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BACKGROUND. The 2022 Society of Radiologists in Ultrasound (SRU) consensus conference recommendations for small gallbladder polyps support management that is less aggressive than earlier approaches and may help standardize evaluation of polyps by radiologists. OBJECTIVE. The purpose of the present study was to assess the interreader agreement of radiologists in applying SRU recommendations for management of incidental gallbladder polyps on ultrasound. METHODS. This retrospective study included 105 patients (75 women and 30 men; median age, 51 years) with a gallbladder polyp on ultrasound (without features highly suspicious for invasive or malignant tumor) who underwent cholecystectomy between January 1, 2003, and January 1, 2021. Ten abdominal radiologists independently reviewed ultrasound examinations and, using the SRU recommendations, assessed one polyp per patient to assign risk category (extremely low risk, low risk, or indeterminate risk) and make a possible recommendation for surgical consultation. Five radiologists were considered less experienced (< 5 years of experience), and five were considered more experienced (≥ 5 years of experience). Interreader agreement was evaluated. Polyps were classified pathologically as nonneoplastic or neoplastic. RESULTS. For risk category assignments, interreader agreement was substantial among all readers (k = 0.710), less-experienced readers (k = 0.705), and more-experienced readers (k = 0.692). For surgical consultation recommendations, inter-reader agreement was substantial among all readers (k = 0.795) and more-experienced readers (k = 0.740) and was almost perfect among less-experienced readers (k = 0.811). Of 10 readers, a median of 5.0 (IQR, 2.0-8.0), 4.0 (IQR, 2.0-7.0), and 0.0 (IQR, 0.0-0.0) readers classified polyps as extremely low risk, low risk, and indeterminate risk, respectively. Across readers, the percentage of polyps classified as extremely low risk ranged from 32% to 72%; as low risk, from 24% to 65%; and as indeterminate risk, from 0% to 8%. Of 10 readers, a median of zero change to 0 (IQR, 0.0-1.0) readers recommended surgical consultation; the percentage of polyps receiving a recommendation for surgical consultation ranged from 4% to 22%. Of a total of 105 polyps, 102 were nonneo-plastic and three were neoplastic (all benign). Based on readers' most common assessments for nonneoplastic polyps, the risk category was extremely low risk for 53 polyps, low risk for 48 polyps, and indeterminate risk for one polyp; surgical consultation was recommended for 16 polyps. CONCLUSION. Ten abdominal radiologists showed substantial agreement for polyp risk categorizations and surgical consultation recommendations, although areas of reader variability were identified. CLINICAL IMPACT. The findings support the overall reproducibility of the SRU recommendations, while indicating opportunity for improvement.
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Achados Incidentais , Pólipos , Ultrassonografia , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Pólipos/diagnóstico por imagem , Pólipos/cirurgia , Estudos Retrospectivos , Ultrassonografia/métodos , Adulto , Doenças da Vesícula Biliar/diagnóstico por imagem , Doenças da Vesícula Biliar/cirurgia , Idoso , Variações Dependentes do Observador , Radiologistas , Sociedades Médicas , Consenso , Guias de Prática Clínica como AssuntoAssuntos
Antibacterianos , Exantema , Linfoma Folicular , Pele , Síndrome de Stevens-Johnson , Idoso , Feminino , Humanos , Diagnóstico Diferencial , Exantema/etiologia , Pele/patologia , Dor/etiologia , Tomografia Computadorizada por Raios X , Exsudatos e Transudatos/diagnóstico por imagem , Canal Anal/diagnóstico por imagem , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/tratamento farmacológico , Síndrome de Stevens-Johnson/etiologia , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Doxiciclina/efeitos adversos , Doxiciclina/uso terapêutico , Períneo , Abdome , Negro ou Afro-Americano , Biópsia , Linfoma Folicular/complicações , Linfoma Folicular/diagnóstico , Linfadenopatia ImunoblásticaAssuntos
Dor Abdominal , Febre , Úlcera Cutânea , Humanos , Feminino , Dor Abdominal/etiologia , Adulto , Febre/etiologia , Diagnóstico Diferencial , Úlcera Cutânea/etiologia , Úlcera Cutânea/patologia , Gravidez , Transtornos Puerperais/diagnóstico , Transtornos Puerperais/etiologia , Período Pós-PartoAssuntos
