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Biomedical subjects

A Stenzl

Publications and source records attributed to A Stenzl.

At least 19 recordsLinked to original sources

Tissue microarrays: applications in urological cancer research.

Tissue microarrays (TMAs) are used to simultaneously study the expression of proteins in hundreds of tissue samples, offering the important advantage to screen large tissue banks for biomarker expression and to simultaneously examine serial sections obtained from the same tumor specimen by a time- and cost-effective analytical approach. This review article presents an overview of the importance and the impact of this technique in cancer research with increasing number of investigations using TMAs in its eighth anniversary. Its application, limitations, and selected previous study results regarding urologic malignancies are presented and discussed.

Biomarkers, Tumor↗

Neurogenic bladder treatment by doubling the recommended antimuscarinic dosage.

INTRODUCTION AND OBJECTIVES: The dosage of the antimuscarinic drugs: Tolterodine ER or Trospium was increased to a higher-than-recommended dosage in patients where the manufacturer's recommended dosage had failed. All patients were suffering from neurogenic detrusor overactivity incontinence. Tolerability and success were evaluated in the present study. MATERIALS AND METHODS: Twenty-one patients with neurogenic detrusor overactivity were evaluated: 17 with spinal cord injury, 3 with multiple sclerosis, and 1 with a meningomyelocele. All patients catheterized themselves or were catheterized. If neurogenic detrusor overactivity continued and the medication was well tolerated, the dosage was doubled to either 8 mg of Tolterodine ER [2 x 4 mg (n = 11)] or 90 mg of Trospium [3 x 30 mg (n = 10)]. The follow-up was monitored by a bladder diary and urodynamic evaluation. RESULTS: Sixteen patients significantly decreased their incontinence episodes from 8-12 episodes before to 0-2 episodes during the doubled treatment. The reflex volume increased from 202 +/- 68 to 332 +/- 50 ml (P < 0.001). Cystometric capacity enlarged from 290 +/- 56 to 453 +/- 63 ml (P < 0.001). One patient had to stop the medication because of intolerable side effects and five patients did not experience satisfactory benefit. CONCLUSION: The increased dosage of Tolterodine or Trospium is an effective treatment in patients with neurogenic bladder.

Adolescent↗

[Systemic therapy of malignant adrenal tumors].

Systemic treatment of advanced-stage adrenal malignancies is most often only palliative. Mitotane alone or in combination with other chemotherapeutic agents such as cisplatin, etoposide, and vincristine are established therapeutic concepts for the treatment of metastatic adrenal cancer. Suramin and gossypol are rarely employed. New therapeutic options are tumor vaccination and treatment with antiangiogenic drugs. Metaiodobenzylguanidine as a radiotherapeutic drug or chemotherapeutic combination therapies that include cyclophosphamide, vincristine, and dacarbazine are applied for systemic treatment of malignant pheochromocytomas.. However, the clinical efficacy of the latter regimen needs further evaluation.

Adrenal Gland Neoplasms↗

[Tumor marker tests in bladder cancer].

The gold standard for detecting bladder cancer is cystoscopy which identifies nearly all papillary and sessile lesions. However, it is an invasive procedure causing some discomfort for patients. Urine cytology is the standard non-invasive marker with very high specificity, but unfavourable poor sensitivity for Ta, G1, and T1 bladder tumors. To improve early detection of bladder cancer as well as to monitor treatment response and tumor recurrence, bladder tumor markers are eligible. An ideal bladder cancer test would have the potential to replace or delay cystoscopy in the follow-up of bladder cancer patients. In recent years, the FDA approved non-invasive tumor marker tests ImmunoCyt / uCyt+, BTA TRAK, BTA stat, NMP22, NMP22 BladderChek, and UroVysion have been investigated. The tests demonstrated higher sensitivity for diagnosis of bladder cancer compared to urine cytology. Overall, the mean sensitivity and mean specificity was 64-80% and 71-95% and the mean positive and negative predictive values to detect malignancy were 49-84% and 79-95%, respectively. BTA TRAK, BTA stat, NMP22, and NMP22 BladderChek assays are limited by false-positive results in patients with benign urological diseases such as hematuria, urocystitis, renal calculi or urinary tract infections. Due to low specificity BTA TRAK, BTA stat, NMP22, and NMP22 BladderChek should not be used without first ruling out benign or malignant genitourinary disease other than bladder cancer. With the exception of UroVysion achieving 80% sensitivity and 94% specificity, none of these non-invasive tests revealed a high sensitivity and specificity at the same time, which is a main demand to be made on an ideal tumor marker. Insufficient sensitivity along with limited specificity does not allow replacing cystoscopy in diagnosis of bladder cancer or treatment decisions based on a positive test result.

