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ABSTRACT: OBJECTIVES: To evaluate the time-course of functional recovery after cavernous nerve injury using glial cell line-derived neurotrophic factor-transduced Schwann cell-seeded silicon tubes. METHODS: Sections of the cavernous nerves were excised bilaterally (5 mm), followed by immediate bilateral surgical repair. A total of 20 study nerves per group were reconstructed by interposition of empty silicon tubes and silicon tubes seeded with either glial cell line-derived neurotrophic factor-overexpressing or green fluorescent protein-expressing Schwann cells. Control groups were either sham-operated or received bilateral nerve transection without nerve reconstruction. Erectile function was evaluated by relaparotomy, electrical nerve stimulation and intracavernous pressure recording after 2, 4, 6, 8 and 10 weeks. The animals underwent re-exploration only once, and were killed afterwards. The nerve grafts were investigated for the maturation state of regenerating nerve fibers and the fascular composition. RESULTS: Recovery of erectile function took at least 4 weeks in the current model. Glial cell line-derived neurotrophic factor-transduced Schwann cell grafts restored erectile function better than green fluorescent protein-transduced controls and unseeded conduits. Glial cell line-derived neurotrophic factor-transduced grafts promoted an intact erectile response (4/4) at 4, 6, 8 and 10 weeks that was overall significantly superior to negative controls (P < 0.001). Maximum intracavernous pressure on electrostimulation was significantly elevated using glial cell line-derived neurotrophic factor-transduced grafts compared with negative controls (P = 0.018) and unseeded tubes (P = 0.034). Return of function was associated with the electron microscopic evidence of preganglionic myelinated nerve fibers and postganglionic unmyelinated axons. CONCLUSIONS: Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor presents a viable approach for the treatment of erectile dysfunction after cavernous nerve injury.
International Journal of Urology 01/2013; · 1.75 Impact Factor
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ABSTRACT: An intraperitoneal bladder perforation occurred during transurethral tumor resection under general anesthesia in a 82 year old woman. The bladder was repaired with a laparoscopic closure and an indwelling urethral catheter. The histopathology revealed T1 high grade urothelial carcinoma. The patient recovered well and was discharged home on postoperative day 7. This case highlights the successful use of laparoscopy in the treatment of a rare urological complication.
Indian Journal of Urology 01/2013; 29(1):61-3.
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ABSTRACT: Single-incision laparoscopic surgery (SILS) is a recent development in minimally invasive surgery. This is an initial SILS experience in reconstructive urology to prove feasibility and provide a comparison with conventional laparoscopy during perioperative and convalescent periods. A single surgeon performed two complex SILS operations (psoas bladder hitch with Boari flap for high ureteric stricture [SILS-PB] and nephropexy for severe nephroptosis [SILS-Np]). A group of 6 patients with previous experience with conventional laparoscopy by the same surgeon with the same operation complexity was selected for retrospective comparison. SILS was performed through multichannel port (intraumbilical or retroperitoneal). There was no conversion to laparoscopy. Operative time (Or-t) was 365 and 185 minutes for SILS-PB and SILS-Np, respectively. Blood loss was 100 ml for SILS-PB without any intraoperative complications. Baseline demographics, Or-t, blood loss, and hospital stay were comparable to the laparoscopic group. Except for prolonged Or-t, patients undergoing SILS had similar surgical outcomes and comparable convalescent periods. Follow-up was uneventful for both groups. Patients' global satisfaction and willingness to recommend their procedure to others were favorable and equivalent between groups. Thus, SILS-reconstructive operations for high ureteric strictures and severe nephroptosis are feasible. It seems equally as efficacious as conventional laparoscopy maintaining surgical standards without differences in perioperative outcomes and convalescence.
Surgical technology international 12/2012; XXI:35-40.
