[Challenges for Urologists in the Care of Patients with Lynch Syndrome: Example of A Patient with Muir-Torre Syndrome, A Subtype of Lynch Syndrome]. / Herausforderungen für den Urologen in der Betreuung von Patienten mit Lynch-Syndrom am Beispiel eines Patienten mit Muir Torre-Syndrom als Unterform des Lynch-Syndroms.

The Muir-Torre syndrome (MTS) is a subtype of the Lynch syndrome (hereditary nonpolyposis colorectal cancer). In addition to tumours typically related to LS, MTS is associated with tumours of the sebaceous gland or keratoacanthoma. MTS is mostly characterised by a mutation of MSH2. In contrast to LS-associated tumours carrying a mutation of MLH1, MSH6 or PMS2, the frequency of urological neoplasms seems to be higher in Lynch syndrome patients with MSH2 mutation. Urological implications for the care of patients with LS or MTS include the early diagnosis of a possible hereditary background in patients presenting with urothelial cancers at an atypically young age and potentially the surveillance of carriers of mutations with an increased risk for urothelial cancers like males harbouring a MSH2 mutation. We report on a patient with various types of LS-associated cancers and cancers without a known association with LS, who died from multifocal metastasis of urothelial cancer. This case report shows that close interdisciplinary cooperation is mandatory for the treatment of patients with complex diseases.

[Vena cava cement embolism after percutaneous kyphoplasty. Interventional radiological recovery in metastasized urothelial cancer]. / Intracavaler Zementzapfen nach Kyphoplastie. Interventionell-radiologische Bergung bei metastasiertem Urothelkarzinom.

For patients suffering from vertebral metastases vertebroplasty and kyphoplasty offer two relatively new treatment options for the stabilization of vertebral compression fractures. This can help to reduce the fracture-associated symptoms and can improve the quality of life. Cement extravasation is a specific complication of this therapy. This article reports a case of multiple cement paravasations in the paravertebral veins, the vena cava inferior and peripheral segmental and subsegmental pumonary arteries after kyphoplasty of an extensive pathological vertebral body fracture in a 64-year-old man suffering from metastatic urothelial cancer.

Prognostic aspects, survival rate, and predisposing risk factors in patients with Fournier's gangrene and necrotizing soft tissue infections: evaluation of clinical outcome of 55 patients.

OBJECTIVE: To determine predisposing or prognostic factors and mortality rates of patients with Fournier's gangrene compared to other necrotizing soft tissue infections (NSTI). MATERIAL AND METHODS: Data of 55 intensive care patients (1981-2010) with NSTI were evaluated. Data were collected prospectively. RESULTS: 43.4% of the patients were in septic condition and 27.3% were hemodynamically unstable. Half of the patients showed predisposing factors (52.7%). The lower extremity (63.2%), abdomen (30.9%), and perineum (14.5%) were most affected. Polymicrobial infections were frequent (65.5%, mean 2.8, range: 1-4). The mortality rate was 16.4% (n = 9). An increase was shown for diabetes mellitus (20%), cardiac insufficiency (22.3%), septic condition at presentation (33.3%), abdominal affection (47.1%), and hemodynamic instability (46.7%). Comparing survivors and nonsurvivors, statistical significance was seen with age (p < 0.001), septic condition at admission (p < 0.001), hemodynamic instability (p < 0.001), low blood pressure (p < 0.001), and abdominal affection (p < 0.001). In laboratory findings, an increase of creatine kinase (p < 0.001) and lactate (p < 0.001) and a decrease of antithrombin III (p < 0.007) and the Quick value (p < 0.01) proved to be significant. CONCLUSION: Patients with Fournier's gangrene do not differ in all aspects from those with other NSTI. Successful treatment consists of immediate surgical debridement, broad-spectrum antibiotic treatment, and critical care management. Supportive hyperbaric oxygen therapy should be considered.

[Value of targeted treatment for testicular cancer: from molecular approaches to clinical possibilities]. / Der Stellenwert der Targeted-Therapie beim Hodentumor: Von molekularen Ansätzen zu klinischen Möglichkeiten.

Due to the introduction of tyrosine kinase-inhibitors in the treatment of metastatic renal cell cancer, targeted therapy raises hopes for other urological tumors as well. Even if excellent cure rates, achieved by standardization of diagnosis und therapy, have made testicular cancer a curable disease, up to 6% of young patients still die from tumors refractory to therapy. The quality of life of patients in advanced stages needing aggressive treatment should be improved by new therapies with reduced side effects. The role of tyrosine kinase inhibitors and angiogenesis inhibitors as well as intervention in the cell cycle and induction of apoptosis are discussed.

