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1.
Scand J Urol ; 59: 39-46, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38406925

RESUMEN

OBJECTIVE: To investigate the impact of neoadjuvant chemotherapy implementation with gemcitabine-cisplatin on survival outcomes for patients with muscle-invasive bladder cancer in Denmark. MATERIALS AND METHODS: Data were collected on all patients in Denmark undergoing radical cystectomy who were potential candidates for neoadjuvant chemotherapy from 2010 to 2015 (n = 851). A cohort before the implementation of neoadjuvant chemotherapy (Cohort 2010-12) was compared with a cohort after implementation (Cohort 2013-15). Patients in Cohort 2013-15 receiving neoadjuvant chemotherapy (+NAC, n = 213) were compared with patients in Cohort 2013-15 not receiving neoadjuvant chemotherapy (-NAC, n = 139). Pathological results after radical cystectomy and oncological outcomes were compared between the study cohorts. Overall survival, disease-free survival, and disease-specific survival were compared with Kaplan-Meier plots and with univariable and multivariable Cox regression. Kaplan-Meier estimates of overall survival were also performed separately for treating hospital and for pathological stage. RESULTS: Pathological T0 (pT0) was more frequent in patients who received neoadjuvant chemotherapy: 34% versus 18% when comparing Cohort 2013-15 with Cohort 2010-12 (p < 0.001), and 46% versus 16% in +NAC compared with -NAC (p < 0.001). Overall survival, disease-free survival, and disease-specific survival at 5 years after cystectomy were not improved in Cohort 2013-15 compared with Cohort 2010-12 with adjusted hazard ratios of 1.11 (95% confidence interval [CI]: 0.87-1.43), 1.02 (95% CI: 0.81-1.29), and 1.06 (95% CI: 0.80-1.41), respectively. CONCLUSIONS: This observational study found no improved survival in a national cohort of patients with muscle-invasive bladder cancer undergoing radical cystectomy after implementation of NAC. However, reservations should be made regarding the study design and the true effect of NAC on survival outcomes.


Asunto(s)
Terapia Neoadyuvante , Neoplasias de la Vejiga Urinaria , Humanos , Cistectomía/métodos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Dinamarca , Músculos/patología , Estudios Retrospectivos , Quimioterapia Adyuvante , Invasividad Neoplásica
2.
Eur Urol Open Sci ; 60: 8-14, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38375343

RESUMEN

Background: Approximately 15% of patients undergoing radical cystectomy (RC) develop benign ureteroenteric strictures. Of these strictures, the majority are located in the left ureter. To lower the rate of strictures, a retrosigmoid ileal conduit has been suggested. Objective: To investigate the feasibility and safety of a retrosigmoid ileal conduit during robot-assisted RC in bladder cancer patients. Design setting and participants: This randomized controlled trial included 303 patients from all five cystectomy centers in Denmark from May 2020 to August 2022. Participants were diagnosed with bladder cancer and scheduled for robot-assisted RC with an ileal conduit. Intervention: Intervention group: a retrosigmoid ileal conduit was constructed using approximately 25 cm of the terminal ileum and tunneled behind the sigmoid where the left ureter was anastomosed from end to side. Control group: the conventional ileal conduit ad modum Bricker with individual end-to-side anastomoses. Outcome measurements and statistical analysis: Patients were analyzed by the intention-to-treat approach. Complications within 90 d were categorized using the Clavien-Dindo grading system and compared using Fisher's exact test. Wilcoxon's test was used for pre- and postoperative renal function. Results and limitations: Of the 149 patients randomized for the retrosigmoid ileal conduit (MOSAIC), a total of 137 (92%) patients received the allocated conduit. Postoperative complications were distributed equally between the two groups. The relative risk of Clavien-Dindo complications of grade ≥III was 1.12 (95% confidence interval: 0.96-1.31) in the intervention group compared with the control group. Conclusions: The retrosigmoid ileal conduit with robot-assisted RC was technically feasible. Early postoperative complications were not significantly different when comparing the two groups. Further investigation of long-term complications, including strictures, is needed. Patient summary: We compared a conventional urinary diversion with a longer conduit to prevent constriction from developing in the ureters. The new conduit is feasible and safe within the first 90 d, with no differences in postoperative complications from those of the conventional diversion.

