Clare A. McLaren

Stem-cell-based, tissue engineered tracheal replacement in a child: A 2-year follow-up study

BACKGROUND Stem-cell-based, tissue engineered transplants might offer new therapeutic options for patients, including children, with failing organs. The reported replacement of an adult airway using stem cells on a biological scaffold with good results at 6 months supports this view. We describe the case of a child who received a stem-cell-based tracheal replacement and report findings after 2 years of follow-up. METHODS A 12-year-old boy was born with long-segment congenital tracheal stenosis and pulmonary sling. His airway had been maintained by metal stents, but, after failure, a cadaveric donor tracheal scaffold was decellularised. After a short course of granulocyte colony stimulating factor, bone marrow mesenchymal stem cells were retrieved preoperatively and seeded onto the scaffold, with patches of autologous epithelium. Topical human recombinant erythropoietin was applied to encourage angiogenesis, and transforming growth factor β to support chondrogenesis. Intravenous human recombinant erythropoietin was continued postoperatively. Outcomes were survival, morbidity, endoscopic appearance, cytology and proteomics of brushings, and peripheral blood counts. FINDINGS The graft revascularised within 1 week after surgery. A strong neutrophil response was noted locally for the first 8 weeks after surgery, which generated luminal DNA neutrophil extracellular traps. Cytological evidence of restoration of the epithelium was not evident until 1 year. The graft did not have biomechanical strength focally until 18 months, but the patient has not needed any medical intervention since then. 18 months after surgery, he had a normal chest CT scan and ventilation-perfusion scan and had grown 11 cm in height since the operation. At 2 years follow-up, he had a functional airway and had returned to school. INTERPRETATION Follow-up of the first paediatric, stem-cell-based, tissue-engineered transplant shows potential for this technology but also highlights the need for further research. FUNDING Great Ormond Street Hospital NHS Trust, The Royal Free Hampstead NHS Trust, University College Hospital NHS Foundation Trust, and Region of Tuscany.

Renovascular hypertension in children

Renovascular disease is an uncommon but important cause of hypertension in children. It is usually diagnosed after a long delay because blood pressure is infrequently measured in children and high values are generally dismissed as inaccurate. Many children with renovascular disease have abnormalities of other blood vessels (aorta, cerebral, intestinal, or iliac). Individuals suspected of having the disorder can be investigated further with CT, MRI, or renal scintigraphy done before and after administration of an angiotensin-converting-enzyme inhibitor, but angiography is still the gold standard. Most children with renovascular disease will need interventional or surgical treatment. Endovascular treatment with or without stenting will cure or reduce high blood pressure in more than half of all affected children. Surgical intervention, if needed, should be delayed preferably until an age when the child is fully grown. Modern treatment provided by a multidisciplinary team of paediatric nephrologists, interventional radiologists, and vascular surgeons offers good long-term treatment results.

First Experience With Biodegradable Airway Stents in Children

PURPOSE We here report our experience with biodegradable polydioxanone stents for tracheal narrowing in children. DESCRIPTION Eleven custom-made polydioxanone stents were implanted in 4 patients with airway narrowing due to external compression or intrinsic collapse. The median stent diameter was 9 mm (range, 6 to 14 mm) and median length was 15 mm (range, 13 to 70 mm). EVALUATION Narrowing was relieved initially in all cases. There was no bleeding or perforation after polydioxanone stent implantation. Size mismatching was a problem in 2 cases. Three patients needed repeat stenting after stent absorption. There was 1 death, unrelated to the stent implantation. All 3 survivors are in good clinical condition up to 12 months after first stenting. CONCLUSIONS This pilot study shows that polydioxanone stents offer an alternative to metallic or silastic stents for collapse or external compression of the trachea in children. They may avoid the need for permanent stenting and allow subsequent growth of the airway.

Vascular compression of the airway in children

Congenital heart disease (CHD) is an important clinical problem. Although survival has improved over recent decades, certain children with CHD remain difficult to treat, usually because of severe co-morbidity or uncorrectable defects. Vascular compression of the airway is one such co-morbidity, occurring in approximately 1-2% of children with CHD. It may be caused by congenital anomalies of the configuration of the great vessels, enlargement of otherwise normal structures or as a result of surgery. The anatomical patterns seen in these children may be complex, and as surgical correction is usually required to relieve the compression, the pre-operative imaging assessment should be as complete as possible. Precise diagnosis and therapy are essential because chronic airway compression in childhood carries a significant morbidity and mortality. Airway stenting is currently reserved for rare occasions when surgical correction is not possible.

Imaging in the evaluation of renovascular disease

Renovascular disease (RVD) is an important cause of hypertension in children, as it often is amenable to potentially curative treatment. Imaging aimed at finding RVD therefore needs to have high sensitivity so as not to miss important findings. Digital subtraction angiography is the gold standard investigation. Doppler ultrasonography, computed tomography (CT) angiography and magnetic resonance (MR) angiography can all be helpful, but none has, at present, high enough sensitivity to rule out RVD in a child with a suggestion of that diagnosis.

