2 months to 13 years. The most common mechanisms of injury were motor vehicle and bicycle crashes. Admission CT scan in 16 children was suggestive of injury in 11, and missed the injury in 5. Distal pancreatectomy was carried out in eight patients with distal duct injuries: one died of central nervous system injury. Nonoperative management in three proximal duct injuries suggested by initial CT scan and in three missed distal duct injuries resulted in pseudocyst formation in five survivors; one patient died of central nervous system injuries. Two children with minimal abdominal pain, normal initial serum amylase, and no initial imaging developed pseudocysts. Two of seven pseudocysts spontaneously resolved and five were treated by delayed cystogastrostomy. Two recent children with suggestive CT scans were definitively diagnosed by acute ERCP and treated by endoscopic stenting. Clinical and chemical improvement was rapid and complete and the stents were removed. Follow-up ERCP, CT scan, and serum amylase levels are normal 1 year after injury. CONCLUSION: Pancreatic ductal injuries are rare in pediatric blunt trauma. CT scanning is suggestive but not accurate for the diagnosis of type and location of injury. Acute ERCP is safe and accurate in children, and may allow for definitive treatment of ductal injury by stenting in selected patients. If stenting is not possible, or fails, distal injuries are best treated by distal pancreatectomy; proximal injuries may be managed nonoperatively, allowing for the formation and uneventful drainage of a pseudocyst.

Treatment of pancreatic duct disruption in children by an endoscopically placed stent.

BACKGROUND: Injuries to the pancreas from blunt abdominal trauma in children are rare. Most are minor and are best treated conservatively. The mainstay for treatment of major ductal injuries has been prompt surgical resection. Diagnostic imaging modalities are the key to the accurate classification of these injuries and planning appropriate treatment. Computed tomography (CT) scan has been the major imaging modality in blunt abdominal trauma for children, but has shortcomings in the diagnosis of pancreatic ductal injury. Endoscopic retrograde cholangiopancreatography (ERCP) has been shown recently to be superior in diagnostic accuracy. The therapeutic placement of stents in the trauma setting has not been described in children. METHODS: Two children sustained major ductal injuries from blunt abdominal trauma that were suspected, but not conclusively noted, on initial CT scan. Both underwent ERCP within hours of injury. In case 1, a stent was threaded through the disruption into the distal duct. In case 2, a similar injury, the stent could only be placed through the ampulla, thereby reducing ductal pressure. In both cases, clinical improvement was rapid with complete resolution of clinical and chemical pancreatitis, resumption of a normal diet, and discharge from the hospital. The stents were removed at 10 and 12 days postinjury, and both children have remained well. Follow-up ERCP and CT scans show complete healing of the ducts and no evidence of pseudocyst formation 1 year post injury. CONCLUSIONS: Acute ERCP should be the imaging modality of choice in suspected major pancreatic ductal injury. Successful treatment by placement of an intrapancreatic ductal stent may be possible at the same time. Surgical resection or reconstruction can then be reserved for cases in which stenting is impossible or fails.

Laparoscopic appendectomy for simple and perforated appendicitis in children: the procedure of choice?

BACKGROUND/PURPOSE: Whether laparoscopic appendectomy (LA) is superior to open appendectomy (OA) for simple (SA) and perforated appendicitis (PA) in children is debatable. The operative experience of 4 senior pediatric surgeons at a single institution was studied over a 6-year period during a transition from OA in all cases to LA in all cases, to answer this question. METHODS: All appendectomies from December 1993 to December 1999 were reviewed for operative technique (OA, LA), presence of perforation (SA, PA), operating time (OT), length of stay (LOS), morbidity, and mortality. RESULTS: There were 1,128 appendectomies in children aged 14 months to 19 years, including 955 LA (653 in SA, 302 in PA) and 173 OA (86 in SA, 87 in PA). OT was equal for LA and OA in SA (52 minutes), but has dropped to less than 40 minutes for LA in the past year. OT in PA was slightly longer in LA versus OA (68 v. 58 minutes; P < .001) but recently has dropped in LA to less than 60 minutes. LOS in SA was 2 days for LA and 3 days for OA; in PA, LOS was 7 days in both LA and OA, but has dropped to 5 days for LA recently. Postoperative abscess rates and incidence of bowel obstruction did not differ between LA and OA in either group. There was no mortality. CONCLUSIONS: LA is at least as safe and effective as, if not superior to, OA for both simple and perforated appendicitis. Postoperative pain is less, and recovery is faster, thereby reducing LOS and overall cost. The growing demand for this procedure can be satisfied without increase in cost, morbidity, or mortality. Laparoscopic appendectomy is our procedure of choice in children.

