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1.
Hum Mol Genet ; 32(9): 1457-1465, 2023 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-36458889

RESUMEN

Mosaic variants in the PIK3CA gene, encoding the catalytic subunit of phosphoinositide 3-kinase (PI3K), produce constitutive PI3K activation, which causes PIK3CA-related overgrowth spectrum disorders. To date, fewer than 20 patients have been described with germline alterations in PIK3CA. In this study, we describe three unrelated individuals with overgrowth and germline PIK3CA variants. These variants were discovered through whole-exome sequencing and confirmed as germline by testing multiple tissue types, when available. Functional analysis using Patient 1's fibroblast cell line and two previously reported patients' cell lines showed increased phosphorylation of AKT during cellular starvation revealing constitutive activation of the phosphoinositide-3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway. Alternatively, stimulation of the cells by fetal bovine serum produced a reduced response, indicating an activated status of the PI3K complex reducing the pathway response to further external stimulation. Additional studies utilizing Biolog Phenotype Microarray technology indicated reduced energy production when cells were exposed to growth factors stimulating the PI3K/AKT/mTOR pathway, confirming the trend observed in the AKT phosphorylation test after stimulation. Furthermore, treatment with inhibitors of the PI3K/AKT/mTOR pathway rescued the normal energy response in the patients' cells. Collectively, these data demonstrate that disease-causing germline PIK3CA variants have a functional consequence, similar to mosaic variants in the PI3K/AKT/mTOR pathway.


Asunto(s)
Fosfatidilinositol 3-Quinasa Clase I , Enfermedades Genéticas Congénitas , Fosfatidilinositol 3-Quinasa Clase I/genética , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Células Germinativas/metabolismo , Mutación , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Enfermedades Genéticas Congénitas/genética , Enfermedades Genéticas Congénitas/metabolismo , Enfermedades Genéticas Congénitas/fisiopatología , Mutación de Línea Germinal , Fosforilación
2.
Breast Cancer Res Treat ; 206(3): 575-583, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38662118

RESUMEN

PURPOSE: The skin and/or nipple-sparing approach has become an oncologically sound and desirable choice for women choosing mastectomy. Indocyanine green (ICG) perfusion imaging has been shown to reduce ischemic complications in mastectomy skin flaps. Immediate reconstruction requires a well-vascularized skin flap capable of tolerating full expansion. Identification of the perforating subcutaneous vessels to the skin envelope may allow for better and more consistent blood vessel preservation and flap perfusion. METHODS: The authors conducted an institutional review board-approved prospective study with 41 patients to assess the feasibility of using ICG perfusion imaging to visualize, cutaneously map, and preserve the vessels that supply the skin flap and nipple-areolar complex. For each patient, the number of vessels initially mapped, the number of vessels preserved, the extent to which each vessel was preserved, and the proportion of the flap with adequate perfusion (as defined by the SPY-Q > 20% threshold) was recorded and analyzed. RESULTS: Vessels were able to be identified and marked in a high majority of patients (90%). There was a moderate linear relationship between the number of vessels marked and the number preserved. Successful mapping of vessels was associated with lower rates of wound breakdown (p = 0.036). Mapping and preserving at least one vessel led to excellent flap perfusion (> 90%). No increase in complications was observed from utilizing ICG angiography preoperatively. CONCLUSION: This prospective study using preoperative ICG perfusion mapping demonstrated safety, feasibility, and good prognostic outcomes. LEVEL OF EVIDENCE: III.


Asunto(s)
Neoplasias de la Mama , Verde de Indocianina , Pezones , Humanos , Femenino , Pezones/cirugía , Pezones/irrigación sanguínea , Persona de Mediana Edad , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/diagnóstico por imagen , Adulto , Anciano , Colgajos Quirúrgicos/irrigación sanguínea , Angiografía/métodos , Estudios Prospectivos , Mastectomía/métodos , Mastectomía/efectos adversos , Piel/irrigación sanguínea , Piel/diagnóstico por imagen , Mamoplastia/métodos , Tratamientos Conservadores del Órgano/métodos
3.
Curr Issues Mol Biol ; 45(2): 954-962, 2023 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-36826006