Imunodeficiência de Variável Comum , Febre , Hepatopatias , Fígado , Esplenomegalia , Idoso , Humanos , Masculino , Antibacterianos/uso terapêutico , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/etiologia , Medula Óssea/patologia , Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/terapia , Diagnóstico Diferencial , Doenças do Sistema Digestório/diagnóstico , Doenças do Sistema Digestório/diagnóstico por imagem , Doenças do Sistema Digestório/tratamento farmacológico , Doenças do Sistema Digestório/etiologia , Progressão da Doença , Febre/etiologia , Granuloma/diagnóstico por imagem , Granuloma/tratamento farmacológico , Granuloma/etiologia , Fígado/patologia , Fígado/diagnóstico por imagem , Hepatopatias/diagnóstico por imagem , Hepatopatias/tratamento farmacológico , Hepatopatias/etiologia , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/tratamento farmacológico , Nódulos Pulmonares Múltiplos/etiologia , Recidiva , Febre Recorrente/diagnóstico , Febre Recorrente/tratamento farmacológico , Febre Recorrente/etiologia , Esplenomegalia/diagnóstico por imagem , Esplenomegalia/tratamento farmacológico , Esplenomegalia/etiologia , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To evaluate efficacy and safety of prophylactic internal iliac occlusion balloon placement before cesarean hysterectomy for invasive placenta. MATERIAL AND METHODS: A retrospective analysis was performed of patients with invasive placenta treated with and without occlusion balloon placement. Preoperative occlusion balloons were placed in 90 patients; 61 patients were treated without balloon placement (control group). Baseline demographics, including patient age, gestational age at delivery, gravidity, parity, and number of previous cesarean sections, were not significantly different (P > .05). Of the balloon placement group, 56% had placenta percreta compared with 25% in the control group (P < .001), and 83% had placenta previa compared with 66% in the control group (P = .012). RESULTS: Median blood loss was 2 L (range, 1.5-2.5 L) in the balloon placement group versus 2.5 L (range, 2-4 L) in the control group (P = .002). Patients with occlusion balloons were transfused a median of 2 U (range, 0-5 U) of packed red blood cells versus 5 U (range, 2-8 U) in patients in the control group (P = .002). In the balloon placement group, 34% had large volume blood loss > 2,500 mL versus 61% in the control group (P = .001), and 21% required blood transfusion > 6 U versus 44% in the control group (P = .002). Eight complications (9%) were attributed to occlusion balloon placement. CONCLUSIONS: Prophylactic internal iliac artery occlusion balloon placement reduces operative blood loss and transfusion requirements in patients undergoing hysterectomy for invasive placenta.
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Oclusão com Balão , Perda Sanguínea Cirúrgica/prevenção & controle , Artéria Ilíaca , Placenta Acreta/cirurgia , Adulto , Transfusão de Sangue/estatística & dados numéricos , Cesárea , Feminino , Número de Gestações , Humanos , Histerectomia , Paridade , Gravidez , Radiografia Intervencionista , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The tumor protein 53 (TP53) tumor suppressor gene is the most frequently somatically altered gene in human cancers. Here we show expression of N-Myc down-regulated gene 1 (NDRG1) is induced by p53 during physiologic low proliferative states, and mediates centrosome homeostasis, thus maintaining genome stability. When placed in physiologic low-proliferating conditions, human TP53 null cells fail to increase expression of NDRG1 compared with isogenic wild-type controls and TP53 R248W knockin cells. Overexpression and RNA interference studies demonstrate that NDRG1 regulates centrosome number and amplification. Mechanistically, NDRG1 physically associates with γ-tubulin, a key component of the centrosome, with reduced association in p53 null cells. Strikingly, TP53 homozygous loss was mutually exclusive of NDRG1 overexpression in over 96% of human cancers, supporting the broad applicability of these results. Our study elucidates a mechanism of how TP53 loss leads to abnormal centrosome numbers and genomic instability mediated by NDRG1.
