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1.
Ann Surg Oncol ; 31(10): 7220-7228, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38969859

RESUMEN

BACKGROUND: Analysis of temporal trends of urinary diversion (UD) and identification of predictive factors for continent urinary diversion (CUD) in patients with bladder cancer (BC) is scarce and data on large cohorts are missing. We aimed to describe longitudinal temporal trends and predictive factors for UD among patients with BC receiving radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analysed institutional data collected from patients undergoing RC from 1986 to 2022 to describe changes in patients' characteristics and UD. Primary end points were patients' characteristics associated with type of UD. Logistic regression analysis was used to determine predictive factors for CUD. RESULTS: In total, 2224 patients (77.16% male, 22.84% female) with a mean age of 66 years [standard deviation (SD), 10.64 years] were included. We observed an increase in mean age from 59.86 (10.8) years (1986-1990) to 69.85 (9.99) years (2016-2022) (p < 0.001). The proportion of CUD gradually declined from 43.72% (94/215; 1986-1990) to 18.38% (86/468; 2016-2022). Patients who were male [odds ratio (OR): 1.92, 95% confidence interval (CI): 1.43-2.57, p < 0.001), younger (OR: 0.88, 95% CI: 0.87-0.89, p < 0.001) and had no hydronephrosis prior to RC (OR: 2.2, 95% CI: 1.66-2.92, p < 0.001) were more likely to receive CUD. CONCLUSIONS: We report the largest European single-center cohort of UD after RC, demonstrating a significant shift from CUD to IUD, accompanied by an increasing age. Finally, our data mirrors the development and extensive experience with the Mainz Pouch-I in the 1980's and 1990's together with other colon pouches.


Asunto(s)
Cistectomía , Neoplasias de la Vejiga Urinaria , Derivación Urinaria , Humanos , Cistectomía/métodos , Cistectomía/tendencias , Masculino , Derivación Urinaria/tendencias , Derivación Urinaria/estadística & datos numéricos , Derivación Urinaria/métodos , Femenino , Neoplasias de la Vejiga Urinaria/cirugía , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Estudios de Seguimiento , Pronóstico , Reservorios Urinarios Continentes , Factores de Tiempo , Centros Médicos Académicos/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología
2.
Arch Orthop Trauma Surg ; 141(5): 855-859, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32728978

RESUMEN

When open-book injuries are neglected and result into a pelvic malunion or nonunion, long-term problems, such as chronic pain, gait abnormalities, sitting discomfort, neurological symptoms and urogenital symptoms can occur. In this case report, we describe the repair of a neglected pelvic disruption with the dislocation of the urinary bladder in a one-stage procedure. The clinical image with which the patient presented could be split into unique sub-problems, for which separate solutions needed to be chosen: large symphysis diastasis, instability and pain in both SI joints, malunion of the superior and inferior pubic rami fractures; and urinary bladder herniation into the upper thigh. In a single-stage procedure, the pelvic ring was reconstructed and the bladder reduced. The patient was thereafter continent for urine and could walk independently. A complex clinical problem was divided into its sub-problems, for which specific solutions were found.


Asunto(s)
Fracturas Óseas , Huesos Pélvicos , Procedimientos de Cirugía Plástica/métodos , Muslo , Vejiga Urinaria , Anciano , Femenino , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Humanos , Huesos Pélvicos/diagnóstico por imagen , Huesos Pélvicos/lesiones , Huesos Pélvicos/cirugía , Muslo/diagnóstico por imagen , Muslo/fisiopatología , Vejiga Urinaria/diagnóstico por imagen , Vejiga Urinaria/lesiones , Vejiga Urinaria/fisiopatología , Vejiga Urinaria/cirugía
4.
World J Urol ; 37(1): 85-93, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30238399

