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1.
Geburtshilfe Frauenheilkd ; 83(4): 410-436, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37034416

RESUMO

Aim This completely revised interdisciplinary S2k-guideline on the diagnosis, therapy, and follow-up care of female patients with urinary incontinence (AWMF registry number: 015-091) was published in December 2021. This guideline combines and summarizes earlier guidelines such as "Female stress urinary incontinence," "Female urge incontinence" and "Use of Ultrasonography in Urogynecological Diagnostics" for the first time. The guideline was coordinated by the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group for Urogynecology and Plastic Pelvic Floor Reconstruction (Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V., AGUB). Methods This S2k-guideline was developed using a structured consensus process involving representative members from different medical specialties and was commissioned by the Guidelines Commission of the DGGG, OEGGG and SGGG. The guideline is based on the current version of the guideline "Urinary Incontinence in Adults" published by the European Association of Urology (EAU). Country-specific items associated with the respective healthcare systems in Germany, Austria and Switzerland were also incorporated. Recommendations The short version of this guideline consists of recommendations and statements on the surgical treatment of female patients with stress urinary incontinence and urge incontinence. Specific solutions for the diagnostic workup and treatment of uncomplicated and complicated urinary incontinence are discussed. The diagnostics and surgical treatment of iatrogenic urogenital fistula are presented.

2.
Geburtshilfe Frauenheilkd ; 83(4): 377-409, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37034417

RESUMO

Aim This completely revised interdisciplinary S2k-guideline on the diagnosis, therapy, and follow-up care of female patients with urinary incontinence (AWMF registry number: 015-091) was published in December 2021. This guideline combines and summarizes earlier guidelines such as "Female stress urinary incontinence," "Female urge incontinence" and "Use of Ultrasonography in Urogynecological Diagnostics" for the first time. The guideline was coordinated by the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group for Urogynecology and Plastic Pelvic Floor Reconstruction (Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V., AGUB). Methods This S2k-guideline was developed using a structured consensus process involving representative members from different medical specialties and was commissioned by the Guidelines Commission of the DGGG, OEGGG and SGGG. The guideline is based on the current version of the guideline "Urinary Incontinence in Adults" published by the European Association of Urology (EAU). Country-specific items associated with the respective healthcare systems in Germany, Austria and Switzerland were also incorporated. Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, etiology, classification, symptoms, diagnostics, and treatment of female patients with urinary incontinence. Specific solutions for the diagnostic workup and appropriate conservative and medical therapies for uncomplicated and complication urinary incontinence are discussed.

3.
Urologie ; 62(2): 123-124, 2023 02.
Artigo em Alemão | MEDLINE | ID: mdl-36757402
4.
Dtsch Arztebl Int ; 120(5): 71-80, 2023 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-36647585

RESUMO

BACKGROUND: Pelvic floor disorders are common, especially in pregnancy and after delivery, in the postmenopausal period, and old age, and they can significantly impact on the patient's quality of life. METHODS: This narrative review is based on publications retrieved by a selective search of the literature, with special consideration to original articles and AWMF guidelines. RESULTS: Pelvic floor physiotherapy (evidence level [EL] 1), the use of pessaries (EL2), and local estrogen therapy can help alleviate stress/urge urinary incontinence and other symptoms of urogenital prolapse. Physiotherapy can reduce urinary incontinence by 62% during pregnancy and by 29% 3-6 months post partum. Anticholinergic and ß-sympathomimetic drugs are indicated for the treatment of an overactive bladder with or without urinary urge incontinence (EL1). For patients with stress urinary incontinence, selective serotonin-noradrenaline reuptake inhibitors can be prescribed (EL1). The tension-free tape is the current standard of surgical treatment (EL1); in an observational follow-up study, 87.2% of patients were satisfied with the outcome 17 years after surgery. Fascial reconstruction techniques are indicated for the treatment of primary pelvic organ prolapse, and mesh-based surgical procedures for recurrences and severe prolapse (EL1). CONCLUSION: Urogynecological symptoms should be specifically asked about by physicians of all relevant specialties; if present, they should be treated conservatively at first. Structured surgical techniques with and without mesh are available for the treatment of urinary incontinence and pelvic organ prolapse. Preventive measures against pelvic floor dysfunction should be offered during pregnancy and post partum.


