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ABSTRACT: PURPOSE: Retroperitoneal lymph node dissection (RPLND) is the most appropriate method for the detection of residual tumor tissue and mature teratoma after chemotherapy in patients with advanced nonseminomatous (NSGCT) or seminomatous (SGCT) germ cell tumors in clinical stage II-III. Open surgical procedures are associated with higher morbidity rates and laparoscopic RPLND offers a minimally invasive procedure with equivalent oncological safety and low morbidity. METHODS: In 39 patients laparoscopic RPLND (L-RPLND) after platinum-based chemotherapy for clinical stage IIa-III NSGCT was performed unilaterally as well as bilaterally by two surgeons. Patients with retroperitoneal residual tumor >1 cm and normalization of tumor markers after chemotherapy were included. Bilateral L-RPLND was performed with complete contralateral nerve sparing while the decision for ipsilateral nerve preservation was based on the volume of the residual mass in the respective standard field. RESULTS: The L-RPLND was completed in all patients without conversion. Median operation time was 248 min (range 95-397 min) and mean hospitalization time was 5 days (range 3-14 days). Furthermore, there was no difference in recurrence rate of the disease (p=0.45) between patients with unilateral or bilateral dissection. The postoperative ejaculatory function was normal in 37 out of 39 patients. The median follow-up period was 18.5 months (range 3-38 months) and 3 out of 39 patients developed recurrence (7.69 %). CONCLUSIONS: Post-chemotherapy L-RPLND is feasible with a lower complication rate and an adequate oncological safety and functional outcome. Due to the complexity of L-RPLND the procedure remains limited to institutions with extensive laparoscopic experience.
Der Urologe 02/2013; · 0.50 Impact Factor
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ABSTRACT: PURPOSE: Many disposable platforms have been available for laparoendoscopic single-site surgery (LESS) for a long time. Besides technical challenges cost remains the limiting factor for the widespread use of LESS. We present our experiences with the first completely reusable LESS platform. METHODS: We performed LESS procedures in 52 patients, including nephrectomy (n=18), adrenalectomy (2), partial nephrectomy (3), pyeloplasty (4), renal cyst ablation (4), pelvic lymphadenectomy (15) and lymphocele ablation (6). All procedures were carried out using a novel reusable single-port device (X-ConeR, Karl-Storz) with a simplified combination of standard and preformed instruments. Perioperative and demographic data including a visual analogue pain scale (VAS) were obtained. Complications were recorded using the Clavien classification. RESULTS: The mean age of the patients was 50.04 years. Conversion to standard laparoscopy was necessary in 3 cases and the additional use of a 3 mm needle instrument in 6 cases. There were no open conversions. Intraoperative and postoperative complications occurred in 3 (Clavien II in 2 and III in 1) cases. Mean operating time was 110, 90, and 89 min and hospital stay was 4.9, 3.1 and 3.6 days for nephrectomy, pelvic lymphadenectomy, and pyeloplasty, respectively. The mean VAS was 2.13, 1.07 and 1.5 while blood loss was 81.3 ml, 25.67 ml and 17.5 ml, respectively. CONCLUSIONS: The LESS technique with a completely reusable platform is applicable to various indications in urology yielding favorable functional and cosmetic results. This novel simplified combination of instruments facilitates handling and shortens the learning curve. Reusable materials may help to reduce cost leading to a wider acceptance of LESS.
Der Urologe 09/2012; · 0.50 Impact Factor
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ABSTRACT: INTRODUCTION: Several influencing factors on false positive rates (FPRs) of urine-based tumor markers in the detection of urothelial cancer (UC) have been identified. We evaluated age as a possible influencing factor. METHODS: Urinary cytology (Cyt), UroVysion (FISH), ImmunoCyt (uCyt+) and NMP22 were determined in 1,554 patients suspicious for UC of the bladder before cystoscopy and in case of cancer detection before TURB. Additionally, upper urinary tract imaging was performed. Maker sensitivity, specificity and FPRs were evaluated in the entire cohort and in subgroups divided by age into <50, ≥50-70 and ≥70 years. Contingency tables and the Cochrane Armitage tests were used for statistical comparisons. RESULTS: UC was found in 377 and no UC in 1,177 (75 %) patients. A total of 336 patients were diagnosed with UC of the bladder and 41 with UC of the upper urinary tract. Overall sensitivity and specificity for Cyt were 82 and 82 %: for FISH, 73 and 79 % and for uCyt+, 79 and 75 %, respectively. For NMP22, regardless of the exclusion criteria they were 72 and 34 % and after exclusion of urinary tract infection (UTI) or prior to manipulation 46 and 86 %, respectively. Significantly higher FPRs were found with increasing age for Cyt (p = 0.001), a trend to higher FPRs for uCyt+ (p = 0.11) and almost no difference for FISH (p = 0.63). For NMP22, differences became significant after exclusion of patients with UTI or prior manipulation (p = 0.02). CONCLUSIONS: The results of the present study give evidence that false positive rates of Cyt and NMP22 increase with age indicating that age should be respected for their correct interpretation.
