Regulation of cutaneous malignancy by gammadelta T cells.

The localization of gammadelta T cells within epithelia suggests that these cells may contribute to the down-regulation of epithelial malignancies. We report that mice lacking gammadelta cells are highly susceptible to multiple regimens of cutaneous carcinogenesis. After exposure to carcinogens, skin cells expressed Rae-1 and H60, major histocompatibility complex-related molecules structurally resembling human MICA. Each of these is a ligand for NKG2d, a receptor expressed by cytolytic T cells and natural killer (NK) cells. In vitro, skin-associated NKG2d+ gammadelta cells killed skin carcinoma cells by a mechanism that was sensitive to blocking NKG2d engagement. Thus, local T cells may use evolutionarily conserved proteins to negatively regulate malignancy.

The effect of graded intake of glycyl-L-tyrosine on phenylalanine and tyrosine metabolism in parenterally fed neonates with an estimation of tyrosine requirement.

Although tyrosine is considered indispensable during the neonatal period, its poor solubility has limited its inclusion in parenteral amino acid solutions to less than 1% of total amino acids. Dipeptides of tyrosine are highly soluble, have been shown to be well used and safe in animal models and humans, and, therefore, may be used as an effective means of providing tyrosine in the parenterally fed neonate. The goal of the present study was to determine the tyrosine requirement of the parenterally fed neonate receiving graded intakes of glycyl-L-tyrosine as a source of tyrosine. Thirteen infants receiving adequate energy (340 +/- 38 kJ. kg(-1).d(-1)) and protein (2.4 +/- 0.4 g.kg(-1).d(-1)) were randomized to receive parenteral nutrition with one of five graded levels of glycyl-L-tyrosine. The mean requirement and safe level of intake were estimated using a 1-(13)C-phenylalanine tracer and linear regression cross-over analysis that identified a break point in the response of label appearance in breath CO(2) (F(13)CO(2)) and phenylalanine oxidation to graded tyrosine intake. Based on the mean estimates of whole-body phenylalanine oxidation, the tyrosine mean requirement and safe level of intake were found to be 74 mg.kg(-1). d(-1) and 94 mg.kg(-1).d(-1), respectively. This represents 3.1 and 3.9% of total amino acids, respectively, considerably higher than levels found in present commercially available pediatric amino acid solutions. These data raise concern regarding the adequacy of aromatic amino acid intake in the parenterally fed neonate.

A new technique for resecting 'unresectable' liver tumors.

BACKGROUND/PURPOSE: Liver tumors that surround the three major hepatic veins traditionally have been considered unresectable. This report describes an extended atypical left hepatectomy technique for tumors around the major hepatic veins. METHODS: Three children with tumors surrounding the 3 hepatic veins underwent intraoperative evaluation for extended atypical left hepatectomy. The left hepatic artery, left branch of the portal vein, and the 3 hepatic veins are occluded with vascular clamps. Perfusion of the remaining liver is through the right hepatic artery and portal vein into the retrohepatic vena cava via the retro hepatic veins. If the liver remains soft and does not become mottled, division of the 3 hepatic veins and resection of the tumor are carried out. RESULTS: Extended atypical left hepatectomy was successful in 2 children. Bile leak occurred in 1 instance and healed spontaneously. Both patients had transiently elevated serum bilirubin and transaminase levels and an elevated prothrombin time for 2 weeks. Both survived after treatment with chemotherapy. In the third child the liver became tense and mottled, and the procedure was abandoned. CONCLUSIONS: Successful extended atypical left hepatectomy depends on the ability of the retro hepatic veins to adequately drain blood into the vena cava after interruption (clamping) of the main hepatic veins. If the liver becomes mottled and tense the procedure must be abandoned and the patient should be considered for hepatic transplantation.

The effects of prebiopsy corticosteroid treatment on the diagnosis of mediastinal lymphoma.

