Salvage cryotherapy for prostate cancer.

BACKGROUND: Most men diagnosed with prostate cancer will be candidates for active treatment and 20 to 50% of patients treated with organ preserving strategies recur within the prostate. Optimal treatment of recurrence is controversial. Prostate cryosurgery has been increasingly used as primary, recurrence and focal treatment for prostate cancer. METHODS: We analysed 55 patients submitted to cryotherapy as salvage treatment after recurrence. RESULTS: Study population presented with a mean age of 70.9 ± 6.2 years, mean initial PSA of 7.6 ng/ml and average prostate volume by ultrasound of 43.2 ± 14.7 grams. Mean follow-up was of 18.0 months. Biochemical free survival at one year of follow-up was of 85%. CONCLUSIONS: Cryotherapy can be an effective and safe treatment for recurrence after primary curative treatment failure.

Prior MRI-imaging impact of patients submitted to brachytherapy for prostate cancer.

INTRODUCTION: Brachytherapy for the treatment of prostate cancer is a well-established option. Use of Multiparametric Magnetic Resonance Imaging (mpMRI) for staging and diagnosis of prostate cancer has come to change the current paradigm. In this study we aim to assess the impact of performing mpMRI to evaluate the presence of extracapsular lesions before brachytherapy in patients with prostate cancer concerning biochemical recurrence and time to nadir. METHODS: Review data from 73 patients submitted to brachytherapy. The following factors were evaluated: age, initial PSA, MRI local staging results, ISUP, nadir, time to nadir, PSA at one-year, biochemical recurrence, and time to recurrence. RESULTS: Median age was 68 years (51-72) and median follow-up 53 months (30-72). Concerning imaging modality 30,1% (n = 22) patients performed mpMRI. In the mpMRI group, 90.9% (n = 20) had at least one suspect lesion on mpMRI. Time to nadir was 27 months (3-64) in patients where mpMRI was not performed and 23.5 months (2-48) in patients submitted to mpMRI (P = .244). The median value of nadir was 0.42 ng/mL (<0.001-2) in patients submitted to mpMRI and vs 0.28 ng/mL (<0.001-4) in patients without MRI (P = .062) Recurrence utilizing Phoenix criteria was 9% (n = 2) in patients with MRI and 9.2% (n = 5) without mpMRI (P = .456), median follow-up of 43 months (12-72) for the MRI group with 58 months (30-78) for the non-mpMRI group. Both groups were statistically similar. CONCLUSION: Our results allow us to conclude that in our series MRI did not influence biochemical recurrence, time to nadir, or nadir value.

Receptor deorphanization in an echinoderm reveals kisspeptin evolution and relationship with SALMFamide neuropeptides.

BACKGROUND: Kisspeptins are neuropeptides that regulate reproductive maturation in mammals via G-protein-coupled receptor-mediated stimulation of gonadotropin-releasing hormone secretion from the hypothalamus. Phylogenetic analysis of kisspeptin-type receptors indicates that this neuropeptide signaling system originated in a common ancestor of the Bilateria, but little is known about kisspeptin signaling in invertebrates. RESULTS: Contrasting with the occurrence of a single kisspeptin receptor in mammalian species, here, we report the discovery of an expanded family of eleven kisspeptin-type receptors in a deuterostome invertebrate - the starfish Asterias rubens (phylum Echinodermata). Furthermore, neuropeptides derived from four precursor proteins were identified as ligands for six of these receptors. One or more kisspeptin-like neuropeptides derived from two precursor proteins (ArKPP1, ArKPP2) act as ligands for four A. rubens kisspeptin-type receptors (ArKPR1,3,8,9). Furthermore, a family of neuropeptides that act as muscle relaxants in echinoderms (SALMFamides) are ligands for two A. rubens kisspeptin-type receptors (ArKPR6,7). The SALMFamide neuropeptide S1 (or ArS1.4) and a 'cocktail' of the seven neuropeptides derived from the S1 precursor protein (ArS1.1-ArS1.7) act as ligands for ArKPR7. The SALMFamide neuropeptide S2 (or ArS2.3) and a 'cocktail' of the eight neuropeptides derived from the S2 precursor protein (ArS2.1-ArS2.8) act as ligands for ArKPR6. CONCLUSIONS: Our findings reveal a remarkable diversity of neuropeptides that act as ligands for kisspeptin-type receptors in starfish and provide important new insights into the evolution of kisspeptin signaling. Furthermore, the discovery of the hitherto unknown relationship of kisspeptins with SALMFamides, neuropeptides that were discovered in starfish prior to the identification of kisspeptins in mammals, presents a radical change in perspective for research on kisspeptin signaling.

