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1.
Urologe A ; 60(12): 1546-1554, 2021 Dec.
Article in German | MEDLINE | ID: mdl-34738151

ABSTRACT

BACKGROUND: Long-term remission can be achieved by surgery in patients with metastatic renal cell carcinoma (mRCC), without chronic toxicity due to systemic treatment. Data on metastasectomy are mostly based on observations of metachronous metastasis. However, it is unclear whether patients with synchronous oligometastasis may also benefit from surgery alone as an alternative to highly effective systemic treatment combined with resection of the primary tumor. MATERIALS AND METHODS: The authors performed an unstructured literature search in PubMed including systematic reviews and meta-analyses. Results are discussed in regard of the current data and clinical practice. RESULTS AND DISCUSSION: Although there is no uniform definition for oligometastasis in mRCC, cytoreductive nephrectomy in selected patients seems to be mandatory before metastasectomy is performed in primary oligometastatic RCC. In particular, in those patients with oligometastasis of the lung, bone, central nervous system, liver, adrenal gland, and thyroid, metastasectomy appears to be an important therapeutic option. Ultimately, among the therapeutic options, surgery is also an important therapeutic approach in primary oligometastatic mRCC. A balanced consideration between surgery, other local therapies, and modern systemic treatment demands interdisciplinary decision-making that takes into account the patients' preference.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Metastasectomy , Carcinoma, Renal Cell/surgery , Humans , Kidney Neoplasms/surgery , Nephrectomy , Treatment Outcome
2.
Georgian Med News ; (313): 7-12, 2021 Apr.
Article in English | MEDLINE | ID: mdl-34103422

ABSTRACT

Phosphodiesterase (PDE) enzymes are considered being key proteins in controlling the function of smooth musculature in the human urinary tract. The use of PDE inhibitors (PDE-Is) to treat erectile dysfunction and lower urinary tract symptomatology (LUTS) secondary to benign prostatic hyperplasia (BPH) is well established. It has been shown that PDE-Is can reverse the tension induced by means of muscarinergic agents of detrusor smooth muscle and enhance the production of cyclic nucleotides. In clinical settings, the PDE1 inhibitor vinpocetine had beneficial effects in patients presenting with voiding dysfunctions. This prompted us to evaluate further the mechanism of action of PDE-Is on bladder smooth musculature. Using the tissue bath technique, relaxant responses of human detrusor smooth muscle, challenged by acetylcholine (1 µM), to vinpocetine (PDE1-I), rolipram (PDE4-I), MY 5445 and sildenafil (PDE5-Is) (0.1 µM, 1 µM, and 10 µM) were investigated with and without pre-exposure of the tissue to threshold concentrations of the NO donor drug sodium nitroprusside (SNP) or adenylyl cyclase activator forskolin (0.02 µM). The non-specific PDE-I papaverine was used as a reference compound. The cumulative addition of forskolin or SNP exerted a pronounced reversion of the tension induced by means of ACh, starting at a concentration of 1 µM (forskolin, -25,6%) and 0.1 µM (SNP, -20%), respectively. There were marginal responses of the detrusor smooth musculature to the PDE-Is, the relaxation measured ranged from -12% (vinpocetine/sildenafil) to -19% (rolipram, MY 5445). Exposure of the tissue to a threshold concentration of SNP increased the reversion of tension induced by vinpocetine (-40%), rolipram (-50%) and MY 5445 (-45%). An enhancement in the potency of the drugs was also registered. A threshold concentration of SNP did not significantly affect the maximum reversion of tension brought about by sildenafil but added positively to the in vitro potency of the PDE5-I. PDE inhibitors may tend to be more effective in systems characterized by an enhanced production of cyclic AMP/GMP (such as urogenital tissues in vivo). Our findings may explain how PDE inhibitors can affect symptoms of the overactive bladder.


