RESUMO
Li-Fraumeni Syndrome (LFS) is a hereditary cancer predisposition syndrome with up to 90% lifetime cancer risk. Cancer screening, including annual whole-body MRI (WB-MRI), is recommended due to known survival advantage, with cancer detection rate of 7% on initial screening. Intervention and cancer detection rates on subsequent screenings are unknown. Clinical data for pediatric and adult patients with LFS (n = 182) were reviewed, including instances of WB-MRI screening and interventions based on screening results. For each WB-MRI screening, interventions including biopsy and secondary imaging, as well as rate of cancer diagnosis, were analyzed comparing initial versus subsequent WB-MRI. Of the total cohort (n = 182), we identified 68 adult patients and 50 pediatric patients who had undergone at least two WB-MRI screenings, with a mean of 3.8 ± 1.9 (adults) and 4.0 ± 2.1 (pediatric) screenings. Findings on initial screening led to an imaging or invasive intervention in 38% of adults and 20% of children. On follow up, overall intervention rates were lower for adults (19%, P = 0.0026) and stable for children (19%, P = NS). Thirteen cancers were detected overall (7% of adult and 14% of pediatric scans), on both initial (pediatric: 4%, adult: 3%) and subsequent (pediatric: 10%, adult: 6%) screenings. Rates of intervention after WB-MRI screening decreased significantly in adults between first and subsequent exams and remained stable in pediatric patients. Cancer detection rates were similar on screening (3%-4% initial, 6%-10% subsequent) for both children and adults. These findings provide important data for counseling patients with LFS about screening outcomes. PREVENTION RELEVANCE: The cancer detection rate, burden of recommended interventions, and rate of false-positive findings found on subsequent WB-MRI screenings in patients with LFS are not well understood. Our findings suggest that annual WB-MRI screening has clinical utility and likely does not result in an unnecessary invasive intervention burden for patients.
Assuntos
Síndrome de Li-Fraumeni , Adulto , Humanos , Criança , Síndrome de Li-Fraumeni/diagnóstico por imagem , Síndrome de Li-Fraumeni/genética , Detecção Precoce de Câncer/métodos , Imagem Corporal Total/métodos , Imageamento por Ressonância Magnética , Genótipo , Predisposição Genética para DoençaRESUMO
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common type of neuroendocrine tumors and are being increasingly identified in clinical practice. The diagnosis, staging, management, and surveillance of GEP-NETs rely heavily on endoscopy, and consequently, it is important for gastroenterologists to have a solid understanding of these tumors. This article reviews the presentation, diagnosis, and management of both localized and advanced GEP-NETs, with increased emphasis on the role of endoscopy, to enable gastroenterologists and other practitioners to have the necessary tools for the care of patients with these tumors.
Assuntos
Neoplasias Intestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/epidemiologia , Neoplasias Intestinais/terapia , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/terapia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/terapiaRESUMO
CASE: We present the case of an 11-year-old girl with spinal muscular atrophy (SMA) type III who suffered an intraoperative venous thromboembolism (VTE), leading to death during bilateral extremity contracture releases for deformity correction. CONCLUSION: Given the increasing incidence of VTE in pediatric patients, further consideration should be given to broadening the patient population offerring preoperative deep vein thrombosis screening or thromboprophylaxis. Specifically, patients with previous trauma, neuromuscular disorders, and prolonged immobilization or contractures should receive special attention. In addition, SMA may cause hypercoagulability independent of its status as a neuromuscular disorder, and this link should be investigated further.
Assuntos
Complicações Intraoperatórias/etiologia , Embolia Pulmonar/complicações , Atrofias Musculares Espinais da Infância/complicações , Atrofias Musculares Espinais da Infância/cirurgia , Criança , Oxigenação por Membrana Extracorpórea/efeitos adversos , Evolução Fatal , Feminino , Humanos , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/terapiaRESUMO
Pancreatic ductal adenocarcinoma (PDAC) requires mitochondrial oxidative phosphorylation (OXPHOS) to fuel its growth, however, broadly inhibiting this pathway might also disrupt essential mitochondrial functions in normal tissues. PDAC cells exhibit abnormally fragmented mitochondria that are essential to its oncogenicity, but it was unclear if this mitochondrial feature was a valid therapeutic target. Here, we present evidence that normalizing the fragmented mitochondria of pancreatic cancer via the process of mitochondrial fusion reduces OXPHOS, which correlates with suppressed tumor growth and improved survival in preclinical models. Mitochondrial fusion was achieved by genetic or pharmacologic inhibition of dynamin related protein-1 (Drp1) or through overexpression of mitofusin-2 (Mfn2). Notably, we found that oral leflunomide, an FDA-approved arthritis drug, promoted a two-fold increase in Mfn2 expression in tumors and was repurposed as a chemotherapeutic agent, improving the median survival of mice with spontaneous tumors by 50% compared to vehicle. We found that the chief tumor suppressive mechanism of mitochondrial fusion was enhanced mitophagy, which proportionally reduced mitochondrial mass and ATP production. These data suggest that mitochondrial fusion is a specific and druggable regulator of pancreatic cancer growth that could be rapidly translated to the clinic.