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1.
Am J Gastroenterol ; 115(12): 2095-2097, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32969947

RESUMO

INTRODUCTION: To assess the upper gastrointestinal (UGI) cancer risk and surveillance outcomes in Li-Fraumeni syndrome (LFS). METHODS: Analysis of the International Agency for Research on Cancer database and a single-center adult LFS cohort. RESULTS: UGI cancer was present in 7.2% of families and 3.9% of individuals with a pathogenic/likely pathogenic TP53 mutation in International Agency for Research on Cancer; 29% occurred before age 30. Our institutional cohort had 35 individuals (31% of the LFS cohort) with 48 cumulative upper endoscopies; 3 (8.5%) individuals had concerning UGI findings. DISCUSSION: UGI cancer is observed in LFS. Upper endoscopy should be part of a comprehensive LFS surveillance program.

3.
Cancer Res ; 80(17): 3732-3744, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32675277

RESUMO

Germline mutations in TP53 cause a rare high penetrance cancer syndrome, Li-Fraumeni syndrome (LFS). Here, we identified a rare TP53 tetramerization domain missense mutation, c.1000G>C;p.G334R, in a family with multiple late-onset LFS-spectrum cancers. Twenty additional c.1000G>C probands and one c.1000G>A proband were identified, and available tumors showed biallelic somatic inactivation of TP53. The majority of families were of Ashkenazi Jewish descent, and the TP53 c.1000G>C allele was found on a commonly inherited chromosome 17p13.1 haplotype. Transient transfection of the p.G334R allele conferred a mild defect in colony suppression assays. Lymphoblastoid cell lines from the index family in comparison with TP53 normal lines showed that although classical p53 target gene activation was maintained, a subset of p53 target genes (including PCLO, PLTP, PLXNB3, and LCN15) showed defective transactivation when treated with Nutlin-3a. Structural analysis demonstrated thermal instability of the G334R-mutant tetramer, and the G334R-mutant protein showed increased preponderance of mutant conformation. Clinical case review in comparison with classic LFS cohorts demonstrated similar rates of pediatric adrenocortical tumors and other LFS component cancers, but the latter at significantly later ages of onset. Our data show that TP53 c.1000G>C;p.G334R is found predominantly in Ashkenazi Jewish individuals, causes a mild defect in p53 function, and leads to low penetrance LFS. SIGNIFICANCE: TP53 c.1000C>G;p.G334R is a pathogenic, Ashkenazi Jewish-predominant mutation associated with a familial multiple cancer syndrome in which carriers should undergo screening and preventive measures to reduce cancer risk.

4.
J Emerg Med ; 59(3): 348-356, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32593579

RESUMO

BACKGROUND: Women with abnormal uterine bleeding are commonly encountered in the emergency department (ED). Contemporary management of severe iron deficiency anemia (IDA) in this setting may be inadequate and expose patients to unnecessary blood transfusions. OBJECTIVE: We sought to describe the characteristics and management of women presenting to the ED with moderate to severe anemia caused by uterine bleeding. We hypothesized that blood transfusions were frequently administered to stable patients without severe symptoms or active bleeding. METHODS: This is a retrospective cohort study of women presenting to the ED from October 31, 2018 to March 31, 2019 with IDA from uterine bleeding. Eligible subjects were adult females with IDA caused by uterine blood loss, hemoglobin ≤10 g/dL, and who were discharged from the ED. RESULTS: One hundred twenty-seven encounters (117 unique patients, mean 40 years of age) met the eligibility criteria. No patients were hemodynamically unstable and clinically significant active bleeding was rare (6%). Blood transfusion was administered during 70 (55%) encounters, with ≥2 units given to more than half (53%) of those transfused. Subsequent ED visits (14%) and transfusions (16%) during the follow-up period were common. CONCLUSION: In this cohort of adult females with moderate to severe IDA caused by uterine bleeding, blood transfusion was often administered in the absence of hemodynamic instability or active hemorrhage, iron deficiency was inadequately treated, and a high rate of subsequent transfusions occurred. Future studies should investigate optimal indications for transfusion and emphasize adequate iron supplementation.