Radon and thoron exhalation rate, emanation factor and radioactivity risks of building materials of the Iberian Peninsula.

Radon (222Rn) and thoron (220Rn) are radioactive gases emanating from geological materials. Inhalation of these gases is closely related to an increase in the probability of lung cancer if the levels are high. The majority of studies focus on radon, and the thoron is normally ignored because of its short half-life (55.6 s). However, thoron decay products can also cause a significant increase in dose. In buildings with high radon levels, the main mechanism for entry of radon is pressure-driven flow of soil gas through cracks in the floor. Both radon and thoron can also be released from building materials to the indoor atmosphere. In this work, we study the radon and thoron exhalation and emanation properties of an extended variety of common building materials manufactured in the Iberian Peninsula (Portugal and Spain) but exported and used in all countries of the world. Radon and thoron emission from samples collected in the closed chamber was measured by an active method that uses a continuous radon/thoron monitor. The correlations between exhalation rates of these gases and their parent nuclide exhalation (radium/thorium) concentrations were examined. Finally, indoor radon and thoron and the annual effective dose were calculated from radon/thoron concentrations in the closed chamber. Zircon is the material with the highest concentration values of 226Ra and 232Th and the exhalation and emanation rates. Also in the case of zircon and some granites, the annual effective dose was higher than the annual exposure limit for the general public of 1 mSv y-1, recommended by the European regulations.

Prognostic value of p16INK4a overexpression in penile cancer.

INTRODUCTION: Penile cancer is rare, accounting for less than 1% of all male cancers in industrialized countries. It is most common in areas of high prevalence of HPV, being a third of cases attributed to the carcinogenic effect of HPV. Tumour cells infected with HPV overexpress p16INK4a, as such p16INK4a has been used as a surrogate of HPV infections. OBJECTIVE: To evaluate the prognostic factor of p16INK4a overexpression in penile cancer. METHODS: Retrospective analysis of patients diagnosed with penile cancer, submitted to surgery in a Portuguese Oncological Institution in the last 20 years (n = 35). Histological review of surgical pieces and immunohistochemical identification of p16INK4a. Relation between p16INK4a and the following factors were studied: age, histological subtype, tumour dimensions, grade, TNM stage, perineural invasion, perivascular invasion, disease free survival (DFS) and cancer specific survival (CSS). RESULTS: p16INK4a was positive in 8 patients (22.9%). Identification of p16INK4a did not correlate with none of the histopathological factors. In this work we identified a better DFS and CSS in patients positive for p16INK4a (DFS at 36 months was 100.0% vs. 66.7%; CSS at 36 months was 100.0% vs. 70.4%), although without statistical significance (p > 0.05). In multivariate analysis of histopathological factors studied, only N staging correlated with DFS and CSS (p = 0.017 and p = 0.014, respectively). DISCUSSION: the percentage of cases positive for p16INK4a is smaller than the one found in literature, which can suggest a less relevant part of HPV infection in the oncogenesis of penile cancer in the studied population. Identification of p16INK4a did not relate with other clinicopathological factors. Tendency for a more favourable prognosis in patients with p16INK4a agrees with results found in literature. The most relevant factor for prognosis is nodal staging. CONCLUSIONS: penile cancer positive for p16INK4a shows a trend for better survival, although the most relevant factor is nodal staging.

