Sublobar Pulmonary Resection in Children With Congenital Lung Abnormalities:A Systematic Review

Background:Lobectomy is currently the advised resection for symptomatic congenital lung abnormalities (CLA). Sublobar surgery is suggested as an alternative that enables to conserve healthy lung parenchyma. This systematic review aims to explore the outcomes of sublobar surgery in CLA patients as well as the corresponding surgical terminology and techniques. Methods: A systematic literature search was performed in adherence to PRISMA-P guidelines. The target population consists of children undergoing sublobar pulmonary resection for CLA. All studies were independently assessed by two reviewers, and evaluated by a third reviewer in case of disagreement. Results: The literature search yielded 901 studies of which 18 studies were included, comprising 1167 cases. The median chest tube insertion duration was 3.6 days (range 2.0–6.9 days), the median hospital admission was 4.9 days (range 2.0–14.5 days), and residual disease was diagnosed in 2% – leading to re-operation in 70%. The median incidence of postoperative complications was 15% (range 0–67%). Follow-up imaging was standard-of-care in 2/3 of studies. Due to the absence of standardised terminology, operative details and specification of resection type did not typically relate between studies. Conclusions: Sublobar resection of CLA lesions could be a viable alternative to lobectomy in certain cases, with the advantage of conserving healthy lung parenchyma. Peri- and postoperative complications are comparable with those reported for conventional lobectomy. The incidence of residual disease following sublobar surgery appears to be lower than commonly stated. To improve comparability between studies, we recommend reporting perioperative characteristics in a structured format. Level of evidence: Level IV.</p

An international survey on anastomotic stricture management after esophageal atresia repair:considerations and advisory statements

BACKGROUND: Endoscopic dilatation is the first-line treatment of stricture formation after esophageal atresia (EA) repair. However, there is no consensus on how to perform these dilatation procedures which may lead to a large variation between centers, countries and doctor’s experience. This is the first cross-sectional study to provide an overview on differences in endoscopic dilatation treatment of pediatric anastomotic strictures worldwide. METHODS: An online questionnaire was sent to members of five pediatric medical networks, experienced in treating anastomotic strictures in children with EA. The main outcome was the difference in endoscopic dilatation procedures in various centers worldwide, including technical details, dilatation approach (routine or only in symptomatic patients), and adjuvant treatment options. Descriptive statistics were performed with SPSS. RESULTS: Responses from 115 centers from 32 countries worldwide were analyzed. The preferred approach was balloon dilatation (68%) with a guidewire (66%), performed by a pediatric gastroenterologist (n = 103) or pediatric surgeon (n = 48) in symptomatic patients (68%). In most centers, hydrostatic pressure was used for balloon dilatation. The insufflation duration was standardized in 59 centers with a median duration of 60 (range 5–300) seconds. The preferred first-line adjunctive treatments in case of recurrent strictures were intralesional steroids and topical mitomycin C, in respectively 47% and 31% of the centers. CONCLUSIONS: We found a large variation in stricture management in children with EA, which confirms the current lack of consensus. International networks for rare diseases are required for harmonizing and comparing the procedures, for which we give several suggestions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00464-020-07844-6) contains supplementary material, which is available to authorized users

Physiological-based cord clamping versus immediate cord clamping for infants born with a congenital diaphragmatic hernia (PinC):study protocol for a multicentre, randomised controlled trial