5.
Genet Med ; 22(8): 1401-1406, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32376981

RESUMO

PURPOSE: To better understand the longitudinal risks and benefits of telephone disclosure of genetic test results in the era of multigene panel testing. METHODS: Adults who were proceeding with germline cancer genetic testing were randomized to telephone disclosure (TD) with a genetic counselor or in-person disclosure (IPD) (i.e., usual care) of test results. All participants who received TD were recommended to return to meet with a physician to discuss medical management recommendations. RESULTS: Four hundred seventy-three participants were randomized to TD and 497 to IPD. There were no differences between arms for any cognitive, affective, or behavioral outcomes at 6 and 12 months. Only 50% of participants in the TD arm returned for the medical follow-up appointment. Returning was associated with site (p < 0.0001), being female (p = 0.047), and not having a true negative result (p < 0.002). Mammography was lower at 12 months among those who had TD and did not return for medical follow-up (70%) compared with those who had TD and returned (86%) and those who had IPD (87%, adjusted p < 0.01). CONCLUSION: Telephone disclosure of genetic test results is a reasonable alternative to in-person disclosure, but attention to medical follow-up may remain important for optimizing appropriate use of genetic results.

7.
J Pediatr ; 222: 141-145.e1, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32444225

RESUMO

OBJECTIVE: To evaluate trends in diagnosis and management of iron deficiency anemia using a large national children's hospital database in pediatric patients admitted with inflammatory bowel disease (IBD). STUDY DESIGN: In this retrospective multicenter cohort study, we used the Pediatric Health Information System de-identified administrative database. Patients age <21 years with ≥2 admissions with International Classification of Disease, Ninth Revision and Tenth Revision codes for Crohn's disease or ulcerative colitis from 2012 to 2018 were included. We extracted data regarding diagnoses of anemia and/or iron deficiency, and receipt of oral iron, intravenous (IV) iron, and/or blood transfusion. Data were analyzed descriptively. RESULTS: We identified 8007 unique patients meeting study criteria for a total of 28 260 admissions. The median age at admission was 15.4 years. A diagnosis of anemia was documented in 29.8% of admissions and iron studies were performed in 12.6%. IV iron was given in 6.3% of admissions and blood transfusions in 7.4%. The prevalence of the diagnosis of anemia among IBD admissions increased from 24.6% in 2012 to 32.4% in 2018 (P < .0001). There was a steady increase in the proportion of IBD admissions that used IV iron, from 3.5% in 2012 to 10.4% in 2018 (P < .0001), and the proportion of admissions with red cell transfusions decreased over time from 9.4% to 4.4% (P < .0001). CONCLUSIONS: Iron deficiency anemia is prevalent among pediatric patients with IBD admitted to US children's hospitals. From 2012 to 2018, there was an increase in the use of inpatient IV iron for the treatment of iron deficiency anemia and a decrease in transfusions.


Assuntos
Anemia Ferropriva/etiologia , Anemia Ferropriva/terapia , Transfusão de Sangue , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Compostos Férricos/uso terapêutico , Óxido de Ferro Sacarado/uso terapêutico , Hematínicos/uso terapêutico , Complexo Ferro-Dextran/uso terapêutico , Adolescente , Anemia Ferropriva/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Hospitalização , Humanos , Lactente , Masculino , Prevalência , Estudos Retrospectivos , Adulto Jovem
8.
Breast Cancer Res Treat ; 181(1): 181-188, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32246378