Subject(s)
Cyclic GMP , Phosphodiesterase Inhibitors , Cyclic AMP , Humans , Male , Muscle, Smooth , Rolipram
3.
Andrologia ; 50(5): e13008, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29574984

ABSTRACT

Peptides, such as C-type natriuretic peptide (CNP), vasoactive intestinal polypeptide (VIP) and endothelin 1 (ET-1), are involved in the control of penile erectile tissue (corpus cavernosum = CC). Inhibiting the degradation of CNP and VIP or conversion of Big ET-1 into ET-1 by endopeptidase enzymes should result in an enhancement of CC smooth muscle relaxation. Using the tissue bath technique, responses of isolated CC, challenged by noradrenaline (NA, 1 µm), to increasing concentrations of the endopeptidase inhibitor KC 12615 (1 nm - 10 µm), CNP and VIP (0.1 nm - 1 µm), were investigated. Effects of CNP, VIP and Big ET-1 (0.1 nm - 100 nm) on the tissue tension were also evaluated following pre-exposure to 10 µm of KC 12615. Big ET-1 induced contraction of the CC amounting to a force generation of 1,200 mg. The contraction was attenuated in the presence of KC 12615 by 35% and 50%, respectively. The tension induced by NA was reversed by VIP and CNP to 38.7% ± 15.8% and 61% ± 13%, respectively, of the initial force. The findings might be of significance with regard to future pharmacological treatment options for male ED, where an endothelial dysfunction exists.


Subject(s)
Endothelin-1/pharmacology , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Penis/drug effects , Protease Inhibitors/pharmacology , Adult , Humans , Male , Middle Aged , Muscle Relaxation/drug effects , Young Adult
4.
Andrologia ; 50(2)2018 Mar.
Article in English | MEDLINE | ID: mdl-28786134

ABSTRACT

The endocannabinoid system (ECS), comprising the cannabinoid receptors (CBR), their ligands, and enzymes controlling the turnover of endocannabinoids, has been suggested to be involved in male reproductive function. As information is scarce on the expression of the ECS in human male reproductive tissues, this study aimed to investigate by means of molecular biology (RT-PCR) and immunohistochemistry/immunofluorescence the expression and distribution of CB1 and CB2, GPR55 (an orphan G protein-coupled receptor that recognises cannabinoid ligands) and FAAH (isoforms 1 and 2) in the human seminal vesicles (SV). The specimens expressed PCR products corresponding to CB1 (66 bp), CB2 (141 bp), GPR55 (112 bp), FAAH1 (260 bp) and FAAH2 (387 bp). Immumohistochemistry revealed dense expression of CB1, CB2 and GPR55 located to the pseudo-stratified columnar epithelium and varicose nerves (also characterised by the expression of vasoactive intestinal polypeptide and calcitonin gene-related peptide). Cytosolic staining for FAAH1 and FAAH2 was seen in cuboidal cells of all layers of the epithelium. No immunoreactivity was detected in the smooth musculature or nerve fibres. CB1, CB2, GPR55, FAAH1 and FAAH2 are highly expressed in the human SV. Considering their localisation, the ECS may be involved in epithelial homeostasis, secretory function or autonomic mechano-afferent signalling.


Subject(s)
Amidohydrolases/metabolism , Endocannabinoids/metabolism , Receptors, Cannabinoid/metabolism , Receptors, G-Protein-Coupled/metabolism , Seminal Vesicles/metabolism , Aged , Epithelial Cells/metabolism , Fluorescent Antibody Technique , Humans , Immunohistochemistry , Male , Middle Aged , Seminal Vesicles/pathology
5.
Int J Impot Res ; 29(5): 179-183, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28469181

ABSTRACT

The transient receptor potential cationic channel ankyrin 1 (TRPA1) is a channel protein assumed to act in various human tissues as mechano- and pain sensor and play a role in neurotransmission. The expression of TRPA has already been investigated in the human prostate and urethra, however, only very few studies have addressed the expression and distribution in the male and female genital tract. The present study aimed to investigate by means of immunohistochemistry (double-labeling technique, laser fluorescence microscopy) in the human clitoris and penile erectile tissue the localization of TRPA1 in relation to nNOS, the vasoactive intestinal polypeptide (VIP) and vesicular acetylcholine transporter (VAChT). In the clitoral tissue, TRPA1 was observed in basal epithelial cells and slender nNOS-positive nerve fibers transversing the subepithelial space. To a certain degree, in the clitoral epithelial cells, TRPA1 was found co-localized with vimentin. In human corpus cavernosum, immunoreactivity for TRPA1 was seen in nerves transversing the cavernous sinusoidal space and running alongside small arteries, these nerves also displayed expression of the vesicular acetylcholine transporter protein (VAChT). Varicose nerves containing nNOS or VIP were not immunoreactive for TRPA1. It seems likely that TRPA1 is involved in nitric oxide-mediated afferent sensory transmission in the clitoris while, in penile erectile tissue, a role for TRPA1 in cholinergic signaling might be assumed.


