Transitional Care for Patients with Congenital Colorectal Diseases: An EUPSA Network Office, ERNICA, and eUROGEN Joint Venture.

BACKGROUND: Transition of care (TOC; from childhood into adulthood) of patients with anorectal malformations (ARM) and Hirschsprung disease (HD) ensures continuation of care for these patients. The aim of this international study was to assess the current status of TOC and adult care (AC) programs for patients with ARM and HD. METHODS: A survey was developed by members of EUPSA, ERN eUROGEN, and ERNICA, including patient representatives (ePAGs), comprising of four domains: general information, general questions about transition to adulthood, and disease-specific questions regarding TOC and AC programs. Recruitment of centres was done by the ERNs and EUPSA, using mailing lists and social media accounts. Only descriptive statistics were reported. RESULTS: In total, 82 centres from 21 different countries entered the survey. Approximately half of them were ERN network members. Seventy-two centres (87.8%) had a self-reported area of expertise for both ARM and HD. Specific TOC programs were installed in 44% of the centres and AC programs in 31% of these centres. When comparing centres, wide variation was observed in the content of the programs. CONCLUSION: Despite the awareness of the importance of TOC and AC programs, these programs were installed in less than 50% of the participating centres. Various transition and AC programs were applied, with considerable heterogeneity in implementation, content and responsible caregivers involved. Sharing best practice examples and taking into account local and National Health Care Programs might lead to a better continuation of care in the future. LEVEL OF EVIDENCE: III.

Anatomy and embryology of tracheo-esophageal fistula.

Anomalies in tracheo-esophageal development result in a spectrum of congenital malformations ranging from, most commonly, esophageal atresia with or without trachea-esophageal fistula (EA+/-TEF) to esophageal web, duplication, stricture, tracheomalacia and tracheal agenesis. Despite the relative frequency of EA, however, the underlying etiology remains unknown and is likely due to a combination of genetic, epigenetic and environmental factors. In recent years, animal models have dramatically increased our understanding of the molecular and morphological processes involved in normal esophageal development during the key stages of anterior-posterior regionalization, dorsal-ventral patterning and morphogenic separation. Moreover, the use of animal models in conjunction with increasingly advanced techniques such as genomic sequencing, sophisticated live imaging studies and organoid models have more recently cast light on potential mechanisms involved in EA pathogenesis. This article aims to unravel some of the mysteries behind the anatomy and embryology of EA whilst providing insights into future directions for research.

Lessons learned from pre-clinical testing of xenogeneic decellularized esophagi in a rabbit model.

Decellularization of esophagi from several species for tissue engineering is well described, but successful implantation in animal models of esophageal replacement has been challenging. The purpose of this study was to assess feasibility and applicability of esophageal replacement using decellularized porcine esophageal scaffolds in a new pre-clinical model. Following surgical replacement in rabbits with a vascularizing muscle flap, we observed successful anastomoses of decellularized scaffolds, cues of early neovascularization, and prevention of luminal collapse by the use of biodegradable stents. However, despite the success of the surgical procedure, the long-term survival was limited by the fragility of the animal model. Our results indicate that transplantation of a decellularized porcine scaffold is possible and vascular flaps may be useful to provide a vascular supply, but long-term outcomes require further pre-clinical testing in a different large animal model.

Regenerative medicine for childhood gastrointestinal diseases.

Several paediatric gastrointestinal diseases result in life-shortening organ failure. For many of these conditions, current therapeutic options are suboptimal and may not offer a cure. Regenerative medicine is an inter-disciplinary field involving biologists, engineers, and clinicians that aims to produce cell and tissue-based therapies to overcome organ failure. Exciting advances in stem cell biology, materials science, and bioengineering bring engineered gastrointestinal cell and tissue therapies to the verge of clinical trial. In this review, we summarise the requirements for bioengineered therapies, the possible sources of the various cellular and non-cellular components, and the progress towards clinical translation of oesophageal and intestinal tissue engineering to date.

Monitoring tissue engineered constructs and protocols with laboratory-based x-ray phase contrast tomography.