RESUMO

PURPOSE: Women with Li-Fraumeni syndrome (LFS), a cancer predisposition syndrome caused by germline mutations in TP53, have an over 50% risk of developing breast cancer by age 70. Patients with LFS are at risk for radiation-induced malignancies; however, only small case series have prior investigated radiation risks in the treatment of breast cancer. We therefore aimed to investigate the risk of malignancy in breast cancer patients with LFS following adjuvant radiotherapy. METHODS: A single-institution retrospective chart review was conducted for female breast cancer patients with confirmed germline TP53 mutation. The frequency of radiation-induced malignancies in LFS patients was compared to non-LFS breast cancer cases reported in the Penn Medicine Cancer Registry via statistical analyses. RESULTS: We identified 51 female LFS breast cancer patients with 74 primary diagnoses. Fifty-seven% had a history of breast cancer only, and 25% had breast cancer as their presenting diagnosis of LFS. LFS-associated breast cancers were predominantly invasive ductal carcinoma (48%) and HER2+ (58%). Twenty patients underwent adjuvant radiotherapy with a median follow-up of 12.5 (2-20) years. Of 18 patients who received radiation in a curative setting, one (6%) patient developed thyroid cancer, and one (6%) patient developed sarcoma in the radiation field. This risk for radiation-induced malignancy associated with LFS was higher for both sarcoma and thyroid cancer in comparison with the control cohort. CONCLUSIONS: We found a lower risk of radiation-induced secondary malignancies in LFS breast cancer patients than previously reported in the literature (33% risk of radiation-induced sarcoma). These findings suggest that LFS may not be an absolute contraindication for radiotherapy in breast cancer. The potential risk for locoregional recurrence without radiotherapy must be weighed against the long-term risk for radiation-induced malignancies in consideration of adjuvant radiotherapy for LFS breast cancer patients.

9.
Clin Genet ; 97(4): 601-609, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32022897

RESUMO

Although multigene panel testing (MGPT) is increasingly utilized in clinical practice, there remain limited data on patient-reported outcomes. BRCA 1/2 negative patients were contacted and offered MGPT. Patients completed pre- and posttest counseling, and surveys assessing cognitive, affective and behavioral outcomes at baseline, postdisclosure and 6 and 12 months. Of 317 eligible BRCA1/2 negative patients who discussed the study with research staff, 249 (79%) enrolled. Decliners were more likely to be older, non-White, and recruited by mail or email. Ninety-five percent of enrolled patients proceeded with MGPT. There were no significant changes in anxiety, depression, cancer specific distress or uncertainty postdisclosure. There were significant but small increases in knowledge, cancer-specific distress and depression at 6-12 months. Uncertainty declined over time. Those with a VUS had significant decreases in uncertainty but also small increases in cancer specific distress at 6 and 12 months. Among those with a positive result, medical management recommendations changed in 26% of cases and 2.6% of all tested. Most BRCA1/2 negative patients have favorable psychosocial outcomes after receipt of MGPT results, although small increases in depression and cancer-specific worry may exist and may vary by result. Medical management changed in few patients.

10.
J Pediatr ; 219: 202-208, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32014276

RESUMO

OBJECTIVE: To characterize barriers to and facilitators of successful iron therapy in young children with iron deficiency anemia (IDA) from an in-depth parental perspective. STUDY DESIGN: Prospective, mixed methods study of children age 9 months to 4 years with a diagnosis of nutritional IDA by clinical history and laboratory criteria and their parents. Clinical data were obtained from the electronic health record. Semistructured interviews focused on knowledge of IDA, clinical effects, experience with iron therapies, and motivation were conducted with the parent who identified as the child's primary caregiver. RESULTS: Twenty patient-parent dyads completed the study; 80% (n = 16) identified as Hispanic/Latino (white). Patients' median age was 23 months (50% male); median initial hemoglobin concentration was 8.2 g/dL and duration of oral iron therapy was 3 months. Parents' median age was 29 years (85% female); 8 interviews (40%) were conducted in Spanish. Barriers included difficulty in administering oral iron owing to side effects and poor taste. Facilitators included provision of specific instructions; support from healthcare providers and additional caregivers at home; motivation to benefit child's health, which was strengthened by strong emotional reactions (ie, stress, anxiety) to therapy and follow-up; and an appreciation of child's improvement with successful completion of therapy. CONCLUSIONS: Our findings support the need for interventions designed to promote oral iron adherence in children with IDA. Rather than focusing on knowledge content related to IDA, interventions should aim to increase parental motivation by emphasizing the health benefits of adhering to iron therapy and avoiding more invasive interventions.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Ferro/administração & dosagem , Administração Oral , Adulto , Pré-Escolar , Feminino , Acesso aos Serviços de Saúde , Humanos , Lactente , Masculino , Pais , Estudos Prospectivos
11.
J Pediatr Hematol Oncol ; 42(8): e765-e767, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31568176