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ABSTRACT: PurposeAlpha1A-adrenoceptors are important regulators of prostatic smooth muscle tone and an important target for therapy of lower
urinary tract symptoms. The function of heptahelical transmembrane receptors such as adrenoceptors can be regulated by β-arrestin-2,
which may bind to receptors besides G proteins. Here, we investigated the expression and α1A-adrenoceptor binding of β-arrestin-2
in the human prostate.
MethodsHuman prostatic tissues were obtained from patients undergoing radical prostatectomies. The expression of β-arrestin-2 and
α1A-adrenoceptors was studied by RT–PCR, Western blot analysis, and immunohistochemistry. The protein–protein interaction
between α1A-adrenoceptors and β-arrestin-2 was investigated by coimmunoprecipitation.
ResultsRT–PCR and Western blot analysis demonstrated the expression of β-arrestin-2 mRNA and protein in the human prostate. Immunohistochemistry
demonstrated β-arrestin-2 expression in smooth muscle and stromal cells. Coimmunoprecipitation studies demonstrated that α1A-adrenoceptors
in the human prostate may interact with β-arrestin-2. Thus, specific binding of β-arrestin-2 to α1A-adrenoceptors was significantly
higher than background during α1A-adrenoceptor detection in β-arrestin-2 precipitates (P<0.001) or during β-arrestin-2 detection in α1A-adrenoceptor precipitates (P<0.005). This interaction may be located to prostate smooth muscle cells, as expression of the α1A-adrenoceptor was exclusively
found in smooth muscle cells after immunohistochemical staining.
ConclusionWith β-arrestin-2, we identified a new binding partner of the α1A-adrenoceptor in human prostate smooth muscle. Binding of
β-arrestin-2 may be involved in posttranslational regulation of prostate α1A-adrenoceptors.
KeywordsProstate hyperplasia–β-arrestin-2–α1-adrenoceptor–Smooth muscle–Contraction
World Journal of Urology 04/2012; 29(2):157-163. · 2.41 Impact Factor
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ABSTRACT: Besides their role in contraction, α1-adrenoceptors may be involved in prostate hyperplasia. This would require receptor signaling by growth-promoting pathways. Akt (syn. Protein kinase B) is an important regulator of growth and differentiation. Objective: To investigate whether α1-adrenoceptors in the human prostate activate Akt.
Prostate tissue was obtained from patients undergoing radical prostatectomy. Akt expression was investigated by RT-PCR, Western blot, and immunohistochemistry. Akt activation by noradrenaline (30 μM) and phenylephrine (10 μM) was assessed by Western blot analyses with a phospho-specific antibody. The effects of the Akt inhibitors FPA-124 and 10-DEBC on phenylephrine-, noradrenaline- and electric field stimulation- (EFS-) induced contraction were studied in myographic measurements.
mRNA of all three Akt isoforms (Akt1, Akt2, Akt3) was detected by RT-PCR in all prostate samples (n=6 patients). Protein expression was confirmed by Western blot analysis (n=8 patients). Immunohistochemical staining for Akt revealed strong immunoreactivity in prostate smooth muscle cells (n=5 patients). Stimulation of prostate tissues with noradrenaline (30 μM, n=8 patients) or phenylephrine (10 μM, n=7 patients) caused significant Akt phosphorylation at serine-473, indicating activation of Akt. FPA124 and 10-DEBC were without effects on noradrenaline-, phenylephrine-, or EFS-induced contraction of prostate strips.
Prostate α1-adrenoceptors activate Akt. Consequently, Akt is a target of α1-blocker therapy, which has been unknown to date. Our findings point to functions of prostate α1-adrenoceptors besides contraction.
Life sciences 03/2012; 90(11-12):446-53. · 2.56 Impact Factor
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ABSTRACT: To report our refinement of open intrafascial retropubic radical prostatectomy (OIF-RP) and 1-year follow-up results.
