Tomas Wester

Nonoperative treatment with antibiotics versus surgery for acute nonperforated appendicitis in children: a pilot randomized controlled trial.

OBJECTIVE The aim of this study was to evaluate the feasibility and safety of nonoperative treatment of acute nonperforated appendicitis with antibiotics in children. METHODS A pilot randomized controlled trial was performed comparing nonoperative treatment with antibiotics versus surgery for acute appendicitis in children. Patients with imaging-confirmed acute nonperforated appendicitis who would normally have had emergency appendectomy were randomized either to treatment with antibiotics or to surgery. Follow-up was for 1 year. RESULTS Fifty patients were enrolled; 26 were randomized to surgery and 24 to nonoperative treatment with antibiotics. All children in the surgery group had histopathologically confirmed acute appendicitis, and there were no significant complications in this group. Two of 24 patients in the nonoperative treatment group had appendectomy within the time of primary antibiotic treatment and 1 patient after 9 months for recurrent acute appendicitis. Another 6 patients have had an appendectomy due to recurrent abdominal pain (n = 5) or parental wish (n = 1) during the follow-up period; none of these 6 patients had evidence of appendicitis on histopathological examination. CONCLUSIONS Twenty-two of 24 patients (92%) treated with antibiotics had initial resolution of symptoms. Of these 22, only 1 patient (5%) had recurrence of acute appendicitis during follow-up. Overall, 62% of patients have not had an appendectomy during the follow-up period. This pilot trial suggests that nonoperative treatment of acute appendicitis in children is feasible and safe and that further investigation of nonoperative treatment is warranted.

Intestinal Neuronal Dysplasia

Intestinal neuronal dysplasia (IND) is a clinical condition that resembles Hirschsprungs disease. In the past many years investigators have raised doubts about the existence of IND as a distinct histopathologic entity. One strong piece of evidence that IND is a real entity stems from animal models. Recently, two different HOX11L1 knockout mouse models and a heterozygous endothelin B receptor-deficient rat demonstrated abnormalities of the submucous plexus similar to that observed in human IND. This review describes in detail the diagnostic criteria of IND, staining techniques, correlation between histological findings and clinical symptoms, and management of IND.

Submucosal injection of stabilized nonanimal hyaluronic acid with dextranomer: a new treatment option for fecal incontinence.

PURPOSE: NASHA™ Dx gel has been used extensively for treatments in the field of urology. This study was performed to evaluate NASHA™ Dx gel as an injectable anal canal implant for the treatment of fecal incontinence. METHODS: Thirty-four patients (5 males, 29 females; median age, 61 years; range, 34 to 80) were injected with 4 × 1 ml of NASHA™ Dx gel, just above the dentate line in the submucosal layer. The primary end point was change in the number of incontinence episodes and a treatment response was defined as a 50 percent reduction compared with pretreatment. All patients were followed up at 3, 6, and 12 months. RESULTS: The median number of incontinence episodes during four weeks was 22 (range, 2 to 77) before treatment, at 6 months it was 9 (range, 0 to 46), and at 12 months it was 10 (range, 0 to 70, P = 0.004). Fifteen patients (44 percent) were responders at 6 months, compared with 19 (56 percent) at 12 months. No long-term side effects or serious adverse events were reported. CONCLUSIONS: Submucosal injection of NASHA™ Dx gel is an effective treatment for fecal incontinence. The effect is sustained for at least 12 months. The treatment is associated with low morbidity

A review of conservative treatment of acute appendicitis.

Appendicitis is a common condition in the pediatric population and appendectomy has been the traditional treatment. Both the urgency of the operation and the need for the appendectomy have recently been challenged. In children, this controversy focuses on operative management of perforated appendicitis and appendix abscesses. In adults, the debate has extended to management of nonperforated appendicitis. This review describes the evidence behind these challenges and updates a per-protocol meta-analysis of randomized controlled trials in adults. In the per-protocol meta-analysis, there was no difference between operative versus nonoperative management in failure of treatment. The complication rate was significantly lower in patients treated nonoperatively. However, in the nonoperative group, 10% of patients needed immediate surgery and 17% developed a recurrence during the 1-year follow-up. Overall, 73% of adults with suspected acute appendicitis may not need operative treatment. There are no data in the literature to support nonoperative treatment of acute appendicitis in children.

Characterization of bacterial and fungal microbiome in children with Hirschsprung disease with and without a history of enterocolitis: A multicenter study

Development of potentially life-threatening enterocolitis is the most frequent complication in children with Hirschsprung disease (HSCR), even after definitive corrective surgery. Intestinal microbiota likely contribute to the etiology of enterocolitis, so the aim of this study was to compare the fecal bacterial and fungal communities of children who developed Hirschsprung-associated enterocolitis (HAEC) with HSCR patients who had never had enterocolitis. Eighteen Hirschsprung patients who had completed definitive surgery were enrolled: 9 had a history of HAEC and 9 did not. Fecal DNA was isolated and 16S and ITS-1 regions sequenced using Next Generation Sequencing and data analysis for species identification. The HAEC group bacterial composition showed a modest reduction in Firmicutes and Verrucomicrobia with increased Bacteroidetes and Proteobacteria compared with the HSCR group. In contrast, the fecal fungi composition of the HAEC group showed marked reduction in diversity with increased Candida sp., and reduced Malassezia and Saccharomyces sp. compared with the HSCR group. The most striking finding within the HAEC group is that the Candida genus segregated into “high burden” patients with 97.8% C. albicans and 2.2% C. tropicalis compared with “low burden” patients 26.8% C. albicans and 73% C. tropicalis. Interestingly even the low burden HAEC group had altered Candida community structure with just two species compared to more diverse Candida populations in the HSCR patients. This is the first study to identify Candida sp. as potentially playing a role in HAEC either as expanded commensal species as a consequence of enterocolitis (or treatment), or possibly as pathobioants contributing to the pathogenesis of HAEC. These findings suggest a dysbiosis in the gut microbial ecosystem of HAEC patients, such that there may be dominance of fungi and bacteria predisposing patients to development of HAEC.