BACKGROUND/PURPOSE: For children with probable mediastinal lymphoma and a high risk of cardiorespiratory morbidity, many centers recommend delaying the diagnostic biopsy for 24 to 48 hours while corticosteroids are administered to reduce tumor size and morbidity. This study was undertaken to determine the effect of preoperative steroid use on the accuracy of the pathological diagnosis and incidence of perioperative cardiorespiratory morbidity. METHODS: From 1988 to 1998, 86 children were treated for mediastinal lymphoma. Twenty-three received steroid before biopsy (study group) because of clinical evidence of respiratory compromise, and the remaining 63 served as controls. Clinical parameters, steroid use, and detailed pathological findings obtained at initial and subsequent biopsies were reviewed. Steroid treatment was considered to have had an adverse effect on the pathological diagnosis if (1) a definitive diagnosis was delayed more that 1 month, (2) a definitive diagnosis could not be made, or (3) the extent of disease could not be staged with certainty. RESULTS: Steroid treatment had an adverse effect on the pathological diagnosis in 5 of 23 (22%) children: 1 diagnostic delay, 3 failures of a definitive diagnosis, and 1 possible failure of staging. A definitive diagnosis was made in all control patients. Perioperative survival was 100% in both groups. At biopsy, only 3 children in the steroid treatment group and 2 children in the control group had moderate, nonfatal cardiorespiratory instability. Parameters of steroid use among children who had inaccurate pathological diagnoses or cardiorespiratory morbidity were not significantly different from those who did not. CONCLUSIONS: Steroid treatment before biopsy of mediastinal lymphoma may adversely affect the pathological accuracy or cause a delay in definitive diagnosis in a minority of cases. The dose and duration of steroid use was not related to outcome. Prebiopsy steroid appears to minimize the likelihood of cardiorespiratory morbidity in high-risk patients.

Unsuccessful air-enema reduction of intussusception: is a second attempt worthwhile?

Pneumatic reduction of idiopathic intussusception is successful in about 80% of cases, while 60% of the failures are reduced at surgery without resection. To determine whether delayed, repeated attempts at enema reduction of failures would reduce the need for operation in selected cases, over a 2-year period (1994-1996 inclusive), 17 infants with idiopathic intussusception underwent delayed repeat enemas 2-19 h following the first failed attempt at reduction. Clinical parameters and radiologic findings were evaluated with respect to outcome. Ten intussusceptions were successfully reduced after the second attempt in 9 and after the fourth attempt in 1. Seven children underwent a laparotomy, 5 because of failure of progressive reduction at air enema (AE). Two were taken to surgery early in the series, 1 because of perforation during a second attempt and 1 while awaiting a third reduction attempt. The 10 successful reductions all showed progressive movement of the intussusceptum on each AE; the 2 who perforated failed to show progressive reduction on their second AE. Because of these cases, the remaining 5 were referred to surgery because of failure of progressive reduction of the intussusceptum on the second attempt. At laparotomy, of the 7 unsuccessful reductions, 4 required resection and 3 had difficult manual reduction. The presence of vomiting, a mass, and/or bloody stools were not predictors of outcome. Failures had higher body temperatures (38.1 +/- 0.3 vs 37.4 +/- 0.1 degrees C, P = 0.07), heart rates (153.7 +/- 8 vs 136.9 +/- 2.1 min, P = 0.03), and longer duration of symptoms (36.8 +/- 4 vs 21.3 +/- 3.6 h; P = 0.01) than successes. Delayed repeat AEs may be safe and effective in selected cases of idiopathic intussusception, but should be considered only if significant movement of the intussusceptum is noted at each attempt. The ideal time for repeat AE reduction prior to surgery is not established, but 2-4 h appears appropriate. Pyrexia, tachycardia, and duration of symptoms greater than 36 h are relative contraindications to this course of management.

Delayed hemorrhage after nonoperative management of blunt hepatic trauma in children: a rare but significant event.

PURPOSE: Nonoperative management of blunt hepatic injury (BHI) has become widely accepted in hemodynamically stable children without ongoing transfusion requirements. However, late hemorrhage, especially after discharge from the hospital can be devastating. The authors report the occurrence of serious late hemorrhage and the sentinel signs and symptoms in children at risk for this complication. METHODS: Nonoperative management of hemodynamically stable children included computed tomography (CT) evaluation on admission and hospitalization with bed rest for 7 days, regardless of injury grade. Activity was restricted for 3 months after discharge. Hepatic injuries were classified according to grade, amount of hemoperitoneum, and periportal hypoattenuation. RESULTS: Over 5 years, nonoperative management was successful in 74 of 75 children. One child returned to the hospital 3 days after discharge with recurrent hemorrhage necessitating surgical control. Review of the CT findings demonstrated that he was the only child with severe liver injury in all four classifications. A second child, initially treated at an outside hospital, presented 10 days after injury with ongoing bleeding and died despite surgical intervention. Only the two children with delayed bleeding had persistent right abdominal and shoulder discomfort in the week after BHI. CONCLUSIONS: Our findings support nonoperative management of BHI. However, late hemorrhage heralded by persistence of right abdominal and shoulder pain may occur in children with severe hepatic trauma and high injury severity scores in multiple classifications.

