Chronic subdural hematoma associated with voiding dysfunction.

We report the case of a 73-year-old male who presented with a chronic subdural hematoma that compressed the frontal lobe, an area known to be active in detrusor control, and caused contralateral hemiparesis and urgency incontinence. Urodynamically, he had a small bladder capacity and high amplitude overactive detrusor contractions with an intact sphincteric response. We concluded that the effect of intracranial lesions on voiding depends upon the site rather than the type of the pathology. Further in-depth studies are needed to clarify the effect of intracranial lesions, and accordingly the function of different brain regions and their influence on voiding.

Voiding dysfunction due to chronic viral encephalitis in a young woman.

We record a case of a 37-year-old female with acute viral encephalitis, frequency and urgency incontinence. Video urodynamics showed small bladder capacity, sensory urgency, high residual urine and a Christmas tree appearance of the bladder. MRI showed inflammation and edema in the area of the thalamus and internal capsule in the early stage, then cavitation and gliosis in the same regions in the late stage.

Urinary sodium dodecyl sulfate electrophoresis with silver staining: a noninvasive diagnostic tool for obstructive uropathy in children.

PURPOSE: Obstructive uropathy such as ureteropelvic junction obstruction in the newborn is a major diagnostic and therapeutic dilemma. We investigated whether urinary sodium dodecyl sulfate electrophoresis with polyacrylamide gel electrophoresis with silver staining could be used to discriminate between children requiring and those not requiring pyeloplasty. MATERIALS AND METHODS: In a pilot study we analyzed the urine of 18 children (mean age 2.7 years) with grade III or IV hydronephrosis according to the Society for Fetal Urology classification. A total of 44 healthy children were studied as controls. Children with hydronephrosis were followed using ultrasound, (99m)technetium mercaptoacetyltriglycine diuretic renography and voiding cystourethrography. Urine was obtained by spontaneous voiding and studied by sodium dodecyl sulfate polyacrylamide gel electrophoresis with silver staining using Melzer's modification. After the study period test results were compared to outcomes, ie whether patients required surgery, and to normalization of previously abnormal protein excretion patterns. RESULTS: All but 1 of the healthy controls had a normal electrophoresis assessment. Of 9 patients followed for hydronephrosis 7 had an abnormal electrophoresis result preoperatively. One child had to be operated on twice because of relapse of ureteropelvic junction obstruction. Six children returned to a normal electrophoresis result postoperatively, including the child who was operated on twice. All children with an initially normal electrophoresis assessment displayed persistent normal values, except 1. Children shifting from a normal to an abnormal electrophoresis result underwent surgery after exclusion of urinary tract infection. CONCLUSIONS: Sodium dodecyl sulfate polyacrylamide gel electrophoresis with silver staining seems to be a good predictive test for clinically relevant ureteropelvic junction obstruction. Further studies are being performed to see whether the test can stand against the gold standard, (99m)technetium mercaptoacetyltriglycine diuretic renography.

TGFbeta-1 and epithelial-mesenchymal interactions promote smooth muscle gene expression in bone marrow stromal cells: possible application in therapies for urological defects.

PURPOSE: For regenerative and cellular therapies of the urinary tract system, autologous bladder smooth muscle cells (SMCs) have several limitations, including constricted in vitro proliferation capacity and, more importantly, inability to be used in malignant conditions. The use of in vitro (pre-)differentiated multipotential adult progenitor cells may help to overcome the shortcomings associated with primary cells. METHODS: By mimicking environmental conditions of the bladder wall, we investigated in vitro effects of growth factor applications and epithelial-mesenchymal interactions on smooth muscle gene expression and on the morphological appearance of adherent bone marrow stromal cells (BMSCs). RESULTS: Transcription growth factor beta-1 (TGFbeta-1) upregulated the transcription of myogenic gene desmin and smooth muscle actin-gamma2 in cultured BMSCs. Stimulatory effects were significantly increased by coculture with urothelial cells. Prolonged stimulation times and epigenetic modifications further enhanced transcription levels, indicating a dose-response relationship. Immunocytochemical staining of in vitro-differentiated BMSCs revealed expression of myogenic protein alpha-smooth muscle actin and desmin, and changes in morphological appearance from a fusiform convex shape to a laminar flattened shape with filamentous inclusions similar to the appearance of bladder SMCs. In contrast to the TGFbeta-1 action, application of vascular endothelial growth factor (VEGF) did not affect the cells. CONCLUSIONS: The combined application of TGFbeta-1 and epithelial-mesenchymal interactions promoted in vitro outgrowth of cells with a smooth muscle-like phenotype from a selected adherent murine bone marrow-derived cell population.

