Contemporary management of Hirschsprung disease in New Zealand.

BACKGROUND: The aim of this study was to report the contemporary management of Hirschsprung disease (HD) in New Zealand. METHODS: We undertook a national multi-centre retrospective review of all newly diagnosed cases of HD during a 16-year period (2000-2015). Demographics, genetic and syndromic associations, family history, radiology and histology results and surgical interventions were analysed. RESULTS: A total of 246 cases (males:females 4:1) were identified, an incidence of 1:3870 live births. Short-segment disease was present in 81.7%, long-segment disease in 8.5%, total colonic aganglionosis in 6.5% and unknown in 3.3%. HD was diagnosed by 4 weeks' corrected gestational age in 67%. Thirty cases (12%) also had Trisomy 21. Fifty-three (21.5%) patients required a repeat rectal biopsy for definitive diagnosis. A contrast enema was performed in 55% and identified the transition zone with 69% accuracy. Primary pull-through surgery was undertaken in 59% (65% of short-segment cases) at a median age of 27 days; others were initially managed by a defunctioning stoma. The commonest definitive procedure was a Soave-Boley endorectal pull-through (79%) (or similar variant). During a median follow-up of 7.4 years, six (2.5%) survivors underwent a redo pull-through, 13 (5.5%) an appendicostomy, 16 (6.8%) a defunctioning stoma and 10 never had a definitive procedure. Total colonic aganglionosis was significantly more likely to be fatal (12.5% versus 0.5%, P < 0.0005) or associated with a permanent end stoma (27.5% versus 4.5%, P < 0.0005). CONCLUSIONS: Most New Zealand born infants with short-segment HD are currently managed by primary pull-through, usually in the first months of life.

Declining incidence of pyloric stenosis in New Zealand.

BACKGROUND: Pyloric stenosis is a relatively common paediatric surgical condition, but a worldwide decline in its incidence has been observed in recent decades. The objective of this study was to identify if the incidence of pyloric stenosis in New Zealand has been declining. METHODS: A retrospective review of the four New Zealand paediatric surgical centres' theatre databases from 2007 to 2017. Demographic data were recorded for all infants who had a pyloromyotomy and annual incidences of pyloric stenosis calculated. RESULTS: A total of 393 infants underwent a pyloromyotomy for pyloric stenosis during the study period. Most infants (81%) were of European ethnicity. There was a significant decline (P = 0.0001) in the national incidence of pyloric stenosis from 0.73/1000 live births (LB) in 2007 to 0.39/1000 LB in 2017. From 2007 to 2017, the incidence of male infants with pyloric stenosis declined from 1.27/1000 LB to 0.62/1000 LB. The current annual incidence of pyloric stenosis in New Zealand is 0.39/1000 LB. CONCLUSIONS: The incidence of pyloric stenosis in New Zealand has significantly declined in the last decade and is currently the lowest reported incidence in the world involving a predominantly European cohort. A decline in male infants developing pyloric stenosis was also observed. Further study is required to investigate causes for this low incidence and declining trend.

Ethnic variations in the childhood prevalence of Hirschsprung disease in New Zealand.

BACKGROUND: Epidemiological studies have suggested that there may be ethnic variations in the prevalence of Hirschsprung disease (HD) but no study has systematically investigated this issue or potential ethnic variations in the extent of aganglionosis in HD. This study aimed to investigate this in a childhood population in New Zealand. METHODS: A multicentre national retrospective review was undertaken of all newly diagnosed cases of HD at each of the four paediatric surgical centres in New Zealand over a 16-year period (January 2000 to December 2015). Original histological, radiological and operative reports were obtained and analysed. Self-identified ethnicity was recorded from admission documents. Birth statistics were obtained from Statistics New Zealand. RESULTS: A total of 246 cases of HD were identified. The prevalence of HD was 1:3790 live births for European, 1:6610 among Maori, 1:1834 among Pacific Peoples, 1:3847 among Asian and 1:5694 among Middle Eastern. The prevalence of HD was statistically significantly greater in Pacific Peoples (P < 0.0005). The proportion of children with long-segment HD was also significantly greater in Pacific and Asian populations than others (P = 0.04). These findings were not due to differences in the proportion of familial cases of HD among the different populations. CONCLUSIONS: The prevalence and phenotype of HD varies significantly between different ethnic groups within New Zealand. This may well be related to variations in the frequencies of HD-associated gene mutations within these populations.

