Hyperthermic Mitomycin C in Intermediate-risk Non-muscle-invasive Bladder Cancer: Results of the HIVEC-1 Trial.

BACKGROUND: Optimising therapeutic strategies of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC) is needed. OBJECTIVE: To compare recurrence-free survival (RFS) with adjuvant intravesical mitomycin C (MMC) at normothermia or hyperthermia using the COMBAT bladder recirculation system at 43 °C for 30 and 60 min. DESIGN, SETTING, AND PARTICIPANTS: A prospective open-label, phase 3 randomised controlled trial (HIVEC-1) accrued across 13 centres between 2014 and 2020 in Spain. After complete transurethral resection of the bladder and immediate postoperative MMC instillation, patients with IR-NMIBC were randomised (1:1:1) to four weekly followed by three monthly 40-mg MMC instillations at normothermia (control; n = 106), 43 °C for 30 min (n = 107), or 43 °C for 60 min (n = 106) were investigated. Therapeutic compliance was defined as four or more instillations. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was RFS at 24 mo in the intention-to-treat (ITT) and per-protocol (PP) populations. The secondary outcomes included progression-free survival at 24 mo, safety outcome measures, and changes in health-related quality of life. Log-rank, Fisher, χ2, and analysis of variance tests were used. RESULTS AND LIMITATIONS: The ITT 24-mo RFS was 77% for control, 82% for 43 °C-30 min, and 80% for 43 °C-60 min (p = 0.6). The PP 24-mo RFS was 77% for control, 83% for 43 °C-30 min, and 80% for 43 °C-60 min (p = 0.59). Six patients progressed to muscle-invasive disease in the ITT population (four in the control, 43 °C-30 min, and 43 °C-60 min groups each) and four in the PP population (all controls). Serious adverse events occurred in 26 patients (8.1%), and we were unable to demonstrate a difference between groups (p = 0.5). Adverse events, mainly dysuria and spasms, occurred in 124 patients (33% in control, 35% in 43 °C-30 min, and 48% in 43 °C-60 min; p = 0.05). The total International Prostate Symptom Score worsened by 1.2 ±â€¯7.3 points, similarly across groups (p = 0.29). The Functional Assessment of Cancer Therapy-Bladder domains and indexes showed no significant change. CONCLUSIONS: Four-month adjuvant hyperthermic MMC using the COMBAT system for 30 and 60 min in IR-NMIBC is well tolerated, but we did not find it to be superior to normothermic MMC at 24 mo. PATIENT SUMMARY: We were unable to demonstrate the effectiveness of hyperthermia using the COMBAT system in intermediate-risk non-muscle-invasive bladder cancer. Further evaluation of long-term recurrence and progression, and maintenance regimens appears mandatory.

Vigencia actual de los nomogramas en la estadificación del cáncer de próstata / Current validity of nomograms for prostate cancer staging

OBJETIVO: En este trabajo se presenta una revisión del concepto de “nomograma” aplicado al cáncer de próstata y específicamente como medio de estadificación.MÉTODOS/RESULTADOS: Para ello se describen los parámetros indispensables para evaluar este tipo de modelos predictivos, a saber: Calibración, Discriminacióny Utilidad Clínica. Estos requisitos son analizados sobre un caso práctico real en nuestro medio asistencial comparando las “Tablas de Partin” y el “Nomograma del Hospital Universitario Miguel Servet”, demostrando su correcta calibración, discriminación y utilidad clínica previa selección de adecuados puntos de corte.CONCLUSIÓN: La aplicación del modelo predictivo a nuestra práctica asistencial ha logrado una infraestadificaciónclínica tras prostatectomía radical del 17,3%

OBJETIVE: This paper presents a review of the concept of “nomogram” applied to prostate cancer, and specifically as a staging tool.METHODS/RESULTS: We describe the essentialparameters for the evaluation of such type of predictive models: Calibration, discrimination and clinical usefulness. Such requisites are analyzed using a real clinical case in our clinical setting, comparing the “Partin`s tables” and the “Miguel Servet University Hospital´s nomogram”. We demonstrate its correct calibration, discrimination and clinical usefulness after previous selection of proper cut points.CONCLUSION: The application of the predictivemodel to our clinical practice has achieved a clinical understaging of 17.3% after radical prostatectomy

Lack of effect of growth hormone replacement therapy on CYP1A2 and xanthine oxidase activities in growth hormone-deficient children.