Subject(s)
Clitoris/innervation , Penis/innervation , TRPA1 Cation Channel/physiology , Adolescent , Adult , Animals , Cadaver , Clitoris/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Nitric Oxide Synthase/metabolism , Penis/pathology , Synaptic Transmission , Young Adult
6.
Int J Impot Res ; 29(4): 127-131, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28405029

ABSTRACT

Aside from phosphodiesterase (PDE) isoenzymes, protein kinases (cAK=cyclic AMP-binding protein kinase, cGK=cyclic GMP-binding protein kinase) have also been identified as important receptors for cyclic nucleotides. A significance of protein kinases in the control of the function of the male and female reproductive tract has been suggested; however, up until today, only a few approaches have addressed these enzymes in female genital tissues. The present study aimed to investigate by means of biochemical and immunohistochemical methods the expression of cAK and cGK. The distribution of cAK(I) and cGK(I) in relation to the vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and PDE type 4 (PDE4) was also evaluated. Cytosolic supernatants prepared from specimens of vaginal wall smooth muscle or epithelium were subjected to anion exchange chromatography and the activities of cAK and cGK(I) measured. To evaluate the distribution of cAK(I) and cGK(I) in relation to VIP, CGRP and PDE4, immunohistochemistry was conducted in sections of the human vaginal wall (full-wall specimens). Activities representing cGK(I) and cAK(I) were resolved from the chromatography column. Staining specific for cAK(Iα) was identified in both vascular and non-vascular vaginal smooth musculature, immunoreactivity for cGK(Iß) was observed in the smooth muscle and endothelium of small arteries interspersing the sections. cAK(Iα)-positive vessels were found innervated by slender varicose nerve fibers presenting the expression of VIP and CGRP. These arteries also expressed PDE4. Localization of cAK and cGK in close relation to key mediators of the cyclic AMP (PDE4, VIP) and cyclic GMP (CGRP) pathways indicate that both signaling systems may synergistically work together in human vaginal tissue.


Subject(s)
Cyclic AMP/metabolism , Cyclic GMP/metabolism , Signal Transduction/physiology , Vagina/enzymology , Aged , Aged, 80 and over , Calcitonin Gene-Related Peptide/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Female , Humans , Middle Aged , Vasoactive Intestinal Peptide/metabolism
7.
Internist (Berl) ; 58(3): 233-242, 2017 Mar.
Article in German | MEDLINE | ID: mdl-28124079

ABSTRACT

Massive bleeding of the urogenital tract is, in the same way as acute bleeding from all other organs, a medical emergency and necessitates precise diagnostics and treatment. In this article the topic is addressed in four main categories: first the inflammatory causes are discussed, followed by surgical, traumatic and neoplastic causes of massive bleeding. Subsequently, the rare but clinically relevant causes of acute and massive bleeding are described.


Subject(s)
Hemorrhage/etiology , Urogenital System , Emergencies , Humans
8.
Urologe A ; 55(10): 1321-1328, 2016 Oct.
Article in German | MEDLINE | ID: mdl-27138634

ABSTRACT

BACKGROUND: Self-concept consists of self-perceptions and is influenced by the life course of the person. OBJECTIVES: This study investigated associations between self-concept and erectile dysfunction (ED) in 45-year-old German men. MATERIALS AND METHODS: Forty-five-year-old, heterosexual men who had participated in the PROBASE-study were included. Erectile Function was evaluated using the International Index of Erectile Function (IIEF-6). The presence of ED was defined by IIEF-6 score ≤ 25. Self-concept was assessed using the facets "body image" (three items from the Dresden Body Image Inventory, DKB-35), "perception of masculinity" (three items from the Male Role Norms Scale, MRNS), "perceived social pressure with regard to sexual performance" (four newly constructed items), and "sexual self-esteem" (three newly constructed items). Scores for these facets of self-concept can range from 1 to 5. Higher scores indicate a more positive body image, higher sexual self-esteem, a more modern understanding of masculinity, and greater perceived social pressure. Differences in self-concept between men with ED and without ED were analyzed using the Mann-Whitney-U-test. Furthermore, Cohen's d effect sizes (ES d) were calculated. RESULTS: The responses of 3143 men were analyzed. Men with ED (16.2 %) have significantly lower scores regarding body image (mean 3.6 ± 0.6 vs 3.8 ± 0.5; p < 0.001; ES d = -0.5), perception of masculinity (mean 3.4 ± 0.7 vs 3.7 ± 0.6; p < 0.001; ES d = -0.4), and sexual self-esteem (mean 3.6 ± 0.6 vs 3.9 ± 0.5; p < 0.001, ES d = -0.4) than men without ED. Furthermore, they had significantly higher scores for perceived social pressure (mean 2.1 ± 0.7 vs 1.5 ± 0.5; p < 0.001; ES d = 1.2). CONCLUSIONS: Self-concept and ED are associated in 45-year-old men. Men with ED have a more negative body image, a more traditional understanding of masculinity, more negative sexual self-esteem, and greater perceived social pressure with regard to sexual performance than men without ED.