Assuntos
Prolapso de Órgão Pélvico , Incontinência Urinária por Estresse , Incontinência Urinária , Humanos , Feminino , Seguimentos , Qualidade de Vida , Incontinência Urinária/etiologia , Incontinência Urinária/terapia , Prolapso de Órgão Pélvico/terapia , Prolapso de Órgão Pélvico/cirurgia , Incontinência Urinária por Estresse/cirurgia
5.
Urologie ; 62(2): 132-140, 2023 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-36625941

RESUMO

The current guideline "Female Urinary Incontinence" of the working group of scientific medical professional associations (AWMF) comprises a recommendation about the optional use of vaginal laser therapy in patients with mild to moderate stress urinary incontinence (SUI). Since to date there is no corresponding recommendation within the European Association of Urology (EAU) guidelines, the scientific evidence of the AWMF recommendation is evaluated. On the basis of limited data, both available laser systems (Erbium:YAG and CO2) seem to work equivalently in patients with mild SUI. The problematic comparability of studies with different definitions of incontinence, severity classifications, outcome parameters, and consideration of diverse etiological aspects is addressed. After thorough consideration of the available prognosticator research, a profile of an ideal laser candidate is developed for proper patient selection. This profile includes younger age, normal body mass index, sufficient estrogenization status, pure stress urinary incontinence due to urethral hypermobility, and urine loss of < 8 g during a 1 h pad test.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Incontinência Urinária por Estresse , Incontinência Urinária , Urologia , Humanos , Feminino , Incontinência Urinária por Estresse/cirurgia , Incontinência Urinária/cirurgia , Lasers de Estado Sólido/efeitos adversos , Terapia a Laser/efeitos adversos
7.
Urologe A ; 60(10): 1269-1276, 2021 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-34495382

RESUMO

As a consequence of the demographic change, the prevalence of female and male bladder and bowel dysfunction, functional pelvic floor disorders and pelvic organ prolapse are steadily increasing. Continence and pelvic floor centers are interdisciplinary facilities that focus on these functional disorders, including malformations, tumors and functional disorders resulting from neurogenic diseases, injuries or surgery. The affected patient clientele includes children, women, and men of all ages. The certification is carried out by the accredited certification company CERT iQ Certification Services. In addition to structural requirements, personal quality criteria are also implemented in the novel harmonized and standardized certification system. The assessment of treatment quality is also a component of the procedure, although it is currently limited to the midurethral sling tracer procedure for the treatment of female stress urinary incontinence. Regarding the other conservative and surgical treatment options for pelvic floor, bladder and bowel functional disorders, no quality of outcome has so far been recorded. Internationally recognized and validated questionnaires to assess preoperative and postoperative quality of life would be valuable tools to define the quality of treatment and outcome. Similarly, supplementary thresholds should be established for complication rates and quality of the success of treatment to identify centers with high expertise. In this context, it is crucial to consider the individual complexity of the patient groups and to distinguish between primary and recurrent interventions.


Assuntos
Distúrbios do Assoalho Pélvico , Prolapso de Órgão Pélvico , Certificação , Criança , Feminino , Humanos , Masculino , Diafragma da Pelve , Distúrbios do Assoalho Pélvico/diagnóstico , Distúrbios do Assoalho Pélvico/terapia , Qualidade de Vida
8.
Urol Int ; 98(3): 350-357, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28147376

RESUMO

INTRODUCTION: The study aimed to evaluate the efficacy and safety of solifenacin in older patients with overactive bladder (OAB). MATERIALS AND METHODS: Observational data on patients aged ≥70 years and the prescribed flexible dose of solifenacin for OAB were collected at 294 offices of German general practitioners. Baseline and week 12 data included type and severity of OAB symptoms, adverse events, quality of life, and change in cognitive function per Mini Mental State Examination (MMSE). RESULTS: Mean age of 774 patients was 78 ± 6 years. A decrease was observed in all OAB symptoms including a reduction of urinary urgency and micturition, each by 4 episodes per 24 h. No change in mean MMSE scores was apparent at week 12. Adverse events and treatment discontinuations were low at 5.8 and 0.5%, respectively. CONCLUSION: Solifenacin was well-tolerated while OAB symptoms declined at week 12. No relevant effect of solifenacin on cognitive function was observed in this elderly population.