Treating myocardial ischemia-reperfusion injury by targeting endothelial cell transcription.

Exacerbation of, rather than improvement in, a hypoxic injury after reperfusion of ischemic tissues is recognized as the specific clinicopathologic entity referred to as ischemia/reperfusion (I/R) injury. Arguably, one of the most common forms of I/R injury occurs during cardiac surgery, which has a mandatory period of myocardial ischemia required to allow surgery in a bloodless, motionless field, followed by coronary artery reperfusion after removal of the aortic cross-clamp. In this review, we examine the endothelial cell activation phenotype that initiates and propagates myocardial I/R injury. Emphasis is given to the biology of one transcription factor, NF-kappaB, that has the principal role in the regulation of many endothelial cell genes expressed in activated endothelium. NF-kappaB-dependent transcription of endothelial cell genes that are transcribed in response to I/R injury may be a favorable approach to preventing tissue injury in the setting of I/R. Elucidating safe and effective therapy to inhibit transcription of endothelial cell genes involved in promoting injury after I/R injury may have wide applicability to the patients with heart disease and other forms of I/R injury.

Oxidative stress induces NF-kappaB nuclear translocation without degradation of IkappaBalpha.

BACKGROUND: Rel/NF-kappaB, an oxidative stress-responsive transcription factor, participates transiently in the control of gene expression. The cellular mechanisms that mediate NF-kappaB activation during ischemia (and during reperfusion in the course of treating ischemia) are not known. METHODS AND RESULTS: To investigate the NF-kappaB activation induced during oxidative stress, we examined human cardiac tissue obtained during surgical procedures requiring cardiopulmonary bypass. In vitro, we examined human umbilical vein endothelial cells (HUVECs) exposed to hypoxia, reoxygenation after hypoxia, or a reactive oxygen intermediate (H(2)O(2)). Electrophoretic mobility shift assays performed on right atrial tissue revealed prominent NF-kappaB activation after hearts had been exposed to ischemia and reperfusion. The assays also showed that NF-kappaB activation was observed in hypoxic HUVECs after reoxygenation and in cultures treated with H(2)O(2) (500 micromol/L). Pervanadate (200 micromol/L) also induced marked NF-kappaB activation in HUVECs, indicating that H(2)O(2)-induced NF-kappaB activation is potentiated by the inhibition of tyrosine phosphatases. Western blotting of cytoplasmic IkappaBalpha demonstrated that NF-kappaB activation induced by oxidative stress was not associated with IkappaBalpha degradation. In contrast, tumor necrosis factor-alpha-induced NF-kappaB activation occurred in concert with degradation of IkappaBalpha. Inhibition of IkappaBalpha degradation with a proteasome inhibitor, MG-115, blocked NF-kappaB activation induced by tumor necrosis factor-alpha; however, MG-115 had no effect on NF-kappaB activation during oxidative stress. CONCLUSIONS: This study demonstrated a stimulus-specific mechanism of NF-kappaB activation in endothelial cells that acts independently of IkappaBalpha degradation and may require tyrosine phosphorylation.

Platelet-activating factor acetylhydrolase prevents myocardial ischemia-reperfusion injury.

BACKGROUND: Platelet-activating factor (PAF) is one of the most potent biological mediators of tissue injury. PAF acetylhydrolase (PAF-AH) is a recently isolated naturally occurring enzyme that hydrolyzes PAF and renders it inactive. We hypothesize that inhibition of PAF with PAF-AH will reduce myocardial ischemia-reperfusion (I/R) injury in vivo. METHODS AND RESULTS: The coronary ligation model was used in New Zealand white rabbits. The large branch of the marginal coronary artery was occluded for 45 minutes, followed by 2 hours of reperfusion. Fifteen minutes before reperfusion, animals were given either 2 mg/kg of vehicle or of PAF-AH. At the completion of 120 minutes of reperfusion, percentage of necrosis, degree of neutrophil infiltration, and measurements of regional contractility were assessed. Data are expressed as the mean+/-SEM and compared by Student's t test or Mann-Whitney ANOVA. Both groups of animals showed an equivalent area at risk; however, 46.7+/-11% was necrotic in the animal treated with vehicle. In contrast, 20.9+/-7.0% was necrotic in the animals treated with PAF-AH (P<0.05). Systolic shortening and wall thickness were significantly greater in those animals treated with PAF-AH at 15, 30, 60, and 120 minutes of reperfusion (P<0.05). Quantification of neutrophil infiltration showed a 62% reduction in the PAF-AH treated animals compared with those treated with vehicle alone. CONCLUSIONS: PAF-AH is a potent cardioprotective agent in an in vivo model of I/R injury.