Subject(s)
Body Image/psychology , Erectile Dysfunction/epidemiology , Erectile Dysfunction/psychology , Quality of Life/psychology , Self Concept , Sexual Behavior/psychology , Erectile Dysfunction/diagnosis , Germany/epidemiology , Humans , Male , Men's Health/statistics & numerical data , Middle Aged
9.
Andrologia ; 48(10): 1214-1219, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27062177

ABSTRACT

Peptides, such as CNP, CGRP and VIP, are involved in the function of male penile erectile tissue. Tissue levels of said peptides are controlled by the endopeptidase enzymes. Theoretically, the inhibition of the degradation of CNP, CGRP and/or VIP should result in an enhancement in penile smooth muscle relaxation. The effects were investigated of CNP or VIP (0.1 nm-1 µm), without and following pre-exposure of the tissue to a threshold concentration of the endopeptidase inhibitor KC 12615 (10 µm, for 20 min), on the reversion of tension induced by means of electrical field stimulation. Drug effects on the production of cyclic AMP/GMP were also evaluated. Neither KC 12615, CNP and VIP nor the combination of CNP plus KC 12615 or VIP plus KC 12615 increased the response of the tissue to EFS. While no effects were observed of a pre-exposure of the tissue to KC 12615 on the production of cyclic AMP in the presence of VIP, an enhancement was registered in the accumulation of cyclic AMP in the presence of CNP plus KC 12615. Further studies are indicated to investigate whether endopeptidase inhibitors might tend to be more effective in tissues affected by a decreased local production of vasoactive peptides.


Subject(s)
Muscle Contraction/drug effects , Muscle Relaxation/drug effects , Muscle, Smooth/drug effects , Natriuretic Peptide, C-Type/pharmacology , Penis/drug effects , Protease Inhibitors/pharmacology , Vasoactive Intestinal Peptide/pharmacology , Adult , Cyclic AMP/metabolism , Cyclic GMP/metabolism , Electric Stimulation , Humans , Male , Middle Aged , Muscle, Smooth/metabolism , Penis/metabolism , Young Adult
10.
Aktuelle Urol ; 46(6): 453-60, 2015 Nov.
Article in German | MEDLINE | ID: mdl-26574950

ABSTRACT

BACKGROUND: Partial nephrectomy is the treatment of choice for clinical stage 1 renal tumours. Open partial nephrectomy is the standard operative technique. The use of minimally-invasive strategies such as laparoscopic, robot-assisted partial nephrectomy or laparoendoscopic single site (LESS) partial nephrectomy has increased in recent years. PATIENTS/MATERIAL AND METHODS: In this retrospective study, patients undergoing laparoscopic partial nephrectomy between December 2008 and November 2013 were evaluated. All patients presented with renal lesions suspicious for malignancy. Operations were performed as conventional laparoscopic transperitoneal partial nephrectomies (cLPN) or LESS partial nephrectomies (LESS-PN) in SITUS technique (single incision transumbilical surgery). The aim of the study was to compare perioperative outcome parameters such as duration of surgery, time of ischaemia, complications, need for transfusion, conversion rates, changes in renal function and duration of hospital stay in both groups. RESULTS: A total of 85 laparoscopic partial nephrectomies were performed in this study (72 cLPN and 13 LESS-PN). The average tumour size was 2.68±1.47 cm (cLPN) vs. 2.46±1.11 cm (LESS-PN). The mean duration of surgery was 175.17±50.026 min (cLPN) and 185.77±35.991 min (LESS-PN). 45 (62.5%) operations (cLPN) vs. 10 (76.9%) (LESS-PN) were performed in zero-ischaemia technique. There were no significant differences in perioperative outcome parameters between both groups. Postoperative complication rates (Clavien-Dindo≥3) were 11.1% (cLPN) vs. 7.7% (LESS-PN). CONCLUSIONS: LESS partial nephrectomy in SITUS technique is an attractive alternative to conventional laparoscopic and open partial nephrectomy.