Computed tomography versus bronchography in the diagnosis and management of tracheobronchomalacia in ventilator dependent infants

Aim: To assess the relative accuracy of dynamic spiral computed tomography (CT) compared with tracheobronchography, in a population of ventilator dependent infants with suspected tracheobroncho-malacia (TBM). Setting: Paediatric intensive care unit in a tertiary teaching hospital. Patients and methods: Infants referred for investigation and management of ventilator dependence and suspected of having TBM were recruited into the study. Tracheobronchography and CT were performed during the same admission by different investigators who were blinded to the results of the other investigation. The study was approved by the hospital research ethics committee, and signed parental consent was obtained. Results: Sixteen infants were recruited into the study. Fifteen had been born prematurely, and five had cardiovascular malformations. In 10 patients there was good or partial correlation between the two investigations, but in six patients there was poor or no correlation. Bronchography consistently showed more dynamic abnormalities, although CT picked up an unsuspected double aortic arch. Radiation doses were 0.27–2.47 mSv with bronchography and 0.86–10.67 mSv with CT. Conclusions: Bronchography was a better investigation for diagnosing TBM and in determining opening pressures. Spiral CT is unreliable in the assessment of TBM in ventilator dependent infants. In addition, radiation doses were considerably higher with CT.

Results of surgical treatment for renovascular hypertension in children: 30 year single centre experience

BACKGROUND We retrospectively reviewed the medical records of all patients who underwent surgery as part of the treatment of renovascular hypertension (RVH) at our centre between 1979 and 2008. Patients. Thirty-seven children (65% male) with a median age of 7.6 (0.4-17.9) years were identified with a median systolic blood pressure (SBP) of 140 (105-300) mm Hg prior to surgery. Bilateral renal artery stenosis and intra-renal disease were present in 19 (51%) patients, mid-aortic syndrome in 15 (40%), involvement of visceral arteries in eight out of 35 (23%) and coexisting cerebral disease in eight out of 30 (26%) investigated patients. RESULTS Surgical procedures (n = 53) included (i) nephrectomy (18, of which two unplanned and two secondary due to technical failure), (ii) renovascular surgery on the renal arteries (28, of which 18 had autologous surgery and 10 synthetic grafts inserted for revascularisation) and (iii) aortic reconstruction with (6) and without (1) a synthetic graft. Post-operative complications were haemorrhage (5), septicaemia (5) and chylous ascites (1). There were no perioperative deaths; two children died during follow-up. The SBP post-surgery improved to a median value of 116 (range 90-160) mm Hg. Twelve months after surgery, 16 (43%) children had normal blood pressure without treatment, 15 (41%) normal or improved on one to four antihypertensive drugs and four (11%) unchanged; no data were available for two (5%) children. CONCLUSION Surgery effectively treated the hypertension of 90% of our children, when performed in conjunction with medical therapy and interventional radiology. In spite of aggressive surgical treatment, RVH is sometimes a progressive disease.

Angioplasty for renovascular hypertension in 78 children

Objectives To evaluate the outcome of percutaneous transluminal angioplasty (PTA) in children with renovascular hypertension (RVH) treated at a single centre over 29 years. Methods A retrospective study of the medical charts of all children with RVH who underwent PTA between 1984 and 2012. The primary outcome measurement was blood pressure (BP) achieved after the procedure. The BP before the procedure was compared with that at last available follow-up, 6 (range 0.6–16) years after the initial procedure. Results Seventy-eight children with median (range) age of 6.5 (0.5–17) years were studied. Twenty-three (29.5%) had an underlying syndrome, 35 (44.9%) children had bilateral renal artery stenosis (RAS), 18 (23%) intrarenal disease and 11(14%) showed bilateral RAS and intrarenal disease. Twenty (25.6%) children had mid-aortic syndrome and 14 (17.9%) cerebrovascular disease. One hundred and fourteen PTA procedures were carried out including 31 stent insertions. Following PTA, BP was improved in 49 (62.8%) children and of those 18 (23.1%) were cured. Children with involvement of only the main renal arteries showed improved BP control in 79.9% of the children with cure in 39.5%. BP was intentionally maintained above the 95th centile for age and height in four children with coexistent cerebrovascular disease. No change in BP was seen in 18 children despite observed technical success of the PTA, and in seven children due to technical failure of the procedure. Conclusions PTA provided a clinical benefit in 62.8% of children with RVH.

Pre- and postcaptopril renal scintigraphy as a screening test for renovascular hypertension in children

We studied the ability of pre- and postcaptopril renal scintigraphy to predict renovascular disease (RVD) in children. Retrospective review of medical notes and radiology reports of all hypertensive children who had had both pre- and postcaptopril renal scintigraphy with [99mTc] dimercaptosuccinic acid (DMSA) and/or [99mTc] mercaptoacetyltriglycine (MAG3) and digital subtraction angiography (DSA). 81 children aged 1–18 (median 10) years were studied with 62% (51) having a diagnosis of RVD. Main renal artery disease, intrarenal disease, and both main and intrarenal artery disease were present in 25, 14, and 12 patients respectively. The isotope study accurately diagnosed RVD, confirmed by DSA, in 47% (24 of 51) children, with eight false positive studies. The sensitivity, specificity, and positive and negative predictive values of the isotope study to predict RVD were 48%, 73%, 76%, and 51%, respectively. Pre- and postcaptopril renal scintigraphy was unable to predict RVD in children.

Gastrointestinal intervention in children

Interventional radiology is a rapidly growing discipline in paediatrics. Many non-vascular interventional techniques may be used in the gastrointestinal tract in children. The technically simpler and more common of these may be adopted by any paediatric radiologist with an interest in interventional radiology. Other rarer and more complex techniques are currently restricted to specialist centres with a higher overall caseload. This review emphasizes the common procedures such as oesophageal dilatation, gastrostomy, insertion of transgastric jejunal feeding tubes and biopsy. Less common salivary, hepatobiliary, pancreatic and intestinal interventions are also described.