Microvascular responses to cardiopulmonary bypass.

Cardiopulmonary bypass can result in proinflammatory and procoagulant changes that can contribute to morbidity and mortality in heart surgery patients. These responses, many of which are mediated by activation of endothelial cells, normally serve to repair damaged tissue or as defenses against infection. Once activated in the setting of surgery and trauma, these responses may cause unwarranted tissue destruction if they occur inappropriately or too diffusely. The proinflammatory response results in the release of cytokines and subsequent localization of neutrophils, which can disrupt the endothelial barrier and damage underlying tissue. The procoagulant response is characterized by the transcriptional activation of tissue factor, subsequent thrombin generation with subsequent microvascular thrombosis. Techniques to inhibit endothelial cell activation while attempting to preserve the body's anti-infectious and repair mechanisms are being investigated. These include hypothermia, blockade of adhesion molecules, blocking of chemotactic factors such as interleukin-8, and prevention of transcriptional activation by inhibiting the action of nuclear factor kappa-B, which activates genes involved in this process.

An essential role for NF-kappaB in the cardioadaptive response to ischemia.

BACKGROUND: Ischemic preconditioning (IP) is the phenomenon whereby brief episodes of ischemia protect the heart against a subsequent ischemic stress. We hypothesize that activation of the transcription factor NF-kappaB mediates IP. METHODS: Rabbits were randomly allocated to one of three groups: (1) 45 minutes of myocardial ischemia followed by 2 hours of reperfusion (I/R); (2) three cycles of 5-minute ischemia and 5 minutes of reperfusion followed by I/R (IP + I/R); or (3) IP in the presence of ProDTC, a specific NF-kappaB inhibitor, followed by I/R (IPProDTC + I/R). Infarct size, indices of regional contractility, and NF-kappaB activation were determined. RESULTS: In preconditioned rabbits (IP + I/R), infarct size was reduced 83% compared with both I/R alone and IPProDTC + I/R groups (p < 0.05). Throughout reperfusion, preconditioned myocardium showed enhanced regional contractile function compared with I/R and IPProDTC + I/R groups (p < 0.05). Gel shift analysis showed NF-kappaB activation with IP that was blocked by ProDTC. I/R and IPProDTC + I/R groups showed NF-kappaB activation with I/R that was absent in preconditioned animals. CONCLUSIONS: The cytoprotective effects induced by IP require activation of NF-kappaB.

Management of pediatric liver injuries: a 13-year experience at a pediatric trauma center.

PURPOSE: This study of traumatic liver injuries (LI) in children reviews the authors' management and identifies the indications for surgical intervention. METHODS: A total of 11,761 admissions over 13 years to a regional pediatric trauma center were surveyed. RESULTS: LI were identified in 328 children. Mechanisms included 39% pedestrians struck by a vehicle, 34% motor vehicle occupants, 13% falls or discrete blows to the abdomen, 5% bicycle injuries, 5% child abuse, and 4% penetrating injuries. Eighty-seven of patients with LI were treated nonoperatively with a mortality rate of 17%. Six percent of deaths were attributed to the LI and massive hemorrhage, all of which presented with cardiopulmonary resuscitation (CPR) in progress, with the remainder of deaths attributed to massive head, neck, or chest injuries (HNCI, 90%) and sepsis (4%). Surgery was performed in 13% of all LI and included major hepatic vascular injury (MHVI) repairs (34%), hepatorrhaphies (34%), lobectomies (27%), and biliary repairs (4%). Excluding the nonoperative group deaths, the need for blood transfusion of more than 25 mL/kg in the first 2 hours as an indicator of surgical necessity or a MHVI had, respectively, a sensitivity of 34% and 67%, specificity of 98% and 97%, positive predictive value of 79% and 53%, negative predictive value of 89% and 98%, and prediction accuracy of 88% and 95%. In the surgical management group, the mortality rate was 23% with 40% of deaths attributed to MHVI, 30% a combination of MHVI and HNCI, 20% massive HNCI, and 10% sepsis. CONCLUSIONS: The majority of pediatric LI are not associated with hemodynamic instability and can be successfully managed nonoperatively (72%). Hemodynamic instability, as defined by the need for blood transfusion in excess of 25 mL/kg within the first 2 hours, was a strong indicator of a MHVI, which was often a lethal injury (70%).