RESUMEN

PURPOSE: To provide a comprehensive overview and update of the joint consultation of the International Consultation on Urological Diseases (ICUD) and Société Internationale d'Urologie on Bladder Cancer Urinary Diversion (UD). METHODS: A detailed analysis of the literature was conducted reporting on the different modalities of UD. For this updated publication, an exhaustive search was conducted in PubMed for recent relevant papers published between October 2013 and August 2018. Via this search, a total of 438 references were identified and 52 of them were finally eligible for analysis. An international, multidisciplinary expert committee evaluated and graded the data according to the Oxford System of Evidence-based Medicine. RESULTS: The incidence of early complications has been reported retrospectively in the range of 20-57%. Unfortunately, only a few randomized controlled studies exist within the field of UD. Consequently, almost all studies used in this report are of level 3-4 evidence including expert opinion based on "first principles" research. CONCLUSIONS: Complications rates overall following RC and UD are significant, and when strict reporting criteria are incorporated, they are much higher than previously published. Complications can occur up to 20 years after surgery, emphasizing the need for lifelong follow-up. Progress has been made to prevent complications implementing robotic surgery and fast track protocols. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good results.


Asunto(s)
Carcinoma de Células Transicionales/cirugía , Cistectomía/métodos , Complicaciones Posoperatorias/epidemiología , Neoplasias de la Vejiga Urinaria/cirugía , Derivación Urinaria/métodos , Carcinoma de Células Transicionales/patología , Humanos , Músculo Liso/patología , Invasividad Neoplásica , Procedimientos Quirúrgicos Robotizados/métodos , Neoplasias de la Vejiga Urinaria/patología , Reservorios Urinarios Continentes
6.
Cell Commun Signal ; 16(1): 35, 2018 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-29954386

RESUMEN

BACKGROUND: Loss of PTEN is involved in tumor progression of several tumor entities including renal cell carcinoma (RCC). During the translation process PTEN generates a number of splice variants, including PTEN-Δ. We analyzed the impact of PTEN-Δ in RCC progression. METHODS: In specimens of RCC patients the expression of PTEN-Δ and PTEN was quantified. The PTEN expressing RCC cell line A498 and the PTEN deficient 786-O cell line were stably transfected with the PTEN-Δ or PTEN transcript. In Caki-1 cells that highly express PTEN-Δ, this isoform was knocked down by siRNA. Cell migration, adhesion, apoptosis and signaling pathways activities were consequently analyzed in vitro. RESULTS: Patients with a higher PTEN-Δ expression had a longer lymph node metastasis free and overall survival. In RCC specimens, the PTEN-Δ expression correlated with the PTEN expression. PTEN-Δ as well as PTEN induced a reduced migration when using extracellular matrix (ECM) compounds as chemotaxins. This effect was confirmed by knockdown of PTEN-Δ, inducing an enhanced migration. Likewise a decreased adhesion on these ECM components could be shown in PTEN-Δ and PTEN transfected cells. The apoptosis rate was slightly increased by PTEN-Δ. In a phospho-kinase array and Western blot analyses a consequently reduced activity of AKT, p38 and JNK could be shown. CONCLUSIONS: We could show that the PTEN splice variant PTEN-Δ acts similar to PTEN in a tumor suppressive manner, suggesting synergistic effects of the two isoforms. The impact of PTEN-Δ in context of tumor progression should thus be taken into account when generating new therapeutic options targeting PTEN signaling in RCC.


Asunto(s)
Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Fosfohidrolasa PTEN/metabolismo , Apoptosis , Carcinoma de Células Renales/genética , Adhesión Celular , Movimiento Celular , Progresión de la Enfermedad , Matriz Extracelular/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Humanos , Integrinas/metabolismo , Neoplasias Renales/genética , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Fosfohidrolasa PTEN/deficiencia , Fosfohidrolasa PTEN/genética , Isoformas de Proteínas/deficiencia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genética
7.
J Urol ; 195(2): 465-70, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26475661

