RESUMO
BACKGROUND: Conservative surgery (CS) brachytherapy (BT) techniques for local therapy in bladder-prostate rhabdomyosarcoma (BP-RMS) seek to retain organ function. We report bladder function after high-dose rate (HDR) BT combined with targeted CS for any vesical component of BP-RMS. PROCEDURE: Prospective cohort of all BP-RMS patients between 2014 and 2019 receiving HDR-BT (iridium-192, 27.5 Gy in five fractions) with/without percutaneous endoscopic polypectomy (PEP) or partial cystectomy (PC). Functional assessment included frequency-volume chart, voided volumes, post-void residual, flow studies, continence status and ultrasound scanning; abnormalities triggered video urodynamics. RESULTS: Thirteen patients (10 male), aged 9 months to 4 years (median 23 months), presented with localised fusion-negative embryonal BP-RMS measuring 23-140 mm (median 43 mm) in cranio-caudal extent. After induction chemotherapy, local treatment consisted of PC+BT in three, PEP+BT in four and BT alone in six. At a median 3.5 years (range 21 months to 7 years) follow-up, all were alive without relapse. At a median age of 6 years (4-9 years), the median bladder capacity was 86% (47%-144%) of that expected for age, including 75% (74%-114%) after PC. Radiation dose to the bladder was associated with urinary urgency, but not bladder capacity or nocturnal enuresis. Complications occurred in two: one urethral stricture and one vesical decompensation in a patient with pre-existing high-grade vesico-ureteric reflux (VUR). The remaining patients were dry by day; five with anticholinergic medication for urinary urgency. Three patients are enuretic. CONCLUSIONS: Day-time dryness at a median 3.5 years after CS-HDR-BT was achieved in 92%, with 85% voiding urethrally, and 62% attaining day-and-night continence aged 4-9 years. We report reduced open surgery with minimally invasive percutaneous surgery, with HDR-BT or BT alone being suitable for many.
Assuntos
Braquiterapia , Neoplasias Pélvicas , Neoplasias da Próstata , Rabdomiossarcoma , Neoplasias da Bexiga Urinária , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Criança , Humanos , Masculino , Recidiva Local de Neoplasia , Estudos Prospectivos , Próstata , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Dosagem Radioterapêutica , Rabdomiossarcoma/radioterapia , Rabdomiossarcoma/cirurgia , Bexiga Urinária , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/radioterapia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
Changes in maternal nutrient intake during gestation alter IGF receptor abundance and leptin (LEP) mRNA expression in fetal adipose tissue. It is not known whether such changes persist into adult life and whether they are associated with an effect on phenotype. We investigated the effect of high (240%) and low (70%) levels of recommended daily crude protein intake for beef heifers during the first and second trimesters of gestation on singleton progeny (n=68): subcutaneous (SC) adipose tissue depth at rump (P8) and rib (RF) sites from 65 until 657 days of age; plasma leptin concentrations from birth until 657 days and expression of IGF1 and IGF2, their receptors (IGF1R and IGF2R) and LEP mRNA in perirenal (PR), omental (OM) and SC adipose tissue at 680 days of age. High-protein diets during the first trimester increased LEP and IGF1 mRNA in PR of males and females, respectively, compared with low-protein diets, and decreased IGF1R mRNA in SC of all progeny but increased RF depth of males between 552 and 657 days. High-protein diets compared with low-protein diets during the second trimester increased IGF1R mRNA in PR and OM of all progeny; LEP mRNA in PR of males; and IGF2 and IGF2R mRNA in OM of all progeny. Conversely, LEP mRNA in OM and IGF2 mRNA in PR of all progeny were decreased following exposure to high- compared with low-protein diets during the second trimester. Heifer diet during gestation has permanent sex- and depot-specific effects on the expression of adipogenic and adipocytokine genes and offspring adiposity.
