Locally Advanced and Metastatic Prostate Cancer Treated with Intermittent Androgen Monotherapy or Maximal Androgen Blockade: Results from a Randomised Phase 3 Study by the South European Uroncological Group

BACKGROUND: Few randomised studies have compared antiandrogen intermittent hormonal therapy (IHT) with continuous maximal androgen blockade (MAB) therapy for advanced prostate cancer (PCa). OBJECTIVE: To determine whether overall survival (OS) on IHT (cyproterone acetate; CPA) is noninferior to OS on continuous MAB. DESIGN, SETTING, AND PARTICIPANTS: This phase 3 randomised trial compared IHT and continuous MAB in patients with locally advanced or metastatic PCa. INTERVENTION: During induction, patients received CPA 200 mg/d for 2 wk and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH; triptoreline 11.25 mg) analogue plus CPA 200 mg/d. Patients whose prostate-specific antigen (PSA) was <4 ng/ml after 3 mo of induction treatment were randomised to the IHT arm (stopped treatment and restarted on CPA 300 mg/d monotherapy if PSA rose to ≥20 ng/ml or they were symptomatic) or the continuous arm (CPA 200 mg/d plus monthly LHRH analogue). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome measurement was OS. Secondary outcomes included cause-specific survival, time to subjective or objective progression, and quality of life. Time off therapy in the intermittent arm was recorded. RESULTS AND LIMITATIONS: We recruited 1045 patients, of which 918 responded to induction therapy and were randomised (462 to IHT and 456 to continuous MAB). OS was similar between groups (p=0.25), and noninferiority of IHT was demonstrated (hazard ratio [HR]: 0.90; 95% confidence interval [CI], 0.76-1.07). There was a trend for an interaction between PSA and treatment (p=0.05), favouring IHT over continuous therapy in patients with PSA ≤1 ng/ml (HR: 0.79; 95% CI, 0.61-1.02). Men treated with IHT reported better sexual function. Among the 462 patients on IHT, 50% and 28% of patients were off therapy for ≥2.5 yr or >5 yr, respectively, after randomisation. The main limitation is that the length of time for the trial to mature means that other therapies are now available. A second limitation is that T3 patients may now profit from watchful waiting instead of androgen-deprivation therapy. CONCLUSIONS: Noninferiority of IHT in terms of survival and its association with better sexual activity than continuous therapy suggest that IHT should be considered for use in routine clinical practice.

Carcinoma da Próstata. Análise Retrospectiva de 370 casos

Os AA estudaram retrospectivamente os processos clínicos de 370 doentes com carcinoma da próstata, com o intuito de dar uma ideia da problemática desta doença em Portugal. Ressalvando o facto de a análise incidir sobre casos tratados por vários urologistas e não haver assim uniformidade nos critérios, são apresentadas sucessivamente as manifestações clínicas, métodos de diagnóstico presumível e definitivo e a terapêutica instituída. Apontam ainda a mortalidade, no país, nos últimos anos, por carcinoma da próstata e por tumores malignos em geral e apresentam uma tabela em que aquela é comparada com a de outros países.

Fístulas Arteriovenosas Renais. Tratamento Conservador por Embolização Arterial

Fazem-se considerações gerais sobre as FAV, incidindo particularmente nas renais. Descrevem-se dois casos de FAV renais traumáticas com hematúria, tratadas por embolização.

Alterações Hidro-Electrolíticas Induzidas por Ressecção Prostática Transuretral

A ressecção prostática transuretral (RTU) foi incriminada como causa de hiponatrémias graves por absorção macissa do soluto de irrigação (SI) vesical. Observámos 41 doentes submetidos a RTU, usando como SI Sorbitol Manitol (Grupo A), e 6 doentes usando água destilada (Grupo B). Um Grupo C, era constituído por 6 doentes operados por motivos não urológicos com intervenções com duração e anestesia semelhantes à RTU. Os três grupos foram estudados segundo um mesmo protocolo com colheitas de sangue antes (tempo 1), imediatamente após (tempo II) e 1 hora depois da intervenção(tempo III). A natrémia diminuiu significativamente nos 3 grupos do tempo 1 para o tempo II, em média 3,4mEq 1 com Manitol Sorbitol, 2,3mEq 1 com água destilada, e 4,4mEq 1 no grupo C. A osmolalidade não se alterou significativamente ao longo dos três tempos de colheita, o gap osmolar subiu do tempo 1 para o tempo II apenas no grupo A com Sorbitol Manitol. Em resumo, descidas moderadas no sódio sérico sem relevância clínica, e sem hipotonicidade, são frequentes post-RTU, mas não deverão ser superiores à restante cirurgia sem irrigação vesical.