OIF-RP was performed in 231 cases of clinically localized Prostate cancer in a prospective study from January 2007 to December 2009. Inclusion criteria were good potency (IIEF-5 score ≥ 15), Gleason score ≤ 6, prostate-specific antigen (PSA) ≤ 10, and clinical T1-2 tumors. Endopelvic fascia was not incised, and the prostate capsule was freed laterally from surrounding fasciae and dorsally from Denonvillier's fascia, keeping all periprostatic fasciae/nerves intact. Functional outcomes were followed at 3 and 12 months (3 M and 12 M). Continence defined as complete (no pads), grade I (1-2 pads/day) and grade II (>2 pads/day).
Median age was 63.3 years, body mass index 25.6, and PSA 5.4 ng/mL. Median operating time was 65 minutes (range 50-250), blood loss was 150 mL (range 50-1000), preoperative IIEF-score was 23 (range 15-25). Pathologic stage was pT2 (91%) and pT3 (9%). Gleason score was ≤ 6 (73%) and ≥ 7 (27%). Positive margins were 10% (pT2) and 65% (pT3). There were no postoperative complications/reinterventions. At 3 M, 60% of patients had full continence, and 86% had full continence at 12 M (≤ 60 years, 64% and 95% after 3 M and 12 M, respectively). At 3 M and 12 M, median IIEF-score was 14 (range 0-25) and 19 (range 0-25), respectively. Baseline IIEF-score was reached by 50% (3 M) and 78% (12 M) (P<.001). IIEF-score was inversely correlated to patients' age (≤ 60 years 92%, 60-69 years 77%, ≥ 70 years 60%).
OIF-RP follows rationales of radical prostatectomy and might be considered for selected patients. Preserving all periprostatic fasciae/nerves recuperates early continence and maintains potency without affecting oncological outcomes.
Urology 03/2012; 79(3):717-21. · 2.43 Impact Factor
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ABSTRACT: To investigate whether 1-adrenoceptor signaling in the human prostate involves regulation of the mitogen-activated protein kinase (MAPK) p38. Although α1-adrenoceptors are an important target for therapy of lower urinary tract symptoms in patients with prostate hyperplasia, intracellular signaling by prostate α1-adrenoceptors is not sufficiently understood.
Prostate tissue was obtained from patients undergoing radical prostatectomy. The effect of phenylephrine (10 μM) on p38 activity was assessed by Western blot analysis with a phospho-specific antibody. Expression of p38 was studied by immunohistochemistry and immunofluorescence staining. The effect of the p38 inhibitor SB 202190 (10 μM) on phenylephrine-induced contraction was studied in myographic measurements.
Stimulation of human prostate tissue with phenylephrine resulted in reduced threonine180/tyrosine182 phosphorylation of p38, indicating deactivation of p38 (P = .039 after 5 minutes). Immunohistochemical staining demonstrated expression of p38 in stromal cells of human prostate tissue. Immunofluorescence staining identified these cells as smooth muscle cells, as p38 colocalized with immunoreactivity for α-smooth muscle actin. The p38 inhibitor SB 202190 was without effect on phenylephrine-induced contraction.
Using intact human prostate tissue, we herewith describe a new signal transduction pathway of prostate α1-adrenoceptors. In addition to mediating contraction, prostate α1-adrenoceptors induce intracellular signaling, which results in deactivation of p38 MAPK. This is not involved in α1-adrenergic contraction, and points to α1-adrenoceptor functions beyond contraction.
Urology 10/2011; 78(4):969.e7-13. · 2.43 Impact Factor
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ABSTRACT: The objective of this study was to describe a simple modification of the laparoscopic pelvic lymphocele marsupialization (LL) following radical prostatectomy lymphoceles (RP-LC). Patients and
Forty-eight patients (57-76 years) with symptomatic RP-LC underwent surgery in our institute. This was through an open approach in 6 (open drainage [OL]) and LL in rest of the patients (12 with 3 [LL3] and 30 with 2 [LL2] trocars). All except 2 patients were refractory to percutaneous tube drainage and/or sclerotherapy. Pelvic ultrasound and/or computed tomography scans revealed LC size (4 × 5-11 × 12 cm) and volumes (100-1100 mL).
