Liver transplantation as a potentially lifesaving measure in neuroblastoma stage 4S

Neuroblastoma (NBL) stage 4s is an incompletely understood phenomenon with variable clinical course. While the majority of patients may undergo spontaneous regression and achieve complete resolution without intensive therapy, a small proportion is at increased risk of developing secondary complications. One such situation is liver insufficiency due to diffuse metastases. We report a patient suffering from NBL 4S who required double lifesaving liver transplantation. Abdominal and respiratory complications due to hepatomegaly are crucial determinants for treatment intensity and duration in 4S NBL [1,2]. We provide an algorithm in order to facilitate the clinical decision when dealing with similar potentially life-threatening events

Contrast Enhanced Transabdominal Ultrasound in the Characterisation of Pancreatic Lesions with Cystic Appearance

Context Contrast enhanced ultrasound (CEUS) has been established for detection and characterisation of liver tumours and differential diagnosis of solid pancreatic lesions. The role of transabdominal CEUS in cystic pancreatic disease is less obvious. Objective We prospectively evaluated CEUS for characterization of undetermined cystic pancreatic lesions with respect to the differential diagnosis of pseudocysts and cystic neoplasia and differentiation between benign and malignant disease (gold standard: histology or cytology). Patients One-hundred and fourteen patients (63 males, 51 females; median age: 62 years, range: 33-87 years) were prospectively examined. Investigations Conventional B-mode and transabdominal CEUS. Main outcome measures Conventional B-mode (criteria: solid nodules, septae), and contrast enhancing features of cystic pancreatic lesions (microperfusion of solid nodules) were analysed. Final diagnoses were made by surgery (47 patients) or histology/cytology and follow-up of at least one year (67 patients). Results Fifty patients proved to have neoplastic lesions (37 malignant, 13 of benign origin). Sixty-four patients had pseudocysts caused by acute (27 patients) or chronic pancreatitis (37 patients). Conventional B-mode had a sensitivity of 94% and a low specificity of 44% in the differentiation of pseudocysts versus neoplasia. CEUS had a higher specificity of 77% with the same sensitivity of conventional B-mode ultrasound. The combination of conventional ultrasound and CEUS improved the specificity even more to 97% with an unchanged sensitivity. CEUS was not reliable in the differentiation of benign and malignant neoplasia. Conclusion CEUS improves the differentiation between pseudocysts and pancreatic neoplasia in comparison to the conventional B-mode imaging. The microvascularisation visualised using CEUS even in small nodules (with or without septae) associated with cystic lesions is an indicator for cystic pancreatic neoplasia.Image: CEUS in a patient with mucinous cystadenoma

Supervised median neural gas

Hammer B, Hasenfuss A, Schleif F-M, Villmann T. Supervised median neural gas. In: Dagli C, Buczak A, Enke D, Embrechts A, Ersoy O, eds. Smart Engineering System Design. Intelligent Engineering Systems Through Artificial Neural Networks, 16. ASME Press; 2006: 623-633

Deregulation of Aurora kinase gene expression in human testicular germ cell tumours.

International audienceThe Aurora kinases regulate chromosome segregation and cytokinesis, and alterations in their expression associate with cell malignant transformation. In this study, we demonstrated by qRT-PCR analysis of 14 seminomas that Aurora-A mRNA was, with respect to control tissues, augmented in five of 14 tumour tissues by 2.17 +/- 0.30 fold (P < 0.05) and reduced in 9 to 0.38 +/- 0.10 (P < 0.01). Aurora-B mRNA was increased in 11 tumour tissues by 4.33 +/- 0.82 fold (P < 0.01) and reduced in 3 to 0.41 +/- 0.11 fold. Aurora-C mRNA was reduced to 0.20 +/- 0.32 fold (P < 0.01) in 13 seminomas and up-regulated in one case. Western blot experiments, performed on protein extracts of nine seminomas and six normal testes, showed an up-regulation of Aurora-B protein by 10.14 +/- 3.51 fold (P < 0.05), while Aurora-A protein was found increased in four seminomas by 2.16 +/- 0.43 (P < 0.05), unchanged in three and reduced in two tumour tissues. Aurora-C protein was increased by 9.2 +/- 2.90 fold (P < 0.05), suggesting that post-transcriptional mechanisms modulate its expression. In conclusion, we demonstrated that expression of Aurora kinases is deregulated in seminomas, suggesting that they may play a role in the progression of testicular cancers