[Urological problems in patients with meningomyelocele. Diagnostic studies and management]. / Urologischer Erkrankungen bei Patienten mit Meningomyelozele. Diagnostik und Management.

Since the 1980s the management of children and adolescents with meningomyelocele has undergone major changes. The introduction of pharmacotherapy with antimuscarinic agents, clean intermittent catheterization (CIC) and antibacterial prophylaxis has revolutionized the management of children with neurogenic bladder. The co-operation between neonatologists, neurosurgeons, paediatric neurologists, paediatricians, paediatric urologists, paediatric nephrologists, paediatric orthopaedists and paediatric surgeons is necessary to achieve an optimized therapy in each individual patient. In this interdisciplinary consensus paper we provide definitions and classifications as well as a timetable for the appropriate investigations. The conservative and surgical options are explained in detail. A short review is given concerning orthopaedic management, incidence of latex allergy, options for bowel management, diagnosis and treatment of urinary tract infections, problems with sexuality and fertility as well as the long-term compliance of these patients and their relatives.

[Sclerosing Sertoli cell tumor of the testis: a rare tumor. Case report and review of the literature on the subtypes of Sertoli-cell tumor]. / Sklerosierender Sertoli-Zell-Tumor des Hodens - ein seltener Tumor : Fallvorstellung und Literaturübersicht über die Subtypen des Sertoli-Zell-Tumors.

Sertoli cell tumors of the testis are extremely rare (0.4-1.5% of all testicular neoplasms) and have a heterogeneous pathology. Histopathologically classic, large cell calcifying and sclerosing subtypes are differentiated.Up to now, 14 cases of sclerosing Sertoli cell tumor are known. This article presents a new case and compares the three subtypes. The subtypes differ in particular in age of onset, malignant potential, prognosis, and therapy. While no cases of sclerosing Sertoli cell tumor with a malignant course have been reported, both other subtypes have been found to be potentially malignant. In the case of malignancy the prognosis is very poor, and it is difficult to select the best treatment because there is so little experience with this type of tumor. Once the diagnosis of a Sertoli cell tumor has been confirmed, exact determination of the histological subtype is essential to allow appropriate risk-adapted therapy. The various histological subtypes are presented with the clinical features, prognosis and treatment of each.

Metanephric adenoma of the kidney: case report and review of the literature.

Metanephric adenoma is a rare tumor of the kidney. So far metanephric adenomas were considered to be benign, slowly growing and non-metastasizing tumors with an excellent prognosis. Only recently two cases of metastasized metanephric adenomas were published. Therefore, diagnostic work up, therapy and follow up of this tumor have to be reassessed. We report the case of a 42 year old male with metanephric adenoma. Current literature concerning metanephric adenoma is reviewed.

Apoptosis in non-tumorous adult human testis tissue. Comparison of so-called 'normal' testis tissues.

INTRODUCTION: Apoptosis seems to play an important role in tumorigenesis, prognosis and therapy of testicular tumors. To understand its biological significance, it is important to quantify the amount of apoptosis and to compare the rate of apoptosis to that of a normal, unaffected reference tissue. Usually tissue from the unaffected site of the testis in patients with testicular cancer or testis tissue from patients who underwent surgical castration due to prostate cancer is used as the reference tissue. However it is not known, if both tissues are equivocal with respect to their apoptotic index. The purpose of the study was to compare the two most often used reference tissues for the quantification of apoptosis in testicular tissues with regard to their apoptotic index. MATERIALS AND METHODS: The apoptotic indices of both tissues were compared, using two standard apoptosis detection methods, i.e. in situ end labeling and a morphological approach. RESULTS: The apoptotic index in testis tissue from patients who were surgically castrated for anti-hormonal treatment of prostate cancer was shown to be significantly higher than the apoptotic index of tumor free but tumor-associated testicular tissue of testis cancer patients. There was a strong relationship between the apoptotic index and the age of the patients. CONCLUSION: Although there might be genetic changes in the tumor-associated testicular tissue influencing the apoptotic index, it seems advisable to use tumor-associated tissue rather than testis tissue of patients with prostate cancer as the reference tissue, due to the significant age dependence of the apoptotic index.

Gene expression profiling in seminoma and nonseminoma.

