Stereotactic radiofrequency ablation of a variety of liver masses in children.

BACKGROUND AND AIMS: Surgical resection is currently the cornerstone of liver tumor treatment in children. In adults radiofrequency ablation (RFA) is an established minimally invasive treatment option for small focal liver tumors. Multiprobe stereotactic RFA (SRFA) with intraoperative image fusion to confirm ablation margins allows treatment for large lesions. We describe our experience with SRFA in children with liver masses. METHODS: SRFA was performed in 10 patients with a median age of 14 years (range 0.5-17.0 years) suffering from liver adenoma (n = 3), hepatocellular carcinoma (n = 1), hepatoblastoma (n = 2), myofibroblastic tumor (n = 1), hepatic metastases of extrahepatic tumors (n = 2) and infiltrative hepatic cysts associated with alveolar echinococcosis (n = 1). Overall, 15 lesions with a mean lesion size of 2.6 cm (range 0.7-9.5 cm) were treated in 11 sessions. RESULTS: The technical success rate was 100%, as was the survival rate. No transient adverse effects higher than grade II (Clavien and Dindo) were encountered after interventions. The median hospital stay was 5 d (range 2-33 d). In two patients who subsequently underwent transplant hepatectomy complete ablation was histologically confirmed. Follow-up imaging studies (median 55 months, range 18-129 months) revealed no local or distant recurrence of disease in any patient. CONCLUSIONS: SRFA is an effective minimal-invasive treatment option in pediatric patients with liver tumors of different etiologies.

Connatal Urinary Ascites in a Female Preterm.

BACKGROUND: Connatal urinary ascites is rare in females without associated malformations and occurs following bladder rupture. CASE PRESENTATION: A female very preterm was delivered by caesarean section because of abnormal Doppler findings. The mother suffered from viral pneumonia requiring intensive care in the third trimester of pregnancy. Serial fetal ultrasound examinations showed a megacystis and ascites. Postnatally, pronounced isolated ascites was drained and its urinary nature was confirmed. The bladder leak was demonstrated when blue dye, instilled via a Foley catheter, appeared in the ascitic drain. After removal of the catheter spontaneous micturition was unremarkable. A micturating cystourethrogram showed spontaneous closure of the bladder leak. CONCLUSION: The female infant experienced fetal bladder rupture and connatal urinary ascites due to maternal pneumonia and intensive care. The use of blue dye is an effective alternative method to any contrast media radiography and should be considered, especially in very preterm infants.

Novel deletion in 11p15.5 imprinting center region 1 in a patient with Beckwith-Wiedemann syndrome provides insight into distal enhancer regulation and tumorigenesis.

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an early-onset overgrowth disorder with a high risk for embryonal tumors. It is mainly caused by dysregulation of imprinted genes on chromosome 11p15.5; however, the driving forces in the development of tumors are not fully understood. PROCEDURE: We report on a female patient presenting with macrosomia, macroglossia, organomegaly and extensive bilateral nephroblastomatosis. Adjuvant chemotherapy was initiated; however, the patient developed hepatoblastoma and Wilms tumor at 5 and 12 months of age, respectively. Subsequent radiofrequency ablation of the liver tumor and partial nephrectomy followed by consolidation therapy achieved complete remission. RESULTS: Molecular genetic analysis revealed a maternally derived large deletion of the complete H19-differentially methylated region (H19-DMR; imprinting control region-1 [ICR1]), the whole H19 gene itself as well as large parts of the distal enhancer region within the imprinting cluster-1 (IC1). Extended analysis showed highly elevated insulin-like growth factor 2 (IGF2) expression, possibly explaining at least in part the distinct BWS features and tumor manifestations. CONCLUSIONS: This study of a large maternal deletion encompassing the H19 gene and complete ICR1 is the first to demonstrate transcriptional consequences on IGF2 in addition to methylation effects resulting in severe overgrowth and occurrence of multiple tumors in a BWS patient. Studying this deletion helps to clarify the complex molecular processes involved in BWS and provides further insight into tumorigenesis.

Bisphosphonates in multicentric osteolysis, nodulosis and arthropathy (MONA) spectrum disorder - an alternative therapeutic approach.

Multicentric osteolysis, nodulosis and arthropathy (MONA) spectrum disorder is a rare inherited progressive skeletal disorder caused by mutations in the matrix metalloproteinase 2 (MMP2) gene. Treatment options are limited. Herein we present successful bisphosphonate therapy in three affected patients. Patients were treated with bisphosphonates (either pamidronate or zoledronate) for different time periods. The following outcome variables were assessed: skeletal pain, range of motion, bone densitometry, internal medical problems as well as neurocognitive function. Skeletal pain was dramatically reduced in all patients soon after initiation of therapy and bone mineral density increased. Range of motion did not significantly improve. One patient is still able to walk with aids at the age of 14 years. Neurocognitive development was normal in all patients. Bisphosphonate therapy was effective especially in controlling skeletal pain in MONA spectrum disorder. Early initiation of treatment seems to be particularly important in order to achieve the best possible outcome.