World Journal of Urology 07/2012; · 2.41 Impact Factor
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ABSTRACT: Patienten mit Prostatakarzinom und Skelettmetastasen erleiden durchschnittlich ein skelettbedingtes Ereignis pro Jahr. Um
Komplikationen zu verhindern, die durch Androgenentzug induzierte Osteoporose und Knochenmetastasen die Mortalität und Therapiekosten
von Patienten mit Prostatakarzinom drastisch steigern, kann auf unterschiedliche Weise medikamentös in den Knochenstoffwechsel
eingegriffen werden. Bisphosphonate, die direkt in den Metabolismus von Osteoklasten eingreifen, können das Auftreten skelettbedingter
Ereignisse beim ossär metastasierten Prostatakarzinom verhindern. Der RANK-Ligand-Antikörper Denosumab, der die Interaktion
zwischen Osteoblasten, Osteoklasten und Tumorzellen beeinflusst, führt sowohl zu einer Reduktion skelettbedingter Ereignisse
beim ossär metastasierten Prostatakarzinom als auch zu einer reduzierten Inzidenz von Wirbelfrakturen bei Patienten mit therapieinduzierter
Osteoporose. Bei Patienten mit kastrationsresistentem Prostatakarzinom verlängert Denosumab das skelettmetastasenfreie Überleben.
Während über die Nebenwirkungen der Bisphosphonate zahlreiche Daten vorliegen, sind Aussagen über das Langzeitsicherheitsprofil
von Denosumab nur eingeschränkt möglich. Daher sollte die Anwendung von Denosumab bei Patienten mit Prostatakarzinom gegenwärtig
unter strenger Indikationsstellung erfolgen.
Patients with prostate cancer and bone metastases on average experience one skeletal-related event per year. To avoid complications
caused by bone metastases and androgen deprivation therapy-induced osteoporosis, which lead to significant increases in costs
and mortality, bone metabolism can be influenced in several ways. Bisphosphonates, which directly inhibit signalling pathways
in osteoclasts, can reduce the rate of skeletal-related events in metastatic prostate cancer. The RANKL antibody denosumab
inhibits the crosstalk between osteoblasts, osteoclasts and tumour cells and has been shown to reduce the rate of vertebral
fractures in patients with treatment-induced osteoporosis. Furthermore, it has been recently shown to prevent skeletal-related
events in prostate cancer patients with metastatic bone disease. In patients with castration resistant prostate cancer, denosumab
prolongs bone-metastasis-free-survival. Whereas ample data are available about side effects of bisphosphonates, limited evidence
exists about the long-term safety profile of denosumab. Therefore, a thorough patient selection is advocated for therapeutic
application of denosumab in patients with prostate cancer.