All surgeries were uneventful with an operative time of 15-60 minutes for LL and 35-90 minutes for OL and it became shorter with increasing experience with LL2 (15-25 minutes). Mean hospitalization time was 2.3 and 8 days after LL (LL2 and LL3) and OL, respectively. LC were at the right side in 10 patients, at the left side in 6, and at both sides in 14. Postoperative ultrasound revealed primary success in all cases. No patient developed recurrence of or had treatment for lymphocele during a mean follow-up time of 19 months.
LL2 is a simple, feasible, and safe procedure that could be used as a first-line treatment for large, noninfected symptomatic or refractive RP-LC.
Journal of Laparoendoscopic & Advanced Surgical Techniques 03/2011; 21(2):145-8. · 1.40 Impact Factor
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ABSTRACT: During laser lithotripsy, working instruments are often in close proximity to the distal fiber tip and may be damaged accidentally or even intentionally. The aim of this study was to compare the amount of damage to a standard guidewire and the nitinol wires of endourologic retrieval baskets that were affected by three different clinically available laser systems.
The impact of pulsed laser irradiation on a standard hydrophilic guidewire and a retrieval basket were investigated. One infrared (IR) laser system (holmium:yttrium-aluminum-garnet [Ho:YAG]: λ = 2100 nm) and two laser systems emitting light in the visible (VIS) spectral range (frequency-doubled double-pulse neodymium:YAG [FREDDY]: λ = 532 nm/1064 nm and flashlamp pulsed dye [FLPD]: λ = 598 nm) were used. Experimental parameters were fiber core diameter, laser pulse energy, and distance between the fiber tip and the investigated tool. Damage was evaluated by microscopic investigation and by quantifying the damage size and magnitude by creating laser impact related damage factors.
After application of one single laser pulse, IR-laser related maximum damage to guidewires occurred, depending on the pulse energy and the fiber core diameter, either in contact mode or in a distance of maximum 2 mm. Maximum VIS-laser related damage occurred in a distance range of 2 to 3 mm. The nitinol wires of the extraction tools could be destroyed completely by IR laser irradiation at pulse energies E(P) > 1200 mJ, depending on the fiber core diameter used. VIS lasers were solely able to set visible damage to guidewires without any disruption of nitinol wires.
Ho:YAG laser induced damage to endourologic tools is significantly higher compared with the impact of the FREDDY or the FLPD-laser. Because complete disruption of guidewires and stone extraction tools occurred, a safety clearance must be kept between the fiber tip and the endourologic tool during Ho:YAG stone disintegration. If disruption is intended, such as in the case of basket-retrieval problems, it can easily be performed with Ho:YAG irradiation.
Journal of endourology / Endourological Society 03/2011; 25(4):667-72. · 1.75 Impact Factor
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ABSTRACT: • To test whether β1-adrenoceptor activation leads to phosphorylation of the β2-adrenoceptor in human prostate tissue.
• Prostate tissue from patients undergoing radical prostatectomy was stimulated in vitro with the α1-adrenergic agonist phenylephrine (10 µM). • α2-adrenoceptor phosphorylation at serines 345/346 was studied using Western blot analysis with a phospho-specific antibody. • The role of second messenger kinases was assessed by studying the effects of the protein kinase C (PKC) inhibitor Ro 31-8425 and the protein kinase A (PKA) inhibitor H89 on phenylephrine-induced phosphorylation. • The expression of G protein-coupled receptor kinases (GRKs) 2/3 was analysed using quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry.
• Stimulation of prostate tissue with phenylephrine resulted in phosphorylation of the β2-adrenoceptor (5, 10 and 20 min after stimulation). • This α1-adrenoceptor-induced phosphorylation of β2-adrenoceptors was resistant to inhibition of PKC and PKA. • Changes in phosphorylation levels were not attributable to changes in receptor levels, as these remained constant during stimulation. • RT-PCR and Western blot analysis showed expression of GRK2/3 in human prostate tissues. • Immunohistochemical staining showed that GRK2/3 expression in human prostate tissue is located to stromal and smooth muscle cells.