Introduction Pulmonary hypertension is a majordeterminant of postnatal survival in infants with acongenital diaphragmatic hernia (CDH). The current careduring the perinatal stabilisation period in these infantsmight contribute to the development of pulmonaryhypertension after birth—in particular umbilical cordclamping before lung aeration. An ovine model ofdiaphragmatic hernia demonstrated that cord clampingafter lung aeration, called physiological-based cordclamping (PBCC), avoided the initial high pressures in thelung vasculature while maintaining adequate blood flow,thereby avoiding vascular remodelling and aggravationof pulmonary hypertension. We aim to investigate if theimplementation of PBCC in the perinatal stabilisation periodof infants born with a CDH could reduce the incidence ofpulmonary hypertension in the first 24 hours after birth.Methods and analysis We will perform a multicentre,randomised controlled trial in infants with an isolatedleft-sided CDH, born at ≥35.0 weeks. Before birth, infantswill be randomised to either PBCC or immediate cordclamping, stratified by treatment centre and severity ofpulmonary hypoplasia on antenatal ultrasound. PBCCwill be performed using a purpose- built resuscitationtrolley. Cord clamping will be performed when the infantis considered respiratory stable, defined as a heartrate &gt;100 bpm, preductal oxygen saturation &gt;85%,while using a fraction of inspired oxygen of &lt;0.5. Theprimary outcome is pulmonary hypertension diagnosedin the first 24 hours after birth, based on clinical andechocardiographic parameters. Secondary outcomesinclude neonatal as well as maternal outcomes.Ethics and dissemination Central ethical approvalwas obtained from the Medical Ethical Committee ofthe Erasmus MC, Rotterdam, The Netherlands (METC2019-0414). Local ethical approval will be obtained bysubmitting the protocol to the regulatory bodies and localinstitutional review boards

Lung epithelium development and airway regeneration

The lung is composed of a highly branched airway structure, which humidifies and warms the inhaled air before entering the alveolar compartment. In the alveoli, a thin layer of epithelium is in close proximity with the capillary endothelium, allowing for an efficient exchange of oxygen and carbon dioxide. During development proliferation and differentiation of progenitor cells generates the lung architecture, and in the adult lung a proper function of progenitor cells is needed to regenerate after injury. Malfunctioning of progenitors during development results in various congenital lung disorders, such as Congenital Diaphragmatic Hernia (CDH) and Congenital Pulmonary Adenomatoid Malformation (CPAM). In addition, many premature neonates experience continuous insults on the lung caused by artificial ventilation and supplemental oxygen, which requires a highly controlled mechanism of airway repair. Malfunctioning of airway progenitors during regeneration can result in reduction of respiratory function or (chronic) airway diseases. Pathways that are active during development are frequently re-activated upon damage. Understanding the basic mechanisms of lung development and the behavior of progenitor cell in the ontogeny and regeneration of the lung may help to better understand the underlying cause of lung diseases, especially those occurring in prenatal development or in the immediate postnatal period of life. This review provides an overview of lung development and the cell types involved in repair of lung damage with a focus on the airway

SOX2 and SOX21 in Lung Epithelial Differentiation and Repair

The lung originates from the ventral foregut and develops into an intricate branched structure of airways, alveoli, vessels and support tissue. As the lung develops, cells become specified and differentiate into the various cell lineages. This process is controlled by specific transcription factors, such as the SRY-related HMG-box genes SOX2 and SOX21, that are activated or repressed through intrinsic and extrinsic signals. Disturbances in any of these processes during the development of the lung may lead to various pediatric lung disorders, such as Congenital Diaphragmatic Hernia (CDH), Congenital Pulmonary Airway Malformation (CPAM) and Broncho-Pulmonary Dysplasia (BPD). Changes in the composition of the airways and the alveoli may result in reduced respiratory function and eventually lead to chronic lung disorders. In this concise review, we describe different intrinsic and extrinsic cellular processes required for proper differentiation of the epithelium during development and regeneration, and the influence of the microenvironment on this process with special focus on SOX2 and SOX21

Cellular Origin(s) of Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) is a structural birth defect characterized by a diaphragmatic defect, lung hypoplasia and structural vascular defects. In spite of recent developments, the pathogenesis of CDH is still poorly understood. CDH is a complex congenital disorder with multifactorial etiology consisting of genetic, cellular and mechanical factors. This review explores the cellular origin of CDH pathogenesis in the diaphragm and lungs and describes recent developments in basic and translational CDH research

Minor and giant omphalocele: long-term outcomes and quality of life

Purpose: Long-term outcome and quality of life in omphalocele (OC) studies are mainly focused on cosmetic disorders with the abdominal scar and gastrointestinal disorders. The aim of this study was to compare long-term mortality, morbidity, and quality o

Long-term follow-up of functional outcome in patients with a cloacal malformation: A systematic review