BACKGROUND AND OBJECTIVES: The recombinant human growth hormone (rhGH) is being increasingly used for a number of metabolic alterations. GH is the main regulator of several hepatic drug metabolizing enzymes in rodents. In addition, GH could play a major role in defining the interface between pharmacogenetics and development. However, little is known about the effect of GH on the activity of hepatic enzymes in children. The aim of this study was to determine the effect of rhGH replacement therapy for 4 weeks on CYP1A2 and xanthine oxidase (XO) activities in children. METHODS: We used caffeine as a probe drug to assess the enzyme activities at two points in time: before starting GH treatment (day 0) and after 4 weeks on rhGH therapy (day A). A total of 31 GH-deficient children (age range: 4.1-13.1 years, mean age: 9.88+/-2.89 years) participated. Urinary concentrations of caffeine and metabolites were determined by high-performance liquid chromatography (HPLC) to calculate the metabolite ratios: (AFMU+1X+1U)/17U for CYP1A2 and 1U/(1X+1U) for XO. RESULTS: Four weeks of GH substitution did not importantly alter the markers of the enzyme activities measured in this study. Median values and 95% confidence intervals (CI) at baseline were 5.17 (3.87-5.59) for the CYP1A2 ratio and 0.62 (0.56-0.65) for the XO ratio. These values, after treatment, were 4.57 (3.90-5.97) for the CYP1A2 marker and 0.62 (0.59-0.67) for the XO ratio. Data comparison between periods showed lack of statistically significant differences (P>0.05). The relative changes measured by the ratios of medians and 90% CI were 1.14 (0.90-1.31) and 0.99 (0.94-1.06) for CYP1A2 and XO, respectively. CONCLUSIONS: The absence of significant changes in the markers of enzyme activities CYP1A2 and XO suggests that rhGH replacement therapy of GH-deficient children for 4 weeks could not noticeably modify the efficacy or toxicity of substrates of these metabolic enzymes.

Epidermal naevus syndrome (Solomon's syndrome) associated with bladder cancer in a 20-year-old female.

Epidermal naevus syndrome was first described by Solomon et al. in 1968, based on a study of 12 patients. Herein we report the case of a 20-year-old female diagnosed with epidermal naevus syndrome at the age of 3 years. Subsequently she experienced several different symptoms and at the last exploration a suspicious lesion was found in her bladder. The definitive pathology diagnosis was transitional cell carcinoma of the bladder, which is extremely rare in patients aged <21 years. It seems that this neoplastic lesion was directly related to the essential pathology of the patient, namely epidermal naevus syndrome.

Malignant mesothelioma of the tunica vaginalis. Report of a case without risk factors and review of the literature.

Malignant mesothelioma of the tunica vaginalis testis is an aggressive tumour with local recurrence being distant metastases the main feature of the clinical course. Usually appears over the fourth decade, having a strong relationship with occupational exposure to asbestos and long lasting hydrocele. We introduce a case of a 78-year-old caucasian male who developed a malignant mesothelioma without personal history of hydrocele or exposure to asbestos. A revision of the current literature is performed to summarize the recent therapeutic options as well as new diagnostic tools.

Derivaciones urinarias: anatomía radiológicay complicaciones / Urinary Derivations: radiological anatomy and complications

La cistectomía con derivación de la vía urinaria es un procedimiento común en el tratamiento del carcinoma de células transicionales de vejiga. Presentamos los hallazgos radiológicos (ecografía, tomografía computarizada [TC] y urografía) de las técnicas quirúrgicas de reconstrucción más habitualmente realizadas por el Servicio de Urología de nuestro hospital, así como de algunas de las complicaciones presentadas.Dichas técnicas se dividen básicamente en dos tipos: derivaciones no continentes, de las que destacamos la técnica de Bricker-Wallace II y las continentes, que a su vez pueden ser ortotópicas, con anastomosis a la uretra (técnica de Hautmann) y heterotópicas, con salida de orina por el ano (técnica de Mainz II) o autocateterizables (técnica de Mainz I) (AU)