Biomarkers, Tumor↗

Correlation of bFGF expression in renal cell cancer with clinical and histopathological features by tissue microarray analysis and measurement of serum levels.

The prognostic value of bFGF for surgically treated renal cell cancer (RCC) patients was evaluated by immunohistochemistry (IHC) and the tissue microarray technique (TMA). Additionally, preoperative serum bFGF levels were correlated to tumour stage and the presence of metastases at initial diagnosis. Serum levels of bFGF were measured by ELISA in 39 healthy volunteers, in 37 patients with benign urologic diseases and in 74 RCC patients, 26 of whom revealed lymph node or distant metastases. bFGF expression as detected by IHC was investigated in 777 tissue cores from 259 different RCC patients [median follow-up: 138 (36-240) months]. Eighty eight patients died from tumour progression. For each patient, the TMA slides contained a tissue core from the primary tumour, its invasion front and the normal renal parenchyma. bFGF serum levels were higher in RCC patients vs healthy volunteers (P<0.01) and vs patients with benign urologic diseases (P<0.01). Metastasized patients revealed higher bFGF serum levels than organ-confined specimens (P<0.01). As detected by IHC only increased bFGF expression in the invasion front tissue correlated with the patients' long-term survival (log rank test) (P=0.03). In multivariate analysis regional LN metastases (P<0.01), the histological grading (P<0.01), and an increased bFGF expression in the invasion front (P=0.04) independently predicted the patients' clinical prognosis. Not the expression of bFGF in the primary tumour but in its invasion front reflects the aggressiveness of RCC, hereby indicating a different biological potential within both areas. The value of bFGF serum levels as indicators of systemic tumour dissemination remains to be determined.

Adult↗

Functional imaging of stress urinary incontinence.

Stress urinary incontinence (SUI) is defined as an involuntary loss of urine during increases in intraabdominal pressure such as coughing or laughing. It is often a consequence of weakness of the pelvic floor. Treatment of SUI consists of pelvic floor muscle training with EMG-biofeedback (PFMT) or contraction-exercises, with voluntary pelvic contractions in order to strengthen the pelvic floor. We investigated neuroplastic changes comparing PFMT with EMG-biofeedback before and after training in ten female patients with SUI using event-related functional Magnetic Resonance Imaging (fMRI). After a 12-week training a more focused activation in the primary motor and somatosensory cortical representation sites of the lower urogenital tract was found. In addition, reductions in brain activation in the insula, right frontal operculum and the anterior cingulate cortex suggest changes in emotional arousal in micturition after treatment. These changes are related to clinical improvement documented by decreased number of incontinence episodes and increased EMG-activity of the pelvic floor muscles after training. The changes in EMG-activity were correlated with heightened BOLD responses in the primary motor and primary sensory cortical representation sites of the lower urogenital tract.

Adult↗

70 Gy or more: which dose for which prostate cancer?

INTRODUCTION: Radical prostatectomy and radiotherapy are currently accepted treatment modalities for localized prostate cancer. Regarding radiotherapy, current evidence suggests that favorable treatment outcome critically depends on adequate radiation doses. However, the exact role of dose in relation to the individual risk profile is complex. In order to evaluate available data on radiation dose response relationships, in prostate cancer, a thorough and critical literature analysis was performed. MATERIAL AND METHODS: Studies on dose response relationships from randomized trials, dose escalation trials, retrospective subgroup analyses and pooled data were identified by Pubmed and ISI web of sciences searches and were critically reviewed. RESULTS AND CONCLUSION: All available data suggest a clear dose response relationship for radiotherapy for localized prostate cancer. In low risk cases, most studies suggest that doses of 70-72 Gy are adequate. Dose escalations up to 78-80 Gy seem to be beneficial for intermediate risk patients. Due to confounding variables, the dose response curves for high-risk patients are less steep. The integration of dose escalation into a more comprehensive treatment protocol is difficult, since trials on the relative impact of either hormonal ablation or inclusion of adjuvant nodal regions on dose escalation are missing.