[Nested-variant urothelial carcinoma. Case report and molecular aspects]. / Die Nested-Variante des Urothelkarzinoms. Fallbericht und molekulare Aspekte.

The nested variant of urothelial carcinoma is a rare urothelial neoplasia which is characterized by relatively bland morphology and early muscle-invasive growth. We report on a 65-year-old male patient with a non-invasive high-grade urothelial lesion (carcinoma in situ and pTa G3). After treatment with BCG an invasive urothelial carcinoma was discovered whereas the carcinoma in situ had disappeared. Examination of the bladder specimen showed a nested-variant urothelial carcinoma. Molecular analyses indicated a de-novo genesis of the invasive urothelial carcinoma.

[Neoadjuvant and adjuvant chemotherapy in patients with advanced penile cancer]. / Neoadjuvante und adjuvante Chemotherapie bei Patienten mit fortgeschrittenem Peniskarzinom.

With an incidence of 0.1-0.9/100,000 men per year penile cancer is a rare cancer of the urogenital tract in Western Europe. At the time of initial diagnosis up to 45% of the patients already demonstrate metastatic disease and need some type of systemic treatment. It is the aim of this paper to review the current concepts of adjuvant and neoadjuvant chemotherapy for locally advanced penile cancer. A curative effect of combined surgical and cytotoxic management can only be achieved in patients with locoregional spread to the lymph nodes, but not with systemic spread. Although there are prospective randomized trials available indicating the optimal cytotoxic regime, cisplatin-based protocols or combination therapies with bleomycin, vincristine, and methotrexate appear to be the most effective options. Finally, there are no data available with regard to the effect of adjuvant chemotherapy on progression-free survival. In patients with locoregional bulky disease or with fixed inguinal lymph nodes, neoadjuvant chemotherapy will result in a partial response in 20-60% of patients and enables complete resection of the mass. For the future, the use of taxane-based chemotherapy as described for squamous cell cancer of other origin might improve outcome.

[Options in palliative therapy for penile cancer]. / Optionen der palliativen Therapie des Peniskarzinoms.

Penile cancer, with an incidence of 0.1-0.9/100,000 males/year, is one of the least common malignant tumors. Most patients are over 50 years old and the tumor is slow growing. Therapeutic success is highly dependent on lymph node status. Cancer related death is usually due to local complications such as arrosion bleeding caused by the tumor or infected inguinal metastases. The therapy for advanced penile cancer and its complications represents a challenge. Taking into consideration quality of life, the therapeutic strategy should be based on the patient's age, his sexual function, motivation and psychological condition, as well as previous illnesses and tumor biology. Palliative therapy requires good interdisciplinary work between oncologists, radiologists, plastic surgeons, physiotherapists and psychologists.

[Magnetic stimulation of the pelvic floor in older patients. Results of a prospective analysis]. / Magnetstimulation des Beckenbodens beim älteren Menschen. Ergebnisse einer prospektiven Untersuchung.