Expression of bcl-2 in enteric neurons in normal human bowel and Hirschsprung disease.

OBJECTIVE The bcl-2 protein has the functional role of blocking apoptosis, ie, programmed cell death. This protein is widely expressed in the developing central and peripheral nervous systems. The purpose of this study was to map bcl-2 expression in the human enteric nervous system, as this has not previously been done. METHODS Rectal specimens were obtained at autopsy of 13 fetuses at 13 to 31 weeks of gestation. Normal colon was also obtained from 5 children and 2 adults, and, in addition, ganglionic and aganglionic bowel resected in 11 patients with Hirschsprung disease was examined. Specimens were fixed in formalin, embedded in paraffin, and analyzed with immunohistochemical methods, using antibodies raised against bcl-2 and neuron-specific enolase (NSE). RESULTS The bcl-2 protein was expressed in myenteric and submucous ganglion cells in fetuses, children, and adults. Nerve fibers of the enteric plexuses that were bcl-2 immunoreactive were few compared with the number of NSE-immunoreactive nerve fibers. In aganglionic bowel no bcl-2-or NSE-immunoreactive ganglion cells were revealed. Results of NSE immunohistochemistry showed clearly stained hypertrophic nerve bundles, known to be of extrinsic origin, which were only weakly bcl-2 immunoreactive. CONCLUSION Expression of bcl-2 in enteric ganglion cells of the myenteric and submucous plexuses is displayed in the fetus and during childhood and is also retained in adult bowel. Immunohistochemical analysis of bcl-2 provides a good marker for identification of ganglion cells in Hirschsprung disease and may also be valuable for the diagnosis of disorders characterized by hypoganglionosis or hyperganglionosis.

Contemporary management of abdominal surgical emergencies in infants and children

Acute abdominal complaints in children are common presentations in the emergency department. The aetiology, presentation, diagnosis and management often differ from those in adults.

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.

Altered fecal short chain fatty acid composition in children with a history of Hirschsprung-associated enterocolitis

PURPOSE Children with Hirschsprung disease (HD) who have a history of enterocolitis (HAEC) have a shift in colonic microbiota, many of which are necessary for short chain fatty acid (SCFA) production. As SCFAs play a critical role in colonic mucosal preservation, we hypothesized that fecal SCFA composition is altered in children with HAEC. METHODS A multicenter study enrolled 18 HD children, abstracting for history of feeding, antibiotic/probiotic use, and enterocolitis symptoms. HAEC status was determined per Pastor et al. criteria (12). Fresh feces were collected for microbial community analysis via 16S sequencing as well as SCFA analysis by gas chromatography-mass spectrometry. RESULTS Nine patients had a history of HAEC, and nine had never had HAEC. Fecal samples from HAEC children showed a 4-fold decline in total SCFA concentration vs. non-HAEC HD patients. We then compared the relative composition of individual SCFAs and found reduced acetate and increased butyrate in HAEC children. Finally, we measured relative abundance of SCFA-producing fecal microbiota. Interestingly, 10 of 12 butyrate-producing genera as well as 3 of 4 acetate-producing genera demonstrated multi-fold expansion. CONCLUSION Children with HAEC history have reduced fecal SCFAs and altered SCFA profile. These findings suggest a complex interplay between the colonic metabolome and changes in microbiota, which may influence the pathogenesis of HAEC.

Vaginal agenesis or distal vaginal atresia associated with anorectal malformations

BACKGROUND Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is defined as Müllerian aplasia with vaginal agenesis and uterine remnants. It is commonly associated with renal and sometimes vertebral anomalies. The MRKH syndrome or distal vaginal atresia is sometimes associated with anorectal malformations. The purpose of this study was to describe 7 girls with vaginal agenesis or distal vaginal atresia and an anorectal malformation and review the literature. METHODS Seven patients with vaginal agenesis or distal vaginal atresia and anorectal malformation were operated on at 3 pediatric surgical centers in Madrid, Helsinki, and Stockholm. Case records were reviewed, and the previous literature was searched. RESULTS Six patients had a reconstruction of the anorectum and vagina during the first year of life. In one case, the vagina was replaced at the time of a redo posterior sagittal anorectoplasty at the age of 11 years. The 4 patients with vaginal agenesis had a sigmoid colovaginoplasty. The 3 patients with a distal vaginal atresia had a vaginal pull-through. Four of the patients needed laxatives or enemas for mild constipation at last follow-up. Short-term gynecologic problems were minor in all patients. CONCLUSION Vaginal reconstruction at the time of anorectoplasty results in good short-term outcome. For vaginal agenesis, a primary colovaginoplasty is suggested to be the preferred technique to replace the vagina.