3.
Int J Clin Oncol ; 29(3): 309-317, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38180599

RESUMEN

BACKGROUND: We assessed the accuracy of four estimated glomerular filtration rate (eGFR) methods: MDRD, Cockcroft-Gault, CKD-EPI, and Wright. METHOD: The four methods were compared to measure GFR (mGFR) in patients with urothelial urinary tract cancer (T2-T4bNxMx) receiving platinum-based chemotherapy at Rigshospitalet, Copenhagen, from January 2019 to December 2021. Using standardized assays, creatinine values were measured, and mGFR was determined using Technetium-99 m diethylenetriaminepentaacetic acid (Tc-99 m-DTPA) or Cr-51-ethylenediaminetetraacetic acid (Cr-51-EDTA) plasma clearance. Patients (n = 146) with both mGFR and corresponding creatinine values available were included (n = 345 measurements). RESULTS: The CKD-EPI method consistently demonstrated superior accuracy, with the lowest Total Deviation Index of 21.8% at baseline and 22.9% for all measurements compared to Wright (23.4% /24.1%), MDRD (26.2%/25.5%), and Cockcroft-Gault (25.x%/25.1%). Bland Altman Limits of agreement (LOA) ranged from - 32 ml/min (Cockcroft-Gault) to + 33 ml/min (MDRD), with CKD-EPI showing the narrowest LOA (- 27 ml/min to + 24 ml/min and lowest bias (0.3 ml/min). Establishing an eGFR threshold at 85 ml/min-considering both the lower limit of agreement (LOA) and the minimum cisplatin limit at 60 ml/min-allows for the safe omission of mGFR in 30% of patients in this cohort. CONCLUSION: CKD-EPI equation emerged as the most suitable for estimating kidney function in this patient group although not meeting benchmark criteria. We recommend its use for initial assessment and ongoing monitoring, and suggest mGFR for patients with a CKD-EPI estimated GFR below 85 ml/min. This approach could reduce costs and decrease laboratory time for 30% of our UC patients.


Asunto(s)
Carcinoma de Células Transicionales , Insuficiencia Renal Crónica , Neoplasias de la Vejiga Urinaria , Humanos , Tasa de Filtración Glomerular , Platino (Metal)/uso terapéutico , Creatinina , Insuficiencia Renal Crónica/tratamiento farmacológico
4.
Ugeskr Laeger ; 185(14)2023 04 03.
Artículo en Danés | MEDLINE | ID: mdl-37057696

RESUMEN

Bladder cancer is the fifth most frequently diagnosed cancer in Europe, with major healthcare costs. For patients with non-muscle invasive bladder cancer, recurrences, treatment and surveillance regimes with multiple invasive procedures are a significant burden. Muscle invasive or metastatic disease is treated with radical surgery, radiation therapy and/or systemic chemo- or immunotherapy, with a five-year overall survival of around 50% and long-term quality of life issues for survivors. We present a brief overview of bladder cancer in various stages and give examples of new developments.


Asunto(s)
Calidad de Vida , Neoplasias de la Vejiga Urinaria , Humanos , Cistectomía/métodos , Europa (Continente) , Neoplasias de la Vejiga Urinaria/terapia
5.
Pilot Feasibility Stud ; 9(1): 7, 2023 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-36639814