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Proteínas de Ciclo Celular/metabolismo , Centrossomo/ultraestrutura , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Aneuploidia , Animais , Mama/metabolismo , Linhagem Celular , Proliferação de Células , Centrossomo/metabolismo , Feminino , Genoma , Heterozigoto , Homeostase , Homozigoto , Humanos , Hibridização in Situ Fluorescente , Camundongos , Camundongos Knockout , Neoplasias/patologia , Fenótipo , Interferência de RNA , Tubulina (Proteína)/metabolismoRESUMO
Recurrent human epidermal growth factor receptor 2 (HER2) missense mutations have been reported in human cancers. These mutations occur primarily in the absence of HER2 gene amplification such that most HER2-mutant tumors are classified as "negative" by FISH or immunohistochemistry assays. It remains unclear whether nonamplified HER2 missense mutations are oncogenic and whether they are targets for HER2-directed therapies that are currently approved for the treatment of HER2 gene-amplified breast cancers. Here we functionally characterize HER2 kinase and extracellular domain mutations through gene editing of the endogenous loci in HER2 nonamplified human breast epithelial cells. In in vitro and in vivo assays, the majority of HER2 missense mutations do not impart detectable oncogenic changes. However, the HER2 V777L mutation increased biochemical pathway activation and, in the context of a PIK3CA mutation, enhanced migratory features in vitro. However, the V777L mutation did not alter in vivo tumorigenicity or sensitivity to HER2-directed therapies in proliferation assays. Our results suggest the oncogenicity and potential targeting of HER2 missense mutations should be considered in the context of cooperating genetic alterations and provide previously unidentified insights into functional analysis of HER2 mutations and strategies to target them.
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Movimento Celular/genética , Mutação de Sentido Incorreto/genética , Neoplasias/genética , Receptor ErbB-2/genética , Transdução de Sinais/genética , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Ensaio de Unidades Formadoras de Colônias , Citometria de Fluxo , Marcação de Genes , Células HEK293 , Humanos , Immunoblotting , Lapatinib , Quinazolinas , Quinolinas , TiazóisRESUMO
BACKGROUND/PURPOSE: The combined contributions of oncogenes and tumor suppressor genes toward carcinogenesis remain poorly understood. Elucidation of cancer gene cooperativity can provide new insights leading to more effective use of therapies. EXPERIMENTAL DESIGN/METHODS: We used somatic cell genome editing to introduce singly and in combination PIK3CA mutations (E545K or H1047R) with TP53 alterations (R248W or knockout), to assess any enhanced cancerous phenotypes. The non-tumorigenic human breast epithelial cell line, MCF10A, was used as the parental cell line, and resultant cells were assessed via various in vitro assays, growth as xenografts, and drug sensitivity assays using targeted agents and chemotherapies. RESULTS: Compared to single-gene-targeted cells and parental controls, cells with both a PIK3CA mutation and TP53 alteration had increased cancerous phenotypes including cell proliferation, soft agar colony formation, aberrant morphology in acinar formation assays, and genomic heterogeneity. Cells also displayed varying sensitivities to anti-neoplastic drugs, although all cells with PIK3CA mutations showed a relative increased sensitivity to paclitaxel. All cell lines remained non-tumorigenic. CONCLUSIONS: This cell line panel provides a resource for further elucidating cooperative genetic mediators of carcinogenesis and response to therapies.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Mutação , Fenótipo , Proteína Supressora de Tumor p53/genética , Animais , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Centrômero/genética , Variações do Número de Cópias de DNA , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Amplificação de Genes , Edição de Genes , Técnicas de Inativação de Genes , Instabilidade Genômica , Genótipo , Humanos , Camundongos , Paclitaxel/farmacologiaRESUMO
Although aerobic glycolysis provides an advantage in the hypoxic tumor microenvironment, some cancer cells can also respire via oxidative phosphorylation. These respiring ("non-Warburg") cells were previously thought not to play a key role in tumorigenesis and thus fell from favor in the literature. We sought to determine whether subpopulations of hypoxic cancer cells have different metabolic phenotypes and gene-expression profiles that could influence tumorigenicity and therapeutic response, and we therefore developed a dual fluorescent protein reporter, HypoxCR, that detects hypoxic [hypoxia-inducible factor (HIF) active] and/or cycling cells. Using HEK293T cells as a model, we identified four distinct hypoxic cell populations by flow cytometry. The non-HIF/noncycling cell population expressed a unique set of genes involved in mitochondrial function. Relative to the other subpopulations, these hypoxic "non-Warburg" cells had highest oxygen consumption rates and mitochondrial capacity consistent with increased mitochondrial respiration. We found that these respiring cells were unexpectedly tumorigenic, suggesting that continued respiration under limiting oxygen conditions may be required for tumorigenicity.