Management of pancreatic injury in pediatric blunt abdominal trauma.

BACKGROUND/PURPOSE: Nonoperative management of low-grade pancreatic injury is widely accepted. Management of major pancreatic parenchymal or ductal injury in children remains controversial. This study will review management strategies as they relate to site and type of pancreatic injury and their outcomes. METHODS: A total of 11,794 consecutive admissions to a regional pediatric trauma center from 1984 to 1997 were reviewed to identify children with pancreatic injury as documented by serum amylase; imaging by computed tomographic (CT) scan, ultrasonography (US), and endoscopic retrograde cholangiopancreatography (ERCP); and surgical or postmortem reports. RESULTS: Pancreatic injury was documented in 56 children, age 2 months to 14 years, with blunt mechanisms of injury. Serum amylase level was elevated on admission in 40 (71%), and no correlation was found between admission amylase values and severity of pancreas injury. An admission CT scan was obtained in 44 (79%) patients and was positive for pancreatic injury in 25 (57%). Twelve children, who had diagnoses of other intraabdominal injury by CT scan, had pancreatic injuries discovered on exploratory laparotomy. Seven children with normal admission CT scans, and the 12 children who did not undergo imaging on admission, had pancreatic injuries that were later documented by imaging, exploration, or autopsy. Thirty children were treated with immediate exploration, 17 for nonpancreatic indications and 13 with pancreatic injuries on admission CT scan. Of 19 minor injuries noted in the operating room, only three were treated with external drainage. Seven patients with distal duct injuries underwent distal pancreatectomy with splenic preservation. Twenty-six children were treated nonoperatively, including 19 with minor pancreas injuries, three with proximal pancreatic duct injuries, and four with duct injuries that were missed at admission. There were no advantages or complications of external drainage versus nondrainage of minor pancreatic injuries. There were seven deaths (overall mortality rate, 12.5%), none related to pancreatic injury. Of the seven patients in whom pseudocysts developed (two not imaged at admission, two from known proximal duct injuries treated nonoperatively, and three from injuries missed by initial studies), five were treated by delayed internal drainage and recovered promptly, and two resolved spontaneously. Pancreas-related complications included one persistent fistula and one prolonged hyperamylasemia, both of which resolved. CONCLUSIONS: Pancreatic injuries are uncommon in children. Initial serum amylase level does not correlate with the severity of pancreatic injury. The majority of pancreatic injuries can be managed nonoperatively. Initial nonoperative management of injuries of the proximal pancreatic duct allows for the formation and uneventful delayed drainage of a pseudocyst, rather than the risks of early radical interventions. Distal duct injuries are best managed by prompt spleen-sparing distal pancreatectomy. There is no benefit of closed drainage for management of minor pancreatic injuries discovered at laparotomy.

Inhibition of the transcriptional activator protein nuclear factor kappaB prevents hemodynamic instability associated with the whole-body inflammatory response syndrome.