RESUMEN

BACKGROUND: Radical cystectomy (RC) with urinary diversion is the recommended treatment for selected cases of non-metastatic high-risk non-muscle-invasive and muscle-invasive bladder cancer. It remains unknown whether robot-assisted laparoscopic cystectomy (RARC) offers any advantage in terms of safety compared to open cystectomy (ORC) in an Enhanced Recovery After Surgery (ERAS) setup. Blinded randomised controlled trials (RCTs) between RARC versus ORC have never been conducted in cystectomy patients. We will investigate the feasibility of conducting a double-blinded RCT comparing ORC with RARC with intra-corporal ileal conduit (iRARC) in an ERAS setup. METHODS: This is a single-centre, double-blinded, randomised (1:1) clinical feasibility study for patients with non-metastatic high-risk non-muscle-invasive or muscle-invasive bladder cancer scheduled for cystectomy. All participants are recruited from Rigshospitalet, Denmark. The planned sample size is 50 participants to investigate whether blinding of the surgical technique is feasible. Participants and postoperative caring physicians and nurses are blinded using a pre-study designed abdominal dressing and blinding of the patient's electronic health record. Study endpoints are assessed 90 days postoperatively. The primary aim is to study the frequency and pattern of unplanned unblinding after surgery and the number of participants who cannot guess the surgical technique at the day of discharge. Eleven secondary endpoints are assessed: length of stay, days alive and out of hospital, in-hospital complication rate, 30-day complication rate, 90-day complication rate, readmission rate, quality of life, blood loss, pain, rate of moderate/severe post-anaesthesia care unit (PACU) complications, and delirium. Participants are managed in an ERAS setup in both arms of the trial. DISCUSSION: We report on the design and objectives of a novel experimental feasibility study investigating whether blinding of the surgical technique in cystectomy patients is possible. This information is essential for the design of future blinded trials comparing ORC to RARC. There is a continued need to compare RARC and ORC in terms of both efficacy, safety, and oncological outcomes. Estimated end of study is March 2021. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03977831. Registered on the 6th of June 2019.

6.
World J Urol ; 40(7): 1669-1677, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35590011

RESUMEN

PURPOSE: This study aims to examine quality of life (QoL) before and after radical cystectomy (RC) and compare robot-assisted laparoscopy with intracorporeal urinary diversion (iRARC) to open radical cystectomy (ORC). METHODS: This study is a predefined secondary analysis of a single-centre, double-blinded, randomised feasibility trial. Fifty patients were randomly assigned to iRARC with ileal conduit (n = 25) or ORC with ileal conduit (n = 25). Patients were followed 90 days postoperatively. The primary outcome was patient-reported QoL using the EORTC Cancer-30 and muscle-invasive bladder cancer BLM-30 QoL questionnaires before and after RC. Differences between randomisation arms as well as changes over time were evaluated. Secondary outcomes included 30- and 90 day complication rates, 90 day readmission rates, and 90 day days-alive-and-out-of-hospital and their relationship to QoL. RESULTS: All patients underwent the allocated treatment. We found no difference in QoL, complication rates, readmission rates, and days-alive-and-out-of-hospital between randomisation arms. An overall improvement in QoL was found in the following domains: future perspectives, emotional functioning, and social functioning. Sexual functioning worsened postoperatively. There was no association between having experienced a major complication or lengthy hospitalisation and worse postoperative QoL. CONCLUSION: The QoL does not appear to depend on surgical technique. Apart from sexual functioning, patients report stable or improved QoL within the first 90 postoperative days.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Robótica , Neoplasias de la Vejiga Urinaria , Derivación Urinaria , Cistectomía/métodos , Estudios de Factibilidad , Humanos , Complicaciones Posoperatorias/etiología , Calidad de Vida , Procedimientos Quirúrgicos Robotizados/métodos , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/etiología , Derivación Urinaria/métodos
7.
Trials ; 23(1): 333, 2022 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-35449008

