Seminars in Pediatric Surgery最新文献

Congenital Diaphragmatic Hernia (CDH) is a complex developmental abnormality characterized by abnormal lung development, a diaphragmatic defect and cardiac dysfunction. Despite significant advances in management of CDH, mortality and morbidity continue to be driven by pulmonary hypoplasia, pulmonary hypertension, and cardiac dysfunction. The etiology of CDH remains unknown, but CDH is presumed to be caused by a combination of genetic susceptibility and external/environmental factors. Current research employs multi-omics technologies to investigate the molecular profile and pathways inherent to CDH. The aim is to discover the underlying pathogenesis, new biomarkers and ultimately novel therapeutic targets. Stem cells and their cargo, non-coding RNAs and agents targeting inflammation and vascular remodeling have produced promising results in preclinical studies using animal models of CDH. Shortcomings in current therapies combined with an improved understanding of the pathogenesis in CDH have given rise to novel promising experimental treatments that are currently being evaluated in clinical trials. This review provides insight into current developments in translational research, ranging from the cellular origins of abnormal cardiopulmonary development in CDH and the identification of novel treatment targets in preclinical CDH models at the bench and their translation to clinical trials at the bedside.

Patients with lymphatic disorders are remarkably complex and require a wide variety of medical and surgical services. Establishing a multidisciplinary program improves the efficiency of the patients’ hospital experience minimizing the compartmentalization of their care. Offering a clear intake process guarantees that patients will be seen promptly by all the required teams. Additionally, having regular multidisciplinary meetings allows all participating teams to learn from each other and gain experience in the care of a population that is extraordinarily heterogeneous. Additionally, establishing a solid program allows for long-term data collection, research and education.

Protein-losing enteropathy (PLE) describes a syndrome of excessive protein loss into the gastrointestinal tract, which may be due to a wide variety of etiologies. For children in whom the protein loss is associated with lymphangiectasia, medical nutrition therapy focused on restricting enteral long-chain triglycerides and thus intestinal chyle production is an integral component of treatment. This approach is based on the principle that reducing intestinal chyle production will concurrently decrease enteric protein losses of lymphatic origin. In patients with ongoing active PLE or those who are on a fat-restricted diet, particularly in infants and young children, supplemental calories may be provided with medium-chain triglycerides (MCT). MCT are absorbed directly into the bloodstream, bypassing intestinal lymphatics and not contributing to intestinal chyle production. Patients with active PLE or who are on dietary fat restriction should be monitored for associated micronutrient deficiencies. In this paper, we seek to formally present recommended nutrition interventions, principles of dietary education and patient counseling, and monitoring parameters in pediatric populations with PLE based on our experience in a busy clinical referral practice focused on this population.

Percutaneous endovascular techniques established in interventional cardiology and radiology are well-suited for managing lymphatic conduction disorders. In this article, we provide a synopsis of technical aspects of these procedures, including access of the thoracic duct, selective lymphatic embolization, and management of thoracic duct obstruction. In aggregate, these techniques have developed into an integral component of multidisciplinary management of these complex diseases.

Objective

The thoracic duct is the largest lymphatic vessel in the body, and carries fluid and nutrients absorbed in abdominal organs to the central venous circulation. Thoracic duct obstruction can cause significant failure of the lymphatic circulation (i.e., protein-losing enteropathy, plastic bronchitis, etc.). Surgical anastomosis between the thoracic duct and central venous circulation has been used to treat thoracic duct obstruction but cannot provide lymphatic decompression in patients with superior vena cava obstruction or chronically elevated central venous pressures (e.g., right heart failure, single ventricle physiology, etc.). Therefore, this preclinical feasibility study sought to develop a novel and optimal surgical technique for creating a thoracic duct-to-pulmonary vein lymphovenous anastomosis (LVA) in swine that could remain patent and preserve unidirectional lymphatic fluid flow into the systemic venous circulation to provide therapeutic decompression of the lymphatic circulation even at high central venous pressures.