RESUMEN

PURPOSE: We evaluated patients with classic bladder exstrophy and a history of urinary diversion for sexual function, social integration and paternity. MATERIALS AND METHODS: We reviewed the medical records of males older than 18 years with exstrophy who had undergone urinary diversion at our department between 1969 and 2014. Patients were invited for structured followup examinations and were asked to complete questionnaires relating to sexual function, social integration and paternity. RESULTS: Of 79 eligible patients 39 (49%) with a mean followup of 23.8 years (range 2 to 45) were included in the study. Of the patients 41% had undergone primary urinary diversion and 59% had undergone secondary urinary diversion after failed reconstruction of the exstrophic bladder. Sexual function as measured by the International Index of Erectile Function was negatively affected in all domains, with mild to moderate dysfunction in 90% of patients. Of the patients 73% had a stable relationship and 32% were married. A high level of education had been achieved by 77% of patients. Sperm quality was poor (oligoasthenoteratozoospermia) in 71% of patients. Among the patients 11 had fathered a total of 16 healthy children. CONCLUSIONS: Despite multiple reconstructive procedures of the genitourinary tract, including removal of the exstrophic bladder and subsequent urinary diversion, sexuality and paternity in this subset of patients was comparable to reported series of men in whom the bladder had been preserved. Evaluation of sexual function and fertility should be part of long-term followup, and treatment should be offered if indicated. Currently staged concepts of exstrophy repair should be applied to improve the cosmetic and functional outcomes of the genitourinary tract in patients with exstrophy.


Asunto(s)
Extrofia de la Vejiga/cirugía , Disfunción Eréctil/etiología , Infertilidad Masculina/etiología , Paternidad , Conducta Social , Derivación Urinaria/efectos adversos , Adulto , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios
8.
J Urol ; 196(1): 140-5, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26802583

RESUMEN

PURPOSE: We evaluated the outcome in female patients with classic bladder exstrophy and continent urinary diversion for sexual function and fertility. MATERIALS AND METHODS: We reviewed the medical records of female exstrophy patients who underwent continent urinary diversion in our department between 1969 and 2014. Patients were invited for followup examination and asked to complete questionnaires relating to sexual function, social integration and maternity. RESULTS: Of 38 eligible patients 29 (response rate 76%) with a followup of 22.3 years were included in study. Primary continent urinary diversion was done in 62% of patients and 38% underwent secondary continent urinary diversion after failed reconstruction of the exstrophic bladder. Sexual function as measured by the Female Sexual Function Index was only little affected in all domains except desire. Mean total Female Sexual Function Index score was 28.4 of a possible 36. Of the women 31% were classified as at risk for sexual dysfunction, 72% had a stable relationship, 41% were married and 31% had completed higher education. The incidence of pelvic organ prolapse requiring surgical repair was 38%. A total of 16 healthy children were conceived by 12 patients. The pregnancy rate after primary continent urinary diversion was higher than after secondary diversion. CONCLUSIONS: The sexuality and fertility of female patients with exstrophy after continent urinary diversion appears to be comparable with those in previously reported series of patients in whom the bladder was preserved. Management of sexual function, gynecologic pathologies and fertility should be an active part of long-term followup.


Asunto(s)
Extrofia de la Vejiga/cirugía , Infertilidad Femenina/etiología , Complicaciones Posoperatorias , Disfunciones Sexuales Fisiológicas/etiología , Derivación Urinaria , Reservorios Urinarios Continentes , Adulto , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Infertilidad Femenina/epidemiología , Persona de Mediana Edad , Prolapso de Órgano Pélvico/epidemiología , Prolapso de Órgano Pélvico/etiología , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Disfunciones Sexuales Fisiológicas/epidemiología , Resultado del Tratamiento , Derivación Urinaria/métodos
9.
Urol Int ; 96(3): 337-44, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26807854

RESUMEN

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.