SchlüsselwörterBisphosphonate–Prostatakarzinom–Knochenmetastasen–Antihormonelle Therapie–Osteoporose
KeywordsBisphosphonates–Prostate cancer–Bone metastases–Androgen deprivation therapy–Osteoporosis
Der Urologe 05/2012; 50(9):1055-1063. · 0.50 Impact Factor
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J Mundhenk,
J Hennenlotter,
L Zug,
S H Alloussi,
T Todenhoefer, G Gakis,
S Aufderklamm,
M Scharpf,
U Kuehs,
A Stenzl,
C Schwentner
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ABSTRACT: In the treatment of advanced bladder cancer (BC), attention has recently focused on small molecule therapy concerning EGFR and the downstream Akt signalling pathway. Cellular deregulation processes are poorly understood, and biological determinants for the selection of therapy and monitoring are currently not available. The proteins PTEN, p-Akt and p27(Kip1) are suggested to be potentially significant biomarkers of Akt signalling. In this study, we investigated the expression of these proteins in advanced BC. PTEN, p-Akt and p27(Kip1) expression was determined immunohistochemically in 86 T2-4 BC specimens using a tissue microarray technique. Staining was documented with regard to intensity, cellular frequency and a multiplied staining score. Staining characteristics of the three proteins were correlated by regression analysis with the parameters of tumour stage and grade. A positive correlation was observed in the expression scores of PTEN and p-Akt, p-Akt and p27(Kip1) as well as PTEN and p27(Kip1) (p<0.02 for all combinations). The positive correlation between PTEN and p-Akt resulted mainly due to the strong correlation of PTEN intensity with p-Akt (p=0.0003 and p=0.0006 to p-Akt frequency and intensity, respectively). A positive correlation between p-Akt and p27(Kip1) was noted for p-Akt frequency as well as intensity (p<0.05 for all combinations). The positive correlation between PTEN and p27(Kip1) resulted due to the correlation of PTEN intensity alone with p27(Kip1) (p<0.03 for p27(Kip1) frequency and intensity), whereas no significance was noted for PTEN frequency. No correlation was found between T or G and expression of the proteins. However, activation of Akt in BC is known to occur independently of PTEN protein loss and appears not to cause a decrease of p27(Kip1). However, a direct regulatory impact of PTEN on p27(Kip1) was found. PTEN intensity, rather than frequency, appears to be a superior biomarker. These results may provide information to support research into protein profiling-predicted targeted therapy for BC. Correlations to benign urothelium, superficial BC specimens and follow-up data remain to be investigated.
Oncology letters 11/2011; 2(6):1089-1093. · 0.11 Impact Factor
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Der Urologe 10/2011; 50(10):1322. · 0.50 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Patients with prostate cancer and bone metastases on average experience one skeletal-related event per year. To avoid complications caused by bone metastases and androgen deprivation therapy-induced osteoporosis, which lead to significant increases in costs and mortality, bone metabolism can be influenced in several ways. Bisphosphonates, which directly inhibit signalling pathways in osteoclasts, can reduce the rate of skeletal-related events in metastatic prostate cancer. The RANKL antibody denosumab inhibits the crosstalk between osteoblasts, osteoclasts and tumour cells and has been shown to reduce the rate of vertebral fractures in patients with treatment-induced osteoporosis. Furthermore, it has been recently shown to prevent skeletal-related events in prostate cancer patients with metastatic bone disease. In patients with castration resistant prostate cancer, denosumab prolongs bone-metastasis-free-survival. Whereas ample data are available about side effects of bisphosphonates, limited evidence exists about the long-term safety profile of denosumab. Therefore, a thorough patient selection is advocated for therapeutic application of denosumab in patients with prostate cancer.
Der Urologe 07/2011; 50(9):1055-63. · 0.50 Impact Factor
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ABSTRACT: To present a versatile large animal model for endoscopic stricture repair using autologous urothelial cells.
12 male minipigs were used. An artificial stricture model was established using suture-ligation, thermo-coagulation and internal urethrotomy. A vesicostomy served for urinary diversion. Stricture formation was confirmed radiologically and histologically. Autologous urothelial cells were harvested from bladder washings, cultivated and labeled. Internal urethrotomy was done in all, and the cultivated cells were injected into the urethrotomy wound. All animals were sacrificed after 4 or 8 weeks. Immunohistology was done to confirm the presence of autologous urothelial cells within the reconstituted urethra.
Stricture formation was verified with all three methods. Histologically, no significant differences in the severity of stricture development could be observed with regard to the method used. The autologous urothelial cells in the area of the urethrotomy could be detected in the urothelium and the corpus spongiosum until 8 weeks after re-implantation.
We created a reliable and reproducible porcine model for artificial urethral strictures. Autologous urothelial cells can be implanted into an artificial stricture after urethrotomy. These cells retain their epithelial phenotype and are integrated in the resident urothelium. Further comparative studies are needed to ultimately determine a superior efficacy of this novel approach.