• Activation of α1-adrenoceptors causes phosphorylation of β2-adrenoceptors in the human prostate. This may enhance α1-adrenergic contraction and is possibly mediated by GRK2, which is expressed in prostate smooth muscle. • Mutual regulation between different adrenergic receptors might be involved in the therapeutic effects of α1-blockers in patients with benign prostate hyperplasia.
BJU International 03/2011; 108(6):922-8. · 2.84 Impact Factor
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ABSTRACT: α1-Adrenoceptors are considered critical for the regulation of prostatic smooth muscle tone. However, previous studies suggested further α1-adrenoceptor functions besides contraction. Here, we investigated whether α1-adrenoceptors in the human prostate may activate extracellular signal-regulated kinases (ERK1/2).
Prostate tissues from patients undergoing radical prostatectomy were stimulated in vitro. Activation of ERK1/2 was assessed by Western blot analysis. Expression of ERK1/2 was studied by immunohistochemistry. The effect of ERK1/2 inhibition by U0126 on phenylephrine-induced contraction was studied in organ-bath experiments.
Stimulation of human prostate tissue with noradrenaline (30 μM) or phenylephrine (10 μM) resulted in ERK activation. This was reflected by increased levels of phosphorylated ERK1/2. Expression of ERK1/2 in the prostate was observed in smooth muscle cells. Incubation of prostate tissue with U0126 (30 μM) resulted in ERK1/2 inhibition. Dose-dependent phenylephrine-induced contraction of prostate tissue was not modulated by U0126.
α1-Adrenoceptors in the human prostate are coupled to ERK1/2. This may partially explain previous observations suggesting a role of α1-adrenoceptors in the regulation of prostate growth.
Urologia Internationalis 02/2011; 86(4):427-33. · 0.99 Impact Factor
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ABSTRACT: Alpha1A-adrenoceptors are important regulators of prostatic smooth muscle tone and an important target for therapy of lower urinary tract symptoms. The function of heptahelical transmembrane receptors such as adrenoceptors can be regulated by β-arrestin-2, which may bind to receptors besides G proteins. Here, we investigated the expression and α1A-adrenoceptor binding of β-arrestin-2 in the human prostate.
Human prostatic tissues were obtained from patients undergoing radical prostatectomies. The expression of β-arrestin-2 and α1A-adrenoceptors was studied by RT-PCR, Western blot analysis, and immunohistochemistry. The protein-protein interaction between α1A-adrenoceptors and β-arrestin-2 was investigated by coimmunoprecipitation.
RT-PCR and Western blot analysis demonstrated the expression of β-arrestin-2 mRNA and protein in the human prostate. Immunohistochemistry demonstrated β-arrestin-2 expression in smooth muscle and stromal cells. Coimmunoprecipitation studies demonstrated that α1A-adrenoceptors in the human prostate may interact with β-arrestin-2. Thus, specific binding of β-arrestin-2 to α1A-adrenoceptors was significantly higher than background during α1A-adrenoceptor detection in β-arrestin-2 precipitates (P < 0.001) or during β-arrestin-2 detection in α1A-adrenoceptor precipitates (P < 0.005). This interaction may be located to prostate smooth muscle cells, as expression of the α1A-adrenoceptor was exclusively found in smooth muscle cells after immunohistochemical staining.
With β-arrestin-2, we identified a new binding partner of the α1A-adrenoceptor in human prostate smooth muscle. Binding of β-arrestin-2 may be involved in posttranslational regulation of prostate α1A-adrenoceptors.