PURPOSE: Gene expression profiles of seminoma were compared with nonseminoma to get insights into tumorigenesis. MATERIALS AND METHODS: Eleven testicular tumor biopsies (five pure seminoma, six nonseminoma; pT1N0M0 to pT2N2M1) and biopsies from unaffected sites were analyzed once per patient using a macroarray (1,176 genes). On the same patients, six genes were validated using real-time quantitative (RTQ) polymerase chain reaction (PCR). Additionally, in a separate cohort of 19 patients, 24 genes selected from the macroarray were measured using RTQ-PCR. RESULTS: (1) The agreement in gene expression was 94% between the two methods and two different patient cohorts. (2) Two features in gene expression were independent of the tumor entity: Most changes of gene expression occurred in five functional groups like "cell cycle" and "apoptosis." Genes within these groups were almost similarly (> 80%) up- or downregulated. (3) Nonseminoma were characterized by downregulated genes (75%), but in seminoma, upregulated genes (64%) prevailed. Furthermore, 64.4% of those genes that were differentially expressed in both tumor entities were usually upregulated in seminoma but downregulated in nonseminoma. A reverse pattern was found in 24.4% of such genes. Eleven percent of these genes showed a similar up- or downregulation in gene expression in both tumor entities. CONCLUSION: Seminoma in this preliminary study can be differentiated from nonseminoma due to almost opposing gene expression profiles (89% of the significantly differentially expressed genes) and are in line with the histological discrimination of both tumor entities. Underlying mechanisms and implications regarding the origin and tumor progression of both entities are discussed.

[Clarification of tissue contamination in a suspected adenocarcinoma of the spermatic cord by microsatellite analysis]. / Vermeintliches Adenokarzinom des Samenstranges. Aufklärung einer Gewebekontamination mittels Mikrosatellitenanalyse.

Malignant tumors of the spermatic cord are rare with primary neoplasms being mostly sarcomas. Adenocarcinomas of the spermatic cord are found extremely seldom and are predominantly metastases of extragonadal tumors. We present an asymptomatic 47-year-old patient who was referred to our clinic after a vasectomy had been performed and the histological examination had surprisingly shown adenocarcinoma of the left spermatic cord. Extensive laboratory analysis and diagnostic imaging did not demonstrate any testicular, spermatic cord, or extragonadal tumor. To exclude a mix-up of specimens, we performed DNA analysis. Microsatellite PCR clearly demonstrated the different origins of the tumor and the vasectomy specimen. Specimen mix-up or contamination may happen in any phase of surgical or pathological processing. In any case of clinical uncertainty concerning the identity of a tissue specimen, this possibility has to be taken into consideration. Microsatellite PCR can clearly identify the origin of tissue samples even on embedded material.

Possible hemodynamic pathways of intraurethral prostaglandin-E1 (MUSE).

Intraurethral application of prostaglandin-E1 (MUSE) is a well-tolerated pharmacotherapy for erectile dysfunction. However, the physiological mechanisms of drug transfer into the cavernous bodies are not completely clear. Using spongiosography in 35 patients, our study tried to elucidate existing shunt mechanisms. The X-rays show venous drainage through the deep dorsal vein up to the plexus Santorini. The circumflex veins are also contrasted and the cavernous bodies show opacification in their distal portion only. Structures shunting directly between the corpus spongiosum and the cavernous bodies were not demonstrable. Retrograde filling of the cavernous bodies through the deep dorsal vein and its circumflex braches seems to be the most relevant way of drug transfer after intraurethral application of prostaglandin-E1. Diffusion into the cavernous bodies or a systemic mechanism of action does not seem probable.

Significance of apoptosis in metastasizing testis tumors.

Testis tumors of embryonal origin (ten metastasized, six non-metastasized) and 17 mixed testis cell carcinomas (eight metastasized, nine non-metastasized) were examined. A triple immunofluorescence microscopic labeling procedure allowed the simultaneous detection of two features of apoptosis, namely morphological changes in the nucleus (DNA condensation visualized by DAPI staining) and the process of DNA fragmentation (TdT-assay) in tumor cells as well as T-cells (recognized by their CD45RO epitope). Both methods for apoptosis detection showed similar apoptotic indices (AI) only in 2.6% of all tumors. Most tumors (81.6%) showed more cells with DNA fragments than condensed chromatin, but in a number of cases (10.5%) the opposite pattern was found. These data add to the few published in vivo examinations of apoptosis using different methods and help to explain differences in the judgment of apoptosis significance for tumor prognosis. With regard to tumorigenesis, non-metastasized testis tumors were characterized by higher AIs of tumor cells and T-cells compared with metastasized tumors, which could be interpreted as a characteristic of tumors in an earlier stage of their development into an apoptosis-resistant phenotype. For the first time, in metastasized tumors a 5 to 25-fold increase of the T-cell's AIs over the corresponding AIs of tumor cells was shown. This suggests a successful counterattack of tumor cells, thus supporting the process of metastasis. However, only ten out of 33 tumors revealed these AI changes, which again highlights that tumor biology cannot be predicted by a single parametric approach. It remains to be seen whether these characteristics might be suitable for a reliable prediction of metastasis.