Since 2001 magnetic stimulation therapy has been available in Germany for treating urinary incontinence as an alternative to traditional electrical stimulation therapy. The results of 83 patients who underwent magnetic stimulation therapy for stress incontinence, OAB, and pelvic pain syndrome were evaluated. The results differed depending on the underlying disease. Patients with stress incontinence who could not properly contract pelvic floor muscles before could do so in 74% when clinically evaluated and patients with OAB symptoms improved in 54% as assessed by objective and subjective criteria, whereas patients with pelvic pain syndrome only benefited in 23%. Comparison of the results according to age revealed no significant difference between patients >65 years and younger patients.

[Perineal approach to repair rectal and cutaneous fistulas involving the urethra and bladder]. / Perinealer Zugang zur Korrektur von rektalen und kutanen Fisteln zu Urethra und Blase.

The perineal approach was used in ten patients for the repair of fistulas involving the bladder or prostatic urethra. In the case of radiotherapy-induced (n=2) or recurrent fistulas (n=4) fecal diversion and interposition of the gracilis muscle was performed. In addition in three patients prostatectomy was performed. All fistulas were repaired successfully with minimal morbidity.

[Nephron-sparing therapy for renal tumors]. / Die organerhaltende Nierentumor-Therapie.

In this article up-to-date, nephron-sparing therapy for renal cell cancer such as radical tumor nephrectomy, partial resection or enucleation is summarised. The results of open and laparoscopic partial nephrectomy and tumor enucleation are presented. Problems and complications associated with the techniques are reviewed. There are as yet no randomized, controlled trials and most published studies show retrospective data. Further new alternative techniques in nephron-sparing therapy like cryosurgery and radiofrequency ablation are presented.

[Solitary peritoneal carcinomatosis in prostate cancer]. / Solitäre Peritonealkarzinose eines Prostatakarzinoms.

INTRODUCTION: Peritoneal carcinomatosis is a rare finding in metastatic prostate cancer. In the literature peritoneal carcinomatosis is usually reported in its final stages with multiple metastases. A single peritoneal carcinomatosis with no further metastases is a very rare finding. CASE REPORT: We report the case of a 75-year-old patient with initial ischuria. A prostate cancer could be confirmed and the further diagnostics showed no metastasis. In a transperitoneal approach for laparoscopic pelvic lymphadenectomy a peritoneal carcinomatosis from prostate cancer was proven. A complete antiandrogen therapy was started and PSA decreased for more than 14 months to a stable level of < 1 microg/L. CONCLUSION: An isolated peritoneal carcinomatosis from prostate cancer is a very rare finding. The complete antiandrogen therapy is effective.

[Interdisciplinary recommendations on targeted therapy in the treatment of renal cell carcinoma]. / Interdisziplinäre Therapieempfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms.

Recently, new data have been published on the treatment of metastasized renal cell cancer using targeted therapies. With the approval of the tyrosine kinase inhibitors Sunitinib and Sorafenib, two of these new therapies are now available in clinical practice. This has raised both new opportunities and new questions for the health care professionals involved. Here we report on a consensus conference addressing these questions with answers based on evidence from the recent literature.

'UroMaix' scaffolds: novel collagen matrices for application in tissue engineering of the urinary tract.

Reconstruction of bladder and ureter tissue is indicated in cases of injury, stenosis, infection or tumor. Substitution by ileum, colon or pure synthetic polymers generates a variety of complications. Biohybrid tissue mimicking structural and functional attributes of the multilayered wall architecture of the urinary conduit may be the solution to current problems. This study reports on porcine urinary tract cells isolated and placed on UroMaix matrices with different degrees of cross-linking produced from highly purified type I collagen from medically approved porcine tissue. A patented procedure revealed membrane structures composed of a dense fibrous side and an open fibrous side. These scaffolds with the porcine urinary tract cells were incubated in a batch culture system for up to 14 days. Cell growth and topographical orientation were examined. Urothelial cells showed maximum attachment and a significant increase of living cells on the dense fiber layer of UroMaix-1. No attachment of urothelial cells occurred on the other prototypes. Smooth muscle cells showed similar behavior within the open fiber layer of all UroMaix matrices. Both urothelial and smooth muscle cells retained their phenotypes as demonstrated by the immunostaining of epithelial cytokeratin 18 and the smooth muscle myosin heavy chain respectively. Thus we could show that UroMaix scaffolds support the attachment and proliferation of urinary tract cells. The elastomeric properties of the collagenous matrices promise attractive applications in the tissue engineering of the urinary tract with its high mechanical demands.