Journal of pediatric urology 03/2011; 8(2):194-200. · 1.38 Impact Factor
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ABSTRACT: Orthotopic neobladder reconstruction is an established treatment option in female patients undergoing radical cystectomy for invasive bladder cancer. Long-term results have proven its oncological safety and functional efficacy in both organ-confined and locally advanced disease. The use of nerve-sparing procedures has the potential to further improve the functional results in terms of postoperative continence and sexual function as long as we adhere to basic oncological principles. One important contraindication for performing neobladder reconstruction in female patients with bladder cancer is a positive urethral margin at radical cystectomy. In this respect, frozen section analysis is associated with a high sensitivity and specificity for the detection of positive urethral margins. The risk of urethral recurrence at 5 years in patients with negative urethral margins at cystectomy is ≤ 1 % and may become clinically apparent as inguinal lymphadenopathy due to changes of the lymphatic drainge after neobladder reconstruction. The 5-year recurrence-free survival after neobladder reconstruction in female patients with organ-confined bladder cancer ranges between 63 and 75 %. In female patients with locally advanced node-negative disease (≥ pT3a-4a, pN0) who underwent an orthotopic neobladder the recurrence free survival at 5 years is 71 % and so does not significantly differ from that of female patients with node-positive disease treated with an cutaneous diversion. Whether robotic cystectomy has the potential to further improve the functional outcome after neobladder reconstruction in female patients and achieve oncological long-term results comparable to those of open series is still under investigation should further be evaluated in prospective trials.
Aktuelle Urologie 03/2011; 42(2):109-14. · 0.27 Impact Factor
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ABSTRACT: The extent of the lymphadenectomy (LAE) as well as the appearance of lymph node metastasis are important prognostic factors in the treatment of the muscle invasive transitional cell carcinoma of the bladder (TCC). However there is still the need to discuss the dimension of the LAE.
Pubmed was searched with regard to guidelines for the treatment of muscle invasive TCC. In particular, operation techniques, the appearance of lymph node metastasis, lymph node mapping, histopathological and radiological detection methods, as well as the risk of positive lymph nodes were analysed.
The confirmation of lymph node metastasis is associated with a poorer outcome. Besides knowledge of metastasis pathways, an extensive and careful pathological reprocessing is one cornerstone of the procedure. Molecular markers seem to support the detection of micrometastasis. The extended LAE is associated with a better long-term survival rate compared to the limited LAE. New operation techniques such as laparoscopic or robot-assisted cystectomy are associated with lower peri- and postoperative morbidity, but the extended LAE is more challenging using these techniques. There are no long-term results available yet for these methods. Most data regarding lymphadenectomy and survival rate are based on retrospective studies thus decreasing the level of evidence.
An extended LAE shows retrospectively a better outcome in patients with lymph node metastasis in TCC. Therefore an extended LAE should be performed in patients with muscle invasive TCC. New methods for detecting lymph node metastasis are elevating the confirmation rate.
Aktuelle Urologie 03/2011; 42(2):115-21. · 0.27 Impact Factor
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ABSTRACT: Disorders of sex (DSD) development represent a serious condition. Most of the underlying mechanisms remain unclear. Disturbances within the androgen receptor (AR) pathway frequently account for 46 XY-DSDs. The individual gender-related outcome often is unsatisfactory. We present a long-term AR gene-mutation-associated follow-up in a group of 46 XY-DSD patients.
Twenty patients (46 XY) who underwent genitoplasty in infancy or early childhood were retrospectively identified. Median follow-up after surgery was 16 years. All were undervirilized at initial presentation. Thirteen had female gender assignment, and 7 were raised as males. A genital skin biopsy and subsequent fibroblast cultures were done. The specific binding of dihydrotestosterone, the thermostability of the receptor hormone complex, and 5-α-reductase activity were measured. AR gene mutations were detected by direct sequencing. The individual outcome was correlated with specific AR mutations.
AR point mutations were detected in 12, 7 were previously unknown. There was no specific androgen binding in 3, reduced affinity in 9, and normal binding in 8 patients. 5-α-Reductase activity was normal in 15, reduced in 4 and completely absent in 1 patient.
