Preoperative metabolic acidosis in infants with gastroschisis.

INTRODUCTION: There is little in literature regarding preoperative management of infants with gastroschisis. It is unclear if these infants develop metabolic acidosis as a consequence of prolonged intrauterine gut compromise or dehydration secondary to increased fluid loss. AIM: To assess the frequency of preoperative metabolic acidosis in infants with gastroschisis and investigate whether this acidosis reflects degree of gut compromise. METHODS: All infants with gastroschisis born between May 2005 and April 2013 in a single tertiary care center were reviewed. Metabolic acidosis was defined by the presence of pH <7.26 and serum bicarbonate <18.5 or base excess < -8.5 mmol/l. Infants with significant birth depression were excluded. Maternal and neonatal data were collected. Frequency of preoperative metabolic acidosis and its association with gastroschisis prognostic score (GPS), time to first and time to reach full feeds were investigated. RESULTS: Sixty infants were identified, 11 were excluded (birth depression/lack of preoperative blood gases). Median preoperative total fluid intake was 130 ml/kg/d. Nine infants (18%) had metabolic acidosis at a median age of 1.2 hours. No association was found between metabolic acidosis or serum lactate and GPS, age at first feed or age at full feeds. CONCLUSION: Preoperative metabolic acidosis was identified in a significant number of patients with gastroschisis despite high fluid intake. It does not appear to be associated with the degree of gut compromise. Using metabolic acidosis as an indication of dehydration in these patients needs more investigation.

Discriminating preoperative features of pleuropulmonary blastomas (PPB) from congenital cystic adenomatoid malformations (CCAM): a retrospective, age-matched study.

BACKGROUND: The etiopathogenesis of pleuropulmonary blastoma (PPB) and its relationship to congenital cystic adenomatoid malformation (CCAM) remain controversial. Our recent analysis indicates that both the co-incidental occurrence and the outcome of PPB among CCAM patients are significant. We report here on our efforts to determine clinical and radiological features discriminating PPB from CCAM preoperatively. MATERIALS & METHODS: A retrospective analysis of all patients treated for PPB and CCAM between 1981 and 2008 at 2 tertiary academic centers under a centralized, single payer healthcare system was performed (REB#1000013239). Clinical, radiological and demographic data were analyzed. PPB patients were secondarily age matched with CCAM patients (± 10% age difference in months), and clinical, radiological and demographic variables were compared. Descriptive statistics and non-parametric analysis were used. RESULTS: A total of 10 PPB patients was identified. Median age at diagnosis was 24 months; the male to female ratio was 5:5. No PPB patients had an antenatal diagnosis (p<0.01). 9 were symptomatic, with symptoms including dyspnea (7/10), upper respiratory infection (6/10), poor weight gain (3/10), and 1 patient was asymptomatic. 5 of 10 patients had solid parts on CT, of which 4 out of 5 were diagnosed preoperatively as PPB and 1 out of 5 as CCAM. 5 of 10 were predominantly cystic of which none was diagnosed preoperatively as PPB (p=0.0476). Given that most CCAM patients are now diagnosed antenatally, only 5 PPB patients could be age-matched with CCAM patients. In the predominantly cystic PPB patients (n=5), no significant discriminating clinical and radiological features were identifiable when compared preoperatively with age-matched CCAM patients. CONCLUSION: PPB patients continue to represent a diagnostic challenge. Asymptomatic and predominantly cystic PPB remain indistinguishable from CCAM preoperatively. A high index of suspicion for PPB must be considered in any child presenting with cystic lung lesions beyond early infancy, particularly in a child with poor weight gain.

Complicated gastroschisis and maternal smoking: a causal association?