BACKGROUND: The transcription factor nuclear factor kappaB mediates the expression of a number of inflammatory genes involved in the whole-body inflammatory response to injury. We and others have found that dithiocarbamates specifically inhibit nuclear factor kappaB-mediated transcriptional activation in vitro. OBJECTIVE: We hypothesized that inhibition of nuclear factor kappaB with dithiocarbamate treatment in vivo would attenuate interleukin 1 alpha-mediated hypotension in a rabbit model of systemic inflammation. METHODS: New Zealand White rabbits were anesthetized and cannulated for continuous hemodynamic monitoring during 240 minutes. Rabbits were treated intravenously with either phosphate-buffered saline solution or 15 mg/kg of a dithiocarbamate, either pyrrolidine dithiocarbamate or proline dithiocarbamate, 60 minutes before the intravenous infusion of 5 micrograms/kg interleukin 1 alpha. Nuclear factor kappaB activation was evaluated by electrophoretic gel mobility shift assay of whole-tissue homogenates. RESULTS: Infusion of interleukin 1 alpha resulted in significant decreases in mean arterial pressure and systemic vascular resistance, both of which were prevented by treatment with dithiocarbamate. Pyrrolidine dithiocarbamate induced a significant metabolic acidosis, whereas proline dithiocarbamate did not. Nuclear factor kappaB-binding activity was increased within heart, lung, and liver tissue 4 hours after interleukin 1 alpha infusion. Treatment with dithiocarbamate resulted in decreased nuclear factor kappaB activation in lung and liver tissue with respect to that in control animals. CONCLUSIONS: These results demonstrate that nuclear factor kappaB is systemically activated during whole-body inflammation and that inhibition of nuclear factor kappaB in vivo attenuates interleukin 1 alpha-induced hypotension. Nuclear factor kappaB thus represents a potential therapeutic target in the treatment of hemodynamic instability associated with the whole-body inflammatory response.

Injuries of the gastrointestinal tract from blunt trauma in children: a 12-year experience at a designated pediatric trauma center.

INTRODUCTION: Nonoperative management of solid organ injury from blunt trauma in children has focused concern on potential delays in diagnosis of hollow viscus injury with resultant increases in morbidity, mortality, and cost. This study of a large pediatric trauma database will review the issues of difficulty and/or delay in diagnosis as it relates specifically to definitive treatment and outcome. METHODS: We surveyed 11,592 consecutive admissions to a designated pediatric trauma center from 1985 to 1997 to identify children with documented injury of the gastrointestinal (GI) tract from blunt trauma. The records were extensively analyzed specifically in regard to mechanism of injury, type and site of injury, time to diagnosis, operative treatment, complications, and final outcome. RESULTS: The 79 children identified, 4 months to 17 years old, included 27 females and 52 males. Mechanism of injury included 15 restrained and 7 unrestrained passengers, 15 pedestrians, 15 child abuse victims, 10 bike handlebar intrusions, 8 discrete blows to the abdomen, 4 bike versus auto, 3 falls, and 2 crush injuries. There were 51 perforations, 6 avulsions, and 22 lesser injuries including contusions. Injury of the small bowel was most common, 44 cases, followed by the duodenum, 18 cases, colon, 17 cases, and stomach, 6 cases. In 45 children, diagnosis was made quickly by a combination of obvious clinical findings, plain x-ray and/or initial computed tomographic findings mandating urgent operative intervention. Diagnosis was delayed beyond 4 hours in 34 children, beyond 24 hours in 17 children and was made by persistent clinical suspicion, aided by delayed computed tomographic findings of bowel wall edema or unexplained fluid. The six deaths were caused by severe head injury. Complications included two delayed abscesses and two cases of intestinal obstruction. All 73 survivors left the hospital with normal bowel function. CONCLUSIONS: Injury to the GI tract from blunt trauma in children is uncommon (<1%). The majority of GI tract injuries (60%) are caused by a discrete point of energy transfer such as a seatbelt (19%), a handle bar (13%), or a blow from abuse (19%), or other blows and is unique to this population. Although diagnosis may be difficult and often delayed, this did not result in excessive morbidity or mortality. Safe and effective treatment of GI tract injuries is compatible with nonoperative management of most other injuries associated with blunt abdominal trauma in children, while reducing the risk of nontherapeutic laparotomy.

Inhibition of nuclear factor-kappa B nuclear localization reduces human E-selectin expression and the systemic inflammatory response.

