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UNLABELLED: What's known on the subject? and What does the study add? The experience with HIFU as a minimally invasive treatment for localized prostate cancer is relatively new and most reports are from European centres. Our study is unique in five regards: 1. Data was collected prospectively. 2. All patients were treated with contemporary technology. 3. Outcomes are reported after a single HIFU session using two definitions of biochemical failure that have the ability to predict longer-term clinical failure after primary ablative therapies for prostate cancer (Stuttgart definition for HIFU and Horwitz definition for radiation). 4. All patients were treated in a single centre. 5. No patients underwent peri-HIFU TURP. The present study represents the largest North American prospective cohort of primary HIFU for prostate cancer with mid-term oncological outcome data. OBJECTIVE: To assess 4-year biochemical failure (BCF) rates in patients after high-intensity focused ultrasonography (HIFU) treatment using the Horwitz and Stuttgart definitions. PATIENTS AND METHODS: A total of 447 consecutive patients were treated with a single session of HIFU between May 2005 and December 2010. Follow-up included prostate-specific antigen (PSA) measurement every 3 months during the first year and every 6 months thereafter. Patients who had previously received radiation, androgen deprivation or HIFU therapy, and patients with <2 consecutive PSA measurements were excluded. BCF was reported using the Stuttgart (PSA nadir + 1.2 ng/mL rising) and the Horwitz (two consecutive increases of at least 0.5 ng/mL) definitions. RESULTS: In all, 402 patients met the inclusion criteria and the median (range) follow-up was 24 (6-48) months. Of these patients, 183 (45.5%) had low and 219 (54.5%) had intermediate D'Amico's risk stratification disease. Mean and median absolute PSA nadir levels were 0.36 ± 0.69 and 0.1 ng/mL (Q(1):0, Q(3):0.37), respectively and these were achieved in median time of 3 months. Overall 4-year mean (range) BCF-free rates were 68 (61-75)% and 72 (68-77)% according to the Stuttgart and Horwitz definitions at 4 years, respectively. Mean (range) BCF-free rates were significantly higher for a PSA nadir ≤0.5 ng/mL and prostate volume ≤30 mL for both definitions at 4-year follow-up [Stuttgart: 79 (72-86)% vs. 25 (13-38)%; Horwitz: 82 (77-87)% vs. 33 (21-44)%] and [Stuttgart: 72 (64-79)% vs. 56 (42-69)%; Horwitz: 75 (69-80)% vs. 63 (53-74)%], respectively. Pre-treatment PSA and PSA nadir of >0.5 ng/mL were the predictors of BCF using both definitions. CONCLUSIONS: Primary HIFU appears to result in promising 4-year BCF-free rates in individuals with low- and intermediate-risk prostate cancer who achieve PSA nadir <0.5 ng/mL. A prostate volume <30 mL is associated with PSA nadir levels of <0.5 ng/mL suggesting a potential role for pretreatment volume reduction (medically or surgically) in larger prostates.
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Neoplasias da Próstata/terapia , Ultrassom Focalizado Transretal de Alta Intensidade , Intervalo Livre de Doença , Humanos , Masculino , Gradação de Tumores , Neoplasias da Próstata/patologiaRESUMO
BACKGROUND: Tissue microarray (TMA) allows for simultaneous rapid expression analysis of multiple molecular targets in many tissue specimens. TMA's are specifically in demand for the screening for diagnostic and prognostic markers in prostate cancer (PC). Consequently, TMAs from prostate needle biopsy (PNB) material taken at diagnosis before any treatment commenced are in demand. However, since PNB contain only limited amount of tumor arranged within a very thin tissue core, TMA construction from PNB is problematic. METHODS: Archival PNB from 30 PC patients with variable Gleason scores (6-10) and % of cores involvement (30-90%) were used. Following selection of representative cores, the paraffin blocks were melted. Each core was sectioned into equal parts of 3-4 mm in length. For each case, a group of fragments was then re-embedded in a vertical orientation. Using Manual TMA Apparatus, 2 mm cores from each of the vertically rearranged fragments were harvested. Sections (4 µm) were stained with H&E and with high-molecular weight cytokeratin (HMWCK), PIN-cocktail (p63 + p504S), and PSA immunohistochemical stains. RESULTS: A TMA from PNB with a capacity of 80 serial 4 µm sections was constructed. In all cases, identical tumor and neighboring tissue morphology (atrophic changes and high-grade prostatic intra-epithelial neoplasia) with no loss of tissue was evident. CONCLUSIONS: The vertical clustering re-arrangement (VCR) technique is suitable for large scale construction of TMA blocks from PNB maintaining the morphological and immunohistochemical characteristics of the original samples. This method is promising both in terms of archival tissue preservation and biomarkers research.