[Systemic therapy of penile cancer]. / Die systemische Therapie des Peniskarzinoms.

Penile cancer is a rare tumor in Europe with an incidence of 0.1-0.9 per 100,000 men per year. The success of our therapy is mainly influenced by the presence of lymph node metastases. At first diagnosis 17-45% of patients already harbor lymph node metastases. Bilateral inguinal and pelvic lymphadenectomy is a curative measure in these patients. In cases of gross inguinal metastases neoadjuvant chemotherapy leads to a remission rate of 21-60% and improves the resectability. The influence on survival is not proven. The same holds true for adjuvant therapy following lymphadenectomy. Polychemotherapy rarely leads to long-lasting complete remission in patients with distant metastases. The protocols consist usually of cisplatin, bleomycin, methotrexate, and 5-fluorouracil. The overall remission rate is around 15-32%. Because of the low efficacy of the present chemotherapy regimens, one should follow new strategies, comparable to those initiated for squamous cell cancer of other organs.

Modulation of pro-epidermal growth factor, pro-transforming growth factor alpha and epidermal growth factor receptor gene expression in human renal carcinomas.

We have analyzed the expression of the genes for the precursors of epidermal growth factor (pro-EGF) and transforming growth factor alpha (proTGF-alpha) as well as for the EGF receptor in tissue specimens of a large number of adult patients with renal cell carcinoma. Since normal kidney tissue was available from the same patients we could directly compare the expression of these genes in tumors with that in adjacent normal renal tissue. Our experiments reveal underexpression of the proEGF gene in all tumors analyzed (21 of 21) and overexpression of the genes for proTGF-alpha (33 of 33 analyzed) and EGF receptor (22 of 23 analyzed) in tumor samples, when compared with normal kidney tissue. The expression of the proTGF-alpha gene appeared to depend on grade and differentiation of the tumor, since well differentiated tumors (grade 1) expressed more proTGF-alpha mRNA than the adjacent normal tissue but significantly less than poorly differentiated tumors (grade 2 or 3), which are the most aggressive ones. In none of these tissue specimens did we find, by Southern analysis, amplification of the proTGF-alpha or EGF receptor gene. Therefore, overexpression of these genes must be due to another effect, perhaps an alteration of their mRNA turnover. Although the EGF receptor gene (c-erbB1) is overexpressed in nearly all carcinomas analyzed, there was no linear coexpression with the proTGF-alpha gene. In contrast, transcription of the proEGF gene was completely turned off in tumor tissue. Although we have found by restriction fragment length polymorphism analysis, in one of three tumor samples, evidence for a somatic mutation within the proEGF gene, we do not know yet, due to the limited number of Southern analyses, whether this somatic mutation is causally involved in the decrease of proEGF mRNA expression and, hence, is representative of renal cell carcinoma. To our knowledge, this is the first observation on primary tumor tissue in humans that upon malignant transformation the gene for a polypeptide growth factor gene is underexpressed.

Prognostic impacts of cytogenetic findings in clear cell renal cell carcinoma: gain of 5q31-qter predicts a distinct clinical phenotype with favorable prognosis.