BACKGROUND: One proinflammatory property observed during endothelial cell activation is the expression of the neutrophil adhesion molecule E-selectin on the surface of endothelial cells. An important regulatory element in endothelial cell E-selectin expression is the nuclear localization of the transcription factor nuclear factor (NK)-kappa B, which binds to and affects the function of several genes encoding proteins mediating inflammation. METHODS AND RESULTS: In this study, we investigated the ability of pyrrolidine dithiocarbamate (PDTC), an agent that inhibits the nuclear localization of NF-kappa B, to (1) block endothelial cell E-selectin expression in vitro in response to tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and lipopolysaccharide (LPS) and (2) reduce neutrophil infiltration in a rabbit model of systemic inflammation. As measured with the use of an enzyme-linked immunosorbent assay, TNF-alpha, IL-1, and LPS each induced a significant increase in surface expression of E-selectin in cultured human umbilical vein endothelial cells (HUVECs) compared with HUVECs treated with medium alone. In contrast, E-selectin surface expression was blocked in HUVECs pretreated with PDTC before TNF-alpha, IL-1, or LPS stimulation. NF-kappa B was present in HUVEC nuclei treated with TNF-alpha, whereas translocation of NF-kappa B to the nucleus was absent in TNF-alpha-treated HUVECs pretreated with PDTC. In vivo, rabbits pretreated with PDTC before LPS infusion showed significantly less neutrophil infiltration in the lungs, liver, and heart compared with animals infused with LPS alone. This correlated with a reduction in E-selectin expression in vivo. CONCLUSIONS: Our data suggest that NF-kappa B regulation of gene expression in the vascular endothelium may be an important cellular mechanism in endothelial cell activation.

Inhibition of interleukin-8 blocks myocardial ischemia-reperfusion injury.

INTRODUCTION: Interleukin-8 is thought to play a role in neutrophil activation and transcapillary migration into the interstitium. Because neutrophils are principal effector cells in acute myocardial ischemia-reperfusion injury, we postulated that the inhibition of interleukin-8 activity with a neutralizing monoclonal antibody directed against rabbit interleukin-8 (ARIL8.2) would attenuate the degree of myocardial injury encountered during reperfusion. METHODS: In New Zealand White rabbits, the large branch of the marginal coronary artery supplying most of the left ventricle was occluded for 45 minutes, followed by 2 hours of reperfusion. Fifteen minutes before reperfusion, animals were given an intravenous bolus of either 2 mg/kg of ARIL8.2 or 2 mg/kg anti-glycoprotein-120, an isotype control antibody that does not recognize interleukin-8. At the completion of the 120-minute reperfusion period, infarct size was determined. RESULTS: In the area at risk for infarction, 44.3% +/- 4% of the myocardium was infarcted in the anti-glycoprotein-120 group compared with 24.8% +/- 9% in the ARIL8.2 group (p < 0.005). In control animals, edema and diffuse infiltration of neutrophils were observed predominantly in the infarct zone and the surrounding area at risk. Tissue myeloperoxidase determinations did not differ significantly between groups, indicating that the cardioprotective effect of ARIL8.2 was independent of an effect on neutrophil infiltration. CONCLUSIONS: A specific monoclonal antibody that neutralizes interleukin-8 significantly reduces the degree of necrosis in a rabbit model of myocardial ischemia-reperfusion injury.

Separation of omphalopagus twins: unique reconstruction using syngeneic cryopreserved tissue.

Omphalopagus twin girls were admitted for evaluation of possible separation and repair at age 7 days. Prenatal sonographic diagnosis occurred late in the third trimester and was followed by cesarean section delivery shortly thereafter. Results of extensive evaluation over the next 7 days including x-rays, computed tomography and ultrasound scan of the head and torso, and cardiac catheterization showed: the gastrointestinal tracts were separate and normal, the livers were joined but had separate biliary and vascular systems, and the hearts were separate with vastly different anatomy and function. One twin (twin A) had a normal heart with a small insignificant VSD. Twin B had a single ventricle, an incompetent A-V valve, stenotic pulmonic valve, ASD, PDA, and congenital heart block. Hemodynamic support of twin B was almost entirely from twin A. The vascular communications between the two consisted of a major connection between the internal mammary arteries and large arterial and venous connections traversing the joined livers. Because of continued deterioration of twin B, separation was undertaken at age 15 days. The separation included dividing the liver and the multiple large vascular connections. Two teams then reconstructed each twin separately. Twin B began showing signs of cardiac decompensation shortly after separation in spite of placement of a pacemaker, pulmonary artery banding, and ligation of the PDA. Cardiac function rapidly deteriorated and she died. Tissue from her chest wall was cryopreserved and placed in the tissue bank. Twin A underwent closure of her abdomen, and received a temporary bovine pericardial patch over the chest defect. She subsequently underwent placement of a graft of twin B's rib cage to bridge the bony chest defect and skin flap closure. She is presently taking a normal diet and thriving at home at age 18 months. The use of cryopreserved tissue from a syngeneic source provides a unique method of reconstruction in this situation.