Tissue engineering (TE) aims to generate bioengineered constructs which can offer a surgical treatment for many conditions involving tissue or organ loss. Construct generation must be guided by suitable assessment tools. However, most current tools (e.g. histology) are destructive, which restricts evaluation to a single-2D anatomical plane, and has no potential for assessing constructs prior to or following their implantation. An alternative can be provided by laboratory-based x-ray phase contrast computed tomography (PC-CT), which enables the extraction of 3D density maps of an organ's anatomy. In this work, we developed a semi-automated image processing pipeline dedicated to the analysis of PC-CT slices of oesophageal constructs. Visual and quantitative (density and morphological) information is extracted on a volumetric basis, enabling a comprehensive evaluation of the regenerated constructs. We believe the presented tools can enable the successful regeneration of patient-specific oesophagus, and bring comparable benefit to a wide range of TE applications. STATEMENT OF SIGNIFICANCE: Phase contrast computed tomography (PC-CT) is an imaging modality which generates high resolution volumetric density maps of biological tissue. In this work, we demonstrate the use of PC-CT as a new tool for guiding the progression of an oesophageal tissue engineering (TE) protocol. Specifically, we developed a semi-automated image-processing pipeline which analyses the oesophageal PC-CT slices, extracting visual and quantitative (density and morphological) information. This information was proven key for performing a comprehensive evaluation of the regenerated constructs, and cannot be obtained through existing assessment tools primarily due to their destructive nature (e.g. histology). This work paves the way for using PC-CT in a wide range of TE applications which can be pivotal for unlocking the potential of this field.

Historical and Contemporary Management of Infantile Hepatic Hemangioma: A 30-year Single-center Experience.

OBJECTIVE: To describe outcome of infants with hemangioma(s) of the liver. SUMMARY OF BACKGROUND DATA: Infantile hepatic hemangiomas exhibit a diverse phenotype. We report our 30-year experience and describe optimal management based on precise radiological classification. METHODS: Retrospective review of 124 infants (66 female) 1986-2016. Categorical analysis with Chi2 and nonparametric comparison. Data expressed as median (range) and P < 0.05 considered significant. RESULTS: Lesions classified as focal (n = 70, 56%); multifocal (n = 47, 38%) or diffuse (n = 7, 6%) and of these 80(65%) were symptomatic (eg, cardiac failure n = 39, 31%; thrombocytopenia n = 12, 10%).Increased hepatic artery velocity was seen in 63 (56%). Median hepatic artery velocity was greatest in diffuse lesions [245 (175-376) cm/s vs focal 120 (34-242) cm/s vs multifocal 93 (36-313) cm/s; P = 0.0001]. Expectant management alone was followed in 55 (44%). Medical therapy was utilised in 57(46%) and sufficient for symptom control in 29/57 (51%). Propranolol therapy (from 2008) was sufficient for symptom control in 22/28 (79%). Surgery (hepatic artery ligation n = 26; resection n = 13; embolization n = 1) was required in 40 (32%). Median maximal lesion diameter was 3 (0.5-17.1) cm and greater in those requiring surgery (7 cm vs 4.9 cm; P = 0.04). The proportion requiring surgery decreased markedly in the propranolol era [pre-propranolol 25/48 (52%) vs post-propranolol 16/76 (21%) (P = 0.0003)]. Systematic follow-up with ultrasound to a median of 2.6 (0.02-16) years. CONCLUSIONS: A proportion of infantile hepatic hemangiomas remain asymptomatic permitting observation until resolution but the majority require complex multi-modal therapy. First-line pharmacotherapy with propranolol has reduced but not abolished the need for surgery.

Prematurity and biliary atresia: a 30-year observational study.