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Biópsia por Agulha/métodos , Próstata/patologia , Neoplasias da Próstata/patologia , Análise Serial de Tecidos/métodos , Humanos , Imuno-Histoquímica , MasculinoRESUMO
BACKGROUND: The goal of this study was to determine the oncologic outcomes in localized resectable soft-tissue sarcoma after pre- versus postoperative radiation. METHODS: Literature searches through MEDLINE, EMBASE, CancerLit, and the Cochrane Database were performed with the following search terms: sarcoma, radiation, preoperative, and postoperative. Two reviewers independently assessed all eligible publications with the Detsky Quality Scale for Randomized Trials and the Newcastle-Ottawa Quality Assessment Scale for case-control studies. The primary outcome measure was the pooled odds ratio and 95% confidence intervals (95% CI) for the risk of local recurrence calculated through the fixed- and random-effects methods. Time-dependent survival data were calculated as an average across all studies. RESULTS: Five eligible studies were identified including a total of 1,098 patients. The P value for heterogeneity was 0.259, and the variability (I (2)) in results across studies due to true differences in treatment effect was 25%. The risk for local recurrence was lower in the preoperative group with an odds ratio of 0.61 (95% CI 0.42-0.89) by means of the fixed-effects method, and an odds ratio of 0.67 (95% CI 0.39-1.15) by means of the random-effects method. Average survival was 76% (range 62-88%) in the preoperative group and 67% (range 41-83%) in the post-operative group. CONCLUSIONS: The delay in surgical resection necessary to complete preoperative radiation does not seem to increase the risk of lethal metastatic spread. The risk of local recurrence may be lower after preoperative radiation. These findings must be interpreted with caution because of the heterogeneity and bias in the available studies.
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Sarcoma/radioterapia , Humanos , Período Pós-Operatório , Resultado do TratamentoRESUMO
We present a case of a 3-year-old girl with a positive family history of neurofibromatosis type-1 (NF1) presented with best corrected visual acuity of 20/40 in the right eye and <20/400 in the left eye. External ocular examination revealed left eye proptosis of 3 mm, grade II left relative afferent pupillary defect and full range of ocular motility with no strabismus. Slit lamp examination revealed iris lisch nodules bilaterally. Dilated fundus examination of the right eye was normal. Left eye disclosed a large mass extending from the optic nerve head, with associated subretinal fluid. There was neovascularization at the optic disc as well as a superior retinal hemorrhage. Computed tomography of brain/orbits showed an enlarged left optic nerve with a large mass at the optic nerve head, with no evidence of calcification. In addition, a large left optic pathway glioma (OPG), multiple hamartomas within the brain and a smaller low-grade right OPG was also reported. The remarkable feature of our case is the rare intraocular optic nerve involvement of the OPG. Early and regular ophthalmological assessment of all NF1 suspect/confirmed cases is of paramount importance in order to detect OPG early, resulting in timely intervention and salvage of vision.
