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1.
World J Urol ; 41(4): 1193-1203, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36930253

RESUMEN

PURPOSE: In selected ADPKD patients, a nephrectomy is required in the work-up for a kidney transplantation. Because the impact of this procedure is unknown, we investigated the effect of pre-transplantation nephrectomy on quality of life in this group. METHODS: In this retrospective cohort study all ADPKD patients, ≥ 18 years, who received a kidney transplantation in 2 ADPKD expertise centers between January 2000 and January 2016, were asked to participate. Quality of life was assessed using three validated questionnaires on three time points. Nephrectomy was performed in preparation for transplantation. RESULTS: Two hundred seventy-six ADPKD patients (53 ± 9 years, 56.2% male) were included. 98 patients (35.5%) underwent native nephrectomy in preparation for transplantation, of which 43 underwent bilateral nephrectomy. Pre-transplantation, ADPKD-IS scores were worse in the nephrectomy group vs. no-nephrectomy group (physical: 2.9 vs. 2.3, p < 0.001; emotional: 2.0 vs. 1.8, p = 0.03; fatigue: 3.0 vs. 2.3, p = 0.01). Post-transplantation and post-nephrectomy, ADPKD-IS scores improved significantly in both groups, with a significantly higher improvement in the nephrectomy group. During follow-up, all scores were still better compared to pre-transplantation. Observed physical QoL (ADPKD-IS physical 1.3 vs. 1.7, p = 0.04; SF-36 physical 50.0 vs. 41.3, p = 0.03) was better post-transplantation after bilateral nephrectomy compared to unilateral nephrectomy. In retrospect, 19.7% of patients would have liked to undergo a nephrectomy, while the decision not to perform nephrectomy was made by the treating physician. CONCLUSION: This study shows that pre-transplantation nephrectomy improves quality of life in selected ADPKD patients. Bilateral nephrectomy may be preferred, although the risk of additional complications should be weighted.


Asunto(s)
Trasplante de Riñón , Riñón Poliquístico Autosómico Dominante , Humanos , Masculino , Femenino , Riñón Poliquístico Autosómico Dominante/cirugía , Riñón Poliquístico Autosómico Dominante/complicaciones , Calidad de Vida , Estudios Retrospectivos , Nefrectomía , Trasplante de Riñón/métodos
2.
Urol Int ; 107(2): 148-156, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35810740

RESUMEN

INTRODUCTION: There is no consensus if nor when a native nephrectomy should be performed in the workup for kidney transplantation in ADPKD patients. In our PKD Expertise Center, a restrictive approach is pursued in which nephrectomy is performed only in patients with severe complaints, i.e., in case of serious volume-related complaints, lack of space for the allograft, recurrent cyst infections, persistent cyst bleedings, or chronic refractory pain. We analyzed in a retrospective cohort study whether this approach is justified. METHODS: All ADPKD patients who received kidney transplantation between January 2000 and January 2019 were reviewed. Patients were subdivided into three groups: no nephrectomy (no-Nx), nephrectomy performed before (pre-Tx), or after kidney transplantation (post-Tx). Simultaneous nephrectomy together with transplantation were not performed in our center. RESULTS: 391 patients (54 ± 9 years, 55% male) were included. The majority of patients did not undergo a nephrectomy (n = 257, 65.7%). A nephrectomy was performed pre-Tx in 114 patients (29.2%). After Tx, nephrectomy was performed in only 30 patients (7.7%, median 4.4 years post-Tx). Surgery-related complication rates did not differ between both groups (38.3% pre-Tx vs. 27.0% post-Tx, p = 0.2), nor were there any differences in 10-year patient survival (74.4% pre-Tx vs. 80.7% post-Tx vs. 67.6% no-Nx, p = 0.4), as well as in 10-year death-censored graft survival (84.4% pre-Tx vs. 85.5% post-Tx vs. 90.0% no-Nx, p = 0.9). CONCLUSIONS: This study indicates that with a restrictive nephrectomy policy in the workup for kidney transplantation, only a part of ADPKD patients need a native nephrectomy.