RESUMO

Sulfhemoglobinemia (SulfHb) is a rare dyshemoglobinemia that can present with cyanosis in the absence of respiratory distress. It has been reported secondary to drug ingestion and chronic constipation. We present a case of SulfHb in an adolescent female with spina bifida and neurogenic bladder in the setting of an Escherichia coli urinary tract infection. An arterial blood gas differentiated a dyshemoglobinemia from other causes of hypoxemia. The resolution was achieved with antibiotics and red cell transfusion. Here we review the pathophysiology of SulfHb and contribute a unique case report to the limited body of literature on this topic.

12.
J Pediatr ; 216: 58-66.e1, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610927

RESUMO

OBJECTIVE: To evaluate the prevalence of iron deficiency and its association with outcomes in children with heart failure. STUDY DESIGN: A single-center retrospective cohort study of patients with heart failure aged 1-21 years from July 2012 to June 2017 with available serum iron studies was performed. Subjects were analyzed in 2 groups: biventricular systolic heart failure (BiV) and single-ventricle congenital heart disease with systolic heart failure (SV). Iron deficiency was defined as ≥2 of the following: serum iron <50 µg/dL, serum ferritin <20 ng/mL, transferrin >300 ng/mL, or transferrin saturation <15%. The primary outcome was a composite adverse event (CAE) of ventricular assist device implantation, heart transplantation, or death, at 3 and 6 months from time of iron studies. RESULTS: Of the 107 subjects (77 BiV, 30 SV) included in the study, 56% were iron deficient. Demographics, etiology of heart failure, and chronicity of heart failure symptoms were not associated with iron deficiency. On multivariable analysis, in group BiV, iron deficiency was associated with CAE at 3 months (79% iron deficiency in CAE group vs 37% iron deficiency in non-CAE, P = .001, OR 7, 95% CI 2-21) and 6 months (76% iron deficiency in CAE vs 35% iron deficiency in non-CAE, P = .002, OR 7, 95% CI 2-24). In group SV, iron deficiency was associated with CAE at 6 months (79% iron deficiency in CAE vs 29% iron deficiency in non-CAE, P = .014, OR 8, 95% CI 2-32). CONCLUSIONS: Iron deficiency was present in 56% of the pediatric patients with heart failure who were evaluated with iron studies. Iron deficiency was associated with greater risk of ventricular assist device implantation, heart transplantation, or death.


Assuntos
Anemia Ferropriva/epidemiologia , Insuficiência Cardíaca/mortalidade , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Insuficiência Cardíaca/cirurgia , Transplante de Coração/estatística & dados numéricos , Coração Auxiliar/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Estudos Retrospectivos
14.
Pediatr Blood Cancer ; 67(4): e28146, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31886613

RESUMO

BACKGROUND: Autoimmune neutropenia (AIN) is a common cause of chronic neutropenia in childhood. Despite an expected benign clinical course, many patients undergo extensive evaluation. Data on healthcare utilization and rates of bloodstream infections in young patients with AIN are limited. METHODS: All patients with a diagnosis code of leukopenia, neutropenia, or AIN followed within the outpatient hematology clinic of a single institution from 2014 to 2016 were identified. Patients aged ≤5 years with absolute neutrophil count (ANC) ≤500/µL persisting for ≥3 months, a clinical diagnosis of AIN, and documented resolution of neutropenia were included. Data on clinical management, including infectious outcomes and emergency center (EC) encounters, were collected. RESULTS: Forty-three patients with AIN (18 male [42%], median age at diagnosis 12 months) met eligibility criteria. Children were followed by hematology for a median duration of 18 (range, 2-85) months. Diagnostic evaluations were variable. Thirty patients (70%) had ≥ 1 EC encounters for evaluation of isolated fever with a total of 113 EC encounters for the overall cohort. Patients with ANC < 500/µL and isolated fever were admitted for observation, which resulted in 24 hospitalizations in 16 patients. Of 138 blood cultures drawn, two were positive, both later determined to be contaminants. CONCLUSION: At a large tertiary care center, no bloodstream infections were identified in a cohort of 43 children with AIN presenting to the EC for assessment of fever. A less-intensive, more cost-effective management paradigm, which continues to prioritize patient safety, among young children with AIN is needed.