Influence of sociodemographic factors on treatment's choice for localized prostate cancer in Portugal.

INTRODUCTION: Patients with localized prostate cancer (PCa) are active participants in the choice of treatment. OBJECTIVES: To access the effects of social and demographic factors in the choice of treatment in cases of localized PCa, in a Portuguese population. METHODS: Identification of all patients with the diagnosis of localized PCa in the last four years in an oncological centre. Evaluation of the effects of sociodemographic factors (age, profession, literacy, marital status, district and number of inhabitants of the place of residence) in the choice of treatment. RESULTS: 300 patients with localized PCa were evaluated: 17.3% (n = 52) opted for radical prostatectomy (RP); 39,3% had (n = 118) external radiotherapy; brachytherapy in 29.3% (n = 88) and other options (active surveillance, cryotherapy and hormonal therapy) in 14.1% (n = 42). In relation to surgical treatment (RP) the following results were obtained: a) > 70 years: 3.9% (n = 5); ≤ 70 years: 27.5% (n = 47), p < 0.001; b) primary sector: 10.3% (n = 3); secondary sector: 16.2% (n = 27); tertiary sector: 24.1% (n = 21); quaternary sector: 8.3% (n = 1), p = 0.296; c) marital status married: 17.9% (n = 47); single: 0% (n = 0); divorced: 25.0% (n = 5); widow: 0% (n = 0), p = 0.734; d) residency in a city: 14.1% (n = 13); city > 4000 habitants: 22.7% (n = 15); city ≤ 4000 habitants: 16.9% (n = 24), p = 0.701. Using multinomial regression with age (p = 0.001), district (p = 0.035), marital status (p = 0.027) and profession (0.179), this model explained 17.2%-28.4% of therapeutic choices (p < 0.001). CONCLUSIONS: The main socioeconomical factor that influence treatment choice was age. Unmarried patients over 70 years choose less radical prostatectomy. Other sociodemographic factors have minor influence in the choice of the treatment.

Primary mesenchymal chondrosarcoma of the kidney: A case report and review of literature.

Primary mesenchymal chondrosarcoma of the kidney is extremely rare, with only nine cases reported in the English literature. We report a new case of this disease. A 35-year-old man, presented with flank pain, episodic gross hematuria and a painless palpable mass in left abdominal quadrant. Computed tomography scan identified a left renal tumor with 20 cm, with no evidence of regional or metastatic spread disease. The patient underwent radical nephrectomy. The immunohistopathological diagnosis was mesenchymal chondrosarcoma of the kidney. At 18 months of follow-up, there was no evidence of recurrence or distant metastasis. Primary renal chondrosarcoma is so rare that its prognosis is unknown. Disease recurrence is unpredictable and when it is detected, the prognosis is poor. The radical nephrectomy with complete resection of the tumor with wide resection free margins is recommended, and the patients need long-term and close surveillance, with particular attention to local recurrence and uncommon sites of metastization.

(60)Co in cast steel matrix: A European interlaboratory comparison for the characterisation of new activity standards for calibration of gamma-ray spectrometers in metallurgy.

Two series of activity standards of (60)Co in cast steel matrix, developed for the calibration of gamma-ray spectrometry systems in the metallurgical sector, were characterised using a European interlaboratory comparison among twelve National Metrology Institutes and one international organisation. The first standard, consisting of 14 disc shaped samples, was cast from steel contaminated during production ("originally"), and the second, consisting of 15 similar discs, from artificially-contaminated ("spiked") steel. The reference activity concentrations of (60)Co in the cast steel standards were (1.077±0.019) Bqg(-1) on 1 January 2013 12h00 UT and (1.483±0.022) Bqg(-1) on 1 June 2013 12h00 UT, respectively.

Pollution by oestrogenic endocrine disruptors and ß-sitosterol in a south-western European river (Mira, Portugal).