Subject(s)
Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Laparoscopy/methods , Minimally Invasive Surgical Procedures/methods , Nephrectomy/methods , Adult , Aged , Female , Humans , Kidney/pathology , Male , Middle Aged , Neoplasm Staging , Operative Time , Retrospective Studies , Tumor Burden
11.
Aktuelle Urol ; 46(6): 481-5, 2015 Nov.
Article in German | MEDLINE | ID: mdl-26560846

ABSTRACT

The era of cytokines, given to patients with metastatic renal cell carcinoma (mRCC) as part of an unspecific immunomodulatory treatment concept, seems to have ended with the introduction of targeted therapies. However, preliminary data from studies on treatment with checkpoint inhibitors (e. g. anti-PD-1 and anti-PD-L1) may point the way to second-generation immunotherapy. The rationale of such immunomodulatory treatment is to stop or interrupt the tumour from "escaping" the body's immune defence. Thompson et al. report that increased protein expression of PD-L1 (CD274/ B7-H1) in tumour cells and tumour-infiltrating immune cells (TILs; lymphocytes and histiocytes) is associated with unfavourable clinical pathological parameters as well as poor survival. In small pilot groups of mRCC patients it was found that increased PD-L1 protein expression in tumours and TILs may be correlated with the objective response to anti-PD-1 treatment. Sometimes, however, a very wide variety of response rates was observed, which raises the question if this can be explained by individual expression levels of PD-L1 (CD 274) or PD-1 (PDCD1).Recently published data from the Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) Network now provide a genome-wide data base that allows us to review or validate the molecular results obtained in clear cell renal cell carcinomas (ccRCC) to date.In this study, we analysed the TCGA KIRC mRNA expression data for PD-L1 and PD-1 for a possible association with clinical pathological parameters and the survival of 417 ccRCC patients.The mRNA expression of PD-L1 in primary nephrectomy specimens revealed no significant association with unfavourable clinical parameters. Interestingly, though, a positive correlation with patient survival was found (HR=0,59, p=0,006).These results, which partly contradict the concept applied to date, point out the necessity to ascertain the characteristics of PD-L1 and PD-1 expression at mRNA and protein level in an appropriately sized patient population and evaluate the clinical significance.


Subject(s)
B7-H1 Antigen/genetics , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/therapy , Databases, Genetic , Gene Expression Regulation, Neoplastic/genetics , Immunotherapy/methods , Kidney Neoplasms/genetics , Kidney Neoplasms/therapy , Molecular Targeted Therapy/methods , Programmed Cell Death 1 Receptor/genetics , RNA, Messenger/genetics , B7-H1 Antigen/antagonists & inhibitors , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Disease Progression , Humans , Kidney/pathology , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Neoplasm Staging , Nephrectomy , Prognosis , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Statistics as Topic , Survival Rate
12.
Urologe A ; 54(9): 1223-33, 2015 Sep.
Article in German | MEDLINE | ID: mdl-26246111

ABSTRACT

Follow-up of patients after curative treatment of urological cancer is an important component of the treatment of patients. The aim of the follow-up is to monitor the success of treatment and to identify local or distant recurrences early to be able to initiate further treatment. Investigations used for the monitoring should follow the principle "as much as necessary, as little as possible". The interval and method of follow-up investigations should be based on the risk of recurrence for the individual patient. In recent years follow-up schemes have been improved and, for example in testicular cancer, have been adjusted to the individual risk group. In contrast, for other tumors, such as metastatic bladder carcinoma, recommendations for follow-up do not seem to be individualized. This article therefore gives an overview on current recommendations and evidence for the follow-up of the most important genitourinary tumor types.