Asunto(s)
Quistes , Trasplante de Riñón , Riñón Poliquístico Autosómico Dominante , Humanos , Masculino , Femenino , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/cirugía , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Reinfección/complicaciones
3.
Nephrol Dial Transplant ; 38(3): 618-629, 2023 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-35512573

RESUMEN

BACKGROUND: Chronic pain is often difficult to manage in autosomal dominant polycystic kidney disease (ADPKD) patients and sometimes even leads to nephrectomy. We analyzed the long-term efficacy of our innovative multidisciplinary protocol to treat chronic refractory pain that aims to preserve kidney function by applying among other sequential nerve blocks. METHODS: Patients were eligible if pain was present ≥3 months with a score of ≥50 on a visual analog scale (VAS) of 100, was negatively affecting quality of life and if there had been insufficient response to previous therapies, including opioid treatment. Treatment options were, in order, analgesics, cyst aspiration and fenestration, nerve blocks and nephrectomy. RESULTS: A total of 101 patients were assessed in our clinic (mean age 50 ± 11 years, 65.3% females). Eight patients were treated with medication, 6 by cyst aspiration or fenestration, 63 by nerve blocks and 6 received surgery as the first treatment option. Overall, 76.9% experienced a positive effect on pain complaints shortly after treatment. The VAS score was reduced from 60/100 to 20/100 (P < 0.001) and patients decreased their number of nonopioid and opioid analgesics significantly (P < 0.001, P = 0.01, respectively). A substantial number of the patients (n = 51) needed additional treatment. At the end of follow-up in only 13 patients (12.9%) was surgical intervention necessary: 11 nephrectomies (of which 10 were in patients already on kidney function replacement treatment), 1 liver transplantation and 1 partial hepatectomy. After a median follow-up of 4.5 years (interquartile range 2.5-5.3), 69.0% of the patients still had fewer pain complaints. CONCLUSIONS: These data indicate that our multidisciplinary treatment protocol appears effective in reducing pain in the majority of patients with chronic refractory pain, while postponing or even avoiding in most patients surgical interventions such as nephrectomy in most patients.


Asunto(s)
Dolor Crónico , Quistes , Dolor Intratable , Riñón Poliquístico Autosómico Dominante , Femenino , Humanos , Adulto , Persona de Mediana Edad , Masculino , Dolor Crónico/terapia , Calidad de Vida , Dolor Intratable/cirugía , Nefrectomía
5.
World J Urol ; 40(9): 2275-2281, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35778577

RESUMEN

PURPOSE: Bladder cancer (BC) is a common malignancy with well-established differences in incidence, clinical manifestation and outcomes between men and women. It is unknown to what extent disparities in outcomes are influenced by differences in treatment approaches. This paper describes treatment patterns among men and women with muscle-invasive BC focusing on curative treatment (radical cystectomy or trimodal therapy). METHODS: A retrospective population-based cohort study was performed with data from the Netherlands Cancer Registry. All patients newly diagnosed with muscle-invasive, non-advanced BC (MIBC, cT2-4a, N0/X, M0/X) in the years 2018, 2019 and 2020 were identified. Patient and tumor characteristics and initial treatment were compared between men and women with descriptive statistics and multivariable logistic regression analyses. RESULTS: A total of 3484 patients were diagnosed with non-advanced MIBC in 2018-2020 in the Netherlands, of whom 28% were women. Women had higher T-stage and more often non-urothelial histology. Among all strata of clinical T-stage, women less often received treatment with curative intent (radical cystectomy [RC] or trimodality treatment). Among RC-treated patients, women more often received neoadjuvant treatment (except for cT4a disease). After adjustment for pre-treatment factors, odds ratios were indicative of women having lower probability of receiving curative treatment and RC specifically, and higher probability to receive NAC when treated with RC then men, although not statistically significant. CONCLUSIONS: Considerable differences in treatment patterns between men and women with MIBC exist. A more considerate role of the patient's sex in treatment decisions could help decrease these differences and might mitigate disparities in outcomes.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Estudios de Cohortes , Cistectomía , Femenino , Humanos , Masculino , Músculos , Terapia Neoadyuvante , Invasividad Neoplásica , Países Bajos/epidemiología , Sistema de Registros , Estudios Retrospectivos , Caracteres Sexuales , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/terapia
6.
BJU Int ; 128(4): 511-518, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33404154