RESUMEN

BACKGROUND: There is a large unused potential for risk reduction in the preoperative period via effective lifestyle intervention targeting co-existing risky lifestyles: Smoking, malNutrition, obesity, risky Alcohol intake and insufficient Physical activity (SNAP). This trial compares the efficacy of the integrated STRONG programme with standard care on preoperative risk reduction and secondly on SNAP factor improvement and frailty, postoperative complications and quality of life. A nested interview study explores the patient preferences and the multi-perspective view of patients, relatives and health professionals. METHODS: In total, 42 surgical patients with ≥1 SNAP factor are allocated to individually tailored STRONG programme or usual care during adjuvant chemotherapy prior to radical bladder cancer surgery. The STRONG programme has ≥6 weekly sessions with patient education, motivational and pharmaceutical support. It is based on intensive smoking and alcohol cessation interventions reporting perioperative quit rates > 50%. Surgical risk reduction is measured as ≥1 step for 1 or more risky lifestyles on the ASA-score, secondly as having no risky SNAP factors, and as any SNAP improvement. The outcomes are validated by measurements and biomarkers. Postoperative complications are categorised according to the Clavien-Dindo classification. Health-related quality of life is measured by EQ-5D. The patients are followed up after 6 weeks at surgery and 6 weeks and 6 months postoperatively. A representative sample of the participants, their relatives and the clinical staff are interviewed until data saturation. Transcription, triangulated analyses and data management are conducted using NVivo computer software. DISCUSSION: The surgical agenda is characterised by fixed dates for surgery focusing on clear risk reduction within a short time. This requires a clinical useful lifestyle intervention programme with a high effect and coverage as well as containing all SNAP factors and tailored to individual needs. The STRONG programme seems to meet these requirements. After development in multi-professional collaboration, STRONG is delivered by a specially trained nurse as part of the surgical patient journey. Overall, this study will bring important new knowledge about risk reduction in a frail patient group undergoing major cancer surgery. TRIAL REGISTRATION: Registration at www.clintrials.gov ( NCT04088968 ) The manuscript form from https://trialsjournal.biomedcentral.com/bmc/journal and the SPIRIT guidelines are followed.


Asunto(s)
Neoplasias , Ejercicio Preoperatorio , Ejercicio Físico , Humanos , Neoplasias/complicaciones , Complicaciones Posoperatorias/etiología , Investigación Cualitativa , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Conducta de Reducción del Riesgo , Fumar
8.
Scand J Urol ; 56(2): 149-154, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35068354

RESUMEN

PURPOSE: To investigate the risk of recurrence and long-term mortality after radical cystectomy (RC) for bladder cancer (BC) at a high-volume tertiary referral center in Denmark over 19 years. MATERIALS AND METHODS: Patients undergoing RC between the 1st of January 2000 to 31st of December 2018 were included. Patient data were manually retrieved from electronic patient files. Follow-up ended 18th of May 2020. Cumulative incidences were used to assess risk of recurrence and mortality using competing risk modelling. Cause-specific Cox regression models were used for multivariable analysis. RESULTS: A total of 1267 patients underwent RC of which 1042 were eligible for analysis. Overall mortality was 40% and 56% after 5 and 10 years, respectively. The cumulative incidence of recurrence and BC specific mortality was high within the first 2 years. Only 3.2% of the patients with recurrence were alive at the end of follow-up. The cumulative incidence of BC mortality after 5 years was 6.7% (95% CI 3.6-9.9) and 10% (95% CI 6.8-14) for patients with ≤ pT1bN0 and pT2N0, respectively. For patients with lymph node positive disease the cumulative incidence of BC mortality after 5 years was 65% (95% CI 58-71). CONCLUSIONS: We found a significant risk of recurrence and disease-specific mortality following RC for BC, especially within the first 2 years following surgery. Our data seem comparable to other large cohorts. The chance of long-term survival following recurrence is low and there is a continuous need to improve adjuvant or salvage strategies following RC.


Asunto(s)
Cistectomía , Neoplasias de la Vejiga Urinaria , Cistectomía/efectos adversos , Femenino , Humanos , Masculino , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/patología
10.
BMJ Open ; 11(4): e043266, 2021 04 14.
Artículo en Inglés | MEDLINE | ID: mdl-33853799

RESUMEN

OBJECTIVE: To study short-term (<90 days) morbidity and mortality following radical cystectomy (RC) for bladder cancer and identify modifiable risk factors associated with these. DESIGN: Systematic review. METHODS: The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed and EMBASE were searched for relevant papers on 11 June 2019 and rerun on 27 May 2020. Studies reporting complications, reoperations, length of stay and mortality within 90 days were included. Studies were reviewed according to criteria from the Oxford Centre for Evidence-Based Medicine and the quality of evidence was assessed using the Newcastle-Ottawa Scale. RESULTS: The search retrieved 1957 articles. Sixty-six articles were included. The quality of evidence was poor to good. Most studies were retrospective, and no randomised clinical trials were identified. Of included studies a median of 6 Martin criteria for reporting complications after surgery were fulfilled. The Clavien-Dindo classification for grading complications was most frequently used. The weighted overall complication rate after RC was 34.9% (range 28.8-68.8) for in-house complications, 39.0% (range 27.3-80.0) for 30-day complications and 58.5% (range 36.1-80.5) for 90-day complications. The most common types of complications reported were gastrointestinal (29.0%) and infectious (26.4%). The weighted mortality rate was 2.4% (range 0.9-4.7) for in-house mortality, 2.1% (0.0-3.7) for 30-day mortality and 4.7% (range 0.0-7.0) for 90-day mortality. Age and comorbidity were identified as the best predictors for complications following RC. CONCLUSION: Short-term morbidity and mortality are high following RC. Reporting of complications is heterogeneous and the quality of evidence is generally low. There is a continuous need for randomised studies to address any intervention that can reduce morbidity and mortality following RC. PROSPERO REGISTRATION NUMBER: 104937.