Participant satisfaction and comfort with multidisciplinary pediatric telemedicine consultations.

PURPOSE: The aim of this study was to measure both satisfaction and comfort levels and estimates of cost savings of families with children receiving health care services from a distant pediatric tertiary care center by readily available telecommunications technologies. METHODS: From February 1996 to September 1997, 140 children at a site 840 miles from the tertiary care center were seen during an evaluative trial of telemedicine consultations (TMC). The TMC visit was the initial encounter with the tertiary care specialist for 31 children. After consultation, each family was asked to complete an anonymous quality management survey that asked for estimates of cost savings and assessed their level of comfort and satisfaction with 13 other aspects of the TMC encounter. A 3- or 5-point Likert scale was used for each question. Comfort scores before and after each consultation were compared by chi2 analysis. Logistic regression was used to determine the independent predictors of satisfaction. RESULTS: 104 of the 140 (74%) families responded. Mean patient estimated cost savings was $1,318+/-677. The highest level of comfort was noted by 58% of respondents before TMC and by 77% after (P = .005). On a 5-point scale, 71% scored 5 (completely satisfied). None scored less than 3. The independent statistically significant predictors of satisfaction were concerns about privacy, comfort with the camera, and perceived specialist comfort. CONCLUSIONS: In addition to providing financial savings, TMC is well accepted by families and children. Those using this new technology must give special attention to issues of patient privacy, camera comfort, and specialist comfort.

Phenylalanine and tyrosine metabolism in neonates receiving parenteral nutrition differing in pattern of amino acids.

Tyrosine is considered to be an indispensable dietary amino acid in the neonate, yet achieving adequate parenteral tyrosine intake is difficult due to its poor solubility. Increasing the supply of phenylalanine is the most common means of compensating for low tyrosine levels. Unfortunately, plasma phenylalanine concentrations are sometimes elevated in infants receiving high phenylalanine intake. This led us to study the phenylalanine and tyrosine metabolism in 16 neonates randomized to receive total parenteral nutrition with either a high or a moderate phenylalanine-containing amino acid solution. A primed, 24-h continuous stable isotope infusion of L-[1-13C]phenylalanine and L-[3,3-2H2]tyrosine was given to enable the measurement of phenylalanine and tyrosine kinetics. Results demonstrated that 1) phenylalanine hydroxylation was significantly greater in infants receiving high phenylalanine, 2) phenylalanine oxidation and percent dose oxidized was also significantly greater in infants receiving high phenylalanine, 3) apparent phenylalanine retention was greater in neonates receiving high phenylalanine, and 4) alternate catabolites of phenylalanine and tyrosine metabolism were significantly greater in infants receiving high phenylalanine compared with moderate phenylalanine. We conclude that neonates respond to increased parenteral phenylalanine intake by increasing their hydroxylation and oxidation rates. The greater oxidation of phenylalanine in infants receiving high phenylalanine in conjunction with the urinary excretion of alternate catabolites of phenylalanine and tyrosine suggests that the high phenylalanine intake may be in excess of needs. However, the lower apparent phenylalanine retention observed in infants receiving moderate phenylalanine suggests that the total aromatic amino acid level of moderate phenylalanine may be deficient for neonatal needs.

Outcome after ileoanal anastomosis in pediatric patients with ulcerative colitis.