The incidence of gastroschisis appears to be rising in developed nations, with epidemiological studies indicating association with young maternal age and smoking. Is there an association between maternal smoking and the development of complicated gastroschisis? A retrospective population-based review of all cases of gastroschisis over 11 years was conducted in three Canadian provinces. Complicated cases were defined as those with an associated intestinal atresia or other vascular compromise of the bowel, those requiring a prolonged time to full enteral feeding (>42 days). Univariate and multivariate regression analyses were conducted. Fifty-four cases of gastroschisis were treated. Seventeen patients had complicated gastroschisis (CG). 47.1% of infants were born to smoking mothers; of those 56.25% were in the CG group. On univariate analysis statistically significant associations with complicated cases were young maternal age (<19 years) (OR = 6.0, CI: 1.3, 28.1), low maternal weight gain (<12 kg) (OR = 4.6, CI: 2.5, 8.5), low birth weight (<2,400 g), (OR = 7.7, CI: 2.0, 28.9), and gestational age under 36 weeks (OR = 11.0, CI: 2.6, 46.2). Seven of 24 cases involving maternal smoking developed atresias or vascular intestinal compromise versus 4 of 27 cases with no maternal smoking, with an odds ratio of 2.1 (CI: 0.60, 7.2). On multivariate analysis, atresias and vascular compromise remained significantly associated with young maternal age, low gestational age and low 1-min Apgar score. Although a positive trend is seen, no statistically significant relationship between maternal smoking and the development of complicated gastroschisis was found. Further clinical and epidemiologic studies are needed to validate our findings.

ATVs: motorized toys or vehicles for children?

OBJECTIVES: To compare the nature of injuries from all-terrain vehicles (ATVs) to those from bicycling, dirtbikes/motocross, and motor vehicle crashes. DESIGN: Data on injuries from the mechanisms outlined above were obtained through CHIRPP (the Canadian Hospitals Injury Reporting and Prevention Program) and hospital records. SETTING: A Canadian tertiary pediatric center. SUBJECTS: Cases presenting to the emergency department over a 10 year period. MAIN OUTCOME MEASURES: Comparison between demographics, mechanisms and natures of injuries sustained, disposition from the emergency department, and lengths of hospital stay. RESULTS: Contrary to bicycling, ATV related injuries occurred among older ages and appeared to result less often from loss of control. Severe injuries resulting in deep soft tissue trauma and fracture/dislocations were 1.7 and 1.5 times, respectively, more frequent among ATV trauma than bicycling (p<0.01). In addition, ATV related injuries were located more frequently in the trunkal, hip, lower extremity, and spinal regions. Conversely, ATV related trauma bore significant similarities regarding body part and nature of the injury to both motor vehicle crash (MVC) and dirtbike related injuries. Akin to dirtbike and MVC related trauma, ATV related injuries more frequently required admission to the ward or intensive care unit compared to bicycling injuries (30.8% v 9.6%, p<0.0001), and used a proportionally larger amount of hospital resources with respect to overall in-hospital and intensive care unit days. CONCLUSIONS: Although ATVs may be considered recreational for children, their associated injury patterns, severity, and costs to the healthcare system more closely resemble those from motorized vehicles and are more significant than bicycling. Strict policy to reflect this must be developed and acknowledged by the public, industry, and legislative bodies.

Sentinel lymph node mapping and biopsy: a potentially valuable tool in the management of childhood extremity rhabdomyosarcoma.

Multimodal therapy, involving surgery, chemotherapy and radiation, now dominates the management of rhabdomyosarcoma (RMS) in childhood. Yet, despite improvements in these practices, extremity tumors continue to fare relatively poorly. Several investigators have identified prognostic factors that can be used to direct therapy and predict outcome. These factors include histology and metastatic disease, the latter requiring accurate staging to identify. The presence of lymph node metastases has been shown to be of prognostic significance and is incorporated into pre-treatment staging schemes. Up to 50% of all surgically evaluated nodes and 17% of clinically negative nodes in extremity RMS may harbor tumor, underscoring the increased risk of understaging the disease if accurate lymph node dissection is not undertaken. Despite its importance, there appears to be no standard format by which regional nodal status is evaluated in extremity RMS. Sentinel lymph node mapping and biopsy are a minimally invasive technique, currently used in the staging of adult breast cancer and melanoma. In adults, the technique is associated with optimum nodal yield and low morbidity. We describe a case in which sentinel node mapping and dissection were used to easily and accurately stage a distal upper extremity alveolar RMS in a child with clinically and radiologically negative regional lymph nodes. The procedure yielded no positive nodes, was associated with no morbidity and spared the child more extensive radiotherapy. We propose the further evaluation of this simple and innovative technique in the overall management of this childhood malignancy.