[Intravesical migration of a polypropylene mesh implant 3 years after laparoscopic transperitoneal hernioplasty]. / Intravesikale Migration eines Polypropylennetzes 3 Jahre nach laparaskopischer transperitonealer Hernioplastik.

The repair of an inguinal hernia is the surgical procedure most often performed. Complication rates after laparoscopic hernioplasty amount up to 19%, with hematoma/seroma, neuralgia, urinary retention, and chronic pain most frequently reported. Significant complications such as trocar site bleeding or bowel injury occur in 0.4-5.6%, and sporadic intraoperative lesions of the bladder have been mentioned. We present a 48-year-old patient with recurrent dysuria 3 years after transabdominal preperitoneal hernioplasty (TAPP). The preoperative diagnostic evaluation led to the assumption of an intravesical mesh dislocation. In spite of extensive adhesions between the mesh and the bladder wall, the mesh including five fixation coils could be removed via a suprapubic access. The postoperative period was without complications, and the patient has no complaints. The incidence of complications after laparoscopic hernioplasty is low. Still, severe problems such as mesh rejection, spermatic granuloma, or mesh migration into the small and large intestine do occur. Migration of a mesh into the urinary bladder has only been described twice.

Apoptosis in human embryonal cell carcinoma: preliminary results.

Disorders in the regulation of apoptotic cell death may contribute to cancer. Furthermore, lymphocytes are supposed to play a role in counteracting tumorigenesis by inducing apoptosis in different human tumors. In this study, for the first time, tumor cell and lymphocyte apoptosis were investigated systematically in human embryonal cell carcinoma. DNA fragmentation and DNA condensation were measured simultaneously on double-fluorescence-labeled testis tumor sections using immunofluorescence microscopy. Different apoptotic indices (AIs), based either on biochemical (DNA fragmentation) or morphological criteria (DNA condensation) alone or on a combination of both, were determined in different histological regions in and around the tumor. Using morphological criteria alone, 40-75% of all apoptotic cells were not detected. Based on previous observations this finding might be related to subsets of apoptotic cells which induce the process of DNA condensation without activation of processes responsible for DNA fragmentation. Moreover, the AIs of tumor cells and lymphocytes were highest in the tumor region, compared with regions around the tumor and distant from it; these findings are discussed in the context of the Fas/FasL system.

Modified approach for apoptosis detection reveals changes in apoptotic processes in the seminoma-associated tissue.

Apoptosis morphology (DNA condensation) and internucleosomal DNA cleavage (TdT assay) were measured simultaneously on double fluorescence labeled testis tumor sections, employing conventional immunofluorescence microscopy. Six different apoptosis indices (Al) were determined based either solely on morphological or biochemical criteria, or on a combination of both processes. Measurements were performed in metastasized and non-metastasized seminoma, and in histological regions located distantly and associated with the tumor. Preliminary results on 19 histologies revealed that up to 66% of apoptotic cells were not detected, depending on the method used for apoptosis detection. Besides, no changes of solely morphologically defined Al was found in the different histological regions. By contrast, significant changes (p < 0.0004) in the different histological regions were detected when measuring Als, e.g., defined by DNA fragmentation occurring without DNA condensation in apoptotic cells. Those changes were not detected in metastasized seminoma. These data, for the first time allow a comparison of two widely used approaches for apoptosis detection. Furthermore, the results revealed differences in apoptotic processes in tissue associated with non-metastasized seminoma detectable by a modified evaluated TdT assay but not by morphological changes, although this TdT method fails to show the total amount fo apoptotic cells.

Intercomparison of apoptosis morphology with active DNA cleavage on single cells in vitro and on testis tumours.