Assuntos
Transtornos Cognitivos/induzido quimicamente , Succinato de Solifenacina/efeitos adversos , Succinato de Solifenacina/uso terapêutico , Bexiga Urinária Hiperativa/complicações , Bexiga Urinária Hiperativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Cognição/efeitos dos fármacos , Transtornos Cognitivos/psicologia , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Antagonistas Muscarínicos/uso terapêutico , Qualidade de Vida , Resultado do Tratamento , Bexiga Urinária Hiperativa/psicologia
9.
Urology ; 100: 249-254, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27890681

RESUMO

OBJECTIVE: To evaluate the long-term outcomes in patients with classic bladder exstrophy and continent anal urinary diversion (CAD) for continence, upper urinary tract status, secondary malignancies, and sexual function. PATIENTS AND METHODS: The medical records of 82 exstrophy patients having undergone CAD in our department between 1970 and 2015 were reviewed. Patients were invited for follow-up examinations and asked to complete validated questionnaires relating to sexual function. RESULTS: Thirty-two of 57 eligible patients with a median follow-up of 23.9 years were included in the study. Ninety-seven percent of patients were fully continent during daytime. Upper urinary tract and renal function remained stable in 75% and 87%, respectively. Five patients developed secondary malignancies originating from the rectal reservoir. Forty-one percent received prophylactic alkaline substitution. Sexual function as measured by the Female Sexual Function Index and the International Index on Erectile Function was negatively affected in all domains in both genders. Eighty-six percent of patients had a stable relationship and 35% were married. Five women conceived a total of 6 healthy children. Paternity rate was 40%. CONCLUSION: CAD constitutes an effective treatment option with acceptable long-term outcomes in exstrophy patients in whom all attempts at restoring the lower urinary tract have failed. Long-term follow-up of the upper urinary tract, assessment of acid-base balance, and endoscopy of the rectosigmoid reservoir are paramount for the safety of this type of management. Evaluation of sexual dysfunction should be an active part of follow-up.


Assuntos
Extrofia Vesical/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/psicologia , Derivação Urinária , Coletores de Urina , Adenocarcinoma/epidemiologia , Adenoma/epidemiologia , Adulto , Neoplasias do Colo/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Comportamento Sexual , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Neoplasias da Bexiga Urinária/epidemiologia , Adulto Jovem
10.
Urol Int ; 97(2): 142-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27287607

RESUMO

INTRODUCTION: The study aimed to compare the incidence of cardiovascular events (CVEs) after donor nephrectomy (DN) and radical tumor nephrectomy (RN), according to an estimated glomerular filtration rate (eGFR), were evaluated over time. MATERIALS AND METHODS: Follow-up was collected for DN who underwent surgery from 1998 to 2007 for CVE and renal function. All DN were matched for age to patients treated by RN or adenoma enucleation (control group), who were eligible for DN. eGFR was estimated using the Cockgroft-Gould formula. Patients with preoperative comorbidities were excluded. RESULTS: Thirty DN (median age 48.9 years) were included with a median follow-up of 138.5 months (interquartile range 119-159). No significant differences in patients' characteristics were found preoperatively (p > 0.5). Four out of 30 DN developed a CVE (3 myocardial infarctions (MI), 1 stroke), 2 of 30 patients in the control group (both MI) and 8 of 30 RN patients (6 MI, 2 strokes, p > 0.05). Arterial hypertension developed in 14 DN (46.7%), in 12 (40%) after RN and in 15 controls. The CVE occurred after a median time of 68 months (5-231) and were related to a drop of ∼30% in the eGFR irrespective of the group. CONCLUSION: Decline of renal function after nephrectomy is the main risk factor for CVE. Close monitoring of renal function and new onset hypertension is warranted.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Neoplasias Renais/cirurgia , Nefrectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Adulto , Feminino , Seguimentos , Humanos , Incidência , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Fatores de Tempo , Doadores de Tecidos
11.
Urol Int ; 96(3): 337-44, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26807854