AIM OF STUDY: The diagnosis of biliary atresia (BA) remains challenging and delay can lead to significant morbidity with time to surgery a key factor in determining outcome. Prematurity may impact on outcome potentially delaying diagnosis. We sought to assess whether the premature BA infants (PBA) have a delayed time to surgery and as such, worse outcomes? METHODS: Review of a single-centre prospectively maintained database. Prematurity was defined as delivery < 37/40 gestation. PBA was compared with date-matched term biliary atresia controls on a 2:1 basis. Primary outcomes were clearance of jaundice (< 20 µmol/L) and native liver survival. A retrospective assessment of liver fibrosis was made on biopsies at diagnosis and at Kasai portoenterostomy (KPE) in both premature and term cohorts. Data are quoted as median (range) unless indicated. A P value of ≤ 0.05 was considered statistically significant. RESULTS: 21 (female n = 14, 67%) premature infants with BA were treated in the period Jan. 1988-Dec. 2016 and compared with 41 contemporaneous term BA controls. Median gestation was 33 (29-36) weeks and birth weight 1930 (948-4230)g. Twin pregnancy (n = 10) was the leading cause for prematurity and significantly higher than the controls (48 vs. 0%; P < 0.0001). Maternal co-morbidity was high (n = 10, 48%) including pre-eclampsia (19%) and diabetes (14%). Liver biopsy was performed in 19 (90%) patients (all diagnostic) at a median of 57 (4-266) days. Delayed diagnosis (> 50 days) was seen in n = 13 but not associated with parenteral nutrition use (46 vs. 33%, P = 0.59) or phototherapy (50 vs. 83%, P = 0.19). Both BASM (33 vs. 7.5%; P = 0.01) and duodenal atresia (19 vs. 0%; P = 0.01) were seen more frequently in the PBA cohort. Mean fibrosis scores (Ishak) from diagnostic biopsies were lower in the premature group than the control group (2.71 vs. 3.53, P = 0.043) indicating less fibrosis but this equalized by time of subsequent KPE (P = 0.17). Primary surgery was Kasai portoenterostomy (n = 20) at an older median age than controls (65 vs. 56 days; P = 0.06). Liver transplantation was the primary procedure in one late-presenting child. There was an increased but non-significant clearance of jaundice in the PBA group [n = 12/20 (60%) vs 20/41 (48%); P = 0.23] post-KPE. Native liver survival and true survival were not different (P = 0.58 and 0.23). CONCLUSIONS: PBA infants have similar outcomes to term infants, despite delayed diagnosis and higher frequency of the syndromic form. The high incidence of discordant twins supports the theory that epigenetic modifications could contribute to the pathogenesis of BA. LEVEL OF EVIDENCE: IIIc Retrospective Matched Cohort Study.

What Is the Evidence for Paediatric/Adolescent Bariatric Surgery?

PURPOSE OF REVIEW: In spite of the increasing prevalence of severe and complex obesity in children, surgery as a potential management option is still not widely accepted. The purpose of this review is to examine the evidence for surgical options in the severely obese paediatric population. Increasing evidence supports early rather than later use of bariatric surgery in the treatment of extreme obesity. RECENT FINDINGS: Prior to 2007, the feasibility and safety of surgery have been reported by predominantly small, sporadic single-centre retrospective case series. Increasing long-term data is now emerging due to the formation of multi-centre prospective national consortiums with two large, prospective long-term outcome studies published within the last year aiding our understanding of the efficacy and safety of bariatric surgery within the adolescent population. It is increasingly clear that adolescent bariatric surgery outcomes are comparable to adults, with similar sustainable weight loss, resolution of co-morbidities and complication rates. However, these studies are solely from dedicated specialist adolescent centres and results may not be reproducible if not performed in regulated environments with specialist multi-disciplinary teams.

The management of boys under 3 months of age with an inguinal hernia and ipsilateral palpable undescended testis.

AIMS: The optimal management for boys under 3 months of age with an indirect inguinal hernia (IIH) and ipsilateral palpable undescended testis (IPUDT) is unknown. We aimed to: 1) determine the current practice for managing these boys across the UK, and 2) compare outcomes of different treatment strategies. METHODOLOGY: We undertook two studies. Firstly, we completed a National Survey of all surgeons on the British Association of Paediatric Surgeons email list in 2014. Subsequently, we undertook a multi-centre, retrospective, 10-year (2005-2015) review across 4 pediatric surgery centers of boys under 3months of age with concomitant IIH and IPUDT. Primary outcome was testicular atrophy. Secondary outcomes included need for subsequent orchidopexy, testicular ascent and hernia recurrence. Data are presented as median (range). Chi-squared test and multivariate binomial logistic regression analysis were used for analysis; p<0.05 was considered significant. RESULTS: Survey: Consultant practice varies widely across the UK, with a tendency towards performing concurrent orchidopexy at the time of herniotomy under 3 months of age. Concurrent orchidopexy is favored less in cases where the hernia is symptomatic. Case Series Review: Forty-one boys with 43 concomitant IIH and IPUDT were identified, and all included. 32 (74%) hernias were reducible, 11 (26%) were symptomatic requiring urgent or emergency repair. Post-conceptual age at surgery was 45weeks (36-65). Primary operations included: 29 (67%) open hernia repair and standard orchidopexy, 8 (19%) open hernia repair with future orchidopexy if required, 4 (9%) laparoscopic hernia repair with future orchidopexy if required, 2 (5%) open hernia repair and suturing of the testis to the inverted scrotum without scrotal incision. Variation in atrophy rate between different surgical approaches did not reach statistical significance (p=0.42). Overall atrophy rate was 18%. If hernia repair alone was undertaken (8 open and 4 laparoscopic), the testis did not descend in 8 patients, requiring subsequent orchidopexy (67%); if orchidopexy was undertaken at the time of hernia repair, 1 in 29 required a repeat orchidopexy (3%) (p=0.0001). No hernia recurred. CONCLUSION: This study suggests that orchidopexy at the time of inguinal herniotomy does not increase the risk of testicular atrophy in boys under 3months of age.