RESUMEN

Sclerosing polycystic adenoma (SPA) is a rare neoplasm occurring in the salivary glands, mainly the parotid gland. Although it was originally thought to represent a non-neoplastic process, recent genetic data have proven its monoclonality, supporting its neoplastic origin. We report a case of a 73-year-old woman who presented with left neck swelling and pain. A 3 cm hypoechoic, heterogeneous, solid mass was identified on neck ultrasonography within the left parotid gland. Fine needle aspiration revealed benign acinar cells and lymphocytes. Left partial superficial parotidectomy was performed and a diagnosis of SPA was made. Targeted next-generation sequencing (NGS) revealed three clinically significant alterations in the PIK3R1, HRAS, and AR genes. Alterations in the PIK3R1 gene have been previously reported in cases of SPA; however, this study is the first to report two novel clinically significant genomic alterations in the HRAS and AR genes. AR protein expression by immunohistochemistry was strongly and diffusely positive in the neoplastic epithelial cells compared to the adjacent normal salivary gland tissue, which was dead negative for AR. This molecular profile will enhance our understanding of the molecular pathways underlying the development of this tumor. Although this entity was initially thought to be a reactive process, evidence from our case and similar cases strongly support the notion that it is neoplastic due to the presence of specific genetic alterations linked to it.

4.
Am J Hum Genet ; 107(6): 1096-1112, 2020 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-33232675

RESUMEN

SWI/SNF-related intellectual disability disorders (SSRIDDs) are rare neurodevelopmental disorders characterized by developmental disability, coarse facial features, and fifth digit/nail hypoplasia that are caused by pathogenic variants in genes that encode for members of the SWI/SNF (or BAF) family of chromatin remodeling complexes. We have identified 12 individuals with rare variants (10 loss-of-function, 2 missense) in the BICRA (BRD4 interacting chromatin remodeling complex-associated protein) gene, also known as GLTSCR1, which encodes a subunit of the non-canonical BAF (ncBAF) complex. These individuals exhibited neurodevelopmental phenotypes that include developmental delay, intellectual disability, autism spectrum disorder, and behavioral abnormalities as well as dysmorphic features. Notably, the majority of individuals lack the fifth digit/nail hypoplasia phenotype, a hallmark of most SSRIDDs. To confirm the role of BICRA in the development of these phenotypes, we performed functional characterization of the zebrafish and Drosophila orthologs of BICRA. In zebrafish, a mutation of bicra that mimics one of the loss-of-function variants leads to craniofacial defects possibly akin to the dysmorphic facial features seen in individuals harboring putatively pathogenic BICRA variants. We further show that Bicra physically binds to other non-canonical ncBAF complex members, including the BRD9/7 ortholog, CG7154, and is the defining member of the ncBAF complex in flies. Like other SWI/SNF complex members, loss of Bicra function in flies acts as a dominant enhancer of position effect variegation but in a more context-specific manner. We conclude that haploinsufficiency of BICRA leads to a unique SSRIDD in humans whose phenotypes overlap with those previously reported.


Asunto(s)
Proteínas Cromosómicas no Histona/genética , Discapacidades del Desarrollo/genética , Mutación Missense , Fenotipo , Proteínas Supresoras de Tumor/genética , Adolescente , Animales , Niño , Preescolar , Proteínas de Drosophila/genética , Drosophila melanogaster , Femenino , Genes Dominantes , Variación Genética , Haploinsuficiencia , Humanos , Lactante , Masculino , Microscopía Confocal , Neuroglía/metabolismo , Neuronas/metabolismo , Unión Proteica , Pez Cebra , Proteínas de Pez Cebra/genética
5.
Ann Surg Oncol ; 30(10): 6053-6058, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37505353

RESUMEN

BACKGROUND: Breast-conserving surgery (BCS) is a mainstay for breast cancer management, and obtaining negative margins is critical. Some have advocated for the use of preoperative magnetic resonance imaging (MRI) in reducing positive margins after BCS. We sought to determine whether preoperative MRI was associated with reduced positive margins. PATIENTS AND METHODS: The SHAVE/SHAVE2 trials were multicenter trials in ten US centers with patients with stage 0-3 breast cancer undergoing BCS. Use of preoperative MRI was at the discretion of the surgeon. We evaluated whether or not preoperative MRI was associated with margin status prior to randomization regarding resection of cavity with shave margins. RESULTS: A total of 631 patients participated. Median age was 64 (range 29-94) years, with a median tumor size of 1.3 cm (range 0.1-9.3 cm). Patient factors included 26.1% of patients (165) had palpable tumors, and 6.5% (41) received neoadjuvant chemotherapy. Tumor factors were notable for invasive lobular histology in 7.0% (44) and extensive intraductal component (EIC) in 32.8% (207). A preoperative MRI was performed in 193 (30.6%) patients. Those who underwent preoperative MRI were less likely to have a positive margin (31.1% versus 38.8%), although this difference was not statistically significant (p = 0.073). On multivariate analysis, controlling for patient and tumor factors, utilization of preoperative MRI was not a significant factor in predicting margin status (p = 0.110). Rather, age (p = 0.032) and tumor size (p = 0.040) were the only factors associated with margin status. CONCLUSION: These data suggest that preoperative MRI is not associated margin status; rather, patient age and tumor size are the associated factors.