Case report of a central venous access device-associated thrombosis with aortic embolism in a preterm infant.

BACKGROUND: Thrombosis in neonates is commonly a central venous access device (CVAD) associated complication. Furthermore, a patent foramen ovale (PFO) is frequently seen in preterm infants. Even though a coincidence of both is not unusual, detaching of the thrombus and organisation of an aortic embolism has not been described until now. Treatment recommendations of CVAD-associated thrombosis in neonates do not consider frequently seen complications of preterm infants e.g. intraventricular haemorrhage. This is the first case of a very preterm infant with pre-existing intraventricular haemorrhage, who developed a CVAD-associated thrombosis and thromboembolic complications. CASE PRESENTATION: The authors report on a very preterm girl with a pre-existing intraventricular haemorrhage and a CVAD-associated thrombus that, after removal of the CVAD, led to assumed pulmonary embolism and to an extended aortic embolism with consequent cerebral stroke. The girl was treated with unfractionated heparin (UFH) for about 50 days. During the further in-hospital stay the girl developed a mild bronchopulmonary dysplasia. Follow-up revealed clinical signs of cerebral palsy. CONCLUSION: Even though preterm infants are often diagnosed with a PFO which constitutes the risk for paradoxical embolism, such complications do not occur frequently due to the physiological heart pressure proportion. Nevertheless, it is important to monitor vital parameters and cerebral perfusion after removing a CVAD with confirmed associated thrombosis, because thromboembolic complications are possible. If practicable, patients with a confirmed CVAD-associated thrombosis should be anticoagulated before removing the CVAD. However, in our patient it was rational to remove the CVAD without prior anticoagulation due to the pre-existing intraventricular haemorrhage. There are various treatment recommendations for thrombosis or embolism in infants. However, there are no clear recommendations in very preterm infants with a high risk of cerebral bleeding respectively a pre-existing intraventricular haemorrhage. We decided to treat our patient with unfractionated heparin until the affected vessels were recanalised. Finally, it remains a case-by-case decision how to treat CVAD-associated thrombosis and consequent embolism depending on the patient's medical history.

Needle detachment in a slim and physically active child with insulin pump treatment.

Insulin pump therapy (CSII) is well established in pediatric patients with type 1 diabetes. In childhood diabetes, insulin pump treatment shows considerable advantages such as fewer injections, increased flexibility, fewer hypoglycemic events and lower HbA1c levels. Side effects such as catheter obstruction, technical pump failure, and dermatological complications have been observed, but are rarely reported. The reported patient is a physically very active and slim 10-year-old boy with reduced subcutaneous fatty tissue. After strong muscular activity an accidental rupture of the infusion set and needle detachment occurred in October 2013. X-ray and ultrasound imaging localized the needle in the musculus rectus femoris dexter. The needle was kept in situ and oral antibiotic treatment to prevent inflammatory reaction was prescribed. Repeated ultrasound measurements documented that the needles position had remained unchanged. Steel needle catheters (Sure-T infusion set, 6 mm) positioned in a thin layer of subcutaneous fat tissue of the thigh, combined with intense sports activity can result in a needle rupture and penetration into the muscle. Careful monitoring provides an alternative to surgery and lowers the risk of muscular necrosis. Because of differences in the distribution of subcutaneous fat tissue, an individualized catheter selection is necessary in pump treatment for children and adolescents, requiring a variety of different catheter sets.

ALG8-CDG: novel patients and review of the literature.

BACKGROUND: Since 1980, about 100 types of congenital disorders of glycosylation (CDG) have been reported representing an expanding group of inherited disorders. ALG8-CDG (= CDG-Ih) is one of the less frequently reported types of CDG, maybe due to its severe multi-organ involvement with coagulation disturbances, edema, massive gastrointestinal protein loosing enteropathy, cataracts, and often early death. We report three additional patients, provide an update on two previously reported, and summarize features of ten patients reported in literature. RESULTS: Of 15 ALG8-CDG patients, three were homozygous and 12 compound heterozygous. There were multiple prenatal abnormalities in 6/12 patients. In 13/15, there were symptoms at birth, 9/15 died within 12 months. Birth weight was appropriate in 11/12, only one was small for gestational age. Prematurity was reported in 7/12. Hydrops fetalis was noticed in 3, edemas in 11/13; gastrointestinal symptoms in 9/14; structural brain pathology, psychomental retardation, seizures, ataxia in 12/13, muscle hypotonia in 13/14. Common dysmorphic signs were: low set ears, macroglossia, hypertelorism, pes equinovarus, campto- and brachydactyly (13/15). In 10/11, there was coagulopathy, in 8/11 elevated transaminases; thrombocytopenia was present in 9/9. Eye involvement was reported in 9/14. CDG typical skin involvement was reported in 8/13. CONCLUSION: In ALG8-CDG, isoelectric focusing of transferrin in serum or plasma shows an abnormal sialotransferrin pattern. The diagnosis is confirmed by mutation analysis in ALG8; all patients reported so far had point mutations or small deletions. The prognosis is generally poor. Thus, a timely and correct diagnosis is important for counselling.