Methods

A thoracic duct-to-pulmonary vein LVA was attempted in 10 piglets (median age 80 [IQR 80–83] days; weight 22.5 [IQR 21.4–26.8] kg). After a right thoracotomy, the thoracic duct was mobilized, transected, and anastomosed to the right inferior pulmonary vein. Animals were systemically anticoagulated on post-operative day 1. Lymphangiography was used to evaluate LVA patency up to post-operative day 7.

Results

A thoracic duct-to-pulmonary vein LVA was successfully completed in 8/10 (80.0%) piglets, of which 6/8 (75.0%) survived to the intended study endpoint without any complication (median 6 [IQR 4–7] days). Initially, 2/10 (20.0%) LVAs were aborted intraoperatively, and 2/10 (20.0%) animals were euthanized early due to post-operative complications. However, using an optimized surgical technique, the success rate for creating a thoracic duct-to-pulmonary vein LVA in six animals was 100%, all of which survived to their intended study endpoint without any complications (median 6 [IQR 4–7] days). LVAs remained patent for up to seven days.

Conclusion

A thoracic duct-to-pulmonary vein LVA can be completed safely and remain patent for at least one week with systemic anticoagulation, which provides an important proof-of-concept that this novel intervention could effectively offload the lymphatic circulation in patients with lymphatic failure and elevated central venous pressures.

Lymphatic disorders presenting in the first year of life are difficult to identify and manage given the broad range of underlying etiologies. Neonatal lymphatic disease arising from congenital or acquired conditions results in the abnormal accumulation of lymph fluid in the pleura (chylothorax), peritoneum (chylous ascites) and skin (edema/anasarca). There is also increasing recognition of lymphatic losses through the intestine resulting in protein-losing enteropathy (PLE). While the incidence of lymphatic disorders in neonates is unclear, advances in genetic testing and lymphatic imaging are improving our understanding of the underlying pathophysiology. Despite these advancements, medical management of neonatal lymphatic disorders remains challenging and variable among clinicians.

Lymphatic failure is a broad term that describes the lymphatic circulation's inability to adequately transport fluid and solutes out of the interstitium and into the systemic venous circulation, which can result in dysfunction and dysregulation of immune responses, dietary fat absorption, and fluid balance maintenance. Several investigations have recently elucidated the nexus between lymphatic failure and congenital heart disease, and the associated morbidity and mortality is now well-recognized. However, the precise pathophysiology and pathogenesis of lymphatic failure remains poorly understood and relatively understudied, and there are no targeted therapeutics or interventions to reliably prevent its development and progression. Thus, there is growing enthusiasm towards the development and application of novel percutaneous and surgical lymphatic interventions. Moreover, there is consensus that further investigations are needed to delineate the underlying mechanisms of lymphatic failure, which could help identify novel therapeutic targets and develop innovative procedures to improve the overall quality of life and survival of these patients. With these considerations, this review aims to provide an overview of the lymphatic circulation and its vasculature as it relates to current understandings into the pathophysiology and pathogenesis of lymphatic failure in patients with congenital heart disease, while also summarizing strategies for evaluating and managing lymphatic complications, as well as specific areas of interest for future translational and clinical research efforts.

Lymphatic imaging plays a crucial role in novel lymphatic interventions, offering valuable insights into central lymphatic drainage. Lymphatic system abnormalities may appear in various pediatric disorders, and accurate imaging is crucial for effective diagnosis and tailored therapeutic interventions. Traditional imaging modalities have offered valuable insights, but the demand for non-invasive, high-resolution techniques has fueled the development of innovative lymphatic imaging methods. In this review, we explore the state of the art in lymphatic imaging specifically within the context of pediatric surgery.

The lymphatic system is one of the most essential and complex systems in the human body. Disorders that affect the development or function of the lymphatic system can lead to multi-system complications and life-long morbidity. The past two decades have seen remarkable progress in our knowledge of the basic biology and function of the lymphatic system, the molecular regulators of lymphatic development, and description of disorders associated with disrupted lymphangiogensis. In this chapter we will touch on the clinical features of complex lymphatic anomalies, new molecular knowledge of the drivers of these disorders, and novel developmental therapeutics for lymphatic disease.