Assuntos
Adiposidade/genética , Fenômenos Fisiológicos da Nutrição Animal , Dieta com Restrição de Proteínas , Proteínas Alimentares/administração & dosagem , Fenômenos Fisiológicos da Nutrição Materna , Efeitos Tardios da Exposição Pré-Natal , RNA Mensageiro/metabolismo , Gordura Subcutânea/metabolismo , Fatores Etários , Envelhecimento , Animais , Bovinos , Feminino , Regulação da Expressão Gênica , Idade Gestacional , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Leptina/sangue , Leptina/genética , Masculino , Gravidez , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Receptor IGF Tipo 2/genética , Receptor IGF Tipo 2/metabolismo , Fatores SexuaisRESUMO
UNLABELLED: This study tested the principle that (68)Ga-DOTATATE PET/CT may be used to select children with primary refractory or relapsed high-risk neuroblastoma for treatment with (177)Lu-DOTATATE and evaluated whether this is a viable therapeutic option for those children. METHODS: Between 2008 and 2010, 8 children with relapsed or refractory high-risk neuroblastoma were studied with (68)Ga-DOTATATE PET/CT. The criterion of eligibility for (177)Lu-DOTATATE therapy was uptake on the diagnostic scan equal to or higher than that of the liver. RESULTS: Of the 8 children imaged, 6 had abnormally high uptake on the (68)Ga-DOTATATE PET/CT scan and proceeded to treatment. Patients received 2 or 3 administrations of (177)Lu-DOTATATE at a median interval of 9 wk and a median administered activity of 7.3 GBq. Of the 6 children treated, 5 had stable disease by the response evaluation criteria in solid tumors (RECIST). Of these 5 children, 2 had an initial metabolic response and reduction in the size of their lesions, and 1 patient had a persistent partial metabolic response and reduction in size of the lesions on CT, although the disease was stable by RECIST. One had progressive disease. Three children had grade 3 and 1 child had grade 4 thrombocytopenia. No significant renal toxicity has been seen. CONCLUSION: (68)Ga-DOTATATE can be used to image children with neuroblastoma and identify those suitable for molecular radiotherapy with (177)Lu-DOTATATE. We have shown, for what is to our knowledge the first time, that treatment with (177)Lu-DOTATATE is safe and feasible in children with relapsed or primary refractory high-risk neuroblastoma. We plan to evaluate this approach formally in a phase I-II clinical trial.
Assuntos
Neuroblastoma/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Adolescente , Criança , Pré-Escolar , Feminino , Radioisótopos de Gálio , Humanos , Masculino , Neuroblastoma/diagnóstico por imagem , Neuroblastoma/metabolismo , Octreotida/uso terapêutico , Tomografia por Emissão de Pósitrons , Receptores de Somatostatina/metabolismo , Recidiva , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
The microsatellite D19S884, located in intron 55 of fibrillin-3 (FBN3) gene, associates with polycystic ovary syndrome (PCOS) in familial studies. The family of fibrillin proteins (FBN1-3), which includes latent TGF-beta binding proteins (LTBP-1 to -4), are extracellular matrix proteins. We localized and examined the expression of these proteins in the adult bovine ovaries (n=7-10 per group, average age 681 days) born to mothers fed high (13% protein per total dry weight) or a low protein diet (5%) in each of the first and second trimesters of pregnancy (n=4 groups). FBN1 and LTBP-1 and -2 were the major members expressed in the mature ovary. Each protein had a unique localization pattern but all were associated with stromal tissue including the tunica albuginea (FBN1 and LTBP-2 near surface, and FBN1 and LTBP-1 deeper in the tunica), cortical stroma (FBN1 and LTBP-1) and follicular thecal layers (FBN1 in theca interna, LTBP-1 in the inner regions of the theca externa, and LTBP-2 in the outer regions of the theca externa). No significant (P>0.05) effects of maternal diet were observed on either the localization or the levels of mRNA of any of these proteins in the tunica. Expression levels of all three FBNs were positively correlated with each other, and FBN1 and 2 were positively correlated with LTBP-2, suggesting some level of co-ordinate regulation. This is the first study to investigate the expression and localization of these genes affecting TGFbeta bioavailability in the ovary.