A new mutation in the KINDLIN-3 gene ablates integrin-dependent leukocyte, platelet, and osteoclast function in a patient with leukocyte adhesion deficiency-III.

Disabling mutations in integrin-mediated cell signaling have been a major focus of interest over the last decade for patients affected with leukocyte adhesion deficiency-III (LAD-III). In this study, we identified a new C>T point mutation in exon 13 in the FERMT3 gene in an infant diagnosed with LAD-III and showed that KINDLIN-3 expression is required for platelet aggregation and leukocyte function, but also osteoclast-mediated bone resorption. After allogeneic bone marrow transplant, all overt symptoms disappeared. This newly identified mutation along with its novel role in dysregulation of bone homeostasis extends our understanding of KINDLIN-3 in humans.

Musculoskeletal ultrasound in childhood.

Ultrasonography is one of the first line imaging modalities for the evaluation of musculoskeletal disorders in children. This article provides an overview of the most important pathologic entities in which ultrasonography significantly contributes to the diagnostic workup.

Stereotactic radiofrequency ablation for liver tumors in inherited metabolic disorders.

PURPOSE: Both glycogen storage disease type Ia (GSD Ia) and tyrosinemia type I (TYR I) are inherited metabolic disorders that can be complicated by formation of liver adenomas in juvenile/young adult age and/or development of hepatocellular carcinoma. We describe the first application of stereotactic radiofrequency ablation (SRFA) in focal lesions in three patients with inherited metabolic disorders affecting the liver. METHODS: SRFA was applied for removal of single large liver adenomas in a 22-year-old woman and a 20-year-old man with GSD Ia and of a suspicious lesion in a 16-year-old girl with TYR I with α-fetoprotein (AFP) elevation. RESULTS: SRFA was successful. Large scars were avoided, and in the TYR I patient, elevated AFP values promptly returned to normal. CONCLUSION: The SRFA technique is a good alternative to surgical resection of focal liver lesions and could greatly help patients with inherited metabolic disorders with liver involvement, including focal liver lesions and potential malignancy.

The diagnosis and management of patients with idiopathic osteolysis.

Idiopathic osteolysis or disappearing bone disease is a condition characterized by the spontaneous onset of rapid destruction and resorption of a single bone or multiple bones. Disappearing bone disorder is a disease of several diagnostic types. We are presenting three patients with osteolysis who have different underlying pathological features. Detailed phenotypic assessment, radiologic and CT scanning, and histological and genetic testing were the baseline diagnostic tools utilized for diagnosis of each osteolysis syndrome. The first patient was found to have Gorham-Stout syndrome (non-heritable). The complete destruction of pelvic bones associated with aggressive upward extension to adjacent bones (vertebral column and skull base) was notable and skeletal angiomatosis was detected. The second patient showed severe and aggressive non-hereditary multicentric osteolysis with bilateral destruction of the hip bones and the tarsal bones as well as a congenital unilateral solitary kidney and nephropathy. The third patient was phenotypically and genotypically compatible with Winchester syndrome resulting in multicentric osteolysis (autosomal recessive). Proven mutation of the (MMP2-Gen) was detected in this third patient that was associated with 3MCC deficiency (3-Methylcrontonyl CoA Carboxylase deficiency). The correct diagnoses in our 3 patients required the exclusion of malignant osteoclastic tumours, inflammatory disorders of bone, vascular disease, and neurogenic arthropathies using history, physical exam, and appropriate testing and imaging. This review demonstrates how to evaluate and treat these complex and difficult patients. Lastly, we described the various management procedures and treatments utilized for these patients.

Uterus didelphys with unilateral vaginal atresia: multicystic dysplastic kidney is the precursor of "renal agenesis" and the key to early diagnosis of this genital anomaly.