RESUMO

OBJECTIVE: To identify clinical parameters influencing German urologists treating cT1a renal tumours, we performed a nationwide survey among members of the German urological associations (DGU and BDU). MATERIAL AND METHODS: In spring 2012, DGU and BDU members were invited to complete our survey. For 8 cases and 3 index patients, participants were asked about their preferred treatment. Multivariate analyses were used to identify significant parameters leading the responders to favour radical nephrectomy (RN) over nephron sparing surgery (NSS) as well as active surveillance (AS) over invasive treatment. RESULTS: Three hundred six (7.4%) forms were included in our analysis. In patients with larger tumours (4 vs. 2 cm, OR 3.16), endophytic growth (endophytic vs. exophytic, OR 2.70), hilar tumour location (perihilar vs. polar, OR 14.37), normal renal function (normal vs. decreased, OR 1.92) and elderly patients (elderly vs. young, OR 2.14) RN was preferred. Based on decreased renal function (decreased vs. normal, OR 12.74), elderly (elderly vs. young, OR 14.31) and hilar tumour location (perihilar vs. polar, OR 2.14), 77.2% of respondents recommended AS for selected patients. Treating physician factors had no influence on the treatment preference. CONCLUSIONS: Elderly patients with small tumours and impaired renal function were candidates for AS. Younger patients mainly underwent NSS. However, when the tumours' location was endophytic or hilar, RN was recommended.


Assuntos
Neoplasias Renais/cirurgia , Nefrectomia/métodos , Néfrons/cirurgia , Urologia/métodos , Adulto , Idoso , Biópsia , Feminino , Alemanha , Humanos , Rim/cirurgia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Inquéritos e Questionários , Tomografia Computadorizada por Raios X
12.
Clin Oral Investig ; 20(4): 753-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26307268

RESUMO

OBJECTIVES: The aim of this study was to evaluate the role of bone scintigraphy (BS) in early prediction of clinically asymptomatic bisphosphonate (BP)-related osteonecrosis of the jaws (BRONJ) in patients with metastatic castration-resistant prostate cancer (mCRPC). MATERIAL AND METHODS: BS of mCRPC patients treated with BP was evaluated for pathologic tracer uptake of the jaws in BS suspicious for BRONJ. Results were compared to development of clinically evident BRONJ. Sensitivity, specificity and predictive values of BS for the detection of BRONJ as well as time from beginning of BP therapy to pathologic tracer uptake in BS and time from pathologic tracer uptake in BS to clinically evident BRONJ were determined. RESULTS: Thirty BP-treated patients were included. Nine patients (30%) had pathologic BS lesions of the jaws. Six patients (20%) developed BRONJ. Sensitivity and specificity of BS for BRONJ prediction were 67 and 79%. Median time from the start of BP treatment to pathologic tracer uptake in BS was 28 months (range 10-33) and from pathologic tracer uptake in BS to clinically evident BRONJ 6.5 months (range 2-19). Pathologic tracer uptake in BS was significantly more often observed in patients who developed BRONJ compared to patients who did not (p = 0.049; OR 7.6). CONCLUSIONS: Patients with pathologic tracer uptake in the jaws in BS significantly more often develop BRONJ. An unsuspicious BS is predictive for absence of BRONJ in the future. CLINICAL RELEVANCE: We conclude that when BS has been performed, it should not only be used to assess tumour stage and treatment response but also to check for pathologic tracer uptake in the jaws in BS to detect BRONJ at an early stage in mCRPC patients receiving bisphosphonates.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico por imagem , Difosfonatos/efeitos adversos , Neoplasias de Próstata Resistentes à Castração/complicações , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/complicações , Conservadores da Densidade Óssea , Difosfonatos/uso terapêutico , Humanos , Arcada Osseodentária , Masculino , Osteonecrose/induzido quimicamente , Cintilografia
13.
Int Urol Nephrol ; 47(11): 1789-96, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26377495