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Neurofibromatose 1/patologia , Glioma do Nervo Óptico/patologia , Neoplasias do Nervo Óptico/patologia , Antineoplásicos Fitogênicos/uso terapêutico , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Neurofibromatose 1/tratamento farmacológico , Neurofibromatose 1/genética , Neurofibromina 1/genética , Disco Óptico/patologia , Glioma do Nervo Óptico/tratamento farmacológico , Glioma do Nervo Óptico/genética , Neoplasias do Nervo Óptico/tratamento farmacológico , Neoplasias do Nervo Óptico/genética , Mutação Puntual , Líquido Sub-Retiniano , Vimblastina/uso terapêutico , Acuidade Visual/fisiologiaRESUMO
PURPOSE: Many women undergo a bilateral reduction mammoplasty after lumpectomy and radiation for breast cancer due to breast hypertrophy. The outcomes of these patients, focusing on complications and the need for additional surgery, are reviewed. METHODS: A matched case-control study with patients serving as their own control (treated breast cancer breasts were 'cases', healthy breasts were 'controls') was performed. Patients were identified through hospital records between 1980 and 2007. Patients treated by lumpectomy and radiation with subsequent bilateral reduction surgery were included. Data regarding demographics, medical history, and peri- and postoperative complications were collected. Measured outcomes included hematoma or seroma, delayed wound healing, infection, nipple-areolar complex problems, scarring, asymmetry and the need for further surgery. Continuous variables are reported as mean ± SD, and categorical variables are reported as proportions. RESULTS: Of the nine patients included in the study, delayed wound healing occurred in 22% of cases. Wound infections occurred in 66.7% of cases, with 22.2% experiencing a second wound infection. One patient experienced partial nipple-areolar complex loss on the radiated breast. There was abnormal scarring in 33.3% of radiated breasts. Postoperative asymmetry occurred in 77.8% of patients. Additional surgery was performed on three patients (33.3%). CONCLUSIONS: Results of the present study suggest that women with a history of breast cancer treated by lumpectomy and radiation experience higher occurrence of postoperative complications on the radiated breast following bilateral breast reduction. Patients must be informed of these potential risks and require careful postoperative follow-up. An appropriately powered, prospective, multicentred study is required to draw definitive conclusions.
OBJECTIF: De nombreuses femmes subissent une réduction mammaire bilatérale après une lumpectomie et des radiations pour traiter un cancer du sein causé par une hypertrophie mammaire. L'issue de ces patientes, axée sur les complications et la nécessité de procéder à des opérations supplémentaires, est analysée. MÉTHODOLOGIE: Les chercheurs ont mené une étude cas-témoins appariée auprès de patientes étant elles-mêmes leur propre sujet témoin (le sein traité contre le cancer était le « cas ¼ et le sein non atteint, le « témoin ¼). Ils ont repéré les patientes au moyen des dossiers hospitaliers de 1980 à 2007. Ils ont inclus les patientes traitées par lumpectomie et radiation qui ont subi une réduction mammaire bilatérale par la suite. Ils ont assemblé les données relatives à la démographie, aux antécédents médicaux et aux complications périopératoires et postopératoires. Les issues mesurées étaient les hématomes ou les séromes, le retard de guérison de la plaie, l'infection, les problèmes du complexe mamelon-aréole, la cicatrisation, l'asymétrie et la nécessité de procéder à d'autres opérations. Les variables continues sont déclarées sous forme de moyenne ± ÉT, et les variables catégoriques, sous forme de proportions. RÉSULTATS: Chez les neuf patientes incluses dans l'étude, les chercheurs ont remarqué un retard de guérison de la plaie dans 22 % des cas et des infections de la plaie dans 66,7 % des cas, dont 22,2 % de deuxième infection. Une patiente a présenté une perte partielle du complexe mamelon-aréole sur le sein ayant subi des radiations. On observait des cicatrices anormales sur 33,3 % des seins traités, et une asymétrie postopératoire chez 77,8 % des patientes. Trois patientes ont subi des opérations supplémentaires (33,3%). CONCLUSIONS: D'après les résultats de la présente étude, les femmes ayant des antécédents de cancer du sein traitées par lumpectomie et radiation présentent une plus forte occurrence de complications postopératoires après une réduction mammaire bilatérale. Les patientes doivent être informées de ces risques potentiels et ont besoin d'un suivi postopératoire attentif. Une étude prospective multicentrique comportant un nombre suffisant de sujets s'impose pour tirer des conclusions définitives.
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OBJECTIVE: To survey the current inclusion criteria used for retinopathy of prematurity (ROP) screening across tertiary level 3 neonatal intensive care units (NICUs) in Canada. PARTICIPANTS: Clinical directors from 29 level 3 NICUs in Canada. METHODS: Survey of all 29 level 3 NICUs in Canada in September 2010. The survey inquired about the current ROP screening criteria in use in each centre including which neonates are enrolled in the screening program and the timing of when screening begins. The survey was sent via email to the clinical directors at each site. Nonrespondents were contacted by telephone. RESULTS: In total, 23 centres replied, representing a 79% response rate with the survey. Seven different ROP screening inclusion criteria were found to be in use, although one of the centres did not have a clear inclusion protocol. The variation between centres was significant, with some using a combination of birth weight and gestational age and others using birth weight or gestational age alone as their criterion. There was also variation in the timing of initial eye examinations, with 8 different criteria currently in use. Discrepancies were also found among treatment patterns at the centres. CONCLUSIONS: Despite the publication of updated Canadian guidelines in 2000, there continues to be significant variation in the actual inclusion criteria being used across the country. Therefore, a need exists for comprehensive, evidence-based Canadian guidelines to optimize the screening inclusion criteria for ROP.