RESUMEN

OBJECTIVE: To contribute to the debate regarding the minimum volume of radical cystectomies (RCs) that a hospital should perform by evaluating the association between hospital volume (HV) and postoperative mortality. PATIENTS AND METHODS: Patients who underwent RC for bladder cancer between 1 January 2008 and 31 December 2018 were retrospectively identified from the Netherlands Cancer Registry. To create a calendar-year independent measure, the HV of RCs was calculated per patient by counting the RCs performed in the same hospital in the 12 months preceding surgery. The relationship of HV with 30- and 90-day mortality was assessed by logistic regression with a non-linear spline function for HV as a continuous variable, which was adjusted for age, tumour, node and metastasis (TNM) stage, and neoadjuvant treatment. RESULTS: The median (interquartile range; range) HV among the 9287 RC-treated patients was 19 (12-27; 1-75). Of all the included patients, 208 (2.2%) and 518 (5.6%) died within 30 and 90 days after RC, respectively. After adjustment for age, TNM stage and neoadjuvant therapy, postoperative mortality slightly increased between an HV of 0 and an HV of 25 RCs and steadily decreased from an HV of 30 onwards. The lowest risks of postoperative mortality were observed for the highest volumes. CONCLUSION: This paper, based on high-quality data from a large nationwide population-based cohort, suggests that increasing the RC volume criteria beyond 30 RCs annually could further decrease postoperative mortality. Based on these results, the volume criterion of 20 RCs annually, as recently recommended by the European Association of Urology Guideline Panel, might therefore be reconsidered.


Asunto(s)
Cistectomía , Complicaciones Posoperatorias/mortalidad , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Anciano de 80 o más Años , Cistectomía/métodos , Femenino , Hospitales/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo
8.
Pharmaceutics ; 12(5)2020 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-32443499

RESUMEN

Animal models are a valuable tool in preclinical research. However, limited predictivity of human biological responses in the conventional models has stimulated the search for reliable preclinical tools that show translational robustness. Here, we used precision-cut kidney slices (PCKS) as a model of renal fibrosis and investigated its predictive capacity for screening the effects of anti-fibrotics. Murine and human PCKS were exposed to TGFß or PDGF pathway inhibitors with established anti-fibrotic efficacy. For each treatment modality, we evaluated whether it affected: (1) culture-induced collagen type I gene expression and interstitial accumulation; (2) expression of markers of TGFß and PDGF signaling; and (3) expression of inflammatory markers. We summarized the outcomes of published in vivo animal and human studies testing the three inhibitors in renal fibrosis, and drew a parallel to the PCKS data. We showed that the responses of murine PCKS to anti-fibrotics highly corresponded with the known in vivo responses observed in various animal models of renal fibrosis. Moreover, our results suggested that human PCKS can be used to predict drug efficacy in clinical trials. In conclusion, our study demonstrated that the PCKS model is a powerful predictive tool for ex vivo screening of putative drugs for renal fibrosis.

9.
Am J Physiol Renal Physiol ; 318(1): F117-F134, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31736352

RESUMEN

Poor translation from animal studies to human clinical trials is one of the main hurdles in the development of new drugs. Here, we used precision-cut kidney slices (PCKS) as a translational model to study renal fibrosis and to investigate whether inhibition of tyrosine kinase receptors, with the selective inhibitor nintedanib, can halt fibrosis in murine and human PCKS. We used renal tissue of murine and human origins to obtain PCKS. Control slices and slices treated with nintedanib were studied to assess viability, activation of tyrosine kinase receptors, cell proliferation, collagen type I accumulation, and gene and protein regulation. During culture, PCKS spontaneously develop a fibrotic response that resembles in vivo fibrogenesis. Nintedanib blocked culture-induced phosphorylation of platelet-derived growth factor receptor and vascular endothelial growth factor receptor. Furthermore, nintedanib inhibited cell proliferation and reduced collagen type I accumulation and expression of fibrosis-related genes in healthy murine and human PCKS. Modulation of extracellular matrix homeostasis was achieved already at 0.1 µM, whereas high concentrations (1 and 5 µM) elicited possible nonselective effects. In PCKS from human diseased renal tissue, nintedanib showed limited capacity to reverse established fibrosis. In conclusion, nintedanib attenuated the onset of fibrosis in both murine and human PCKS by inhibiting the phosphorylation of tyrosine kinase receptors; however, the reversal of established fibrosis was not achieved.