Duration of postoperative intravenous antibiotics in childhood complicated appendicitis: a propensity score-matched comparison study.

INTRODUCTION: Postoperative antibiotics complement surgery in managing childhood-complicated appendicitis. However, there is limited evidence to guide clinicians on appropriate duration of therapy. A comparison cohort study was performed to determine whether tailoring duration of inpatient intravenous (IV) antibiotic therapy to patient response, assessed using a set of clinical criteria, leads to shortened hospital length of stay (LOS) without compromising patient outcomes. PATIENTS AND METHODS: Over a 6-month period, 47 children (aged 5-14 years) with complicated appendicitis were treated with postoperative IV antibiotics until each satisfied a set of bedside clinical parameters suggesting resolved intraperitoneal infection (core temperature < 38°C for 24 hours, tolerated two consecutive meals, mobilizing independently, requiring only oral analgesia). Complicated appendicitis was defined as the presence of generalized peritonitis, appendiceal perforation or gangrene, and/or abscess. Postoperative recovery parameters were prospectively recorded and compared with those of 47 historical control patients, matched by propensity scores, who received 5 days minimum of postoperative IV antibiotics. Sample size was determined by a priori power calculation based on reduction in LOS. Severity of postoperative complications was graded using the Clavien-Dindo system. RESULTS: Study group variables were comparable including patient demographics, duration of presenting symptoms, severity of presenting disease, preoperative antibiotics received, length of operation, seniority of primary surgeon, surgical approach taken, and intraoperative findings. The prospective cohort had a significantly shorter median LOS compared with the historical control cohort (5 vs. 6 nights, p = 0.010) while readmission rates and the incidence and severity of complications were similar, including incidence of postoperative intra-abdominal infections (6 vs. 8 cases, p = 0.562). CONCLUSION: Using bedside clinical parameters indicative of resolved intraperitoneal infection to tailor duration of postoperative IV antibiotics for children with complicated appendicitis shortens LOS without apparent compromise to patient outcomes.

Brain natriuretic peptide is not reno-protective during renal ischemia-reperfusion injury in the rat.

BACKGROUND: Acute kidney injury (AKI) occurs in 30% of patients undergoing complex cardiovascular surgery, and renal ischemia-reperfusion (I/R) injury is often a contributing factor. A recent meta-analysis observed that perioperative natriuretic peptide administration was associated with a reduction in AKI requiring dialysis in cardiovascular surgery patients. This study was designed to further clarify the potential reno-protective effect of brain natriuretic peptide (BNP) using an established rat model of renal I/R injury. METHODS: The study comprised three groups (n = 10 kidneys each): (1) control (no injury); (2) I/R injury (45 min of bilateral renal ischemia followed by 3 h of reperfusion); and (3) BNP (I/R injury plus rat-BNP pretreatment at 0.01 µg/kg/min). Glomerular filtration rate (GFR) and a biomarker of AKI, urinary neutrophil gelatinase-associated lipocalin (uNGAL), were measured at baseline and at 30 minute intervals post-ischemia. Groups were compared using two-way repeated measures analysis of variance (mean ± SD, significance P < 0.05). RESULTS: Baseline GFR measurements for control, I/R, and BNP groups were 1.07 ± 0.55, 0.88 ± 0.51, and 1.03 ± 0.59 mL/min (P = 0.90), respectively. Post-ischemia, GFR was significantly lower in I/R and BNP compared with controls at 30 min, 1.29 ± 0.97, 0.08 ± 0.04, and 0.06 ± 0.05 mL/min (P < 0.01), and remained lower through 3 h, 1.79 ± 0.44, 0.30 ± 0.17, and 0.32 ± 0.12 mL/min (P < 0.01). Comparing I/R to BNP groups, GFR did not differ significantly at any time point. There was no significant difference in uNGAL levels at 1 h (552 ± 358 versus 516 ± 259 ng/mL, P = 0.87) or 2 h (1073 ± 589 versus 989 ± 218 ng/mL, P = 0.79) between I/R and BNP. CONCLUSIONS: BNP does not reduce the renal injury biomarker, urinary NGAL, or preserve GFR in acute renal ischemia-reperfusion injury.