Asunto(s)
Neoplasias Renales/cirugía , Nefrectomía/métodos , Nefronas/cirugía , Urología/métodos , Adulto , Anciano , Biopsia , Femenino , Alemania , Humanos , Riñón/cirugía , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Encuestas y Cuestionarios , Tomografía Computarizada por Rayos X
10.
Urol Int ; 97(2): 142-7, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27287607

RESUMEN

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.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Neoplasias Renales/cirugía , Nefrectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Adulto , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Análisis por Apareamiento , Persona de Mediana Edad , Factores de Tiempo , Donantes de Tejidos
11.
Clin Oral Investig ; 20(4): 753-8, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26307268

RESUMEN

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.


Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos/diagnóstico por imagen , Difosfonatos/efectos adversos , Neoplasias de la Próstata Resistentes a la Castración/complicaciones , Osteonecrosis de los Maxilares Asociada a Difosfonatos/complicaciones , Conservadores de la Densidad Ósea , Difosfonatos/uso terapéutico , Humanos , Maxilares , Masculino , Osteonecrosis/inducido químicamente , Cintigrafía
13.
J Urol ; 193(2): 714-21, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25200805

RESUMEN

PURPOSE: Unilateral ureteral obstruction halts ureteral peristalsis, and may cause pain and lead to infection. Ureteral ability to recover after obstruction removal remains unclear. Erythropoietin has protective effects in nonhematopoietic organs and restores peristalsis in hypocontractile intestinal smooth muscle cells. We investigated the role of erythropoietin in ureteral smooth muscle function and its therapeutic value for unilateral ureteral obstruction. MATERIALS AND METHODS: Unilateral ureteral obstruction was created for 24, 48 and 72 hours in 22 mice per group using a nontraumatic microclip via laparotomy. We determined erythropoietin, erythropoietin receptor and ß-common receptor expression in obstructed and unobstructed ureters by reverse transcriptase-polymerase chain reaction and immunohistochemistry. Ten mice per group received 20 IU erythropoietin for 4 days and controls received saline. Hydronephrosis regression after obstruction removal was assessed by ultrasound. Peristalsis was determined microscopically before and after obstruction removal. RESULTS: Erythropoietin, erythropoietin receptor and ß-common receptor were expressed in the unobstructed and obstructed ureters of untreated mice. Erythropoietin mRNA was up-regulated in response to obstruction and erythropoietin expression was identified in ureteral smooth muscle. After obstruction removal hydronephrosis and ureteral dysfunction correlated with obstruction duration. Hydronephrosis resolution and ureteral peristalsis restoration were significantly accelerated in erythropoietin treated mice compared to controls. CONCLUSIONS: Erythropoietin treatment significantly promoted functional recovery of the ureter after obstruction removal. Erythropoietin may be a helpful strategy for ureteral motility recovery and hydronephrosis resolution in ureteral obstruction.


Asunto(s)
Eritropoyetina/uso terapéutico , Hidronefrosis/tratamiento farmacológico , Obstrucción Ureteral/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Eritropoyetina/fisiología , Masculino , Ratones , Músculo Liso/fisiología , Recuperación de la Función , Uretra/fisiología
14.
J Urol ; 194(2): 427-32, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25640647

RESUMEN

PURPOSE: Ureteropelvic junction obstruction in association with a duplex collecting system is a rare but challenging upper urinary tract pathology. We report our 21-year experience with this anomaly in terms of presentation, diagnostic evaluation and management. MATERIALS AND METHODS: We retrospectively identified all patients with ureteropelvic junction obstruction in a duplex collecting system between 1991 and 2012. We reviewed each case for presenting symptoms, anatomy and management. Median followup was 10.8 years (range 2 to 22). RESULTS: Ureteropelvic junction obstruction in duplex kidneys was diagnosed in 21 patients. Ten patients presented with clinical symptoms such as flank pain and urinary tract infection but 11 were asymptomatic. Six patients were diagnosed by prenatal ultrasound. The lower pole and the upper pole were affected in 22 and 3 renal units, respectively. Bilateral ureteropelvic junction obstruction was found in 4 cases. Duplication was complete in 5 patients, incomplete in 11 and undetermined in 5. Surgery was performed in 14 patients, including pyelopyelostomy or ureteropyelostomy in 7, dismembered pyeloplasty in 6 and heminephrectomy in 1. Reintervention was required in 1 case. Conservative treatment was adopted in 7 patients with clinically insignificant obstruction and unimpaired renal function. In all of these patients upper urinary tract dilatation gradually improved during 3 years. CONCLUSIONS: Ureteropelvic junction obstruction in a duplex kidney is a rare but challenging anomaly that requires careful evaluation. Treatment should be individualized according to clinical presentation (symptomatic/asymptomatic), anatomy (lower/upper pole), duplication type (complete/incomplete) and obstruction with time (severity/development) on dynamic renogram.