Asunto(s)
Cistectomía , Neoplasias de la Vejiga Urinaria , Cistectomía/efectos adversos , Humanos , Morbilidad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/cirugía
11.
Semin Oncol Nurs ; 37(1): 151104, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33541734

RESUMEN

OBJECTIVE: To provide a narrative overview of contemporary surgical management of muscle-invasive bladder cancer with focus on radical cystectomy and urinary tract reconstruction. DATA SOURCES: International guidelines and a search for articles in PubMed, Medline, and Cochrane Database for single and collaborative studies on surgical management of muscle-invasive bladder cancer. CONCLUSION: Patients diagnosed with muscle invasive bladder cancer often have complex treatment and care needs. For those who undergo radical cystectomy as the curative treatment, there is a considerable risk of general complications after major surgery and short- and long-term complications specific to reconstruction of the urinary tract after radical cystectomy. Contemporary care focuses on perioperative optimization to lower rates of major complications, enhanced recovery protocols, and focus on rehabilitation and cancer survivorship. IMPLICATIONS FOR NURSING PRACTICE: Nurses are integral members of the multidisciplinary team around patients undergoing surgery for muscle-invasive bladder cancer, and are in a position to coordinate pathways for these patients who often have complex care needs because of preexisting comorbidity and limited personal resources that impede recovery after major surgery and cancer survivorship.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Derivación Urinaria , Cistectomía , Humanos , Músculos , Neoplasias de la Vejiga Urinaria/cirugía
12.
Ugeskr Laeger ; 183(2)2021 01 11.
Artículo en Danés | MEDLINE | ID: mdl-33491636

RESUMEN

A male factor plays a role in half of infertility cases. The causes are summarised in this review, and they include hormonal disturbances, genetic alterations, testicular disease, obstruction, and ejaculatory dysfunction. Evaluation may reveal a correctable cause or uncover underlying disease. In a few cases of pretesticular infertility, medical treatment may have effect, and in cases of obstruction or varicoceles, surgical treatment may correct the problem. In cases with ejaculatory dysfunction, assisted ejaculation often produce viable sperm. Sperm for assisted reproduction may also be obtained by aspiration or surgery.


Asunto(s)
Infertilidad Masculina , Enfermedades Urológicas , Varicocele , Humanos , Infertilidad Masculina/diagnóstico , Infertilidad Masculina/etiología , Infertilidad Masculina/terapia , Masculino , Espermatozoides , Varicocele/cirugía
13.
Hum Reprod ; 36(3): 543-550, 2021 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-33367654

