Anna Svenningsson

In-hospital Surgical Delay Does Not Increase the Risk for Perforated Appendicitis in Children: A Single-center Retrospective Cohort Study.

OBJECTIVE To investigate the correlation between in-hospital surgical delay before appendectomy for suspected appendicitis and the finding of perforated appendicitis in children. METHODS All children undergoing acute appendectomy for suspected acute appendicitis at Karolinska University Hospital, Stockholm, Sweden from 2006 to 2013 were reviewed for the exposure of surgical delay. Primary endpoint was the histopathologic finding of perforated appendicitis. The main explanatory variable was in-hospital surgical delay, using surgery within 12 hours as reference. Secondary endpoints were postoperative wound infection, intra-abdominal abscess, reoperation, length of hospital stay, and readmission. To adjust for selection bias, a logistic regression model was created to estimate odds ratios for the main outcome measures. Missing data were replaced using multiple imputation. RESULTS The study comprised 2756 children operated for acute appendicitis. Six hundred sixty-one (24.0%) had a histopathologic diagnosis of perforated appendicitis. In the multivariate logistic regression analysis, increased time to surgery was not associated with increased risk of histopathologic perforation. There was no association between the timing of surgery and postoperative wound infection, intra-abdominal abscess, reoperation, or readmission. CONCLUSIONS In-hospital delay of acute appendectomy in children was not associated with an increased rate of histopathologic perforation. Timing of surgery was not an independent risk factor for postoperative complications. The results were not dependent on the magnitude of the surgical delay. The findings are analogous with previous findings in adults and may aid the utilization of available hospital- and operative resources.Objective: To investigate the correlation between in-hospital surgical delay before appendectomy for suspected appendicitis and the finding of perforated appendicitis in children. Methods: All children undergoing acute appendectomy for suspected acute appendicitis at Karolinska University Hospital, Stockholm, Sweden from 2006 to 2013 were reviewed for the exposure of surgical delay. Primary endpoint was the histopathologic finding of perforated appendicitis. The main explanatory variable was in-hospital surgical delay, using surgery within 12 hours as reference. Secondary endpoints were postoperative wound infection, intra-abdominal abscess, reoperation, length of hospital stay, and readmission. To adjust for selection bias, a logistic regression model was created to estimate odds ratios for the main outcome measures. Missing data were replaced using multiple imputation. Results: The study comprised 2756 children operated for acute appendicitis. Six hundred sixty-one (24.0%) had a histopathologic diagnosis of perforated appendicitis. In the multivariate logistic regression analysis, increased time to surgery was not associated with increased risk of histopathologic perforation. There was no association between the timing of surgery and postoperative wound infection, intra-abdominal abscess, reoperation, or readmission. Conclusions: In-hospital delay of acute appendectomy in children was not associated with an increased rate of histopathologic perforation. Timing of surgery was not an independent risk factor for postoperative complications. The results were not dependent on the magnitude of the surgical delay. The findings are analogous with previous findings in adults and may aid the utilization of available hospital- and operative resources.

Plasma lipids, genetic variants near APOA1, and the risk of infantile hypertrophic pyloric stenosis.

IMPORTANCE Infantile hypertrophic pyloric stenosis (IHPS) is a serious condition in which hypertrophy of the pyloric sphincter muscle layer leads to gastric outlet obstruction. Infantile hypertrophic pyloric stenosis shows strong familial aggregation and heritability, but knowledge about specific genetic risk variants is limited. OBJECTIVES To search the genome comprehensively for genetic associations with IHPS and validate findings in 3 independent sample sets. DESIGN, SETTING, AND PARTICIPANTS During stage 1, we used reference data from the 1000 Genomes Project for imputation into a genome-wide data set of 1001 Danish surgery-confirmed samples (cases diagnosed 1987-2008) and 2371 disease-free controls. In stage 2, the 5 most significantly associated loci were tested in independent case-control sample sets from Denmark (cases diagnosed 1983-2010), Sweden (cases diagnosed 1958-2011), and the United States (cases diagnosed 1998-2005), with a total of 1663 cases and 2315 controls. MAIN OUTCOMES AND MEASURES Association of genetic variation with the presence of infantile hypertrophic pyloric stenosis. RESULTS We found a new genome-wide significant locus for IHPS at chromosome 11q23.3. The single-nucleotide polymorphism (SNP) with the lowest P value at the locus, rs12721025 (odds ratio [OR], 1.59; 95% CI, 1.38-1.83; P = 1.9 × 10(-10)), is located 301 bases downstream of the apolipoprotein A-I (APOA1) gene and is correlated (r2 between 0.46 and 0.80) with SNPs previously found to be associated with levels of circulating cholesterol. For these SNPs, the cholesterol-lowering allele consistently was associated with increased risk of IHPS. CONCLUSIONS AND RELEVANCE This study identified a new genome-wide significant locus for IHPS. Characteristics of this locus suggest the possibility of an inverse relationship between levels of circulating cholesterol in neonates and IHPS risk, which warrants further investigation.

