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Clear cell tubopapillary renal cell carcinoma (CCTP-RCC) is a distinct histologic subtype of RCC recognized for its unique clinicopathologic and immunohistochemical features. A 72-year-old man with presumed polycystic kidney disease (PKD) and bilateral clear cell RCC (CC-RCC) underwent left radical nephrectomy and right partial nephrectomy 20 years ago at an outside hospital. On surveillance imaging, RCC recurrence was suspected and right radical nephrectomy was performed. Histologic and gross examination of the right remaining kidney was consistent with CCTP-RCC. Review of his original pathology report revealed both kidneys in fact represented CCTP-RCC, mimicking PKD.
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BACKGROUND: Sharing influenza viruses within the WHO Global Influenza Surveillance and Response System is crucial for monitoring evolution of influenza viruses. OBJECTIVES: Analysis of timeliness and geographic representativeness of viruses shared by National Influenza Centres (NICs) in the WHO European Region with the London WHO Collaborating Centre for Reference and Research on Influenza for the Northern Hemisphere's 2010-2011 and 2011-2012 influenza seasons. MATERIALS AND METHODS: Data from NICs on influenza-positive specimens shared with WHO CC London for the above-mentioned influenza seasons were analyzed for timeliness of sharing with respect to the February deadline (31 January) for inclusion in the WHO consultations on the composition of influenza virus vaccines for the Northern Hemisphere and geographic representativeness. RESULTS: The 2010-2011 and 2011-2012 seasons were different in terms of the seasonal pattern, the timing of the epidemic, and the dominant virus. Consistent patterns of virus sharing across the seasons were observed. Approximately half the viruses collected before the deadline were not shared within the deadline; the average delay between date of specimen collection and shipment receipt was 3 and 1·5 months for the first and second season, respectively. CONCLUSION: A baseline was provided for future work on enhancement of specimen sharing in the WHO European Region and improving the vaccine virus selection process. Greater insight into virus selection criteria applied by countries and the causes of delays in shipment are needed to understand the representativeness of viruses shared and to assess the importance of this for vaccine strain selection.
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Vacunas contra la Influenza , Gripe Humana/virología , Orthomyxoviridae , Conducta Cooperativa , Europa (Continente)/epidemiología , Humanos , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/aislamiento & purificación , Gripe Humana/epidemiología , Londres , Orthomyxoviridae/clasificación , Orthomyxoviridae/aislamiento & purificación , Vigilancia de la Población , Estaciones del Año , Organización Mundial de la SaludRESUMEN
We hypothesized that (i) preclinical biologic evidence exists for the role of androgens in ovarian cancer development and (ii) flutamide treatment of women at high risk for ovarian cancer may identify meaningful tissue biomarkers of androgen action and of ovarian cancer initiation. We showed that androgen ablation of male mice led to a 24-fold decrease in tumor burden from serous ovarian cells. In a phase II study, we studied the effect of preoperative flutamide treatment (125 mg/day × 6 weeks) in 12 women versus 47 controls, 47% with BRCA mutation. We analyzed immunohistochemical scores of candidate proteins CSF-1, CSF-1R, and ErbB4 in the epithelium and stroma of fallopian tube, ovary, and ovarian endosalpingiosis. Flutamide decreased the levels, notably, of CSF-1 and ErbB4 in ovarian stroma (P ≤ 0.0006) and ovarian endosalpingiosis (P ≤ 0.01), ErbB4 in ovarian epithelium (P = 0.006), and CSF-1R in ovarian endosalpingiosis (P = 0.009). Our logistic regression model clearly distinguished the flutamide patients from controls (P ≤ 0.0001). Our analysis of the precision of this model of CSF-1 and ErbB4 expression in ovarian stroma achieved 100% sensitivity and 97% specificity (AUC = 0.99). Thus, our data suggest that a short 6-week exposure of flutamide reversed elevated levels of CSF-1 and ErbB4 (both of which we had previously found correlated with high risk status). CSF-1 and ErbB4 in ovarian stroma led to a model with high predictive value for flutamide sensitivity. The effect of flutamide on marker expression in ovarian endosalpingiosis, previously associated with BRCA carrier status, suggests that ovarian endosalpingiosis may be a latent precursor to pelvic serous cancers.