Clinical Trials as Topic↗

Impact of tumor size on the long-term survival of patients with early stage renal cell cancer.

As the biological behaviour of even early stage renal cell cancer (RCC) strongly correlates with tumor size, it has been argued that the inclusion of RCC up to a maximum diameter of 7 cm into a common subgroup classified as T1 according to the 5th edition of the TNM system would not adequately represent the different biological aggressiveness of these malignancies. Taking this into account, the TNM classification, which now categorizes T1 RCC as T1a and T1b according to a cutoff size of 4 cm, was recently modified. However, only a few larger investigations, mainly based on univariate statistical analyses, that support the suitability of this cutoff are at present available from the literature. Therefore, it was the aim of the present investigation to determine the tumor size that best separates patients with low responses from those with high risk for tumor progression by univariate (log rank test) and multivariate (Cox regression model) statistical analyses. Between 1981 and 2000, 652 patients (443 males and 209 females) underwent tumor nephrectomy in our clinic for the diagnosis of RCC. Of these, 243 patients revealed primary tumors with a local growth not extending beyond the renal capsula at the time of surgery. For the different cutoff levels (starting from 2 cm in increments of 1 cm up to 8 cm) that were selected to subdivide the patients into groups according to the maximum tumor diameter, the correlation between tumor size and overall survival was determined by univariate and multivariate statistical analyses. It became evident that although during univariate analysis the prognostic value of a cutoff size of 4 cm was confirmed, multivariate analysis identified the highest relative risk for cause-specific death (2.93) for patients having tumors larger than 5 cm in maximum diameter. Therefore, the 5 cm cutoff seems to best determine the clinical prognosis of patients undergoing tumor nephrectomy for early stage RCC. The present study demonstrates the need for multivariate statistical approaches when the latest modification of the TNM classification system is critically evaluated.

Adult↗

[In vitro stratified urothelium and its relevance in reconstructive urology].

There are two main objectives regarding tissue engineering in reconstructive urology: (1) to provide the surgeon with autologous tissue for urogenital reconstructive purposes and (2) to create the framework for experimental investigations to better understand the structure and function of the tissues involved. In the last years urothelial cell culture has become a routine laboratory technique. There is sufficient cellular output after isolation and propagation to seed cells as single cell suspensions on biodegradable matrices for the construction of cell-matrix implants. In recent publications attention was directed toward using established primary cell cultures for in vitro stratification of multilayered urothelial sheets. Urothelial sheets have been used quite successfully for covering acellular matrices for bladder augmentation in dog and minipig models. However, up to now there has been no clinical application in humans of urothelial sheets generated in vitro. Here we review facts about the different strategies for generating multilayered urothelial sheets.

Cell Culture Techniques↗

[Complicated urethral reconstruction in the adult and adult and infant males].

The urethral reconstruction is a challenge in the adult, but even more in infant and young male patients. Good knowledge of the anatomy of the penis (blood supply and the course of the nerve fibers) with the availability of microsurgery suturing and instruments improved the outcome significantly. The growing knowledge opened the possibility to reconstruct complicate strictures with grafts. The buccal mucosa flap is one of those improvements, which made a tremendous impact to have a successful outcome. Recently we looked into the outcome of urethral reconstruction of long urethral strictures by using a buccal mucosa only flap. We used a modified technique for hypospadias repair to reconstruct coronar or subcoronar defects by meatal mobilization (MEMO). In cases with a long urethral stricture the success rate was over 90% with a mean follow up of 16 months. In all children the outcome with the MEMO-technique was successful without any major complication with a mean follow-up of 12.5 months.

Humans↗

[Voluntary micturition after intradural nerve anastomosis].