World Journal of Urology 01/2011; 29(2):157-63. · 2.41 Impact Factor
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ABSTRACT: Thromboxane A(2) (TXA(2)) induces contraction in different smooth muscle types via its receptor (TXA(2) receptor). However, any motoric role of TXA(2) in prostate smooth muscle tone has not been studied to date. Here, we investigated whether TXA(2) induces contraction of human prostate tissue. After ethical approval, prostate tissue was obtained from 47 patients undergoing radical prostatectomy. Effects of the TXA(2) analogue U46619 ((5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxy-1-octenyl]-2-oxabicyclo[2.2.1]hept-5-yl]-5-heptonic acid) in isolated human prostate strips were studied in organ bath experiments with or without the Rho kinase inhibitor, Y27632 (trans-4-[(1R)-1-aminoethyl]-N-4-pyridinylcyclohexanecarboxamide dihydrochloride), or the calmodulin antagonist W7 (N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide hydrochloride). Expression of TXA(2) synthase and TXA(2) receptors were examined by Western blot analysis and immunohistochemistry. Endogenous TXA(2) was quantified by enzyme immunoassay. U46619 induced concentration-dependent contractions of human prostate strips, with a maximum contraction at 3 μM. U46619-induced prostate contraction was significantly inhibited by Y27632 (30 μM) and by W7 (100 μM). TXA(2) synthase and TXA(2) receptors were detected by Western blot analysis. Immunohistochemical stainings showed that expression of TXA(2) synthase in prostate tissue was located to glandular cells, while prostate TXA(2) receptors were located to smooth muscle and glandular cells. The stable TXA(2) metabolite TXB(2) was detected by enzyme immunoassay in the prostate. TXA(2) induces contraction of isolated human prostate tissue by TXA(2) receptor activation. Prostate smooth muscle TXA(2) receptors are coupled to Rho kinase and Ca(2+)-dependent mechanisms. The distribution of TXA(2) synthase and TXA(2) receptors in the human prostate suggests TXA(2)-mediated paracrine epithelial-stromal interactions.
European journal of pharmacology 10/2010; 650(2-3):650-5. · 2.59 Impact Factor
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ABSTRACT: To retrospectively analyse the long-term follow-up of 54 patients treated with organ-preserving laser therapy for penile carcinoma, as such therapy provides excellent cosmetic and functional results, but recurrence rates are high, which might impair the oncological outcome and worsen tumour-related survival.
Between 1979 and 2008, 54 patients with penile carcinoma were treated with the neodymium-doped yttrium-aluminium-garnet (Nd:YAG) laser at our institution; 11 were classified as having carcinoma in situ (Tis), 39 as T1 and four as T2.
There was local recurrence in 16 patients (42%); the mean (range) time to local recurrence was 53 (9-132) months. In half the patients the time to local recurrence was >53 months, with the latest recurrence at 132 months after initial therapy of primary tumour. There was no statistically significant difference in recurrence rates with Tis or invasive penile carcinoma. In lymph-node-negative patients at initial presentation, there were no newly developed positive lymph nodes during the follow-up.
Organ-preserving laser therapy showed a relatively high recurrence rate in patients with a long-term follow up, but the oncological outcome and survival were not compromised by local recurrence. Therefore, laser therapy appears to be appropriate for treating premalignant lesions and early stages of penile carcinoma. Patients should be informed about the potential for late recurrence.
BJU International 09/2010; 106(6):786-90. · 2.84 Impact Factor
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ABSTRACT: To characterize the mechanical and optical properties of the PolyScope endoscope system and to examine the clinical outcome in patients who were undergoing ureteronephroscopy. Materials and
Mechanical assessment involved measurement of the deflection angle and irrigation flow rate. Optical resolution and distortion, field and angle of view, and light transmission and output formed the optical assessment. Clinical assessment was made in a series of consecutive ureteronephroscopy procedures. The optical cord was disconnected after each procedure, and the image fiber was assessed for damage.