The Mira River is a Portuguese water body widely known for its wilderness and is advertised as one of the less polluted European rivers. On this presumption, the levels of endocrine-disrupting compounds (EDCs) in Mira waters were never measured. However, because environmentalists have claimed that the Mira could be moderately polluted, a range of 17 EDCs were measured not only at the estuary but also along the river. The targeted EDCs included natural and pharmaceutical oestrogens (17ß-oestradiol, oestrone and 17α-ethynylestradiol), industrial/household pollutants (octylphenols, nonylphenols and their monoethoxylates and diethoxylates and bisphenol A), phytoestrogens (formononetin, biochanin A, daidzein, genistein) and the phytosterol sitosterol (SITO). For this propose, waters from six sampling sites were taken every 2 months, over a 1-year period (2011), and analysed by gas chromatography-mass spectrometry. Unexpectedly high levels of oestrogens and of industrial/household pollutants were measured at all sampling sites, including those located inside natural protected areas. Indeed, the annual average sum of EDCs was ≈57 ng/L for oestrogens and ≈1.3 µg/L for industrial/household chemicals. In contrast, the global average levels of phytoestrogens (≈140 ng/L) and of SITO (≈295 ng/L) were lower than those reported worldwide. The EDC concentrations were normalised for ethynylestradiol equivalents (EE2eq). In view of these, the oestrogenic load of the Mira River attained ≈47 ng/L EE2eq. In addition, phosphates were above legal limits at both spring and summer (>1 mg/L). Overall, data show EDCs at toxicant relevant levels in the Mira and stress the need to monitor rivers that are allegedly less polluted.

Pollution by endocrine disruptors in a southwest European temperate coastal lagoon (Ria de Aveiro, Portugal).

Ria de Aveiro is a Portuguese lagoon renowned for its ecological and economic importance. Nonetheless, in literature, few data exist about its organic pollution. Accordingly, this study chemically monitored for the first time a series of 17 endocrine disruptor compounds (EDCs). The target EDCs include natural (17ß-oestradiol, oestrone) and pharmaceutical (17α-ethynylestradiol) oestrogens, industrial/household xenoestrogenic pollutants (octylphenols, nonylphenols and their mono and diethoxylates and bisphenol A), phytoestrogens (formononetin, biochanin A, daidzein, genistein) and the phytosterol sitosterol (SITO). For the investigation of these EDCs, water samples were taken from eight sampling sites widely spread along the lagoon, at three different occasions in 2011, and analysed by gas chromatography-mass spectrometry. Results not only proved the ubiquitous distribution of all analysed EDCs but revealed that their amounts were extremely high at all sampling sites. The annual average concentrations were ≈ 46 ng/L for oestrogens, ≈ 3962 ng/L for industrial/household chemicals, ≈ 1740 ng/L for phytoestrogens and ≈ 908 ng/L for SITO. Normalising these values in ethynylestradiol equivalents (EE2eq), the oestrogenic load in this lagoon attained ≈ 50 ng/L EE2eq, which is a value well above that known to produce oestrogenic-induced disorders in aquatic fauna. Additionally, phosphate concentrations were also above the legal limits (>1 mg/L). Overall, data show EDCs at toxic relevant levels in the Ria de Aveiro and stress the need to enforce depollution measures in this habitat.