INTRODUCTION: One of the major challenges in neuro-urology is the restoration of voluntary voiding in a patient after spinal cord injury (SCI). ANIMAL EXPERIMENTS: The earliest reports on reconstruction of urinary bladder function by bridging nerve roots from above the SCI to the below this level were published by Carlsson and Sundin 1968. In another approach, a possible reflex pathway below the SCI to reinitiate voluntary voiding was investigated. The result was a modified somatic reflex arc rostral to the sacral spinal micturition center. FUTURE RESEARCH: Medical reports in numerous publications are still very enthusiastic about the possibility of cell or gene therapy. Such results report the successful bridging of small nerve gaps. The latest approach is the intravenous application of stem cells to aid the recovery of the SCI. CLINICAL APPROACH: The first reports on attempts to reconstruct the nervous pathways to the bladder in patients were published 1967. In two cases, a nerve anastomosis from Th(12) (the lowest intact segment) to S(2+3), bilaterally to the SCI, allowed spontaneous micturition after 8-12 months with reported sensitivity at the base of the penis. With a modification in surgical technique, another group reported a success rate of 100% using the anastomosis of intercostal nerves Th(11+12) to sacral roots S(2+3) to establish a reflex voiding and, in 72% of patients, reappearance of the bulbocavernous and cremaster reflexes. Xiao et al. published, with a 3 year follow-up, the creation of a micturition reflex through anastomosing the ventral roots of L(5) to S(2/3) in complete SCI patients with a 67% success rate a year after surgery. CONCLUSION: There is still a great deal of work required before cell therapy becomes a therapeutic option. Today, the published data strongly suggest that it is possible to treat first line urinary bladder dysfunctions in SCI or spina bifida patients. Before one of these techniques becomes widely used, it should be proven effective in specialized institutions, such as the Department of Urology in collaboration with the Department of Neurosurgery at the University of Tuebingen, Germany.

Anastomosis, Surgical↗

[Free and pedicled muscle transfer as a therapy option in urological surgery].

Various demands of reconstruction define restoration technique. The basic principle involves optimal anatomical and functional reconstruction with concurrent minimal donor-site morbidity. Dependent on the aetiology of the defect, there are various reconstructive possibilities available for obtaining an optimal result. An immediate single stage reconstruction, with the best possible result for the individual patient as the primary consideration, can be carried out by interdisciplinary teams. In this overview, the most common indications and principles of flap choice are presented in relation to the reconstructive requirements necessary for early rehabilitation of the patient or the earlier start of necessary adjuvant therapy.

Humans↗

Laparoscopic retroperitoneal lymphadenectomy in the management of low-stage testicular cancer: technique and results.

Retroperitoneal lymph node dissection (RPLND) is still the most sensitive and specific method for detection of lymph node metastases of testicular cancer. Because of its invasiveness and morbidity the acceptance of open RPLND has decreased significantly resulting in a diagnostic deficit. To reduce morbidity and to increase the acceptance of RPLND, laparoscopy has been introduced. Meanwhile, clinical data with long-term follow-ups are available demonstrating the technical feasibility and oncological safety of laparoscopic RPLND. Studies comparing laparoscopy and open surgery could show advantages for the laparoscopic approach concerning blood loss, intraoperative complications and operative time. Antegrade ejaculation can be preserved in the majority of patients. In conclusion, laparoscopic RPLND is a safe method for the management of low-stage germ cell tumors with minimal invasiveness and excellent clinical results. With an increasing number of urologists trained in laparoscopy and an increasing number of published data, it may become a standard approach for low-stage nonseminomatous testicular cancer.

Journal Article↗

[Autonomic innervation of the female pelvis. Anatomic basis].

The pelvic plexus with its sympathetic (hypogastric nerves, sacral sympathetic trunk) and parasympathetic (pelvic splanchnic nerves) sources provides and distributes the autonomic nervous supply for the pelvic organs. This homogeneous autonomic nerve plate is located within and deeply to the peritoneal fold (recto-uterine in the female pelvis) lying medially to the internal iliac vessels. Autonomic nerve fibres emerge from the pelvic plexus and travel to the anterolateral aspect of the rectum and the inferolateral and posterolateral aspects of the bladder and female genital tract. In addition, pelvic organs are innervated by nerves accompanying the vessels and the ureter which penetrate the pelvic plexus. Knowledge of the topography of the pelvic plexus indicates the most common sites for iatrogenic lesions and should help us in avoiding postoperative autonomic dysfunction.

Autonomic Pathways↗

[Advantages of nerve-sparing pelvic surgery. Animal experiments and clinical results].

Traditionally, oncological factors have been the only ones used in the evaluation of treatment outcome for urological tumor patients. With increased diagnoses of early, curable tumors in younger individuals, health-related quality of life and functional aspects are gaining importance. Sexual and urinary function are significant aspects of quality of life, which are especially vulnerable in urological patients. New insights into the anatomy and physiology of the pelvic organs have resulted in an improvement in surgical therapy. In this article, we present the results of current experimental and clinical studies, which underline the importance of nerve sparing techniques for maintaining a satisfying urinary and sexual function in this patient population.

Animals↗