Aortic arch anomalies associated with long gap esophageal atresia and tracheoesophageal fistula.

PURPOSE: The purpose of this study was to determine whether aortic arch anomalies are associated with long gap esophageal atresia and tracheoesophageal fistula (EA-TEF). METHODS: The authors performed a retrospective review of all infants who had EA-TEF from 1980 to 1996 at two pediatric surgery centers. Two hundred three infants who had EA-TEF were identified. RESULTS: Twelve infants were noted to have both long gap EA-TEF defined as a gap length greater than 3 cm and aortic arch anomalies. Of these 12, 7 had aberrant right subclavian arteries originating from the descending aorta. Four of the seven infants who had aberrant right subclavian artery (SCA) had gap lengths greater than 4 cm. All four had their fistulae divided initially through a right thoracotomy with primary repair performed at a later date. The remaining five infants who had long gap EA-TEF had right-sided aortic arch with aberrant left subclavian arteries. All five initially underwent exploration through the right chest. On discovery of the long gap EA and concurrent vascular anomaly, the thoracotomies were closed, and the infants underwent definitive repair of both their EA-TEF and their vascular anomaly through a left thoracotomy. CONCLUSIONS: The authors find that aortic arch anomalies are associated with long gap EA-TEF. Patients who have these two anomalies tend to have a long gap. Preoperative diagnosis of these anomalies may alter the timing and technique of surgical intervention. The embryogenesis of these vascular lesions may account for this more severe form of esophageal atresia.

Regulation of integrin-mediated p130(Cas) tyrosine phosphorylation in human B cells. A role for p59(Fyn) and SHP2.

Engagement of beta1 integrins in terminally differentiated human B cell lines, such as ARH-77, leads to prominent tyrosine phosphorylation of the p130 Crk-associated substrate (Cas). Cas regulates the assembly of several SH2 and SH3 domain-containing proteins into signaling complexes, which are potentially involved in the propagation of downstream signals. We demonstrate here that immunoprecipitated Cas from beta1 integrin-stimulated ARH-77 cells was associated with tyrosine kinase and phosphatase activities and that integrin ligation led to the recruitment of at least p59(Fyn) tyrosine kinase and SHP2 tyrosine phosphatase in Cas immune complexes. Cotransfection studies in COS-7 cells further indicated that Fyn/Cas physical interaction and Fyn-mediated Cas phosphorylation required amino acids 638-889 in the C-terminal region of Cas. This sequence contains both c-Src SH2 and SH3 domain-binding motifs. In vitro binding studies using glutathione S-transferase fusion proteins derived from the SH2 or SH3 domains of Fyn suggested that both Fyn domains can participate in Fyn/Cas interaction. These data implicate Fyn and SHP2 as potential modulators of Cas signaling complexes in B cells.

Comparison of the Injury Severity Score and ICD-9 diagnosis codes as predictors of outcome in injury: analysis of 44,032 patients.