Asunto(s)
Neoplasias de la Mama , Carcinoma Ductal de Mama , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/cirugía , Carcinoma Ductal de Mama/patología , Imagen por Resonancia Magnética/métodos , Márgenes de Escisión , Mastectomía Segmentaria/métodos
6.
Ann Surg Oncol ; 29(10): 6225-6233, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35951135

RESUMEN

BACKGROUND: We sought to better understand breast-specific sensuality (BSS) in sexually inactive breast cancer survivors. METHODS: We conducted an anonymous cross-sectional survey of breast cancer survivors during surveillance appointments from 2014 to 2016. Sexual inactivity was defined as no sexual activity within 4 weeks prior. Categorical data were analyzed using Fisher's exact test. Multiple logistic regression adjusted for age and menopausal status, and Firth's bias correction accommodated sparse data. RESULTS: Of 585 respondents, 546 (93.3%) were between the ages of 40 and 79 years, of whom 285 (48.7%) were sexually inactive. Favorable post-treatment appearance satisfaction was reported by 413 (71.0%) respondents. Sexually inactive respondents were more likely to score discomfort with their partner seeing their chest after surgery compared with sexually active respondents (41 [20.4%] vs. 34 [11.4%]; p = 0.002). Both sexually inactive and active respondents reported that their chest was important in intimacy after surgery but at significantly different rates (117 [44.3%] vs. 217 [72.6%]; p < 0.001). Post-surgical appearance satisfaction for sexually inactive respondents was positively associated with level of comfort with partner seeing their chest after surgery (p < 0.001) and with rating of a pleasurable caress of the treated breast (p < 0.001). CONCLUSIONS: Over 40% of sexually inactive respondents reported their chest was important in intimacy after surgery, suggesting that BSS may be a route to intimacy for sexually inactive breast cancer survivors. Post-surgical breast appearance satisfaction significantly correlated with comfort being seen by one's partner and appreciation of a pleasurable breast caress. Optimizing breast cancer surgical aesthetic outcomes may improve survivorship.


Asunto(s)
Neoplasias de la Mama , Supervivientes de Cáncer , Adulto , Anciano , Neoplasias de la Mama/cirugía , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Encuestas y Cuestionarios , Sobrevivientes , Supervivencia
7.
J Surg Res ; 279: 393-397, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35835032

RESUMEN

INTRODUCTION: De-escalation of breast cancer treatment aims to reduce patient and financial toxicity without compromising outcomes. Level I evidence and National Comprehensive Cancer Network guidelines support omission of adjuvant radiation in patients aged >70 y with hormone-sensitive, pT1N0M0 invasive breast cancer treated with endocrine therapy. We evaluated radiation use in patients eligible for guideline concordant omission of radiation. METHODS: Subgroup analysis of patients eligible for radiation omission from two pooled randomized controlled trials, which included stage 0-III breast cancer patients undergoing breast conserving surgery, was performed to evaluate factors associated with radiation use. RESULTS: Of 631 patients, 47 (7.4%) met radiation omission criteria and were treated by 14 surgeons at eight institutions. The mean age was 75.3 (standard deviation + 4.4) y. Majority of patients identified as White (n = 46; 97.9%) and non-Hispanic (n = 44; 93.6%). The mean tumor size was 1.0 cm; 37 patients (88.1%) had ductal, 4 patients (9.5%) had lobular, and 17 patients (40.5%) had low-grade disease. Among patients eligible for radiation omission, 34 (72.3%) patients received adjuvant radiation. Those who received radiation were significantly younger than those who did not (74 y, interquartile range = 4 y, versus 78 y, interquartile range = 11 y, P = 0.03). There was no difference in radiation use based on size (P = 0.4), histology (P = 0.5), grade (P = 0.7), race (P = 1), ethnicity (P = 0.6), institution (P = 0.1), gender of the surgeon (P = 0.7), or surgeon (P = 0.1). CONCLUSIONS: Fewer than 10% of patients undergoing breast conservation met criteria for radiation omission. Nearly three-quarters received radiation therapy with younger age being a driver of radiation use, suggesting ample opportunity for de-escalation, particularly among younger eligible patients.