Significance of the clinical course and early upper gastrointestinal studies in predicting complications associated with repair of esophageal atresia.

BACKGROUND/PURPOSE: In many centers, use of upper gastrointestinal (UGI) contrast studies in the early postoperative period after esophageal atresia (EA) repair is considered routine. Indications for this are many, including searching for existing problems and predicting future complications. However, most major complications, both early and late, usually are identified clinically before any radiologic studies. The purpose of this study was to investigate factors that may anticipate the development of postoperative complications after EA repair, looking particularly at the predictive value of routine early postoperative UGI studies. METHODS: A total of 111 consecutive cases of EA were identified retrospectively over a 10-year period from 2 major Canadian pediatric health centers. One hundred one were associated with a distal tracheoesophageal fistula (TEF), of which, 90 had repairs. Ninety-seven percent of these had a UGI study at a median of 9.1 postoperative days (range, 2 to 23) before consideration of oral feeding. Charts were reviewed looking at patient variables, surgical factors, early UGI findings, and postoperative courses. Complications that required intervention were noted, including anastomotic leaks, gastroesophageal reflux (GER), strictures, and recurrent and missed fistulae. All initial UGI studies were reexamined by 1 of 2 pediatric radiologists. Logistic regression was used to examine relationships between these clinical and radiologic variables and outcomes. RESULTS: Of the variables analyzed, univariate analysis showed clinically significant leaks to be associated with intraoperative factors (subjective degree of anastomotic tension, and the use of myotomies) and early postoperative clinical evidence suggesting a leak. In a multivariate model, all remained independently significant except for the use of myotomies. Later development of clinically significant GER also was associated with the degree of tension. It had no relationship, however, with findings of dysmotility, esophageal shortening, or reflux at the initial UGI study. Development of a stricture requiring dilatations or resection was associated with a history of clinically evident GER only; no relationships were seen with a history of an anastomotic leak or any other clinical, operative, or radiographic variables. Missed or recurrent fistulae were all suspected clinically before radiologic confirmation. CONCLUSIONS: Early and late complications after repair of EA can be identified and potentially anticipated based on clinical findings at the time of repair and during the postoperative period. The use of early "routine" UGI studies, with no suspicion of a problem, has little value in terms of predicting complications or future clinical course.

Pitfalls in the interpretation of MIBG scans in cervical neuroblastoma.

Cervical neuroblastoma (CNB) is relatively rare, accounting for less than 5% of these tumors. Because it arises from the cervical sympathetic chain, complete resection will leave the child with Horner's syndrome in a high proportion of cases. Advances in technology have allowed for the development of diagnostic and imaging modalities more specific to the disease. One of these has been the advent of radiolabeled meta-iodobenzylguanidine (MIBG) to assess the primary tumor and focal metastatic involvement. This nuclide is also taken up by normal salivary-gland tissue; this may be altered, however, in the presence of sympathetic denervation. We present a case of a primary CNB associated with Horner's syndrome, which led to confusion in interpretation of the subsequent MIBG scan. We alert the reader to potential pitfalls in the use of this examination in this disease entity.

Long-term outcome after Hirschsprung's disease: patients' perspectives.