Plastic surgery in chest wall reconstruction: relevant aspects - case series / A cirurgia plástica na reconstrução da parede torácica: aspectos relevantes - série de casos

Objective: to discuss the participation of Plastic Surgery in the reconstruction of the chest wall, highlighting relevant aspects of interdisciplinaryness. Methods: we analyzed charts from 20 patients who underwent extensive resection of the thoracic integument, between 2000 and 2014, recording the indication of resection, the extent and depth of the raw areas, types of reconstructions performed and complications. Results: among the 20 patients, averaging 55 years old, five were males and 15 females. They resections were: one squamous cell carcinoma, two basal cell carcinomas, five chondrosarcomas and 12 breast tumors. The extent of the bloody areas ranged from 4x9 cm to 25x40 cm. In 12 patients the resection included the muscular plane. In the remaining eight, the tumor removal achieved a total wall thickness. For reconstruction we used: one muscular flap associated with skin grafting, nine flaps and ten regional fasciocutaneous flaps. Two patients undergoing reconstruction with fasciocutaneous flaps had partially suffering of the flap, solved with employment of a myocutaneous flap. The other patients displayed no complications with the techniques used, requiring only one surgery. Conclusion: the proper assessment of local tissues and flaps available for reconstruction, in addition to the successful integration of Plastic Surgery with the specialties involved in the treatment, enable extensive resections of the chest wall and reconstructions that provide patient recovery.

Objetivo: discorrer sobre a participação da Cirurgia Plástica na reconstrução da parede torácica, ressaltando os aspectos relevantes das associações interdisciplinares. Métodos: foram analisados prontuários de 20 pacientes submetidos a extensas ressecções do tegumento torácico, no período entre 2000 e 2014, quanto à indicação das ressecções, à extensão e à profundidade das áreas cruentas, aos tipos de reconstruções realizadas e às complicações. Resultados: entre os 20 pacientes, com média de 55 anos de idade, cinco eram do sexo masculino e 15 do feminino. Foram ressecados: um carcinoma espinocelular, dois carcinomas basocelulares, cinco condrossarcomas e 12 tumores de mama. A extensão das áreas cruentas variou de 4x9 cm até 25x40 cm. Em 12 pacientes as ressecções abrangeram o plano muscular. Nos oito restantes, a retirada do tumor atingiu a espessura total da parede. Para reconstrução foram utilizados: um retalho muscular associado à enxertia de pele, nove retalhos miocutâneos e dez retalhos fasciocutâneos da região. Em dois pacientes submetidos à reconstrução com retalhos fasciocutâneos houve sofrimento parcial do retalho, resolvido com o emprego de retalho miocutâneo. Nos outros pacientes não houve intercorrências com as técnicas empregadas, sendo necessária somente uma cirurgia. Conclusão: a adequada avaliação dos tecidos locais e dos retalhos disponíveis para a reconstrução, além da boa integração da Cirurgia Plástica com as especialidades envolvidas no tratamento, possibilitam extensas ressecções da parede torácica e reconstruções que propiciam a recuperação do paciente.

Plastic surgery in chest wall reconstruction: relevant aspects - case series.

OBJECTIVE: to discuss the participation of Plastic Surgery in the reconstruction of the chest wall, highlighting relevant aspects of interdisciplinaryness. METHODS: we analyzed charts from 20 patients who underwent extensive resection of the thoracic integument, between 2000 and 2014, recording the indication of resection, the extent and depth of the raw areas, types of reconstructions performed and complications. RESULTS: among the 20 patients, averaging 55 years old, five were males and 15 females. They resections were: one squamous cell carcinoma, two basal cell carcinomas, five chondrosarcomas and 12 breast tumors. The extent of the bloody areas ranged from 4x9 cm to 25x40 cm. In 12 patients the resection included the muscular plane. In the remaining eight, the tumor removal achieved a total wall thickness. For reconstruction we used: one muscular flap associated with skin grafting, nine flaps and ten regional fasciocutaneous flaps. Two patients undergoing reconstruction with fasciocutaneous flaps had partially suffering of the flap, solved with employment of a myocutaneous flap. The other patients displayed no complications with the techniques used, requiring only one surgery. CONCLUSION: the proper assessment of local tissues and flaps available for reconstruction, in addition to the successful integration of Plastic Surgery with the specialties involved in the treatment, enable extensive resections of the chest wall and reconstructions that provide patient recovery.

Spatial and seasonal distribution of 17 endocrine disruptor compounds in an urban estuary (Mondego River, Portugal): evaluation of the estrogenic load of the area.