Asunto(s)
Neoplasias de la Mama , Carcinoma in Situ , Anciano , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Carcinoma in Situ/cirugía , Tratamiento Conservador , Femenino , Hormonas , Humanos , Mastectomía Segmentaria , Radioterapia Adyuvante
8.
AJR Am J Roentgenol ; 218(2): 249-257, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34523954

RESUMEN

BACKGROUND. Prior studies comparing cancer screening by digital breast tomosynthesis (DBT) and digital mammography (DM) have largely entailed prospective trials and investigations at tertiary academic centers, which may encounter high-risk patient populations and lack heterogeneity among interpreting radiologists. Thus, results may not generalize across real-world community settings in the United States. OBJECTIVE. The purpose of this study was to compare DBT and DM in terms of screening performance and tumor characteristics of screen-detected cancers in a community practice setting. METHODS. Data were retrospectively retrieved for all screening mammography examinations performed by DBT or DM at four outpatient private practice facilities from January 1, 2012, to July 10, 2019. Examinations were interpreted by one of 26 radiologists (21 breast radiologists, five general radiologists). Further detailed information was recorded from radiology and pathology reports for all screen-detected cancers. Statistical comparisons were performed between DBT and DM in terms of screening performance and tumor characteristics of screen-detected cancers. RESULTS. A total of 310 cancers were detected in 47,096 screening DBT examinations and 83,200 screening DM examinations. Cancer detection rate was higher (p < .001) for DBT (3.4 per 1000 women) than for DM (1.8 per 1000 women). PPV1 was higher (p < .001) for DBT (3.5% [161/4641]) than for DM (2.1% [149/7116]). Patients with DBT-detected cancer were younger than those with DM-detected cancer (mean age [range], 61 years [40-87 years] vs 64 years [37-88 years]; p = .02). A greater percentage of DBT-detected than DM-detected cancers were invasive (85.1% [137/161] vs 72.5% [108/149]; p = .006), grade 1 when invasive (27.9% [38/136] vs 17.8% [19/107]; p = .04), and node negative (92.2% [71/77] vs 78.4% [58/74]; p = .02). Cancers detected by DBT and DM were not significantly different in histologic subtype, molecular subtype, or mean size (all p > .05). CONCLUSION. DBT showed a higher cancer detection rate and PPV1 than DM, and patients were younger at cancer diagnosis with DBT. Cancers detected on DBT were more often invasive, grade 1, and node negative. CLINICAL IMPACT. The findings support the generalizability of insights into DBT-based screening, which previously have been investigated primarily in academic settings.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Detección Precoz del Cáncer/métodos , Mamografía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Mama/diagnóstico por imagen , Servicios de Salud Comunitaria/métodos , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos
9.
Am J Hum Genet ; 102(4): 696-705, 2018 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-29606302

RESUMEN

AEBP1 encodes the aortic carboxypeptidase-like protein (ACLP) that associates with collagens in the extracellular matrix (ECM) and has several roles in development, tissue repair, and fibrosis. ACLP is expressed in bone, the vasculature, and dermal tissues and is involved in fibroblast proliferation and mesenchymal stem cell differentiation into collagen-producing cells. Aebp1-/- mice have abnormal, delayed wound repair correlating with defects in fibroblast proliferation. In this study, we describe four individuals from three unrelated families that presented with a unique constellation of clinical findings including joint laxity, redundant and hyperextensible skin, poor wound healing with abnormal scarring, osteoporosis, and other features reminiscent of Ehlers-Danlos syndrome (EDS). Analysis of skin biopsies revealed decreased dermal collagen with abnormal collagen fibrils that were ragged in appearance. Exome sequencing revealed compound heterozygous variants in AEBP1 (c.1470delC [p.Asn490_Met495delins(40)] and c.1743C>A [p.Cys581∗]) in the first individual, a homozygous variant (c.1320_1326del [p.Arg440Serfs∗3]) in the second individual, and a homozygous splice site variant (c.1630+1G>A) in two siblings from the third family. We show that ACLP enhances collagen polymerization and binds to several fibrillar collagens via its discoidin domain. These studies support the conclusion that bi-allelic pathogenic variants in AEBP1 are the cause of this autosomal-recessive EDS subtype.


Asunto(s)
Alelos , Carboxipeptidasas/genética , Colágeno/metabolismo , Tejido Conectivo/patología , Síndrome de Ehlers-Danlos/genética , Mutación/genética , Proteínas Represoras/genética , Adulto , Secuencia de Aminoácidos , Carboxipeptidasas/química , Niño , Preescolar , Femenino , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Masculino , Dominios Proteicos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Represoras/química , Piel/patología , Piel/ultraestructura , Adulto Joven
10.
Ann Surg ; 273(5): 876-881, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-31290763