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Fidelidade a Diretrizes/normas , Triagem Neonatal , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Retinopatia da Prematuridade/diagnóstico , Peso ao Nascer , Canadá , Idade Gestacional , Pesquisas sobre Atenção à Saúde , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Inquéritos e Questionários , Fatores de TempoRESUMO
Persistent cloaca is a rare urogenital anomaly that can pose significant challenges for adequate diagnosis and management. We describe the case of an infant girl with a cloacal malformation, having a single perineal orifice and an accessory phallic urethra, who presented with ambiguous genitalia at birth. The distal part of the accessory phallic urethra was used to create a mucosa-lined vestibule as a part of the total urogenital sinus mobilization. This technical maneuver allowed a more natural looking, and possibly functioning, vaginal introitus, improving the final cosmetic result.
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Cloaca/anormalidades , Transtornos do Desenvolvimento Sexual/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Uretra/anormalidades , Transtornos do Desenvolvimento Sexual/patologia , Feminino , Genitália Feminina/cirurgia , Humanos , Recém-Nascido , Procedimentos Cirúrgicos UrogenitaisRESUMO
Central to the malignant behaviour that endows cancer cells with growth advantage is their unique metabolism. Cancer cells can process nutrient molecules differently from normal cells and use it to overcome stress imposed on them by various therapies. This metabolic conversion is controlled by specific genetic mutations that are associated with activation of oncogenes and loss of tumour suppressor proteins. Understanding these processes is important as it can lead to the discovery of biomarkers that can predict the aggressiveness of the disease and its response to therapy, and even more importantly, to the development of novel therapeutics. A classic tumour in this respect is clear-cell renal cell carcinoma (RCC). In this review, we will begin with a brief summary of normal cellular bioenergetic pathways, which will be followed by a description of the characteristic metabolism of glucose and lipids in clear-cell RCC cells and its clinical implications. Data relating to the potential effect of dietary nutrients on RCC will also be reviewed along with potential therapies targeted at interrupting specific metabolic pathways in clear-cell RCC.
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BACKGROUND: Prostatic oxidative stress (OS) is androgen-regulated and a key event in the development of prostate cancer (PC). Thus, reducing prostatic OS is an attractive target for PC prevention strategies. We sought to determine if the individual's prostatic OS status can be determined by examining the OS in surrogate androgen regulated tissues from the same host. METHODOLOGY/PRINCIPAL FINDINGS: Adult male rats were divided equally into three groups: (A-) underwent bilateral orchiectomy, (A+) received continuous testosterone supplementation or (C) were eugonadal. Serum testosterone, 8-hydroxy-2-deoxyguanosine (8-OHdG) and anti-oxidative capacity (AOC) were determined after 72 hrs and the prostate, salivary glands and the hair follicles' Dermal Papillary Cells (DPC) from each animal were harvested, embedded into tissue microarray and examined for the expression of 8-OHdG by immuno-staining. Multi-variate regression was used to analyze inter-individual differences in OS staining within each androgen group and if there was a correlation between serum testosterone, 8-OHdG or AOC and Prostatic OS in tissues of same host. At the group level, 8-OHdG staining intensity directly correlated with serum testosterone levels in all three target tissues (p>0.01, Mann-Whitney Test). Although different levels of prostatic OS were noted between rats with similar serum testosterone levels and similar systemic OS measurements (p<0.01), there were no intra-individual differences between the OS status of the prostate and DPC (p<0.05). CONCLUSIONS/SIGNIFICANCE: The level of prostatic OS is correlated with the OS of hair follicles and salivary glands, but not systemic OS. Moreover, systemic AOC negatively correlates with both prostatic and hair follicle OS. This suggests that hair follicle and salivary gland OS can serve as surrogate markers for the efficiency of OS reduction. This has tremendous potential for the rational evaluation of patient response to prevention strategies.