Apoptosis morphology (DNA condensation) and endonucleolytical DNA cleavage (TdT assay) were measured simultaneously on double fluorescence labelled cells employing confocal laser scanning and conventional immunofluorescence microscopy. In vitro experiments on irradiated HL-60 cells revealed a high correspondence of non-apoptotic (normal) cells without detectable DNA cleavage, versus apoptotic cells and apoptotic bodies showing DNA cleavage. Experiments performed on histological slides of testis tumours reflected a heterogeneous picture: non-apoptotic (normal) cells, apoptotic cells, and apoptotic bodies appeared either with or without detectable DNA cleavage. These data allowed the characterization and quantitation of the grade of disturbance/heterogeneity of the apoptosis programme in vivo. Furthermore, the measured apoptotic index (AI) based on apoptosis morphology was lower than the AI assessed by DNA cleavage, in contrast to published work. Taken together, these methods represent a new approach and might be suitable for improved correlation with clinical parameters. In addition, the data presented confirm frequently published doubts regarding the ability of the TdT assay to detect apoptosis as defined by morphological criteria in tumours.

Role of intracellular Ca2+ stores in smooth muscle of human penile erectile tissue.

OBJECTIVE: In human erectile tissue smooth muscle contraction and detumescence are highly dependent on an increase in cytosolic [Ca2+]. The Ca2+ influx can be derived from the extracellular space or from intracellular sarcoplasmic stores. The role of both pathways was evaluated in an organ bath study on human cavernosal strips. PATIENTS AND METHODS: The tissue was obtained from 12 patients with chronic erectile dysfunction. The effects of Ca2+-free solution, ryanodine, caffeine and of nifedipine on electrically and adrenergically induced contractions were evaluated. RESULTS: Following an incubation period of 10 min in Ca2+-free solution the electrically induced contraction was reduced to 20%, whereas the contraction induced by phenylephrine (PE) was only reduced to 64 +/- 6% (mean +/- SEM). Ryanodine inhibited the PE-contraction to 30 +/- 6% and the additional application of caffeine or nifedipine further reduced the contraction to 11% and 8%. CONCLUSION: The results give evidence for a role of intracellular Ca2+-stores in human cavernosal tissue. Whether the more marked effect of ryanodine in tissue from patients with erectile failure in comparison with similar experiments in rabbit cavernosal tissue might be a sign of an increased cavernosal contractility in these patients remains to be shown in future experiments with normal erectile tissue.

[Metastatic spread of renal cell carcinoma in the area of the ethmoid and frontal sinuses]. / Metastatische Absiedelung eines Nierenzellkarzinoms im Bereich von Siebbein und Stirnhöhle.

Metastatic lesions represent 1-8% of all malignant tumors of the mouth and jaws, with rare sites of metastasis originating from different primary tumors, especially the lung and breast. The vast majority of these lesions (up to 90%) have been observed in the mandible and maxilla (5-20%). Another rare type of cancer that usually metastasizes to the lungs, lymph nodes, bones, liver or brain may occasionally also show spread to the paranasal sinuses. In the present paper we report our management of a 50-year-old male with renal cell carcinoma who developed metastases to the frontal and ethmoid sinuses.

Effect of contrast medium on corpus cavernosum smooth muscle.

RATIONALE AND OBJECTIVES: Changes in contractility of corpus cavernosum (CC) smooth muscle caused by radio contrast medium may result in misinterpretations of cavernosography used diagnostically in erectile dysfunction. METHODS: The authors investigated the direct effect of various contrast media on rabbit CC smooth muscle tissue strips in an in vitro model by adding contrast medium to the tissue in a perfusion bath and recording the resulting contractions. Glucose addition was used as control. RESULTS: Application of high-osmolar, ionic contrast medium diatrizoate-induced CC smooth muscle contractions of 57% of the control potassium chloride (124 mM) induced contractions. The low-osmolar (862 mOsm/kg) nonionic monomer contrast medium, iohexol, and the iso-osmolar (300 mOsm/kg) nonionic-dimer contrast medium, iodixanol, elicited contractions of 34% and 36% of the potassium chloride control contractions, respectively. High- and Iso-osmolar glucose solutions caused contractions of 51%, 38%, and 24% of the control, respectively. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) regulate CC smooth muscle contractions. These are influenced by different drugs including phosphodiesterases (PDEs), forskolin, and 3-morpholinsydnonimine hydrochloride (SIN-1). The nonspecific PDE inhibitors papaverine (0.1 mM) and theophylline (1 mM) reduced the contrast medium-induced contractions to 66% and 69%, respectively. The specific PDE inhibitor milrinone (0.1 mM) reduced the contractions to 69%; 0.1 mM forskolin and SIN-1 reduced the contractions to 34% and 41%, respectively. CONCLUSIONS: Contrast medium induces CC smooth muscle contractions, depending mainly on the osmolality of the solution. The contractions are reduced but not abolished by elevating the intracellular cAMP and cGMP concentrations. The clinical applications in cavernosography are discussed.