Asunto(s)
Fibrosis/tratamiento farmacológico , Indoles/farmacología , Enfermedades Renales/tratamiento farmacológico , Riñón/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Progresión de la Enfermedad , Fibrosis/patología , Humanos , Indoles/uso terapéutico , Riñón/patología , Enfermedades Renales/patología , Ratones , Fosforilación/efectos de los fármacos , Inhibidores de Proteínas Quinasas/uso terapéutico , Transducción de Señal/efectos de los fármacos
10.
Kidney Int ; 91(4): 972-981, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28159317

RESUMEN

Autosomal dominant polycystic kidney disease (ADPKD) patients can suffer from chronic pain that can be refractory to conventional treatment, resulting in a wish for nephrectomy. This study aimed to evaluate the effect of a multidisciplinary treatment protocol with sequential nerve blocks on pain relief in ADPKD patients with refractory chronic pain. As a first step a diagnostic, temporary celiac plexus block with local anesthetics was performed. If substantial pain relief was obtained, the assumption was that pain was relayed via the celiac plexus and major splanchnic nerves. When pain recurred, patients were then scheduled for a major splanchnic nerve block with radiofrequency ablation. In cases with no pain relief, it was assumed that pain was relayed via the aortico-renal plexus, and catheter-based renal denervation was performed. Sixty patients were referred, of which 44 were eligible. In 36 patients the diagnostic celiac plexus block resulted in substantial pain relief with a change in the median visual analogue scale (VAS) score pre-post intervention of 50/100. Of these patients, 23 received a major splanchnic nerve block because pain recurred, with a change in median VAS pre-post block of 53/100. In 8 patients without pain relief after the diagnostic block, renal denervation was performed in 5, with a borderline significant change in the median VAS pre-post intervention of 20/100. After a median follow-up of 12 months, 81.8% of the patients experienced a sustained improvement in pain intensity, indicating that our treatment protocol is effective in obtaining pain relief in ADPKD patients with refractory chronic pain.


Asunto(s)
Anestésicos Locales/administración & dosificación , Desnervación Autonómica/métodos , Ablación por Catéter , Plexo Celíaco/efectos de los fármacos , Dolor Crónico/terapia , Riñón/inervación , Bloqueo Nervioso/métodos , Riñón Poliquístico Autosómico Dominante/complicaciones , Nervios Esplácnicos/cirugía , Adulto , Anestésicos Locales/efectos adversos , Desnervación Autonómica/efectos adversos , Ablación por Catéter/efectos adversos , Dolor Crónico/diagnóstico , Dolor Crónico/etiología , Dolor Crónico/fisiopatología , Protocolos Clínicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Bloqueo Nervioso/efectos adversos , Dimensión del Dolor , Riñón Poliquístico Autosómico Dominante/diagnóstico , Recurrencia , Factores de Tiempo , Resultado del Tratamiento
11.
Nephrol Dial Transplant ; 32(1): 144-150, 2017 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-26908766

RESUMEN

Background: Renal cyst infection is one of the complications faced by patients with autosomal dominant polycystic kidney disease (ADPKD). Cyst infection is often difficult to treat and potentially leads to sepsis and death. No evidence-based treatment strategy exists. We therefore performed a systematic review to develop an effective approach for the management of renal cyst infection in ADPKD patients based on the literature. Methods: A systematic search was performed in PubMed (January 1948-February 2014), EMBASE (January 1974-February 2014) and the Cochrane Library (until February 2014) according to the PRISMA guidelines. Results: We identified 60 manuscripts that included 85 ADPKD patients with renal cyst infection (aged 52 ± 12 years, 45% male, 27% on dialysis, 13% history of renal transplantation and 6% diabetes mellitus). Included patients received a total of 160 treatments of which 92 were antimicrobial, 29 percutaneous and 39 surgical. Initial management often consisted of antimicrobials (79%), and quinolone-based regimens were favoured (34%). Overall, 61% of patients failed initial treatment, but treatment failure has decreased over time (before the year 2000: 75%; during and after the year 2000: 51%, P = 0.03). Post-renal obstruction, urolithiasis, atypical or resistant pathogens, short duration of antimicrobial treatment and renal function impairment were documented in patients failing treatment. Conclusions: First-line treatment of renal cyst infection in ADPKD consists of antimicrobials and is associated with a high rate of failure, but treatment success has increased over recent years. A large-scale unbiased registry is needed to define the optimal strategy for renal cyst infection management in ADPKD.