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Antagonistas de Andrógenos/uso terapéutico , Biomarcadores de Tumor/análisis , Flutamida/uso terapéutico , Neoplasias Ováricas/prevención & control , Adulto , Animales , Antineoplásicos Hormonales/uso terapéutico , Área Bajo la Curva , Ensayo de Inmunoadsorción Enzimática , Neoplasias de las Trompas Uterinas/metabolismo , Neoplasias de las Trompas Uterinas/patología , Neoplasias de las Trompas Uterinas/prevención & control , Trompas Uterinas/metabolismo , Femenino , Predisposición Genética a la Enfermedad , Humanos , Inmunohistoquímica , Factor Estimulante de Colonias de Macrófagos/análisis , Factor Estimulante de Colonias de Macrófagos/biosíntesis , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Ovariectomía , Ovario/metabolismo , Curva ROC , Receptor ErbB-4/análisis , Receptor ErbB-4/biosíntesis , Factores de Riesgo , SalpingectomíaRESUMEN
INTRODUCTION: BRCA mutations increase the risk for development of high-grade pelvic serous carcinomas. Tissue biomarkers distinguishing women at high-risk (HR) for ovarian cancer from those at low-risk (LR) may provide insights into tumor initiation pathways. METHODS: A prospective study of 47 HR women (40% BRCA carriers) undergoing risk-reducing salpingo-oophorectomy and 48 LR controls undergoing salpingo-oophorectomy was performed. Ovarian/tubal tissues were harvested. Immunohistochemical analysis of candidate proteins CSF-1, CSF-1R, ErbB4 is presented, with scores separately analyzed in epithelium and stroma, in ampulla, fimbria, ovary, and ovarian endosalpingiosis (ES). Comparison was performed between HR and LR groups. RESULTS: Elevated levels of CSF-1 (p=0.005) or ErbB4 (p=0.005) in the ovarian epithelium, or ErbB4 (p=0.005) in the ovarian stroma, were significantly associated with both the HR status and carrying a BRCA mutation, as was nuclear ErbB4 staining. Ovarian ES, an entity which likely derives from the tubal mucosal epithelium, was also associated with HR (p=0.038) and BRCA mutation status (p=0.011). Among the BRCA carriers only, markers also found association when present in the tube as well as in ovarian ES (p < 0.05). ROCs were generated including in the regression model both CSF-1 and ErbB4 expression levels. A model including CSF-1 in ovarian epithelium, ErbB4 in ovarian stroma, and younger age achieves AUC=0.87 (73% sensitivity, 93% specificity) of detection of the HR status. In BRCA carriers, CSF-1 in ovarian epithelium alone achieves AUC=0.85. CONCLUSIONS: Our data suggest that elevated levels of CSF-1/ErbB4 in the adnexae correlate with HR/BRCA carrier status. CSF-1/CSF-1R signaling is active in ovarian cancer progression; our data suggests a role in its initiation. ErbB4, in particular nuclear ErbB4, may have a role in tumor initiation as well. Ovarian ES, an entity which may represent a latent precursor to low-grade pelvic serous carcinomas, was surprisingly associated with both HR status and the BRCA carrier cohort. In line with these findings, both ErbB4 and CSF-1R expression in ovarian ES correlated with carrying a BRCA mutation. This analysis, which needs to be validated, indirectly suggests a potential link between ovarian ES and the development of pelvic serous carcinoma in women who are BRCA mutation carriers.
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PURPOSE OF REVIEW: The aim of this article is to review recent reports on whole pancreas and islet cell transplantation. It focuses on 'what the call to the future looks like' for both therapies as treatment options for those type 1 diabetes patients who do not respond well to conventional therapy. RECENT FINDINGS: The major benefit of pancreas transplantation is the reversal of diabetes improvement of diabetes complications. Although the procedure requires major surgery and life-long immunosuppression, it remains the gold standard for a specific population of patients who suffer from type 1 diabetes and who do not respond to conventional therapy. Allogeneic islet transplantation is a promising alternative to pancreas transplantation, but patient outcomes remain less than optimal and significant progress is required in order for this procedure to be considered a reliable therapy. CONCLUSION: Several factors have to be taken into consideration before making the decision of which of these procedures would better suit a patient with type 1 diabetes.
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Diabetes Mellitus Tipo 1/cirugía , Trasplante de Islotes Pancreáticos , Trasplante de Páncreas , Complicaciones de la Diabetes/etiología , Complicaciones de la Diabetes/cirugía , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/historia , Predicción , Supervivencia de Injerto , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Inmunosupresores , Trasplante de Islotes Pancreáticos/efectos adversos , Trasplante de Islotes Pancreáticos/historia , Trasplante de Islotes Pancreáticos/tendencias , Trasplante de Páncreas/efectos adversos , Trasplante de Páncreas/historia , Trasplante de Páncreas/tendencias , Selección de Paciente , Trasplante Homólogo , Resultado del TratamientoRESUMEN
The advantages of living donor pancreas transplants for the recipient include good HLA matching, lower immunologic risk, less immunosuppression, lower risk of infection and of posttransplant malignancies, and shorter pancreas graft preservation time. In 2008, a total of 155 segmental pancreas transplants using living donors were reported to the International Pancreas Transplant Registry from six countries. Pancreas living donors need to undergo a thorough pretransplant endocrinologic workup in order to minimize the risk of metabolic complications. The pretransplant workup has evolved over time, after initial reports showed that up to 25% of living donors had elevated hemoglobin A(1c) levels after donation. Avoiding obesity after donation diminishes the risk of long-term metabolic complications. The risk of surgical complications for the donor (such as pancreatitis, pancreatic leak or fistula, pancreatic abscess, and pancreatic pseudocyst) is less than 5%. If both the donor and recipient operations are technically successful, the long-term graft survival rate is significantly higher for living (versus deceased) donor pancreas transplant recipients. Future long-term studies of metabolic function in living donors are warranted to determine whether living donor pancreas transplants can safely be applied more widely and whether living donors can be used for islet transplants.