Prostate Cancer: The Role of Multiparametric Magnetic Resonance Imaging

Multiparametric Magnetic Resonance Imaging has been increasingly used for detection, localization and staging of prostate cancer over the last years. It combines high-resolution T2 Weighted-Imaging and at least two functional techniques, which include Dynamic Contrast–Enhanced Magnetic Resonance Imaging, Diffusion-Weighted Imaging, and Magnetic Resonance Imaging Spectroscopy. Although the combined use of a pelvic phased-array and an Endorectal Coil is considered the state-of-the-art for Magnetic Resonance Imaging evaluation of prostate cancer, Endorectal Coil is only absolute mandatory for Magnetic Resonance Imaging Spectroscopy at 1.5 T. Sensitivity and specificity levels in cancer detection and localization have been improving with functional technique implementation, compared to T2 Weighted-Imaging alone. It has been particularly useful to evaluate patients with abnormal PSA and negative biopsy. Moreover, the information added by the functional techniques may correlate to cancer aggressiveness and therefore be useful to select patients for focal radiotherapy, prostate sparing surgery, focal ablative therapy and active surveillance. However, more studies are needed to compare the functional techniques and understand the advantages and disadvantages of each one. This article reviews the basic principles of prostatic mp-Magnetic Resonance Imaging, emphasizing its role on detection, staging and active surveillance of prostate cancer.

Post-Treated Prostate Cancer: Normal Findings and Signs of Local Relapse on Multiparametric Magnetic Resonance Imaging

The use of multiparametric magnetic resonance imaging (mp-MRI) for prostate cancer has increased over recent years, mainly for detection, staging, and active surveillance. However, suspicion of recurrence in the set of biochemical failure is becoming a significant reason for clinicians to request mp-MRI. Radiologists should be able to recognize the normal post-treatment MRI findings. Fibrosis and atrophic remnant seminal vesicles after prostatectomy are often found and must be differentiated from local relapse. Moreover, brachytherapy, external beam radiotherapy, cryosurgery, and hormonal therapy tend to diffusely decrease the signal intensity of the peripheral zone on T2-weighted images (T2WI) due to the loss of water content, consequently mimicking tumor and hemorrhage. The combination of T2WI and functional studies like diffusion-weighted imaging and dynamic contrast-enhanced improves the identification of local relapse. Tumor recurrence tends to restrict on diffusion images and avidly enhances after contrast administration either within or outside the gland. The authors provide a pictorial review of the normal findings and the signs of local tumor relapse after radical prostatectomy, external beam radiotherapy, brachytherapy, cryosurgery, and hormonal therapy.

HAART: a risk factor for development of porphyria cutanea tarda?

Porphyria cutanea tarda (PCT) is caused by inherited or acquired partial deficiency of the uroporphyrinogen-decarboxylase (Uro-D) enzyme activity. It is the most common form of porphyria. The main triggering factors to the development of porphyria cutanea tarda are alcohol, hepatitis C virus and human immunodeficiency virus. There are several reports of PCT associated with drugs, among them, antiretroviral therapy. We describe three HIV-positive patients, which showed photosensitivity as well as the emergence of tense blisters on sun-exposed areas during the use of highly active antiretroviral therapy (HAART) and discuss the possibility of PCT after the use of these drugs by those patients.

Selectividad de las redes de enmalle para los recursos costeros en la Región Grau

Da a conocer los resultados obtenidos de la evaluación para la determinación de la eficiencia y estimados de parámetros de selectividad con redes de enmalle para los recursos costeros en la Región Grau (Los Órganos, Ñuro, Lobitos y Cabo Blanco), llevado a cabo los meses de octubre, noviembre y diciembre de 1996.

Lithiases d'infection [Infective lithiasis].

We report the case of a 69-year-old woman, with a BMI of 42.9, suffering from bilateral struvite calculi and who raised end stage renal failure. Urease-synthesizing bacteria, leading to the hydrolysis of urea into ammonium and to an alkaline urine (pH > 7.2), are required for struvite stone formation in humans. Struvite component constitutes the majority of staghom calculi. Patients with struvite stones could lose renal function because of obstructive or pyelonephritic episodes and surgical interventions on the kidney. Therapeutic success needs a follow up by a specialized uro-nephrologist team as soon as possible.