RESUMEN

STUDY QUESTION: Is testicular function associated within father-son pairs? SUMMARY ANSWER: Familial resemblance in testis volume and serum markers of spermatogenesis was observed in father-son pairs. WHAT IS KNOWN ALREADY: Studies suggest familial clustering of male subfertility and impaired spermatogenesis, but in men from the general population little is known about concordance in testicular function between fathers and sons. STUDY DESIGN, SIZE, DURATION: This cross-sectional study with simultaneous collection of data in fathers and sons included 72 pairs (144 fathers and sons), unselected regarding testicular function were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: A subgroup of men from the background population and participating in a study on testicular function were asked permission to invite their fathers to participate in a similar setup. Fathers (median age of 53 years) and sons (median age of 19 years) participated in the same study setup including assessment of testis size, having a blood sample taken and analysed for serum levels of reproductive hormones (FSH, inhibin B, LH, testosterone, oestradiol, sex hormone-binding globulin (SHBG) and calculated free testosterone) and delivering a semen sample for assessment of traditional semen parameters. Mixed-effects models were fitted to estimate the familial resemblance as the proportion of variance in markers of testicular function due to shared factors for fathers and sons accounted for using random-effects. Variance components were calculated from both unadjusted and adjusted models. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustments, variance component analyses showed that familial resemblance between fathers and sons accounted for 48% (P < 0.001) of the variation in testicular volume, 32% (P = 0.009) of the variation in FSH, 31% (P = 0.009) of the variation in the inhibin B/FSH ratio, 33% (P = 0.007) and 45% (P < 0.001) of the variation in testosterone and free testosterone, respectively, and 31% (P = 0.009) of the variation in SHBG. None of the semen parameters were associated within father-son pairs. LIMITATIONS, REASONS FOR CAUTION: The present study may have lacked power to detect associations for semen quality, as large intra- and inter-individual variation occur in semen parameters. WIDER IMPLICATIONS OF THE FINDINGS: In this study, testis volume, serum testosterone and serum markers of spermatogenesis including FSH were associated in fathers and sons, suggesting an impact of paternal genetics for testicular function in the son. However, the estimated familial resemblance for spermatogenesis markers highlights that other factors, such as maternal genetics and prenatal as well as adult exposures, are also of major importance for testicular function. STUDY FUNDING/COMPETING INTEREST(S): The study has received funding from Danish Health Authority, Research Fund of the Capital Region of Denmark and Independent Research Fund Denmark (8020-00218B). None of the funders had any role in the study design, collection, analysis or interpretation of data, writing of the paper of publication decisions. The authors have nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.


Asunto(s)
Padre , Análisis de Semen , Adulto , Biomarcadores , Estudios Transversales , Femenino , Humanos , Hormona Luteinizante , Masculino , Persona de Mediana Edad , Núcleo Familiar , Embarazo , Testosterona , Adulto Joven
14.
Andrology ; 9(2): 618-631, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33236519

RESUMEN

BACKGROUND: Spermatogenesis depends on stimulation by follicle-stimulating hormone (FSH) which binds to FSH receptors (FSHR) on testicular Sertoli cells. Three FSH-related single-nucleotide polymorphisms (SNPs), FSHB -211G>T (rs10835638), FSHR -29G>A (rs1394205) and FSHR 2039A>G (rs6166) affect FSH action, and have been suggested to affect testicular function, but the evidence is uncertain. OBJECTIVE: To describe the associations between the three SNPs and testicular function in a large and well-characterised cohort of men from the general population. MATERIALS AND METHODS: A cross-sectional study of 2020 Danish men unselected regarding testicular function. Outcome variables were semen parameters, reproductive hormones and testis size. Genotyping was done by competitive allele-specific quantitative PCR. Differences in genotype frequencies were tested by chi-square test and associations between genotypes and outcomes were assessed by multivariate linear regressions. RESULTS: The SNPs affected serum FSH; carriers of the variant affecting FSH secretion (FSHB -211G>T) had lower FSH levels while carriers of variants affecting receptor expression (FSHR -29G>A) and receptor sensitivity (FSHR 2039A>G) had higher FSH levels. Carriers of FSHB -211G>T had lower calculated free testosterone/LH ratio. Although both FSHB -211G>T and FSHR 2039A>G were associated with smaller testis size, no clear association was detected in relation to any semen parameters, except a lower total number of morphologically normal spermatozoa in the heterozygous carriers of the FSHB -211G>T DISCUSSION AND CONCLUSION: The studied polymorphisms have only minor modulating influence on testis size and function in healthy men. We detected subtle effects of the three SNPs on FSH levels, but also effects of FSHB -211G>T on calculated free testosterone/LH ratio, compatible with altered Leydig cell function. Thus, the role of these FSH-related polymorphisms is complex and modest in men with normal testicular function, but the possible importance of FSH polymorphisms in men with impaired testicular function should be evaluated in future studies in more detail.