RESUMEN

OBJECTIVE: Single-center studies have demonstrated that resection of cavity shave margins (CSM) halves the rate of positive margins and re-excision in breast cancer patients undergoing partial mastectomy (PM). We sought to determine if these findings were externally generalizable across practice settings. METHODS: In this multicenter randomized controlled trial occurring in 9 centers across the United States, stage 0-III breast cancer patients undergoing PM were randomly assigned to either have resection of CSM ("shave" group) or not ("no shave" group). Randomization occurred intraoperatively, after the surgeon had completed their standard PM. Primary outcome measures were positive margin and re-excision rates. RESULTS: Between July 28, 2016 and April 13, 2018, 400 patients were enrolled in this trial. Four patients (2 in each arm) did not meet inclusion criteria after randomization, leaving 396 patients for analysis: 196 in the "shave" group and 200 to the "no shave" group. Median patient age was 65 years (range; 29-94). Groups were well matched at baseline for demographic and clinicopathologic factors. Prior to randomization, positive margin rates were similar in the "shave" and "no shave" groups (76/196 (38.8%) vs. 72/200 (36.0%), respectively, P = 0.604). After randomization, those in the "shave" group were significantly less likely than those in the "no shave" group to have positive margins (19/196 (9.7%) vs. 72/200 (36.0%), P < 0.001), and to require re-excision or mastectomy for margin clearance (17/196 (8.7%) vs. 47/200 (23.5%), P < 0.001). CONCLUSION: Resection of CSM significantly reduces positive margin and re-excision rates in patients undergoing PM.


Asunto(s)
Neoplasias de la Mama/cirugía , Márgenes de Escisión , Mastectomía Segmentaria/métodos , Estadificación de Neoplasias , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
11.
Ann Surg Oncol ; 28(5): 2529-2542, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33221977

RESUMEN

BACKGROUND: Accurate identification of the tumor bed after breast-conserving surgery (BCS) ensures appropriate radiation to the tumor bed while minimizing normal tissue exposure. The BioZorb® three-dimensional (3D) bioabsorbable tissue marker provides a reliable target for radiation therapy (RT) planning and follow-up evaluation while serving as a scaffold to maintain breast contour. METHODS: After informed consent, 818 patients (826 breasts) implanted with the BioZorb® at 14 U.S. sites were enrolled in a national registry. All the patients were prospectively followed with the BioZorb® implant after BCS. The data collected at 3, 6, 12, and 24 months included all demographics, treatment parameters, and provider/patient-assessed cosmesis. RESULTS: The median follow-up period was 18.2 months (range, 0.2-53.4 months). The 30-day breast infection rate was 0.5 % of the patients (n = 4), and re-excision was performed for 8.1 % of the patients (n = 66), whereas 2.6 % of the patients (n = 21) underwent mastectomy. Two patients (0.2 %) had local recurrence. The patient-reported cosmetic outcomes at 6, 12, and 24 months were rated as good-to-excellent by 92.4 %, 90.6 %, and 87.3 % of the patients, respectively and similarly by the surgeons. The radiation oncologists reported planning of target volume (PTV) reduction for 46.2 % of the patients receiving radiation boost, with PTV reduction most commonly estimated at 30 %. CONCLUSIONS: This report describes the first large multicenter study of 818 patients implanted with the BioZorb® tissue marker during BCS. Radiation oncologists found that the device yielded reduced PTVs and that both the patients and the surgeons reported good-to-excellent long-term cosmetic outcomes, with low adverse effects. The BioZorb® 3D tissue marker is a safe adjunct to BCS and may add benefits for both surgeons and radiation oncologists.


Asunto(s)
Neoplasias de la Mama , Implantes Absorbibles , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Humanos , Mastectomía , Mastectomía Segmentaria , Recurrencia Local de Neoplasia/radioterapia , Medición de Resultados Informados por el Paciente
12.
J Intensive Care Med ; 35(9): 903-908, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30244638

RESUMEN

OBJECTIVE: This study investigated the percentage of patients who achieved hemostasis with 4-factor prothrombin complex concentrate (4-factor PCC) 35 U/kg. The primary end point was to determine the effect of 4-factor PCC 35 U/kg on bleeding progression, assessed using computed tomography. METHODS: This was a retrospective, observational, single-center study conducted in patients with a major bleed admitted to a level 1 trauma center from May 1, 2013, to June 15, 2015, who received 4-factor PCC 35 U/kg for reversal of a direct factor Xa inhibitor taken prior to admission. RESULTS: Thirty-three patients were included in the study, with 31 patients in the final analysis. The mean (standard deviation) age was 73 (14.8) years; 54.5% of patients were female. Of the 33 patients, 13 presented with a traumatic brain injury, 9 with an aneurysmal subarachnoid hemorrhage, 8 with an intracerebral hemorrhage, 1 with a gastrointestinal bleed, 1 with a hematoma with active extravasation, and 1 with an intra-abdominal bleed. The most frequently used direct factor Xa inhibitor was rivaroxaban (81.8%). Overall, 83.8% of patients achieved hemostasis with 4-factor PCC 35 U/kg. Progression of hemorrhage was observed in 4 patients on repeat computed tomography scan and 1 patient had continued surgical bleeding. No thromboembolic events were reported. CONCLUSIONS: Low-dose, 4-factor PCC 35 U/kg appeared to produce hemostasis in a majority of the patients. This may be an effective dosing regimen for anticoagulant reversal of factor Xa inhibitors in clinically bleeding patients.