BACKGROUND: The results of treatment of Hirschsprung's disease (HD) are not uniformly successful, and the parents' and child's interpretation of the outcome may be different from that of the surgeon. METHODS: One hundred seven children treated for HD over 22 1/2 years were reviewed retrospectively. Adequate clinical data regarding functional outcomes were available in 78, of which, an additional questionnaire was completed by 69. Follow-ups were divided into type of pull-through (PT), age at time of PT (< 4 months and > 4 months) and age at last follow-up (< 5 years, 5 to 15 years and > 15 years). Degrees of constipation and incontinence were determined using standard scoring systems. RESULTS: The median age at presentation was 9 days (range, 1 day to 9.4 years), and 41% presented within the first 72 hours of life. Aganglionosis extended to the rectosigmoid region in 75%, proximal to the splenic flexure in 11%, and total colon in 6.5%. Treatments included a Soave procedure in 57, Duhamel in 31, Swenson in 10, and sphincterotomy-myectomy in two. No surgical treatment or only a decompressing enterostomy was performed in two and three children, respectively, and two underwent a PT elsewhere. Complications related to the enterostomy occurred in 39 patients. Postoperative enterocolitis and bowel obstructions occurred in nine and 13 patients, respectively. Staple-line fusion, anastomotic stenosis, and anastomotic leak occurred in nine, 17, and two patients, respectively. Seven children died, only one directly related to the PT. Aside from more constipation associated with the Duhamel procedure, functional outcomes were not significantly different among the types of PTs. No differences were found between patients who underwent a PT at less than 4 months of age and those at greater than 4 months of age. Significantly, however, fecal continence was relatively poor in those less than 15 years of age (50% with only fair to poor continence), but improved markedly once the child reached later adolescence (8%, P < .0002). Correspondingly, the negative impact on the child's social life was much greater in the younger age groups compared with later adolescence (50% of those aged 5 to 15 years v 18% of those > 15 years; P = .007). The effect on the families' lives mirrored this. Finally, only 64% of patients were interpreted as having "normal" stooling habits, yet 90% of parents were moderately or very satisfied with their child's outcome, with no differences found among the three sets of comparison groups. CONCLUSIONS: The outcomes for HD are not always as good as surgeons may perceive; long term follow-up is important. With time, most children significantly improve with respect to fecal continence, but this may not be until later adolescence. In the meantime, the impacts on their social and family lives may be significant. Despite high complication rates, often poor continence, and relative infrequency of normal stooling habits, most parents are satisfied with their child's outcome and adapt to their functional abnormalities along with them.

Poor outcome of gastrointestinal perforations associated with childhood abdominal non-Hodgkin's lymphoma.

BACKGROUND/PURPOSE: With modern chemotherapeutic protocols and advances in medical care, the outcome of intraabdominal non-Hodgkin's lymphoma (NHL) in children can be excellent for limited disease. Advanced disease, however, is associated with increased tumor aggression and requires more rigorous adjuvant therapy. Hence, complications early in the course of the disease process or its management often lead to a poor outcome. Perforation of the gastrointestinal tract, either iatrogenic, tumor related or chemotherapeutically induced is one such complication and may result significant morbidity and mortality. METHODS: The authors reviewed their experience with this disease, and present two cases of children with abdominal NHL, which poignantly demonstrate these points. Results and a review of the literature are then discussed. RESULTS: Fifteen cases of abdominal NHL were examined with an overall mortality rate of 40%. This increased to 100% in the presence of perforation. In two cases, inadvertent entry into the bowel occurred at the time of laparotomy for tumor biopsy. In the first case, intestinal wall was included in the biopsy specimen; in the second, laparotomy unmasked an already sealed-off perforation secondary to tumor invasion. Sepsis ensued in both cases. In the first, this resulted in repeated delays in chemotherapy, and the child succumbed to the disease. In the second, chemotherapy was continued, and although the small bowel leak was controlled, the initial insult hampered marrow recovery and host defenses, resulting in fatal sepsis. CONCLUSIONS: These data and other reported cases in the literature indicate that intestinal perforation associated with abdominal lymphomas in children portends an extremely poor prognosis. All attempts to avoid this complication should be made, including avoiding direct tumor biopsy whenever possible.

Lipoblastoma and liposarcoma in children: an analysis of 9 cases and a review of the literature.

OBJECTIVES: To review the experience at a children's hospital of lipoblastoma and liposarcoma and to identify any factors that would differentiate one type of tumour from the other. DESIGN: A retrospective case series. SETTING: British Columbia's Children's Hospital a tertiary-care pediatric centre. PATIENTS: All patients with a pathological diagnosis of lipoblastoma and liposarcoma recorded over 12 years. MAIN OUTCOME MEASURES: The frequency of lipoblastoma and liposarcoma, identified from biopsy specimens of pediatric adipose tumours. The clinical, pathological and cytogenetic variables between lipoblastoma and liposarcoma. RESULTS: One hundred and forty-nine adipose tumours were recorded. Seven (4.7%) were lipoblastomas and 2 (1.3%) were liposarcomas. All tumours presented as asymptomatic, slow-growing, soft-tissue masses. The children with lipoblastoma tended to be younger, but 29% were over 3 years of age. The liposarcoma patients were aged 9 and 14 years. One liposarcoma was of myxoid type and the other was a round cell variant. Karyotypes were reported for 1 lipoblastoma and 1 liposarcoma. The myxoid liposarcoma karyotype was 46,XY,t(12;16)(q13;p11), and the lipoblastoma was reported as 46,XY,der(8)?t(8q;?),+mar. CONCLUSIONS: Lipoblastoma is an unusual childhood neoplasm and liposarcoma is very rare in children. Both tumours may present in a similar fashion, and differentiating them histologically can be difficult. Age cannot be relied upon to accurately predict their behaviour. The tumour karyotype is very helpful in differentiating these neoplasms.