Subject(s)
Ambulatory Care/standards , Medical Oncology/standards , Practice Guidelines as Topic , Urologic Neoplasms/diagnosis , Urologic Neoplasms/therapy , Urology/standards , Germany , Humans
13.
Aktuelle Urol ; 46(3): 242-7, 2015 May.
Article in German | MEDLINE | ID: mdl-26077309

ABSTRACT

Advanced urothelial carcinoma of the bladder is associated with a high metastatic potential. Life expectancy for metastatic patients is poor and rarely exceeds more than one year without further therapy. Neoadjuvant chemotherapy can decrease the tumour burden while reducing the risk of death. Adjuvant chemotherapy has been discussed controversially. Patients with lymph node-positive metastases seem to benefit the most from adjuvant chemotherapy. In selected patients, metastasectomy can prolong survival. In metastastic patients, the combination of gemcitabine and cisplatin has become the new standard regimen due to a lower toxicity in comparison to the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). For second-line treatment, vinflunine is the only approved therapeutic agent.


Subject(s)
Carcinoma, Transitional Cell/therapy , Chemotherapy, Adjuvant , Neoadjuvant Therapy , Urinary Bladder Neoplasms/therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Combined Modality Therapy , Humans , Lymphatic Metastasis/pathology , Metastasectomy , Neoplasm Staging , Survival Analysis , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology
14.
Aktuelle Urol ; 46(2): 151-7, 2015 Mar.
Article in German | MEDLINE | ID: mdl-25897537

ABSTRACT

Patients with metastatic renal cell carcinoma have a life-limiting prognosis. Therefore, the aim of therapy is normally palliative care. Nevertheless, substantial achievements have been made in the past years. Cytokines as long-term standard therapy have been replaced by new targeted therapies. Sunitinib, the combination of bevacizumab+interferon-alfa, pazopanib and temsirolimus are now approved for first-line therapy. Sunitinib and pazopanib can also be administered as second-line options - for pazopanib the use is restricted to the event of cytokine failure. Everolimus (after TKI therapy) und sorafenib (after cytokines) are other compounds now available for second-line therapy. In addition, axitinib was approved for second-line therapy after failure of sunitinib or cytokines. For questions regarding the optimal sequence, first study results are now available from the phase III trial.The purpose of an interdisciplinary expert meeting held in 2014 was to debate about which criteria should influence the therapy decision. The members discussed several aspects of treating patients with the disease. Results from the 2012 conference provided the basis for the 2014 meeting 1. As in previous years, the experts intended to provide common recommendations for clinical practice. The results of the 2012 conference are presented as short theses and a current therapy algorithm.


Subject(s)
Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/therapy , Interdisciplinary Communication , Kidney Neoplasms/pathology , Kidney Neoplasms/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Humans , Neoplasm Metastasis , Palliative Care , Retreatment
15.
Aktuelle Urol ; 46(1): 59-65, 2015 Jan.
Article in German | MEDLINE | ID: mdl-25658232

ABSTRACT

Prostate cancer is still the most common urological cancer of the elderly man. In some patients, a metastatic prostate cancer arises which may remain a stable disease for years with palliative antiandrogen therapy. On average, after 3-4 years, affected men develop a PSA rise and disease progression with the formation of a so-called castration-resistant disease. 5 years ago cytotoxic chemotherapy with docetaxel was the only life-prolonging treatment option in this situation. In the last 5 years, the results of randomised phase III studies have led to the approval of 5 new agents for the treatment of metastatic castration resistant prostate cancer (mCRPC). The results and approval status of the substances, Abiraterone, Enzalutamide, Cabazitaxel, Sipuleucel-T and radium-223 are described below. In addition, some aspects of sequential therapy and possible future molecular approaches are discussed.


