Therapy of vesico-ureteral reflux in children

The operation after Lich-Gregoir is a technically simple and successful method for the treatment of primary vesicoureteral reflux. The operation is performed extravesically without opening of the bladder and without splinting the ureter. The stay in the hospital is short

Primary melanoma of the prostate: case report and review of the literature

Background: Primary melanoma of the prostate has an extremely rare incidence. Only five cases have been reported in the literature and prognosis is poor. The most likely origin of prostatic melanoma is the transitional epithelium of the prostatic urethra. Surgical care for primary melanoma of mucosal sites is less well established than for primary cutaneous melanoma, but excision of the primary is recommended if the patient has no systemic disease. Case presentation: Here, we describe a case of primary malignant melanoma of the prostate. A 37-year-old male patient with history of both chemo- and radiation therapy for Hodgkin’s disease was admitted to the University Hospital Heidelberg on suspicion of pleomorphic sarcoma of the bladder. In-house diagnostic work-up revealed a malignant melanoma of the prostate. We then performed radical prostatectomy with extended lymphadenectomy. Despite presumably curative surgery, the patient suffered from early relapse of disease with pulmonary metastasis. Systemic chemotherapy and subsequent immuno-oncologic treatment was thereafter initiated. Conclusion: Since prostatic melanoma is a rare disease and a melanoma metastasis of unknown primary is the differential diagnosis, a multidisciplinary approach including early imaging to rule out possible metastases and to search for another potentially existing primary is advisable. To prevent complications related to local tumor progression and to receive tissue for mutational analysis, we recommend complete surgical resection to reduce the tumor mass. Novel immune and targeted oncologic therapies can lead to an improved survival in some cases and support of clinical trials is needed

Hypospadias

Objective. The great possibility of variations in the clinical presentation of hypospadia, makes its therapy challenging. This has led to the development of a number of techniques for hypospadia repair. This article assesses past and present concepts and operative techniques with the aim of broadening our understanding of this malformation. Materials and Methods. The article not only reviews hypospadia in general with its development and clinical presentation as well as historical and current concepts in hypospadiologie on the basis of available literature, but it is also based on our own clinical experience in the repair of this malformation. Results and Conclusion. The fact that there are great variations in the presentation and extent of malformations existent makes every hypospadia individual and a proposal of a universal comprehensive algorithm for hypospadia repair difficult. The Snodgrass technique has found wide popularity for the repair of distal hypospadias. As far as proximal hypospadias are concerned, their repair is more challenging because it not only involves urethroplasty, but can also, in some cases, fulfil the dimensions of a complex genital reconstruction. Due to the development of modern operating materials and an improvement in current surgical techniques, there has been a significant decrease in the complication rates. Nonetheless, there still is room and, therefore, need for further improvement in this field

Bladder inflammatory transcriptome in response to tachykinins: Neurokinin 1 receptor-dependent genes and transcription regulatory elements

Background Tachykinins (TK), such as substance P, and their neurokinin receptors which are ubiquitously expressed in the human urinary tract, represent an endogenous system regulating bladder inflammatory, immune responses, and visceral hypersensitivity. Increasing evidence correlates alterations in the TK system with urinary tract diseases such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis. However, despite promising effects in animal models, there seems to be no published clinical study showing that NK-receptor antagonists are an effective treatment of pain in general or urinary tract disorders, such as detrusor overactivity. In order to search for therapeutic targets that could block the tachykinin system, we set forth to determine the regulatory network downstream of NK1 receptor activation. First, NK1R-dependent transcripts were determined and used to query known databases for their respective transcription regulatory elements (TREs). Methods: An expression analysis was performed using urinary bladders isolated from sensitized wild type (WT) and NK1R-/- mice that were stimulated with saline, LPS, or antigen to provoke inflammation. Based on cDNA array results, NK1R-dependent genes were selected. PAINT software was used to query TRANSFAC database and to retrieve upstream TREs that were confirmed by electrophoretic mobility shift assays. Results: The regulatory network of TREs driving NK1R-dependent genes presented cRel in a central position driving 22% of all genes, followed by AP-1, NF-kappaB, v-Myb, CRE-BP1/c-Jun, USF, Pax-6, Efr-1, Egr-3, and AREB6. A comparison between NK1R-dependent and NK1R-independent genes revealed Nkx-2.5 as a unique discriminator. In the presence of NK1R, Nkx2-5 _01 was significantly correlated with 36 transcripts which included several candidates for mediating bladder development (FGF) and inflammation (PAR-3, IL-1R, IL-6, α-NGF, TSP2). In the absence of NK1R, the matrix Nkx2-5_02 had a predominant participation driving 8 transcripts, which includes those involved in cancer (EYA1, Trail, HSF1, and ELK-1), smooth-to-skeletal muscle trans-differentiation, and Z01, a tight-junction protein, expression. Electrophoretic mobility shift assays confirmed that, in the mouse urinary bladder, activation of NK1R by substance P (SP) induces both NKx-2.5 and NF-kappaB translocations. Conclusion: This is the first report describing a role for Nkx2.5 in the urinary tract. As Nkx2.5 is the unique discriminator of NK1R-modulated inflammation, it can be imagined that in the near future, new based therapies selective for controlling Nkx2.5 activity in the urinary tract may be used in the treatment in a number of bladder disorders