To evaluate the prognostic significance of cytogenetic findings in clear cell renal cell carcinoma (RCC), cytogenetic results of 118 primary RCCs were evaluated in relation to classical indicators of prognosis and overall survival. Losses in 3p (98.3%) were most prevalent and included 32 (27.6%) monosomies of chromosome 3 and 84 (72.4%) structural aberrations involving 3p, of which 36 were unbalanced translocations, der(3)t(3;5)(p11-p22;q13-q31), resulting in duplication of 5q sequences. Patients with gain of 5q31-qter resulting from either polysomies or structural rearrangements of 5q, the most frequent of which was der(3)t(3;5), had a significantly better outcome than those without this aberration (P = 0.001). There was no association between gain of 5q or der(3)t(3;5) and any of the well-known variables for prognosis, including low versus high clinical stage and grade of malignancy. Among additional chromosomal aberrations, loss of chromosome 9/9p was associated with distant metastasis at diagnosis (P = 0.006). The data indicate that gain of 5q identifies a clinically favorable cytogenetic variant of clear cell RCC and demonstrate the impact of specific chromosome aberrations as additional prognostic indicators in clear cell RCC.

Multiinstitutional home-therapy trial of recombinant human interleukin-2 and interferon alfa-2 in progressive metastatic renal cell carcinoma.

PURPOSE: In a phase II multiinstitutional outpatient trial, patients with progressive metastatic renal cell carcinoma were treated with a combination of subcutaneous (SC) recombinant interleukin-2 (rIL-2) and recombinant interferon alfa-2 (rIFN alpha 2). PATIENTS AND METHODS: One hundred fifty-two patients with metastatic renal cell carcinoma were treated. Treatment courses consisted of SC rIL-2 at 20 x 10(6) IU/m2 three times per week in weeks 1 and 4, and at 5 x 10(6) IU/m2 three times per week in weeks 2, 3, 5, and 6. Additionally, patients received SC rIFN alpha 2 6 x 10(6) U/m2 once per week in weeks 1 and 4, and three times per week in weeks 2, 3, 5, and 6. RESULTS: There were nine (6%) complete responses (CRs) and 29 (19%) partial responses (PRs), for an overall response rate of 25% (95% confidence interval, 19% to 32%). The median duration of responses for CRs and PRs was 16+ and 9 months, respectively. Additionally, 55 patients (36%) had stable disease (SD). Fifty-nine patients (39%) had continued disease progression (PD) despite treatment, or went off study after less than 4 weeks of therapy. The majority of patients treated experienced fever, chills, malaise, nausea, vomiting, and anorexia, side effects that were mostly limited to World Health Organization (WHO) grade 1 and 2. However, one patient developed grade 4 CNS toxicity with extended somnolence. On cessation of therapy, the neurologic symptoms in this patient were fully reversible, with no neurologic deficiency. CONCLUSION: In summary, this multiinstitutional home-therapy setting of SC rIL-2 and SC rIFN alpha 2 in patients with progressive metastatic renal cell carcinoma demonstrated drastically reduced systemic toxicity, while it confirmed the therapeutic efficacy of the low-dose SC immunotherapy combination schedule.

The role of urinary cytology for detection of bladder cancer.

PURPOSE: The aim of the present study was to test the value of urinary cytology in the diagnosis of bladder cancer. MATERIALS AND METHODS: One thousand three hundred and eighty voided urine and bladder wash specimens of 495 patients were evaluated by urinary cytology. All patients then underwent transurethral resection of suspicious bladder areas if cystoscopy and/or preceding biopsy were positive. Statistical differences were analysed using the two-sided Fisher's exact test and Cochran's test (p<0.05). RESULTS: In 495 patients including 142 patients with bladder cancer urinary cytology revealed a sensitivity of 38.0% and a specificity of 98.3% with a positive and negative predictive value of 90.6 and 78.6, respectively. Sensitivity increased significantly with malignancy grade (p<0.05). In high grade tumours sensitivity improved from initial 52.2% up to 78.3% after the third sample. In sensitivity and specificity of voided urine and barbotage washing samples no significant difference was detected. CONCLUSIONS: Urinary cytology has its place as an additive diagnostic tool to cystoscopy. None of the currently available urinary markers can replace cystoscopy but are helpful for specific diagnostic problems.