Retrospective evaluation revealed previously unknown and established AR gene mutations being associated with a distinct long-term outcome. Identification of the molecular mechanisms causing DSD will likely improve timely diagnosis and therapy. Exact characterization of AR activation and function may offer a treatment modality in affected patients. These data may allow us to give prognostic estimations on the individual outcome adding objective criteria for gender assignment in 46 XY-DSD patients.
World Journal of Urology 12/2010; 29(5):677-82. · 2.41 Impact Factor
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ABSTRACT: The optimal treatment options for lower pole stones with a diameter below 15 mm are controversially discussed. Extracorporeal shock wave lithotripsy (ESWL) is non-invasive but is hampered by low stone-free rates and a significant retreatment rate. Flexible ureterorenoscopy (URS) has been demonstrated to have high stone-free rates but the treatment costs - consisting of OR time, repair costs and expenditure for laser fibers, guide wires and stone baskets - as well as low stone-free rates with increasing stone size render this procedure highly expensive. Minimally invasive percutaneous litholapaxy (MIP) has shown low morbidity and high efficacy in the treatment of nephrolithiasis. The goal of this study was to investigate the efficacy and -safety of MIP for the treatment of small lower pole stones.
The charts of 29 patients who were treated with MIP were reviewed and clinical data like OR time, drop in haemoglobin, complication rate, stone-free rate and duration of hospital stay were collected.
28 of 29 patients were primarily stone-free; one had to undergo additional flexible URS to become stone-free. All procedures were undertaken with only one access, no severe complications occurred; none of the patients had to be transfused.
The MIP concept has a low complication rate and has been shown to be safe and effective in previous studies. We demonstrate that the feasibility and efficacy justify the percutaneous approach also for small lower pole stones.
Aktuelle Urologie 09/2009; 40(6):351-4. · 0.27 Impact Factor
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ABSTRACT: The study aim was to investigate potential influences on human nerves and pelvic organs through early implantation of bilateral sacral nerve modulators (SNMs) in complete spinal cord injury (SCI) patients during the acute bladder-areflexia phase.
Ten patients with neurologically-confirmed complete spinal cord lesions (SCLs) were provided with bilateral SNMs during the phase of atonic-detrusor muscle. Modulation was achieved by two electrodes implanted into each S(3)-foramen. Six patients declined and served as controls. The mean follow-up was 26.2 months.
Videourodynamics (VU) confirmed detrusor acontractility, resulting in urinary continence as well as significant reductions in urinary tract infections (UTIs). Bowel movements did not require oral laxatives; additional preprogrammed parameters achieved erections for intercourse.
Early SNM implantation in SCI patients may revolutionize neurogenic lower urinary tract (LUT) dysfunction management; it prevented detrusor overactivity and urinary incontinence, ensured normal bladder capacity, reduced UTI rates, and improved bowel and erectile functionality without nerve damage.
Future SCI investigations will be conducted to evaluate the potential benefits of even earlier SNM placement to progressively enhance pelvic organ functionality. This new approach may provide important clues required for assessing whether neuronal information is passed through the sympathetic trunk ganglion to the brain after complete SCI. Further investigations are needed to determine if functional magnetic resonance imaging (fMRI) might be helpful for analyzing changes in brain function in patients with SNMs and those taking antimuscarinics.
Annals of Neurology 08/2009; 67(1):74-84. · 11.09 Impact Factor
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ABSTRACT: Inflammation during systemic lipopolysaccharide (LPS) seems to be modulated by the CNS via afferent and efferent vagal pathways. We hypothesized that similar to systemic inflammation, local LPS in the gut lumen may also activate central neurons and aimed to identify potential molecular mechanisms.
Male Wistar rats were equipped with an exteriorized canula in the proximal jejunum. LPS or vehicle were administered into the jejunum (10 mg ml(-1)). For further study of molecular mechanisms, LPS or vehicle were administered systemically (1 mg kg(-1)). Brain stem activation was quantified by Fos-immunohistochemistry in the vagal nucleus of the solitary tract (NTS) and the Area postrema which is exposed to systemic circulation. Serum LPS concentrations were also determined.