Assuntos
Doenças Autoimunes/complicações , Bacteriemia/prevenção & controle , Infecções/diagnóstico , Neutropenia/complicações , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Bacteriemia/diagnóstico , Bacteriemia/etiologia , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Infecções/economia , Infecções/etiologia , Masculino , Prognóstico , Estudos Retrospectivos
15.
Curr Treat Options Gastroenterol ; 17(4): 636-649, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31761969

RESUMO

PURPOSE OF REVIEW: Advances in genomics have led to the discovery of multiple predisposition genes linked to increased risk for gastrointestinal (GI) cancer. The goal of this review is to assist physicians and allied health care professionals in understanding the current paradigm shift in clinical genetic testing for hereditary GI cancer predisposition syndromes; with a focus on multigene panel testing (MGPT) and test results interpretation. Additionally, this review introduces direct-to-consumer and at-home genetic testing. Both delivery models are increasing in popularity and clinicians will be expected to address results from patients who utilize these approaches. RECENT FINDINGS: Technological advancement and reduced costs have transformed the genetic testing approach from single syndrome genetic testing to broad-based MGPT. MGPT has the benefit of aiding in efficient genetic diagnosis; however, clinicians should be knowledgeable of possible results including variants of uncertain significance, secondary findings, and pathogenic variants within high- and low-to-moderate risk genes, as well as genes for which risks are ill-defined. The landscape of clinical cancer genetics continues to evolve rapidly. Timely updates are critical to ensure the medical community is familiar with current considerations and ongoing challenges regarding genetic testing for hereditary GI cancer susceptibility.

16.
Can J Urol ; 26(5 Suppl 2): 57-59, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31629436

RESUMO

Demand for cancer genetic counseling has grown rapidly in recent years as germline genomic information has integrated into cancer care. There are currently an insufficient number of genetic counselors (GC) to address genetic testing need through traditional pre- and post-test counseling. Alternative genetic counseling frameworks, discussed here, are under study to increase access to genetic testing while optimizing the skillsets of existent master's-trained GCs.


Assuntos
Aconselhamento Genético , Testes Genéticos , Neoplasias da Próstata/diagnóstico , Assistência à Saúde/métodos , Humanos , Masculino , Neoplasias da Próstata/genética
17.
J Emerg Med ; 57(5): 637-645, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31629581

RESUMO

BACKGROUND: Iron deficiency anemia is the most common hematologic disorder in the United States and worldwide. Yet, clinical guidelines for the identification and management of this disorder in the emergency department are lacking. OBJECTIVE OF REVIEW: This clinical review examines strategies for identifying and treating iron deficiency anemia in the emergency department, with a focus on the role of oral iron therapy, intravenous iron therapy, as well as red blood cell transfusion. The article highlights both the available evidence on this topic and the need for future research. DISCUSSION: The diagnosis of iron deficiency anemia has important clinical implications and, although testing is generally straightforward, it may be under-recognized. The scant literature available describing emergency department practice patterns for iron deficiency anemia suggests there is room for improvement. In particular, intravenous iron may be underutilized and red blood cell transfusions administered too liberally. CONCLUSIONS: Iron deficiency anemia is common and many patients can be treated effectively with oral iron. For selected patients with moderate-to-severe iron deficiency anemia, intravenous iron is safe and more effective than oral iron. Red blood cell transfusions should be used rarely for hemodynamically stable patients with iron deficiency irrespective of hemoglobin levels.