Differential diagnosis and evaluation of the clinical course of transurethrally resected T1G3 urothelial carcinoma of the bladder by DNA image cytometry.

The value of DNA image cytometry in the differential diagnosis of 106 T1G3 urothelial carcinomas of the bladder and the long-term prognosis (recurrence-free interval, survival) of the patients was tested in comparison with Ta/T1G1 (n=30) and Ta/T1G2 carcinoma (n=54). Monolayer smears were prepared from three 50-microm-thick sections by a cell separation technique and were stained according to Feulgen. The DNA content of 250 epithelial cells, chosen at random, was determined using a TV-image analysis system CM-1 (Hund, Wetzlar, Germany). The DNA content of 30 lymphocytes served as an internal standard for the normal diploid value in every individual case. Different DNA cytometric parameters and the mean nuclear area were calculated. In comparison with G1- and G2-cases, the mean values of all DNA cytometric variables were markedly increased in the group of T1G3 cases, most obviously for the 5cEE, the mean ploidy and the ploidy imbalance (0.0006 > or = p > or = 0.0001). However, a remarkable overlay of the data distribution had to be considered. An aneuploid DNA stemline ploidy was highly characteristic for T1G3 urothelial carcinoma (sensitivity: 92%), but not sufficiently specific (57%). However, if increased values for the mean ploidy, the 2cDI, the 5cEE or the 9cEE (specificity: 86%-89%) were present additionally, the diagnosis of a T1G3 urothelial carcinoma could be made cytometrically. Follow-up data for survival (recurrence) analysis was available for 90 (82) patients of the T1G3 group. Using the median value as threshold, significant differences in survival were found for the mean ploidy only (p=0.0353). The length of the recurrence-free interval was significantly different for the entropy (p=0.0205), the 2cDI (p=0.0309) and the mean ploidy (p=0.0442). In conclusion, DNA single cell cytometry represents a highly relevant tool in the objective identification of T1G3 urothelial carcinoma of the bladder, with a sufficient sensitivity and specificity. Further, this method enables prediction of tumor recurrence if suitable variables are chosen. The long-term survival of patients with T1G3 urothelial carcinoma can be estimated by DNA cytometry only in a limited manner, possibly due to the fact that the causes of death in the mostly elderly patients will be independent from the limited tumor disease.

[Lymphadenectomy for penile cancer. Diagnostic and prognostic significance as well as therapeutic benefit]. / Lymphadenektomie beim Peniskarzinom. Diagnostische und prognostische Bedeutung sowie therapeutischer Nutzen.

Lymphadenectomy is an essential part of diagnosis and treatment of the squamous cell carcinoma of the penis. Lymphadenectomy is performed depending on various characteristics of penile cancer such as depth of invasion, tumor grade, invasion into the corpora cavernosa, invasion into vascular and lymphatic vessels. In case the inguinal lymphnodes are not palpable a modified lymphadenectomy is indicated. The limits of lymphadenectomy are extended to the radical type of dissection when the frozen section indicates cancer. Inguinal lymphadenectomy is always performed on both sides. Are more than 2 nodes positive the lymphnodes in the true pelvis have to be resected as well. The dynamic sentinel lymphnode dissection may replace the modified approach in case randomized prospective studies will confirm the initial positive results and morbidity can be reduced as well. The immediate lymphadenectomy is superior to the delayed lymphadenectomy (palpable nodes during followup) in terms of local recurrence and survival. According to the risk profile patients with palpable inguinal lymphnodes can be initially managed conservatively. In case the lymphnodes remain palpable, lymphadenectomy is indicated. In this situation it is reasonable to perform imaging studies of the pelvis and abdomen for adequate planning of the surgical approach. Neoadjuvant chemotherapy is reasonable for patients with bulky nodes fixed to the skin or fascia because this improves respectability, freedom from local recurrence and increases survival. Adjuvant chemo- and/or radio-therapy are reserved for extended disease or palliative situations.