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PURPOSE: To investigate the risk factors related to decrease in vessel density (VD) observed in primary open-angle glaucoma (POAG), due to acute increase in intraocular pressure (IOP) by an ophthalmodynamometer (OPD). METHODS: This cross-sectional study involved 42 eyes of participants (22 Controls and 20 POAG patients) that underwent optical coherence tomography angiography (OCT-A) to assess VD in the peripapillary region in three examination sets: primary gaze position (1), 25-degree adduction (2) and 25-degree adduction with OPD compression (3). Individual relationships between IOP levels and changes in the superficial complex VD were evaluated after image processing and exclusion of large retinal vessels. Multivariable regression analysis was used to verify factors associated with differences in VD induced by IOP elevation. RESULTS: A significant increase in IOP was induced by OPD compression during adduction (mean ± SD, Control: + 13.8 ± 2.8; POAG: + 13.4 ± 2.1 mmHg). Only during IOP elevation (set 3), a significant VD decrease was observed both in POAG eyes (p = 0.008) and controls (p = 0.022). Baseline IOP (p = 0.022), maximum IOP (p = 0.003), and scleral rigidity (p = 0.029) were significantly associated with VD decreases in eyes with POAG. No changes were observed in VD during adduction gaze exclusively. CONCLUSION: Acute IOP elevation induced with OPD, but not adduction gaze, decreased peripapillary VD measured with OCT-A imaging. IOP levels and scleral rigidity significantly affected VD reduction in POAG patients. Thus, high scleral rigidity may decrease the ability of the globe to dampen the well-known effects of IOP fluctuation on glaucoma onset and progression. KEY MESSAGES: What is known Decrease vascular density in the peripapillary retina was associated with POAG, but factors related to the vascular response to elevated IOP are unexplored. What is new OCT-A quantification shows decreases in vascular density of the superficial layers of the peripapillary retina during an acute elevation in IOP. High IOP levels and scleral rigidity significantly affected vascular density reduction in POAG patients.
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BACKGROUND: The literature supporting high-dose rate brachytherapy (HDR) in the treatment of cervical carcinoma derives primarily from retrospective series. However, controversy still persists regarding the efficacy and safety of HDR brachytherapy compared to low-dose rate (LDR) brachytherapy, in particular, due to inadequate tumor coverage for stage III patients. Whether LDR or HDR brachytherapy produces better results for these patients in terms of survival rate, local control rate and the treatment complications remain controversial. METHODS: A meta-analysis of RCT was performed comparing LDR to HDR brachytherapy for cervix cancer treated for radiotherapy alone. The MEDLINE, EMBASE, CANCERLIT and Cochrane Library databases, as well as abstracts published in the annual proceedings were systematically searched. We assessed methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. We used "recommend" for strong recommendations, and "suggest" for weak recommendations. RESULTS: Pooled results from five randomized trials (2,065 patients) of HDR brachytherapy in cervix cancer showed no significant increase of mortality (p = 0.52), local recurrence (p = 0.68), or late complications (rectal; p = 0.7, bladder; p = 0.95 or small intestine; p = 0.06) rates as compared to LDR brachytherapy. In the subgroup analysis no difference was observed for overall mortality and local recurrence in patients with clinical stages I, II and III. The quality of evidence was low for mortality and local recurrence in patients with clinical stage I, and moderate for other clinical stages. CONCLUSION: Our meta-analysis shows that there are no differences between HDR and LDR for overall survival, local recurrence and late complications for clinical stages I, II and III. By means of the GRADE system, we recommend the use of HDR for all clinical stages of cervix cancer.
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Braquiterapia , Neoplasias do Colo do Útero/radioterapia , Ensaios Clínicos como Assunto , Relação Dose-Resposta à Radiação , Feminino , Humanos , Estadiamento de Neoplasias , Recidiva , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologiaRESUMO
PURPOSE: The aim of this study was to evaluate the results of keloidectomy and strontium 90 brachytherapy in the prevention of keloid recurrence following excision and to identify outcome and the prognostic factors that predict keloid recurrence after irradiation. METHODS AND MATERIALS: Data of 612 patients with 892 keloids treated between 1992 and 2006 were evaluated retrospectively. Brachytherapy was performed using a Sr-90Y surface applicator. Total dose was 20 Gy in 10 fractions. RESULTS: With a median follow-up of 61 months, the overall recurrence-free response rate for all keloids was 87.6%. Multivariate analysis revealed the following prognostic factors for recurrence: keloid size > 5 cm (p < 0.0001), burn scars as the keloid etiology (p < 0.0001), and previous treatment (p < 0.0001). Outcome was not found to be significantly related to the interval between surgery and radiotherapy, sex, or age. Pruritus and skin reddening were the most common symptoms of keloids, but all signs and symptoms abated with time after treatment. Cosmetic results from the keloid treatment were considered good or excellent in 70.6% of the patients. CONCLUSION: Our study findings show that excision plus Sr-90 brachytherapy is effective in the eradication of keloids. Sr-90 radiotherapy (20 Gy in 10 fractions) achieved a similar local control rate, as have higher doses per fraction in other series. It also resulted in a good cosmetic rate and relief of symptoms. Our data further suggest that the initiation of postoperative irradiation within hours of surgical excision is not important to therapeutic outcome.