Post-traumatic liver and splenic pseudoaneurysms in children: Diagnosis, management, and follow-up screening using contrast enhanced ultrasound (CEUS).

BACKGROUND: Pseudoaneurysm (PA) formation following blunt and penetrating abdominal trauma is a recognized complication in solid organ injury, usually diagnosed by contrast-enhanced CT (CECT) imaging. Delayed rupture is a potentially life-threatening event, although its frequency is not known in pediatric trauma. Contrast enhanced ultrasound (CEUS) is a novel radiation-free alternative to CECT with the potential to identify PA. METHODS: A retrospective review of consecutive cases of significant liver and splenic injuries admitted to single institution (tertiary and quaternary referrals) over more than a 12year period was performed. From 2011, CEUS was performed routinely postinjury (5-10days) using SonoVue™ as contrast. Initially, CECT and CEUS were performed in tandem to ensure accurate correlation. RESULTS: From January 2002-December 2014, 101 (73M) children [median age was 14.2 (1.3-18)years] with liver and splenic injuries were admitted. Injuries included: liver [n=57, grade 3 (1-5)], splenic [n=35, grade 3 (1-5)], and combined liver/spleen [n=8, (1-4)]. Median Injury Severity Score (ISS) was 13 (2-72). The predominant mechanisms of injury were blunt trauma n=73 (72%) and penetrating trauma n=28 (28%). Seventeen children (17%) developed PA. Six children became symptomatic (35%), and five went on to have embolization [at 7 (3-11)days]. These were detected by CECT (n=4) and CEUS (n=2). Eleven children remained asymptomatic [detected by CECT (n=8) and CEUS (n=3) at median 5 (4-8)days]. One underwent embolization owing to evidence of interval bleeding. Sensitivity of CEUS at detection of PA was 83%, with specificity of 92% (PPV=71%, NPV=96%). There was no association between grade of injury and presence of PA in either liver or splenic trauma (P=0.4), nor was there an association between size of PA and symptoms (P=0.68). Children sustaining splenic PA were significantly younger than those with hepatic PA (P=0.03). Follow-up imaging confirmed resolution of PA in 16 cases. One child was lost to follow-up. CONCLUSIONS: The incidence of PA is higher than previously reported in the pediatric literature (<5%). Postinjury imaging appears mandatory, and CEUS appears to be highly sensitive and specific for diagnosis and follow-up.

Accuracy of clinical coding from 1210 appendicectomies in a British district general hospital.

AIMS: The primary aim of this study was to assess the accuracy of clinical coding in identifying negative appendicectomies. The secondary aim was to analyse trends over time in rates of simple, complex (gangrenous or perforated) and negative appendicectomies. METHODS: Retrospective review of 1210 patients undergoing emergency appendicectomy during a five year period (2006-2010). Histopathology reports were taken as gold standard for diagnosis and compared to clinical coding lists. Clinical coding is the process by which non-medical administrators apply standardised diagnostic codes to patients, based upon clinical notes at discharge. These codes then contribute to national databases. Statistical analysis included correlation studies and regression analyses. RESULTS: Clinical coding had only moderate correlation with histopathology, with an overall kappa of 0.421. Annual kappa values varied between 0.378 and 0.500. Overall 14% of patients were incorrectly coded as having had appendicitis when in fact they had a histopathologically normal appendix (153/1107), whereas 4% were falsely coded as having received a negative appendicectomy when they had appendicitis (48/1107). There was an overall significant fall and then rise in the rate of simple appendicitis (B coefficient -0.239 (95% confidence interval -0.426, -0.051), p = 0.014) but no change in the rate of complex appendicitis (B coefficient 0.008 (-0.015, 0.031), p = 0.476). CONCLUSIONS: Clinical coding for negative appendicectomy was unreliable. Negative rates may be higher than suspected. This has implications for the validity of national database analyses. Using this form of data as a quality indictor for appendicitis should be reconsidered until its quality is improved.