Asunto(s)
Factores de Coagulación Sanguínea/administración & dosificación , Hemorragia/tratamiento farmacológico , Técnicas Hemostáticas , Hemostáticos/administración & dosificación , Anciano , Anticoagulantes/efectos adversos , Resultados de Cuidados Críticos , Inhibidores del Factor Xa/efectos adversos , Femenino , Hemorragia/diagnóstico por imagen , Hemostasis/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
13.
Breast J ; 26(10): 2045-2047, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32755067

RESUMEN

Raynaud's phenomenon of the nipple (RPN) is a cause of nipple pain scarcely reported in the literature and frequently missed by physicians. We present a case of RPN in a pregnant mother who sought breast surgical consultation for episodic nipple pain. Review of the literature reveals RPN is predominant in lactating and pregnant patients and missed diagnosis can cause cessation of breastfeeding or mistreatment with antifungals. Clinical suspicion should be raised if symptoms are precipitated by cold, associated with color change, occur during pregnancy or breastfeeding, or with a history of Raynaud's. Treatment is generally supportive, with nifedipine used for severe cases.


Asunto(s)
Neoplasias de la Mama , Enfermedad de Raynaud , Femenino , Humanos , Lactancia , Pezones , Embarazo , Enfermedad de Raynaud/diagnóstico , Enfermedad de Raynaud/etiología , Dedos del Pie
14.
Ann Surg Oncol ; 26(10): 3159-3165, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31342358

RESUMEN

BACKGROUND: Sexual dysfunction is common for breast cancer survivors. Premenopausal women with breast cancer are increasingly offered ovarian suppression and aromatase inhibitor (AI) therapy. We evaluated the association of menopausal status and treatment modalities on sexual dysfunction. METHODS: We conducted a cross-sectional anonymous Female Sexual Function Index (FSFI) survey of breast cancer survivors between 2000 and 2016. Analysis utilized Kruskal-Wallis test for FSFI scores, Chi square, or Fisher's exact test for categorical data, and regression analysis for associations. RESULTS: Of 585 respondents, 278 (47.5%) had complete FSFI scores. Of these, 24 (8.6%) were premenopausal and 80 (28.8%) were pre/perimenopausal at survey completion. Median FSFI scores for premenopausal (31.2, interquartile range [IQR] 26.8-33.6) and pre/perimenopausal (29.2, IQR 25.9-32.2) were similar, whereas postmenopausal women (25.9, IQR 21.0-30.3) were significantly lower (p = 0.0007 and p = 0.0002, respectively). Premenopausal women were less likely to meet criteria for sexual dysfunction (FSFI score ≤ 26.55) than postmenopausal women (21 versus 55%, p < 0.0001, univariate analysis [odds ratio (OR) 0.32, 95% confidence interval (CI) 0.18-0.56]). Adjusting for treatment modality did not impact the significance (OR 0.43, 95% [CI] 0.23-0.80) but revealed that AIs independently are associated with sexual dysfunction (OR 2.41, 95% CI 1.32-4.40). The interaction between menopausal status and AIs was not significant (p = 0.24). CONCLUSIONS: Our study demonstrates that menopausal status is associated with sexual dysfunction in breast cancer patients and sexual dysfunction in premenopausal women is not impacted by treatment modality outside of aromatase inhibitor therapy. As more premenopausal patients are treated with ovarian suppression, these data may guide clinicians in counseling patients regarding sexual dysfunction expectations.


Asunto(s)
Inhibidores de la Aromatasa/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Supervivientes de Cáncer/psicología , Posmenopausia , Premenopausia , Disfunciones Sexuales Fisiológicas/epidemiología , Adulto , Inhibidores de la Aromatasa/efectos adversos , Neoplasias de la Mama/psicología , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Persona de Mediana Edad , Pronóstico , Rhode Island/epidemiología , Disfunciones Sexuales Fisiológicas/etiología , Encuestas y Cuestionarios
15.
Ann Surg Oncol ; 26(11): 3436-3444, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30977016