Assuntos
Anemia Ferropriva/diagnóstico , Anemia Ferropriva/tratamento farmacológico , Contagem de Células Sanguíneas , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Transfusão de Eritrócitos/efeitos adversos , Transfusão de Eritrócitos/métodos , Humanos , Ferro/análise , Ferro/sangue , Ferro/uso terapêutico
18.
Artigo em Inglês | MEDLINE | ID: mdl-31511844

RESUMO

PURPOSE: Tumor-only genomic profiling (TGP) is increasingly advocated for all patients with cancer given the possible therapeutic implications. It is critical to develop clinical algorithms to identify and address potentially actionable germline findings identified by TGP. METHODS: A multidisciplinary team analyzed publicly available data for genes in which mutations are implicated in germline cancer susceptibility and established a pipeline to automate clinical referral for evaluation of TGP findings. RESULTS: A total of 2,308 patients underwent TGP, with 81 patients (3.5%) identified by the automatic referral pipeline; 37 patients (1.6%) were referred outside the pipeline based on concerns by the molecular geneticist, pathologist, or oncologist regarding genotype-phenotype correlation. Thirty-one patients (38%) and 17 patients (46%) underwent germline testing from the automatic pipeline and other referrals, respectively, and of these patients, 23 (72%) and four (24%) had confirmed germline pathogenic variants (GPVs), respectively. The majority of confirmed GPVs were in automatic referral genes, with BRCA2 being most common (confirmed GPVs in 11 [85%] of 13 patients tested), followed by PALB2 (five [67%] of six patients), BRCA1 (two [40%] of five patients), MSH6 (two of three patients), and MLH1 (two of two patients). Forty-eight percent of confirmed GPVs were found in tumors known to be associated with germline mutations in the gene. Germline testing was not performed in 50 (62%) of 81 patients identified by automatic referral as a result of poor patient health or death (30%), lack of follow-up (30%), and patient refusal (30%). CONCLUSION: Of patients undergoing TGP, 5% had somatic findings triggering referral, and implementation of an automatic referral pipeline based solely on gene versus other clinical or molecular features resulted in a 74% germline confirmation. However, only 41% of referred patients underwent germline testing. Systems-based approaches are needed to identify carriers of actionable germline cancer susceptibility mutations identified by TGP.

19.
Eur Urol ; 76(6): 831-842, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31537406

RESUMO

BACKGROUND: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations. OBJECTIVE: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status. DESIGN, SETTING, AND PARTICIPANTS: Men aged 40-69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians. RESULTS AND LIMITATIONS: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p = 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65). CONCLUSIONS: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers. PATIENT SUMMARY: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening.

20.
Mol Genet Genomic Med ; 7(9): e898, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31376244

RESUMO

BACKGROUND: While there is increasing interest in sharing genetic research results with participants, how best to communicate the risks, benefits and limitations of research results remains unclear. METHODS: Participants who received genetic research results answered open and closed-ended questions about their experiences receiving results and interest in and advantages and disadvantages of a web-based alternative to genetic counseling. RESULTS: 107 BRCA1/2 negative women with a personal or family history of breast cancer consented to receive genetic research results and 82% completed survey items about their experience. Most participants reported there was nothing they disliked (74%) or would change (85%) about their predisclosure or disclosure session (78% and 89%). They most frequently reported liking the genetic counselor and learning new information. Only 24% and 26% would not be willing to complete predisclosure counseling or disclosure of results by a web-based alternative, respectively. The most frequently reported advantages included convenience and reduced time. Disadvantages included not being able to ask questions, the risk of misunderstanding and the impersonal nature of the encounter. CONCLUSION: Most participants receiving genetic research results report high satisfaction with telephone genetic counseling, but some may be willing to consider self-directed web alternatives for both predisclosure genetic education and return of results.


Assuntos
Neoplasias da Mama/genética , Aconselhamento Genético , Predisposição Genética para Doença , Testes Genéticos , Satisfação do Paciente , Adulto , Idoso , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade
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