Asunto(s)
Infecciones/terapia , Trasplante de Riñón/efectos adversos , Riñón Poliquístico Autosómico Dominante/complicaciones , Femenino , Humanos , Infecciones/diagnóstico , Infecciones/etiología , Masculino , Persona de Mediana Edad , Pronóstico
12.
Clin Exp Nephrol ; 21(3): 375-382, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27339446

RESUMEN

BACKGROUND: Tolvaptan, a vasopressin V2 receptor antagonist, has been shown to reduce the rates of growth in total kidney volume (TKV) and renal function loss in ADPKD patients, but also leads to polyuria because of its aquaretic effect. Prolonged polyuria can result in ureter dilatation with consequently renal function loss. Therefore, we aimed to investigate the effect of tolvaptan-induced polyuria on ureter diameter in ADPKD patients. METHODS: 70 ADPKD patients were included (51 were randomized to tolvaptan and 19 to placebo). At baseline and after 3 years of treatment renal function was measured (mGFR) and MRI was performed to measure TKV and ureter diameter at the levels of renal pelvis and fifth lumbar vertebral body (L5). RESULTS: In these patients [65.7 % male, age 41 ± 9 years, mGFR 74 ± 27 mL/min/1.73 m2 and TKV 1.92 (1.27-2.67) L], no differences were found between tolvaptan and placebo-treated patients in 24-h urine volume at baseline (2.5 vs. 2.5 L, p = 0.8), nor in ureter diameter at renal pelvis and L5 (4.0 vs. 4.2 mm, p = 0.4 and 3.0 vs. 3.1 mm, p = 0.3). After 3 years of treatment 24-h urine volume was higher in tolvaptan-treated patients when compared to placebo (4.7 vs. 2.3 L, p < 0.001), but no differences were found in ureter diameter between both groups (renal pelvis: 4.2 vs. 4.4 mm, p = 0.4 and L5: 3.1 vs. 3.3 mm, p = 0.4). CONCLUSIONS: Tolvaptan-induced polyuria did not lead to an increase in ureter diameter, suggesting that tolvaptan is a safe therapy from a urological point of view.


Asunto(s)
Antagonistas de los Receptores de Hormonas Antidiuréticas/efectos adversos , Benzazepinas/efectos adversos , Riñón Poliquístico Autosómico Dominante/tratamiento farmacológico , Poliuria/inducido químicamente , Receptores de Vasopresinas/efectos de los fármacos , Uréter/efectos de los fármacos , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Países Bajos , Riñón Poliquístico Autosómico Dominante/diagnóstico por imagen , Riñón Poliquístico Autosómico Dominante/metabolismo , Poliuria/fisiopatología , Receptores de Vasopresinas/metabolismo , Factores de Riesgo , Factores de Tiempo , Tolvaptán , Resultado del Tratamiento , Uréter/diagnóstico por imagen , Urodinámica/efectos de los fármacos
13.
Am J Kidney Dis ; 69(2): 210-219, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27856088

RESUMEN

BACKGROUND: Kidney pain is a common complication in patients with autosomal dominant polycystic kidney disease (ADPKD), and data from the TEMPO 3:4 trial suggested that tolvaptan, a vasopressin V2 receptor antagonist, may have a positive effect on kidney pain in this patient group. Because pain is difficult to measure, the incidence of kidney pain leading to objective medical interventions was used in the present study to assess pain. STUDY DESIGN: Secondary analysis from a randomized controlled trial. SETTING & PARTICIPANTS: Patients with ADPKD with preserved kidney function. INTERVENTION: Tolvaptan or placebo. OUTCOMES: Kidney pain events defined by objective medical interventions. MEASUREMENTS: Kidney pain events were recorded and independently adjudicated. Incidence of a first kidney pain event was assessed overall and categorized into 5 subgroups according to severity. RESULTS: Of 1,445 participating patients (48.4% women; mean age, 39±7 [SD] years; mean estimated glomerular filtration rate, 81±22mL/min/1.73m2; median total kidney volume, 1,692 [IQR, 750-7,555] mL), 50.9% reported a history of kidney pain at baseline. History of urinary tract infections, kidney stones, or hematuria (all P<0.001) and female sex (P<0.001) were significantly associated with history of kidney pain. Tolvaptan use resulted in a significantly lower incidence of kidney pain events when compared to placebo: 10.1% versus 16.8% (P<0.001), with a risk reduction of 36% (HR, 0.64; 95% CI, 0.48-0.86). The reduction in pain event incidence by tolvaptan was found in all groups irrespective of pain severity and was independent of predisposing factors (P for interaction > 0.05). The effect of tolvaptan was explained at least in part by a decrease in incidence of urinary tract infections, kidney stones, and hematuria when compared to placebo. LIMITATIONS: Trial has specific inclusion criteria for total kidney volume and kidney function. CONCLUSIONS: Tolvaptan decreased the incidence of kidney pain events independent of patient characteristics predisposing for kidney pain and possibly in part due to reductions in ADPKD-related complications.