Ledelse - en bevegelse i ansvar og kjærlighet

Bakgrunn for denne studien har vært en uro over markedskreftenes innflytelse i samfunnet generelt og i helsevesenet spesielt. Økonomiske organisasjonsmodeller er utviklet for det private næringsliv, hvor organisasjonens mål er å tjene penger. Når kostnadsbesparelser og effektivitet er førende tenkning i kulturen, er det en fare for at mennesket blir sett på som et verktøy eller middel for effektivisering av organisasjonen. Det synes derfor å være et behov for ny tenkning om ledelse, hvor lederens ansvar i større grad er knyttet til ansvar for medmennesket og for mellommenneskelige relasjoner, fremfor ytre strukturer og økonomiske resultater. Hensikten med denne studien har vært å studere hva ansvarlig ledelse er med bakgrunn i vårdvitenskapen, filosofiske tekster av Levinas og Gadamer, samt empirisk materiale. Studien viser at ansvarlig ledelse er styrt av et indre ansvar og har sin etiske grunn i kjærligheten til medmennesket. Ansvarlig ledelse er en del av det å være menneske, og dette innebærer å føre seg selv og andre frem mot ansvaret for de som er sårbare og hjelpeløse. Å føre andre frem mot ansvaret for medmennesket og for fellesskapet er å ivareta egen og andres verdighet ved å fremme menneskets naturlige retningsbestemmelse. Ansvaret for andre danner menneskets menneskelighet i berørthet og følsomhet ved andres smerte og lidelse. Dette vekker menneskets potensial for godhet og nestekjærlighet. Forståelsen for ansvarets betydning bidrar til et fellesskap som opprøres over den urett som rammer andre, og kjennetegnes av solidaritet med de svakeste. Studien viser at ansvarlig ledelse er å tjene den andre i stedfortredelse og ydmykhet. Den andre er den egentlige leder og ledestjerne, og den andre er den som kan avgjøre om ledelse er ansvarlig ledelse. Overført til sykehus vil dette innebære at ansvarlig ledelse er å fremme en kultur, hvor pasienten er den naturlige ledestjerne i fellesskapet. Et slikt fellesskap verner om og gir vekstvilkår for det gode vårdande. Teorimodellen om ansvarlig ledelse er rettet mot hva det innebærer å være ansvarlig som menneske. Det vises til et ansvar som kan betraktes som et vilkår, eller som en mulighet ved livet selv. Å påta seg ansvar for andre gir kraft og mot, og bidrar til at mennesket utvikler sitt iboende potensial for å kunne styres av et ”indre bør” fremfor ytre regler og direktiver. Ledelse knyttet til et slikt ansvar innebærer noe mer enn ledelse som en rolle eller funksjon i organisasjoner, da det er et ansvar som strekker seg utover det som kan rommes i en stillingsinstruks.

Spot urine porphyrins/creatinine ratio profile of healthy Brazilian individuals adjusted for personal habits

Changes in urinary porphyrin excretion may be the result of hereditary causes and/or from environmental or occupational exposure. The objective of this study was to measure the amount of some porphyrins in spot urine samples obtained from volunteers randomly selected from a healthy adult population of São Paulo with a sensitive HPLC method and to estimate normal ranges for a non-exposed population. Spot urine samples were collected from 126 subjects (both genders, 18 to 65 years old) not occupationally exposed to porphyrinogenic agents. Porphyrin fractions were separated on RP-18 HPLC column eluted with a methanol/ammonium acetate buffer gradient, pH 4.0, and measured fluorometrically (excitation 405 nm/emission 620 nm). The amount of porphyrins was corrected for urinary creatinine excretion. Only 8-carboxyl (uro) and 4-carboxyl (copro) porphyrins were quantified as µg/g creatinine. Data regarding age, gender, occupational activities, smoking and drinking habits were analyzed by Mann-Whitney and Kruskal-Wallis tests. Uroporphyrin results did not differ significantly between the subgroups studied. Copro and uro + copro porphyrins were significantly different for smokers (P = 0.008) and occupational activities (P = 0.004). With respect to alcohol consumption, only men drinking >20 g/week showed significant differences in the levels of copro (P = 0.022) and uro + copro porphyrins (P = 0.012). The 2.5-97.5th percentile limit values, excluding those for subjects with an alcohol drinking habit >20 g/week, were 0-20.8, 11.7-93.1, and 15.9-102.9 µg/g creatinine for uro, copro and uro + copro porphyrins, respectively. These percentile limit values can be proposed as a first attempt to provide urinary porphyrin reference values for our population, serving for an early diagnosis of porphyrinopathies or as biomarkers of exposure to porphyrinogenic agents.