Asunto(s)
Hormona Folículo Estimulante Humana/sangre , Hormona Folículo Estimulante de Subunidad beta/genética , Receptores de HFE/genética , Análisis de Semen , Testículo/anatomía & histología , Adolescente , Alelos , Dinamarca , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Tamaño de los Órganos/genética , Polimorfismo de Nucleótido Simple , Adulto Joven
15.
Ugeskr Laeger ; 182(4)2020 01 20.
Artículo en Danés | MEDLINE | ID: mdl-32052735

RESUMEN

This review covers the possible treatment modalities of organic erectile dysfunction (ED). About 30% of men over 40 years of age suffer from ED. At diagnosis, organic ED should be distinguished from psychological ED, and it is crucial to identify underlying diseases including endocrine disorders, neurological problems and cardiovascular diseaplase. Management of organic ED is initiated by treating such underlying problems, and lifestyle changes are central. Symptomatic treatments include tablets, injections, intraurethral medication, vacuum pumps, and penile implants. Current research focuses on regenerative medicine, which may play a future role.


Asunto(s)
Disfunción Eréctil , Prótesis de Pene , Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/terapia , Humanos , Inyecciones , Masculino
16.
APMIS ; 128(2): 92-103, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31755155

RESUMEN

Bacillus Calmette-Guérin (BCG) immunotherapy for bladder cancer has been used since 1976 when the first evidence of its ability to lower recurrence and progression rates was published. Today, BCG immunotherapy is the choice of care for high-grade non-muscle invasive bladder cancer (NMIBC) after transurethral resection. This article presents indications and procedure of BCG instillations, and outlines the effects on recurrence and progression of NMIBC. The BCG-induced immunity in NMIBC is not yet fully understood. Animal studies point towards BCG inducing specific tumour immunity. We describe the current knowledge of how this immunity is induced, from internalization of BCG bacilli in urothelial cells, to cytokine- and chemokine-mediated recruitment of neutrophils, monocytes, macrophages, T cells, B cells and natural killer cells. In addition, we describe the process of trained immunity, the non-specific protective effects of BCG. Recent studies also indicate that dysbiosis of the urinary microbiome may cause lower urinary tract dysfunction. Side effects of BCG bladder instillations range from common, mild and transient symptoms, such as dysuria and flu-like symptoms, to more severe and rarely occurring life-threatening complications. We review the literature and give an overview of reported incidences and management of BCG infections after intravesical instillation.


Asunto(s)
Vacuna BCG/inmunología , Mycobacterium bovis/inmunología , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/terapia , Administración Intravesical , Animales , Humanos , Inmunoterapia/métodos , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/terapia , Vejiga Urinaria/inmunología
17.
Scand J Urol ; 53(6): 398-402, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31578115

RESUMEN

Background: Management of renal trauma injuries is shifting towards more conservative approaches in hemodynamically stable adult patients, even for high grade and/or penetrating trauma. The objective of this study was to analyze the patterns of injury, management and complications in renal trauma patients at a Danish university hospital with a level 1 trauma center.Method: Patients diagnosed with renal trauma at Rigshospitalet, Copenhagen, Denmark, between January 2010 and December 2015 were identified retrospectively by the ICD-10 code. Data were collected from electronic patient records. Imaging was classified by radiologists.Results: Out of 107 patients identified, blunt injuries comprised 93%. Median age was 28. The distribution of injury grade according to AAST was 20% grade I, 4% grade II, 33% grade III, 33% grade IV and 10% grade V. All patients with grade I-III were managed conservatively. Two patients were treated with angioembolization (1 with grade IV and 1 with grade V). Five patients with grade IV were treated with an internal ureteral stent and one patient with grade IV blunt trauma had an emergency nephrectomy performed. Overall complication rate was 7%. No patient died due to their renal injury. Renal function was normal in all patients at discharge, assessed by eGFR measurement. Of the 50% of patients who were followed up with a renography, none developed obstruction due to the renal trauma.Conclusion: The vast majority of renal injuries were due to blunt trauma. Hemodynamically stable patients, even with penetrating and/or high-grade blunt trauma, were managed non-operatively and there was a low rate of complications.