∆4-3-oxo-5β-reductase deficiency: favorable outcome in 16 patients treated with cholic acid

Abstract Background Oral cholic acid therapy is an effective therapy in children with primary bile acid synthesis deficiencies. Most reported patients with this treatment have 3β-hydroxy-Δ5-C27-steroid oxidoreductase deficiency. The aim of the study was the evaluation of cholic acid therapy in a cohort of patients with the rarer Δ4-3-oxosteroid 5β-reductase (Δ4-3-oxo-R) deficiency. Methods Sixteen patients with Δ4-3-oxo-R deficiency confirmed by AKR1D1 gene sequencing who received oral cholic acid were retrospectively analyzed. Results First symptoms were reported early in life (median 2 months of age), with 14 and 3 patients having cholestatic jaundice and severe bleeding respectively. Fifteen patients received ursodeoxycholic acid before diagnosis, with partial improvement in 8 patients. Four patients had liver failure at the time of cholic acid initiation. All 16 patients received cholic acid from a median age of 8.1 months (range 3.1–159) and serum liver tests normalized in all within 6–12 months of treatment. After a median cholic acid therapy of 4.5 years (range 1.1–24), all patients were alive with their native liver. Median daily cholic acid dose at last follow-up was 8.3 mg/kg of body weight. All patients, but one, had normal physical examination and all had normal serum liver tests. Fibrosis, evaluated using liver biopsy (n = 4) or liver elastography (n = 9), had stabilized or improved. Cholic acid therapy enabled a 12-fold decrease of 3-oxo-∆4 derivatives in urine. Patients had normal growth and quality of life. The treatment was well tolerated without serious adverse events and signs of hepatotoxicity. Conclusions Oral cholic acid therapy is a safe and effective treatment for patients with Δ4-3-oxo-R deficiency

Low levels of urinary epidermal growth factor predict chronic kidney disease progression in children

Urinary epidermal growth factor (uEGF) has recently been identified as a promising biomarker of chronic kidney disease (CKD) progression in adults with glomerular disease. Low levels of uEGF predict CKD progression and appear to reflect the extent of tubulointerstitial damage. We investigated the relevance of uEGF in pediatric CKD. We performed a post hoc analysis of the Cardiovascular Comorbidity in Children with CKD (4C) study, which prospectively follows children aged 6-17 years with baseline estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1.73 m(2). uEGF levels were measured in archived urine collected within 6 months of enrollment. Congenital abnormalities of the kidney and urinary tract were the most common cause of CKD, with glomerular diseases accounting for <10% of cases. Median eGFR at baseline was 28 ml/min/1.73 m(2), and 288 of 623 participants (46.3%) reached the composite endpoint of CKD progression (50% eGFR loss, eGFR < 10 ml/min/1.73 m(2), or initiation of renal replacement therapy). In a Cox proportional hazards model, higher uEGF/Cr was associated with a decreased risk of CKD progression (HR 0.76; 95% CI 0.69-0.84) independent of age, sex, baseline eGFR, primary kidney disease, proteinuria, and systolic blood pressure. The addition of uEGF/Cr to a model containing these variables resulted in a significant improvement in C-statistics, indicating better prediction of the 1-, 2- and 3-year risk of CKD progression. External validation in a prospective cohort of 222 children with CKD demonstrated comparable results. Thus, uEGF may be a useful biomarker to predict CKD progression in children with CKD