RESUMO

PURPOSE: In bladder cancer (BCa) patients undergoing radical cystoprostatectomy (RCPx), concomitant prostate cancer (PCa) is a common finding. Up to now there is no clear evidence to suggest that concomitant PCa is a predictor of outcome in these patients. Aim of this study was to assess incidence and clinicopathologic characteristics of concomitant PCa in RCPx specimen and correlate it to survival parameters from a single-centre material over two decades. METHODS: All men who had undergone RCPx for BCa at our institution between 1994 and 2013 were included in this study. Clinicopathologic parameters for BCa and PCa were evaluated and correlated with outcome parameters. Survival analysis was performed for the subgroup of nonmetastatic organ-confined BCa to evaluate the role of concomitant Gleason Score (GS) ≥7 PCa. RESULTS: Of 945 men who had undergone RCPx for BCa, concomitant PCa was present in 237 patients (25.1 %). There was a significant increase in PCa incidence from 18.9 to 32.3 % between 1994 and 2013 (p = 0.009). Concomitant PCa represented a more aggressive phenotype at the end of the study (p = 0.037). In nonmetastatic organ-confined BCa, concomitant GS ≥7 PCa (HR 3.09; p = 0.0001) and age > 68 (HR 1.80; p = 0.0004) were independent negative predictors for overall survival. CONCLUSIONS: Concomitant PCa in RCPx specimen of BCa patients is a common finding. The incidence of concomitant PCa has significantly increased within 2 decades, presenting a more aggressive phenotype. Age and in particular concomitant GS ≥7 PCa are independent prognosticators for poor survival in patients with nonmetastatic organ-confined BCa.


Assuntos
Neoplasias Primárias Múltiplas/mortalidade , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Neoplasias da Bexiga Urinária/mortalidade , Fatores Etários , Idoso , Cistectomia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prostatectomia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
14.
J Immunother Cancer ; 3: 26, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26082837

RESUMO

BACKGROUND: CV9103 is a prostate-cancer vaccine containing self-adjuvanted mRNA (RNActive®) encoding the antigens PSA, PSCA, PSMA, and STEAP1. This phase I/IIa study evaluated safety and immunogenicity of CV9103 in patients with advanced castration-resistant prostate-cancer. METHODS: 44 Patients received up to 5 intra-dermal vaccinations. Three dose levels of total mRNA were tested in Phase I in cohorts of 3-6 patients to determine a recommended dose. In phase II, 32 additional patients were treated at the recommended dose. The primary endpoint was safety and tolerability, the secondary endpoint was induction of antigen specific immune responses monitored at baseline and at weeks 5, 9 and 17. RESULTS: The most frequent adverse events were grade 1/2 injection site erythema, injection site reactions, fatigue, pyrexia, chills and influenza-like illness. Possibly treatment related urinary retention occurred in 3 patients. The recommended dose was 1280 µg. A total of 26/33 evaluable patients treated at 1280 µg developed an immune response, directed against multiple antigens in 15 out of 33 patients. One patient showed a confirmed PSA response. In the subgroup of 36 metastatic patients, the Kaplan-Meier estimate of median overall survival was 31.4 months [95 % CI: 21.2; n.a]. CONCLUSIONS: The self-adjuvanted RNActive® vaccine CV9103 was well tolerated and immunogenic. The technology is a versatile, fast and cost-effective platform allowing for creation of vaccines. The follow-up vaccine CV9104 including the additional antigens prostatic acid phosphatase (PAP) and Muc1 is currently being tested in a randomized phase IIb trial to assess the clinical benefit induced by this new vaccination approach. TRIAL REGISTRATION: EU Clinical Trials Register: EudraCT number 2008-003967-37, registered 27 Jan 2009.