Newborn Screening: Review of its Impact for Cystinosis

Clinical course; Infantile nephropathic cystinosis; Newborn screeningCurso clínico; Cistinosis nefropática infantil; Cribado de recién nacidosCurs clínic; Cistinosi nefropàtica infantil; Cribratge de nounatsNewborn screening (NBS) programmes are considered to be one of the most successful secondary prevention measures in childhood to prevent or reduce morbidity and/or mortality via early disease identification and subsequent initiation of therapy. However, while many rare diseases can now be detected at an early stage using appropriate diagnostics, the introduction of a new target disease requires a detailed analysis of the entire screening process, including a robust scientific background, analytics, information technology, and logistics. In addition, ethics, financing, and the required medical measures need to be considered to allow the benefits of screening to be evaluated at a higher level than its potential harm. Infantile nephropathic cystinosis (INC) is a very rare lysosomal metabolic disorder. With the introduction of cysteamine therapy in the early 1980s and the possibility of renal replacement therapy in infancy, patients with cystinosis can now reach adulthood. Early diagnosis of cystinosis remains important as this enables initiation of cysteamine at the earliest opportunity to support renal and patient survival. Using molecular technologies, the feasibility of screening for cystinosis has been demonstrated in a pilot project. This review aims to provide insight into NBS and discuss its importance for nephropathic cystinosis using molecular technologies

Neuromuscular conditions and the impact of cystine‐depleting therapy in infantile nephropathic cystinosis: A cross‐sectional analysis of 55 patients

Infantile nephropathic cystinosis (INC) is a rare lysosomal storage disease caused by biallelic mutations in the cystinosin gene, leading to cystine accumulation in various organs. The aim of this cross-sectional study was to investigate neuromuscular complications in a cohort of 55 patients (aged 2.8-41.3 years, median 18.5 years) with INC. Clinical examination, jumping mechanography, clinical neurophysiology, and muscle/nerve ultrasound were performed. Physical performance, measured by mechanography, was below average in all patients. However, this reduction in physical performance was not always detected by conventional muscle power assessment. Twenty-eight percent of patients had mostly mild axial weakness of the neck flexors and/or of the abdominal rectus muscles, the latter often presenting during childhood. One adult patient had generalized muscle weakness. Two patients had evidence of specific neuromuscular conditions, which may not have been directly related to cystinosis. 30% of patients presented with mild, 7% with moderate, and 5% with severe weakness of the intrinsic muscles of the hand. Muscle wasting was more pronounced in the older cystinosis patients with multiple organ complications. Sonographic increase in muscle echogenicity corresponded only with severe weakness. Electromyography of the intrinsic hand muscles, performed in selected patients, showed myopathic, neurogenic, or mixed myopathic-neurogenic abnormalities. A particularly important finding of this study is that the neuromuscular complications were largely independent from both the age of initiation of pharmacological cystine-depleting therapy and from adherence to treatment. Significant correlation was observed between better physical performance in jumping and cysteine levels in leukocytes