The Mondego River estuary demonstrates signs of pollution, but the levels of endocrine disrupting compounds (EDCs), such as the natural (17ß-estradiol and estrone) and pharmaceutical (17α-ethynylestradiol) estrogens, xenoestrogenic industrial pollutants (4-octylphenol, 4-nonylphenol, and their mono- and diethoxylates and bisphenol A), phytoestrogens (formononetin, biochanin A, daidzein, and genistein), and sitosterol were either poorly or never measured in this area. Thus, to conclude about the influx of EDCs in this estuary, water samples were taken every 2 months, during 1 year (2010) in low tide, at eight sites distributed along the estuary. Water samples (1 L) were preconcentrated in the Oasis HLB cartridges and cleaned in silica cartridges before their analysis by GC-MS. In summer, potentially hazardous amounts of estrogens (≈ 26 ng L(-1)), alkylphenols (≈ 11.5 µg L(-1)), alkylphenolethoxylates (≈ 13 µg L(-1)), and phytoestrogens (≈ 5.6 µg L(-1)) were measured. These data suggest that changes in the hydrodynamics of the estuary coupled with the increase of water temperatures interfere with the amount of EDCs in the water. Complementary physicochemical parameters also point to high levels of anthropogenic pollution in this area. Globally, the estrogenic load, expressed in ethynylestradiol equivalents, attained 71.8 ng L(-1) demonstrating that, all together, the measured EDCs pose important health risks for both biota and humans.

Acquired male urethral diverticulum: a complication following artificial urethral sphincter implantation.

The authors report a case of a 72-year-old patient who underwent radical prostatectomy in 2003 due to prostate cancer. During follow-up, he presented with permanent and severe urinary stress incontinence for which he underwent an artificial urinary sphincter implantation in 2009. After infection of the device, followed by the development of a urinary fistula, the artificial urinary sphincter was removed. He presented no new signs or symptoms for 2 years, during which he remained completely incontinent. In April 2012, he developed a painless scrotal swelling close to the median raphe. On manual compression, it showed urinary leakage and disappeared completely, only to reappear several hours later. Auxiliary examinations revealed a bulbar urethral diverticulum which was subsequently excised. A urethroplasty was performed during the same procedure. The patient presented with no further complications. Although still suffering from complete urinary incontinence, he refused any kind of surgery for the time being.

[Mitral valve obstruction by tumor embolus as a cause of irreversible cardiac arrest during right pneumonectomy]. / Obstrução de valva mitral por embolização tumoral per-operatória (pneumectomia direita) com parada cardíaca irreversível.

A 26-year-old patient with a voluminous primary pulmonary hemangiopericytoma in the right lung, diagnosed through previous surgical biopsy, presented irreversible cardiac arrest during the hilar dissection portion of a right pneumonectomy. The patient did not respond to resuscitation efforts. Autopsy showed total obstruction of the mitral valve by a tumor embolism. In cases of large lung masses with hilar involvement, as in the case presented, we recommend preoperative evaluation using transesophageal echocardiography, magnetic resonance imaging or angiotomography. If injury to the pulmonary vessels or atrial cavities is detected, surgery with extracorporeal circulation should be arranged in order to allow resection of the intravascular or cardiac mass, together with pulmonary resection. We recommend that care be taken in order to recognize and treat this problem in patients not receiving a preoperative diagnosis.