15.
Urol Int ; 95(3): 346-51, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25871316

RESUMO

INTRODUCTION: To evaluate incidence, symptoms and management of postoperative pancreatic fistula (POPF) after urologic surgery based on our experience. MATERIAL AND METHODS: Database was searched for clinically evident POPF after urologic surgery between 1998 and 2014. Fistulae were graded using the POPF classification. Clinical course of every POPF patient was evaluated. RESULTS: During this time, 3,200 surgeries for renal, adrenal and retroperitoneal pathologies were performed. Twelve POPF occurred postoperatively in this series. Eight fistulae were POPF grade A, 3 POPF grade B and one POPF grade C. POPF became clinically evident after a median of 3 days (IQR 2-3). In all POPF grade A/B patients, secretion from the pancreatic fistula completely subsided under conservative therapy. In one POPF grade C patient with positive surgical margins of urothelial cancer, conservative treatment failed and the patient died due to POPF-related sepsis. CONCLUSIONS: POPF is a rare complication after urologic surgery. Conservative therapy is the first choice of treatment and will be successful in the majority of cases. Pancreatic fistula after surgery of recurrent malignancy may have a poor outcome.


Assuntos
Fístula Pancreática , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/diagnóstico , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Fístula Pancreática/terapia , Estudos Retrospectivos , Procedimentos Cirúrgicos Urológicos/efeitos adversos , Adulto Jovem
16.
J Urol ; 194(2): 539-46, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25623744

RESUMO

PURPOSE: Bone metastasis develops in 30% of all patients with renal cell carcinoma. We elucidated the mechanisms that lead to and predict bone metastasis of renal cell carcinoma. MATERIALS AND METHODS: Nine renal cell carcinoma primary cell lines and 30 renal cell carcinoma tissue specimens (normal and tumor tissue) were collected from 3 patients with no metastasis and 10 with lung or bone metastasis within 5 years after nephrectomy. Cell migration was analyzed in a Boyden chamber and proliferation was assessed by bromodeoxyuridine incorporation. Adhesion to fibronectin, and collagen I and IV was determined after cell staining. The expression and/or activity of cellular signaling molecules was quantified by Western blot. RESULTS: Compared to renal cell carcinoma cells from patients without metastasis, the migration of cells from patients with bone metastasis was enhanced 13.5-fold (p = 0.034), and adhesion to fibronectin and collagen I was enhanced 5.8-fold and 6.1-fold (p = 0.002 and 0.014, respectively). In general proliferation was decreased in metastasizing cells. In accordance with these results we detected higher activity of AKT (p = 0.011) and FAK (p = 0.054), higher integrin α5 expression (p = 0.052) and lower PTEN expression in primary cells from patients with bone metastasis compared to nonmetastasizing cells. An almost similarly altered expression pattern was also observed in the renal cell carcinoma tissue specimens and the normal renal tissue of patients with bone metastasis. CONCLUSIONS: We describe evidence that molecular predispositions determine the potential for bone metastasis to develop in renal cell carcinoma, which may serve as prognostic markers after initial tumor detection.


Assuntos
Neoplasias Ósseas/secundário , Carcinoma de Células Renais/secundário , DNA de Neoplasias/genética , Regulação Neoplásica da Expressão Gênica , Integrina alfa5/genética , Neoplasias Renais/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Western Blotting , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Movimento Celular , Humanos , Integrina alfa5/biossíntese , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , PTEN Fosfo-Hidrolase/biossíntese , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas c-akt/biossíntese , Transdução de Sinais , Proteínas Supressoras de Tumor
17.
Mol Cancer ; 13: 42, 2014 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-24576174