Assuntos
Ciclo Celular/fisiologia , Hipóxia Celular/fisiologia , Neoplasias/metabolismo , Neoplasias/patologia , Animais , Ciclo Celular/genética , Hipóxia Celular/genética , Respiração Celular , Expressão Gênica , Genes Mitocondriais , Genes Reporter , Células HEK293 , Xenoenxertos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Camundongos , Camundongos Nus , Modelos Biológicos , Transplante de Neoplasias , Neoplasias/genética , Oncogenes , Consumo de OxigênioRESUMO
Tamoxifen is effective for treating estrogen receptor-alpha (ER) positive breast cancers. However, few molecular mediators of tamoxifen resistance have been elucidated. Here we describe a previously unidentified gene, MACROD2 that confers tamoxifen resistance and estrogen independent growth. We found MACROD2 is amplified and overexpressed in metastatic tamoxifen-resistant tumors. Transgene overexpression of MACROD2 in breast cancer cell lines results in tamoxifen resistance, whereas RNAi-mediated gene knock down reverses this phenotype. MACROD2 overexpression also leads to estrogen independent growth in xenograft assays. Mechanistically, MACROD2 increases p300 binding to estrogen response elements in a subset of ER regulated genes. Primary breast cancers and matched metastases demonstrate MACROD2 expression can change with disease evolution, and increased expression and amplification of MACROD2 in primary tumors is associated with worse overall survival. These studies establish MACROD2 as a key mediator of estrogen independent growth and tamoxifen resistance, as well as a potential novel target for diagnostics and therapy.
Assuntos
Neoplasias da Mama/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Resistencia a Medicamentos Antineoplásicos , Estrogênios/metabolismo , Hidrolases/metabolismo , Tamoxifeno/farmacologia , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células , Epigênese Genética , Feminino , Deleção de Genes , Dosagem de Genes , Humanos , Dados de Sequência Molecular , Transplante de Neoplasias , Fenótipo , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores de Estrogênio/metabolismo , Transgenes , Resultado do TratamentoAssuntos
Internato e Residência , Tutoria/métodos , Seleção de Pessoal/métodos , Radiologia/educação , Pesquisa , Estudantes de Medicina , Animais , Cães , HumanosRESUMO
The PIK3CA gene encodes for the p110 alpha isoform of PI3 kinase and is one of the most frequently mutated oncogenes in human cancers. However, the mechanisms by which PIK3CA mutations activate cell signaling are not fully understood. Here we used a phosphoproteomic approach to compare differential phosphorylation patterns between human breast epithelial cells and two isogenic somatic cell knock in derivatives, each harboring a distinct PIK3CA mutation. We demonstrated differential phosphorylation patterns between isogenic cell lines containing a PIK3CA helical domain mutation (E545K) compared to cells with a PIK3CA kinase domain mutation (H1047R). In particular, the receptor tyrosine kinase, HER3, showed increased phosphorylation at tyrosine 1328 in H1047R cells versus E545K cells. Genetic studies using shRNA demonstrated that H1047R cells have a profound decrease in growth factor independent proliferation upon HER3 knock down, but this effect was attenuated in E545K cells. In addition, HER3 knock down led to reductions in both PI3 kinase and MAP kinase pathway activation in H1047R cells, but in E545K cells only PI3 kinase pathway diminution was observed. These studies demonstrate the power of using paired isogenic cell lines for proteomic analysis to gain new insights into oncogenic signal transduction pathways.
Assuntos
Neoplasias da Mama/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteômica , Receptor ErbB-3/metabolismo , Transdução de Sinais , Neoplasias da Mama/genética , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Classe I de Fosfatidilinositol 3-Quinases , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Mutação , Fosfatidilinositol 3-Quinases/química , Fosfatidilinositol 3-Quinases/genética , Fosforilação , Estrutura Terciária de Proteína , Interferência de RNA , Receptor ErbB-3/genéticaRESUMO
Magnetic resonance venography (MRV) represents a distinct imaging approach that may be used to evaluate a wide spectrum of venous pathology. Despite duplex ultrasound and computed tomography venography representing the dominant imaging modalities in investigating suspected venous disease, MRV is increasingly used due to its lack of ionizing radiation, unique ability to be performed without administration of intravenous contrast, and recent technical improvements resulting in improved sensitivity, image quality, and faster acquisition times. In this review, the authors discuss commonly used body and extremity MRV techniques, different clinical applications, and future directions.