The mean value for the angle of maximum active tip deflection with an empty working channel was 265 degrees (261-275 degrees). Deflection was impaired most with insertion of the 3.0 F basket (10% decrease) and least with an indwelling 220 microm laser fiber (2% decrease). Irrigation flow rate was 57 mL/min with an empty working channel. Flow was reduced by 50% and 68%, with the insertion of a 200 microm or 365 microm laser probe, respectively, and by 92.5% with a 3.2F basket. No damage to the image fiber occurred. The PolyScope optics system could identify a target of about 0.125 mm at a distance of 2 to 4 mm, based on 3 line-pairs/mm needed for clear identification. Lithotripsy of renal calculi was performed for 40 stone burdens in 32 patients; the resulting stone-free rate was 87.5%. Conclusion: The novel semidisposable ureteroscope system PolyScope was simple to use, effective, and reliable in this preliminary clinical evaluation. It overcomes the inherent fragility of comparable devices, which renders the need for maintenance unnecessary.
Journal of endourology / Endourological Society 07/2010; 24(7):1061-6. · 1.75 Impact Factor
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Boris Schlenker,
Kaspar Matiasek,
Dieter Saur,
Christian Gratzke,
Ricarda M Bauer,
Yared Herouy,
Christian Arndt,
Armin Blesch,
Rudolf Hartung,
Christian G Stief,
Norbert Weidner,
Florian May
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ABSTRACT: To evaluate the expression of nitric oxide synthase (NOS) isoforms after various reconstruction techniques in rats, to improve the understanding of neuronal repair mechanisms after radical prostatectomy, as Schwann cell-seeded guidance tubes have been shown to promote cavernous nerve regeneration, and glial cell-line-derived neurotrophic factor (GDNF)-overexpressing Schwann cells enhance nerve regenerative capacity.
Segments (5 mm) of the cavernous nerve were excised bilaterally, followed by immediate bilateral microsurgical reconstruction. In four rats per group, the eight nerves were reconstructed by autologous nerve grafting (A), interposition of Schwann cell-seeded silicon tubes (B), or silicon tubes seeded with GDNF-hypersecreting Schwann cells (C). Further rats were either sham-operated (D) or had nerve excision without repair (E). Erectile function was evaluated after 6 weeks by re-laparotomy, electrical nerve stimulation and morphological evaluation of reconstructed nerves. NOS isoform mRNA expression was analysed by reverse transcription-polymerase chain reaction in tissue specimens taken from the corpora cavernosa.
GDNF-transduced Schwann cell grafts restored erectile function better than untransduced Schwann cell and autologous nerve grafts (88% vs 75% vs 38%; not significant). Tissue specimens in group C had the highest expression of neuronal NOS mRNA in relation to the neuronal marker PGP9.5 among all treatment groups (not significant). Compared to nerve grafts (A) and negative controls (E) nNOS/PGP9.5 expression was significantly higher (P < 0.05). Both inducible NOS and endothelial NOS expression did not differ significantly among the various groups. Morphological evaluation showed significantly larger cross-sectional areas and a higher percentage of neural tissue than in untransduced Schwann cell grafts (P < 0.05).
Restoration of erectile function is paralleled by an increase of neuronal NOS expression in rats. Further experiments will determine the physiological role of neuronal NOS in erectile nerve repair processes.
BJU International 04/2010; 106(11):1726-31. · 2.84 Impact Factor
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Boris Schlenker,
Bernhard Scher,
Reinhold Tiling,
Sabine Siegert,
Edwin Hungerhuber,
Christian Gratzke,
Derya Tilki,
Oliver Reich,
Peter Schneede,
Peter Bartenstein,
Christian G Stief,
Michael Seitz
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ABSTRACT: The extent of lymph node involvement is the most relevant prognostic factor in patients with penile cancer.
To prospectively analyze the diagnostic accuracy of 18F-FDG-PET/CT-scan in the assessment of inguinal lymph node involvement in patients with invasive penile carcinoma.
Thirty-five patients with invasive penile carcinoma were staged prospectively by 18F-FDG-PET/CT-scan, and blindly evaluated by 2 nuclear medicine physicians. In total, lymph node involvement was assessed in 70 inguinal groins. Reference standard was either histology or clinical follow-up with a minimum of 31 months (mean: 48.4 months; range: 31-68 months).