RESUMO

BACKGROUND: The prognosis for renal cell carcinoma (RCC) is related to a high rate of metastasis, including 30% of bone metastasis. Characteristic for bone tissue is a high concentration of calcium ions. In this study, we show a promoting effect of an enhanced extracellular calcium concentration on mechanisms of bone metastasis via the calcium-sensing receptor (CaSR) and its downstream signaling molecules. METHODS: Our analyses were performed using 33 (11/category) matched specimens of normal and tumor tissue and 9 (3/category) primary cells derived from RCC patients of the 3 categories: non-metastasized, metastasized into the lung and metastasized into bones during a five-year period after nephrectomy. Expression of CaSR was determined by RT-PCR, Western blot analyses and flow cytometry, respectively. Cells were treated by calcium and the CaSR inhibitor NPS 2143. Cell migration was measured in a Boyden chamber with calcium (10 µM) as chemotaxin and proliferation by BrdU incorporation. The activity of intracellular signaling mediators was quantified by a phospho-kinase array and Western blot. RESULTS: The expression of CaSR was highest in specimens and cells of patients with bone metastases. Calcium treatment induced an increased migration (19-fold) and proliferation (2.3-fold) exclusively in RCC cells from patients with bone metastases. The CaSR inhibitor NPS 2143 elucidated the role of CaSR on the calcium-dependent effects. After treatment with calcium, the activity of AKT, PLCγ-1, p38α and JNK was clearly enhanced and PTEN expression was almost completely abolished in bone metastasizing RCC cells. CONCLUSIONS: Our results indicate a promoting effect of extracellular calcium on cell migration and proliferation of bone metastasizing RCC cells via highly expressed CaSR and its downstream signaling pathways. Consequently, CaSR may be regarded as a new prognostic marker predicting RCC bone metastasis.


Assuntos
Neoplasias Ósseas/secundário , Osso e Ossos/química , Cálcio/metabolismo , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Receptores de Detecção de Cálcio/metabolismo , Western Blotting , Carcinoma de Células Renais/secundário , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Neoplasias Renais/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
World J Urol ; 32(4): 1041-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24135915

RESUMO

PURPOSE: To evaluate the efficacy and safety of solifenacin for the treatment of OAB in men. METHODS: This prospective observational study, reflective of actual practice patterns, was conducted in men older than 18 years who were prescribed solifenacin for the treatment of OAB symptoms. Men with suspected bladder outlet obstruction were excluded. The primary efficacy measure was change in OAB symptoms after 12 weeks of solifenacin. Also assessed were changes in severity of urinary urgency, IPSS, quality of life, cognitive function, and adverse events. Data were analyzed using descriptive methods. RESULTS: A total of 799 men recruited at 251 centers, average age 67 years (range 27-92), received solifenacin 5 mg or 10 mg/day. Mean episodes of urinary urgency, frequency, and nocturia decreased by 4.4, 3.6, and 1.4 episodes/24 h, respectively. As per IPSS, severe urinary symptoms were reported by 20.4 % at baseline versus by 2.3 % at week 12. Both voiding and storage symptoms showed improvement. Patient-reported general health condition was excellent/good for 39 % at baseline increasing to 76 % at week 12. Adverse event rate was 5.5 %, and discontinuation of solifenacin due to an event was 1.6 %. No change in post-void residual urine volume was experienced in 80%, while an increase of ≥50 mL was observed in 2.2 %; no cases of acute urinary retention occurred. Baseline mean MMSE was 27.5 points versus 27.9 points at week 12. CONCLUSIONS: Solifenacin reduced all OAB symptoms, was well tolerated, and had no apparent effect on post-void residual urine volume. Cognitive function was unaltered in this population of older men with OAB.