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Braquiterapia/métodos , Queloide/prevenção & controle , Radioisótopos de Estrôncio/uso terapêutico , Adolescente , Adulto , Feminino , Humanos , Queloide/etiologia , Queloide/patologia , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Recidiva , Análise de Regressão , Adulto JovemRESUMO
BACKGROUND: Breast cancer is the most common cancer in women in the U.S. and Western Europe. Amplification of the her-2/neu gene occurs in approximately 25% of invasive ductal carcinomas of the breast. The first HER-2/neu-targeted approach to reach the clinic was trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER-2/neu protein. Trastuzumab therapy prolongs the survival of patients with metastático HER-2/neu-overexpressing breast cancer when combined with chemotherapy and has recently been demonstrated to lead to dramatic improvements in disease-free survival when used in the adjuvant therapy setting in combination with or following chemotherapy. Here, we performed a meta-analysis of completed clinical trials of adjuvant trastuzumab in the adjuvant setting. Survival, recurrence, brain metastases, cardiotoxicity and directions for future research are discussed. METHODS: A meta-analysis of randomized controlled trials (RCT) was performed comparing adjuvant trastuzumab treatment for HER2-positive early breast cancer (EBC) to observation. The MEDLINE, EMBASE, CANCERLIT and Cochrane Library databases, and abstracts published in the annual proceedings were systematically searched for evidence. Relevant reports were reviewed by two reviewers independently and the references from these reports were searched for additional trials, using guidelines set by QUOROM statement criteria. RESULTS: Pooled results from that five randomized trials of adjuvant Trastuzumab showed a significant reduction of mortality (p < 0.00001), recurrence (p < 0.00001), metastases rates (p < 0.00001) and second tumors other than breast cancer (p = 0.007) as compared to no adjuvant Trastuzumab patients. There were more grade III or IV cardiac toxicity after trastuzumab (203/4555 = 4.5%) versus no trastuzumab (86/4562 = 1.8%). The likelihood of cardiac toxicity was 2.45-fold higher (95% CI 1.89 - 3.16) in trastuzumab arms, however that result was associated with heterogeneity. The likelihood of brain metastases was 1.82-fold higher (95% CI 1.16 - 2.85) in patients who received trastuzumab. CONCLUSION: The results from this meta-analysis are sufficiently compelling to consider 1 year of adjuvant trastuzumab treatment for women with HER-2-positive EBC based on the risk: benefit ratio demonstrated in these studies. Adequate assessment of HER-2/neu status is critical, and careful cardiac monitoring is warranted because of cardiac toxicity. Clinical trials should be designed to answer unsolved questions.
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Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Anticorpos Monoclonais Humanizados , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/secundário , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Causalidade , Quimioterapia Adjuvante , Comorbidade , Feminino , Amplificação de Genes/efeitos dos fármacos , Saúde Global , Cardiopatias/epidemiologia , Humanos , Incidência , Razão de Chances , Receptor ErbB-2/efeitos dos fármacos , Recidiva , Análise de Sobrevida , Trastuzumab , Resultado do TratamentoRESUMO
BACKGROUND: To investigate whether Radiation therapy (RT) should follow breast conserving surgery in women with ductal carcinoma in situ from breast cancer (DCIS) with objective of decreased mortality, invasive or non invasive recurrence, distant metastases and contralateral breast cancer rates. We have done a meta-analysis of these results to give a more balanced view of the total evidence and to increase statistical precision. METHODS: A meta-analysis of randomized controlled trials (RCT) was performed comparing RT treatment for DCIS of breast cancer to observation. The MEDLINE, EMBASE, CANCERLIT, Cochrane Library databases, Trial registers, bibliographic databases, and recent issues of relevant journals were searched. Relevant reports were reviewed by two reviewers independently and the references from these reports were searched for additional trials, using guidelines set by QUOROM statement criteria. RESULTS: The reviewers identified four large RCTs, yielding 3665 patients. Pooled results from this four randomized trials of adjuvant radiotherapy showed a significant reduction of invasive and DCIS ipsilateral breast cancer with odds ratio (OR) of 0.40 (95% CI 0.33-0.60, p < 0.00001) and 0.40 (95% CI 0.31-0.53, p < 0.00001), respectively. There was not difference in distant metastases (OR = 1.04, 95% CI 0.57-1.91, p = 0.38) and death rates (OR = 1.08, 95%CI 0.65-1.78, p = 0.45) between the two arms. There was more contralateral breast cancer after adjuvant RT (66/1711 = 3.85%) versus observation (49/1954 = 2.5%). The likelihood of contralateral breast cancer was 1.53-fold higher (95% CI 1.05-2.24, p = 0.03) in radiotherapy arms. CONCLUSION: The conclusion from our meta-analysis is that the addition of radiation therapy to lumpectomy results in an approximately 60% reduction in breast cancer recurrence, no benefit for survival or distant metastases compared to excision alone. Patients with high-grade DCIS lesions and positive margins benefited most from the addition of radiation therapy. It is not yet clear which patients can be successfully treated with lumpectomy alone; until further prospective studies answer this question, radiation should be recommended after lumpectomy for all patients without contraindications.