Background Reconstructive surgery is performed in patients with cloacal malformations to achieve anorectal, urological, and gynecological function. The aim of this study was to evaluate the functional outcome of cloacal malformation repair as reported in literature. Methods A systematic literature search was conducted according to PRISMA guidelines using PubMed, EMbase, and Web-of-Science. Records were assessed for the reporting of functional outcomes, which was divided into anorectal, urological, or gynecological function. Studies were used in qualitative (Rangel score) and quantitative syntheses. Results Twelve publications were eligible for inclusion. Voluntary bowel movements were reported in 108 of 188 (57%), soiling in 146 of 205 (71%), and constipation in 31 of 61 patients (51%). Spontaneous voiding was reported for 138 of 299 patients (46%). 141 of 332 patients (42%) used intermittent catheterization, and 53 of 237 patients (22%) had a urinary diversion. Normal menstruations were reported for 25 of 71 patients (35%). Centers with limited experience reported similar outcome compared to centers with more experience (≥ 1 patients/year). Conclusion In this review we present functional outcome of the largest pooled cohort of patients with cloacal malformations as reported from 1993 to 2012. Functional disturbances are frequently encountered in anorectal, urological, as well as gynecological systems. Reporting of functional outcome in these patients should improve to increase knowledge about long-term results in patients with this rare malformation and to reach higher study quality. Especially, sacral and spinal anomalies should always be reported given their impact on functional outcome. Specialized care centers may be of great importance for patients with rare and complex conditions. © 2013 Elsevier Inc.All rights reserved

A combinatorial panel for flow cytometry-based isolation of enteric nervous system cells from human intestine

Efficient isolation of neurons and glia from the human enteric nervous system (ENS) is challenging because of their rare and fragile nature. Here, we describe a staining panel to enrich ENS cells from the human intestine by fluorescence-activated cell sorting (FACS). We find that CD56/CD90/CD24 co-expression labels ENS cells with higher specificity and resolution than previous methods. Surprisingly, neuronal (CD24, TUBB3) and glial (SOX10) selective markers appear co-expressed by all ENS cells. We demonstrate that this contradictory staining pattern is mainly driven by neuronal fragments, either free or attached to glial cells, which are the most abundant cell types. Live neurons can be enriched by the highest CD24 and CD90 levels. By applying our protocol to isolate ENS cells for single-cell RNA sequencing, we show that these cells can be obtained with high quality, enabling interrogation of the human ENS transcriptome. Taken together, we present a selective FACS protocol that allows enrichment and discrimination of human ENS cells, opening up new avenues to study this complex system in health and disease

Associations of perioperative characteristics with motor function in preschool children born with esophageal atresia

Background: Children born with esophageal atresia experience long-term neurodevelopmental deficits, with unknown origin. Aims: To find associations between perioperative variables during primary esophageal atresia repair and motor function at age 5 years. Methods: This ambidirectional cohort study included children born with esophageal atresia who consecutively had been operated on in the Erasmus MC-Sophia Children's Hospital, University Medical Center, Rotterdam, from January 2007 through June 2013. The perioperative data of this cohort were collected retrospectively; the motor function data prospectively. Results: After exclusion of patients with syndromal congenital diseases (n = 8) and lost to follow-up (n = 10), the data of 53 children were included. The mean (SD) total motor function impairment z-score at 5 years of age was −0.66 (0.99), significantly below normal (p <.001). In multivariable linear regression analysis, number of postoperative days endotracheal intubation (B = −0.211, 95% CI: −0.389 to −0.033, p =.021) was negatively associated with motor outcome, whereas high blood pressure (B = 0.022, 95% CI 0.001 to 0.042, p =.038) was positively associated. Preoperative nasal oxygen supplementation versus room air (B = 0.706, 95% CI: 0.132 to 1.280, p =.016) was positively associated with motor outcome, which we cannot explain. Conclusions: Motor function in 5-year-old esophageal atresia patients was impaired and negatively associated with the number of postoperative days of endotracheal intubation and positively associated with high blood pressure. Prospective studies with critical perioperative monitoring and monitoring during stay at the intensive care unit are recommended