BACKGROUND: To review the outcome after restorative proctocolectomy among children and adolescents with ulcerative colitis at a pediatric inflammatory bowel disease center. METHODS: The records of all patients with ulcerative colitis undergoing colectomy and ileoanal anastomosis at The Hospital for Sick Children, Toronto, Canada, were reviewed. Questionnaires concerning functional results were sent to patients with restored transanal defecation. RESULTS: Seventy three patients (mean age, 13.2 years; range, 2.6-18.8 years) underwent ileoanal anastomosis (19 straight ileoanal anastomosis, 41 J pouch, 13 S pouch) between January 1980 and June 1995 and were observed 5.8+/-3.3 years. The ileoanal anastomosis is nonfunctional in 19 (26%) patients. Excision rates according to type of restorative procedure were J pouch, 7% (3 of 41); S pouch, 32% (4 of 13); and straight ileoanal anastomosis, 32% (6 of 19). Failure was usually attributable to intractable diarrhea among patients with straight ileoanal anastomosis but was caused by anastomotic leak or pelvic-perianal sepsis among patients with pouch procedures. Failure rates did not vary with age at ileoanal anastomosis. Among patients retaining ileoanal continuity, continence problems reported in the questionnaire were frequent and tended to be more extreme among younger patients. Overall, 90% of respondents reported satisfaction with the functional outcome of the restorative operation. CONCLUSIONS: The success rate of the ileoanal anastomosis/J-pouch procedure is comparable to that in adult series. The ileoanal anastomosis/J-pouch procedure is the operation of choice for children and adolescents who want ileoanal continuity restored after colectomy for ulcerative colitis.

Enteric duplications of the pancreatic head: definitive management by local resection.

BACKGROUND/PURPOSE: Enteric duplications can occur throughout the entire alimentary tract. When they occur in the pancreatic head, they present a formidable challenge in both diagnosis and treatment. Surgical management has ranged from simple drainage to local excision or radical resection (eg, Whipple procedure). The authors propose that with identification of the local anatomic relationships, definitive management can be achieved by complete local resection of the cyst mucosa. METHODS: The authors have treated four patients, ages 13 months to 4 years for enteric duplication cysts within the pancreatic head. RESULTS: Clinical presentations were quite varied, including pancreatitis (n = 2), gastritis (secondary to increased production of gastrin), and recurrent pleural effusion with high amylase content. Two of the four cysts had been drained initially using Roux-en-Y cystenterostomies. Our preoperative imaging studies included abdominal ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP), angiography, computerized tomography (CT) or magnetic resonance imaging (MRI) scanning. When necessary intraoperatively, ultrasonography was used for cyst localization and transduodenal pancreatography to define precise ductal relationships. All four duplication cysts were completely excised, including two that communicated directly with the main pancreatic duct. One of the latter extended into the pleural cavity and required a thoracotomy for complete excision. Pathological exam of the excised cysts demonstrated gastric, duodenal, or respiratory mucosa. All four patients have remained entirely asymptomatic during a follow-up of 2 to 7 years postoperatively. CONCLUSION: The authors conclude that complete local resection of enteric duplication cysts in the pancreatic head can be performed for definitive management, avoiding the complications of more radical procedures.

Enterocolitis after the surgical treatment of Hirschsprung's disease: risk factors and financial impact.

BACKGROUND/PURPOSE: Enterocolitis (EC) represents a serious complication after the surgical correction of Hirschsprung's disease (HD). Although previous studies have identified risk factors associated with the development of this complication before definitive repair, the factors leading to EC after pull-through have not been examined. This study was therefore designed to determine risk factors for the development of post-pull-through EC. METHODS: Patients with HD treated from 1991 through 1996 at the Hospital for Sick Children in Toronto, Canada were assessed. Risk factors were examined in three areas: patient factors (gender, age at diagnosis, age and weight at pull-through), technical factors (type of repair, number of stages, location of transition zone, previous EC), and mechanical factors. RESULTS: In 105 consecutive patients, the incidence of postoperative EC was 32%. There was no mortality. The risk of postoperative EC was significantly increased by mechanical factors related to anastomotic complications (relative risk, 2.8) and intestinal obstruction (relative risk, 3.5). This finding was not attributable to the general occurrence of any postoperative complication because the incidence of postoperative complications was equally distributed in patients with and without EC. The presence of EC significantly increased the number of hospital admissions, mean length of stay, and total treatment cost. CONCLUSION: These findings suggest the use of measures to decrease mechanical obstruction so as to decrease the incidence and impact of this potentially devastating complication.