Maternal Risk Factors and Perinatal Characteristics for Hirschsprung Disease.

BACKGROUND AND OBJECTIVES: Hirschsprung disease (HSCR) is a congenital defect of the enteric nervous system characterized by a lack of ganglion cells in the distal hindgut. The aim of this study was to assess the birth prevalence, perinatal characteristics, and maternal risk factors in HSCR patients in Sweden. METHODS: This was a nationwide, population-based, case-control study of all children born in Sweden between 1982 and 2012 and registered in the Swedish Medical Birth Register. Cases were identified in the Swedish National Patient Register and data on potential maternal risk factors and patient characteristics were collected from the Swedish National Patient Register and the Swedish Medical Birth Register. Five age- and sex-matched controls were randomly selected for each case. The association between studied risk factors and HSCR was analyzed using conditional logistic regression to calculate the odds ratio (OR) and 95% confidence interval (CI). RESULTS: The study population comprised 600 HSCR cases and 3000 controls with a male-to-female ratio of 3.7:1. The birth prevalence of HSCR was 1.91/10 000. Maternal obesity was associated with an increased risk for the child to have HSCR (OR 1.74; CI 1.25–2.44). Children with HSCR were born at an earlier gestational age (OR 1.60; CI 1.18–2.17) than control children. Associated malformations were identified in 34.5% of the cases. CONCLUSIONS: This study showed that the Swedish birth prevalence of HSCR was 1.91/10 000. Children with HSCR disease were born at a lower gestational age than controls. Maternal obesity may increase the risk for the child to have HSCR.

Maternal and pregnancy characteristics and risk of infantile hypertrophic pyloric stenosis

BACKGROUND/PURPOSE The incidence of infantile hypertrophic pyloric stenosis (IHPS) in Sweden decreased dramatically during the 1990s. The aim of the study was to examine IHPS risk factors and the possible change in them as the incidence declined. METHODS This is a case-control study including 3608 surgically treated IHPS cases and 17588 matched controls during 1973-2008. Cases were identified in the Swedish National Patient Register and data on possible risk factors were collected from the Swedish Medical Birth Register. The association between study variables and IHPS was analyzed using conditional logistic regression for the whole study period and separately for periods with high and low IHPS incidences. RESULTS Prematurity (OR, 2.54; 95% CI, 2.06-3.14), caesarean delivery (OR, 1.67; 95% CI, 1.51-1.86), maternal smoking (OR, 1.82; 95% CI, 1.53-2.16), and young maternal age (< 20yrs) (OR, 1.42; 95% CI, 1.17-1.73) were associated with an increased IHPS risk. Birth order 2 (OR, 0.78; 95% CI, 0.71-0.85) or more was associated with a lower IHPS risk. ORs for smoking increased at low incidence rate. CONCLUSION We report caesarean section, prematurity, primiparity, young maternal age, and smoking as significant IHPS risk factors. The impact of smoking was higher during periods with a low incidence.

Absence of motilin gene mutations in infantile hypertrophic pyloric stenosis

BACKGROUND Erythromycin treatment before 2 weeks of age has been shown to increase the risk of infantile hypertrophic pyloric stenosis (IHPS) up to 10 times. Erythromycin is a motilin agonist, a hormone that induces gastrointestinal contractions. The purpose of this study was to investigate if mutations in the motilin gene (MLN) cause IHPS or if the V15A polymorphism in MLN is associated with the disease. METHODS The MLN was screened for mutations, and the V15A polymorphism was determined in a total of 57 patients with IHPS using polymerase chain reaction and DNA sequencing. The polymorphism genotype and allele frequencies among the patients were compared with 184 controls. RESULTS We detected 3 different, not previously reported, MLN sequence variants in 4 patients. One of these variants results in an amino acid exchange in the motilin signal peptide (A25G). All 3 detected sequence variants were also found in controls or were not inherited with the disease. We found no significant association between the V15A polymorphism and the disease. CONCLUSIONS We have excluded the MLN coding region as a major cause of IHPS. Future studies will evaluate the importance of this metabolic pathway in the pathogenesis of IHPS.