Subject(s)
Antineoplastic Agents/therapeutic use , Prostatic Neoplasms, Castration-Resistant/therapy , Radium/therapeutic use , Aged , Biomarkers, Tumor/blood , Humans , Male , Prostate-Specific Antigen/blood , Prostatic Neoplasms, Castration-Resistant/blood , Prostatic Neoplasms, Castration-Resistant/pathology , Radioisotopes/therapeutic use
16.
Int J Impot Res ; 27(1): 16-9, 2015.
Article in English | MEDLINE | ID: mdl-25056810

ABSTRACT

The transient receptor potential cationic channel type A1 (TRPA1), belonging to a superfamily of cationic membrane channels, has been suggested to act as mechano- and pain sensor and, thus, to play a role in neurotransmission in the human body, including the urogenital tract. While the expression of TRPA1 has been investigated in a variety of tissues, up until today, no study has addressed the expression and distribution in the female genital tract. The present study aimed to investigate the expression and distribution of TRPA1 protein in human vaginal tissue. Reverse transcriptase PCR (RT-PCR) was applied in order to identify messenger ribonuleic acid specifically encoding for TRPA/A1. The distribution of TRPA1 in relation to the neuronal nitric oxide synthase (nNOS) and the signaling peptide calcitonin gene-related peptide (CGRP) was examined by means of immunohistochemical methods (double-antibody technique, laser fluorescence microscopy). RT-PCR analysis revealed the expression of mRNA encoding sequences specific for TRPA in the vaginal wall and epithelium. Immunostaining related to TRPA1 was observed in the basal epithelium and in slender varicose nerve fibers transversing the subepithelial and stromal space of the vaginal sections. In addition, these fibers presented immunoreactivity specific for nNOS or CGRP. The smooth musculature of the vaginal wall and small vessels interspersing the tissue did not present signals related to TRPA1. The findings indicate that TRPA1 might be involved in afferent neurotransmission in the vagina and work synergistically together with the nitric oxide/cyclic guanosine monophosphate pathway.


Subject(s)
Calcium Channels/genetics , Calcium Channels/metabolism , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Transient Receptor Potential Channels/genetics , Transient Receptor Potential Channels/metabolism , Vagina/metabolism , Calcitonin Gene-Related Peptide/analysis , Epithelium/chemistry , Female , Humans , Microscopy, Fluorescence/methods , Nerve Fibers/chemistry , Nitric Oxide Synthase Type I/analysis , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Synaptic Transmission , TRPA1 Cation Channel , Vagina/innervation
17.
Georgian Med News ; (234): 89-93, 2014 Sep.
Article in German | MEDLINE | ID: mdl-25341246

ABSTRACT

The so-called Induratio penis plastica (IPP), also known as Peyronie Disease or Morbus Peyronie, is the most common cause for deviation of the male penis. In most cases, the deviation is directed to the dorsal side. In face of a lawsuit related to a sexual offence, the opponent might argue that, due to an existing IPP, he is generally unable to insert his penis into a female's vagina. The aim of the present study was to examine the clinical files of thirty (30) consecutive patients who presented with IPP. Particular attention was given to the individual degree of penile deviation and the ability of the subjects to conduct vaginal intercourse. Subjects who had a dorsal penile deviation of 800 to 900, or a lateral deviation of 600, were unable to commence vaginal coitus. In contrast, three (3) subjects who presented with a ventral deviation of 30° to 40° had no difficulties in performing vaginal penetration. The medicolegal aspects of these findings are being discussed.


Subject(s)
Forensic Pathology , Penile Induration/physiopathology , Penis/physiopathology , Adult , Aged , Female , Humans , Male , Middle Aged , Sexual Behavior/physiology , Vagina/physiology
18.
Urologe A ; 53(11): 1639-43, 2014 Nov.
Article in German | MEDLINE | ID: mdl-25123560

ABSTRACT

INTRODUCTION: The gold standard for diagnosis and immediate therapy of bladder cancer is a transurethral resection (TURB) followed by histopathologic evaluation. The aim of this study was to assess the reliability of visual diagnosis by the operating urologist concerning dignity (malignant/benign) and staging compared to histopathologic evaluation. This is especially crucial since early mitomycin C instillation is based on the urologist's first impression. STUDY DESIGN AND METHODS: This prospective study included 311 cases of TURB from five German institutions. Surgeons were asked to estimate dignity of the neoplasm, tumor stage, and grade according to a standardized questionnaire. RESULTS: The subjective estimation/visual diagnosis of the operating urologist achieved a sensitivity with respect to identifying malignant tumors as such of 97%, while specificity was only 41%. Accordingly, the positive (PPV) and negative predictive values (NPV) were 76% and 88%, respectively. In general, muscle invasive cancer was predicted more often than confirmed by pathology (PPV 52%). However, whenever muscle invasive cancer was excluded by the urologist, this was confirmed by the pathologist in most the cases (NPV 95%). The educational degree did not influence the reliability and predictive value of visual diagnosis. CONCLUSION: This study shows that urologists cannot reliably distinguish benign from malignant lesions of bladder mucosa-regardless of their educational degree. A reliable diagnosis of a pathologist is definitely needed to plan final therapeutic steps.