Tumor karyotype differentiates lipoblastoma from liposarcoma.

Lipoblastoma is a rare benign pediatric soft tissue tumor that may be difficult to distinguish from a myxoid liposarcoma clinically or histologically. The authors present a case of a progressively growing, locally invasive soft tissue tumor in a child. Tissue culture for cytogenetic study showed a breakpoint in the long arm of chromosome 8. A review of the literature showed seven case reports of lipoblastoma karyotype, six of which had a similar breakpoint in chromosome 8. This distinguishes it from the histologically alike myxoid liposarcoma, the karyotype of which typically contains the clonal anomaly t(12;16)(q13:p11). The authors recommend that when performing a biopsy of a childhood adipose tumor with unusual features, such as progressive or invasive growth, that fresh tissue be submitted for cell culture. The tumor karyotype will, in most cases, aid in differentiating lipoblastoma from myxoid liposarcoma.

Nutritional and intestinal effects of the novel immunosuppressive agents: deoxyspergualin, rapamycin, and mycophenolate mofetil.

OBJECTIVES: Transplantation of the small intestine would be an attractive therapeutic option for treatment of short bowel syndrome if effective, nontoxic immunosuppressive agents could be developed. This study examines the effect of three newly developed immuno-suppressive agents: rapamycin, deoxyspergualin, and mycophenolate mofetil, on the nutritional status and intestinal function of normal juvenile rats. DESIGN & METHODS: Rapamycin (2 mg/kg every second day), deoxyspergualin (2 mg/kg every second day) and mycophenolate mofetil (MM) (25 mg/kg every second day) were injected subcutaneously for six weeks. RESULTS: Rapamycin and deoxyspergualin caused significant reductions in weight gain without impairing feed intake. Both drugs caused small decreases in fat absorption; treatment with DSG induced an increase in permeability to 99Tc-DTPA. However, the permeability to other markers, such as mannitol and lactulose, was decreased in the rapamycin and mycophenolate mofetil-treated animals. Intestinal function in vitro was quantified using glucose flux (absorption). In the rapamycin group, there was a significant decrease in ileal uptake of glucose, with the net flux (absorption) being zero; there was an associated loss of villous size histologically. In the deoxyspergualin-treated groups, there was a decrease in the jejunal glucose flux. In the mycophenolate mofetil-treated animals, there was a decrease in jejunal with a compensatory increase in ileal glucose absorption. There were minor variations in intestinal morphology, but these were not consistent. CONCLUSIONS: Rapamycin and deoxyspergualin in these doses cause a significant reduction in weight gain in healthy juvenile animals, and all the drugs caused changes in the active transport characteristics of the intestine. Accordingly, the use of these drugs for intestinal transplantation should be evaluated carefully for their nutritional impact.

Is early response to portoenterostomy predictive of long-term outcome for patients with biliary atresia?