18-FDG-PET/CT showed a sensitivity of 88.2% and a specificity of 98.1%. Positive predictive value (PPV) was 93.8%, while negative predictive value (NPV) was 96.3%. In two groins, metastasis of 5 and 7 mm were missed by PET/CT scan.
18F-FDG-PET/CT is a promising staging tool in assessing the inguinal lymph node involvement of patients with penile carcinoma. Integration of PET/CT scanning into preoperative staging algorithms may avoid surgical staging in selected patients.
Urologic Oncology 12/2009; 30(1):55-9. · 3.22 Impact Factor
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ABSTRACT: OBJECTIVES AND AIMS: Due to the low prevalence of penile cancer, little evidence exists on the metastatic potential and the ideal treatment strategies in intermediate-differentiated invasive (pT1 G2) penile cancer. The current study aimed to analyze the oncologic outcome of patients with penile carcinoma with long-term follow-up in a single-center study.
In this retrospective study, 38 patients with histologically proven T1 G2 squamous cell carcinoma of the penis were included. Only the 'classic' subtype was analyzed. Treatment of the primary tumor was Nd:YAG laser-therapy, excision, or partial amputation. Follow-up was performed according to EAU guidelines (2004).
Mean follow-up was 78.1 months (range: 9-285 months). Local recurrence was seen in 12 patients (31.6%), but was not correlated with disease related death (P = 0.7944). Rate of local recurrence was not dependent on treatment modality (P = 0.3481); 13 patients died, accounting for a disease related survival rate of 81.6% during observation period. Positive lymph nodes were seen in 28.9% of patients and were significantly correlated with disease related death (P = 0.00004). Clinically enlarged inguinal lymph nodes were not correlated with histologically confirmed positive lymph nodes (P = 0.5785).
For patients with T1 G2 penile cancer, organ preserving therapy appears to be a suitable treatment option. In our series, nearly one third of patients developed inguinal lymph node metastases, which highlights the potential benefit of surgical staging. Larger prospective multicenter studies are needed to define the best treatment strategy for intermediate-differentiated invasive penile cancer.
Urologic Oncology 11/2009; 29(6):782-7. · 3.22 Impact Factor
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ABSTRACT: OBJECTIVES AND AIMS: Laser therapy for penile carcinoma is commonly used despite high recurrence rates of up to 48%. The aim of our study was to investigate the long-term recurrence rate of patients treated by fluorescence-guided laser therapy for penile carcinoma and its impact on oncologic outcome.
Between 1999 and 2005, a total of 26 patients with premalignant carcinoma in situ (Tis) (n = 11) or invasive penile carcinoma (n = 15) were treated by fluorescence-guided laser therapy in our center. The mean follow-up was 71.1 months (range 41-104 months). Recurrence rate, time to recurrence, and impact on survival was investigated for Tis patients and penile carcinoma patients separately.
No patient died tumor-associated recurrence during follow-up. No local progression of T stage was observed in patients with Tis tumor. In the group with invasive penile cancer, there were 4 (15.4%) local recurrences. However, 3 of them occurred after more than 3 years and, therefore, are more likely to be considered as "de novo" carcinoma. No intra- or perioperative side effects of photodynamic diagnosis (PDD) were observed.
Local recurrence rate of laser therapy can be reduced by fluorescence guidance without impairing cosmetic or functional results. The necessary equipment is available in many centers that perform PDD for urothelial bladder cancer. PDD, therefore, can be considered to be cost-effective and easy to perform. Prospective multi-center studies to directly compare recurrence rates between white light and fluorescence-guided laser therapy for penile carcinoma are required.
Urologic Oncology 11/2009; 29(6):788-93. · 3.22 Impact Factor
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MMW Fortschritte der Medizin 10/2009; 151(41):31-2.