Inhibition of renal glucose reabsorption as a novel treatment for diabetes patients

The importance of the kidney in glucose homeostasis has been recognized for many years. Recent observations indicating a greater role of renal glucose metabolism in various physiologic and pathologic conditions have rekindled the interest in renal glucose handling as a potential target for the treatment of diabetes. The enormous capacity of the proximal tubular cells to reabsorb the filtered glucose load entirely, utilizing the sodium-glucose co-transporter system (primarily SGLT-2), became the focus of attention. Original studies conducted in experimental animals with the nonspecific SGLT inhibitor phlorizin showed that hyperglycemia after pancreatectomy decreased as a result of forced glycosuria. Subsequently, several compounds with more selective SGLT-2 inhibition properties (“second-generation”) were developed. Some agents made it into pre-clinical and clinical trials and a few have already been approved for commercial use in the treatment of type 2 diabetes. In general, a 6-month period of therapy with SGLT-2 inhibitors is followed by a mean urinary glucose excretion rate of ~80 g/day accompanied by a decline in fasting and postprandial glucose with average decreases in HgA1C ~1.0%. Concomitant body weight loss and a mild but consistent drop in blood pressure also have been reported. In contrast, transient polyuria, thirst with dehydration and occasional hypotension have been described early in the treatment. In addition, a significant increase in the occurrence of uro-genital infections, particularly in women has been documented with the use of SGLT-2 inhibitors. Conclusion: Although long-term cardiovascular, renal and bone/mineral effects are unknown SGLT-2 inhibitors, if used with caution and in the proper patient provide a unique insulin-independent therapeutic option in the management of obese type 2 diabetes patients.

Effect of intravaginal electrical stimulation on pelvic floor muscle strength

The aim of this study was to evaluate the effect of intravaginal electrical stimulation (IES) on pelvic floor muscle (PFM) strength in patients with mixed urinary incontinence (MUI). Between January 2001 and February 2002, 40 MUI women (mean age: 48 years) were studied. Urge incontinence was the predominant symptom; 92.5% also presented mild stress urinary incontinence (SUI). Selection criteria were clinical history and urodynamics. Pre-treatment urodynamic study showed no statistical differences between the groups. Ten percent of the women in each group had involuntary detrusor contractions. Patients were randomly distributed, in a double-blind study, into two groups. Group G 1 (n=20), effective IES, and group G2 (n=20), sham IES, with follow-up at 1 month. The following parameters were studied: (1) clinical questionnaire, (2) examiner's evaluation of perineal muscle strength, (3) objective evaluation of perineal muscle by perineometry, (4) vaginal weight test, and (5) urodynamic study. The IES protocol consisted of three 20-min sessions per week over a 7-week period using a Dualpex Uro 996 at 4 Hz. There was no statistically significant difference in the demographic data of both groups. The number of micturitions per 24 h after treatment was reduced significantly in both groups. Urge incontinence, present in all patients before treatment, was reduced to 15% in G1 and 31.5% in G2 post-treatment. The subjective evaluation of PFM strength demonstrated a significant improvement in G1. Objective evaluation of PFM force by perineometer showed a significant improvement in maximum peak contraction post-treatment in both groups. In the vaginal weight test, there was a significant increase in average number of cone retentions post-treatment in both groups. With regard to satisfaction level, after treatment, 80% of the patients in G1 and 65% of the patients in G2 were satisfied. There was no statistically significant difference between the groups. There was a significant improvement in PFM strength from both effective and sham electrostimulation, questioning the effectiveness of electrostimulation as a monotherapy in treating MUI.

Intravaginal electrical stimulation: a randomized, double-blind study on the treatment of mixed urinary incontinence

Background the aim of this study was to compare effective and sham intravaginal electrical stimulation (IES) in treating mixed urinary incontinence. Methods. Between January 2001 and February 2002, 40 women were randomly distributed, in a double-blind study, into two groups: group G1 (n = 20), effective IES, and group G2 (n = 20), sham IES, with follow up at one month. Different parameters was studied: 1. clinical questionnaire, 2. body mass index; 3. 60-min pad test; 4. urodynamic study. The protocol of IES consisted of three 20-min sessions per week over a seven-week period. The Dualpex Uro 996 used a frequency of 4 Hz. Results. There was no statistically significant difference in the demographic data of both groups. The number of micturitions per 24 h after treatment was reduced significantly in both groups. Urge incontinence was reduced to 15% in G1 and 31.5% in G2; there was no significant difference between the groups. In the analog wetness and discomfort sensation evaluations were reduced significantly in both groups. The pretreatment urodynamic study showed no statistical difference in urodynamic parameters between the groups. Ten percent of the women presented involuntary detrusor contractions. In the 60-min pad test, there was a significant reduction in both groups. In regards to satisfaction level, after treatment, 80% of G1 patients and 65% of G2 patients were satisfied. There was no statistically significant difference between the groups. Conclusion. Significant improvement was provided by effective and sham electrostimulation, questioning the effectiveness of electrostimulation as a monotherapy.