Familial ileal perforation: prenatal diagnosis and postnatal follow-up.

We report sibs (a brother and a sister) who presented prenatally with ultrasound findings of meconium peritonitis and postnatally were found to have perforation of the terminal ileum. The sister presented with fetal ultrasound findings of severe ascites and peritoneal calcifications. She had no prenatal intervention and was born at 38 weeks' gestation. Laparatomy revealed perforation of the terminal ileum with meconium peritonitis. Her post-surgical course was uncomplicated and at 30 months of age her growth and development are normal. Her brother presented prenatally with signs of meconium peritonitis including severe ascites and peritoneal calcifications. Prenatal aspiration of the ascitic fluid was performed and unlike his sister he was born prematurely, was operated on at 8 days, and developed bronchopulmonary dysplasia. He is currently 1 year old and has normal growth and development. The aetiology of the ileal perforation is not known. There were no findings suggesting connective tissue disorder and the aetiology of the intestinal perforation is not known. The occurrence of the same rare abnormality in sibs of different sexes points towards an autosomal recessive disorder.

Tracheobronchial stenting for the treatment of airway obstruction.

PURPOSE: The authors report a 5-year experience of inserting the Palmaz stent into infants and children who had a variety of major airway obstructions. METHODS: From 1992 to 1997, 30 balloon expandable stents (Palmaz) were inserted in the trachea (n = 18) and bronchi (n = 12) of 16 infants, ages 1 week to 26 months (median, 9 months), suffering from three types of serious airway obstruction. In group 1, 10 stents were placed in eight children for tracheal or bronchomalacia. In group II, 11 stents were inserted in four infants for stricture at the site of surgical repair of stenosis. In group III, nine stents were placed to relieve airway compression from enlarged pulmonary arteries associated with severe congenital heart disease in three children and mediastinal lymphangioma in one. Tracheal stents were 30 mm long and were expanded to 8 to 10 mm at placement. Bronchial stents were 12 to 15 mm long and were expanded to 7 to 9 mm. The nonexpanded stents were placed on an inflatable balloon catheter and were inserted into the desired position in the airway through a bronchoscope or endotracheal tube using x-ray control. They were expanded and fixed in place by inflating the balloon to its rated diameter. RESULTS: In group I, granulation tissue developed over the stents in five of eight cases. Obstructing granulations were removed by scraping or balloon compression in three and resulted in earlier than the planned removal in two. Stents have now been removed in six of eight cases. Major airway obstruction has not recurred. In group II, stents have been in place in all cases for 13 to 56 months after insertion, but in one child with three stents, two were removed for obstructive granulations 44 months after insertion. All are well. All group III patients could be extubated after stenting, but two with heart disease died after 3 and 12 months of palliation. During the course of follow-up, stents in the bronchi of two had migrated, and an additional stent was required. Autopsy in one showed full-thickness bronchial erosion but no perforation by the stent. A total 11 of 30 stents have been removed bronchoscopically in seven children without complications. Another child referred here for tracheal stent removal after laser resection of granulations died at attempted removal because the stent was "welded" into the tracheal wall by the inflammatory reaction. Manipulation of the stent completely occluded the airway. CONCLUSIONS: Airway stents can be inserted easily and safely and left in-situ for prolonged periods to relieve major airway obstruction from a variety of causes. Tissue reaction may necessitate bronchoscopic manipulation and early stent removal, and adds to the difficulty of removal.

Nonoperative management of pancreatic injuries in children.