PURPOSE: Therapy for biliary atresia (BA) typically involves portoenterostomy (PE). In light of the development of liver transplantation (LT) as an option for therapy in infancy, the authors reviewed their experience to determine factors that might predict the requirement for LT. METHODS: Cases of BA diagnosed between September 1980 and September 1994 were reviewed. Responses to PE were rated as poor (PR; death or LT by 3 years), temporary (TR; LT > 3 years), or good (GR; anicteric). RESULTS: Twenty-nine patients were identified; 24% were native indian or Inuit. Twenty-three had PE; 11 responded. Seven (32%) became anicteric and continue to do well (GR). Four (18%) required LT after age 3 (TR). Twelve patients had PR; 3 underwent LT (average age, 1.3 years), 4 are listed for LTX, and 5 died by age 2.8 years. (Six patients did not have PE; 2 died in infancy and 4 had LT.) All transplant recipients are well. Factors associated with PR were older age at time of surgery (67 +/- 7 days v 51 +/- 4 days in the GR group), nadir of AST (273 +/- 84 U/Lv 70 +/- 26 U/L in the GR group), and number of post-PE complications (3.6 v per patient v 1 per patient in the GR group). TR was differentiated from GR by bilirubin nadir (46 +/- 10 mumol/Lv 14 +/- 3 mumol/L, respectively) and rate of bilirubin decline (2.6 +/- 1.5 mumol/L/d v 10.8 +/- 3.0 mumol/L/d, respectively). (P < .05 for all comparisons.) CONCLUSION: Outcomes are comparable to those of North American series, but the incidence is lower overall and is higher among natives. Factors that correlate with outcome include age at time of surgery, post-PE complications, postoperative decline and rate of decline of bilirubin and AST. The latter had not been reported previously and may prove useful in planning therapy for partial responders after PE.

Tacrolimus (FK506)--its effects on intestinal glucose transport.

Tacrolimus (FK506) is at present the mainstay of immunosuppression for small intestinal transplantation. This study investigates the effects of chronic treatment with varying dosages of tacrolimus on animal well-being, weight gain, intestinal permeability, and the active transport of nutrients as measured by in vitro studies quantifying glucose flux. The effect of acute treatment with high-dose tacrolimus on glucose flux was also investigated. In the chronic studies, juvenile male Lewis rats were given tacrolimus in a dosage of 0.1 mg/kg, 0.5 mg/kg, and 2 mg/kg q. second day by subcutaneous injection for five weeks. In the acute studies, animals were treated with 2 mg/kg given q. 24 hr [mult] 48 hr, 24 hr and 12 hr prior to sacrifice. In the acute treatment groups, tacrolimus caused no change in glucose flux. In the chronically treated animals, FK506 levels were within the clinically relevant range. Chronic treatment with 0.5 and 2 mg/kg caused a significant reduction in weight gain. These same groups of animals had a significant increase in intestinal permeability as measured by absorption of 99Te-DTPA. Glucose flux was affected in all chronically treated groups, with net flux increasing in the jejunum and decreasing in the ileum. These findings show that chronic treatment with low-dose tacrolimus is well tolerated, but in higher doses there are significant effects in intestinal permeability and nutrient uptake, and animal weight gain. We suggest that these changes are due to alterations in intestinal permeability that do not appear to be mediated by an acute drug effect and more likely represent chronic changes, possibly from alterations in gene expression. These findings suggest that further studies regarding the effects of tacrolimus on nutrient transport, intestinal permeability, and the known immunologically related functions of tacrolimus should be done.

FK506 increases permeability in rat intestine by inhibiting mitochondrial function.

BACKGROUND & AIMS: Under normal physiological conditions, the intestine presents an adenosine triphosphate (ATP)-dependent barrier to luminal contents. Disruption of this barrier function can occur when cellular metabolism is compromised. This study examined the effects of FK506 on intestinal permeability and enterocyte metabolic function in Lewis rats. METHODS: Rats were administered FK506 at a dose of 0.1, 0.5, or 2 mg/kg on alternate days for 6 weeks. Intestinal permeability was assessed by measuring urinary recovery of 99mTc-diethylenetriamine pentacetate, and electrophysiological conductance measurements were performed in Ussing chambers. Metabolic function was assessed in isolated enterocytes by measuring total ATP and CO2 release from [14C]pyruvate and [14C]glucose. RESULTS: Rats treated with FK506 showed a dose-dependent reduction in weight gain as well as increased in vivo and in vitro intestinal permeability. There was no difference in plasma creatinine or urinary output. Changes in permeability correlated with reduced ATP levels and CO2 release because of diminished mitochondrial function. Lactate production, as a measure of glycolytic activity, was not altered by FK506. CONCLUSIONS: In a dose-dependent manner, FK506 treatment in rats reduces weight gain, increases intestinal permeability, and decreases the ability of the small intestine to use glucose as an energy source.