Genome-wide linkage analysis in families with infantile hypertrophic pyloric stenosis indicates novel susceptibility loci

Infantile hypertrophic pyloric stenosis (IHPS) is a common cause of upper gastrointestinal obstruction during infancy. A multifactorial background of the disease is well established. Multiple susceptibility loci including the neuronal nitric oxide synthase (NOS1) gene have previously been linked to IHPS, but contradictory results of linkage studies in different materials indicate genetic heterogeneity. To identify IHPS susceptibility loci, we conducted a genome-wide linkage analysis in 37 Swedish families. In regions where the Swedish material showed most evidence in favor of linkage, 31 additional British IHPS families were analyzed. Evidence in favor of significant linkage was observed in the Swedish material to two loci on chromosome 2q24 (non-parametric linkage (NPL) =3.77) and 7p21 (NPL=4.55). In addition, evidence of suggestive linkage was found to two loci on chromosome 6p21 (NPL=2.97) and 12q24 (NPL=2.63). Extending the material with British samples did not enhance the level of significance. Regions with linkage harbor interesting candidate genes, such as glucagon-like peptide-2 (GLP-2 encoded by the glucagon gene GCG), NOS1, motilin (MLN) and neuropeptide Y (NPY). The coding exons for GLP-2, and NPY were screened for mutations with negative results. In conclusion, we could confirm suggestive linkage to the region harboring the NOS1 gene and detected additional novel susceptibility loci for IHPS.

No association between a promoter NOS1 polymorphism (rs41279104) and Infantile Hypertrophic Pyloric Stenosis.

Infantile hypertrophic pyloric stenosis (IHPS) is a condition affecting infants in the first few months of life. The condition is manifested by persistent vomiting and is caused by a hypertrophied muscle obstructing the gastric outlet. The condition is treated by pyloromyotomy. The incidence is 1–8/1000 births and varies among different populations. The etiology of IHPS is unknown, but both genetic and environmental factors are thought to contribute to the disease. Genetic linkage analysis has so far localized five loci that could harbor genes contributing to IHPS. The only gene implicated in IHPS is the nitric oxide synthase gene (NOS1), in which a single nucleotide polymorphism (rs41279104) in the promoter region has been associated with the disease in 16 patients. In this study, we examined an association of this SNP in 54 familial and 28 sporadic cases with IHPS, and compared the results with normal controls using univariate and multiple logistic regression analysis. We could not confirm any association between the analyzed SNP and infantile hypertrophic pyloric stenosis.

Population-based study shows that Hirschsprung disease does not have a negative impact on education and income.

Hirschsprung disease is a multifactorial disease, which is mainly treated during childhood. There is a risk of impaired bowel function for a long time after surgery, and its impact on adult life has not been well studied. This study assessed whether having Hirschsprung disease affected social parameters such as educational level and income.

Early central line-associated blood stream infections in children with cancer pose a risk for premature catheter removal

This study examined the clinical characteristics of central line‐associated blood stream infections occurring within 30 days after insertion versus later infections in paediatric cancer patients and the subsequent risk for premature catheter removal.

Supraumbilical incision with U–u umbilicoplasty for congenital duodenal atresia: The Stockholm experience

BACKGROUND Minimizing scars has become a major concern in pediatric surgery. Since Tan and Bianchi introduced the minimally invasive umbilical incision for Ramstedts pyloromyotomy, their technique has been adopted for a variety of neonatal abdominal conditions. The aim of this study was to evaluate a modification of the skin incision. MATERIAL AND METHODS We have modified Bianchis original technique to access the abdomen through the linea alba by introducing a novel U-to-u umbilicoplasty and compare the results with the traditional transverse incision. This new approach improves the abdominal access and is easy to perform. RESULTS The operating time with the U-to-u umbilicoplasty is not longer than in standard transverse laparotomy, the access to the abdomen is more than adequate, the incidence of postoperative complications is similar and the cosmetic results are excellent. CONCLUSIONS We conclude that the umbilical approach with this novel U-to-u umbilicoplasty to treat congenital duodenal obstruction in the newborn is a safe and effective method and a good alternative to the standard transverse laparotomy approach.