Asunto(s)
Manejo de la Enfermedad , Predicción , Enfermedades Renales/congénito , Riñón/anomalías , Uréter/cirugía , Obstrucción Ureteral/cirugía , Procedimientos Quirúrgicos Urológicos/métodos , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Enfermedades Renales/complicaciones , Enfermedades Renales/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Obstrucción Ureteral/etiología , Adulto Joven
15.
J Urol ; 194(2): 539-46, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25623744

RESUMEN

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.


Asunto(s)
Neoplasias Óseas/secundario , Carcinoma de Células Renales/secundario , ADN de Neoplasias/genética , Regulación Neoplásica de la Expresión Génica , Integrina alfa5/genética , Neoplasias Renales/patología , Proteínas Proto-Oncogénicas c-akt/genética , Western Blotting , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/genética , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/genética , Línea Celular Tumoral , Movimiento Celular , Humanos , Integrina alfa5/biosíntesis , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Fosfohidrolasa PTEN/biosíntesis , Fosfohidrolasa PTEN/genética , Proteínas Proto-Oncogénicas c-akt/biosíntesis , Transducción de Señal , Proteínas Supresoras de Tumor
16.
BJU Int ; 116(1): 93-101, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25359658

RESUMEN

OBJECTIVES: To explore the views of experts about the development and validation of a robotic surgery training curriculum, and how this should be implemented. MATERIALS AND METHODS: An international expert panel was invited to a structured session for discussion. The study was of a mixed design, including qualitative and quantitative components based on focus group interviews during the European Association of Urology (EAU) Robotic Urology Section (ERUS) (2012), EAU (2013) and ERUS (2013) meetings. After introduction to the aims, principles and current status of the curriculum development, group responses were elicited. After content analysis of recorded interviews generated themes were discussed at the second meeting, where consensus was achieved on each theme. This discussion also underwent content analysis, and was used to draft a curriculum proposal. At the third meeting, a quantitative questionnaire about this curriculum was disseminated to attendees to assess the level of agreement with the key points. RESULTS: In all, 150 min (19 pages) of the focus group discussion was transcribed (21 316 words). Themes were agreed by two raters (median agreement κ 0.89) and they included: need for a training curriculum (inter-rater agreement κ 0.85); identification of learning needs (κ 0.83); development of the curriculum contents (κ 0.81); an overview of available curricula (κ 0.79); settings for robotic surgery training ((κ 0.89); assessment and training of trainers (κ 0.92); requirements for certification and patient safety (κ 0.83); and need for a universally standardised curriculum (κ 0.78). A training curriculum was proposed based on the above discussions. CONCLUSION: This group proposes a multi-step curriculum for robotic training. Studies are in process to validate the effectiveness of the curriculum and to assess transfer of skills to the operating room.


Asunto(s)
Curriculum , Robótica/educación , Procedimientos Quirúrgicos Urológicos/educación , Procedimientos Quirúrgicos Urológicos/métodos , Urología/educación , Consenso , Humanos
17.
Urol Int ; 95(3): 346-51, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25871316

RESUMEN

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.


Asunto(s)
Fístula Pancreática , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Fístula Pancreática/diagnóstico , Fístula Pancreática/epidemiología , Fístula Pancreática/etiología , Fístula Pancreática/terapia , Estudios Retrospectivos , Procedimientos Quirúrgicos Urológicos/efectos adversos , Adulto Joven
18.
Mol Cancer ; 13: 42, 2014 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-24576174

RESUMEN

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.