Assuntos
Quinuclidinas/efeitos adversos , Quinuclidinas/uso terapêutico , Tetra-Hidroisoquinolinas/efeitos adversos , Tetra-Hidroisoquinolinas/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Agentes Urológicos/efeitos adversos , Agentes Urológicos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cognição/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Qualidade de Vida/psicologia , Quinuclidinas/farmacologia , Índice de Gravidade de Doença , Succinato de Solifenacina , Tetra-Hidroisoquinolinas/farmacologia , Resultado do Tratamento , Bexiga Urinária Hiperativa/psicologia , Agentes Urológicos/farmacologia
19.
BJU Int ; 112(7): 972-81, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24118958

RESUMO

OBJECTIVES: To evaluate the clinical efficiency of a third generation electromagnetic shock wave lithotripter, the Lithoskop(®) (Siemens, Erlangen, Germany), regarding outcomes, stone disintegration, retreatment and complication rates. To compare the results of the Lithoskop with other currently available systems and the reference standard lithotripter, the HM-3 (Dornier MedTech Europe GmbH, Wessling, Germany). PATIENTS AND METHODS: We analysed the data from 183 patients, including 13 children, undergoing extracorporeal shock wave lithotripsy (ESWL) for renal and ureteric calculi collected from a prospectively populated database. Outcomes were assessed by plain abdominal film of kidney, ureter and bladder and renal ultrasonography for radiopaque and computerized tomography for radiolucent stones 1 day after treatment and after 3 months. We analysed stone size and location before and after treatment, stone disintegration rate, retreatment rate, stone-free and residual fragment rates after 3 months, along with auxiliary procedures and complications. RESULTS: The mean (range) patient age was 48.6 (1.3-81.4) years, including 13 children with a mean (range) age of 8.4 (1.3-16.7) years, and 77% of the patients were male. In all, 46% of the calculi were localized in the kidney and 54% in the ureter. Renal stones were localized in the upper, middle and lower calyx and in the renal pelvis in 9, 29, 30 and 32% of patients, respectively. Ureteric stones were localized in the upper, mid- and distal ureter in 29, 19 and 52% of patients, respectively. The median (range) stone size before ESWL was 10 (4-25) mm in the kidney and 8 (4-28) mm in the ureteric calculi. The overall stone-free rate after 3 months was 91% (88% for renal and 93% for ureteric calculi); the mean number of sessions to achieve these rates was 1.3. Stone-free rates and the required number of sessions were determined only by stone size. In 7.1% of the patients (n = 13) post-interventional auxiliary procedures were necessary. We observed one perirenal haematoma as a major complication (0.5%), but this did not require any further therapy. CONCLUSIONS: Clinical stone-free rates with the Lithoskop are high and similar to those of other available systems, including the reference standard HM-3 lithotripter. Retreatment and complication rates are low, supporting the use of ESWL as first-line therapy for urinary calculi <10 mm, independent of stone location.


Assuntos
Cálculos Renais/terapia , Litotripsia/instrumentação , Cálculos Ureterais/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Desenho de Equipamento , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
20.
Dig Surg ; 30(4-6): 459-65, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24481247

RESUMO

BACKGROUND: The objective was to investigate whether two-dimensional intraoperative neuromonitoring (IONM) of pelvic autonomic nerves has the potential to predict erectile function (EF) following surgery for rectal cancer. METHODS: A consecutive series of 17 sexually active male rectal cancer patients undergoing IONM-based nerve-sparing low anterior rectal resection were evaluated prospectively. IONM was performed by electric stimulation of the pelvic splanchnic nerves with concomitant electromyography of the internal anal sphincter and cystomanometry. Sexual function was assessed using a validated questionnaire. RESULTS: The degree of agreement between electromyography-based and cystomanometry-based IONM with postoperative EF was moderate and good (κ = 0.43 and κ = 0.66). Combined assessment yielded the best agreement (κ = 0.76) with sensitivity of 90%, specificity of 86%, positive predictive value of 90%, negative predictive value of 86%, and overall accuracy of 88%, respectively, in terms of prediction of postoperative EF. CONCLUSION: The method may be suitable to predict male EF following rectal resection.


Assuntos
Canal Anal/inervação , Vias Autônomas/fisiopatologia , Disfunção Erétil/diagnóstico , Disfunção Erétil/prevenção & controle , Monitorização Intraoperatória/métodos , Neoplasias Retais/cirurgia , Bexiga Urinária/inervação , Idoso , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Disfunção Erétil/etiologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/métodos , Estudos Prospectivos , Neoplasias Retais/patologia
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