Low dietary calcium levels modulate mucosal caspase expression and increase disease activity in mice with dextran sulfate sodium induced colitis.

Dietary calcium (Ca) positively modulates the susceptibility to colon cancer, but its effects on related or earlier colonic pathologies, such as inflammation and mucosal dysregulation, are poorly understood. We tested the effects of differing dietary Ca levels on acute dextran sulfate sodium (DSS)-induced colitis in mice. BALB/c mice received a normal Ca (NCa) diet (0.5% Ca), a high Ca (HCa) diet (1.5% Ca), a low Ca (LCa) diet (0.05% Ca), or a very low Ca (VLCa) diet (0.009% Ca) for 3 wk. Mucosal caspases 1, 3, and 9 were assessed by Western blotting, and the histological crypt score was assessed by microscopy. Half of the mice in each group received DSS (1.5%) for 20 d in their drinking water, and disease activity was assessed. Increasing or lowering dietary Ca increased mucosal caspases (P < 0.0001 vs. NCa). Crypt scores increased with decreasing dietary Ca levels (P < 0.0001, r = -0.675), indicating that elevated caspases in LCa groups reflected early subclinical inflammation. DSS-induced disease activity was higher in mice fed low dietary Ca levels [P < 0.0001, VLCa and DSS vs. NCa and DSS (NCaDSS) and P < 0.005, LCa and DSS vs. NCaDSS], and mice from the VLCa group were moribund within 11 d of DSS administration. Those in the HCa group did not differ greatly from controls. Together, these data indicate that Ca protects against DSS-induced colitis in mice. The mechanisms are unclear, but the calcium-sensing receptor and/or luminal precipitates of calcium phosphate microparticles may be involved. Whether these observations can be extended to patients with colitis or infectious diarrhea deserves consideration.

The role of dietary microparticles and calcium in apoptosis and interleukin-1beta release of intestinal macrophages.

BACKGROUND & AIMS: The intestinal mucosa is exposed to micron-sized, man-made exogenous particles (e.g., titanium dioxide) and freshly formed endogenous particles (calcium phosphate). A role for such microparticles in inflammation has been proposed, and here we examined their effects on lamina propria mononuclear cells. METHODS: Lamina propria mononuclear cells were isolated from patients with and without inflammatory bowel disease and incubated with lipopolysaccharide, titanium dioxide, and calcium +/- citrate, as well as a conjugate of lipopolysaccharide, calcium, and titanium dioxide. Interleukin-1beta and interleukin-1 receptor antagonist were measured by enzyme-linked immunosorbent assay in culture supernatants and macrophage apoptosis by flow cytometry. Mechanistic studies were undertaken in normal peripheral blood mononuclear cells. RESULTS: Baseline levels of interleukin-1beta and macrophage apoptosis were greater in inflammatory bowel disease than in normal lamina propria mononuclear cells. Lipopolysaccharide and titanium dioxide had no additional effect, but calcium, and more so the conjugate, induced interleukin-1beta release in proportion to the degree of inflammation. Citrate, used to prevent in situ calcium phosphate formation, negated lamina propria mononuclear cell stimulation. Macrophage apoptosis was also increased by calcium and the conjugate. In peripheral blood mononuclear cells, inhibition of caspase 1 reduced interleukin-1beta secretion, whereas blockade of phagocytosis inhibited calcium-induced apoptosis and interleukin-1beta release. CONCLUSIONS: The endogenous luminal microparticle calcium phosphate Promotes apoptosis of intestinal macrophages. Concomitantly, interleukin-1beta is released, which is enhanced in the presence of inflamed cells and/or exogenous dietary microparticles. Endogenous or exogenous microparticles could aggravate the ongoing inflammation of inflammatory bowel disease.