Asunto(s)
Riñón/lesiones , Centros Traumatológicos , Heridas no Penetrantes , Heridas Penetrantes , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Dinamarca , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/diagnóstico , Heridas no Penetrantes/terapia , Heridas Penetrantes/complicaciones , Heridas Penetrantes/diagnóstico , Heridas Penetrantes/terapia , Adulto Joven
19.
Environ Int ; 121(Pt 1): 365-374, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30245359

RESUMEN

BACKGROUND: The filaggrin gene (FLG) encodes an epidermal protein, filaggrin, which is important for normal skin barrier functions. We previously showed that FLG loss-of-function mutation carriers have a higher internal exposure to some non-persistent chemicals such as certain phthalates and parabens, suggesting increased trans-epidermal penetration. Several groups of non-persistent chemicals are suspected endocrine disrupters with potential to affect testicular function. OBJECTIVES: To investigate associations between exposure to non-persistent chemicals and testicular function in young Danish men with and without FLG mutations. METHODS: We measured urinary concentrations of bisphenol A (BPA) and other simple phenols, parabens, and UV filters including benzophenones (BP-1, BP-3 and 4-HBP) in men genotyped for FLG R501X, 2282del4, and R2447X loss-of-function mutations; in total 65 mutation carriers and 130 non-carriers (controls) were included. Outcomes were markers of testicular function, assessed by serum reproductive hormones and semen quality. RESULTS: We found that associations between urinary chemical concentrations and outcomes were different in cases and controls. Within the group of FLG mutation carriers, higher urinary concentrations of BPA, BP-1 and BP-3 were associated with higher testosterone and estradiol serum levels and lower FSH. Similar trends in hormone levels were observed for FLG mutation carriers with measurable levels of 4-HBP compared to those who had no detectable levels of urinary 4-HBP. Furthermore, those in the highest urinary BPA quartile had lower sperm motility than those in the lower quartiles. None of these associations were evident in the control group. In the control group, however, lower sperm motility and sperm concentration were observed in the men with detectable urinary 4-HBP compared to the men non-detectable urinary 4-HBP. We found no association between any parabens and outcomes, nor for the other measured phenols or UV filters. CONCLUSIONS: Associations between male reproductive health parameters and urinary levels of BPA and benzophenones such as BP-3, BP-1 and 4-HBP were observed in FLG mutation carriers but not in controls from the same study population. This difference between FLG mutation carriers and non-carriers is not explained solely by differences in exposure levels of the examined compounds as e.g. BPA and 4-HBP urinary levels did not differ between the two groups. We hypothesise that effects of exposure to these compounds may be modulated in FLG mutation carriers by either different levels of co-exposures or by route of uptake, with a higher fraction of the uptake by dermal uptake.


Asunto(s)
Benzofenonas/orina , Hormonas Esteroides Gonadales/sangre , Proteínas de Filamentos Intermediarios/genética , Parabenos/metabolismo , Fenoles/orina , Análisis de Semen , Compuestos de Bencidrilo/orina , Disruptores Endocrinos/orina , Femenino , Proteínas Filagrina , Genotipo , Humanos , Masculino , Mutación , Ácidos Ftálicos/orina , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Adulto Joven
20.
Ugeskr Laeger ; 178(40)2016 Oct 03.
Artículo en Danés | MEDLINE | ID: mdl-27697121

RESUMEN

This article describes penile fracture and testicular rupture and offers recommendations for management. Both conditions occur most commonly after blunt trauma. Diagnosis can be supported by imaging but is usually confirmed on surgical exploration, which in both cases should be carried out promptly. Penile fracture occurs most commonly related to coitus, and surgical correction decreases the risk of long-term erectile dysfunction, deformity and pain. Testicular rupture usually presents with persisting pain and haematoma after trauma, and surgery is recommended to minimize permanent organ damage.


Asunto(s)
Pene , Rotura/cirugía , Testículo , Coito , Humanos , Masculino , Pene/anatomía & histología , Pene/lesiones , Pene/cirugía , Rotura/patología , Testículo/lesiones , Testículo/patología , Testículo/cirugía , Heridas no Penetrantes/patología , Heridas no Penetrantes/cirugía
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