Subject(s)
Cystoscopy/methods , Monitoring, Intraoperative/methods , Physical Examination/methods , Urethra , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/surgery , Adult , Aged , Clinical Competence , Female , Humans , Male , Middle Aged , Observer Variation , Reproducibility of Results , Sensitivity and Specificity
19.
Urologe A ; 53(11): 1656-60, 2014 Nov.
Article in German | MEDLINE | ID: mdl-25123561

ABSTRACT

BACKGROUND: Due to a worldwide rise of incidence, urolithiasis presents an increasing strain on the health system. Ureterorenoscopy (URS) is a standard treatment to extract stones in case of ureteral calculi. To increase the success rate of URS and to minimize complications, preoperative ureteral stenting (prestenting) has previously been described as suitable. However, published data are still conflicting. This article describes our single-center experience on the influence of prestenting on the outcome of ureterorenoscopic stone therapy. METHODS: A total of 442 patients who had undergone ureterorenoscopic stone extraction at the Wolfsburg Clinic between 2010 and 2011 were retrospectively evaluated regarding peri- and postoperative results. The Fisher's exact, the χ(2), and the Mann-Whitney U test were used to compare the group of patients with and without prestenting. RESULTS: Even though patients with prestenting suffered from stones with larger diameter that were more frequently located in the proximal ureter, the rates for postoperative stenting, perioperative complications, and retreatment were much lower then in the group of patients without prestenting (p<0.001). Furthermore, patients who had received prestenting had a significantly shorter hospital stay (median, 3 vs. 2 days, p<0.001) and higher rates of stone clearance (83.0 vs. 69.7%, p=0.001). CONCLUSION: According to our retrospective monocentric analysis, prestenting may significantly reduce the risk of complications as well as intra-/post-URS restenting and can increase the rate of complete stone clearance.


Subject(s)
Length of Stay/statistics & numerical data , Postoperative Complications/epidemiology , Stents/statistics & numerical data , Ureteral Calculi/epidemiology , Ureteral Calculi/surgery , Ureteroscopy/statistics & numerical data , Adult , Aged , Combined Modality Therapy/instrumentation , Combined Modality Therapy/methods , Combined Modality Therapy/statistics & numerical data , Comorbidity , Female , Germany/epidemiology , Humans , Male , Middle Aged , Prevalence , Retrospective Studies , Treatment Outcome , Ureteral Calculi/pathology
20.
Aktuelle Urol ; 45(1): 39-44, 2014 Jan.
Article in German | MEDLINE | ID: mdl-24500960

ABSTRACT

Patients with metastatic renal cell carcinoma have a life-limiting prognosis. Therefore, the aim of therapy is normally palliative care. Nevertheless, substantial achievements have been made in the past years. Cytokines as long-term standard therapy have been more and more replaced by new targeted therapies. Sunitinib, the combination of bevacizumab+interferon alfa, pazopanib and temsirolimus are now approved for first-line therapy. Sunitinib and pazopanib can also be applied as second-line options - for pazopanib the use is restricted to cases of cytokine failure. Everolimus (after TKI therapy) and sorafenib (after cytokines) are other compounds available for second-line therapy. In addition, axitinib was recently approved for second-line therapy after failure of sunitinib or cytokines. For questions regarding the optimal sequence, first study results are now available from the phase III trial. The purpose of an interdisciplinary expert meeting held in 2012 was to debate upon which criteria should influence the therapy decision. The members discussed several aspects of treating patients with the disease. Results from the 2011 conference provided the basis for the 2012 meeting 1. As in previous years, the experts intended to provide common recommendations for clinical practice. The results of the 2012 conference are presented as short theses and a current therapy algorithm.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Renal Cell/drug therapy , Cooperative Behavior , Disease Progression , Interdisciplinary Communication , Kidney Neoplasms/drug therapy , Molecular Targeted Therapy , Carcinoma, Renal Cell/pathology , Humans , Kidney Neoplasms/pathology , Palliative Care , Prognosis
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