Jejunal LPS exposure entailed 91+/-12 (n=7) Fos-positive neurons in the NTS compared to 39+/-9 in controls (n=6; p<0.01), while serum LPS concentrations and Fos-positive neurons in the Area postrema were not different. Systemic LPS triggered 150+/-25 (n=6) and vehicle 52+/-6 Fos-positive neurons (n=7; p<0.01). The Fos count after systemic LPS was reduced to 99+/-30 following pretreatment with the cyclooxygenase inhibitor Naproxen (10 mg kg(-1); p>0.05 versus vehicle controls) and increased to 242+/-66 following the iNOS-inhibitor Aminoguanidine (15 mg kg(-1); p<0.01). In the Area postrema, 97+/-17 (n=6) neurons were counted in animals pretreated with systemic LPS compared to 14+/-4 in controls (n=7, p<0.001).
Central neuronal activation following inflammation after systemic LPS is modulated by cyclooxygenase and NO pathways. Local exposure to bacterial LPS in the gut lumen activates the NTS which may set the stage for efferent vagal modulation of intestinal inflammation.
Autonomic neuroscience: basic & clinical 05/2009; 148(1-2):63-8. · 1.82 Impact Factor
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ABSTRACT: After an average of 18-24 months under androgen suppression therapy, almost all patients with prostate cancer show a PSA progress. At this hormone-independent stage, a PSA regress can be achieved by secondary hormonal manipulation in approximately 50% of patients for 6-12 months before they become hormone-refractory. After progress under complete androgen ablation, in 40% of cases a temporary regress can be achieved by discontinuing of the anti-androgen. The administration of an alternative anti-androgen results in a PSA decrease in 80% of the patients responding to anti-androgen deprivation. Inhibition of the adrenal testosterone synthesis by oral administration of ketoconazol can further delay disease progression. Transdermal application of estrogens also allows temporary control of tumor activity by modulating the LHRH and testosterone release as well as directly effecting tumor cell apoptosis. Recent therapeutic modalities as for example somatostatin analogues influence the microenvironment of tumor cells and thereby intensify the effect of anti-tumor therapy.
Der Urologe 03/2009; 48(2):183-8; quiz 189-90. · 0.50 Impact Factor
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ABSTRACT: Nach durchschnittlich 18–24Monaten kommt es beim Prostatakarzinom unter Androgensuppression zum PSA-Progress. Bei ungefähr
der Hälfte der Patienten kann in diesem hormonunabhängigen Stadium durch eine sekundäre Hormonmanipulation eine erneute PSA-Regression
über 6–12Monate erreicht werden, bevor das Stadium der totalen Hormonrefraktärität eintritt.
Nach Progress unter kompletter Androgenablation kann durch das Absetzen des Antiandrogens in 40% der Fälle ein temporärer
Regress erzielt werden. Die Gabe eines alternativen Antiandrogens führt bei 80% der Responder auf einen Antiandrogenentzug
erneut zu einem PSA-Rückgang. Die Hemmung der adrenalen Testosteronfunktion mit Ketoconazol kann ebenfalls den Krankheitsprogress
hinauszögern. Auch die transdermale Applikation von Östrogenen führt über Modulation der LHRH- und Testosteronausschüttung
sowie über eine direkte Wirkung auf die Tumorzellen zu einer vorübergehenden Kontrolle der Tumoraktivität. Neuere Therapieformen
wie z.B. Somatostatinanaloga beeinflussen das Mikro-Environment der Tumorzellen und bewirken so eine verstärkte Wirkung der
Antitumortherapie.
After an average of 18–24months under androgen suppression therapy, almost all patients with prostate cancer show a PSA progress.
At this hormone-independent stage, a PSA regress can be achieved by secondary hormonal manipulation in approximately 50% of
patients for 6–12months before they become hormone-refractory.
After progress under complete androgen ablation, in 40% of cases a temporary regress can be achieved by discontinuing of the
anti-androgen. The administration of an alternative anti-androgen results in a PSA decrease in 80% of the patients responding
to anti-androgen deprivation. Inhibition of the adrenal testosterone synthesis by oral administration of ketoconazol can further
delay disease progression. Transdermal application of estrogens also allows temporary control of tumor activity by modulating
the LHRH and testosterone release as well as directly effecting tumor cell apoptosis. Recent therapeutic modalities as for
example somatostatin analogues influence the microenvironment of tumor cells and thereby intensify the effect of anti-tumor
therapy.
Der Urologe 01/2009; 48(2):183-190. · 0.50 Impact Factor