Asunto(s)
Antagonistas de los Receptores de Hormonas Antidiuréticas/uso terapéutico , Benzazepinas/uso terapéutico , Dolor/etiología , Dolor/prevención & control , Riñón Poliquístico Autosómico Dominante/complicaciones , Adulto , Femenino , Humanos , Incidencia , Enfermedades Renales/epidemiología , Enfermedades Renales/etiología , Enfermedades Renales/prevención & control , Masculino , Dolor/epidemiología , Estudios Prospectivos , Método Simple Ciego , Factores de Tiempo , Tolvaptán
15.
Transl Res ; 170: 8-16.e1, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26687735

RESUMEN

Chronic kidney disease is a major health concern, and experimental models bridging the gap between animal studies and clinical research are currently lacking. Here, we evaluated precision-cut kidney slices (PCKSs) as a potential model for renal disease. PCKSs were prepared from human cortical tissue obtained from tumor nephrectomies and cultured up to 96 hours. Morphology, cell viability, and metabolic functionality (ie, uridine 5'-diphospho-glucuronosyltransferase and transporter activity) were determined to assess the integrity of PCKSs. Furthermore, inflammatory and fibrosis-related gene expressions were characterized. Finally, to validate the model, renal fibrogenesis was induced using transforming growth factor ß1 (TGF-ß1). Preparation of PCKSs induced an inflammatory tissue response, whereas long-term incubation (96 hours) induced fibrogenesis as shown by an increased expression of collagen type 1A1 (COL1A1) and fibronectin 1 (FN1). Importantly, PCKSs remained functional for more than 48 hours as evidenced by active glucuronidation and phenolsulfonphthalein uptake. In addition, cellular diversity appeared to be maintained, yet we observed a clear loss of nephrin messenger RNA levels suggesting that our model might not be suitable to study the role of podocytes in renal pathology. Moreover, TGF-ß1 exposure augmented fibrosis, as illustrated by an increased expression of multiple fibrosis markers including COL1A1, FN1, and α-smooth muscle actin. In conclusion, PCKSs maintain their renal phenotype during culture and appear to be a promising model to investigate renal diseases, for example, renal fibrosis. Moreover, the human origin of PCKSs makes this model very suitable for translational research.


Asunto(s)
Enfermedades Renales , Riñón/patología , Técnicas de Cultivo de Órganos/métodos , Adenosina Trifosfato/metabolismo , Adulto , Anciano , Biomarcadores/metabolismo , Colágeno Tipo I/genética , Cadena alfa 1 del Colágeno Tipo I , Femenino , Fibrosis/genética , Fibrosis/metabolismo , Expresión Génica , Humanos , Riñón/efectos de los fármacos , Riñón/fisiología , Enfermedades Renales/genética , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Masculino , Persona de Mediana Edad , Proteína 1 de Transporte de Anión Orgánico/genética , Proteína 1 de Transporte de Anión Orgánico/metabolismo , Transportadores de Anión Orgánico/metabolismo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/farmacología , Umbeliferonas/metabolismo
16.
Int J Cancer ; 135(4): 905-12, 2014 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-24420527

RESUMEN

Our study assessed whether rising age, socioeconomic status (SES) and the presence of serious comorbidity affected treatment choice and survival in a population-based series of patients with muscle-invasive bladder cancer (MIBC) in The Netherlands. Therefore, a consecutive series was studied, including all patients diagnosed with MIBC between 1995 and 2009 in the Eindhoven Cancer Registry, preceding centralization of cystectomy. The independent effects of age, SES and serious comorbidity on therapy choice and their effects on overall survival were estimated by multivariate logistic regression and multivariate Cox proportional hazard analyses, respectively. Out of the 2,445 patients, 38% were aged ≥ 75 years at diagnosis and 63% had at least one serious comorbid condition. Higher age and serious comorbidity were independent predictors for abstaining from cystectomy, where SES was not (61-74 vs. ≤ 60: odds ratio [OR], 0.8; 95% confidence interval [CI], 0.6-1.0; ≥ 75 vs. ≤ 60: OR, 0.1; 95% CI,0.1-0.2; one comorbid condition vs. none: OR, 0.7; 95% CI, 0.5-0.9; two vs. none: OR, 0.6; 95% CI, 0.5-0.8). Patients undergoing cystectomy, external beam radiotherapy or interstitial radiotherapy survived longer independent of age, SES and serious comorbidity (hazard ratio [HR]: 0.4; 95% CI: 0.4-0.5; HR: 0.8; 95% CI: 0.7-0.9; HR: 0.4; 95% CI: 0.3-0.5, respectively). Consequently, preceding centralization of cystectomy, higher age and serious comorbidity were independent predictors for abstaining from cystectomy owing to an expected high rate of short-term medical problems. As cystectomy is associated with a better survival, independently of age, SES and serious comorbidity, it can be questioned whether cystectomy has been underutilised in elderly and in patients with serious comorbidity. Centralization might be a solution for this suggested underutilisation.