Asunto(s)
Neoplasias Óseas/secundario , Huesos/química , Calcio/metabolismo , Carcinoma de Células Renales/metabolismo , Neoplasias Renales/metabolismo , Receptores Sensibles al Calcio/metabolismo , Western Blotting , Carcinoma de Células Renales/secundario , Citometría de Flujo , Humanos , Inmunohistoquímica , Neoplasias Renales/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
19.
J Urol ; 192(6): 1842-8, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25046620

RESUMEN

PURPOSE: Aberrant HH signaling has proved important in the pathogenesis of several solid cancers. Limited in vitro analyses suggested an oncogenic role for HH in renal cell carcinoma. In this explorative study we sought to validate aberrant HH expression in patients with renal cell carcinoma. MATERIALS AND METHODS: A tissue microarray was constructed from 140 radical nephrectomy specimens of patients with clear cell renal cell carcinoma. We performed immunohistochemistry for Ki67 and HH pathway biomarkers, including PTCH1, Smo, SHH, IHH, DHH, Gli1, Gli2 and Gli3. Staining intensity was measured by automated image processing and related to tumor stage and grade. The impact of biomarker expression on cancer specific survival was determined by univariate and multivariate Cox regression analysis. RESULTS: Gli3, PTCH1, DHH and SHH demonstrated markedly higher expression in high than in low grade tumors. Tumor stage was not associated with marker expression. On univariate analysis DHH expression, and tumor grade and stage were associated with cancer specific survival. Multivariate analysis revealed that DHH, grade and stage were independent predictors of cancer specific survival. CONCLUSIONS: To our knowledge we report for the first time that a biomarker of the HH pathway is associated with adverse pathological features and poor disease outcomes in patients with clear cell renal cell carcinoma. DHH may serve as an independent predictor of cancer specific survival in clear cell renal cell carcinoma cases. This supports further evaluation of HH signaling to validate the pathway as a target for novel therapy.


Asunto(s)
Carcinoma de Células Renales/metabolismo , Proteínas Hedgehog/biosíntesis , Neoplasias Renales/metabolismo , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
20.
BMC Cancer ; 14: 372, 2014 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-24885955

RESUMEN

BACKGROUND: Partial nephrectomy (PN) preserves renal function and has become the standard approach for T1a renal cell carcinoma (RCC). However, there is still an ongoing debate as to which patients will actually derive greater benefit from partial than from radical nephrectomy (RN). The aim of this study was to retrospectively evaluate the impact of the type of surgery on overall survival (OS) in patients with localized RCC. METHODS: Renal surgery was performed in 4326 patients with localized RCC (pT ≤ 3a N/M0) at six German tertiary care centers from 1980 to 2010: RN in 2955 cases (68.3%), elective (ePN) in 1108 (25.6%), and imperative partial nephrectomy (iPN) in 263 (6.1%) cases. The median follow-up for all patients was 63 months. Kaplan-Meier and Cox regression analyses were carried out to identify prognosticators for OS. RESULTS: PN was performed significantly more often than RN in patients presenting with lower tumor stages, higher RCC differentiation, and non-clear cell histology. Accordingly, the calculated 5 (10)-year OS rates were 90.0 (74.6)% for ePN, 83.9 (57.5)% for iPN, and 81.2 (64.7)% for RN (p < 0.001). However, multivariate analysis including age, sex, tumor diameter and differentiation, histological subtype, and the year of surgery showed that ePN compared to RN still qualified as an independent factor for improved OS (HR 0.79, 95% CI 0.66-0.94, p = 0.008). CONCLUSION: Even allowing for the weaknesses of this retrospective analysis, our multicenter study indicates that in patients with localized RCC, PN appears to be associated with better OS than RN irrespective of age or tumor size.


Asunto(s)
Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Nefrectomía/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Femenino , Humanos , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Programa de VERF , Resultado del Tratamiento
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