BACKGROUND: Uterus didelphys with obstructed hemivagina (UDWOH) and ipsilateral renal agenesis is a distinct but rare entity. OBJECTIVE: To demonstrate the association between UDWOH and a multicystic dysplastic kidney (MCDK) in neonates. To demonstrate the usefulness of sonography with vaginal fluid instillation in the early and reliable diagnosis of this genital anomaly in girls with MCDK. MATERIALS AND METHODS: Our patients were five female neonates with a MCDK, which had been detected in utero. We performed sonography of the internal genitalia in all patients before and after filling the vagina with saline. RESULTS: In all five girls, sonographic examination revealed uterus didelphys with obstruction of the vagina ipsilateral to the MCDK. In three girls, a dilated ureter originating from the MCDK and extending to the level of the vagina could be clearly demonstrated, with one of these including the ureteric insertion into the atretic vagina. CONCLUSION: MCDK is key to the early diagnosis of UDWOH and will facilitate the provision of appropriate treatment. The neonatal period provides a unique opportunity for detecting uterine anomalies by sonography. An MCDK usually involutes and eventually mimics renal agenesis later in life.

Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature.

We studied ten individuals from eight families showing features consistent with the immuno-osseous dysplasia spondyloenchondrodysplasia. Of particular note was the diverse spectrum of autoimmune phenotypes observed in these individuals (cases), including systemic lupus erythematosus, Sjögren's syndrome, hemolytic anemia, thrombocytopenia, hypothyroidism, inflammatory myositis, Raynaud's disease and vitiligo. Haplotype data indicated the disease gene to be on chromosome 19p13, and linkage analysis yielded a combined multipoint log(10) odds (LOD) score of 3.6. Sequencing of ACP5, encoding tartrate-resistant acid phosphatase, identified biallelic mutations in each of the cases studied, and in vivo testing confirmed a loss of expressed protein. All eight cases assayed showed elevated serum interferon alpha activity, and gene expression profiling in whole blood defined a type I interferon signature. Our findings reveal a previously unrecognized link between tartrate-resistant acid phosphatase activity and interferon metabolism and highlight the importance of type I interferon in the genesis of autoimmunity.

Segmental bowel-wall thickening on abdominal ultrasonography: an additional diagnostic sign in Kawasaki disease.

Abdominal complaints are a frequent early feature of Kawasaki disease, an acute systemic febrile vasculitis of childhood. The only well known correlating morphological finding on abdominal US is gallbladder hydrops. We report two boys with Kawasaki disease who showed segmental thickening of the small-bowel wall on abdominal US. These changes are thought to result from bowel-wall oedema due to vasculitis of the supplying vessels. We conclude that in an acutely ill febrile child with the finding of segmental bowel-wall thickening on abdominal US, Kawasaki disease should be considered in the differential diagnosis. The search for gallbladder hydrops and segmental bowel-wall thickening on abdominal US may serve as an important diagnostic tool in Kawasaki disease, supporting early recognition and prompt treatment.

Pure esophageal atresia with normal outer appearance: case report.

Isolated esophageal atresia is characterized by a long segment between the 2 esophageal pouches. This article presents a case of pure esophageal atresia with a 1-cm-long segment at the midportion without discontinuity that resembled the subtype II3 according to the Kluth atlas. Resection of the atretic segment and primary anastomosis were performed successfully.

Imaging the neonatal heart--essentials for the radiologist.

Modern radiological imaging provides precise diagnosis in congenital heart disease (CHD). The most important and readily available radiological examination is still chest radiography. The diagnostically most important imaging method is echocardiography. Magnetic resonance imaging and computed tomography have gained much ground over the more invasive cardiac catheter angiography, which is still needed in more complex conditions and for interventional procedures, which are performed more frequently. This article is focused on imaging of the neonatal heart. Basically, characteristics of the chest radiograph in CHD are illustrated. To establish an understanding of CHD haemodynamics are reviewed. It is not the role of the radiologist to make a detailed anatomic or physiologic diagnosis on the basis of a plain film, but the radiologist should be aware of changes in a neonatal chest X-ray that CHD can cause and should point out that the child might have CHD thus initiating further work-up.

Fluid-debris level in follicular cysts: a pathognomonic sign of ovarian torsion.

BACKGROUND: Early diagnosis of ovarian torsion is mandatory to avoid common complications. Sonography is the imaging modality of choice, but diagnosis is still a challenge. OBJECTIVE: To report an additional sonographic feature of ovarian torsion in order to improve diagnostic accuracy. MATERIALS AND METHODS: Grey-scale and colour Doppler pelvic sonography was performed in 12 patients with acute onset of intermittent lower abdominal pain and in 1 asymptomatic patient with a palpable mass in the labium majus. Patient ages ranged from 4 months to 17 years. RESULTS: In all patients an enlarged ovary with peripheral cysts was demonstrated. High-resolution sonography detected fluid-debris levels within these cystic structures in 11 of the 13 patients (sensitivity 85%) and provided an additional diagnostic sign. Six patients had cystic teratoma. CONCLUSIONS: We confirm the fluid-debris level as a pathognomonic sonographic sign of ovarian torsion with or without associated teratoma.