Asunto(s)
Neoplasias de la Vejiga Urinaria/complicaciones , Neoplasias de la Vejiga Urinaria/mortalidad , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Comorbilidad , Cistectomía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Músculo Liso/patología , Invasividad Neoplásica , Países Bajos , Oportunidad Relativa , Pronóstico , Modelos de Riesgos Proporcionales , Clase Social , Resultado del Tratamiento , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/epidemiología
17.
World J Urol ; 31(2): 319-23, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22814886

RESUMEN

PURPOSE: To evaluate the effect of total PSA (tPSA) and PSA kinetics on the detection rates of (11)C-Choline PET in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) or external beam radiotherapy (EBRT). METHODS: We included 185 patients with BCR after RP (PSA >0.2 ng/ml) or after EBRT (ASTRO definition). After injection of 400 MBq 11C-Choline i.v., a scan was made using the ECAT HR + PET camera with CT fusion images or Siemens mCT PET/CT. Biopsy-proven histology, confirmative imaging (CT or bone scan) and/or clinical follow-up (PSA) were used as composite reference. Statistical analysis was performed using PASW Statistics 18. RESULTS: 11C-Choline PET was positive in 124/185 cases (65%) (in 22/61 (36%) after RP, 102/124 (82%) after EBRT). In 79 patients a local recurrence was identified, and 45 patients showed locoregional metastases on PET/CT. In 20 cases a proven false-negative PET scan was observed. Positive PET scans were confirmed by histology in 87/124 (70%) cases, by confirmatory imaging in 34/124 (28%) and by clinical follow-up after salvage treatment in 3 (2%) cases. The ROC analysis to detect a recurrence showed significant difference in area under the curve (AUC) of tPSA 0.721(p < 0.001) and PSA velocity 0.730 (p < 0.001). PSA doubling time showed no significant difference with an AUC of 0.542 (p = 0.354). Detection rates are <50% in tPSA <2 ng/ml and/or PSA velocity <1 ng/ml/year. CONCLUSIONS: Total serum PSA and PSA velocity have significant effect on the detection rates of 11C-Choline PET/CT in men with a BCR after RP or EBRT.


Asunto(s)
Biomarcadores de Tumor/sangre , Calicreínas/sangre , Recurrencia Local de Neoplasia/diagnóstico por imagen , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico por imagen , Anciano , Biomarcadores de Tumor/metabolismo , Radioisótopos de Carbono , Colina , Progresión de la Enfermedad , Humanos , Calicreínas/metabolismo , Masculino , Imagen Multimodal , Recurrencia Local de Neoplasia/sangre , Tomografía de Emisión de Positrones , Antígeno Prostático Específico/metabolismo , Prostatectomía , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/terapia , Radiofármacos , Radioterapia , Estudios Retrospectivos , Sensibilidad y Especificidad , Factores de Tiempo , Tomografía Computarizada por Rayos X
18.
Int Braz J Urol ; 37(2): 203-10; discussion 210-2, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21557837