PURPOSE: The safety and efficacy of nonoperative management of pancreatic contusions and transections was examined by reviewing the case histories of 35 consecutive children with pancreatic injuries treated over the past 10 years. METHODS/RESULTS: Surgical exploration was performed for the management of associated injuries only. The diagnosis of pancreatic trauma was suspected in children with abdominal pain, tenderness, elevated serum amylase levels and findings consistent with pancreatic injury on abdominal ultrasound scan or computerized tomography (CT) examination. After children were diagnosed with pancreatic injury, enteral feedings were withheld and total parenteral nutrition administered until abdominal pain resolved and serum amylase levels and radiographic findings improved. Twenty-three children received diagnosis within 24 hours of injury, and in 12, the diagnosis was delayed 2 to 14 days. Hyperamylasemia was found in 27 of 35 children. Twenty-eight children sustaining pancreatic injuries were treated nonoperatively. Abdominal imaging in these children demonstrated pancreatic contusion in 14, transection in 11, and pseudocyst in three. Enteral feeding resumed an average of 15 days after injury. The average hospital stay was 21 days. Pseudocysts formed in 10 children (2 of 14 with contusion; 5 of 11 with transection; three children presented late, and the type of pancreatic injury could not be determined), whose average hospital stay was 25 days. All pseudocysts were successfully managed nonoperatively, although percutaneous aspiration or drainage was required in six children. Children underwent follow-up for an average of 10 months after injury (range, 1 to 144 months). Abdominal pain and radiological abnormalities resolved in all children before discharge from the clinic. CONCLUSIONS: Nonoperative management of pancreatic contusion and transection diagnosed radiologically is effective and safe. Pseudocysts may form after pancreatic injury, and if large or symptomatic, can be managed successfully by percutaneous drainage.

Extrauterine twin-twin transfusion affects renal function and perioperative management of conjoined twins.

This series describes the occurrence of unbalanced circulatory shunting in three consecutively treated pairs of conjoined twins. The impact of renal functional changes and compensatory cardiac physiology on the timing of surgery and perioperative management are illustrated. The craniopagus set of twins presented in renal failure (1A) and cardiac failure (1B) to our hospital at age 2.5 years. Renal transplantation for anuria was performed in 1A before separation of the twins. This did not improve urine output in the hypoperfused twin, and normal renal function was not restored until the twins were separated. Two sets of omphalopagus twins were delivered and transferred to our hospital and separated during the first week of life. In each case a preoperative oliguric state in the underperfused twin reversed after separation, and a postoliguric diuresis ensued. Serum creatinine levels were similar in each pair preoperatively despite the inequality in urine volumes. In conjoined twins, assessment of renal function is necessary and should include serial measurements of urine volumes and urine creatinine clearance. Serum creatinine is not a useful marker of individual twin renal function in this situation. When disparity in renal function exists, early separation is indicated to prevent renal failure and compensatory cardiac failure.

Immaturity alters plasma lipoprotein composition of intravenously alimented newborn infants.

Plasma lipoprotein composition in infants receiving fat-free parenteral nutrition reflects the endogenous synthesis and metabolism of lipids. We studied the composition of plasma lipoproteins in 49 appropriate for gestational age newborn infants after surgery who received only glucose and amino acid solutions for 5.4 +/- 0.3 days (M +/- SE). Of the infants studied, 31 were fullterm (gestational age 39.5 +/- 0.2 weeks) and 18 premature (34.3 +/- 0.7 weeks). Plasma lipid levels (total lipids, triglycerides, free cholesterol, sterol, esters, phospholipids) did not differ between term and premature infants, but triglycerides and cholesterol were markedly lower than in young, fasting adults. The contribution of triglycerides to lipoprotein lipids was strikingly low in chylomicrons (21% vs. 90% in young fasting adults) and VLDL (34 vs 60%) and the infants had a consistently lower cholesterol content of HDL (21 mg/dl vs. 45-50 mg/dl in adults) and LDL (43 mg/dl vs. 100 mg/dl). All infantile lipoproteins were enriched with phospholipids. These results are comparable to those reported for cord plasma. In premature babies, VLDL were markedly reduced and contained less triglycerides, free and esterified cholesterol than in term infants. In contrast, HDL were increased in preterm infants and carried more phospholipids. VLDL contributed to al lesser and HDL to a greater extent to plasma lipid transport in premature infants. We conclude that in premature infants hepatic synthesis of triglycerides and cholesterol and their secretion as VLDL is reduced, which may be caused by low substrate availability or an immaturity of the synthetic pathway. In premature infants, HDL appears to play a major role in transporting plasma lipids to peripheral tissues.

Experience with papillary and solid epithelial neoplasms of the pancreas in children.

BACKGROUND: Papillary cystic tumour of the pancreas in children is a rare tumour. METHODS: Ten patients admitted to The Hospital for Sick Children, Toronto, have been reviewed, and presentation and management are documented. RESULTS: One patient who had disseminated disease at presentation died. CONCLUSION: Excision of the tumour irrespective of size is recommended.