Assuntos
Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Flebografia/métodos , Angiografia por Ressonância Magnética/métodos , Extremidades , Tomografia Computadorizada por Raios XRESUMO
Hemorrhagic cholecystitis is a rare disorder associated with considerable morbidity and mortality. The clinical presentation of hemorrhagic cholecystitis is non-specific and imaging findings can be difficult to accurately interpret without a high level of suspicion. Most recent reports of hemorrhagic cholecystitis have been associated with concurrent therapeutic anticoagulation. Here, we report imaging findings of a case of acute, spontaneous hemorrhagic cholecystitis in a 67-year-old male patient admitted for hypoxic respiratory failure secondary to COVID-19 pneumonia.
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IgG4-related disease (IgG4-RD) is an immune-mediated multiorgan fibroinflammatory disorder with variable clinical presentations. IgG4-RD cardiovascular involvement is considered rare, with pulmonary arterial involvement reported in a small subset of cases. Known pulmonary artery manifestations include pulmonary arteritis, pulmonary artery stenoses and central pulmonary artery aneurysms. Here we report 2 different patients with multifocal dilatation of the segmental and subsegmental pulmonary arteries with differing degrees of severity. Both patients also had coronary arterial abnormalities.
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PURPOSE: Diabetic patients are at increased risk of developing lower extremity peripheral arterial disease (PAD) requiring revascularization. This study assessed the effect of insulin dependence in diabetics on post-procedural outcomes following infra-inguinal endovascular intervention. MATERIALS AND METHODS: The American College of Surgeon's National Surgical Quality Improvement Program database was used to identify 8022 patients undergoing infra-inguinal endovascular interventions between 2014 and 2017. Thirty-day post-procedural outcomes for patients without diabetes, with non-insulin-dependent diabetes mellitus (NIDDM), and with insulin-dependent diabetes mellitus (IDDM) were compared. RESULTS: At presentation, IDDM patients were more likely to present with critical limb ischemia compared to NIDDM and non-diabetic patients. In propensity score-weighted logistic regression analysis, IDDM status was an independent predictor for increased renal complication (odds ratio [OR] = 3.08, confidence interval [CI] = 1.44-6.65), sepsis (OR = 1.68, CI = 1.13-2.48), wound complication (OR = 1.57, CI = 1.09-2.25, p = 0.006), UTI (OR = 2.07, CI = 1.09-3.94, p = 0.03), and readmission (OR = 1.21, CI = 1.03-1.42). NIDDM status was an independent predictor for increased risk of renal complications (OR = 2.80, CI = 1.18-6.63). CONCLUSIONS: IDDM status is an independent predictor for increased risk of 30-day post-procedural complications and readmission compared to both NIDDM and non-diabetic status in patients undergoing lower extremity endovascular interventions for PAD.
Assuntos
Diabetes Mellitus/sangue , Procedimentos Endovasculares/métodos , Insulina/sangue , Isquemia/etiologia , Doença Arterial Periférica/complicações , Doença Arterial Periférica/cirurgia , Complicações Pós-Operatórias/etiologia , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Isquemia/sangue , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/cirurgia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Doença Arterial Periférica/sangue , Complicações Pós-Operatórias/sangue , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
PURPOSE: To determine the pathologic response of computed tomography-guided percutaneous microwave ablation as bridging therapy for patients with hepatocellular carcinoma awaiting liver transplant, and its subsequent effect on survival. MATERIALS AND METHODS: A single-center retrospective analysis was conducted on 62 patients (M:F = 50:12) with mean age of 59.6 years ± 7.2 months (SD). Sixty-four total MWA procedures were performed for hepatocellular carcinomas within Milan criteria as bridging therapy to subsequent orthotopic liver transplant between August 2014 and September 2018. The pathology reports of the explanted livers were reviewed to assess for residual disease. Residual disease was categorized as complete or incomplete necrosis. Patient demographics, tumor/procedural characteristics, and laboratory values were evaluated. Survival from time of ablation and time of transplantation were recorded and compared between cohorts using log rank tests. RESULTS: The mean tumor size was 2.4 cm ± 0.7 cm (SD), (range = 1-4.6 cm). 32 (50%) cases required hydrodissection. Histopathologic necrosis was seen in 66% of cases at time of liver transplantation. Median time to liver transplant post-MWA was 12.6 months. [IQR = 8.6-14.8 months]. The median survival from ablation was 60.8 months [IQR = 45.5-73.7 months], and the median survival from transplant was 49.3 months [IQR = 33.7-60.1 months]. There was no significant difference in survival for patients with complete versus incomplete necrosis from ablation or liver transplant (p = 0.49, p = 0.46, respectively). CONCLUSIONS: Computed tomography-guided percutaneous microwave ablation is an effective bridge to orthotopic liver transplantation for patients with hepatocellular carcinoma. CEBM LEVEL OF EVIDENCE: Level 3, non-randomized controlled cohort study/follow-up study.
Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Transplante de Fígado , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Estudos de Coortes , Seguimentos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Micro-Ondas/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The COVID-19 pandemic has challenged the capacity of interventional radiology departments worldwide to effectively treat COVID-19 and non-COVID-19 patients while preventing disease transmission among patients and healthcare workers. In this review, we describe the various data driven infection control measures implemented by the interventional radiology department of a large tertiary care center in the United States including the use and novel re-use of personal protective equipment, COVID-19 testing strategies, modifications in procedural workflows and the leveraging of telehealth visits. Herein, we provide effective triage, procedural, and management algorithms that may guide other interventional radiology departments during the ongoing COVID-19 pandemic and in future infectious disease outbreaks.
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COVID-19/prevenção & controle , Controle de Infecções/métodos , Serviço Hospitalar de Radiologia , Radiologia Intervencionista/métodos , Humanos , Pandemias , Equipamento de Proteção Individual , SARS-CoV-2 , Centros de Atenção Terciária , Estados UnidosRESUMO
BACKGROUND: Genomic testing is often limited by the exhaustible nature of human tissue and blood samples. Here we describe biotinylated amplicon sequencing (BAmSeq), a method that allows for the creation of PCR amplicon based next-generation sequencing (NGS) libraries while retaining the original source DNA. DESIGN AND METHODS: Biotinylated primers for different loci were designed to create NGS libraries using human genomic DNA from cell lines, plasma, and formalin-fixed paraffin embedded (FFPE) tissues using the BAmSeq protocol. DNA from the original template used for each BAmSeq library was recovered after separation with streptavidin magnetic beads. The recovered DNA was then used for end-point, quantitative and droplet digital PCR (ddPCR) as well as NGS using a cancer gene panel. RESULTS: Recovered DNA was analyzed and compared to the original DNA after one or two rounds of BAmSeq. Recovered DNA revealed comparable genomic distributions and mutational allelic frequencies when compared to original source DNA. Sufficient quantities of recovered DNA after BAmSeq were obtained, allowing for additional downstream applications. CONCLUSIONS: We demonstrate that BAmSeq allows original DNA template to be recovered with comparable quality and quantity to the source DNA. This recovered DNA is suitable for many downstream applications and may prevent sample exhaustion, especially when DNA quantity or source material is limiting.
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Purpose: Although most human cancers display a single histology, there are unusual cases where two or more distinct tissue types present within a primary tumor. One such example is metaplastic breast carcinoma, a rare but aggressive cancer with a heterogeneous histology, including squamous, chondroid, and spindle cells. Metaplastic carcinomas often contain an admixed conventional ductal invasive or in situ mammary carcinoma component, and are typically triple-negative for estrogen receptor, progesterone receptor, and HER-2 amplification/overexpression. An unanswered question is the origin of metaplastic breast cancers. While they may arise independently from their ductal components, their close juxtaposition favors a model that postulates a shared origin, either as two derivatives from the same primary cancer or one histology as an outgrowth of the other. Understanding the mechanism of development of these tumors may inform clinical decisions.Experimental Design: We performed exome sequencing for paired metaplastic and adjacent conventional invasive ductal carcinomas in 8 patients and created a pipeline to identify somatic variants and predict their functional impact, without having normal tissue. We then determined the genetic relationships between the histologically distinct compartments.Results: In each case, the tumor components have nearly identical landscapes of somatic mutation, implying that the differing histologies do not derive from genetic clonal divergence.Conclusions: A shared origin for tumors with differing histologies suggests that epigenetic or noncoding changes may mediate the metaplastic phenotype and that alternative therapeutic approaches, including epigenetic therapies, may be required for metaplastic breast cancers. Clin Cancer Res; 23(16); 4875-84. ©2017 AACR.