RESUMEN

PURPOSE: To evaluate the pattern of care in patients with high risk non muscle invasive bladder cancer (NMIBC) in the Comprehensive Cancer Center North-Netherlands (CCCN) and to assess factors associated with the choice of treatment, recurrence and progression free survival rates. MATERIALS AND METHODS: Retrospective analysis of 412 patients with newly diagnosed high risk NMIBC. Clinical, demographic and follow-up data were obtained from the CCCN Cancer Registry and a detailed medical record review. Uni and multivariate analysis was performed to identify factors related to choice of treatment and 5 year recurrence and progression free survival. RESULTS: 74/412 (18%) patients with high risk NMIBC underwent a transurethral resection (TUR) as single treatment. Adjuvant treatment after TUR was performed in 90.7% of the patients treated in teaching hospitals versus 71.8% in non-teaching hospitals (p < 0.001). In multivariate analysis, age (60-79 years OR 0.40 and > 80 years OR 0.1 p = 0.001) and treatment in non-teaching hospitals (OR 0.25; p < 0.001) were associated with less adjuvant treatment after TUR. Tumor recurrence occurred in 191/392 (49%) and progression in 84/392 (21.4%) patients. The mean 5-years progression free survival was 71.6% (95% CI 65.5-76.8). CONCLUSION: In this pattern of care study in high risk NMIBC, 18% of the patients were treated with TUR as single treatment. Age and treatment in non-teaching hospitals were associated with less adjuvant treatment after TUR. None of the variables sex, age, comorbidity, hospital type, stage and year of treatment was associated with 5 year recurrence or progression rates.


Asunto(s)
Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico
19.
Int. braz. j. urol ; 37(2): 203-212, Mar.-Apr. 2011. tab
Artículo en Inglés | LILACS | ID: lil-588993

RESUMEN

PURPOSE: To evaluate the pattern of care in patients with high risk non muscle invasive bladder cancer (NMIBC) in the Comprehensive Cancer Center North-Netherlands (CCCN) and to assess factors associated with the choice of treatment, recurrence and progression free survival rates. MATERIALS AND METHODS: Retrospective analysis of 412 patients with newly diagnosed high risk NMIBC. Clinical, demographic and follow-up data were obtained from the CCCN Cancer Registry and a detailed medical record review. Uni and multivariate analysis was performed to identify factors related to choice of treatment and 5 year recurrence and progression free survival. RESULTS: 74/412 (18 percent) patients with high risk NMIBC underwent a transurethral resection (TUR) as single treatment. Adjuvant treatment after TUR was performed in 90.7 percent of the patients treated in teaching hospitals versus 71.8 percent in non-teaching hospitals (p < 0.001). In multivariate analysis, age (60-79 years OR 0.40 and > 80 years OR 0.1 p = 0.001) and treatment in non-teaching hospitals (OR 0.25; p < 0.001) were associated with less adjuvant treatment after TUR. Tumor recurrence occurred in 191/392 (49 percent) and progression in 84 /392 (21.4 percent) patients. The mean 5-years progression free survival was 71.6 percent (95 percent CI 65.5-76.8). CONCLUSION: In this pattern of care study in high risk NMIBC, 18 percent of the patients were treated with TUR as single treatment. Age and treatment in non-teaching hospitals were associated with less adjuvant treatment after TUR. None of the variables sex, age, comorbidity, hospital type, stage and year of treatment was associated with 5 year recurrence or progression rates.


Asunto(s)
Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/cirugía , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Estudios de Seguimiento , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico
20.
World J Urol ; 28(4): 439-44, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20383640

RESUMEN

OBJECTIVE: To assess treatments and survival of patients with muscle invasive bladder cancer (MIBC) in the Comprehensive Cancer Center Northern Netherlands (CCCN) region. STUDY DESIGN AND SETTING: Retrospective cohort analysis. Data of 548 patients with MIBC diagnosed between 1997 and 2002 were collected from the CCCN cancer registry. All had a follow-up of at least 5 years. Logistic regression analysis on treatments as well as survival analysis was performed. RESULTS: The treatments were radical cystectomy in 205/548 (37.5%) patients. TUR plus radiotherapy in 246 (44.9%) and palliation in 97 (17.7%). Multivariate analysis identified TNM stage (P < 0.0001) and age (P < 0.0001) as independent variables for cystectomy. Hospital type and year of diagnosis were not significant different between patients treated by cystectomy versus other type of treatment. TNM stage (P < 0.0001), age (P = 0.0043), and comorbidity (P = 0.0028) were independent variables for disease-specific survival (DSS) after cystectomy. CONCLUSION: In the CCCN region, only 1/3 of patients with MIBC were treated with radical cystectomy. TNM stage and age were identified as main variables for the choice for cystectomy. TNM stage, age, and comorbidity were independent variables for disease-specific survival after cystectomy.


Asunto(s)
Cistectomía/mortalidad , Encuestas de Atención de la Salud , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Liso/patología , Invasividad Neoplásica , Países Bajos/epidemiología , Sistema de Registros/estadística & datos numéricos , Estudios Retrospectivos , Análisis de Supervivencia , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/radioterapia
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