RESUMEN

BACKGROUND: Several definitions of oncoplastic surgery have been reported in the literature. In an effort to facilitate communication regarding oncoplastic surgery to patients, trainees, and among colleagues, the American Society of Breast Surgeons (ASBrS) aimed to create a consensus definition and classification system for oncoplastic surgery. METHODS: We performed a comprehensive literature search for oncoplastic surgery definitions using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Following this, a consensus definition and classification system was created by the ASBrS. RESULTS: Overall, 30 articles defining oncoplastic surgery were identified, with several articles contradicting each other. The ASBrS definition for oncoplastic surgery defines this set of breast-conserving operations using volume displacement and volume replacement principles as: "Breast conservation surgery incorporating an oncologic partial mastectomy with ipsilateral defect repair using volume displacement or volume replacement techniques with contralateral symmetry surgery as appropriate". Volume displacement is defined as closing the lumpectomy defect and redistributing the resection volume over the preserved breast, and is divided into two levels: level 1 (< 20%) and level 2 (20-50%). Volume replacement includes those situations when volume is added using flaps or implants to correct the partial mastectomy defect. CONCLUSION: The ASBrS oncoplastic surgery definition and classification system provides language to facilitate discussion and teaching of oncoplastic surgery among breast surgeons, trainees, and patients.


Asunto(s)
Neoplasias de la Mama/cirugía , Mamoplastia/métodos , Mastectomía Segmentaria/métodos , Mastectomía/clasificación , Mastectomía/métodos , Guías de Práctica Clínica como Asunto/normas , Cirujanos/normas , Implantes de Mama , Consenso , Femenino , Humanos , Pronóstico , Sociedades Médicas , Colgajos Quirúrgicos
16.
Ann Surg Oncol ; 26(10): 3052-3062, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31342382

RESUMEN

BACKGROUND: There is limited compensation data for breast surgery benchmarking. In 2018, the American Society of Breast Surgeons conducted its second membership survey to obtain updated compensation data as well as information on practice type and setting. METHODS: In October 2018, a survey was emailed to 2676 active members. Detailed information on compensation was collected, as well as data on gender, training, years in and type of practice, percent devoted to breast surgery, workload, and location. Descriptive statistics and multivariate analyses were performed to analyze the impact of various factors on compensation. RESULTS: The response rate was 38.2% (n = 1022, of which 73% were female). Among the respondents, 61% practiced breast surgery exclusively and 54% were fellowship trained. The majority of fellowship-trained surgeons within 5 years of completion of training (n = 126) were female (91%). Overall, mean annual compensation was $370,555. On univariate analysis, gender, years of practice, practice type, academic position, ownership, percent breast practice, and clinical productivity were associated with compensation, whereas fellowship training, region, and practice setting were not. On multivariate analysis, higher compensation was significantly associated with male gender, years in practice, number of cancers treated per year, and wRVUs. Compensation was lower among surgeons who practiced 100% breast compared with those who did a combination of breast and other surgery. CONCLUSIONS: Differences in compensation among breast surgeons were identified by practice type, academic position, ownership, years of practice, percent breast practice, workload, and gender. Overall, mean annual compensation increased by $40,000 since 2014.


Asunto(s)
Neoplasias de la Mama/cirugía , Mastectomía/economía , Pautas de la Práctica en Medicina/estadística & datos numéricos , Salarios y Beneficios/estadística & datos numéricos , Cirujanos/economía , Neoplasias de la Mama/patología , Becas , Femenino , Humanos , Masculino , Mastectomía/educación , Persona de Mediana Edad , Sociedades Médicas , Encuestas y Cuestionarios , Factores de Tiempo
17.
BMC Cancer ; 19(1): 342, 2019 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-30971201

RESUMEN

BACKGROUND: The surgical treatment of breast cancer has been associated with negative consequences for patients' body image, sexual functioning, mental health, and social adjustment. Recent advances in the surgical approach to breast cancer allow the oncologic surgeon to safely optimize cosmetic outcomes. Little is known about the possible relevance of surgical scars. The aim of this research was to gather the perspective of breast cancer survivors themselves on the issue of surgical scars and their negative impact on survivorship. METHODS: An internet survey was conducted nationwide in the United States among women who reported being surgically treated by lumpectomy, mastectomy, or both procedures for breast cancer. To improve generalizability, census-based enrollment quotas were applied for geographic region, health insurance, and income. RESULTS: The five hundred respondents reported lumpectomy only (n = 215), mastectomy only (n = 140), or both surgeries (n = 132). In response to the statement, "I do not like the location of my surgical scar", 64% of lumpectomy-only respondents and 67% of mastectomy-only respondents agreed somewhat or strongly. Only 26% of lumpectomy respondents and 14% of mastectomy respondents reported minimal or no negative impact as a consequence of the surgical scars. CONCLUSION: Consistent with previous literature, this nationwide US survey shows that the majority of women feel negatively affected by their breast cancer surgery scars. Surgeons should consider this outcome when planning surgery, which may improve patients' survivorship journey.