INTRODUCTION: Appropriate stratification of injury severity is a critical tool in the assessment of the treatment and the prevention of injury. Since its inception, the Injury Severity Score (ISS) has been the generally recognized "gold standard" for anatomic injury severity assessment. However, there is considerable time and expense involved in the collection of the information required to calculate an accurate ISS. In addition, the predictive power of the ISS has been shown to be limited. Previous work has demonstrated that the anatomic information about injury contained in the International Classification of Diseases Version 9 (ICD-9) can be a significant predictor of survival in trauma patients. The goal of this study was to utilize the San Diego County Trauma Registry (SDTR), one of the nation's leading trauma registries, to compare the predictive power of the ISS with the predictive power of the information contained in the injured patients' ICD-9 diagnoses codes. It was our primary hypothesis that survival risk ratios derived from patients' ICD-9 diagnoses codes would be equal or better predictors of survival than the Injury Severity Score. The implications of such a finding would have the potential for significant cost savings in the care of injured patients. METHODS: Data for the test population were obtained from the SDTR, which contains data from 1985 through 1993 from five participating hospitals. Four data sources were utilized to estimate the expected survival rate/mortality rate for each ICD-9 code in the SDTR. These were (1) the SDTR patients themselves, (2) the North Carolina State Hospital Discharge Database, (3) the North Carolina Trauma Registry Database, and (4) the Agency for Health Care Policy Research's Health Care Utilization Project Database. Each of these data sources was separately utilized to develop a survival risk ratio (SRR) for each ICD-9 diagnoses code. The SRR was calculated by dividing the number of survivors for patients with each ICD-9 code by the total number of all patients with the particular ICD-9 diagnoses code. The four groups of SRRs derived from our four data sources were used as predictors of survival and the ability of the SRRs to predict survival was compared with the predictive power of the ISS using measures of accuracy, sensitivity, specificity, and receiver operator characteristic curves. RESULTS: During the years 1985 through 1993, complete data were available for analysis on 44,032 patients. Of these, 2,848 patients died during their hospitalization (6%). Survival risk ratios were calculated for each of the diagnoses in the data base. Logistic regression, using the SAS System for statistical analysis, was used to assess the relative predictive power of the ISS and the survival risk ratios derived from the ICD-9 diagnoses codes from each of the four data bases. The analyses demonstrated that the regression models using the SRRs were generally as good or better than ISS as predictors of survival. The predictive power of the SRRs derived from the SDTR data, the North Carolina Trauma Registry data and the Health Care Utilization Report data were the best. In a subsequent analysis, the SRR values and the ISS were added to the patient's age and the revised Trauma Scores to create new predictive models in the mode of TRISS methodology. The analyses again indicated that the models using SRRs had as good or better predictive power than the model using the ISS. CONCLUSIONS: The present study confirms previous work showing that survival risk ratios derived from injured patients' ICD-9 diagnoses codes are as good as or better than ISS as predictors of survival.

One-stage esophagectomy and in situ colon interposition for esophageal replacement in children.

PURPOSE: Esophageal replacement has been achieved using stomach, gastric tube, small intestine, and colon in various positions and in single or multiple stages. Long-term functional results are of prime importance in children with benign disease. The aim of this study is to present the immediate and long-term results of one-stage esophagectomy and in situ colon interposition esophageal replacement in children. METHODS: Seven children have undergone one-stage esophagectomy and in situ colon interposition esophageal replacement for stricture secondary to caustic ingestion (n = 4), battery ingestion (n = 2), and epidermolysis bullosa (n = 1). TECHNIQUE: Via thoracoabdominal and cervical incisions, the transverse colon, isolated on the left colic artery, is pulled through the esophageal hiatus and normal esophageal bed into the neck at the time of simultaneous esophagectomy. The stomach is partially wrapped around the colon as an antireflux procedure and a pyloroplasty are performed. RESULTS: There was no immediate postoperative morbidity or mortality. All patients were discharged taking a soft diet by mouth. There were no anastomotic leaks or strictures, and functional swallowing is excellent. Contrast studies show no dilation of the colon in the chest. Growth and development have been normal up to 7 years postoperatively. CONCLUSION: The one-stage esophagectomy and in situ colon interposition is an excellent technique for esophageal replacement in children. Continued evaluation of this technique will be necessary to confirm these preliminary results.

Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells.

The Crk-associated substrate p130(Cas) (Cas) and the recently described human enhancer of filamentation 1 (HEF1) are two proteins with similar structure (64% amino acid homology), which are thought to act as "docking" molecules in intracellular signaling cascades. Both proteins contain an N-terminal Src homology (SH), three domain and a cluster of SH2 binding motifs. Here we show that ligation of either beta1 integrin or B cell antigen receptor (BCR) on human tonsillar B cells and B cell lines promoted tyrosine phosphorylation of HEF1. In contrast, Cas tyrosine phosphorylation was observed in certain B cell lines but not in tonsillar B cells, indicating a more general role for HEF1 in B cell signaling. Interestingly, pretreatment of tonsillar B cells with cytochalasin B dramatically reduced both integrin- and BCR-induced HEF1 phosphorylation, suggesting that some component of the BCR-mediated signaling pathway is closely linked with a cytoskeletal reorganization. Both HEF1 and Cas were found to complex with the related adhesion focal tyrosine kinase (RAFTK), and when tyrosine phosphorylated, with the adapter molecule CrkL. In addition, the two molecules were detected in p53/56(Lyn) immunoprecipitates, and Lyn kinase was found to specifically bind the C-terminal proline-rich sequence of Cas in an in vitro binding assay. These associations implicate HEF1 and Cas as important components in a cytoskeleton-linked signaling pathway initiated by ligation of beta1 integrin or BCR on human B cells.