Obstrução de valva mitral por embolização tumoral per-operatória (pneumectomia direita) com parada cardíaca irreversível / Mitral valve obstruction by tumor embolus as a cause of irreversible cardiac arrest during right pneumonectomy

Um paciente de 26 anos, portador de volumoso hemangiopericitoma primário de pulmão direito, diagnosticado por biópsia cirúrgica prévia, apresentou parada cardíaca irreversível durante dissecção hilar de pneumectomia direita. O paciente não respondeu às manobras de ressuscitação. A necropsia mostrou obstrução total de valva mitral por êmbolo tumoral. Os autores recomendam, em casos de grandes massas pulmonares com envolvimento hilar, como no caso aqui apresentado, a avaliação pré-operatória com ecocardiografia transesofágica, ressonância magnética nuclear ou angiotomografia. Se for detectada lesão em vasos pulmonares ou cavidades atriais, deve-se programar a cirurgia com circulação extracorpórea, para permitir ressecção da massa intra-vascular ou cardíaca, combinada com a ressecção pulmonar. Os autores recomendam cuidados para reconhecer e tratar este problema, se o diagnóstico pré-operatório não for feito.

A 26-year-old patient with a voluminous primary pulmonary hemangiopericytoma in the right lung, diagnosed through previous surgical biopsy, presented irreversible cardiac arrest during the hilar dissection portion of a right pneumonectomy. The patient did not respond to resuscitation efforts. Autopsy showed total obstruction of the mitral valve by a tumor embolism. In cases of large lung masses with hilar involvement, as in the case presented, we recommend preoperative evaluation using transesophageal echocardiography, magnetic resonance imaging or angiotomography. If injury to the pulmonary vessels or atrial cavities is detected, surgery with extracorporeal circulation should be arranged in order to allow resection of the intravascular or cardiac mass, together with pulmonary resection. We recommend that care be taken in order to recognize and treat this problem in patients not receiving a preoperative diagnosis.

Estrogens and aspects of prostate disease.

Estrogens have long been associated with the processes involved in prostate carcinogenesis, particularly in cancer suppression. However, the synergistic influence of low concentrations of estrogens, together with androgens, in promoting aberrant growth of the gland has also been recognized. As new insights into the complex molecular events implicated in growth regulation of the prostate are revealed, the role of the estrogens has become clearer. The present review considers this role in relation to the pathogenesis of prostate cancer and the potential cancer-repressive influence of the dietary estrogens.

Fogo em via aérea durante traqueostomia cervical eletiva / Airway fire during elective cervical tracheostomy

Um caso de fogo em via aérea durante traqueostomia cervical eletiva é apresentado. São discutidos os fatores desencadeantes e as medidas para evitar que esta temida complicação ocorra.

Efficacy and safety of long-term treatment with the dual 5 alpha-reductase inhibitor dutasteride in men with symptomatic benign prostatic hyperplasia.

OBJECTIVES: Dutasteride, a dual inhibitor of Type 1 and Type 2 5 alpha-reductase, has been shown to improve disease measures in patients with symptomatic benign prostatic hyperplasia (BPH) in three randomised, placebo-controlled, large-scale, 2-year Phase III clinical studies. This paper reports the pooled results of a 2-year open-label extension of the three randomised studies assessing the long-term efficacy and safety of dutasteride. METHODS: Patients randomised to dutasteride or placebo in the double-blind portion of the Phase III studies were eligible for a 2-year open-label extension, where all patients received dutasteride 0.5mg daily (dutasteride/dutasteride [D/D] group and placebo/dutasteride [P/D group]). RESULTS: Significant improvements in AUA-SI score and Q(max) were observed from Month 24 to 48 in both study groups. At Month 48, patients in the D/D group had significantly greater improvements in AUA-SI score and Q(max), and significantly greater reductions in prostate volume, than those in the P/D group. Acute urinary retention and BPH-related surgery occurred in a small percentage of patients during the open-label phase. No new safety issues were noted with long-term therapy. Onset of new drug-related adverse events were reported most frequently at the start of therapy and declined over time in patients receiving dutasteride. CONCLUSIONS: Long-term treatment with dutasteride results in continuing improvements in urinary symptoms and flow rate, and further reductions in TPV, in men with symptomatic BPH. The reduction in risk of AUR and BPH-related surgery, seen in the double-blind phase, was durable over 4-year treatment. Dutasteride was also well tolerated in long-term use.