Asunto(s)
Neoplasias de la Mama/epidemiología , Cicatriz , Supervivencia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/psicología , Neoplasias de la Mama/cirugía , Terapia Combinada , Femenino , Encuestas de Atención de la Salud , Humanos , Mastectomía/efectos adversos , Mastectomía/métodos , Persona de Mediana Edad , Morbilidad , Factores de Riesgo , Factores Socioeconómicos , Estados Unidos/epidemiología , Adulto Joven
18.
Ann Pharmacother ; 53(2): 171-177, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30132336

RESUMEN

BACKGROUND: Cangrelor is an intravenous P2Y12 receptor antagonist approved for use during percutaneous coronary intervention (PCI) to reduce ischemic events associated with new stent placement and has been used off-label at reduced doses guided by platelet function testing as a "bridge" from discontinuation of oral P2Y12 receptor antagonists to surgical procedures when the long-term effects of oral agents are undesirable. OBJECTIVE: To describe the dosing, laboratory monitoring, and clinical outcomes of a series of patients who received cangrelor as a "bridging" antiplatelet agent. METHODS: This study is a retrospective analysis of all patients within the study center with coronary stents who received cangrelor as a bridge to surgical procedure and had VerifyNow monitoring during treatment. RESULTS: A total of 11 patients were identified for inclusion. The median cangrelor dose was 0.5 µg/kg/min (interquartile range = 0.5-0.5) and was maintained in 7 of 11 patients. Doses ranged from 0.25 to 2 µg/kg/min during therapy, and 81.6% of VerifyNow results assessed were within goal range (⩽208 P2Y12 reaction units). Bleeding complications during therapy occurred in 3 patients, all of whom were receiving concomitant heparin infusions, and no stent thrombosis was reported. Conclusion and Relevance: Low-dose cangrelor may represent an effective option for bridging antiplatelet therapy in patients with coronary stents. This study demonstrated that the majority of patients received adequate platelet inhibition without any incidence of stent thrombosis on 0.5 µg/kg/min using the VerifyNow assay to monitor platelet inhibition, which represents a lower dose than previously reported in the literature.


Asunto(s)
Adenosina Monofosfato/análogos & derivados , Trombosis Coronaria/cirugía , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/administración & dosificación , Stents , Adenosina Monofosfato/administración & dosificación , Adenosina Monofosfato/efectos adversos , Administración Oral , Anciano , Anciano de 80 o más Años , Trombosis Coronaria/complicaciones , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Sustitución de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Pruebas de Función Plaquetaria , Cuidados Posoperatorios/métodos , Complicaciones Posoperatorias/prevención & control , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Estudios Retrospectivos , Stents/efectos adversos , Resultado del Tratamiento
19.
Ann Surg Oncol ; 25(10): 2790-2794, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30003450

RESUMEN

INTRODUCTION: Oncoplastic surgery is emerging as a validated, safe, patient-centric approach to breast cancer surgery in the United States. The American Society of Breast Surgeons Oncoplastic Surgery Committee (ASBrS-OSC) conducted a survey to assess the scope of practice and level of interest in oncoplastic surgery among its members. Furthermore, the group sought to identify barriers to incorporating oncoplastic skills in a surgeon's practice. METHODS: A 10-question survey was administered in March 2017 to the entire ASBrS membership using an online format. Three solicitations were sent. Unique identifiers allowed a single response. RESULTS: Of the 2655 surveys sent out, 708 members responded. Nearly all (99%) respondents had at least some interest in oncoplastic surgery. The current rates of performing nipple-sparing mastectomy, adjacent tissue transfer, and breast reduction with lumpectomy were 80, 60, and 51%, respectively. A minority of respondents reported independently performing breast reductions/mammaplasties (19%) or contralateral symmetrization (10%). Barriers to learning oncoplastic surgery included surgeon's time and access to oncoplastic educational material/courses. Most respondents felt that training courses and videos may allow them to better incorporate oncoplastic techniques in their practices. CONCLUSIONS: The interest in oncoplastic surgery among U.S. surgeons is significant, yet there are barriers to incorporate these surgical techniques into a breast surgeon's practice. As professional organizations provide access to effective training and enduring educational resources, breast surgeons will be enabled to develop their oncoplastic skill set and safely offer these techniques to their patients.


Asunto(s)
Neoplasias de la Mama/cirugía , Mastectomía/tendencias , Oncología Quirúrgica/tendencias , Competencia Clínica , Encuestas de Atención de la Salud , Humanos , Mastectomía/métodos , Mastectomía/normas , Pautas de la Práctica en Medicina/normas , Pautas de la Práctica en Medicina/tendencias , Oncología Quirúrgica/normas
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